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  • 51.
    Lind, Torbjörn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Waernbaum, Ingeborg
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Berhan, Yonas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Socioeconomic factors, rather than diabetes mellitus per se, contribute to an excessive use of antidepressants among young adults with childhood onset type 1 diabetes mellitus: a register-based study2012In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 55, no 3, p. 617-624Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: Mood disorders, including depression, are suggested to be prevalent in persons with type 1 diabetes and may negatively affect self-management and glycaemic control and increase the risk of diabetic complications. The aim of this study was to analyse the prevalence of antidepressant (AD) use in adults with childhood onset type 1 diabetes and to compare risk determinants for AD prescription among diabetic patients and a group of matched controls. METHODS: Young adults ≥18 years on 1 January 2006 with type 1 diabetes (n = 7,411) were retrieved from the population-based Swedish Childhood Diabetes Registry (SCDR) and compared with 30,043 age- and community-matched controls. Individual level data were collected from the Swedish National Drug Register (NDR), the Hospital Discharge Register (HDR) and the Labor Market Research database (LMR). RESULTS: ADs were prescribed to 9.5% and 6.8% of the type 1 diabetes and control subjects, respectively. Female sex, having received economic or other social support, or having a disability pension were the factors with the strongest association with AD prescription in both groups. Type 1 diabetes was associated with a 44% (OR 1.44, 95% CI 1.32, 1.58) higher risk of being prescribed ADs in crude analysis. When adjusting for potential confounders including sex, age and various socioeconomic risk factors, this risk increase was statistically non-significant (OR 1.11, 95% CI 0.99, 1.21). CONCLUSIONS/INTERPRETATION: The risk factor patterns for AD use are similar among type 1 diabetic patients and controls, and socioeconomic risk factors, rather than the diabetes per se, contribute to the increased risk of AD use in young adults with type 1 diabetes.

  • 52. Lowe, R M
    et al.
    Graham, J
    Sund, G
    Kockum, I
    Landin-Olsson, M
    Schaefer, J B
    Törn, C
    Lernmark, A
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    The length of the CTLA-4 microsatellite (AT)N-repeat affects the risk for type 1 diabetes. Diabetes Incidence in Sweden Study Group.2000In: Autoimmunity, ISSN 0891-6934, E-ISSN 1607-842X, Vol. 32, no 3, p. 173-80Article in journal (Refereed)
    Abstract [en]

    CTLA-4 is important to down-regulating T cell responses and has been implicated in type 1 (insulin dependent) diabetes mellitus in both linkage and association studies. The aim of our study was to relate the polymorphic (AT)n microsatellite in the 3' untranslated sequence of the CTLA-4 gene to diabetes risk. We studied 616 consecutively diagnosed 0-34 year-old Swedish patients and 502 matched controls by PCR-based genotyping fo determine the length of the 3'-end (AT)n repeat region of the CTLA-4 gene and categorizing alleles as predominantly monomorphic short (S) or highly polymorphic (in length) long (L) alleles. The odds of type 1 diabetes of subjects with the L/L genotype was estimated to be 1.84 times that of subjects with the S/S genotype (95% CI 1.44-2.73, p=0.002). Further analysis of the long alleles, partitioned into intermediate (I) length and very long (VL) alleles, suggested that L alleles act recessively in conferring diabetes risk (p=0.0009). This study suggests that the 3'-end (AT)n repeat region of the CTLA-4 gene represents a recessive risk factor for type 1 diabetes.

  • 53.
    Lynöe, Niels
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Social medicine.
    Sandlund, Mikael
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Jacobsson, Lars
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Informed consent: study of quality of information given to participants in a clinical trial1991In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 303, no 6803, p. 610-613Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine whether the participants in a clinical trial had perceived adequate information about the trial according to the guidelines of the Declaration of Helsinki. DESIGN: About 18 months after the end of a gynaecological clinical trial the participants received a questionnaire by post, which focused on the quality of the information given to them before entering the trial. Neither researchers nor participants were aware in advance that the trial would become the subject of this follow up investigation. SETTING: Eight different centres in Sweden. SUBJECTS: 43 women out of the 53 who completed the trial (mean (range) age 23 (16 to 35) years) returned the questionnaire. MAIN OUTCOME MEASURES: Adequacy of the information (based on requirements of the Declaration of Helsinki) to enable the following: understanding of the aims of the study; awareness of what participation meant; and awareness of the possibility of withdrawing from participation at any time. Motives for agreeing to participate, and a subjective evaluation of the given information were also recorded. RESULTS: All but one of the participants had been aware that they were taking part in a research project. Five women stated that they had not been aware that a second laparoscopy was performed only for research reasons. Seven women reported that they had not been aware of the meaning of participating in the project and 17 that they had had no information about the possibility of withdrawing from the study whenever they wanted. In the subjective rating 22 women considered the information given as good or very good. There was a systematic variation in the quality of the given information among the eight centres. CONCLUSION: Although all but one of the participants had been aware that they were taking part in a clinical trial, the quality of the information understood and recalled by participants varied, and in many cases clearly did not meet the guidelines of the Declaration of Helsinki. Variations among centres in participants' perception of information suggest that deficiencies in perception may be caused by informers rather than the participants.

  • 54. Ma, J
    et al.
    Möllsten, A
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Prázny, M
    Falhammar, H
    Brismar, K
    Dahlquist, G
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Efendic, S
    Gu, H F
    Genetic influences of the intercellular adhesion molecule 1 (ICAM-1) gene polymorphisms in development of Type 1 diabetes and diabetic nephropathy.2006In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 23, no 10, p. 1093-1099Article in journal (Refereed)
    Abstract [en]

    AIM: The intercellular adhesion molecule-1 (ICAM-1) gene is located on chromosome 19p13, which is linked to Type 1 diabetes (T1D). ICAM-1 expression is related to development of T1D and diabetic nephropathy. The present study aims to evaluate the genetic influence of ICAM-1 gene polymorphisms on the development of T1D and diabetic nephropathy. METHODS: Five valid single nucleotide polymorphisms (SNPs) were genotyped in 432 T1D patients (196 patients had diabetic nephropathy) and 187 non-diabetic control subjects by using dynamic allele-specific hybridization (DASH) and pyrosequencing. RESULTS: SNPs rs281432(C/G) and rs5498 E469K(A/G) had high heterozygous indexes. They were significantly associated with T1D [P = 0.026, OR = 1.644 (95% CI 1.138-2.376) and P < 0.001, OR = 2.456 (1.588-3.8)]. Frequencies of the C allele in SNP rs281432(C/G) and the A allele in SNP rs5498 E469K(A/G) increased stepwise from non-diabetic control subjects to T1D patients without diabetic nephropathy and T1D patients with diabetic nephropathy. Further analysis for these two SNPs indicated that T1D patients had increased frequency of the common haplotype C-A, in comparison with non-diabetic control subjects (38.1 vs. 32.1%, P = 0.035). CONCLUSION: The present study provided evidence that SNPs rs281432(C/G) and rs5498 E469K(A/G) in the ICAM-1 gene confer susceptibility to the development of T1D and might also be associated with diabetic nephropathy in Swedish Caucasians.

  • 55. Ma, Jun
    et al.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Falhammar, Henrik
    Brismar, Kerstin
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Efendic, Suad
    Gu, Harvest F
    Genetic association analysis of the adiponectin polymorphisms in type 1 diabetes with and without diabetic nephropathy.2007In: J Diabetes Complications, ISSN 1056-8727, Vol. 21, no 1, p. 28-33Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Adiponectin [adipocyte C1q and collagen domain containing (ACDC)] is the most abundant adipose-specific protein. It is beneficial in that it improves insulin sensitivity and mitigates vascular damage, in addition to the possibility of it having anti-inflammatory properties. Clinical evidences demonstrate that serum adiponectin concentrations are increased in patients with type 1 diabetes (T1D) as well as in patients with microvascular complications. However, the genetic influence of the ACDC gene in T1D and diabetic microvascular complications is still unclear. The present study aims to evaluate the association of the ACDC genetic variation in T1D and diabetic nephropathy (DN). MATERIALS AND METHODS: Ten single nucleotide polymorphisms (SNPs) of the ACDC gene were genotyped in 432 T1D patients (of which, 196 had DN) and 187 nondiabetic control subjects, who were all Swedish Caucasians, by using dynamic allele specific hybridization. RESULTS: Single-marker association analysis demonstrated that SNPs +45G15G(T/G) and +276(G/T) were strongly associated with T1D [P=.002, OR=1.855 (1.266-2.717) and P=.001, OR=1.694 (1.337-2.147)]. Further analysis for haplotypes of these two SNPs indicated that one of the common haplotype (T_G) was strongly associated with T1D [P<.001, OR=1.769 (1.430-2.188)]. However, there was no significant difference in the allele frequencies of these two SNPs between the groups of T1D patients with nephropathy and the patients without nephropathy. CONCLUSIONS: The present study thus suggests that SNPs +45G15G(T/G) and +276(G/T) in the ACDC gene are associated with T1D but not with DN among Swedish Caucasians.

