| 1. |
- Zimmerman, Malin, et al.
(författare)
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Temporal trend of autonomic nerve function and HSP27, MIF and PAI-1 in type 1 diabetes
- 2017
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Ingår i: Journal of Clinical and Translational Endocrinology. - : Elsevier BV. - 2214-6237. ; 8, s. 15-21
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Tidskriftsartikel (refereegranskat)abstract
- Aim Diabetes mellitus type 1 (T1D) has numerous complications including autonomic neuropathy, i.e. dysfunction of the autonomous nervous system. This study focuses on Heat Shock Protein 27 (HSP27), Macrophage Migration Inhibitory Factor (MIF), Plasminogen Activator Inhibitor-1 (PAI-1) and HbA1c and their possible roles in effects of diabetes on the autonomic nervous system. Methods Patients with T1D (n = 32, 41% women) were recruited in 1985 and followed up on four occasions (1989, 1993, 1998, and 2005). Autonomic function was tested using expiration/inspiration (E/I-ratio). Blood samples, i.e. HSP27 (last three occasions), MIF, PAI-1 (last two occasions) and HbA1c (five occasions), were analyzed. Results Autonomic nerve function deteriorated over time during the 20-year-period, but levels of HSP27, MIF, and PAI-1 were not associated with cardiovascular autonomic neuropathy. MIF and PAI-1 were lower in T1D than in healthy controls in 2005. Increased HbA1c correlated with a decrease in E/I-ratio. Conclusions Neither the neuroprotective substance HSP27 nor the inflammatory substances, MIF and PAI-1 were associated with measures of cardiovascular autonomic nerve function, but a deterioration of such function was observed in relation to increasing HbA1c in T1D during a 20-year follow-up period. Improved glucose control might be associated with protection against autonomic neuropathy in T1D.
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| 2. |
- Abbas, S., et al.
(författare)
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Dietary vitamin D intake and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition: the EPIC-InterAct study
- 2014
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 68:2, s. 196-202
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/OBJECTIVES: Prospective cohort studies have indicated that serum vitamin D levels are inversely related to risk of type 2 diabetes. However, such studies cannot determine the source of vitamin D. Therefore, we examined the association of dietary vitamin D intake with incident type 2 diabetes within the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study in a heterogeneous European population including eight countries with large geographical variation. SUBJECTS/METHODS: Using a case-cohort design, 11 245 incident cases of type 2 diabetes and a representative subcohort (N = 15 798) were included in the analyses. Hazard ratios (HR) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using a Prentice-weighted Cox regression adjusted for potential confounders. Twenty-four-hour diet-recall data from a subsample (N = 2347) were used to calibrate habitual intake data derived from dietary questionnaires. RESULTS: Median follow-up time was 10.8 years. Dietary vitamin D intake was not significantly associated with the risk of type 2 diabetes. HR and 95% CIs for the highest compared to the lowest quintile of uncalibrated vitamin D intake was 1.09 (0.97-1.22) (P-trend = 0.17). No associations were observed in a sex-specific analysis. The overall pooled effect (HR (95% CI)) using the continuous calibrated variable was 1.00 (0.97-1.03) per increase of 1 mg/day dietary vitamin D. CONCLUSIONS: This observational study does not support an association between higher dietary vitamin D intake and type 2 diabetes incidence. This result has to be interpreted in light of the limited contribution of dietary vitamin D on the overall vitamin D status of a person.
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| 3. |
- Albrechtsen, A., et al.
(författare)
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Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes
- 2013
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 56:2, s. 298-310
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Tidskriftsartikel (refereegranskat)abstract
- Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) > 1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8x) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI > 27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF > 1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 x 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 x 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 x 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.
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| 4. |
- Andersen, Caroline, et al.
