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  • 1. Abbas, S
    et al.
    Linseisen, J
    Rohrmann, S
    Beulens, JWJ
    Buijsse, B
    Amiano, P
    Ardanaz, E
    Balkau, B
    Boeing, H
    Clavel-Chapelon, F
    Fagherazzi, G
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gavrila, D
    Grioni, S
    Kaaks, R
    Key, TJ
    Khaw, KT
    Kuehn, T
    Mattiello, A
    Molina-Montes, E
    Nilsson, PM
    Overvad, K
    Quiros, JR
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sacerdote, C
    Saieva, C
    Slimani, N
    Sluijs, I
    Spijkerman, AMW
    Tjonneland, A
    Tumino, R
    van der A, DL
    Zamora-Ros, R
    Sharp, SJ
    Langenberg, C
    Forouhi, NG
    Riboli, E
    Wareham, NJ
    Dietary vitamin D intake and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition: the EPIC-InterAct study2014Inngår i: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 68, nr 2, s. 196-202Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND/OBJECTIVES: Prospective cohort studies have indicated that serum vitamin D levels are inversely related to risk of type 2 diabetes. However, such studies cannot determine the source of vitamin D. Therefore, we examined the association of dietary vitamin D intake with incident type 2 diabetes within the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study in a heterogeneous European population including eight countries with large geographical variation.

    SUBJECTS/METHODS: Using a case-cohort design, 11 245 incident cases of type 2 diabetes and a representative subcohort (N = 15 798) were included in the analyses. Hazard ratios (HR) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using a Prentice-weighted Cox regression adjusted for potential confounders. Twenty-four-hour diet-recall data from a subsample (N = 2347) were used to calibrate habitual intake data derived from dietary questionnaires.

    RESULTS: Median follow-up time was 10.8 years. Dietary vitamin D intake was not significantly associated with the risk of type 2 diabetes. HR and 95% CIs for the highest compared to the lowest quintile of uncalibrated vitamin D intake was 1.09 (0.97-1.22) (P-trend = 0.17). No associations were observed in a sex-specific analysis. The overall pooled effect (HR (95% CI)) using the continuous calibrated variable was 1.00 (0.97-1.03) per increase of 1 mg/day dietary vitamin D.

    CONCLUSIONS: This observational study does not support an association between higher dietary vitamin D intake and type 2 diabetes incidence. This result has to be interpreted in light of the limited contribution of dietary vitamin D on the overall vitamin D status of a person.

  • 2. Abrahamsson, Niclas
    et al.
    Borjesson, Joey Lau
    Sundbom, Magnus
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Karlsson, F. Anders
    Eriksson, Jan W.
    Gastric Bypass Reduces Symptoms and Hormonal Responses in Hypoglycemia2016Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, nr 9, s. 2667-2675Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.

  • 3.
    Adamo, Karin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Gunnarsson, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Eeg-Olofsson, Katarina
    Strigård, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Brännström, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Department of Surgery, Södertälje Hospital, Södertälje, Sweden.
    Risk for developing perianal abscess in type 1 and type 2 diabetes and the impact of poor glycemic control2021Inngår i: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 36, nr 5, s. 999-1005Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: The primary aim of this study was to see whether perianal abscess rate differs between patients with type 1 and type 2 diabetes. A secondary aim was to determine whether poor glycemic control increases the risk for perianal abscess.

    Methods: Data from the Swedish National Diabetes Registry and the Swedish National Patient Registry between January 2008 and June 2015 were matched. The risk for anal abscess was evaluated in univariate and multivariate analyses with type of diabetes, HbA1c level, BMI, and various diabetes complications as independent factors.

    Results: Patients with type 1 diabetes had a lower rate of perianal abscess than patients with type 2 diabetes when adjusted for HbA1c, sex, and age (OR 0.65; 95% CI 0.57–0.73). The risk for perianal abscess increased with higher HbA1c. Incidence of perianal abscess was also elevated in diabetes patients with complications related to poor glycemic control such as ketoacidosis and coma (OR 2.63; 95% CI 2.06–3.35), gastroparesis, and polyneuropathy (OR 1.81; 95% CI 1.41–2.32).

    Conclusions: The prevalence of perianal abscess was higher among patients with type 2 diabetes than those with type 1, suggesting that metabolic derangement may be more important than autoimmune factors. Poor glycemic control was associated with higher risk for perianal abscess.

    Fulltekst (pdf)
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  • 4. Ahmad, S
    et al.
    Poveda, A
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Lund University, Malmö, Sweden.
    Barroso, I
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Lund University, Malmö, Sweden.
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Established BMI-associated genetic variants and their prospective associations with BMI and other cardiometabolic traits: the GLACIER Study2016Inngår i: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, nr 9, s. 1346-1352Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Recent cross-sectional genome-wide scans have reported associations of 97 independent loci with body mass index (BMI). In 3541 middle-aged adult participants from the GLACIER Study, we tested whether these loci are associated with 10-year changes in BMI and other cardiometabolic traits (fasting and 2-h glucose, triglycerides, total cholesterol, and systolic and diastolic blood pressures).

    METHODS: A BMI-specific genetic risk score (GRS) was calculated by summing the BMI-associated effect alleles at each locus. Trait-specific cardiometabolic GRSs comprised only the loci that show nominal association (P⩽0.10) with the respective trait in the original cross-sectional study. In longitudinal genetic association analyses, the second visit trait measure (assessed ~10 years after baseline) was used as the dependent variable and the models were adjusted for the baseline measure of the outcome trait, age, age(2), fasting time (for glucose and lipid traits), sex, follow-up time and population substructure.

    RESULTS: The BMI-specific GRS was associated with increased BMI at follow-up (β=0.014 kg m(-2) per allele per 10-year follow-up, s.e.=0.006, P=0.019) as were three loci (PARK2 rs13191362, P=0.005; C6orf106 rs205262, P=0.043; and C9orf93 rs4740619, P=0.01). Although not withstanding Bonferroni correction, a handful of single-nucleotide polymorphisms was nominally associated with changes in blood pressure, glucose and lipid levels.

    CONCLUSIONS: Collectively, established BMI-associated loci convey modest but statistically significant time-dependent associations with long-term changes in BMI, suggesting a role for effect modification by factors that change with time in this population.

  • 5.
    Alanentalo, Tomas
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Hahn, Max
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Willekens, Stefanie M. A.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Ahlgren, Ulf
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Mesoscopic Optical Imaging of the Pancreas: Revisiting Pancreatic Anatomy and Pathophysiology2021Inngår i: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 12, artikkel-id 633063Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The exocrine-endocrine multipart organization of the pancreas makes it an exceedingly challenging organ to analyze, quantitatively and spatially. Both in rodents and humans, estimates of the pancreatic cellular composition, including beta-cell mass, has been largely relying on the extrapolation of 2D stereological data originating from limited sample volumes. Alternatively, they have been obtained by low resolution non-invasive imaging techniques providing little detail regarding the anatomical organization of the pancreas and its cellular and/or molecular make up. In this mini-review, the state of the art and the future potential of currently existing and emerging high-resolution optical imaging techniques working in the mm-cm range with μm resolution, here referred to as mesoscopic imaging approaches, will be discussed regarding their contribution toward a better understanding of pancreatic anatomy both in normal conditions and in the diabetic setting. In particular, optical projection tomography (OPT) and light sheet fluorescence microscopy (LSFM) imaging of the pancreas and their associated tissue processing and computational analysis protocols will be discussed in the light of their current capabilities and future potential to obtain more detailed 3D-spatial, quantitative, and molecular information of the pancreas.

    Fulltekst (pdf)
    fulltext
  • 6.
    Alanentalo, Tomas
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Hörnblad, Andreas
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Mayans, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Nilsson, Anna Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Sharpe, James
    Larefalk, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Ahlgren, Ulf
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Holmberg, Dan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Quantification and 3-D imaging of the insulitis-induced destruction of β-cells in murine type 1 diabetes2010Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 59, nr 7, s. 1756-1764Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: The aim of this study was to refine the information regarding the quantitative and spatial dynamics of infiltrating lymphocytes and remaining beta-cell volume during the progression of type 1 diabetes in the NOD mouse model of the disease.

    Research design and methods: Using an ex vivo technique, optical projection tomography (OPT), we quantified and assessed the 3D spatial development and progression of insulitis and beta-cell destruction in pancreas from diabetes prone NOD and non-diabetes prone congenic NOD.H-2b mice between 3 and 16 weeks of age.

    Results: Together with results showing the spatial dynamics of the insulitis process we provide data of beta-cell volume distributions down to the level of the individual islets and throughout the pancreas during the development and progression of type 1 diabetes. Our data provide evidence for a compensatory growth potential of the larger insulin(+) islets during the later stages of the disease around the time point for development of clinical diabetes. This is in contrast to smaller islets, which appear less resistant to the autoimmune attack. We also provide new information on the spatial dynamics of the insulitis process itself, including its apparently random distribution at onset, the local variations during its further development, and the formation of structures resembling tertiary lymphoid organs at later phases of insulitis progression.

    Conclusions: Our data provides a powerful tool for phenotypic analysis of genetic and environmental effects on type 1 diabetes etiology as well as for evaluating the potential effect of therapeutic regimes.

  • 7. Albertsson-Wikland, Kerstin
    et al.
    Mårtensson, Anton
    Sävendahl, Lars
    Niklasson, Aimon
    Bang, Peter
    Dahlgren, Jovanna
    Gustafsson, Jan
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Norgren, Svante
    Pehrsson, Nils-Gunnar
    Oden, Anders
    Birth Characteristics Explain One Third of Expected Deaths in rhGH-treated Patients Diagnosed with IGHD, ISS & SGA2016Inngår i: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 86, s. 49-49Artikkel i tidsskrift (Annet vitenskapelig)
  • 8.
    Alhaidan, Yazeid
    et al.
    Department of Clinical Genetics, Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Medical Genomics Research, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
    Christesen, Henrik Thybo
    Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, Denmark; Odense Pancreas Center, Odense, Denmark.
    Lundberg, Elena
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Balwi, Mohammed A. Al
    Department of Medical Genomics Research, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, NGHA, Riyadh, Saudi Arabia.
    Brusgaard, Klaus
    Department of Clinical Genetics, Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Near East University, Nicosia, Cyprus.
    CRISPR/Cas9 ADCY7 Knockout Stimulates the Insulin Secretion Pathway Leading to Excessive Insulin Secretion2021Inngår i: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 12, artikkel-id 657873Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: Despite the enormous efforts to understand Congenital hyperinsulinism (CHI), up to 50% of the patients are genetically unexplained. We aimed to functionally characterize a novel candidate gene in CHI.

    Patient: A 4-month-old boy presented severe hyperinsulinemic hypoglycemia. A routine CHI genetic panel was negative.

    Methods: A trio-based whole-exome sequencing (WES) was performed. Gene knockout in the RIN-m cell line was established by CRISPR/Cas9. Gene expression was performed using real-time PCR.

    Results: Hyperinsulinemic hypoglycemia with diffuse beta-cell involvement was demonstrated in the patient, who was diazoxide-responsive. By WES, compound heterozygous variants were identified in the adenylyl cyclase 7, ADCY7 gene p.(Asp439Glu) and p.(Gly1045Arg). ADCY7 is calcium-sensitive, expressed in beta-cells and converts ATP to cAMP. The variants located in the cytoplasmic domains C1 and C2 in a highly conserved and functional amino acid region. RIN-m(-/-Adcy7) cells showed a significant increase in insulin secretion reaching 54% at low, and 49% at high glucose concentrations, compared to wild-type. In genetic expression analysis Adcy7 loss of function led to a 34.1-fold to 362.8-fold increase in mRNA levels of the insulin regulator genes Ins1 and Ins2 (p ≤ 0.0002), as well as increased glucose uptake and sensing indicated by higher mRNA levels of Scl2a2 and Gck via upregulation of Pdx1, and Foxa2 leading to the activation of the glucose stimulated-insulin secretion (GSIS) pathway.

    Conclusion: This study identified a novel candidate gene, ADCY7, to cause CHI via activation of the GSIS pathway.