  • 56. Ma, Jun
    et al.
    Nordman, Sofia
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Falhammar, Henrik
    Brismar, Kerstin
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Efendic, Suad
    Gu, Harvest F
    Distribution of neuropeptide Y Leu7Pro polymorphism in patients with type 1 diabetes and diabetic nephropathy among Swedish and American populations.2007In: Eur J Endocrinol, ISSN 1479-683X, Vol. 157, no 5, p. 641-5Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The distribution of Leu7Pro polymorphism in the neuropeptide Y gene shows a geographical north to south gradient of decreasing frequency, suggesting that it may be a population-specific causal variant. This polymorphism is found to be associated with diabetic nephropathy (DN) and coronary heart disease in Finnish women with type 1 diabetes (T1D). The present study aims to evaluate the susceptibility of this polymorphism to the development of DN in two different populations. DESIGN: One sample set consists of 174 (females 98 and males 76) Swedish T1D patients with DN and 249 (females 132 and males 117) patients without DN. Another sample set includes 597 (females 356 and males 241) American T1D patients without DN and 577 (females 264 and males 313) patients with DN, who were descents of European Caucasians and were from the Genetics of Kidneys in Diabetes (GoKinD) Study. METHODS: Genotyping of Leu7Pro polymorphism was performed by dynamic allele-specific hybridization. RESULTS: The C allele frequencies of Leu7Pro polymorphism in T1D patients between Swedish and American GoKinD populations were significantly different (6.3 vs 4.0%; P=0.006). Particularly, the C allele frequency in Swedish female T1D patients with DN was significantly higher in comparison with T1D patients without DN (10.2 vs 4.2%; P=0.011, OR=2.614, 95% confidence intervals: 1.249-5.467). No significant association of this polymorphism with DN was observed in Swedish male T1D patients and the patients from GoKinD. CONCLUSIONS: The present study provides further evidence that Leu7Pro polymorphism confers the susceptibility to the development of DN in Swedish female T1D patients.

  • 57. Madsen, O D
    et al.
    Olsson, M L
    Bille, G
    Sundkvist, G
    Lernmark, A
    Dahlquist, Gisela
    Department of Pediatrics, Sachs' Children Hospital, Stockholm.
    Ludvigsson, J
    A two-colour immunofluorescence test with a monoclonal human proinsulin antibody improves the assay for islet cell antibodies1986In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 29, no 2, p. 115-118Article in journal (Refereed)
    Abstract [en]

    The conventional indirect immunofluorescence assay for islet cell antibodies was compared with a two-colour immunofluorescent assay to detect both islet cell antibodies with fluorescein isothiocyanate-labeled rabbit anti-human IgG and pancreatic B cells with a monoclonal human proinsulin antibody and Texas red-labeled sheep anti-mouse IgG. Determinations of end-point titres showed a correlation between the new two-colour immunofluorescent assay and the conventional indirect immunofluorescent assay in 1) selected sera positive for islet cell antibodies and insulin autoantibodies r s= 0.93 (p<0.01) or for islet cell antibodies alone r s=0.99 (p<0.005) and 2) sera from children or young adults with newly diagnosed Type 1 (insulin-dependent) diabetes r s=0.95 (p<0.0001). No interference between the monoclonal human proinsulin antibodies and islet cell antibodies with or without insulin autoantibodies or between the two second fluorescent antibodies was detected. It is concluded that the two-colour immunofluorescence assay is advantageous since a) it is possible to mix the reagents to avoid a more time-consuming and technically complicated assay, b) the presence of B cells can be confirmed in each section to permit detection of B cell cytoplasmic antibodies and c) microscopic evaluation is easier and more accurate, particulary in islet cell antibody negative samples.

  • 58.
    Mayans, Sofia
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Ruikka, Karin
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Eliasson, Mats
    Holmberg, Dan
    Association of type 1 diabetes and autoimmune thyroid disease to previously identified risk genes: a replication study in northern SwedenManuscript (Other academic)
  • 59. Munck, Johan
    et al.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Grönlund, Eva
    [The possibility to perform research on severely ill elderly. We hope there will be a change of the law soon]2011In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 44, p. 2201-Article in journal (Refereed)
  • 60.
    Munck, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Centrala etikprövningsnämnden.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Centrala etikprövningsnämnden.
    Johansson, Gunn
    Petersson, Bo
    Ringborg, Ulrik
    Etikprövningsnämnderna bör bli en enda myndighet2013In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, no 15, p. 773-774Article in journal (Other (popular science, discussion, etc.))
  • 61.
    Möllsten, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stattin, Eva-Lena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Rudberg, Susanne
    Higher intakes of fish protein are related to a lower risk of microalbuminuria in young Swedish type 1 diabetic patients.2001In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 24, no 5, p. 805-810Article in journal (Refereed)
  • 62.
    Möllsten, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Kockum, Ingrid
    Svensson, Maria
    Rudberg, Susanne
    Ugarph-Morawski, Anna
    Brismar, Kerstin
    Eriksson, Jan
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    The effect of polymorphisms in the renin-angiotensin-aldosterone system on diabetic nephropathy riskManuscript (Other academic)
  • 63.
    Möllsten, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Kockum, Ingrid
    Svensson, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rudberg, Susanne
    Ugarph-Morawski, Anna
    Brismar, Kerstin
    Eriksson, Jan W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    The effect of polymorphisms in the renin-angiotensin-aldosterone system on diabetic nephropathy risk2008In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Journal of diabetes and its complications, ISSN 1873-460X, Vol. 22, no 6, p. 377-383Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The risk of diabetic nephropathy (DN) can be increased by elevated intraglomerular pressure and glomerular filtration rate, leading to glomerular damage. This can be controlled by the renin-angiotensin-aldosterone (RAA) system, which has an important function regulating both systemic and intrarenal blood pressure. Smoking increases the risk of DN, but not all diabetic patients who smoke develop DN. There is a possibility that smoking has different effects depending on the different genotypes of the individual. We investigated the association of DN with seven polymorphisms in the RAA system and their possible interaction with smoking. SUBJECTS AND METHODS: In the present case-control study, type 1 diabetic patients with diabetes duration > or =20 years, without albuminuria and without antihypertensive treatment (n=197), were included as controls. An albumin excretion rate (AER) of 20-200 microg/min (n=73) was considered as incipient DN, and an AER >200 microg/min was considered as overt DN (n=48). Smoking habits were obtained from questionnaires. RESULTS: Homozygosity for the A allele, of the angiotensin II type 1 receptor (AGTR1) A1166C polymorphism, was associated with increased risk of overt DN (OR=3.04; 99% CI=1.02-9.06), independently of the other associated variables: age, duration of diabetes, ever smoking, HbA1c, and sex. The effect of the AA genotype was enhanced to a four times risk increase among ever-smoking patients. Two alleles of the microsatellite marker adjacent to the angiotensinogen gene were less common among nephropathy cases than among controls, but this was not significant when controlling for the same variables as above. CONCLUSIONS: The risk of having overt DN was increased in patients homozygous for the A1166 allele, and smoking seemed to enhance the effect of the AGTR1 genotype.

  • 64.
    Möllsten, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Marklund, Stefan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Wessman, Maija
    Svensson, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Forsblom, Carol
    Parkkonen, Maikki
    Brismar, Kerstin
    Groop, Per-Henrik
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    A functional polymorphism in the manganese superoxide dismutase gene and diabetic nephropathy.2007In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 56, no 1, p. 265-269Article in journal (Refereed)
    Abstract [en]

    Oxidative stress has been suggested to contribute to the development of diabetic nephropathy. Manganese superoxide dismutase (MnSOD) protects the cells from oxidative damage by scavenging free radicals. The demand for antioxidants is increased by smoking, which could disturb the balance between antioxidants and radicals. The present study aimed to determine whether a valine/alanine polymorphism in MnSOD (V16A, rs4880), alone or in combination with smoking, can contribute to development of diabetic nephropathy in 1,510 Finnish and Swedish patients with type 1 diabetes. Overt diabetic nephropathy (n = 619) was defined as having an albumin excretion rate (AER) >200 microg/min or renal replacement therapy; incipient diabetic nephropathy was defined as having an AER of 20-200 microg/min (n = 336). The control subjects had diabetes duration of >or=20 years, without albuminuria (AER <20 microg/min) and without antihypertensive treatment (n = 555). In addition to male sex and elevated A1C, smoking was significantly associated with diabetic nephropathy (overt plus incipient), odds ratio (OR) 2.00 (95% CI 1.60-2.50). When controlling for age at onset, diabetes duration, A1C, smoking, and sex, the Val/Val genotype was associated with an increase in risk of diabetic nephropathy (1.32 [1.00-1.74], P = 0.049). When evaluating the combined effect of genotype and smoking, we used logistic regression with stratification according to smoking status and genotype. The high-risk group (ever smoking plus Val/Val genotype) had 2.52 times increased risk of diabetic nephropathy (95% CI 1.73-3.69) compared with the low-risk group, but no departure from additivity was found. Our results indicate that smoking and homozygosity for the MnSOD Val allele is associated with an increased risk of diabetic nephropathy, which supports the hypothesis that oxidative stress contributes to the development of diabetic nephropathy.