(författare)
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Worse glycaemic control in LADA patients than in those with type 2 diabetes, despite a longer time on insulin therapy
- 2013
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 56:2, s. 252-258
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Tidskriftsartikel (refereegranskat)abstract
- Our aim was to study whether glycaemic control differs between individuals with latent autoimmune diabetes in adults (LADA) and patients with type 2 diabetes, and whether it is influenced by time on insulin therapy. We performed a retrospective study of 372 patients with LADA (205 men and 167 women; median age 54 years, range 35-80 years) from Swedish cohorts from SkAyenne (n = 272) and Vasterbotten (n = 100). Age- and sex-matched patients with type 2 diabetes were included as controls. Data on the use of oral hypoglycaemic agents (OHAs), insulin and insulin-OHA combination therapy was retrieved from the medical records. Poor glycaemic control was defined as HbA(1c) a parts per thousand yen7.0% (a parts per thousand yen53 mmol/mol) at follow-up. The individuals with LADA and with type 2 diabetes were followed for an average of 107 months. LADA patients were leaner than type 2 diabetes patients at diagnosis (BMI 27.7 vs 31.0 kg/m(2); p < 0.001) and follow-up (BMI 27.9 vs 30.2 kg/m(2); p < 0.001). Patients with LADA had been treated with insulin for longer than those with type 2 diabetes (53.3 vs 28.8 months; p < 0.001). There was no significant difference between the patient groups with regard to poor glycaemic control at diagnosis, but more patients with LADA (67.8%) than type 2 diabetes patients (53.0%; p < 0.001) had poor glycaemic control at follow-up. Patients with LADA had worse glycaemic control at follow-up compared with participants with type 2 diabetes (OR = 1.8, 95% CI 1.2, 2.7), adjusted for age at diagnosis, HbA(1c), BMI at diagnosis, follow-up time and duration of insulin treatment. Individuals with LADA have worse glycaemic control than patients with type 2 diabetes despite a longer time on insulin therapy.
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| 5. |
- Andersen, Mette, et al.
(författare)
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Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes
- 2014
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 57:9, s. 1859-1868
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Latent autoimmune diabetes in adults (LADA) is phenotypically a hybrid of type 1 and type 2 diabetes. Genetically LADA is poorly characterised but does share genetic predisposition with type 1 diabetes. We aimed to improve the genetic characterisation of LADA and hypothesised that type 2 diabetes-associated gene variants also predispose to LADA, and that the associations would be strongest in LADA patients with low levels of GAD autoantibodies (GADA). Methods We assessed 41 type 2 diabetes-associated gene variants in Finnish (phase I) and Swedish (phase II) patients with LADA (n=911) or type 1 diabetes (n=406), all diagnosed after the age of 35 years, as well as in non-diabetic control individuals 40 years or older (n=4,002). Results Variants in the ZMIZ1 (rs12571751, p=4.1 x 10(-5)) and TCF7L2 (rs7903146, p=5.8 x 10(-4)) loci were strongly associated with LADA. Variants in the KCNQ1 (rs2237895, p=0.0012), HHEX (rs1111875, p=0.0024 in Finns) and MTNR1B (rs10830963, p=0.0039) loci showed the strongest association in patients with low GADA, supporting the hypothesis that the disease in these patients is more like type 2 diabetes. In contrast, variants in the KLHDC5 (rs10842994, p=9.5 x 10(-4) in Finns), TP53INP1 (rs896854, p=0.005), CDKAL1 (rs7756992, p=7.0 x 10(-4); rs7754840, p=8.8 x 10(-4)) and PROX1 (rs340874, p=0.003) loci showed the strongest association in patients with high GADA. For type 1 diabetes, a strong association was seen for MTNR1B (rs10830963, p=3.2 x 10(-6)) and HNF1A (rs2650000, p=0.0012). Conclusions/interpretation LADA and adult-onset type 1 diabetes share genetic risk variants with type 2 diabetes, supporting the idea of a hybrid form of diabetes and distinguishing them from patients with classical young-onset type 1 diabetes.
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| 6. |
- Andersson, Jenny, et al.
(författare)
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Att skapa läkare i glesbygd
- 2018
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Ingår i: Allmänmedicin : tidskrift för Svensk förening för allmänmedicin. - Stockholm : Svensk förening för allmänmedicin (SFAM). - 0281-3513 .- 2001-8169. ; :3, s. 26-27
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 7. |
- Awad, Anna, et al.