    Fulltekst (pdf)
    fulltext
  • 9.
    Ali, Rewaa
    et al.
    Department of Botany, Faculty of Science, Mansoura University, Mansoura, Egypt.
    Khamis, Tarek
    Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
    Enan, Gamal
    Department of Botany and Microbiology, Faculty of Sciences, Zagazig University, Zagazig, Egypt.
    El-Didamony, Gamal
    Department of Botany and Microbiology, Faculty of Sciences, Zagazig University, Zagazig, Egypt.
    Sitohy, Basel
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Abdel-Fattah, Gamal
    Department of Botany, Faculty of Science, Mansoura University, Mansoura, Egypt.
    The Healing Capability of Clove Flower Extract (CFE) in Streptozotocin-Induced (STZ-Induced) Diabetic Rat Wounds Infected with Multidrug Resistant Bacteria2022Inngår i: Molecules, ISSN 1431-5157, E-ISSN 1420-3049, Vol. 27, nr 7, artikkel-id 2270Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Treatment of diabetic foot ulcer (DFU) is of great challenge as it is shown to be infected by multidrug resistant bacteria (MDR bacteria). Sixty four bacterial isolates were isolated from DFU cases; antibiotic susceptibility tests were carried out for all of them. One bacterial isolate (number 11) was shown to resist the action of 8 out of 12 antibiotics used and was identified by both a Vitek-2 system and 16S rRNA fingerprints as belonging to Proteus mirabilis, and was designated Proteus mirabilis LC587231 (P. mirabilis). Clove flower extract (CFE) inhibited distinctively the P. mirabilis bacterium obtained. GC-MS spectroscopy showed that this CFE contained nine bioactive compounds. The effect of CFE on wound healing of Type 1 diabetic albino rats (Rattus norvegicus) was studied. The results indicated that topical application of CFE hydrogel improved wound size, wound index, mRNA expression of the wound healing markers (Coli1, MMP9, Fibronectin, PCNA, and TGFβ), growth factor signaling pathways (PPAR-α, PGC1-α, GLP-1, GLPr-1, EGF-β, EGF-βr, VEGF-β, and FGF-β), inflammatory cytokine expression (IL8, TNFα, NFKβ, IL1β, and MCP1), as well as anti-inflammatory cytokines (IL4 & IL10), pro-apoptotic markers (FAS, FAS-L, BAX, BAX/BCL-2, Caspase-3, P53, P38), as well as an antiapoptotic one (BCL2). Furthermore, it improved the wound oxidative state and reduced the wound microbial load, as the cefepime therapy improved the wound healing parameters. Based on the previous notions, it could be concluded that CFE represents a valid antibiotics alternative for DFU therapy since it improves diabetic wound healing and exerts antibacterial activity either in vitro or in vivo.

    Fulltekst (pdf)
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  • 10. Allin, Kristine H.
    et al.
    Tremaroli, Valentina
    Caesar, Robert
    Jensen, Benjamin A. H.
    Damgaard, Mads T. F.
    Bahl, Martin I.
    Licht, Tine R.
    Hansen, Tue H.
    Nielsen, Trine
    Dantoft, Thomas M.
    Linneberg, Allan
    Jørgensen, Torben
    Vestergaard, Henrik
    Kristiansen, Karsten
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Hansen, Torben
    Bäckhed, Fredrik
    Pedersen, Oluf
    Aberrant intestinal microbiota in individuals with prediabetes2018Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, nr 4, s. 810-820Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims/hypothesis: Individuals with type 2 diabetes have aberrant intestinal microbiota. However, recent studies suggest that metformin alters the composition and functional potential of gut microbiota, thereby interfering with the diabetes-related microbial signatures. We tested whether specific gut microbiota profiles are associated with prediabetes (defined as fasting plasma glucose of 6.1-7.0 mmol/l or HbA1c of 42-48 mmol/mol [6.0-6.5%]) and a range of clinical biomarkers of poor metabolic health.

    Methods: In the present case-control study, we analysed the gut microbiota of 134 Danish adults with prediabetes, overweight, insulin resistance, dyslipidaemia and low-grade inflammation and 134 age-and sex-matched individuals with normal glucose regulation.

    Results: We found that five bacterial genera and 36 operational taxonomic units (OTUs) were differentially abundant between individuals with prediabetes and those with normal glucose regulation. At the genus level, the abundance of Clostridium was decreased (mean log2 fold change -0.64 (SEM 0.23), p adj = 0.0497), whereas the abundances of Dorea, [Ruminococcus], Sutterella and Streptococcus were increased (mean log2 fold change 0.51 (SEM 0.12), p adj = 5 x 10-4; 0.51 (SEM 0.11), p adj = 1 x 10-4; 0.60 (SEM 0.21), p adj = 0.0497; and 0.92 (SEM0.21), p adj = 4 x 10-4, respectively). The two OTUs that differed the most were a member of the order Clostridiales (OTU 146564) and Akkermansia muciniphila, which both displayed lower abundance among individuals with prediabetes (mean log2 fold change -1.74 (SEM0.41), p adj = 2 x 10-3 and -1.65 (SEM0.34), p adj = 4 x 10-4, respectively). Faecal transfer from donors with prediabetes or screen-detected, drug-naive type 2 diabetes to germfree Swiss Webster or conventional C57BL/6 J mice did not induce impaired glucose regulation in recipient mice.

    Conclusions/interpretation: Collectively, our data show that individuals with prediabetes have aberrant intestinal microbiota characterised by a decreased abundance of the genus Clostridium and the mucin-degrading bacterium A. muciniphila. Our findings are comparable to observations in overt chronic diseases characterised by low-grade inflammation.

    Fulltekst (pdf)
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  • 11. Almby, K. E.
    et al.
    Abrahamsson, N.
    Lundqvist, M. H.
    Hammar, U.
    Thombare, K.
    Panagiotou, A.
    Karlsson, F. A.
    Sundbom, M.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Eriksson, J. W.
    Effects of GLP-1 receptor activation on counterregulatory responses during hypoglycaemia after gastric bypass surgery: no evidence for GLP-1 as a counterregulatory hormone2019Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, s. S416-S416Artikkel i tidsskrift (Annet vitenskapelig)
  • 12. Almby, K. E.
    et al.
    Katsogiannos, P.
    Kamble, P.
    Pereira, M. J.
    Wiklund, U.
    Umeå universitet.
    Eriksson, J. W.
    Two-year follow-up after gastric bypass surgery: sustained beneficial effect on metabolic health and hormonal dynamics in subjects with type 2 diabetes2020Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 63, nr SUPPL 1, s. S263-S263, artikkel-id 547Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background and aims: Gastric bypass surgery (GBP) not only reduces weight but improves glycaemic control in type 2 diabetes (T2DM) patients as well. To explore the mechanisms behind this, we studied the metabolic effects of GBP over time using an integrative approach.

    Materials and methods: We conducted a prospective study of 13 subjects with T2DM since 4 ±3 years, treated with oral glucose lowering drugs (GLD), recruited before their GBP surgery (3M/ 10F, age 51 ± 9 years). Subjects were assessed at preoperative baseline (BL) and four weeks (4W), six months (6M) and two years (2Y) post-operatively. During visits, fasting hormone and metabolite levels were measured, as well as resting heart rate variability (HRV) followed by subcutaneous adipose tissue (AT) biopsies, a 30 min 5 gram IV-arginine challenge (ARG) and a 180 min oral glucose tolerance test (OGTT).

    Results: All but one subject discontinued their GLD after surgery and remained without antidiabetic drugs at 2Y follow-up. HbA1c was reduced after surgery and remained at non-diabetic levels at 2Y (see Table. SD=standard deviation. SEM=standard error of the mean. P-value from Student’s T-test). Fasting insulin was reduced significantly 4W after surgery (28.0 ±10.8 mE/L vs 14.4 ±10.8 mE/L) and even lower at 6M (8.9 ±5.6 mE/L) and 2Y (8.0 ±6.2 mE/L). Fasting cortisol was significantly lower than BL at 4W, but significantly increased relative to BL levels at 6M. ACTH was lower than BL at 4W and 6M (borderline significant), but returned to BL levels at 2Y. Insulin excursions after arginine stimulation were markedly reduced 4W after surgery and remained so at 6M and 2Y (data not shown). At all time points after surgery, peak p-glucose during OGTT occurred earlier, as did the consequent drop in glucose levels. The secretion of insulin during OGTT mirrored this pattern. Total GLP-1 levels during OGTT (area under the curve=AUC) increased significantly 4W after surgery and remained increased at 6M and 2Y. AUC for GIP during OGTT had decreased significantly 4W after surgery and continued to do so for 6M and 2Y. Both GLP-1 and GIP however showed an earlier peak in secretion. HOMA-IR improved after surgery (see Table) and remained so at 2Y. Total body fat decreased with GBP (Table), as did adipocyte cell size vs BL (diameter 110.7±11.2 μm) at 4W (94.9±13.1 μm, p=0.013), 6M (101.6±13.1 μm, p=0.0035) and 2Y (93.1±12.7 μm, p<0.001).

    Conclusion: GBP improves glucose control in T2DM and reduces the need for GLD. Beneficially effects on metabolic parameters and adipocyte morphology are still seen after 2Y of follow-up. A marked increase in AUC for GLP-1 whereas AUC for GIP decreases after surgery, although both have an earlier peak in secretion during OGTT. A decrease in morning cortisol is seen at 4W after GBP, but no concomitant rise in ACTH, suggesting a central mechanism might affect cortisol and in turn contribute to early improvements in glucose homeostasis.

  • 13. Almby, Kristina E.
    et al.
    Abrahamsson, Niclas
    Lundqvist, Martin H.
    Hammara, Ulf
    Thombare, Ketan
    Panagiotou, Amalia
    Karisson, F. Anders
    Sundbom, Magnus
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Eriksson, Jan W.
    Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery2019Inngår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 181, nr 2, s. 161-171Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: The aim of the study was to explore the role of GLP-1 receptor activation on the counter-regulation and symptoms of hypoglycemia in subjects who have undergone gastric bypass surgery (GBP).

    Design: Experimental hyperinsulinemic–hypoglycemic clamp study.

    Methods: Twelve post-GBP subjects participated in a randomized cross-over study with two hyperinsulinemic, hypoglycemic clamps (glucose nadir 2.7 mmol/L) performed on separate days with concomitant infusions of the GLP-1 analog exenatide or with saline, respectively. Continuous measurements of metabolites and counter-regulatory hormones as well as assessments of heart rate variability and symptoms of hypoglycemia were performed throughout the clamps.

    Results: No effect of GLP-1 receptor activation on counter-regulatory hormones (glucagon, catecholamines, cortisol, GH) or glucose infusion rate was seen, but we found indications of a downregulation of the sympathetic relative to the parasympathetic nerve activity, as reflected in heart rate variability. No significant differences in symptom of hypoglycemia were observed.

    Conclusions/interpretation: Short-term exposure to a GLP-1 receptor agonist does not seem to impact the counter-regulatory hormonal and metabolic responses in post-GBP subjects during hypoglycemic conditions, suggesting that the improvement in symptomatic hypoglycemia post-GBP seen following treatment with GLP-1 receptor agonists may be mediated by mechanism not directly involved in counter-regulation.

  • 14.
    Almby, Kristina E.
    et al.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Katsogiannos, Petros
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Pereira, Maria J.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Anders Karlsson, F.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Sundbom, Magnus
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Kamble, Prasad G.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Eriksson, Jan W.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Time course of metabolic, neuroendocrine, and adipose effects during 2 years of follow-up after gastric bypass in patients with type 2 diabetes2021Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 106, nr 10, s. E4049-E4061Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Context: Roux-en-Y gastric bypass surgery (RYGB) markedly improves glycemia in patients with type 2 diabetes (T2D), but underlying mechanisms and changes over time are incompletely understood.

    Objective: Integrated assessment of neuroendocrine and metabolic changes over time inT2D patients undergoing RYGB.

    Design and Setting: Follow-up of single-center randomized study.

    Patients: Thirteen patients with obesity andT2D compared to 22 healthy subjects.

    Interventions: Blood chemistry, adipose biopsies, and heart rate variability were obtained before and 4, 24, and 104 weeks post-RYGB.

    Results: After RYGB, glucose-lowering drugs were discontinued and hemoglobin A1c fell from mean 55 to 41 mmol/mol by 104 weeks (P < 0.001). At 4 weeks, morning cortisol (P < 0.05) and adrenocorticotropin (P = 0.09) were reduced by 20%. Parasympathetic nerve activity (heart rate variability derived) increased at 4 weeks (P < 0.05) and peaked at 24 weeks (P < 0.01). C-reactive protein (CRP) and white blood cells were rapidly reduced (P < 0.01). At 104 weeks, basal and insulin-stimulated adipocyte glucose uptake increased by 3-fold vs baseline and expression of genes involved in glucose transport, fatty acid oxidation, and adipogenesis was upregulated (P < 0.01). Adipocyte volume was reduced by 4 weeks and more markedly at 104 weeks, by about 40% vs baseline (P < 0.01).

    Conclusions: We propose this order of events: (1) rapid glucose lowering (days); (2) attenuated cortisol axis activity and inflammation and increased parasympathetic tone (weeks); and (3) body fat and weight loss, increased adipose glucose uptake, and whole-body insulin sensitivity (months-years; similar to healthy controls).Thus, neuroendocrine pathways can partly mediate early glycemic improvement after RYGB, and adipose factors may promote long-term insulin sensitivity and normoglycemia.

    Fulltekst (pdf)
    fulltext
  • 15.
    Almby, Kristina E.
    et al.
    Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden.
    Lundqvist, Martin H.
    Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden.
    Abrahamsson, Niclas
    Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden.
    Kvernby, Sofia
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Fahlström, Markus
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Pereira, Maria J.
    Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden.
    Gingnell, Malin
    Department of Neurosciences and Department of Psychology, Uppsala University, Uppsala, Sweden.
    Karlsson, F Anders
    Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden.
    Fanni, Giovanni
    Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden.
    Sundbom, Magnus
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Haller, Sven
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Faculty of Medicine, University of Geneva, Geneva, Switzerland.
    Lubberink, Mark
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Wikström, Johan
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Eriksson, Jan W.
    Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden.
    Effects of Gastric Bypass Surgery on the Brain: Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia2021Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 70, nr 6, s. 1265-1277Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by 18F-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.

