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  • 1. Campmans-Kuijpers, Marjo J. E.
    et al.
    Sluijs, Ivonne
    Noethlings, Ute
    Freisling, Heinz
    Overvad, Kim
    Weiderpass, Elisabete
    Fagherazzi, Guy
    Kuehn, Tilman
    Katzke, Verena A.
    Mattiello, Amalia
    Sonestedt, Emily
    Masala, Giovanna
    Agnoli, Claudia
    Tumino, Rosario
    Spijkerman, Annemieke M. W.
    Barricarte, Aurelio
    Ricceri, Fulvio
    Chamosa, Saioa
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Winkvist, Anna
    Tjonneland, Anne
    Sluik, Diewertje
    Boeing, Heiner
    Beulens, Joline W. J.
    Isocaloric substitution of carbohydrates with protein: the association with weight change and mortality among patients with type 2 diabetes2015In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 14, article id 39Article in journal (Refereed)
    Abstract [en]

    Background: The health impact of dietary replacement of carbohydrates with protein for patients with type 2 diabetes is still debated. This study aimed to investigate the association between dietary substitution of carbohydrates with (animal and plant) protein and 5-year weight change, and all-cause and cardiovascular (CVD) mortality risk in patients with type 2 diabetes.

    Methods: The study included 6,107 diabetes patients from 15 European cohorts. Patients with type 1 diabetes were excluded. At recruitment, validated country-specific food-frequency questionnaires were used to estimate dietary intake. Multivariable adjusted linear regression was used to examine the associations between dietary carbohydrate substitution with protein and 5-year weight change, and Cox regression to estimate hazard ratios (HRs) for (CVD) mortality.

    Results: Annual weight loss of patients with type 2 diabetes was 0.17 (SD 1.24) kg. After a mean follow-up of 9.2 (SD 2.3)y, 787 (13%) participants had died, of which 266 (4%) deaths were due to CVD. Substitution of 10 gram dietary carbohydrate with total (ß = 187 [75;299]g) and animal (ß = 196 [137;254]g) protein was associated with mean 5-year weight gain. Substitution for plant protein was not significantly associated with weight change (β = 82 [−421;584]g). Substitution with plant protein was associated with lower all-cause mortality risk (HR = 0.79 [0.64;0.97]), whereas substitution with total or animal protein was not associated with (CVD) mortality risk.

    Conclusions: In diabetes patients, substitution with plant protein was beneficial with respect to weight change and all-cause mortality as opposed to substitution with animal protein. Therefore, future research is needed whether dietary guidelines should not actively promote substitution of carbohydrates by total protein, but rather focus on substitution of carbohydrates with plant protein.

  • 2.
    Hernestål-Boman, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Medicine, Sunderby Hospital, Luleå, Sweden.
    Eriksson, Jan W
    Department of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Gothenburg and AstraZeneca R&D, Mölndal, Sweden.
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study2012In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 11, p. 152-Article in journal (Refereed)
    Abstract [en]

    Background: Diabetic patients experience stimulated coagulation and dysfibrinolysis, which is associated with an increased risk of cardiovascular events. This imbalance may precede the manifest diagnosis. We investigated whether elevated antigen levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), the tPA/PAI-1 complex, or von Willebrand Factor (VWF) precede type 2 diabetes mellitus (T2DM) diagnosis, and whether this elevation occurs before increased fasting plasma glucose (FPG) or 2-hour plasma glucose (2hPG) in individuals who later develop T2DM.

    Methods: We conducted a prospective incident case-referent study within the Vasterbotten Intervention Programme. Cardiovascular risk factor data as well as FPG and 2hPG and blood samples for future research were collected at a baseline health examination between 1989 and 2000, (n= 28 736). During follow-up in January 2001, 157 cases had developed T2DM. Referents without T2DM were matched for sex, age, and year of participation (n=277). Subgroup analysis was performed for cases with normal baseline glucose levels (FPG <6.1 mmol/L and 2hPG < 8.9 mmol/L) and cases with elevated levels (FPG 6.1-6.9 mmol/L and/or 2hPG 8.9-12.1 mmol/L).

    Results: After adjusting for BMI, family history of diabetes, physical activity, smoking, systolic blood pressure and levels of C-reactive protein and triglycerides, independent associations were found between incident T2DM and elevated levels of tPA (OR=1.54, 95% CI 1.06-2.23), PAI-1 (OR=1.61, 95% CI 1.14-2.28), and tPA/PAI-1 complex (OR=2.45, 95% CI 1.56-3.84). In participants with normal glucose levels, PAI-1 (OR=2.06, 95% CI 1.10 - 3.86) exhibited an independent relationship with incident T2DM after the adjustments.