(författare)
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Lower cognitive performance among long-term type 1 diabetes survivors : A case-control study
- 2017
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Ingår i: Journal of diabetes and its complications. - : Elsevier. - 1056-8727 .- 1873-460X. ; 31:8, s. 1328-1331
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Patients with type 1 diabetes (T1D) have an increased risk of cognitive dysfunction. The cognitive decrement is believed to depend on macro- and microvascular complications and long disease duration. Some patients do not develop these complications, but still report cognitive symptoms. We examined if long-standing T1D without complications is associated with lower cognitive performance.METHODS: A group of patients (n=43) with long-standing T1D (>30years) without micro- or macro vascular complications was compared with a non-diabetic control group (n=86) on six cognitive tests which probed episodic memory, semantic memory, episodic short-term memory, visual attention and psychomotor speed. Each patient was matched with two controls regarding age, gender and education. A linear mixed effect model was used to analyze the data.RESULTS: The mean age was 57years and mean duration was 41years. Patients with diabetes had lower diastolic blood pressure but BMI, waist circumference, systolic blood pressure and smoking did not differ between groups. Patients had lower results than non-diabetic controls in episodic short-term memory (p<0.001) and also lower values on a test that mirrors visual attention and psychomotor speed (p=0.019).CONCLUSIONS: Long-standing T1D was associated with lower cognitive performance, regardless of other diabetes-related complications.
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| 8. |
- Backeström, Anna, et al.
(författare)
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Acute hyperglycaemia leads to altered frontal lobe brain activity and reduced working memory in type 2 diabetes.
- 2021
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- How acute hyperglycaemia affects memory functions and functional brain responses in individuals with and without type 2 diabetes is unclear. Our aim was to study the association between acute hyperglycaemia and working, semantic, and episodic memory in participants with type 2 diabetes compared to a sex- and age-matched control group. We also assessed the effect of hyperglycaemia on working memory-related brain activity. A total of 36 participants with type 2 diabetes and 34 controls (mean age, 66 years) underwent hyperglycaemic clamp or placebo clamp in a blinded and randomised order. Working, episodic, and semantic memory were tested. Overall, the control group had higher working memory (mean z-score 33.15 ± 0.45) than the group with type 2 diabetes (mean z-score 31.8 ± 0.44, p = 0.042) considering both the placebo and hyperglycaemic clamps. Acute hyperglycaemia did not influence episodic, semantic, or working memory performance in either group. Twenty-two of the participants (10 cases, 12 controls, mean age 69 years) were randomly invited to undergo the same clamp procedures to challenge working memory, using 1-, 2-, and 3-back, while monitoring brain activity by blood oxygen level-dependent functional magnetic resonance imaging (fMRI). The participants with type 2 diabetes had reduced working memory during the 1- and 2-back tests. fMRI during placebo clamp revealed increased BOLD signal in the left lateral frontal cortex and the anterior cingulate cortex as a function of working memory load in both groups (3>2>1). During hyperglycaemia, controls showed a similar load-dependent fMRI response, whereas the type 2 diabetes group showed decreased BOLD response from 2- to 3-back. These results suggest that impaired glucose metabolism in the brain affects working memory, possibly by reducing activity in important frontal brain areas in persons with type 2 diabetes.
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| 9. |
- Backeström, Anna, et al.
(författare)
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Glucose but not insulin or insulin resistance is associated with memory performance in middle-aged non-diabetic women : a cross sectional study
- 2015
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Ingår i: Diabetology & Metabolic Syndrome. - : Springer Science and Business Media LLC. - 1758-5996. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Elevated concentrations of plasma glucose appear to play a role in memory impairment, and it has been suggested that insulin might also have a negative effect on cognitive function. Our aim was to study whether glucose, insulin or insulin resistance are associated with episodic or semantic memory in a non-diabetic and non-demented population. Methods: We linked and matched two population-based data sets identifying 291 participants (127 men and 164 women, mean age of 50.7 +/- 8.0 years). Episodic and semantic memory functions were tested, and fasting plasma insulin, fasting plasma glucose, and 2-hour glucose were analysed along with other potential influencing factors on memory function. Since men and women display different results on memory functions they were analysed separately. Insulin resistance was calculated using the HOMA-IR method. Results: A higher fasting plasma glucose concentration was associated with lower episodic memory in women (r = -0.08, 95% CI -0.14; -0.01), but not in men. Plasma insulin levels and insulin resistance were not associated with episodic or semantic memory in women or in men after adjustments for age, fasting glucose, 2-hour glucose, BMI, education, smoking, cardiovascular disease, hypertension, cholesterol, and physical activity. Conclusions: This indicates that fasting glucose but not insulin, might have impact on episodic memory in middle-aged women.
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| 10. |
- Badian, Reza A., et al.