  • 16.
    Al-Shamkhi, Nasrin
    et al.
    Department of Internal Medicine, Örebro University Hospital and School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Endocrinology and Diabetology, Uppsala University Hospital, Uppsala, Sweden.
    Berinder, Katarina
    Department of Endocrinology, Karolinska University Hospital and Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Borg, Henrik
    Department of Endocrinology, Skåne University Hospital, Lund University, Lund, Sweden.
    Burman, Pia
    Department of Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.
    Dahlqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Höybye, Charlotte
    Department of Endocrinology, Karolinska University Hospital and Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Olsson, Daniel S.
    Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
    Ragnarsson, Oskar
    Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Göteborg, Sweden.
    Ekman, Bertil
    Departments of Endocrinology in Linköping and Norrköping, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Engström, Britt Eden
    Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University, Uppsala University Hospital, Uppsala, Sweden.
    Pituitary function before and after surgery for nonfunctioning pituitary adenomas-data from the Swedish pituitary register2023Inngår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 189, nr 2, s. 217-224Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Data on pre- and postoperative pituitary function in nonfunctioning pituitary adenomas (NFPA) are not consistent. We aimed to investigate pituitary function before and up to 5 years after transsphenoidal surgery with emphasis on the hypothalamic-pituitary-adrenal axis (HPA).

    Design and methods: Data from the Swedish Pituitary Register was used to analyze anterior pituitary function in 838 patients with NFPA diagnosed between 1991 and 2014. Patients who were reoperated or had received radiotherapy were excluded.

    Results: Preoperative ACTH, TSH, LH/FSH, and GH deficiencies were reported in 31% (236/755), 39% (300/769), 51% (378/742), and 28% (170/604) of the patients, respectively. Preoperative median tumor volume was 5.0 (2.4-9.0) cm(3). Among patients with preoperative, 1 year and 5 years postoperative data on the HPA axis (n = 428), 125 (29%) were ACTH-deficient preoperatively. One year postoperatively, 26% (32/125) of them had recovered ACTH function while 23% (70/303) patients had developed new ACTH deficiency. Thus, 1 year postoperatively, 163 (38%) patients were ACTH-deficient (P < .001 vs. preoperatively). No further increase was seen 5 years postoperatively (36%, P = .096). At 1 year postoperatively, recoveries in the TSH and LH/FSH axes were reported in 14% (33/241) and 15% (46/310), respectively, and new deficiencies in 22% (88/403) and 29% (83/288), respectively.

    Conclusions: Adrenocorticotrophic hormone deficiency increased significantly at 1 year postoperatively. Even though not significant, some patients recovered from or developed new deficiency between 1 and 5 years postoperatively. This pattern was seen in all axes. Our study emphasizes that continuous individual evaluations are needed during longer follow-up of patients operated for NFPA.

    Fulltekst (pdf)
    fulltext
  • 17. Alssema, M
    et al.
    Vistisen, D
    Heymans, MW
    Nijpels, G
    Glümer, C
    Zimmet, PZ
    Shaw, JE
    Eliasson, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stehouwer, CDA
    Tabák, AG
    Colagiuri, S
    Borch-Johnsen, K
    Dekker, JM
    The evaluation of screening and early detection strategies for type 2 diabetes and impaired glucose tolerance (DETECT-2) update of the Finnish diabetes risk score for prediction of incident type 2 diabetes2011Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 54, nr 5, s. 1004-1012Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIMS/HYPOTHESIS: The Finnish diabetes risk questionnaire is a widely used, simple tool for identification of those at risk for drug-treated type 2 diabetes. We updated the risk questionnaire by using clinically diagnosed and screen-detected type 2 diabetes instead of drug-treated diabetes as an endpoint and by considering additional predictors.

    METHODS: Data from 18,301 participants in studies of the Evaluation of Screening and Early Detection Strategies for Type 2 Diabetes and Impaired Glucose Tolerance (DETECT-2) project with baseline and follow-up information on oral glucose tolerance status were included. Incidence of type 2 diabetes within 5 years was used as the outcome variable. Improvement in discrimination and classification of the logistic regression model was assessed by the area under the receiver-operating characteristic (ROC) curve and by the net reclassification improvement. Internal validation was by bootstrapping techniques.

    RESULTS: Of the 18,301 participants, 844 developed type 2 diabetes in a period of 5 years (4.6%). The Finnish risk score had an area under the ROC curve of 0.742 (95% CI 0.726-0.758). Re-estimation of the regression coefficients improved the area under the ROC curve to 0.766 (95% CI 0.750-0.783). Additional items such as male sex, smoking and family history of diabetes (parent, sibling or both) improved the area under the ROC curve and net reclassification. Bootstrapping showed good internal validity.

    CONCLUSIONS/INTERPRETATION: The predictive value of the original Finnish risk questionnaire could be improved by adding information on sex, smoking and family history of diabetes. The DETECT-2 update of the Finnish diabetes risk questionnaire is an adequate and robust predictor for future screen-detected and clinically diagnosed type 2 diabetes in Europid populations.

  • 18.
    Alvehus, Malin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Burén, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sjöström, Michael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Goedecke, Julia
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    The human visceral fat depot has a unique inflammatory profile2010Inngår i: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 18, nr 5, s. 879-883Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Obesity can be considered as a low-grade inflammatory condition, strongly linked to adverse metabolic outcomes. Obesity-associated adipose tissue inflammation is characterized by infiltration of macrophages and increased cytokine and chemokine production. The distribution of adipose tissue impacts the outcomes of obesity, with the accumulation of fat in visceral adipose tissue (VAT) and deep subcutaneous adipose tissue (SAT), but not superficial SAT, being linked to insulin resistance. We hypothesized that the inflammatory gene expression in deep SAT and VAT is higher than in superficial SAT. A total of 17 apparently healthy women (BMI: 29.3 +/- 5.5 kg/m2) were included in the study. Body fat (dual-energy X-ray absorptiometry) and distribution (computed tomography) were measured, and insulin sensitivity, blood lipids, and blood pressure were determined. Inflammation-related differences in gene expression(real-time PCR) from VAT, superficial and deep SAT biopsies were analyzed using univariate and multivariate data analyses. Using multivariate discrimination analysis, VAT appeared as a distinct depot in adipose tissue inflammation,while the SAT depots had a similar pattern, with respect to gene expression. A significantly elevated (P < 0.01)expression of the CC chemokine receptor 2 (CCR2) and macrophage migration inhibitory factor (MIF) in VAT contributed strongly to the discrimination. In conclusion, the human adipose tissue depots have unique inflammatory patterns, with CCR2 and MIF distinguishing between VAT and the SAT depots.

  • 19. Andersen, Mette K.
    et al.
    Sterner, Maria
    Forsen, Tom
    Käräjämäki, Annemari
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Forsblom, Carol
    Groop, Per-Henrik
    Lahti, Kaj
    Nilsson, Peter M.
    Groop, Leif
    Tuomi, Tiinamaija
    Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes2014Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, nr 9, s. 1859-1868Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims/hypothesis Latent autoimmune diabetes in adults (LADA) is phenotypically a hybrid of type 1 and type 2 diabetes. Genetically LADA is poorly characterised but does share genetic predisposition with type 1 diabetes. We aimed to improve the genetic characterisation of LADA and hypothesised that type 2 diabetes-associated gene variants also predispose to LADA, and that the associations would be strongest in LADA patients with low levels of GAD autoantibodies (GADA). Methods We assessed 41 type 2 diabetes-associated gene variants in Finnish (phase I) and Swedish (phase II) patients with LADA (n=911) or type 1 diabetes (n=406), all diagnosed after the age of 35 years, as well as in non-diabetic control individuals 40 years or older (n=4,002). Results Variants in the ZMIZ1 (rs12571751, p=4.1 x 10(-5)) and TCF7L2 (rs7903146, p=5.8 x 10(-4)) loci were strongly associated with LADA. Variants in the KCNQ1 (rs2237895, p=0.0012), HHEX (rs1111875, p=0.0024 in Finns) and MTNR1B (rs10830963, p=0.0039) loci showed the strongest association in patients with low GADA, supporting the hypothesis that the disease in these patients is more like type 2 diabetes. In contrast, variants in the KLHDC5 (rs10842994, p=9.5 x 10(-4) in Finns), TP53INP1 (rs896854, p=0.005), CDKAL1 (rs7756992, p=7.0 x 10(-4); rs7754840, p=8.8 x 10(-4)) and PROX1 (rs340874, p=0.003) loci showed the strongest association in patients with high GADA. For type 1 diabetes, a strong association was seen for MTNR1B (rs10830963, p=3.2 x 10(-6)) and HNF1A (rs2650000, p=0.0012). Conclusions/interpretation LADA and adult-onset type 1 diabetes share genetic risk variants with type 2 diabetes, supporting the idea of a hybrid form of diabetes and distinguishing them from patients with classical young-onset type 1 diabetes.

  • 20. Andersson, B.
    et al.
    Swolin-Eide, D.
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Gelander, L.
    Magnusson, P.
    Albertsson-Wikland, K.
    Seasonal variations in vitamin D in relation to growth in short prepubertal children before and during first year growth hormone treatment2015Inngår i: Journal of Endocrinological Investigation, ISSN 0391-4097, E-ISSN 1720-8386, Vol. 38, nr 12, s. 1309-1317Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose This study investigated the relationship between seasonal variations in 25-hydroxyvitamin D (25(OH) D) levels and growth in prepubertal children during both the pretreatment year and the first year of GH treatment. Methods The study included 249 short prepubertal children with a broad range of GH secretion, GH(max) during a 24 h profile median 23; range 1-127 mU/L, 191 boys (mean age +/- SD, 8.6 +/- 2.6 years), 58 girls (7.5 +/- 1.9 years) receiving GH treatment (mean 43 mu g/kg/day; range 17-99 mu g/kg/day). Serum 25(OH) D was measured using an automated IDS-iSYS immunoassay. Results 25(OH) D levels showed seasonal variation, and decreased significantly during GH treatment. 25(OH) D levels at start and first year reduction in 25(OH) D, correlated (-) with the first year growth response during treatment. The degree of GH secretion capacity within our study population of mainly non-GH deficient children and 25(OH) D sufficient (67 +/- 29 nmol/L) had no influence on 25(OH) D levels. Growth during GH treatment were independent of seasonal variations in 25(OH) D. Multiple regression analysis showed that 25(OH) D levels at treatment start, together with auxological data and IGF-binding protein-3(SDS), explained 61 % of the variation in first year gain in height(SDS). Conclusion 25(OH) D levels were associated with first year growth response to GH and may be a useful contribution to future growth prediction models.

  • 21.
    Andersson, Håkan
    Umeå universitet, Medicinska fakulteten.
    Clinical Reproductive Endocrinology2008Inngår i: Clinical Biochemistry of Domestic Animals, 6th Edition, Amsterdam: Elsevier, 2008, s. 635-662Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    This chapter helps in understating the basics of clinical reproductive endocrinology. Clinical reproductive endocrinology includes the study of diseases and secretory status of the endocrine glands involved in reproduction and their secretory products, the reproductive hormones. To obtain a satisfactory understanding of the complex endocrinological events that occur during normal and abnormal reproductive function, it is necessary to quantify specific hormones. The best understood humoral control system in the body is the endocrine system. This system uses specific messengers, termed hormones, to regulate important body functions. Hormones are chemical substances synthesized and secreted directly into the blood vascular system by ductless endocrine glands in minute quantities and are transported to a remote target organ, where they regulate the rates of specific biochemical processes. The classic endocrine glands include the pituitary, thyroid, parathyroid, adrenal, pancreas, ovary, testis, placenta, and pineal gland. This chapter emphasizes the determination of hormones and the use of the data as diagnostic aids. General reproductive endocrinology in domestic species is broadly covered in this chapter.