  • 65.
    Möllsten, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Svensson, Maria
    Department of Nephrology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Waernbaum, Ingeborg
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Berhan, Yonas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Schön, Staffan
    Department of Internal Medicine, Ryhov County Hospital, Jönköping, Sweden.
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Arnqvist, Hans J.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Cumulative risk, age at onset, and sex-specific differences for developing end-stage renal disease in young patients with type 1 diabetes: A nationwide population-based cohort study2010In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 59, no 7, p. 1803-1808Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE—This study aimed to estimate the current cumulativerisk of end-stage renal disease (ESRD) due to diabeticnephropathy in a large, nationwide, population-based prospectivetype 1 diabetes cohort and specifically study the effects ofsex and age at onset.RESEARCH DESIGN AND METHODS—In Sweden, all incidentcases of type 1 diabetes aged 0–14 years and 15–34 years arerecorded in validated research registers since 1977 and 1983,respectively. These registers were linked to the Swedish RenalRegistry, which, since 1991, collects data on patients who receiveactive uremia treatment. Patients with 13 years duration of type1 diabetes were included (n 11,681).RESULTS—During a median time of follow-up of 20 years, 127patients had developed ESRD due to diabetic nephropathy. Thecumulative incidence at 30 years of type 1 diabetes duration waslow, with a male predominance (4.1% [95% CI 3.1–5.3] vs. 2.5%[1.7–3.5]). In both male and female subjects, onset of type 1diabetes before 10 years of age was associated with the lowestrisk of developing ESRD. The highest risk of ESRD was found inmale subjects diagnosed at age 20–34 years (hazard ratio 3.0 [95%CI 1.5–5.7]). In female subjects with onset at age 20–34 years, therisk was similar to patients’ diagnosed before age 10 years.CONCLUSIONS—The cumulative incidence of ESRD is exceptionallylow in young type 1 diabetic patients in Sweden. There isa striking difference in risk for male compared with femalepatients. The different patterns of risk by age at onset and sexsuggest a role for puberty and sex hormones.

  • 66.
    Möllsten, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Wessman, M
    Svensson, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Forsblom, C
    Parkkonen, M
    Brismar, K
    Groop, PH
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Glu298Asp and NOS4ab polymorphisms in diabetic nephropathy.2006In: Annals of Medicine, ISSN 0785-3890, E-ISSN 1365-2060, Vol. 38, no 7, p. 522-528Article in journal (Other (popular science, discussion, etc.))
    Abstract [en]

    BACKGROUND AND AIMS: The risk of diabetic nephropathy (DN) increases with increase in intraglomerular pressure, which may partly be regulated by nitric oxide (NO). NO-production can be affected by polymorphisms in the endothelial NO-synthase gene (NOS3), hyperglycaemia and smoking. We therefore studied association between DN and two polymorphisms in NOS3, Glu298Asp and NOS4ab, in Caucasian type 1 diabetes (T1D) patients. PATIENTS AND METHODS: A total of 1510 Finnish and Swedish T1D patients were included in a cross-sectional case-control study. Incipient DN was defined as an albumin excretion rate (AER) of 20-200 microg/min (n = 336). Overt DN = AER>200 microg/min or renal replacement therapy (n = 619). All patients with DN were considered as cases. The controls were T1D patients with diabetes duration 20 years, AER<20 microg/min and without antihypertensive treatment (n = 555). The genetic markers studied were a 27 bp repeat (NOS4ab) and Glu298Asp (rs1799983). RESULTS: Age at onset of diabetes, male sex, duration of diabetes, HbA1c, blood pressure and smoking were assessed as possible confounders in the logistic regression analysis, which showed that homozygosity for the Glu-allele of the Glu298Asp-polymorphism was independently associated with increased risk of DN (OR = 1.46; 95% CI = 1.12-1.91). The variables smoking (OR = 2.13; 95% CI = 1.63-2.78), male sex (OR = 1.61; 95% CI = 1.23-2.10), HbA1c (OR per % increase above upper limit of the normal reference range = 1.02; 95% CI = 1.02-1.03), systolic (OR = 1.05; 95% CI = 1.04-1.06) and diastolic blood pressure (OR = 1.04; 95% CI = 1.02-1.05) also significantly and independently increased the risk of DN when taking age at diabetes onset and diabetes duration into account. The NOS4 a-allele was not associated with DN. CONCLUSIONS: The Glu/Glu-genotype of the NOS3 Glu298Asp polymorphism may increase the risk of developing DN independently of other known risk factors.

  • 67.
    Nyström, Lennarth
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    'Dead in bed' in Norway1996In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 13, no 5, p. 495-496Article in journal (Refereed)
  • 68. Padaiga, Z
    et al.
    Tuomilehto, J
    Karvonen, M
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Podar, T
    Adojaan, B
    Urbonaite, B
    Zalinkevicius, R
    Brigis, G
    Virtala, E
    Kohtamäki, K
    Cepaitis, Z
    Tuomilehto-Wolf, E
    Seasonal variation in the incidence of Type 1 diabetes mellitus during 1983 to 1992 in the countries around the Baltic Sea.1999In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 16, no 9, p. 736-43Article in journal (Refereed)
    Abstract [en]

    The seasonal pattern with two cycles among older children and one cycle only among younger children may indicate different triggers of Type 1 diabetes mellitus for different age groups.

  • 69. Patterson, C C
    et al.
    Dahlquist, G
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Harjutsalo, V
    Joner, G
    Feltbower, R G
    Svensson, J
    Schober, E
    Gyürüs, E
    Castell, C
    Urbonaité, B
    Rosenbauer, J
    Iotova, V
    Thorsson, A V
    Soltész, G
    Early mortality in EURODIAB population-based cohorts of type 1 diabetes diagnosed in childhood since 1989.2007In: Diabetologia, ISSN 0012-186X, Vol. 50, no 12, p. 2439-42Article in journal (Other academic)
  • 70. Patterson, C C
    et al.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Soltész, G
    Maternal age and risk of type 1 diabetes in children. Relative risks by maternal age are biased.2001In: BMJ (Clinical research ed.), ISSN 0959-8138, Vol. 322, no 7300, p. 1489-90; author reply 1490Article in journal (Refereed)
  • 71. Patterson, C C
    et al.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Soltész, G
    Green, A
    Is childhood-onset type I diabetes a wealth-related disease? An ecological analysis of European incidence rates.2001In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 44 Suppl 3, p. B9-16Article in journal (Refereed)
    Abstract [en]

    The wide variation in childhood Type I diabetes incidence rates within Europe could be partially explained by indicators of national prosperity. These indicators could reflect differences in environmental risk factors such as nutrition or lifestyle that are important in determining a country's incidence rate.

  • 72. Patterson, C. C.
    et al.
    Gyuerues, E.
    Rosenbauer, J.
    Cinek, O.
    Neu, A.
    Schober, E.
    Parslow, R. C.
    Joner, G.
    Svensson, J.
    Castell, C.
    Bingley, P. J.
    Schoenle, E.
    Jarosz-Chobot, P.
    Urbonaite, B.
    Rothe, U.
    Krzisnik, C.
    Ionescu-Tirgoviste, C.
    Weets, I.
    Kocova, M.
    Stipancic, G.
    Samardzic, M.
    de Beaufort, C. E.
    Green, A.
    Dahlqvist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Soltesz, G.
    Trends in childhood type 1 diabetes incidence in Europe during 1989-2008: evidence of non-uniformity over time in rates of increase2012In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 55, no 8, p. 2142-2147Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to describe 20-year incidence trends for childhood type 1 diabetes in 23 EURODIAB centres and compare rates of increase in the first (1989-1998) and second (1999-2008) halves of the period. All registers operate in geographically defined regions and are based on a clinical diagnosis. Completeness of registration is assessed by capture-recapture methodology. Twenty-three centres in 19 countries registered 49,969 new cases of type 1 diabetes in individuals diagnosed before their 15th birthday during the period studied. Ascertainment exceeded 90% in most registers. During the 20-year period, all but one register showed statistically significant changes in incidence, with rates universally increasing. When estimated separately for the first and second halves of the period, the median rates of increase were similar: 3.4% per annum and 3.3% per annum, respectively. However, rates of increase differed significantly between the first half and the second half for nine of the 21 registers with adequate coverage of both periods; five registers showed significantly higher rates of increase in the first half, and four significantly higher rates in the second half. The incidence rate of childhood type 1 diabetes continues to rise across Europe by an average of approximately 3-4% per annum, but the increase is not necessarily uniform, showing periods of less rapid and more rapid increase in incidence in some registers. This pattern of change suggests that important risk exposures differ over time in different European countries. Further time trend analysis and comparison of the patterns in defined regions is warranted.