    Conclusions: Elevated levels of fibrinolytic variables precede the manifestation of T2DM after adjusting for metabolic and cardiovascular risk factors and can be detected several years before changes in glucose tolerance.

  • 3. Hyvärinen, Marjukka
    et al.
    Tuomilehto, Jaakko
    Laatikainen, Tiina
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Peter
    Qiao, Qing
    The impact of diabetes on coronary heart disease differs from that on ischaemic stroke with regard to the gender.2009In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 8, no 17Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To study the diabetes related CVD risk between men and women of different ages. METHODS: Hazards ratios (HRs) (95%CI) for acute CHD and ischaemic stroke events were estimated based on data of Finnish and Swedish cohorts of 5111 women and 4167 men. RESULTS: 182 (3.6%) women and 348 (8.4%) men had CHD and 129 (2.5%) women and 137 (3.3%) men ischaemic stroke events. The multivariate adjusted HRs for acute CHD at age groups of 40-49, 50-59 and 60-69 years were 1.00 (1.94), 1.78 (4.23), 3.75 (8.40) in women (men) without diabetes and 4.35 (5.40), 5.49 (9.54) and 8.84 (13.76) in women (men) with diabetes. The corresponding HRs for ischaemic stroke were 1.00 (1.26), 2.48 (2.83) and 5.17 (5.11) in women (men) without diabetes and 4.14 (4.91), 3.32 (6.75) and 13.91 (18.06) in women (men) with diabetes, respectively. CONCLUSION: CHD risk was higher in men than in women but difference reduced in diabetic population. Diabetes, however, increased stroke risk more in men than in women.

  • 4.
    Håglin, Lena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Bäckman, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Törnkvist, Birgitta
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    A structural equation model for assessment of links between changes in serum triglycerides, -urate, and -glucose and changes in serum Calcium, -magnesium and -phosphate in Type 2 diabetes and non-diabetes metabolism2011In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 10, no 1, p. 116-Article in journal (Refereed)
    Abstract [en]

    Background: This study investigates the associations between changes in serum Triglycerides (S-TG), -Urate (S-Urate), and -Glucose (S-Glu) and changes in serum Calcium (S-Ca), -Magnesium (S-Mg), and -Phosphate (S-P) in patients with type 2 diabetes compared with non-diabetic patients. Methods: The analysis is based on data collected from a secondary prevention population of women and men (W/M) at risk for cardiovascular disease (type 2 diabetes, 212/200; non-diabetes 968/703). The whole population (n = 2083) had a mean age of 51.0 (9.7) years and was stratified for sex and according to type 2 diabetes or non-diabetes. The patients were followed for, either half a year or one year and changes in risk factors were calculated from follow-up to baseline, the time when patients were admitted to the health center. The pattern of relationships was evaluated using a structural equation model. Results: Higher S-TG and S-Glu but lower S-Urate was revealed at baseline in type 2 diabetes women and men as compared to their counterparts, non-diabetes patients. Women with type 2 diabetes had higher S-Ca and lower S-Mg than non-diabetes women. Changes in S-Glu were associated with changes in S-Ca (+), baseline S-Ca (+), and S-Urate (-) in type 2 diabetes men. Changes in S-Urate were associated with changes in S-Mg (+) in type 2 diabetes women and non-diabetes men. In men with non-diabetes, changes in S-Glu were associated with changes in S-Mg (-). In women with non-diabetes, changes in S-Glu were associated with changes in S-P (-) and changes in S-Urate with changes in S-Ca (+). Conclusion: With respect to metabolic disturbances in non-diabetes and the awareness of risk for type 2 diabetes, changes in S-Glu and changes in S-Ca, S-Mg, and S-P should be considered as risk factors for cardiovascular disease. Increased early detection and corrections of high S-Ca, low S-Mg, and S-P in obese patients may improve their metabolism and reduce the risk of CVD in patients with type 2 diabetes. Trial registration number: ISRCTN: ISRCTN79355192

  • 5. Mohammedi, Kamel
    et al.
    Bellili-Muñoz, Naïma
    Marklund, Stefan L.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Driss, Fathi
    Le Nagard, Hervé
    Patente, Thiago A.
    Fumeron, Frédéric
    Roussel, Ronan
    Hadjadj, Samy
    Marre, Michel
    Velho, Gilberto
    Plasma extracellular superoxide dismutase concentration, allelic variations in the SOD3 gene and risk of myocardial infarction and all-cause mortality in people with type 1 and type 2 diabetes2015In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 14, article id 845Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Oxidative stress is involved in development of diabetes complications. Extracellular superoxide dismutase (EC-SOD, SOD3) is a major extracellular antioxidant enzyme and is highly expressed in arterial walls. Advanced oxidation protein products (AOPP) and 8-iso-prostaglandin (isoprostane) are markers of oxidative stress. We investigated association of SOD3 gene variants, plasma concentrations of EC-SOD, AOPP and isoprostane with myocardial infarction and mortality in diabetic patients.