  • 22.
    Andersson, Therese
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    McInnes, Kerry
    Endocrine Unit, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
    Simonyte, Kotryna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Söderström, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Rask, Eva
    Institutionen för medicin, Örebro universitetssjukhus, Örebro, Sverige.
    Mattsson, Cecilia
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Seckl, Jonathan R
    Endocrinology Unit, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Estrogen upregulates 11β-hydroxysteroid dehydrogenase type 1 in adipose tissues via estrogen receptor βManuskript (preprint) (Annet vitenskapelig)
  • 23.
    Andersson, Therése
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Estrogen and Glucocorticoid Metabolism2010Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background: Cardiovascular disease (CVD) is the leading cause of death among women in Sweden. The risk of CVD increases rapidly after the menopause. A major contributing factor may be the redistribution of adipose tissue, from the peripheral to central depots, associated with menopause. This change in body composition is commonly attributed to declining estrogen levels but may also be affected by tissue-specific alterations in exposure to other steroid hormones, notably glucocorticoids – mainly cortisol in humans. Indeed, adipose tissue-specific overexpression of the glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) induces central obesity, insulin resistance and hypertension in mice. Interestingly, estrogen may regulate this enzyme. The aim of this thesis was to investigate putative links between estrogen and glucocorticoid activation by 11βHSD1. Materials and Methods: 11βHSD1 expression and/or activity in adipose tissue and liver, and adipose estrogen receptor α and β (ERα and ERβ) gene expression, were investigated in lean pre- and postmenopausal women and ovariectomized rodents with and without estrogen supplementation. In lean women measures of 11βHSD1 were correlated to risk markers for CVD. The association between adipose 11βHSD1 and ER mRNA expression was investigated in both lean women and rats and in an additional cohort of obese premenopausal women. In vitro experiments with adipocyte cell lines were used to explore possible pathways for estrogen regulation of 11βHSD1. Results: Subcutaneous adipose tissue transcript levels and hepatic activity of 11βHSD1 were higher in postmenopausal vs. premenopausal women. In rodents, estrogen treatment to ovariectomized rats decreased visceral adipose tissue 11βHSD1, resulting in a shift towards higher subcutaneous (vs. visceral) 11βHSD1 mRNA expression/activity. Increased adipose and hepatic 11βHSD1 were associated with increased blood pressure and a disadvantageous blood lipid profile in humans. We found significant positive associations between 11βHSD1 and ERβ transcript levels in adipose tissue. The in vitro experiments showed upregulation of 11βHSD1 mRNA expression and activity with estrogen or ERβ-agonist treatment at low (corresponding to physiological) concentrations. Conclusions: Our studies show for the first time increased local tissue glucocorticoid activation with menopause/age in women. This may contribute to an increased risk of CVD. Estrogen treatment in rodents induces a shift in 11βHSD1 activity towards the subcutaneous adipose tissue depots, which may direct fat accumulation to this metabolically “safer” depot. The in vitro studies suggest that low-dose estrogen treatment upregulates 11βHSD1 via ERβ. In summary, estrogen - glucocorticoid metabolism interactions may be key in the development of menopause-related metabolic dysfunction and in part mediate the beneficial effects of postmenopausal estrogen treatment on body fat distribution.

    Fulltekst (pdf)
    FULLTEXT02
  • 24. Ankarberg-Lindgren, Carina
    et al.
    Gawlik, Aneta
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Mazzanti, Laura
    Ruijgrok, Elisabeth J.
    Sas, Theo C. J.
    Estradiol matrix patches for pubertal induction: stability of cut pieces at different temperatures2019Inngår i: Endocrine Connections, E-ISSN 2049-3614, Vol. 8, nr 4, s. 360-366Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Transdermal estradiol patches are primarily designed for adult women. No low-dose patches are licensed for pubertal induction in hypogonadal girls. Low doses can be achieved by cutting a matrix patch into smaller pieces. However, the manufacturers do not guarantee stability or utility of cut estradiol patches. The aim of the study was to assess 1-month stability of cut estradiol patches from four different manufacturers in the laboratory at room temperature (+21 degrees C) and at an elevated temperature (+35 degrees C).

    Design and methods: Estraderm MX 50 mu g, Systen 50 mu g and Oesclim 25 mu g matrix patches were cut into eight pieces while Estradot 50 mu g small patches were cut in half. The cut patches were stored in their respective pouches at +21 degrees C or at +35 degrees C for up to 1 month. The estradiol drug was extracted from the patch by ethyl acetate n-hexane and determined by radioimmunoassay.

    Results: Storage at +21 degrees C or +35 degrees C up to 1 month did not reduce the estradiol concentration in Estraderm MX, Systen and Oesclim patches. However, although the estradiol in Estradot patches was not affected by storage at +21 degrees C, at +35 degrees C, estradiol decreased by 57% (+/- 1%) in cut pieces.

    Conclusions: Unused Estraderm MX, Systen and Oesclim patch pieces may be stored for at least 1 month at <=+35 degrees C. Where estradiol patches for children are not available, cut pieces of these or similar patches can be used for pubertal induction. The Estradot patch was too small to properly cut into low doses and not stable in elevated temperatures.

    Fulltekst (pdf)
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  • 25.
    Arlien-Søborg, Mai C.
    et al.
    Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
    Dal, Jakob
    Department of Endocrinology, Aalborg University Hospital, Aarhus, Denmark; Steno Diabetes Center North Jutland, Aalborg, Denmark.
    Heck, Ansgar
    Oslo University Hospital, Oslo, Norway.
    Stochholm, Kirstine
    Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
    Husted, Eigil
    Department of Endocrinology, Aalborg University Hospital, Aarhus, Denmark.
    Feltoft, Claus Larsen
    Copenhagen University Hospital—Herlev and Gentofte, Kobenhavn, Denmark.
    Rasmussen, Åse Krogh
    Copenhagen University Hospital, Kobenhavn, Denmark.
    Feldt-Rasmussen, Ulla
    Copenhagen University Hospital, Kobenhavn, Denmark.
    Andreassen, Mikkel
    Copenhagen University Hospital, Kobenhavn, Denmark.
    Klose, Marianne Christina
    Copenhagen University Hospital, Kobenhavn, Denmark.
    Nielsen, Torben Leo
    Odense University Hospital, Odense, Denmark.
    Andersen, Marianne Skovsager
    Odense University Hospital, Odense, Denmark.
    Christensen, Louise Lehmann
    Odense University Hospital, Odense, Denmark.
    Krogh, Jesper
    Copenhagen University Hospital, Kobenhavn, Denmark.
    Jarlov, Anne
    Copenhagen University Hospital, Kobenhavn, Denmark.
    Bollerslev, Jens
    Oslo University Hospital, Oslo, Norway.
    Nermoen, Ingrid
    Akershus University Hospital, lørenskog, Norway.
    Oksnes, Marianne
    Haukeland University Hospital, Bergen, Norway.
    Dahlqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Norrlands University Hospital, Umeå, Sweden.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Norrlands University Hospital, Umeå, Sweden.
    Berinder, Katarina
    Karolinska University Hospital, Sweden.
    Hoybye, Charlotte
    Karolinska University Hospital, Sweden.
    Petersson, Maria
    Karolinska University Hospital, Sweden.
    Akerman, Anna-karin
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Sweden; Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Wahlberg, Jeanette
    Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Ekman, Bertil
    Department of Endocrinology and the Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Engstrom, Britt Eden
    Uppsala University Hospital, Uppsala, Sweden.
    Johannsson, Gudmundur
    Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden; Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg & Sahlgrenska University Hospital, Gothenburg, Sweden.
    Ragnarsson, Oskar
    Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Olsson, Daniel
    Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden; Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg & Sahlgrenska University Hospital, Gothenburg, Sweden; Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
    Sigurjónsdóttir, Helga Ágústa
    The National University Hospital of Iceland, Gothenburg, Iceland; School of Medicine, University of Iceland, Reykjavik, Iceland.
    Fougner, Stine Lyngvi
    Department of Endocrinology, St. Olavs hospital, Trondheim University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
    Matikainen, Niina
    Helsinki University Hospital, Helsinki, Finland.
    Vehkavaara, Satu
    Helsinki University Hospital, Helsinki, Finland.
    Metso, Saara
    Tampere University Hospital, Tampere, Finland.
    Jaatinen, Pia
    Tampere University Hospital, Tampere, Finland.
    Hämäläinen, Päivi
    Tampere University Hospital, Tampere, Finland.
    Rintamäki, Reeta
    Kuopio University Hospital, Kuopio, Finland.
    Yliaska, Iina
    Oulu University Hospital, Oulu, Finland.
    Immonen, Heidi
    Turku University Hospital, Turku, Finland.
    Mäkimattila, Sari
    Helsinki University Hospital, Helsinki, Finland.
    Cederberg-Tamminen, Henna
    Helsinki University Hospital, Helsinki, Finland.
    Viukari, Marianna
    Helsinki University Hospital, Helsinki, Finland.
    Nevalainen, Pasi
    Tampere University Hospital, Tampere, Finland.
    Nuutila, Pirjo
    Turku University Hospital, Turku, Finland.
    Schalin-Jäntti, Camilla
    Helsinki University Hospital, Helsinki, Finland.
    Burman, Pia
    Skåne University Hospital, Lund University, Malmö, Sweden.
    Jørgensen, Jens Otto Lunde
    Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
    Acromegaly management in the nordic countries: a Delphi consensus survey2024Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.

    Methods: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1−7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale.

    Results: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.

    Conclusion: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.

    Fulltekst (pdf)
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  • 26.
    Arnardóttir, Steinunn
    et al.
    Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University, Uppsala, Sweden; Department of Endocrinology and Diabetes, Uppsala University Hospital, Uppsala, Sweden.
    Järås, Jacob
    Regional Cancer Center (RCC) Stockholm Gotland, Stockholm, Sweden.
    Burman, Pia
    Department of Endocrinology, Skånes University Hospital, University of Lund, Malmö, Sweden.
    Berinder, Katarina
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
    Dahlqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Erfurth, Eva Marie
    Department of Endocrinology, Skånes University Hospital, University of Lund, Malmö, Sweden.
    Höybye, Charlotte
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
    Larsson, Karin
    Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University, Uppsala, Sweden; Department of Endocrinology and Diabetes, Uppsala University Hospital, Uppsala, Sweden.
    Ragnarsson, Oskar
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Ekman, Bertil
    Department of Endocrinology in Linköping, Department of Internal Medicine in Norrköping, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Edén Engström, Britt
    Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University, Uppsala, Sweden; Department of Endocrinology and Diabetes, Uppsala University Hospital, Uppsala, Sweden.
    Long-term outcomes of patients with acromegaly: a report from the Swedish Pituitary Register2022Inngår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 186, nr 3, s. 329-339Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To describe the treatment and long-term outcomes of patients with acromegaly from all healthcare regions in Sweden.

    Design and methods: Analysis of prospectively reported data from the Swedish Pituitary Register of 698 patients (51% females) with acromegaly diagnosed from 1991 to 2011. The latest clinical follow-up date was December 2012, while mortality data were collected for 28.5 years until June 2019.

    Results: The annual incidence was 3.7/million; 71% of patients had a macroadenoma, 18% had visual field defects, and 25% had at least one pituitary hormone deficiency. Eighty-two percent had pituitary surgery, 10% radiotherapy, and 39% medical treatment. At the 5- and 10-year follow-ups, insulin-like growth factor 1 levels were within the reference range in 69 and 78% of patients, respectively. In linear regression, the proportion of patients with biochemical control including adjuvant therapy at 10 years follow-up increased over time by 1.23% per year. The standardized mortality ratio (SMR) (95% CI) for all patients was 1.29 (1.11-1.49). For patients with biochemical control at the latest follow-up, SMR was not increased, neither among patients diagnosed between 1991 and 2000, SMR: 1.06 (0.85-1.33) nor between 2001 and2011, SMR: 0.87 (0.61-1.24). In contrast, non-controlled patients at the latest follow-up from both decades had elevated SMR, 1.90 (1.33-2.72) and 1.98 (1.24-3.14), respectively.

    Conclusions: The proportion of patients with biochemical control increased over time. Patients with biochemically controlled acromegaly have normal life expectancy, while non-controlled patients still have increased mortality. The high rate of macroadenomas and unchanged age at diagnosis illustrates the need for improvements in the management of patients with acromegaly.

  • 27.
    Asplund, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Att förebygga diabetes: vilka är styrinstrumenten?2008Inngår i: DiabetologNytt, ISSN 1401-2618, Vol. 21, nr 7-8Artikkel i tidsskrift (Annet vitenskapelig)
  • 28.
    Assani, Bashar
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Tandläkarutbildning.
    Hamza, Ibrahim
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Tandläkarutbildning.
    Dental Caries and Self-Reported Type 2 Diabetes2023Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    ABSTRACT

    Patients with poorly controlled blood sugar levels and type 2 diabetes have been suggested to be at greater risk of tooth decay; however, the number of studies on this topic is scarce. This study aims to evaluate the association between self-reported diabetes, blood sugar levels, and dental caries in Swedish 40-year-old Swedes.

    Here we utilized the Gene Lifestyle Interactions in Dental Diseases (GLIDE) database, which provides access to self-reported diabetes, blood sugar levels, and the Decay, Missing, Filled Surfaces (DMFS) status in approximately 90,000 individuals. For this study, we identified 1,617 self-reported diabetes patients, and for each case, two sex- and age-matched controls were randomly selected (n = 3,234). Logistic and linear regression were employed, with appropriate adjustment for age, sex, and years between the dental caries examination and the reported diabetic diagnosis.

    Patients with self-reported type 2 diabetes displayed a 2.2 DMFS increase (p = 0.019). Additionally, increased blood sugar levels were associated with self-reported type (p < 0.001) and an increased DMFS score (p < 0.001).

    In conclusion, patients with self-reported type 2 diabetes and poorly controlled blood sugar are associated with an increased DMFS score in Sweden.