  • 73. Patterson, Cc
    et al.
    Gyürüs, E
    Rosenbauer, J
    Cinek, O
    Neu, A
    Schober, E
    Parslow, Rc
    Joner, G
    Svensson, J
    Castell, C
    Bingley, Pj
    Schoenle, E
    Jarosz-Chobot, P
    Urbonaité, B
    Rothe, U
    Kržišnik, C
    Ionescu-Tirgoviste, C
    Weets, I
    Kocova, M
    Stipancic, G
    Samardzic, M
    de Beaufort, Ce
    Green, A
    Soltész, G
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Seasonal variation in month of diagnosis in children with type 1 diabetes registered in 23 European centers during 1989-2008: little short-term influence of sunshine hours or average temperature2015In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 16, no 8, p. 573-580Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The month of diagnosis in childhood type 1 diabetes shows seasonal variation.

    OBJECTIVE: We describe the pattern and investigate if year-to-year irregularities are associated with meteorological factors using data from 50 000 children diagnosed under the age of 15 yr in 23 population-based European registries during 1989-2008.

    METHODS: Tests for seasonal variation in monthly counts aggregated over the 20 yr period were performed. Time series regression was used to investigate if sunshine hour and average temperature data were predictive of the 240 monthly diagnosis counts after taking account of seasonality and long term trends.

    RESULTS: Significant sinusoidal pattern was evident in all but two small centers with peaks in November to February and relative amplitudes ranging from ±11 to ±38% (median ±17%). However, most centers showed significant departures from a sinusoidal pattern. Pooling results over centers, there was significant seasonal variation in each age-group at diagnosis, with least seasonal variation in those under 5 yr. Boys showed greater seasonal variation than girls, particularly those aged 10-14 yr. There were no differences in seasonal pattern between four 5-yr sub-periods. Departures from the sinusoidal trend in monthly diagnoses in the period were significantly associated with deviations from the norm in average temperature (0.8% reduction in diagnoses per 1 °C excess) but not with sunshine hours.

    CONCLUSIONS: Seasonality was consistently apparent throughout the period in all age-groups and both sexes, but girls and the under 5 s showed less marked variation. Neither sunshine hour nor average temperature data contributed in any substantial way to explaining departures from the sinusoidal pattern.

  • 74. Patterson, Chris
    et al.
    Guariguata, Leonor
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Soltész, Gyula
    Ogle, Graham
    Silink, Martin
    Diabetes in the young - a global view and worldwide estimates of numbers of children with type 1 diabetes2014In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 103, no 2, p. 161-175Article in journal (Refereed)
    Abstract [en]

    This paper describes the methodology, results and limitations of the 2013 International Diabetes Federation (IDF) Atlas (6th edition) estimates of the worldwide numbers of prevalent cases of type 1 diabetes in children (<15 years). The majority of relevant information in the published literature is in the form of incidence rates derived from registers of newly diagnosed cases. Studies were graded on quality criteria and, if no information was available in the published literature, extrapolation was used to assign a country the rate from an adjacent country with similar characteristics. Prevalence rates were then derived from these incidence rates and applied to United Nations 2012 Revision population estimates for 2013 for each country to obtain estimates of the number of prevalent cases. Data availability was highest for the countries in Europe (76%) and lowest for the countries in sub-Saharan Africa (8%). The prevalence estimates indicate that there are almost 500,000 children aged under 15 years with type 1 diabetes worldwide, the largest numbers being in Europe (129,000) and North America (108,700). Countries with the highest estimated numbers of new cases annually were the United States (13,000), India (10,900) and Brazil (5000). Compared with the prevalence estimates made in previous editions of the IDF Diabetes Atlas, the numbers have increased in most of the IDF Regions, often reflecting the incidence rate increases that have been well-documented in many countries. Monogenic diabetes is increasingly being recognised among those with clinical features of type 1 or type 2 diabetes as genetic studies become available, but population-based data on incidence and prevalence show wide variation due to lack of standardisation in the studies. Similarly, studies on type 2 diabetes in childhood suggest increased incidence and prevalence in many countries, especially in Indigenous peoples and ethnic minorities, but detailed population-based studies remain limited.

  • 75.
    Patterson, Christopher C
    et al.
    Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK.
    Dahlquist, Gisela G
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gyürüs, Eva
    Department of Paediatrics, Faculty of Medicine, Pécs University, Pécs, Hungary.
    Green, Anders
    Centre for National Clinical Databases, South Odense University Hospital, and Department of Epidemiology, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
    Soltész, Gyula
    Department of Paediatrics, Faculty of Medicine, Pécs University, Pécs, Hungary.
    Incidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005-20: a multicentre prospective registration study.2009In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 373, no 9680, p. 2027-2033Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The incidence of type 1 diabetes in children younger than 15 years is increasing. Prediction of future incidence of this disease will enable adequate fund allocation for delivery of care to be planned. We aimed to establish 15-year incidence trends for childhood type 1 diabetes in European centres, and thereby predict the future burden of childhood diabetes in Europe. METHODS: 20 population-based EURODIAB registers in 17 countries registered 29 311 new cases of type 1 diabetes, diagnosed in children before their 15th birthday during a 15-year period, 1989-2003. Age-specific log linear rates of increase were estimated in five geographical regions, and used in conjunction with published incidence rates and population projections to predict numbers of new cases throughout Europe in 2005, 2010, 2015, and 2020. FINDINGS: Ascertainment was better than 90% in most registers. All but two registers showed significant yearly increases in incidence, ranging from 0.6% to 9.3%. The overall annual increase was 3.9% (95% CI 3.6-4.2), and the increases in the age groups 0-4 years, 5-9 years, and 10-14 years were 5.4% (4.8-6.1), 4.3% (3.8-4.8), and 2.9% (2.5-3.3), respectively. The number of new cases in Europe in 2005 is estimated as 15 000, divided between the 0-4 year, 5-9 year, and 10-14 year age-groups in the ratio 24%, 35%, and 41%, respectively. In 2020, the predicted number of new cases is 24 400, with a doubling in numbers in children younger than 5 years and a more even distribution across age-groups than at present (29%, 37%, and 34%, respectively). Prevalence under age 15 years is predicted to rise from 94 000 in 2005, to 160 000 in 2020. INTERPRETATION: If present trends continue, doubling of new cases of type 1 diabetes in European children younger than 5 years is predicted between 2005 and 2020, and prevalent cases younger than 15 years will rise by 70%. Adequate health-care resources to meet these children's needs should be made available. FUNDING: European Community Concerted Action Program.

  • 76. Patterson, Christopher C.
    et al.
    Harjutsalo, Valma
    Rosenbauer, Joachim
    Neu, Andreas
    Cinek, Ondrej
    Skrivarhaug, Torild
    Rami-Merhar, Birgit
    Soltesz, Gyula
    Svensson, Jannet
    Parslow, Roger C.
    Castell, Conxa
    Schoenle, Eugen J.
    Bingley, Polly J.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Jarosz-Chobot, Przemyslawa K.
    Marciulionyte, Dale
    Roche, Edna F.
    Rothe, Ulrike
    Bratina, Natasa
    Ionescu-Tirgoviste, Constantin
    Weets, Ilse
    Kocova, Mirjana
    Cherubini, Valentino
    Putarek, Natasa Rojnic
    Debeaufort, Carine E.
    Samardzic, Mira
    Green, Anders
    Trends and cyclical variation in the incidence of childhood type 1 diabetes in 26 European centres in the 25year period 1989-2013: a multicentre prospective registration study2019In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, no 3, p. 408-417Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6years.

    Methods: Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25years during the period 1989-2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends.

    Results: Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004-2008 period. Rates of increase were similar in boys and girls in the 0- to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5- to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10- to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012.

    Conclusions/interpretation: Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4year periodicity, no plausible explanation for this can be given.