(författare)
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Comparison of novel wide-field in vivo corneal confocal microscopy with skin biopsy for assessing peripheral neuropathy in type 2 diabetes
- 2023
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 72:7, s. 908-917
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic peripheral neuropathy (DPN) is a serious complication of diabetes, where skin biopsy assessing intraepi-dermal nerve fiber density (IENFD) plays an important diagnostic role. In vivo confocal microscopy (IVCM) of the corneal subbasal nerve plexus has been proposed as a noninvasive diagnostic modality for DPN. Direct compari-sons of skin biopsy and IVCM in controlled cohorts are lacking, as IVCM relies on subjective selection of images depicting only 0.2% of the nerve plexus. We compared these diagnostic modalities in a fixed-age cohort of 41 participants with type 2 diabetes and 36 healthy participants using machine algorithms to create wide-field image mosaics and quantify nerves in an area 37 times the size of prior studies to avoid human bias. In the same partici-pants, and at the same time point, no correlation between IENFD and corneal nerve density was found. Corneal nerve density did not correlate with clinical measures of DPN, including neuropathy symptom and disability scores, nerve conduction studies, or quantitative sensory tests. Our findings indicate that corneal and intraepidermal nerves likely mirror different aspects of nerve degeneration, where only intraepidermal nerves appear to reflect the clinical status of DPN, suggesting that scrutiny is warranted concerning methodologies of studies using corneal nerves to assess DPN.
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| 11. |
- Bendinelli, B., et al.
(författare)
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Association between dietary meat consumption and incident type 2 diabetes : the EPIC-InterAct study
- 2013
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 56:1, s. 47-59
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: A diet rich in meat has been reported to contribute to the risk of type 2 diabetes. The present study aims to investigate the association between meat consumption and incident type 2 diabetes in the EPIC-InterAct study, a large prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Methods: During 11.7 years of follow-up, 12,403 incident cases of type 2 diabetes were identified among 340,234 adults from eight European countries. A centre-stratified random subsample of 16,835 individuals was selected in order to perform a case-cohort design. Prentice-weighted Cox regression analyses were used to estimate HR and 95% CI for incident diabetes according to meat consumption.Results: Overall, multivariate analyses showed significant positive associations with incident type 2 diabetes for increasing consumption of total meat (50 g increments: HR 1.08; 95% CI 1.05, 1.12), red meat (HR 1.08; 95% CI 1.03, 1.13) and processed meat (HR 1.12; 95% CI 1.05, 1.19), and a borderline positive association with meat iron intake. Effect modifications by sex and class of BMI were observed. In men, the results of the overall analyses were confirmed. In women, the association with total and red meat persisted, although attenuated, while an association with poultry consumption also emerged (HR 1.20; 95% CI 1.07, 1.34). These associations were not evident among obese participants.Conclusions/interpretation: This prospective study confirms a positive association between high consumption of total and red meat and incident type 2 diabetes in a large cohort of European adults.
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| 12. |
- Bennet, L., et al.
(författare)
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Mortality in first- and second- generation immigrants to Sweden diagnosed with type 2 diabetes
- 2020
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 63:Suppl. 1, s. S43-S43
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Non-western immigrants to Europe are at high risk for type 2 diabetes (T2D). In this nationwide study including incident cases of T2D, the aim was to compare mortality in first- and second generation immigrants with native Swedes.Materials and methods: Patients living in Sweden diagnosed with a new-onset pharmacologically treated T2D between 2006 to 2012 were identified through the Swedish Prescription Drug Register. Patients were followed until December 31, 2016 for all-cause mortality (ACM) and until December 31, 2012 for cause-specific mortality (CSM). Analyses were adjusted for age at diagnosis, sex, year of diagnosis, socioeconomy, education, treatment and region. Comparisons were assessed using coxregression analysis.Results: In total, 169 300 individuals (129 533 (76.3%) native Swedes; 31 988 (18.9%) first-generation immigrants, and 7 799 (4.8%) second-generation immigrants with either one or both parents born outside Sweden) were diagnosed with T2D between 2006 and 2012 and fulfilled inclusion criteria. First-generation immigrants had lower ACM rate [hazard ratio (HR): 0.85, 95% CI 0.82 to 0.89] compared with native Swedes. The mortality was particularly low in persons born in the Middle East [0.45,0.40 to 0.51], Asia [0.56, 0.46 to 0.68], and Africa [0.88. 0.82 to 0.95]. Mortality rates decreased with older age at migration and shorter stay in Sweden, with the lowest rate in those originating from the Middle East living in Sweden <25 years [0.40, 0.34 to 0.46]. First-generation immigrants born in the Middle East (0.43; 0.30-0.62), and Asia (0.38; 0.19- 0.77) had lower cardiovascular disease related mortality rates compared with native Swedes. Middle Eastern immigrants further displayed lower cancer related mortality rate (0.59, 0.42 to 0.84) compared with native Swedes. Second generation immigrants displayed similar survival rates as native Swedes.Conclusion: Our data indicate that in T2D patients, exposure to the Swedish environment seems to have a larger impact on mortality risk than region of origin. This study indicates protecting mechanisms on mortality related to the non-western environment.