    Fulltekst (pdf)
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  • 29. Atabaki-Pasdar, Naeimeh
    et al.
    Ohlsson, Mattias
    Shungin, Dmitry
    Kurbasic, Azra
    Ingelsson, Erik
    Pearson, Ewan R.
    Ali, Ashfaq
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, SE-205 02, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Statistical power considerations in genotype-based recall randomized controlled trials2016Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 6, artikkel-id 37307Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Randomized controlled trials (RCT) are often underpowered for validating gene-treatment interactions. Using published data from the Diabetes Prevention Program (DPP), we examined power in conventional and genotype-based recall (GBR) trials. We calculated sample size and statistical power for genemetformin interactions (vs. placebo) using incidence rates, gene-drug interaction effect estimates and allele frequencies reported in the DPP for the rs8065082 SLC47A1 variant, a metformin transported encoding locus. We then calculated statistical power for interactions between genetic risk scores (GRS), metformin treatment and intensive lifestyle intervention (ILI) given a range of sampling frames, clinical trial sample sizes, interaction effect estimates, and allele frequencies; outcomes were type 2 diabetes incidence (time-to-event) and change in small LDL particles (continuous outcome). Thereafter, we compared two recruitment frameworks: GBR (participants recruited from the extremes of a GRS distribution) and conventional sampling (participants recruited without explicit emphasis on genetic characteristics). We further examined the influence of outcome measurement error on statistical power. Under most simulated scenarios, GBR trials have substantially higher power to observe gene-drug and gene-lifestyle interactions than same-sized conventional RCTs. GBR trials are becoming popular for validation of gene-treatment interactions; our analyses illustrate the strengths and weaknesses of this design.

    Fulltekst (pdf)
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  • 30. Atiomo, William
    et al.
    Shafiee, Mohamad Nasir
    Chapman, Caroline
    Metzler, Veronika M.
    Abouzeid, Jad
    Latif, Ayşe
    Chadwick, Amy
    Kitson, Sarah
    Sivalingam, Vanitha N.
    Stratford, Ian J.
    Rutland, Catrin S.
    Persson, Jenny L.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Clinical Research Center, Lund University, Malmö, Sweden.
    Ødum, Niels
    Fuentes-Utrilla, Pablo
    Jeyapalan, Jennie N.
    Heery, David M.
    Crosbie, Emma J.
    Mongan, Nigel P.
    Expression of NAD(P)H quinone dehydrogenase 1 (NQO1) is increased in the endometrium of women with endometrial cancer and women with polycystic ovary syndrome2017Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 87, nr 5, s. 557-565Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Women with a prior history of polycystic ovary syndrome (PCOS) have an increased risk of endometrial cancer (EC). Aim: To investigate whether the endometrium of women with PCOS possesses gene expression changes similar to those found in EC. Design and Methods: Patients with EC, PCOS and control women unaffected by either PCOS or EC were recruited into a cross-sectional study at the Nottingham University Hospital, UK. For RNA sequencing, representative individual endometrial biopsies were obtained from women with EC, PCOS and a woman unaffected by PCOS or EC. Expression of a subset of differentially expressed genes identified by RNA sequencing, including NAD(P)H quinone dehydrogenase 1 (NQO1), was validated by quantitative reverse transcriptase PCR validation (n = 76) and in the cancer genome atlas UCEC (uterine corpus endometrioid carcinoma) RNA sequencing data set (n = 381). The expression of NQO1 was validated by immunohistochemistry in EC samples from a separate cohort (n = 91) comprised of consecutive patients who underwent hysterectomy at St Mary's Hospital, Manchester, between 2011 and 2013. A further 6 postmenopausal women with histologically normal endometrium who underwent hysterectomy for genital prolapse were also included. Informed consent and local ethics approval were obtained for the study. Results: We show for the first that NQO1 expression is significantly increased in the endometrium of women with PCOS and EC. Immunohistochemistry confirms significantly increased NQO1 protein expression in EC relative to nonmalignant endometrial tissue (P < .0001). Conclusions: The results obtained here support a previously unrecognized molecular link between PCOS and EC involving NQO1.

    Fulltekst (pdf)
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  • 31. Avall, Karin
    et al.
    Ali, Yusuf
    Leibiger, Ingo B.
    Leibiger, Barbara
    Moede, Tilo
    Paschen, Meike
    Dicker, Andrea
    Dare, Elisabetta
    Kohler, Martin
    Ilegems, Erwin
    Abdulreda, Midhat H.
    Graham, Mark
    Crooke, Rosanne M.
    Tay, Vanessa S. Y.
    Refai, Essam
    Nilsson, Stefan K.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Jacob, Stefan
    Selander, Lars
    Berggren, Per-Olof
    Juntti-Berggren, Lisa
    Apolipoprotein CIII links islet insulin resistance to beta-cell failure in diabetes2015Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, nr 20, s. E2611-E2619Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Insulin resistance and beta-cell failure are the major defects in type 2 diabetes mellitus. However, the molecular mechanisms linking these two defects remain unknown. Elevated levels of apolipoprotein CIII (apoCIII) are associated not only with insulin resistance but also with cardiovascular disorders and inflammation. We now demonstrate that local apoCIII production is connected to pancreatic islet insulin resistance and beta-cell failure. An increase in islet apoCIII causes promotion of a local inflammatory milieu, increased mitochondrial metabolism, deranged regulation of beta-cell cytoplasmic free Ca2+ concentration ([Ca2+](i)) and apoptosis. Decreasing apoCIII in vivo results in improved glucose tolerance, and pancreatic apoCIII knockout islets transplanted into diabetic mice, with high systemic levels of the apolipoprotein, demonstrate a normal [Ca2+](i) response pattern and no hallmarks of inflammation. Hence, under conditions of islet insulin resistance, locally produced apoCIII is an important diabetogenic factor involved in impairment of beta-cell function and may thus constitute a novel target for the treatment of type 2 diabetes mellitus.

  • 32.
    Awad, Anna
    et al.
    Department of Public Health and Clinical Medicine, Sunderby Research Unit, Umeå University, Sweden..
    Lundqvist, Robert
    Research and Innovation Unit, Norrbotten County Council, Luleå, Sweden..
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sundström, Anna
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Eliasson, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Public Health and Clinical Medicine, Sunderby Research Unit, Umeå University, Sweden..
    Lower cognitive performance among long-term type 1 diabetes survivors: A case-control study2017Inngår i: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 31, nr 8, s. 1328-1331Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Patients with type 1 diabetes (T1D) have an increased risk of cognitive dysfunction. The cognitive decrement is believed to depend on macro- and microvascular complications and long disease duration. Some patients do not develop these complications, but still report cognitive symptoms. We examined if long-standing T1D without complications is associated with lower cognitive performance.

    METHODS: A group of patients (n=43) with long-standing T1D (>30years) without micro- or macro vascular complications was compared with a non-diabetic control group (n=86) on six cognitive tests which probed episodic memory, semantic memory, episodic short-term memory, visual attention and psychomotor speed. Each patient was matched with two controls regarding age, gender and education. A linear mixed effect model was used to analyze the data.

    RESULTS: The mean age was 57years and mean duration was 41years. Patients with diabetes had lower diastolic blood pressure but BMI, waist circumference, systolic blood pressure and smoking did not differ between groups. Patients had lower results than non-diabetic controls in episodic short-term memory (p<0.001) and also lower values on a test that mirrors visual attention and psychomotor speed (p=0.019).

    CONCLUSIONS: Long-standing T1D was associated with lower cognitive performance, regardless of other diabetes-related complications.

  • 33. Azizi, F
    et al.
    Mehran, L
    Sheikholeslam, R
    Ordookhani, A
    Naghavi, M
    Hedayati, M
    Padyab, Mojgan
    Mirmiran, P
    Sustainability of a well-monitored salt iodization program in Iran: marked reduction in goiter prevalence and eventual normalization of urinary iodine concentrations without alteration in iodine content of salt.2008Inngår i: Journal of Endocrinological Investigation, ISSN 0391-4097, E-ISSN 1720-8386, Vol. 31, nr 5, s. 422-31Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    Two yr after legislation of salt iodization of 40 parts per million (ppm) in 1994, goiter was still endemic and urinary iodine concentration (UIC) remained elevated in many provinces of Iran. Goiter prevalence and UIC were compared 2 and 7 yr after sustained consumption of uniformly iodized salt by Iranian households.

    METHODS:

    Schoolchildren (7-10 yr) of all provinces were randomly selected by cluster sampling from December 2000 to June 2001. Goiter rate, UIC, and household salt iodine values were compared to those in 1996. Factory salt iodine was also compared in 2001 vs 1996. Ultrasonographically determined thyroid volumes of 7-10 yr old children were compared in 2001 vs 1999.

    RESULTS:

    In 2001 (no.=33600) vs 1996 (no.=36178), total, grade 1, and grade 2 goiter rates were 13.9 vs 53.8%, 11.0 vs 44.8%, and 2.9 vs 9.0%, respectively (p<0.0001). Weighted total goiter rate was 9.8% in 2001. Median (range) UIC in 2001 (no.=3329) was 165 (18-499) microg/l and in 1996 (no.=2917) was 205 (10-2300) microg/l (p<0.0001). In 2001 vs 1996, mean+/-SD for iodine salt content was 32.7+/-10.1 vs 33.0+/-10.2 ppm (p=0.68) in households and was 33.2+/-13.4 and 33.8+/-13.2 ppm (p=0.57) in factories, respectively. Among 7-10 yr old children in 2001 (no.=400) vs 1999 (no.=396), only 7-yr-old children in 2001 (the only group with probably no history of iodine deficiency) showed significant smaller thyroid volumes by ultrasonography compared to those in 1999.

    CONCLUSIONS:

    After 7 yr of optimized iodized-salt supplementation in Iran, adequate UIC values and marked reduction in goiter rate have been achieved.

  • 34. Backeljauw, Philippe
    et al.
    Kanumakala, Shankar
    Loche, Sandro
    Schwab, Karl Otfried
    Pfäffle, Roland Werner
    Höybye, Charlotte
    Lundberg, Elena
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Battelino, Tadej
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Giemza, Tomasz
    Zouater, Hichem
    Safety and Effectiveness of Recombinant Human Growth Hormone in Children with Turner Syndrome: Data from the PATRO Children Study2021Inngår i: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 94, nr 3-4, s. 133-143Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: PATRO Children is an international, observational, postmarketing surveillance study for a biosimilar recombinant human growth hormone (rhGH; somatropin, Omnitrope (R); Sandoz), approved by the European Medicines Agency in 2006. We report safety and effectiveness data for patients with Turner syndrome (TS).

    Methods: The study population included infants, children, and adolescents with TS who received Omnitrope (R) treatment according to standard clinical practice. Adverse events (AEs) were monitored for safety evaluation, and height velocity (HV), height standard deviation score (HSDS), and HVSDS were calculated to evaluate treatment effectiveness.

    Results: As of August 2019, 348 TS patients were enrolled from 130 centers. At baseline, 314 patients (90.2%) were prepubertal and 284 patients (81.6%) were rhGH treatment naive. The mean ( range) age at baseline was 9.0 (0.7-18.5) years, and mean (SD) treatment duration in the study was 38.5 (26.8) months. Overall, 170 patients (48.9%) reported AEs, which were considered treatment related in 25 patients (7.2%). One treatment-related serious AE was reported (intracranial hypertension). Mean.HSDS after 3 years of therapy was +1.17 in treatment-naive prepubertal patients and +0.1 in pretreated prepubertal patients. In total, 51 patients (31.1%) reached adult height (AH), 35 of whom were rhGH treatment naive; in these patients, mean (SD) HSDS was -2.97 (1.03) at the start of Omnitrope (R) treatment, and they achieved a mean (SD) AHSDS of -2.02 (0.9).

    Conclusion: These data suggest that biosimilar rhGH is well tolerated and effective in TS patients managed in reallife clinical practice. Optimization of rhGH dose may contribute to a higher AH. (C) 2021 S. Karger AG, Basel

    Fulltekst (pdf)
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  • 35.
    Backeström, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Eriksson, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nilsson, Lars-Göran
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Glucose but not insulin or insulin resistance is associated with memory performance in middle-aged non-diabetic women: a cross sectional study2015Inngår i: Diabetology & Metabolic Syndrome, E-ISSN 1758-5996, Vol. 7, artikkel-id 20Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Elevated concentrations of plasma glucose appear to play a role in memory impairment, and it has been suggested that insulin might also have a negative effect on cognitive function. Our aim was to study whether glucose, insulin or insulin resistance are associated with episodic or semantic memory in a non-diabetic and non-demented population. 

    Methods: We linked and matched two population-based data sets identifying 291 participants (127 men and 164 women, mean age of 50.7 +/- 8.0 years). Episodic and semantic memory functions were tested, and fasting plasma insulin, fasting plasma glucose, and 2-hour glucose were analysed along with other potential influencing factors on memory function. Since men and women display different results on memory functions they were analysed separately. Insulin resistance was calculated using the HOMA-IR method. 

    Results: A higher fasting plasma glucose concentration was associated with lower episodic memory in women (r = -0.08, 95% CI -0.14; -0.01), but not in men. Plasma insulin levels and insulin resistance were not associated with episodic or semantic memory in women or in men after adjustments for age, fasting glucose, 2-hour glucose, BMI, education, smoking, cardiovascular disease, hypertension, cholesterol, and physical activity. 