  • 77. Persson, S.
    et al.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gerdtham, U. -G
    Carlsson, K. Steen
    Impact of childhood-onset type 1 diabetes on schooling: a population-based register study2013In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, no 6, p. 1254-1262Article in journal (Refereed)
    Abstract [en]

    We investigated the impact of type 1 diabetes on educational achievements in compulsory and upper secondary school, as well as potential long-lasting effects. Altogether 2,485 individuals with type 1 diabetes, diagnosed at the age of < 15 years and born in 1972-1978, were selected from the Swedish Childhood Diabetes Register, which was linked to national population registers including the Swedish Education Register. For each individual, four controls from the general population, matched for year of birth and residence at the time of diagnosis, were selected by Statistics Sweden (n = 9,940). We analysed the impact of diabetes on final school grades at 16 years (compulsory school) and 19 years (upper secondary school) and on participation in the labour market at 29 years using linear, logistic, ordered logistic and quantile regression analyses, controlling for demographics and socioeconomic background. Diabetes had a negative effect on mean final grades (scale of 1-5) in compulsory school (-0.07, p < 0.001) and theoretical programmes in upper secondary school (-0.07, p = 0.001). Children with early-onset diabetes (0-4 years) suffered a greater disadvantage as a result of the disease (-0.15, p = 0.001 in compulsory school). The strongest effect was seen in the lowest deciles of the conditional distribution on mean final grades. At age 29, individuals with diabetes were less likely to be gainfully employed (OR 0.82, 95% CI 0.73, 0.91). The small but significant negative effect of type 1 diabetes on schooling could affect opportunities for further education and career development. Attention must be paid in school to the special needs of children with diabetes.

  • 78. Persson, S.
    et al.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gerdtham, U. G.
    Carlsson, K. Steen
    The impact of a childhood onset of type 1 diabetes on higher education and labour market outcomes2013In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, no Supplement: 1, p. S22-S23, Meeting Abstract: 39Article in journal (Other academic)
  • 79. Persson, Sofie
    et al.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gerdtham, Ulf-G.
    Carlsson, Katarina Steen
    Why childhood-onset type 1 diabetes impacts labour market outcomes: a mediation analysis2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, no 2, p. 342-353Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Previous studies show a negative effect of type 1 diabetes on labour market outcomes such as employment and earnings later in life. However, little is known about the mechanisms underlying these effects. This study aims to analyse the mediating role of adult health, education, occupation and family formation.

    Methods: A total of 4179 individuals from the Swedish Childhood Diabetes Register and 16,983 individuals forming a population control group born between 1962 and 1979 were followed between 30 and 50 years of age. The total effect of having type 1 diabetes was broken down into a direct effect and an indirect (mediating) effect using statistical mediation analysis. We also analysed whether type 1 diabetes has different effects on labour market outcome between the sexes and across socioeconomic status.

    Results: Childhood-onset type 1 diabetes had a negative impact on employment (OR 0.68 [95% CI 0.62, 0.76] and OR 0.76 [95% CI 0.67, 0.86]) and earnings (−6%, p < 0.001 and −8%, p < 0.001) for women and men, respectively. Each of the mediators studied contributed to the total effect with adult health and occupational field accounting for the largest part. However, some of the effect could not be attributed to any of the mediators studied and was therefore likely related to other characteristics of the disease that hamper career opportunities. The effect of type 1 diabetes on employment and earnings did not vary significantly according to socioeconomic status of the family (parental education and earnings).

    Conclusions/interpretation: A large part of the effect of type 1 diabetes on the labour market is attributed to adult health but there are other important mediating factors that need to be considered to reduce this negative effect.

  • 80. Pundziute-Lyckå, A
    et al.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nyström, L
    Arnqvist, H
    Björk, E
    Blohmé, G
    Bolinder, J
    Eriksson, J W
    Sundkvist, G
    Ostman, J
    The incidence of Type I diabetes has not increased but shifted to a younger age at diagnosis in the 0-34 years group in Sweden 1983-1998.2002In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 45, no 6, p. 783-91Article in journal (Refereed)
    Abstract [en]

    During a 16-year period the incidence of Type I diabetes did not increase in the 0-34 years age group in Sweden, while median age at diagnosis decreased. A shift to younger age at diagnosis seems to explain the increasing incidence of childhood Type I diabetes.

  • 81.
    Pundziute-Lyckå, Auste
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Persson, Lars-Ake
    Cedermark, Gunilla
    Jansson-Roth, Agneta
    Nilsson, Ulla
    Westin, Vera
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Diet, growth, and the risk for type 1 diabetes in childhood: a matched case-referent study.2004In: Diabetes Care, ISSN 0149-5992, Vol. 27, no 12, p. 2784-9Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study the association between type 1 diabetes risk and previous intake of energy, accounting for body size and previous intake of nutrients and foods, accounting for the energy intake. RESEARCH DESIGN AND METHODS: We conducted an incident population-based case-referent study in Stockholm, Sweden, including 99 of 100 eligible 7- to 14-year-old diabetic children and 180 of 200 age-, sex-, and area-matched referent children identified through the Swedish population register. Average daily energy and nutrient intake 1 year before diabetes diagnosis/interview was estimated using the food frequency questionnaire with assessment of consumed food amounts. Mean SD scores of growth measurements taken during the last 4 years before the diagnosis were used. Odds ratios (ORs) were calculated by conditional logistic regression. RESULTS: Average intake of energy, carbohydrate, fat, and protein was significantly higher among the case subjects as well as mean weight-for-age SD score. Higher energy intake and weight-for-age were both associated with increased diabetes risk after adjustment for each other: OR (95% CI) for medium and high levels of energy intake were 1.33 (0.52-3.42) and 5.23 (1.67-16.38), respectively, and for weight-for-age were 3.20 (1.30-7.88) and 3.09 (1.16-8.22), respectively. High intake of carbohydrates, especially disaccharides and sucrose, increased diabetes risk. CONCLUSIONS: Higher energy intake and larger body size were independently associated with increased diabetes risk. Of the different nutrients, higher intake of carbohydrates, particularly disaccharides and sucrose, increased the risk. Lifestyle habits leading to higher energy intake and more rapid growth in childhood may contribute to the increase of childhood-onset type 1 diabetes by different mechanisms.

  • 82.
    Pundziute-Lyckå, Auste
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Persson, Lars-Åke
    Cedermark, Gunilla
    Jansson, Agneta
    Nilsson, Ulla
    Westin, Vera
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Diet, growth and the risk for insulin-dependent diabetes mellitus in childhoodManuscript (Other academic)
  • 83.
    Pundziūte-Lyckå, Auste
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Urbonaite, Brone
    Zalinkevicius, Rimas
    Time trend of childhood type 1 diabetes incidence in Lithuania and Sweden, 1983-20002004In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 93, no 11, p. 1519-1524Article in journal (Refereed)
    Abstract [en]

    AIM: To compare the time trend of childhood type 1 diabetes over an 18-y period in Lithuania and Sweden--countries with different incidence levels and different socio-economic conditions. METHODS: Percent average incidence change per year between 1983 and 2000, based on 8031 Swedish and 1100 Lithuanian cases in the age group 0-14 y, was calculated using Poisson regression. RESULTS: Average age- and sex-standardized incidence/100 000/y was 28.9 (95% CI: 28.2-29.5) in Sweden and 7.5 (95% CI: 7.1-8.0) in Lithuania. Between 1983 and 2000, the average increase per year was 2.2% in Sweden (95% CI: 1.7-2.6) and 2.3% in Lithuania (95% CI: 1.1-3.5), but the latter trend depended on an increase during the last few years of the period, and only for girls. In Sweden, incidence increased significantly in all age groups, but more so in the younger groups (3.0%, 2.2% and 1.7% per year in 0-4, 5-9 and 10-14-y age groups, respectively), while in Lithuania a significant increase was found only in the 10-14-y age group (3.0%). In Sweden, a trend towards a younger age at diagnosis was indicated for both boys and girls when comparing 1983-1991 and 1992-2000, whereas in Lithuania, the changes in age distribution over time were small, with an opposite tendency for boys. CONCLUSION: Incidence variability over time differed considerably in the two countries in the region of the Baltic Sea, suggesting a complex effect of environmental risk factors, some of which may be associated with wealth and socio-economic conditions.