    METHODS: We studied three cohorts designed to evaluate the vascular complications of diabetes: the GENEDIAB study (469 participants with type 1 diabetes at baseline; follow-up data for 259 participants), the GENESIS study (603 participants with type 1 diabetes at baseline; follow-up data for 525 participants) and the DIABHYCAR study (3137 participants with type 2 diabetes at baseline and follow-up). Duration of follow-up was 9, 5, and 5 years, respectively. Main outcome measures were incidence of myocardial infarction, and cardiovascular and total mortality during follow-up. Six single nucleotide polymorphisms in the SOD3 locus were genotyped in the three cohorts. Plasma concentrations of EC-SOD, AOPP, and isoprostane were measured in baseline samples of GENEDIAB participants.

    RESULTS: In GENEDIAB/GENESIS pooled cohorts, the minor T-allele of rs2284659 variant was inversely associated with the prevalence at baseline (Odds Ratio 0.48, 95% CI 0.29-0.78, p = 0.004) and the incidence during follow-up of myocardial infarction (Hazard Ratio 0.58, 95% CI 0.40-0.83, p = 0.003) and with cardiovascular (HR 0.33, 95% CI 0.08-0.74, p = 0.004) and all-cause mortality (HR 0.44, 95% CI 0.21-0.73, p = 0.0006). The protective allele was associated with higher plasma EC-SOD and lower plasma AOPP concentrations in GENEDIAB. It was also inversely associated with incidence of myocardial infarction (HR 0.75, 95% CI 0.59-0.94, p = 0.01) and all-cause mortality (HR 0.87, 95% CI 0.79-0.97, p = 0.008) in DIABHYCAR.

    CONCLUSIONS: The T-allele of rs2284659 in the promoter of SOD3 was associated with a more favorable plasma redox status and with better cardiovascular outcomes in diabetic patients. Our results suggest that EC-SOD plays an important role in the mechanisms of vascular protection against diabetes-related oxidative stress.

  • 6.
    Song, Xin
    et al.
    Univ Helsinki, Hjelt Inst, Dept Publ Hlth, Helsinki, Finland.
    Tabak, Adam G.
    UCL, Dept Epidemiol & Publ Hlth, London, England.
    Zethelius, Björn
    Uppsala Univ, Dept Publ Hlth & Caring Sci Geriatr, Uppsala, Sweden.
    Yudkin, John S.
    UCL, Dept Med, London, England.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia.
    Laatikainen, Tiina
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
    Stehouwer, Coen D. A.
    Maastricht Univ, Med Ctr, Dept Internal Med, Maastricht, Netherlands.
    Dankner, Rachel
    Sheba Med Ctr, Gertner Inst, Cardiovasc Epidemiol Unit, Tel Hashomer, Israel.
    Jousilahti, Pekka
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
    Onat, Altan
    Cerrahpasa Med Fac, Dept Cardiol, Istanbul, Turkey.
    Nilsson, Peter M.
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Satman, Ilhan
    Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey.
    Vaccaro, Olga
    Univ Naples Federico II, Dept Clin Med & Surg, Naples, Italy.
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
    Qiao, Qing
    Univ Helsinki, Hjelt Inst, Dept Publ Hlth, Helsinki, Finland.
    Obesity attenuates gender differences in cardiovascular mortality2014In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 13, p. 144-Article in journal (Refereed)
    Abstract [en]

    Background: To estimate cardiovascular disease (CVD) mortality in relation to obesity and gender. Methods: Data from 11 prospective cohorts from four European countries including 23 629 men and 21 965 women, aged 24 to 99 years, with a median follow-up of 7.9 years were analyzed. Hazards ratios (HR) for CVD mortality in relation to baseline body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were estimated using Cox proportional hazards models with age as the timescale. Results: Men had higher CVD mortality than women in all four BMI categories (<25.0, 25.0-29.9, 30.0-34.9 and >= 35.0 kg/m(2)). Compared with the lowest BMI category in women, multivariable adjusted HRs (95% confidence intervals) for higher BMI categories are 1.0 (0.8-1.4), 1.6 (1.1-2.1) and 2.8 (2.0-3.8) in women and 2.8 (2.2-3.6), 3.1 (2.5-3.9), 3.8 (2.9-4.9) and 5.4 (3.8-7.7) in men, respectively. Similar findings were observed for abdominal obesity defined by WC, WHR or WHtR. The gender difference was slightly smaller in obese than in non-obese individuals; but the interaction was statistically significant only between gender and WC (p = 0.02), and WHtR (p = 0.01). None of the interaction terms was significant among non-diabetic individuals. Conclusions: Men had higher CVD mortality than women across categories of anthropometric measures of obesity. The gender difference was attenuated in obese individuals, which warrants further investigation.