    Conclusions: This indicates that fasting glucose but not insulin, might have impact on episodic memory in middle-aged women.

    Fulltekst (pdf)
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  • 36.
    Backeström, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Papadopoulos, Konstantin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Eriksson, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Blennow, Kaj
    Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at University of Gothenburg, Mö lndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mö lndal, Sweden.
    Zetterberg, Henrik
    Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mö lndal, Sweden; Department of Neurodegenerative Disease, Ucl Institute of Neurology, Queen Square, London, United Kingdom; UK Dementia Research Institute at Ucl, London, United Kingdom.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Acute hyperglycaemia leads to altered frontal lobe brain activity and reduced working memory in type 2 diabetes2021Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 16, nr 3, artikkel-id e0247753Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    How acute hyperglycaemia affects memory functions and functional brain responses in individuals with and without type 2 diabetes is unclear. Our aim was to study the association between acute hyperglycaemia and working, semantic, and episodic memory in participants with type 2 diabetes compared to a sex- A nd age-matched control group. We also assessed the effect of hyperglycaemia on working memory-related brain activity. A total of 36 participants with type 2 diabetes and 34 controls (mean age, 66 years) underwent hyperglycaemic clamp or placebo clamp in a blinded and randomised order. Working, episodic, and semantic memory were tested. Overall, the control group had higher working memory (mean z-score 33.15 ± 0.45) than the group with type 2 diabetes (mean z-score 31.8 ± 0.44, p = 0.042) considering both the placebo and hyperglycaemic clamps. Acute hyperglycaemia did not influence episodic, semantic, or working memory performance in either group. Twenty-two of the participants (10 cases, 12 controls, mean age 69 years) were randomly invited to undergo the same clamp procedures to challenge working memory, using 1-, 2-, and 3-back, while monitoring brain activity by blood oxygen level-dependent functional magnetic resonance imaging (fMRI). The participants with type 2 diabetes had reduced working memory during the 1- A nd 2-back tests. fMRI during placebo clamp revealed increased BOLD signal in the left lateral frontal cortex and the anterior cingulate cortex as a function of working memory load in both groups (3>2>1). During hyperglycaemia, controls showed a similar load-dependent fMRI response, whereas the type 2 diabetes group showed decreased BOLD response from 2-to 3-back. These results suggest that impaired glucose metabolism in the brain affects working memory, possibly by reducing activity in important frontal brain areas in persons with type 2 diabetes.

    Fulltekst (pdf)
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  • 37.
    Backman, Olof
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Bruze, Gustaf
    Naslund, Ingmar
    Ottosson, Johan
    Marsk, Richard
    Neovius, Martin
    Naslund, Erik
    Gastric Bypass Surgery Reduces De Novo Cases of Type 2 Diabetes to Population Levels A Nationwide Cohort Study From Sweden2019Inngår i: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 269, nr 5, s. 895-902Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: The aim of this study was to determine long-term changes in pharmacological treatment of type 2 diabetes after primary Roux-en-Y gastric bypass (RYGB) surgery, in patients with and without pharmacological treatment of diabetes preoperatively.

    Summary of Background Data: Several studies have shown that gastric bypass has good effect on diabetes, at least in the short-term. This study is a nationwide cohort study using Swedish registers, with basically no patients lost to follow-up during up to 7 years after surgery.

    Methods: The effect of RYGB on type 2 diabetes drug treatment was evaluated in this nationwide matched cohort study. Participants were 22,047 adults with BMI ≥30 identified in the nationwide Scandinavian Surgical Obesity Registry, who underwent primary RYGB between 2007 and 2012. For each individual, up to 10 general population comparators were matched on birth year, sex, and place of residence. Prescription data were retrieved from the nationwide Swedish Prescribed Drug Register through September 2015. Incident use of pharmacological treatment was analyzed using Cox regression.

    Results: Sixty-seven percent of patients with pharmacological treatment of type 2 diabetes before surgery were not using diabetes drugs 2 years after surgery and 61% of patients were not pharmacologically treated up to 7 years after surgery. In patients not using diabetes drugs at baseline, there were 189 new cases of pharmacological treatment of type 2 diabetes in the surgery group and 2319 in the matched general population comparators during a median follow-up of 4.6 years (incidence: 21.4 vs 27.9 per 10,000 person-years; adjusted hazard ratio 0.77, 95% confidence interval 0.67–0.89; P < 0.001).

    Conclusions: Gastric bypass surgery not only induces remission of pharmacological treatment of type 2 diabetesbut also protects from new onset of pharmacological diabetes treatment. The effect seems to persist in most, but not all, patients over 7 years of follow-up.

  • 38.
    Badian, Reza A.
    et al.
    Department of Medical Biochemistry, Unit of Regenerative Medicine, Oslo University Hospital, Oslo, Norway.
    Ekman, Linnéa
    Department of Translational Medicine, Hand Surgery, Lund University, Malmöo, Sweden.
    Pripp, Are Hugo
    Oslo Centre of Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital, Oslo, Norway.
    Utheim, Tor Paaske
    Department of Ophthalmology, Oslo University Hospital, Oslo, Norway; Department of Ophthalmology, Sørlandet Hospital Arendal, Arendal, Norway.
    Englund, Elisabet
    Department of Clinical Sciences, Pathology, Lund University, Lund, Sweden.
    Dahlin, Lars B.
    Department of Translational Medicine, Hand Surgery, Lund University, Malmöo, Sweden; Department of Biomedical and Clinical Sciences, Linköoping University, Linköoping, Sweden; Department of Hand Surgery, Skåne University Hospital, Malmöo, Sweden.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Lagali, Neil
    Department of Ophthalmology, Sørlandet Hospital Arendal, Arendal, Norway; Department of Biomedical and Clinical Sciences, Linköoping University, Linköoping, Sweden.
    Comparison of novel wide-field in vivo corneal confocal microscopy with skin biopsy for assessing peripheral neuropathy in type 2 diabetes2023Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 72, nr 7, s. 908-917Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Diabetic peripheral neuropathy (DPN) is a serious complication of diabetes, where skin biopsy assessing intraepi-dermal nerve fiber density (IENFD) plays an important diagnostic role. In vivo confocal microscopy (IVCM) of the corneal subbasal nerve plexus has been proposed as a noninvasive diagnostic modality for DPN. Direct compari-sons of skin biopsy and IVCM in controlled cohorts are lacking, as IVCM relies on subjective selection of images depicting only 0.2% of the nerve plexus. We compared these diagnostic modalities in a fixed-age cohort of 41 participants with type 2 diabetes and 36 healthy participants using machine algorithms to create wide-field image mosaics and quantify nerves in an area 37 times the size of prior studies to avoid human bias. In the same partici-pants, and at the same time point, no correlation between IENFD and corneal nerve density was found. Corneal nerve density did not correlate with clinical measures of DPN, including neuropathy symptom and disability scores, nerve conduction studies, or quantitative sensory tests. Our findings indicate that corneal and intraepidermal nerves likely mirror different aspects of nerve degeneration, where only intraepidermal nerves appear to reflect the clinical status of DPN, suggesting that scrutiny is warranted concerning methodologies of studies using corneal nerves to assess DPN.

  • 39.
    Ballin, Marcel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Niklasson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Alamäki, Antti
    Condell, Joan
    Tedesco, Salvatore
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa. School of Sport Sciences, UiT the Arctic University of Norway, Tromsø, Norway.
    Daily step count and incident diabetes in community-dwelling 70-year-olds: a prospective cohort study2020Inngår i: BMC Public Health, E-ISSN 1471-2458, Vol. 20, nr 1, artikkel-id 1830Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Older adults with diabetes take fewer steps per day than those without diabetes. The purpose of the present study was to investigate the association of daily step count with incident diabetes in community-dwelling 70-year-olds.

    Methods: This prospective cohort study included N = 3055 community-dwelling 70-year-olds (52% women) who participated in a health examination in Umeå, Sweden during 2012–2017, and who were free from diabetes at baseline. Daily step count was measured for 1 week using Actigraph GT3X+ accelerometers. Cases of diabetes were collected from the Swedish National Patient Register. The dose-response association was evaluated graphically using a flexible parametric model, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox regressions.

    Results: During a mean follow-up of 2.6 years, diabetes was diagnosed in 81 participants. There was an inverse nonlinear dose-response association between daily step count and incident diabetes, with a steep decline in risk of diabetes from a higher daily step count until around 6000 steps/day. From there, the risk decreased at a slower rate until it leveled off at around 8000 steps/day. A threshold of 4500 steps/day was found to best distinguish participants with the lowest risk of diabetes, where those taking ≥ 4500 steps/day, had 59% lower risk of diabetes, compared to those taking fewer steps (HR, 0.41, 95% CI, 0.25–0.66). Adjusting for visceral adipose tissue (VAT) attenuated the association (HR, 0.64, 95% CI, 0.38–1.06), which was marginally altered after further adjusting for sedentary time, education and other cardiometabolic risk factors and diseases (HR, 0.58, 95% CI, 0.32–1.05).

    Conclusions: A higher daily step count is associated with lower risk of incident diabetes in community-dwelling 70-year-olds. The greatest benefits occur at the lower end of the activity range, and much earlier than 10,000 steps/day. With the limitation of being an observational study, these findings suggest that promoting even a modest increase in daily step count may help to reduce the risk of diabetes in older adults. Because VAT appears to partly mediate the association, lifestyle interventions targeting diabetes should apart from promoting physical activity also aim to prevent and reduce central obesity.

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  • 40.
    Bang, P
    et al.
    Department of Women’s and Children’s Health, Karolinska Institute and University Hospital, Stockholm, Sweden.
    Bjerknes, R
    Department of Clinical Medicine, Section for Pediatrics, University of Bergen, Norway.
    Dahlgren, J
    Department of Pediatrics, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Dunkel, L
    Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland.
    Gustafsson, J
    Department of Women’s and Children’s Health, University of Uppsala, Sweden.
    Juul, A
    Department of Growth and Reproduction, University of Copenhagen, Denmark.
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Tapanainen, P
    Department of Pediatrics and Adolescence, University of Oulu, Finland.
    Åberg, V
    Institut Produits Synthèse (IPSEN) AB, Kista, Sweden.
    A comparison of different definitions of growth response in short prepubertal children treated with growth hormone2011Inngår i: Hormone research in paediatrics, ISSN 1663-2826, Vol. 75, nr 5, s. 335-345Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: How to define poor growth response in the management of short growth hormone (GH)-treated children is controversial.

    Aim: Assess various criteria of poor response.

    Subjects and Methods: Short GH-treated prepubertal children [n = 456; height (Ht) SD score (SDS) ≤-2] with idiopathic GH deficiency (IGHD, n = 173), idiopathic short stature (ISS, n = 37), small for gestational age (SGA, n = 54), organic GHD (OGHD, n = 40), Turner syndrome (TS, n = 43), skeletal dysplasia (n = 15), other diseases (n = 46) or syndromes (n = 48) were evaluated in this retrospective multicenter study. Median age at GH start was 6.3 years and Ht SDS -3.2.

    Results: Median [25-75 percentile] first-year gain in Ht SDS was 0.65 (0.40-0.90) and height velocity (HtV) 8.67 (7.51-9.90) cm/year. Almost 50% of IGHD children fulfilled at least one criterion for poor responders. In 28% of IGHD children, Ht SDS gain was <0.5 and they had lower increases in median IGF-I SDS than those with Ht SDS >0.5. Only IGHD patients with peak stimulated growth hormone level <3 μg/l responded better than those with ISS. A higher proportion of children with TS, skeletal dysplasia or born SGA had Ht SDS gain <0.5.

    Conclusion: Many children respond poorly to GH therapy. Recommendations defining a criterion may help in managing short stature patients.