  • 84. Rudberg, S
    et al.
    Dahlquist, Gisela
    Sachs' Children's Hospitals, Department of Pediatrics.
    Aperia, A
    Lindblad, B S
    Efendic, S
    Skottner, A
    Persson, B
    Indications that branched chain amino acids, in addition to glucagon, affect the glomerular filtration rate after a high protein diet in insulin-dependent diabetes1991In: Diabetes research, ISSN 0265-5985, Vol. 16, no 3, p. 101-109Article in journal (Refereed)
    Abstract [en]

    Hormonal changes and whole blood free amino acid levels and their relation to renal function were measured in 12 insulin-dependent diabetic patients after two 10-day periods with a diet consisting of 10% and 20% respectively of the energy as protein. The patients were 15-21 years old and mean duration of diabetes was 12 (5-20) years. Glomerular filtration rate, renal plasma flow, and albumin excretion rate were measured together with plasma concentrations of glucagon, growth hormone, insulin-like growth factor 1 (IGF-1), somatostatin, serum insulin and free amino acids in blood. Glomerular filtration rate was 123 +/- 3 ml/min/1.73 m2 on high protein diet and 113 +/- 3 ml/min/1.73 m2 on low protein diet (p = 0.02). Renal plasma flow was unchanged. Glucagon, IGF-1, branch chained amino acids (BCAA), tyrosine, phenylalanine, lysine, and methionine were increased after the high protein diet. Growth hormone, somatostatin, insulin, and other amino acids remained unchanged. The increase in glomerular filtration rate was significantly correlated to the increase in glucagon, isoleucine, and valine (glucagon r = 0.71, p = 0.01, isoleucine r = 0.59, p = 0.04, valine r = 0.62, p = 0.03). In a multiple regression model the increase in glomerular filtration correlated most strongly to the increase in isoleucine, followed by valine and glucagon. Together these variables explained 88% of the total variance of the change in glomerular filtration rate (r2 = 0.88, p = 0.001). Albumin excretion rate was correlated to IGF-1 (r = 0.86, p < 0.001) on the high protein diet. The regulation of GFR seems to depend on a combined effect of BCCA and glucagon, whereas microalbuminuria seems to be related to IGF-1.

  • 85. Rudberg, S
    et al.
    Osterby, R
    Bangstad, H J
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Persson, B
    Effect of angiotensin converting enzyme inhibitor or beta blocker on glomerular structural changes in young microalbuminuric patients with Type I (insulin-dependent) diabetes mellitus.1999In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 42, no 5, p. 589-95Article in journal (Refereed)
    Abstract [en]

    Contrary to findings in the group without antihypertensive treatment, no progression of glomerulopathy was seen in those treated with enalapril or metoprolol.

  • 86. Sanjeevi, C B
    et al.
    Landin-Olsson, M
    Kockum, I
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lernmark, A
    The combination of several polymorphic amino acid residues in the DQalpha and DQbeta chains forms a domain structure pattern and is associated with insulin-dependent diabetes mellitus.2002In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 958, p. 362-75Article in journal (Refereed)
    Abstract [en]

    IDDM is positively associated with HLA-DQA1*0301-DQB1*0302 (DQ8) and DQA1*0501-DQB1*0201 (DQ2) and negatively associated with DQA1*0102-DQB1*0602 (DQ6). The aim of the present study was to analyze the importance of several polymorphic residues and domains of DQalpha and DQbeta, in addition to residue 52 DQalpha and residue 57 DQbeta, with regard to susceptibility or resistance in new-onset 0- to 15-year-old Swedish children with IDDM (n = 425) and matched controls (n = 367). HLA genotyping identified several polymorphic residues of the DQalpha and DQbeta to be either positively or negatively associated with IDDM, including Arg 52 DQalpha and Asp 57 DQbeta. Leu 69 DQalpha was positively (OR 7.02, P < 0.0001), Ala 69 DQalpha was negatively (OR 0.22, P < 0.0001), Gln 47 DQalpha was positively (OR 5.8, P < 0.0001), Cys 47 DQalpha was positively (OR 2.2, P < 0.0001), Lys 47 DQalpha was negatively (OR 0.47, P < 0.005), and Arg 47 DQalpha was negatively (OR 0.22, P < 0.005) associated with IDDM. Similarly, residues at 11, 18, 45, 48, 50, 53, 55, 61, 64, 66, 76, and 80 were either positively or negatively associated with IDDM. Likewise, for DQbeta, Leu 53 DQbeta was positively (OR 11.01, P < 0.0001), Gln 53 DQbeta was negatively (OR 0.22, P < 0.0005), Arg 70 DQbeta was positively (OR 11.01, P < 0.0001), and Gly 70 DQbeta was negatively (OR 0.19, P < 0.0001) associated like other residues at 71, 74, 84, 85, 86, 89, and 90 DQbeta with IDDM. Certain domains in the DQalpha, RFTIL (at DQalpha positions 52, 61, 64, 66, and 69), were present in 95% of patients compared to 69% of controls (OR 9.01, P(c) < 0.0001), and DQbeta domain GR (at DQbeta positions 45 and 70) was present in 95% of patients and 68% of controls (OR 8.68, P < 0.0001), which correlated better than the individual amino acid residues with IDDM. A combination of the DQalpha and DQbeta chain domains was present in 94% of patients compared to 60% of controls (OR 10.6, P < 0.001). In conclusion, domains in the DQalpha, DQbeta, or both in the DQ molecule explain susceptibility or resistance to IDDM better than individual amino acid residues of DQA1 and DQB1.

  • 87. Sedimbi, S K
    et al.
    Luo, X R
    Sanjeevi, C B
    Lernmark, Ake
    Landin-Olsson, Mona
    Arnqvist, Hans
    Björck, Elizabeth
    Nyström, Lennarth
    Ohlson, Lars Olof
    Scherstén, Bengt
    Ostman, Jan
    Aili, M
    Bååth, L E
    Carlsson, E
    Edenwall, H
    Forsander, G
    Granström, B W
    Gustavsson, I
    Hanås, R
    Hellenberg, L
    Hellgren, H
    Holmberg, E
    Hörnell, H
    Ivarsson, Sten-A
    Johansson, C
    Jonsell, G
    Kockum, K
    Lindblad, B
    Lindh, A
    Ludvigsson, J
    Myrdal, U
    Neiderud, J
    Segnestam, K
    Sjöblad, S
    Skogsberg, L
    Strömberg, L
    Ståhle, U
    Thalme, B
    Tullus, K
    Tuvemo, T
    Wallensteen, M
    Westphal, O
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Aman, J
    SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients.2007In: Genes Immun, ISSN 1466-4879, Vol. 8, no 6, p. 518-21Article in journal (Other academic)
  • 88. Soltesz, G
    et al.
    Patterson, C C
    Dahlquist, G
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Worldwide childhood type 1 diabetes incidence--what can we learn from epidemiology?2007In: Pediatr Diabetes, ISSN 1399-543X, Vol. 8 Suppl 6, p. 6-14Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes is the most common form of diabetes in most part of the world, although reliable data are still unavailable in several countries. Wide variations exist between the incidence rates of different populations, incidence is lowest in China and Venezuela (0.1 per 100,000 per year) and highest in Finland and Sardinia (37 per 100,000 per year). In most populations girls and boys are equally affected. In general, the incidence increases with age, the incidence peak is at puberty. After the pubertal years, the incidence rate significantly drops in young women, but remains relatively high in young adult males up to the age 29-35 years. Prospective national and large international registries (DIAMOND and EURODIAB) demonstrated an increasing trend in incidence in most regions of the world over the last few decades and increases seem to be the highest in the youngest age group. Analytical epidemiological studies have identified environmental risk factors operating early in life which might have contributed to the increasing trend in incidence. These include enteroviral infections in pregnant women, older maternal age (39-42 years), preeclampsia, cesarean section delivery, increased birthweight, early introduction of cow's milk proteins and an increased rate of postnatal growth (weight and height). Optimal vitamin D supplementation during early life has been shown to be protective. Some of these environmental risk factors such as viruses may initiate autoimmunity toward the beta cell, other exposures may put on overload on the already affected beta cell and thus accelerate the disease process.

  • 89. Sun, Chengjun
    et al.
    Sedimbi, Saikiran K
    Ashok, Ayyappa K
    Sanjeevi, Carani B
    Landin-Olsson, Mona
    Arnqvist, Hans
    Björck, Elisabeth
    Eriksson, Jan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Ohlson, Lars Olof
    Scherstén, Bengt
    Östman, Jan
    Aili, M
    Bååth, LE
    Carlsson, E
    Edenwall, H
    Forsander, G
    Granström, BW
    Gustavsson, I
    Hanås, R
    Hellenberg, L
    Hellgren, H
    Holmberg, E
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hörnell, H
    Ivarsson, S-A
    Johansson, C
    Jonsell, G
    Kockum, K
    Lindblad, B
    Lindh, A
    Ludvigsson, J
    Myrdal, U
    Neiderud, J
    Segnestam, K
    Sjöblad, S
    Skogsberg, L
    Strömberg, L
    Ståhle, U
    Thalme, B
    Tullus, K
    Tuvemo, T
    Wallensteen, M
    Westphal, O
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Åman, J
    CRYAB-650 C>G (rs2234702) affects susceptibility to type 1 diabetes and IAA-positivity in Swedish population2012In: Human Immunology, ISSN 0198-8859, E-ISSN 1879-1166, Vol. 73, no 7, p. 759-766Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).