  • 7. Svensson, Maria K.
    et al.
    Lindmark, Stina
    Wiklund, Urban
    Rask, Peter
    Karlsson, Marcus
    Myrin, Jan
    Kullberg, Joel
    Johansson, Lars
    Eriksson, Jan W.
    Alterations in heart rate variability during everyday life are linked to insulin resistance. A role of dominating sympathetic over parasympathetic nerve activity?2016In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 15, article id 91Article in journal (Refereed)
    Abstract [en]

    Aims: To evaluate the role of the autonomic nervous system (ANS) in the development of insulin resistance (IR) and assess the relationship between IR and activity of ANS using power spectrum analysis of heart rate variability (HRV).

    Subjects and methods: Twenty-three healthy first-degree relatives of patients with type 2 diabetes (R) and 24 control subjects without family history of diabetes (C) group-matched for age, BMI and sex were included. Insulin sensitivity (M value) was assessed by hyperinsulinemic (56 mU/m2/min) euglycemic clamp. Activity of the ANS was assessed using power spectrum analysis of HRV in long-term recordings, i.e., 24-h ECG monitoring, and in short-term recordings during manoeuvres activating the ANS. Computed tomography was performed to estimate the amount and distribution of abdominal adipose tissue.

    Results: Insulin sensitivity (M value, mg/kg lbm/min) did not differ significantly between the R and C groups. Total spectral power (Ptot) and very low-frequency (PVLF) power was lower in R than C during 24 h ECG-recordings (p = 0.02 and p = 0.03). The best fit multiple variable linear regression model (r2 = 0.37, p < 0.001 for model) indicated that body composition (BMI) and long-term low to high frequency (LF/HF) power ratio (std β = −0.46, p = 0.001 and std β = −0.28, p = 0.003, respectively) were significantly and independently associated with the M value.

    Conclusion: Altered heart rate variability, assessed by power spectrum analysis, during everyday life is linked to insulin resistance. The data suggest that an increased ratio of sympathetic to parasympathetic nerve activity, occurring via both inherited and acquired mechanisms, could potentially contribute to the development of type 2 diabetes.

  • 8. Timpka, Simon
    et al.
    Markovitz, Amanda
    Schyman, Tommy
    Mogren, Ingrid
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Fraser, Abigail
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Clinical Sciences Malmö, Lund University, Malmö, Sweden; Harvard T.H. Chan School of Public Health, Boston, MA, USA.
    Rich-Edwards, Janet W.
    Midlife development of type 2 diabetes and hypertension in women by history of hypertensive disorders of pregnancy2018In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 17, article id 124Article in journal (Refereed)
    Abstract [en]

    Background: Women with history of hypertensive disorders of pregnancy (HDP) are at increased risk of early onset cardiovascular disease and type 2 diabetes (T2D). We aimed to investigate the extent to which HDP is also associated with midlife development of T2D and hypertension above and beyond established risk factors.

    Methods: We included parous women who attended population-based structured clinical visits at age 50 and 60 years in Sweden 1991-2013 (N = 6587). Women with prior diabetes mellitus, stroke, or ischemic heart disease at age 50 years were excluded. Data on reproductive history were collected from registries. To study the association between history of HDP and the between-visits development of T2D, hypertension, and clinical risk factors of cardio-metabolic disease (body mass index (BMI), blood pressure, and total cholesterol), we utilized multivariable adjusted regression models (logistic, log binomial, and linear regression, respectively). Models included data on outcome risk factors at age 50 years, e.g. BMI, 75 g 2 h oral glucose tolerance test result, and mean arterial pressure, respectively.

    Results: Between ages 50 and 60 years, 5.8% of initially disease-free women developed T2D and 31.6% developed hypertension. History of HDP was associated with increased risk of developing T2D between age 50 and 60 years even when adjusting for risk factors, including BMI, at age 50 years (odds ratio (OR) 1.96, 95% confidence interval (CI) 1.29-2.98). By contrast, the higher risk of developing hypertension observed in women with history of HDP (relative risk (RR) 1.47, 95% CI 1.22-1.78) was attenuated when adjusted for risk factors (RR 1.09, 95% CI 0.94-1.25). Participants with a history of HDP had higher mean BMI and blood pressure at age 50 years, with levels roughly corresponding to those observed at age 60 years in unaffected women.

    Conclusions: Women with history of HDP are not only at higher risk of cardiometabolic disease during their reproductive years, but HDP is also associated with midlife T2D development above and beyond established risk factors.

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