  • 41.
    Barbera, Mariagnese
    et al.
    Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1C, Kuopio, Finland; The Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, Charing Cross Hospital, St Dunstan’s Road, London, United Kingdom.
    Lehtisalo, Jenni
    Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1C, Kuopio, Finland; Population Health Unit, Finnish Institute for Health and Welfare, Mannerheimintie 166, P.O. Box 30, Helsinki, Finland.
    Perera, Dinithi
    The Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, Charing Cross Hospital, St Dunstan’s Road, London, United Kingdom; FINGERS Brain Health Institute, C/O Stockholms Sjukhem, Box 122 30, Stockholm, Sweden.
    Aspö, Malin
    Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska Vägen 37A, Solna, Sweden; Theme Inflammation and Aging, Medical Unit Aging, Karolinska University Hospital, Karolinska Vägen 37A, Solna, Sweden.
    Cross, Mary
    Imperial Clinical Trials Unit, School of Public Health, Faculty of Medicine, Imperial College London, Imperial College London, Stadium House, 68 Wood Lane, London, United Kingdom.
    De Jager Loots, Celeste A.
    The Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, Charing Cross Hospital, St Dunstan’s Road, London, United Kingdom.
    Falaschetti, Emanuela
    Imperial Clinical Trials Unit, School of Public Health, Faculty of Medicine, Imperial College London, Imperial College London, Stadium House, 68 Wood Lane, London, United Kingdom.
    Friel, Naomi
    The Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, Charing Cross Hospital, St Dunstan’s Road, London, United Kingdom.
    Luchsinger, José A.
    Departments of Medicine and Epidemiology, Columbia University Irving Medical Center, 622 W 168Th St, NY, New York, United States.
    Malmberg Gavelin, Hanna
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Peltonen, Markku
    Population Health Unit, Finnish Institute for Health and Welfare, Mannerheimintie 166, P.O. Box 30, Helsinki, Finland; FINGERS Brain Health Institute, C/O Stockholms Sjukhem, Box 122 30, Stockholm, Sweden.
    Price, Geraint
    The Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, Charing Cross Hospital, St Dunstan’s Road, London, United Kingdom.
    Neely, Anna Stigsdotter
    Department of Social and Psychological Studies, Karlstad University, Karlstad, Sweden; Department of Health, Education and Technology, Luleå University of Technology, 971 87, Luleå, Sweden.
    Thunborg, Charlotta
    Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska Vägen 37A, Solna, Sweden; Theme Inflammation and Aging, Medical Unit Aging, Karolinska University Hospital, Karolinska Vägen 37A, Solna, Sweden.
    Tuomilehto, Jaakko
    Population Health Unit, Finnish Institute for Health and Welfare, Mannerheimintie 166, P.O. Box 30, Helsinki, Finland; Department of Public Health, University of Helsinki, PO BOX 20, Helsinki, Finland; Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
    Mangialasche, Francesca
    FINGERS Brain Health Institute, C/O Stockholms Sjukhem, Box 122 30, Stockholm, Sweden; Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska Vägen 37A, Solna, Sweden; Theme Inflammation and Aging, Medical Unit Aging, Karolinska University Hospital, Karolinska Vägen 37A, Solna, Sweden.
    Middleton, Lefkos
    The Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, Charing Cross Hospital, St Dunstan’s Road, London, United Kingdom; Directorate of Public Health, Imperial College NHS Healthcare Trust Hospitals, Praed Street, London, United Kingdom.
    Ngandu, Tiia
    Population Health Unit, Finnish Institute for Health and Welfare, Mannerheimintie 166, P.O. Box 30, Helsinki, Finland; Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska Vägen 37A, Solna, Sweden.
    Solomon, Alina
    Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1C, Kuopio, Finland; The Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, Charing Cross Hospital, St Dunstan’s Road, London, United Kingdom; Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska Vägen 37A, Solna, Sweden.
    Kivipelto, Miia
    The Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, Charing Cross Hospital, St Dunstan’s Road, London, United Kingdom; Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska Vägen 37A, Solna, Sweden; Theme Inflammation and Aging, Medical Unit Aging, Karolinska University Hospital, Karolinska Vägen 37A, Solna, Sweden; Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Yliopistonranta 1C, Kuopio, Finland.
    A multimodal precision-prevention approach combining lifestyle intervention with metformin repurposing to prevent cognitive impairment and disability: the MET-FINGER randomised controlled trial protocol2024Inngår i: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 16, nr 1, artikkel-id 23Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Combining multimodal lifestyle interventions and disease-modifying drugs (novel or repurposed) could provide novel precision approaches to prevent cognitive impairment. Metformin is a promising candidate in view of the well-established link between type 2 diabetes (T2D) and Alzheimer's Disease and emerging evidence of its potential neuro-protective effects (e.g. vascular, metabolic, anti-senescence). MET-FINGER aims to test a FINGER 2.0 multimodal intervention, combining an updated FINGER multidomain lifestyle intervention with metformin, where appropriate, in an APOE ε4-enriched population of older adults (60–79 years) at increased risk of dementia.

    Methods: MET-FINGER is an international randomised, controlled, parallel-group, phase-IIb proof-of-concept clinical trial, where metformin is included through a trial-within-trial design. 600 participants will be recruited at three sites (UK, Finland, Sweden). Participants at increased risk of dementia based on vascular risk factors and cognitive screening, will be first randomised to the FINGER 2.0 intervention (lifestyle + metformin if eligible; active arm) or to receive regular health advice (control arm). Participants allocated to the FINGER 2.0 intervention group at risk indicators of T2D will be additionally randomised to receive metformin (2000 mg/day or 1000 mg/day) or placebo. The study duration is 2 years. The changes in global cognition (primary outcome, using a Neuropsychological Test Battery), memory, executive function, and processing speed cognitive domains; functional status; lifestyle, vascular, metabolic, and other dementia-related risk factors (secondary outcomes), will be compared between the FINGER 2.0 intervention and the control arm. The feasibility, potential interaction (between-groups differences in healthy lifestyle changes), and disease-modifying effects of the lifestyle-metformin combination will be exploratory outcomes. The lifestyle intervention is adapted from the original FINGER trial (diet, physical activity, cognitive training, monitoring of cardiovascular/metabolic risk factors, social interaction) to be consistently delivered in three countries. Metformin is administered as Glucophage®XR/SR 500, (500 mg oral tablets). The metformin/placebo treatment will be double blinded.

    Conclusion: MET-FINGER is the first trial combining a multimodal lifestyle intervention with a putative repurposed disease-modifying drug for cognitive impairment prevention. Although preliminary, its findings will provide crucial information for innovative precision prevention strategies and form the basis for a larger phase-III trial design and future research in this field.

    Trial registration: ClinicalTrials.gov (NCT05109169).

    Fulltekst (pdf)
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  • 42. Barkhordari, Mahnaz
    et al.
    Padyab, Mojgan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Sardarinia, Mahsa
    Hadaegh, Farzad
    Azizi, Fereidoun
    Bozorgmanesh, Mohammadreza
    Survival Regression Modeling Strategies in CVD Prediction2016Inngår i: International journal of endocrinology and metabolism, ISSN 1726-9148, Vol. 14, nr 2, artikkel-id e32156Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: A fundamental part of prevention is prediction. Potential predictors are the sine qua non of prediction models. However, whether incorporating novel predictors to prediction models could be directly translated to added predictive value remains an area of dispute. The difference between the predictive power of a predictive model with (enhanced model) and without (baseline model) a certain predictor is generally regarded as an indicator of the predictive value added by that predictor. Indices such as discrimination and calibration have long been used in this regard. Recently, the use of added predictive value has been suggested while comparing the predictive performances of the predictive models with and without novel biomarkers. Objectives: User-friendly statistical software capable of implementing novel statistical procedures is conspicuously lacking. This shortcoming has restricted implementation of such novel model assessment methods. We aimed to construct Stata commands to help researchers obtain the aforementioned statistical indices. Materials and Methods: We have written Stata commands that are intended to help researchers obtain the following. 1, Nam-D'Agostino X-2 goodness of fit test; 2, Cut point-free and cut point-based net reclassification improvement index (NRI), relative absolute integrated discriminatory improvement index (IDI), and survival-based regression analyses. We applied the commands to real data on women participating in the Tehran lipid and glucose study (TLGS) to examine if information relating to a family history of premature cardiovascular disease (CVD), waist circumference, and fasting plasma glucose can improve predictive performance of Framingham's general CVD risk algorithm. Results: The command is adpredsurv for survival models. Conclusions: Herein we have described the Stata package "adpredsurv" for calculation of the Nam-D'Agostino X2 goodness of fit test as well as cut point-free and cut point-based NRI, relative and absolute IDI, and survival-based regression analyses. We hope this work encourages the use of novel methods in examining predictive capacity of the emerging plethora of novel biomarkers.

    Fulltekst (pdf)
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  • 43.
    Belsti, Yitayeh
    et al.
    Monash Centre for Health Research and Implementation (MCHRI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia; University of Gondar, College of Medicine and Health Science, Ethiopia.
    Moran, Lisa
    Monash Centre for Health Research and Implementation (MCHRI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.
    Du, Lan
    Monash University, Faculty of Information Technology.
    Mousa, Aya
    Monash Centre for Health Research and Implementation (MCHRI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.
    De Silva, Kushan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Enticott, Joanne
    Monash Centre for Health Research and Implementation (MCHRI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.
    Teede, Helena
    Monash Centre for Health Research and Implementation (MCHRI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia; Monash Health, Melbourne, Australia.
    Comparison of machine learning and conventional logistic regression-based prediction models for gestational diabetes in an ethnically diverse population: the Monash GDM Machine learning model2023Inngår i: International Journal of Medical Informatics, ISSN 1386-5056, E-ISSN 1872-8243, Vol. 179, artikkel-id 105228Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Early identification of pregnant women at high risk of developing gestational diabetes (GDM) is desirable as effective lifestyle interventions are available to prevent GDM and to reduce associated adverse outcomes. Personalised probability of developing GDM during pregnancy can be determined using a risk prediction model. These models extend from traditional statistics to machine learning methods; however, accuracy remains sub-optimal.

    Objective: We aimed to compare multiple machine learning algorithms to develop GDM risk prediction models, then to determine the optimal model for predicting GDM.

    Methods: A supervised machine learning predictive analysis was performed on data from routine antenatal care at a large health service network from January 2016 to June 2021. Predictor set 1 were sourced from the existing, internationally validated Monash GDM model: GDM history, body mass index, ethnicity, age, family history of diabetes, and past poor obstetric history. New models with different predictors were developed, considering statistical principles with inclusion of more robust continuous and derivative variables. A randomly selected 80% dataset was used for model development, with 20% for validation. Performance measures, including calibration and discrimination metrics, were assessed. Decision curve analysis was performed.

    Results: Upon internal validation, the machine learning and logistic regression model's area under the curve (AUC) ranged from 71% to 93% across the different algorithms, with the best being the CatBoost Classifier (CBC). Based on the default cut-off point of 0.32, the performance of CBC on predictor set 4 was: Accuracy (85%), Precision (90%), Recall (78%), F1-score (84%), Sensitivity (81%), Specificity (90%), positive predictive value (92%), negative predictive value (78%), and Brier Score (0.39).

    Conclusions: In this study, machine learning approaches achieved the best predictive performance over traditional statistical methods, increasing from 75 to 93%. The CatBoost classifier method achieved the best with the model including continuous variables.

    Fulltekst (pdf)
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  • 44.
    Benckert, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lilja, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Eliasson, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Improved metabolic health among the obesein six population surveys 1986 to 2009: the Northern Sweden MONICA study2015Inngår i: BMC Obesity, ISSN 2052-9538, Vol. 2, nr 7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    The incidence of CVD is decreasing in spite of increasing BMI in the population. We examined trends in metabolic health among overweight and obese individuals and the influence of lifestyle and socioeconomic status. Six cross sectional population surveys in the Northern Sweden MONICA Study between 1986 and 2009. 8 874 subjects 25 to 64 years participated (74% participation rate). Metabolic health was defined as a total cholesterol level below 5.0 mmol/l, blood pressure below 140/90 mmHg and not having diabetes. In 2009 the age span 25 to 74 years was studied.

    Results

    The prevalence of metabolic health among obese subjects increased by 7.9 % per year (95% confidence interval 5.4; 10.5), reaching 21.0% in 2009. The corresponding figures for overweight subjects were 5.9% per year (4.6; 7.3), reaching 18% in 2009, whereas for the normal-weight subjects, the increase was 6.2% per year (5.3; 7.2), reaching 39% in 2009. The prevalence of metabolic health among subjects with abdominal obesity increased by 5.8% (4.6; 7.0) per year, reaching 17.3% in 2009. Among those with no abdominal obesity the increase was 6.2% (5.2; 7.1), reaching 38% in 2009 (p = <0.001 for all groups). Only among non-obese men and obese women did the increase continue between 2004 and 2009. In the other groups a slight decline or levelling off was noted.

    In 2009 women had a 27% higher prevalence of metabolic health than men. The prevalence of metabolic health among the obese was 19.8% which declined to 15.8% if subjects treated for hypertension or hypercholesterolemia were classified as not healthy. Overweight and obese subjects were less often metabolically healthy (odds ratio 0.54 and 0.59 respectively) compared with normal-weight subjects, independent of sex and age as were subjects with abdominal obesity (odds ratio 0.52). Adjustments for smoking, physical activity and education level did not influence any estimates.

    Conclusions

    This report shows a large increase in prevalence of metabolic health from 1986 to 2009 for all anthropometric categories. Metabolic health remains considerably less prevalent among overweight and obese subjects than among those with normal weight.