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| 13. |
- Bennet, Louise, et al.
(författare)
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Mortality in first- and second-generation immigrants to Sweden diagnosed with type 2 diabetes : a 10 year nationwide cohort study
- 2021
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 64:1, s. 95-108
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Non-Western immigrants to Europe are at high risk for type 2 diabetes. In this nationwide study including incident cases of type 2 diabetes, the aim was to compare all-cause mortality (ACM) and cause-specific mortality (CSM) rates in first- and second-generation immigrants with native Swedes.Methods: People living in Sweden diagnosed with new-onset pharmacologically treated type 2 diabetes between 2006 and 2012 were identified through the Swedish Prescribed Drug Register. They were followed until 31 December 2016 for ACM and until 31 December 2012 for CSM. Analyses were adjusted for age at diagnosis, sex, socioeconomic status, education, treatment and region. Associations were assessed using Cox regression analysis.Results: In total, 138,085 individuals were diagnosed with type 2 diabetes between 2006 and 2012 and fulfilled inclusion criteria. Of these, 102,163 (74.0%) were native Swedes, 28,819 (20.9%) were first-generation immigrants and 7103 (5.1%) were second-generation immigrants with either one or both parents born outside Sweden. First-generation immigrants had lower ACM rate (HR 0.80 [95% CI 0.76, 0.84]) compared with native Swedes. The mortality rates were particularly low in people born in non-Western regions (0.46 [0.42, 0.50]; the Middle East, 0.41 [0.36, 0.47]; Asia, 0.53 [0.43, 0.66]; Africa, 0.47 [0.38, 0.59]; and Latin America, 0.53 [0.42, 0.68]). ACM rates decreased with older age at migration and shorter stay in Sweden. Compared with native Swedes, first-generation immigrants with <= 24 years in Sweden (0.55 [0.51, 0.60]) displayed lower ACM rates than those spending >24 years in Sweden (0.92 [0.87, 0.97]). Second-generation immigrants did not have better survival rates than native Swedes but rather displayed higher ACM rates for people with both parents born abroad (1.28 [1.05, 1.56]).Conclusions/interpretation: In people with type 2 diabetes, the lower mortality rate in first-generation non-Western immigrants compared with native Swedes was reduced over time and was equalised in second-generation immigrants. These findings suggest that acculturation to Western culture may impact ACM and CSM in immigrants with type 2 diabetes but further investigation is needed.
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| 14. |
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| 15. |
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| 16. |
- Beulens, J. W. J., et al.
(författare)
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Alcohol consumption and risk of type 2 diabetes in European men and women : influence of beverage type and body size The EPIC-InterAct study
- 2012
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Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell. - 0954-6820 .- 1365-2796. ; 272:4, s. 358-370
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the association between alcohol consumption and type 2 diabetes, and determine whether this is modified by sex, body mass index (BMI) and beverage type. Design: Multicentre prospective casecohort study. Setting: Eight countries from the European Prospective Investigation into Cancer and Nutrition cohort. Subjects: A representative baseline sample of 16 154 participants and 12 403 incident cases of type 2 diabetes. Interventions: Alcohol consumption assessed using validated dietary questionnaires. Main outcome measures: Occurrence of type 2 diabetes based on multiple sources (mainly self-reports), verified against medical information. Results: Amongst men, moderate alcohol consumption was nonsignificantly associated with a lower incidence of diabetes with a hazard ratio (HR) of 0.90 (95% CI: 0.781.05) for 6.112.0 versus 0.16.0 g day-1, adjusted for dietary and diabetes risk factors. However, the lowest risk was observed at higher intakes of 24.196.0 g day-1 with an HR of 0.86 (95% CI: 0.750.98). Amongst women, moderate alcohol consumption was associated with a lower incidence of diabetes with a hazard ratio of 0.82 (95% CI: 0.720.92) for 6.112.0 g day-1 (P interaction gender <0.01). The inverse association between alcohol consumption and diabetes was more pronounced amongst overweight (BMI = 25 kg m-2) than normal-weight men and women (P interaction < 0.05). Adjusting for waist and hip circumference did not alter the results for men, but attenuated the association for women (HR=0.90, 95% CI: 0.791.03 for 6.112.0 g day-1). Wine consumption for men and fortified wine consumption for women were most strongly associated with a reduced risk of diabetes. Conclusions: The results of this study show that moderate alcohol consumption is associated with a lower risk of type 2 diabetes amongst women only. However, this risk reduction is in part explained by fat distribution. The relation between alcohol consumption and type 2 diabetes was stronger for overweight than normal-weight women and men.