    METHODS: Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.

    RESULTS: CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.

    CONCLUSIONS: CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.

  • 90.
    Svensson, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Eriksson, J. W.
    Dahlquist, G.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Early glycemic control, age at onset and development of microvascular complications in childhood-onset type 1 diabetes: A population-based study in Northern SwedenManuscript (Other academic)
  • 91.
    Svensson, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Schön, S
    Dahlquist, G
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Age at onset of childhood-onset type 1 diabetes and the development of end-stage renal disease: a nationwide population-based study.2006In: Diabetes Care, Vol. 29, no 3, p. 538-42Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To analyze the impact of age at onset on the development of end-stage renal disease (ESRD) due to diabetic nephropathy in a nationwide population-based cohort with childhood-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: A record linkage between two nationwide registers, the Swedish Childhood Diabetes Registry, including 12,032 cases with childhood-onset diabetes, and the Swedish Registry for Active Treatment of Uraemia was performed. Log-rank test was used to test differences between cumulative risk curves of developing ESRD due to diabetic nephropathy in three different strata of age at onset (0-4, 5-9, and 10-14 years). RESULTS: At a maximum follow-up of 27 years, 33 patients had developed ESRD due to diabetic nephropathy and all had a diabetes duration >15 years. In total, 4,414 patients had diabetes duration >15 years, and thus the risk in this cohort to develop ESRD was 33 of 4,414 (0.7%). A significant difference in risk of developing ESRD was found between the youngest (0-4 years) and the two older (5-9 and 10-14 years) age-at-onset strata (P = 0.03 and P = 0.001, respectively). A significant difference in the risk of developing ESRD was also found between children with prepubertal (0-4 and 5-9 years, n = 2,424) and pubertal (10-14 years, n = 2000) onset of diabetes (P = 0.002). No patient with onset of diabetes before 5 years of age had developed ESRD. CONCLUSIONS: With a median duration of 21 years in this population-based Swedish cohort with childhood-onset diabetes, <1% of the patients had developed ESRD due to diabetic nephropathy, and a prepubertal onset of diabetes seems to prolong the time to development of ESRD.

  • 92.
    Toppe, C.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Jönköping.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Jönköping.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Jönköping.
    Schon, S.
    Swedish Renal Registry, Jönköping.
    Socioeconomic risk factors for developing end stage renal disease in patients with childhood onset type 1 diabetes: a population based register study2013In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, no Supplement: 1, p. S475-S475, Meeting Abstract: 1182Article in journal (Other academic)
  • 93.
    Toppe, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Ryhov City Hospital, Department of Internal Medicin, Jönköping, Sweden.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Schon, S.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Socio-economic factors influencing the development of end-stage renal disease in people with Type 1 diabetes: a longitudinal population study2017In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 34, no 5, p. 676-682Article in journal (Refereed)
    Abstract [en]

    Aims: The development of end-stage renal disease (ESRD) in Type 1 diabetes is multifactorial. Familial socio-economic factors may influence adherence to and understanding of diabetes treatment, and also general health behaviour. We investigate how parental and personal education level and exposure to low economic status, indicated by the need for income support, influence the development of ERSD caused by Type 1 diabetes.

    Methods: Participants were retrieved from the nationwide Swedish Childhood Diabetes Registry, which was linked to the Swedish Renal Registry, to find people with ESRD caused by Type 1 diabetes, and to Statistic Sweden to retrieve longitudinal socio-economic data on participants and their parents. Data were analysed using Cox regression modelling.

    Results: Of 9287 people with diabetes of duration longer than 14 years, 154 had developed ESRD due to diabetes. Median diabetes duration (range) for all participants was 24.2 years (14.0-36.7 years). Low maternal education ( 12 years) more than doubled the risk of developing ESRD, hazard ration (HR) = 2.9 [95% confidence interval (95% CI): 1.7-4.8]. For people with a low personal level of education HR was 5.7 (3.4-9.5). In an adjusted model, the person's own education level had the highest impact on the risk of ESRD. If at least one of the parents had ever received income support the HR was 2.6 (1.9-3.6).

    Conclusions: Socio-economic factors, both for the parents and the person with diabetes, have a strong influence on the development of ESRD in Type 1 diabetes. It is important for caregivers to give enough support to more vulnerable people and their families.

  • 94.
    Toppe, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Schön, Staffan
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Improved survival in Renal Replacement Therapy for type 1 diabetes patients in Sweden: a national register studyManuscript (preprint) (Other academic)
  • 95.
    Toppe, Cecilia
    et al.
    Lanssjukhuset Ryhov, Dept Internal Med, Jonkoping, Sweden.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Schön, Staffan
    Swedish Renal Registry, Jönköping, Sweden; Diaverum Renal Serv Grp, Lund, Sweden.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Low cumulative incidence of end-stage renal disease in young patients with type 1 diabetes in Sweden: a population based study2015In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no Suppl. 1 Abstr. 402, p. S201-S202Article in journal (Other academic)
    Abstract [en]

    Background and aims: A previous study from our group showed a low cumulative incidence of end-stage renal disease (ESRD) in a Swedish cohort of type 1 diabetes (T1D) patients with median duration of 20 years. We speculated that a good diabetes health care system might have postponed the peak incidence of ESRD and that young age at onset of T1D can postpone the development of diabetic nephropathy (DN) and ESRD. Moreover, diabetes onset during puberty may promote the development of diabetic complications. Our previous study also indicated differences by sex in ESRD development and a possible interaction with age at onset. Female patients who developed T1D after puberty had similar risk of ESRD as those with onset before 10 years of age. Male patients had the same high risk with onset during puberty and after puberty, those with onset before 10 years had the lowest risk. The aims of the present study are to assess the cumulative incidence of ESRD due to DN in a large prospective population-based cohort of T1D patients at maximum 36 years of diabetes duration and to study the effects of sex and age at onset of T1D.

    Materials andmethods: Since 1977 all incident cases of T1D in the ages 0-14 years are recorded in the Swedish Childhood Diabetes Register (SCDR). The Swedish Renal Registry (SRR) started in 1991 and collects data on all patients with active uraemia treatment, ESRD. We decided to include patients with diabetes duration ≥14 years. In total 9381 patients from the SCDR were included. We have recently received permission to include data from the Swedish National Diabetes Register, a national quality register, and are awaiting data to include patients with age at onset 15-34 years.

    Results: For the childhood onset cases the median diabetes duration was 23.8 years, maximum 36.7 years, and 154 patients had developed ESRD due to diabetes. The cumulative incidence was 4.5%. There was no statistical difference between male and female patients with age at diabetes onset before 15 years of age, males 5.0%, females 3.8%.We confirm that onset of diabetes before 10 years of age postpones the development of ESRD when compared to onset during 10-14 years, HR 2.3 (95% CI= 1.7-3.3). Further analyses will be available for presentation in September.

    Conclusion: The cumulative risk of ESRD due to diabetic nephropathy in Swedish T1D patients at maximum36 years of diabetes duration is still exceptionally low. There is no difference in the development of ESRD between male and female patients with onset of diabetes before 15 years of age.

  • 96.
    Toppe, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Department of Internal Medicine, Ryhov County Hospital, Jönköping, Sweden.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Schön, Staffan
    Jonsson, Anders
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Renal replacement therapy due to type 1 diabetes; time trends during 1995-2010: a Swedish population based register study2014In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 28, no 2, p. 152-155Article in journal (Refereed)
    Abstract [en]

    Background: End stage renal disease (ESRD), is the most severe complication of diabetes mellitus. This population-based study analysed time trends for start of renal replacement therapy (RRT) due to type 1 diabetes compared to type 2 diabetes and other diagnoses. Material and Methods: We used data on patients who were registered 1995-2010 in the Swedish Renal Registry, a nationwide register covering 95 % of all patients with uraemia. The patients were analysed according to their original kidney disease. The incidence was analysed by calendar year, age at start of RRT and gender. Results: Of 17389 patients who were registered, 1833 had type 1 diabetes; 65% were men. The mean age at onset of RRT for patients with type 1 diabetes was 52.8 years which increased by more than 3 years over the studied period. The number of patients in need of RRT due to type 1 diabetes decreased, while RRT due to type 2 diabetes increased during the period studied. Conclusions: The overall incidence of RRT in Sweden is rather constant over the years but the need for RRT in type 1 diabetes patients decreased and patients with type 1 diabetes tend to become older at onset of RRT. 