    Fulltekst (pdf)
    fulltext
  • 45. Bendinelli, B.
    et al.
    Palli, D.
    Masala, G.
    Sharp, S. J.
    Schulze, M. B.
    Guevara, M.
    van der A, D. L.
    Sera, F.
    Amiano, P.
    Balkau, B.
    Barricarte, A.
    Boeing, H.
    Crowe, F. L.
    Dahm, C. C.
    Dalmeijer, G.
    de Lauzon-Guillain, B.
    Egeberg, R.
    Fagherazzi, G.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden.
    Krogh, V.
    Huerta, J. M.
    Jakszyn, P.
    Khaw, K. T.
    Li, K.
    Mattiello, A.
    Nilsson, P. M.
    Overvad, K.
    Ricceri, F.
    Rodríguez-Suárez, L.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Sánchez, M. J.
    Slimani, N.
    Sluijs, I.
    Spijkerman, A. M. W.
    Teucher, B.
    Tjonneland, A.
    Tumino, R.
    van den Berg, S. W.
    Forouhi, N. G.
    Langenberg, C.
    Feskens, E. J. M.
    Riboli, E.
    Wareham, N. J.
    Association between dietary meat consumption and incident type 2 diabetes: the EPIC-InterAct study2013Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, nr 1, s. 47-59Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims/hypothesis: A diet rich in meat has been reported to contribute to the risk of type 2 diabetes. The present study aims to investigate the association between meat consumption and incident type 2 diabetes in the EPIC-InterAct study, a large prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

    Methods: During 11.7 years of follow-up, 12,403 incident cases of type 2 diabetes were identified among 340,234 adults from eight European countries. A centre-stratified random subsample of 16,835 individuals was selected in order to perform a case-cohort design. Prentice-weighted Cox regression analyses were used to estimate HR and 95% CI for incident diabetes according to meat consumption.

    Results: Overall, multivariate analyses showed significant positive associations with incident type 2 diabetes for increasing consumption of total meat (50 g increments: HR 1.08; 95% CI 1.05, 1.12), red meat (HR 1.08; 95% CI 1.03, 1.13) and processed meat (HR 1.12; 95% CI 1.05, 1.19), and a borderline positive association with meat iron intake. Effect modifications by sex and class of BMI were observed. In men, the results of the overall analyses were confirmed. In women, the association with total and red meat persisted, although attenuated, while an association with poultry consumption also emerged (HR 1.20; 95% CI 1.07, 1.34). These associations were not evident among obese participants.

    Conclusions/interpretation: This prospective study confirms a positive association between high consumption of total and red meat and incident type 2 diabetes in a large cohort of European adults.

  • 46.
    Bendix, Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Uvnäs-Moberg, Kerstin
    Petersson, Maria
    Kaldo, Viktor
    Åsberg, Marie
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Insulin and glucagon in plasma and cerebrospinal fluid in suicide attempters and healthy controls2017Inngår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 81, s. 1-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mental disorders and related behaviors such as suicidality and violence have been associated to dysregulation of e g carbohydrate metabolism. We hypothesized that patients after suicide attempt, compared to healthy controls, would have higher insulin and lower glucagon levels in plasma and cerebrospinal fluid and that these changes would be associated to violent behavior. Twenty-eight medication-free patients (10 women, 18 men), hospitalized after suicide attempt, and 19 healthy controls (7 women, 12 men) were recruited with the aim to study risk factors for suicidal behavior. Psychological/psychiatric assessment was performed with SCID I and II or the SCID interview for healthy volunteers respectively, the Karolinska Interpersonal Violence Scale (KIVS) for assessment of lifetime violence expression behavior, the Montgomery-Asberg-Depression-Scale (MADRS) and the Comprehensive Psychological Rating Scale (CPRS) for symptomatic assessment of depression and appetite. Fasting levels of insulin and glucagon were measured in plasma (P) and cerebrospinal fluid (CSF). Suicide attempters had higher insulin- and lower glucagon-levels in plasma- and CSF compared to controls. Except for P-glucagon these associations remained significant after adjusting for age and/or BMI. Patients reported significantly more expressed interpersonal violence compared to healthy volunteers. Expressed violence was significantly positively correlated with P- and CSF-insulin and showed a significant negative correlation with P-glucagon in study participants. These findings confirm and extend prior reports that higher insulin and lower glucagon levels in plasma and cerebrospinal fluid are associated with suicidal behavior pointing towards a potential autonomic dysregulation in the control of insulin and glucagon secretion in suicidal patients. 

  • 47. Benetou, V
    et al.
    Orfanos, P
    Pettersson-Kymmer, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Bergström, Ulrica
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Kariologi.
    Berrino, F
    Tumino, R
    Borch, K B
    Lund, E
    Peeters, P H M
    Grote, V
    Li, K
    Altzibar, J M
    Key, T
    Boeing, H
    von Ruesten, A
    Norat, T
    Wark, P A
    Riboli, E
    Trichopoulou, A
    Mediterranean diet and incidence of hip fractures in a European cohort2013Inngår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 24, nr 5, s. 1587-1598Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Prevention of hip fractures is of critical public health importance. In a cohort of adults from eight European countries, evidence was found that increased adherence to Mediterranean diet, measured by a 10-unit dietary score, is associated with reduced hip fracture incidence, particularly among men. INTRODUCTION: Evidence on the role of dietary patterns on hip fracture incidence is scarce. We explored the association of adherence to Mediterranean diet (MD) with hip fracture incidence in a cohort from eight European countries. METHODS: A total of 188,795 eligible participants (48,814 men and 139,981 women) in the European Prospective Investigation into Cancer and nutrition study with mean age 48.6 years (±10.8) were followed for a median of 9 years, and 802 incident hip fractures were recorded. Diet was assessed at baseline through validated dietary instruments. Adherence to MD was evaluated by a MD score (MDs), on a 10-point scale, in which monounsaturated were substituted with unsaturated lipids. Association with hip fracture incidence was assessed through Cox regression with adjustment for potential confounders. RESULTS: Increased adherence to MD was associated with a 7 % decrease in hip fracture incidence [hazard ratio (HR) per 1-unit increase in the MDs 0.93; 95 % confidence interval (95 % CI) = 0.89-0.98]. This association was more evident among men and somewhat stronger among older individuals. Using increments close to one standard deviation of daily intake, in the overall sample, high vegetable (HR = 0.86; 95 % CI = 0.79-0.94) and high fruit (HR = 0.89; 95 % CI = 0.82-0.97) intake was associated with decreased hip fracture incidence, whereas high meat intake (HR = 1.18; 95 % CI = 1.06-1.31) with increased incidence. Excessive ethanol consumption (HR high versus moderate = 1.74; 95 % CI = 1.32-2.31) was also a risk factor. CONCLUSIONS: In a prospective study of adults, increased adherence to MD appears to protect against hip fracture occurrence, particularly among men.

  • 48.
    Bengtsson, Daniel
    et al.
    Department Of Biomedical And Clinical Sciences, Linköping University, Linköping, Sweden.
    Ragnarsson, Oskar
    Department Of Internal Medicine And Clinical Nutrition, Institute Of Medicine, Sahlgrenska Academy, University Of Gothenburg, Gothenburg, Sweden; Department Of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Berinder, Katarina
    Department Of Endocrinology, Karolinska University Hospital, Stockholm, Sweden; Department Of Molecular Medicine And Surgery, Karolinska Institutet, Stockholm, Sweden.
    Dahlqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Edén Engström, Britt
    Department Of Medical Sciences Endocrinology And Mineral Metabolism, Uppsala University, Uppsala, Sweden; Department Of Endocrinology And Diabetes, Uppsala University Hospital, Uppsala, Sweden.
    Ekman, Bertil
    Department Of Endocrinology, Linköping University, Linköping, Sweden; Department Of Health Medicine And Caring Sciences, Linköping University, Linköping, Sweden.
    Höybye, Charlotte
    Department Of Endocrinology, Karolinska University Hospital, Stockholm, Sweden; Department Of Molecular Medicine And Surgery, Karolinska Institutet, Stockholm, Sweden.
    Järås, Jacob
    Regional Cancer Centre, Stockholm/Gotland, Stockholm, Sweden.
    Valdemarsson, Stig
    Department Of Clinical Sciences, Skåne University Hospital, University Of Lund, Lund, Sweden.
    Burman, Pia
    Department Of Endocrinology, Skåne University Hospital, University Of Lund, Malmö, Sweden.
    Wahlberg, Jeanette
    Department Of Endocrinology, Linköping University, Linköping, Sweden; Department Of Health Medicine And Caring Sciences, Linköping University, Linköping, Sweden; Faculty Of Medical Sciences, Örebro University, Örebro, Sweden.
    Increased Mortality Persists after Treatment of Cushing's Disease: A Matched Nationwide Cohort Study2022Inngår i: Journal of the Endocrine Society, E-ISSN 2472-1972, Vol. 6, nr 6, artikkel-id bvac045Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Context: Whether biochemical remission normalizes life expectancy in Cushing's disease (CD) patients remains unclear. Previous studies evaluating mortality in CD are limited by using the expected number of deaths in the background population instead of the actual number in matched controls. Objective and setting: To study mortality by time-to-event analysis in an unselected nationwide CD patient cohort. Design and participants: Longitudinal data from the Swedish Pituitary Register of 371 patients diagnosed with CD from 1991 to 2018 and information from the Swedish Cause of Death Register were evaluated. Four controls per patient (n = 1484) matched at the diagnosis date by age, sex, and residential area were included. Main outcome measures: Mortality and causes of death. Results: The median diagnosis age was 44 years (interquartile range 32-56), and the median follow-up was 10.6 years (5.7-18.0). At the 1-, 5-, 10-, 15-, and 20-year follow-ups, the remission rates were 80%, 92%, 96%, 91%, and 97%, respectively. Overall mortality was increased in CD patients compared with matched controls [hazard ratio (HR) 2.1 (95% CI 1.5-2.8)]. The HRs were 1.5 (1.02-2.2) for patients in remission at the last follow-up (n = 303), 1.7 (1.03-2.8) for those in remission after a single pituitary surgery (n = 177), and 5.6 (2.7-11.6) for those not in remission (n = 31). Cardiovascular diseases (32/66) and infections (12/66) were overrepresented causes of death. Conclusions: Mortality was increased in CD patients despite biochemical remission compared to matched controls. The study highlights the importance of careful comorbidity monitoring, regardless of remission status.

    Fulltekst (pdf)
    fulltext
  • 49.
    Bengtsson, Sara K. S.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Hedström, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Zingmark, Elisabeth
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Jonsson, Bjorn
    Bäckström, Torbjörn
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Isoallopregnanolone antagonize allopregnanolone-induced effects on saccadic eye velocity and self-reported sedation in humans2015Inngår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 52, s. 22-31Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Allopregnanolone (AP) is an endogenous neurosteroid. It modulates the effect of gamma-amino-butyric acid (GABA) on the GABA type A (GABA(A)) receptor, which leads to increased receptor activity. Since the GABA-system is mainly inhibitory, increased AP activity leads to modulation of neuronal activity. In vitro studies of GABA(A) receptor activity and in vivo animal studies of sedation have shown that AP-induced effects can be inhibited by another endogenous steroid, namely isoallopregnanolone (ISO). In this study we investigated if ISO can antagonize AP-induced effects in healthy female volunteers, via measurements of saccadic eye velocity (SEV) and self-rated sedation. With a single-blind cross-over design, 12 women were studied on three separate occasions; given AP alone or AP in combination with one of two ISO doses. Congruent with previous reports, AP administration decreased SEV and induced sedation and these effects were diminished by simultaneous ISO administration. Also, the ISO effect modulation was seemingly stronger for SEV than for sedation. These effects were observed already at an ISO dose exposure that was approximately half of that of AP. In conclusion, ISO antagonized AP-induced decrease in SEV and self-reported sedation, probably in a non-competitive manner.

  • 50. Bennet, L.
    et al.
    Lindblad, U.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    A family history of diabetes determines poorer glycaemic control and younger age of diabetes onset in immigrants from the Middle East compared with native Swedes2015Inngår i: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 41, nr 1, s. 45-54Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims. - Immigrant populations from the Middle East develop diabetes earlier than indigenous European populations; however, the underlying etiology is poorly understood. This study looked at the risk factors associated with early diabetes onset and, in non-diabetics, glycaemic control in immigrants from Iraq compared with native Swedes.

    Methods. - This cross-sectional population-based study comprised 1398 Iraqi immigrants and 757 Swedes (ages 30-75 years) residing in the same area of Malmo, Sweden. Outcomes were age at diabetes onset and glycaemic control (HbA(1c)) as assessed by Cox proportional hazards and linear regression, respectively.

    Results. - In Iraqis vs Swedes, clustering in the family history (in two or more relatives) was more prevalent (23.2% vs 3.6%, P<0.001) and diabetes onset occurred earlier (47.6 years vs 53.4 years, P=0.001). Having an Iraqi background independently raised the hazard ratio (HR) for diabetes onset. Diabetes risk due to family history was augmented by obesity, with the highest HRs observed in obese participants with clustering in the family history (HR: 5.1, 95% CI: 3.2-8.2) after adjusting for country of birth and gender. In participants without previously diagnosed diabetes (Iraqis: n=1270; Swedes: n=728), HbA(1c), levels were slightly higher in Iraqis than in Swedes (4.5% vs 4.4%, P=0.038). This difference was explained primarily by clustering in the family history rather than age, obesity, lifestyle or socioeconomic status.

    Conclusion. - The study shows that the greater predisposition to diabetes in Middle Eastern immigrants may be explained by a more extensive family history of the disorder; clinical interventions tailored to Middle Eastern immigrants with such a family history are thus warranted.

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