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| 17. |
- Brand, Judith S., et al.
(författare)
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Age at Menopause, Reproductive Life Span, and Type 2 Diabetes Risk
- 2013
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 36:4, s. 1012-1019
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-Age at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk.RESEARCH DESIGN AND METHODS-Data were obtained from the InterAct study, a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 3,691 postmenopausal type 2 diabetic case subjects and 4,408 subcohort members were included in the analysis, with a median follow-up of 11 years. Prentice weighted Cox proportional hazards models were adjusted for age, known risk factors for diabetes, and reproductive factors, and effect modification by BMI, waist circumference, and smoking was studied.RESULTS-Mean (SD) age of the subcohort was 59.2 (5.8) years. After multivariable adjustment, hazard ratios (HRs) of type 2 diabetes were 1.32 (95% CI 1.04-1.69), 1.09 (0.90-1.31), 0.97 (0.86-1.10), and 0.85 (0.70-1.03) for women with menopause at ages <40, 40-44, 45-49, and >= 55 years, respectively, relative to those with menopause at age 50-54 years. The HR per SD younger age at menopause was 1.08 (1.02-1.14). Similarly, a shorter reproductive life span was associated with a higher diabetes risk (HR per SD lower reproductive life span 1.06 [ 1.01-1.12]). No effect modification by BMI, waist circumference, or smoking was observed (P interaction all > 0.05).CONCLUSIONS-Early menopause is associated with a greater risk of type 2 diabetes. Diabetes Care 36:1012-1019, 2013
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| 18. |
- Brand, J. S., et al.
(författare)
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Diabetes and onset of natural menopause : results from the European Prospective Investigation into Cancer and Nutrition
- 2015
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Ingår i: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 30:6, s. 1491-1498
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Do women who have diabetes before menopause have their menopause at an earlier age compared with women without diabetes? SUMMARY ANSWER: Although there was no overall association between diabetes and age at menopause, our study suggests that early-onset diabetes may accelerate menopause. WHAT IS KNOWN ALREADY: Today, more women of childbearing age are being diagnosed with diabetes, but little is known about the impact of diabetes on reproductive health. STUDY DESIGN, SIZE, DURATION: We investigated the impact of diabetes on age at natural menopause (ANM) in 258 898 women from the European Prospective Investigation into Cancer and Nutrition (EPIC), enrolled between 1992 and 2000. PARTICIPANTS/MATERIALS, SETTING, METHODS: Determinant and outcome information was obtained through questionnaires. Time-dependent Cox regression analyses were used to estimate the associations of diabetes and age at diabetes diagnosis with ANM, stratified by center and adjusted for age, smoking, reproductive and diabetes risk factors and with age from birth to menopause or censoring as the underlying time scale. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, no association between diabetes and ANM was found (hazard ratio (HR) = 0.94; 95% confidence interval (CI) 0.89-1.01). However, women with diabetes before the age of 20 years had an earlier menopause (10-20 years: HR = 1.43; 95% CI 1.02-2.01, <10 years: HR = 1.59; 95% CI 1.03-2.43) compared with non-diabetic women, whereas women with diabetes at age 50 years and older had a later menopause (HR = 0.81; 95% CI 0.70-0.95). None of the other age groups were associated with ANM. LIMITATIONS, REASONS FOR CAUTION: Strengths of the study include the large sample size and the broad set of potential confounders measured. However, results may have been underestimated due to survival bias. We cannot be sure about the sequence of the events in women with a late age at diabetes, as both events then occur in a short period. We could not distinguish between type 1 and type 2 diabetes. WIDER IMPLICATIONS OF THE FINDINGS: Based on the literature, an accelerating effect of early-onset diabetes on ANM might be plausible. A delaying effect of late-onset diabetes on ANM has not been reported before, and is not in agreement with recent studies suggesting the opposite association.