  • 97.
    Toppe, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Department of Internal Medicine, Ryhov County Hospital, Jönköping, Sweden.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Waernbaum, Ingeborg
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Schön, Staffan
    Swedish Renal Registry, Jönköping, Sweden.
    Gudbjörnsdottir, Soffia
    Swedish National Diabetes Register, Gothenburg, Sweden.
    Landin-Olsson, Mona
    Diabetes Incidence Study in Sweden Department of Clinical Sciences, Lund University, Lund, Sweden.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Decreasing Cumulative Incidence of End-Stage Renal Disease in Young Patients With Type 1 Diabetes in Sweden: a 38-Year Prospective Nationwide Study2019In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 42, no 1, p. 27-31Article in journal (Refereed)
    Abstract [en]

    Objective: Diabetic nephropathy is a serious complication of type 1 diabetes. Recent studies indicate that end-stage renal disease (ESRD) incidence has decreased or that the onset of ESRD has been postponed; therefore, we wanted to analyze the incidence and time trends of ESRD in Sweden.

    Research design and methods: In this study, patients with duration of type 1 diabetes >14 years and age at onset of diabetes 0–34 years were included. Three national diabetes registers were used: the Swedish Childhood Diabetes Register, the Diabetes Incidence Study in Sweden, and the National Diabetes Register. The Swedish Renal Registry, a national register on renal replacement therapy, was used to identify patients who developed ESRD.

    Results: We found that the cumulative incidence of ESRD in Sweden was low after up to 38 years of diabetes duration (5.6%). The incidence of ESRD was lower in patients with type 1 diabetes onset in 1991–2001 compared to onset in 1977–1984 and 1985–1990, independently of diabetes duration.

    Conclusion: The risk of developing ESRD in Sweden in this population is still low and also seems to decrease with time.

  • 98.
    Waernbaum, Ingeborg
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Low mean temperature rather than few sunshine hours are associated with an increased incidence of type 1 diabetes in children2016In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 31, no 1, p. 61-65Article in journal (Refereed)
    Abstract [en]

    The well-known north-south gradient and the seasonal variability in incidence of childhood type1 diabetes indicate climatological factors to have an effect on the onset. Both sunshine hours and a low temperature may be responsible. In the present study we tried to disentangle these effects that tend to be strongly connected.

    Exposure data were sunshine hours and mean temperature respectively obtained from eleven meteorological stations in Sweden which were linked to incidence data from geographically matched areas. Incident cases during 1983-2008 were retrieved from the population based Swedish childhood diabetes register. We used generalized additive models to analyze the incidence as a function of mean temperature and hours of sun adjusted for the time trend, age and sex.

    In our data set the correlation between sun hours and temperature was weak (r=0.36) implying that it was possible to estimate the effect of these variables in a regression model. We fit a general additive model with a smoothing term for the time trend. In the model with sun hours we found no significant effect on T1 incidence (p=0.17) whereas the model with temperature as predictor was significant (p=0.05) when adjusting for the time trend, sex and age. Adding sun hours in the model where mean temperature was already present did not change the effect of temperature.

    There is an association with incidence of type1 diabetes in children and low mean temperature independent of a possible effect of sunshine hours after adjustment for age, sex and time trend. The findings may mirror the cold effect on insulin resistance and accords with the hypothesis that overload of an already ongoing beta cell destruction may accelerate disease onset.

  • 99.
    Waernbaum, Ingeborg
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lind, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Perinatal risk factors for type 1 diabetes revisited: a population-based register study2019In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, no 7, p. 1173-1184Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Single-centre studies and meta-analyses have found diverging results as to which early life factors affect the risk of type 1 diabetes during childhood. We wanted to use a large, nationwide, prospective database to further clarify and analyse the associations between perinatal factors and the subsequent risk for childhood-onset type 1 diabetes using a case–control design.

    Methods: The Swedish Childhood Diabetes Register was linked to the Swedish Medical Birth Register and National Patient Register, and 14,949 cases with type 1 diabetes onset at ages 0–14 years were compared with 55,712 matched controls born from the start of the Medical Birth Register in 1973 to 2013. After excluding confounders (i.e. children multiple births, those whose mother had maternal diabetes and those with a non-Nordic mother), we used conditional logistic regression analyses to determine risk factors for childhood-onset type 1 diabetes. We used WHO ICD codes for child and maternal diagnoses.

    Results: In multivariate analysis, there were small but statistically significant associations between higher birthweight z score (OR 1.08, 95% CI 1.06, 1.10), delivery by Caesarean section (OR 1.08, 95% CI 1.02, 1.15), premature rupture of membranes (OR 1.08, 95% CI 1.01, 1.16) and maternal urinary tract infection during pregnancy (OR 1.39, 95% CI 1.04, 1.86) and the subsequent risk of childhood-onset type 1 diabetes. Birth before 32 weeks of gestation was associated with a lower risk of childhood-onset type 1 diabetes compared with full-term infants (OR 0.54, 95% CI 0.38, 0.76), whereas birth between 32 and 36 weeks’ gestation was associated with a higher risk (OR 1.24, 95% CI 1.14, 1.35). In subgroup analyses (birth years 1992–2013), maternal obesity was independently associated with subsequent type 1 diabetes in the children (OR 1.27, 95% CI 1.15, 1.41) and rendered the association with Caesarean section non-significant. In contrast to previous studies, we found no association of childhood-onset type 1 diabetes with maternal–child blood-group incompatibility, maternal pre-eclampsia, perinatal infections or treatment of the newborn with phototherapy for neonatal jaundice. The proportion of children with neonatal jaundice was significantly higher in the 1973–1982 birth cohort compared with later cohorts.

    Conclusions/interpretation: Perinatal factors make small but statistically significant contributions to the overall risk of childhood-onset type 1 diabetes. Some of these risk factors, such as maternal obesity, may be amendable with improved antenatal care. Better perinatal practices may have affected some previously noted risk factors over time.

  • 100.
    Zachrisson, I
    et al.
    Astrid Lindgren Children’s Hospital, Karolinska Hospital and Institute, Stockholm, Sweden.
    Brismar, K
    Department of Endocrinology and Diabetology, Karolinska Hospital and Institute, Stockholm, Sweden.
    Carlsson-Skwirut, C
    Astrid Lindgren Children’s Hospital, Karolinska Hospital and Institute, Stockholm, Sweden.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Wallensteen, M
    Astrid Lindgren Children’s Hospital, Karolinska Hospital and Institute, Stockholm, Sweden.
    Bang, P
    Astrid Lindgren Children’s Hospital, Karolinska Hospital and Institute, Stockholm, Sweden.
    Increased 24 h mean insulin-like growth factor binding protein-3 proteolytic activity in pubertal type 1 diabetic boys.2000In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 10, no 6, p. 324-31Article in journal (Refereed)
    Abstract [en]

    Hyperglycaemia and increased variability of blood glucose in pubertal children with type 1 diabetes may be related to increased growth hormone (GH) secretion and insulin resistance. The role of changes in insulin-like growth factor-I (IGF-I) bioavailability for the glycaemic control in these patients has not been completely elucidated. In particular, the possible role of increased IGF binding protein-3 (IGFBP-3) proteolysis reported in other insulin resistant states awaits further characterization. The aims of this study were to assess if hyperglycaemia in children with type 1 diabetes was associated with changes in free dissociable IGF-I (fdIGF-I) and IGF binding protein-3 protease activity (IGFBP-3-PA) and if increased insulin resistance during puberty was associated with changes in IGFBP-3-PA in healthy and diabetic children. In diabetic boys in the period of maximal linear growth (Tanner stage 3, n = 5), the mean level and the variability of IGFBP-3-PA, determined every second hour throughout 24 h, were significantly higher both compared to postpubertal diabetic boys (n = 6; P = 0.003 and P = 0.001, respectively), and to age matched healthy boys (n = 4; P = 0.006 and P < 0.001 respectively). This activation of IGFBP-3-PA was most prominent during the day time. The mean 24 h blood glucose level (determined hourly) was the only parameter studied that significantly predicted the changes in mean 24 h IGFBP-3-PA in the diabetes group. The mean 24 h concentrations of fdIGF-I were decreased in the diabetic boys compared to the healthy controls but statistical significance was only achieved in Tanner Stage 5 (p = 0.03). We speculate that the elevated levels of IGFBP-3-PA in Tanner 3 diabetic boys are related to deteriorated glucose homeostasis and that it may be a compensatory mechanism to attenuate the decrease in fdIGF-I in order to partly restore insulin sensitivity and glycemic control.

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