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| 19. |
- Brazel, David M., et al.
(författare)
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Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use
- 2019
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 85:11, s. 946-955
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk.METHODS: We analyzed ∼250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci.RESULTS: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals.CONCLUSIONS: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.
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| 20. |
- Brännholm Syrjälä, Maria, et al.
(författare)
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Health effects of reduced occupational sedentary behaviour in type 2 diabetes using a mobile health intervention : a study protocol for a 12-month randomized controlled trial—the ROSEBUD study
- 2022
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Ingår i: Trials. - : BioMed Central. - 1745-6215. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Short-term trials conducted in adults with type 2 diabetes mellitus (T2DM) showed that reducing sedentary behaviour by performing regular short bouts of light-intensity physical activity enhances health. Moreover, support for reducing sedentary behaviour may be provided at a low cost via mobile health technology (mHealth). There are a wide range of mHealth solutions available including SMS text message reminders and activity trackers that monitor the physical activity level and notify the user of prolonged sitting periods. The aim of this study is to evaluate the effects of a mHealth intervention on sedentary behaviour and physical activity and the associated changes in health in adults with T2DM.Methods: A dual-arm, 12-month, randomized controlled trial (RCT) will be conducted within a nationwide Swedish collaboration for diabetes research in primary health care. Individuals with T2DM (n = 142) and mainly sedentary work will be recruited across primary health care centres in five regions in Sweden. Participants will be randomized (1:1) into two groups. A mHealth intervention group who will receive an activity tracker wristband (Garmin Vivofit4), regular SMS text message reminders, and counselling with a diabetes specialist nurse, or a comparator group who will receive counselling with a diabetes specialist nurse only. The primary outcomes are device-measured total sitting time and total number of steps (activPAL3). The secondary outcomes are fatigue, health-related quality of life and musculoskeletal problems (self-reported questionnaires), number of sick leave days (diaries), diabetes medications (clinical record review) and cardiometabolic biomarkers including waist circumference, mean blood pressure, HbA1c, HDL-cholesterol and triglycerides.Discussion: Successful interventions to increase physical activity among those with T2DM have been costly and long-term effectiveness remains uncertain. The use of mHealth technologies such as activity trackers and SMS text reminders may increase awareness of prolonged sedentary behaviour and encourage increase in regular physical activity. mHealth may, therefore, provide a valuable and novel tool to improve health outcomes and clinical management in those with T2DM. This 12-month RCT will evaluate longer-term effects of a mHealth intervention suitable for real-world primary health care settings.
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| 21. |
- Buijsse, B, et al.
(författare)
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Consumption of fatty foods and incident type 2 diabetes in populations from eight European countries.
- 2015
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 69:4, s. 455-461
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Tidskriftsartikel (refereegranskat)abstract
- Background/Objectives:Diets high in saturated and trans fat and low in unsaturated fat may increase type 2 diabetes (T2D) risk, but studies on foods high in fat per unit weight are sparse. We assessed whether the intake of vegetable oil, butter, margarine, nuts and seeds and cakes and cookies is related to incident T2D.Subjects/Methods:A case-cohort study was conducted, nested within eight countries of the European Prospective Investigation into Cancer (EPIC), with 12 403 incident T2D cases and a subcohort of 16 835 people, identified from a cohort of 340 234 people. Diet was assessed at baseline (1991-1999) by country-specific questionnaires. Country-specific hazard ratios (HRs) across four categories of fatty foods (nonconsumers and tertiles among consumers) were combined with random-effects meta-analysis.Results:After adjustment not including body mass index (BMI), nonconsumers of butter, nuts and seeds and cakes and cookies were at higher T2D risk compared with the middle tertile of consumption. Among consumers, cakes and cookies were inversely related to T2D (HRs across increasing tertiles 1.14, 1.00 and 0.92, respectively; P-trend <0.0001). All these associations attenuated upon adjustment for BMI, except the higher risk of nonconsumers of cakes and cookies (HR 1.57). Higher consumption of margarine became positively associated after BMI adjustment (HRs across increasing consumption tertiles: 0.93, 1.00 and 1.12; P-trend 0.03). Within consumers, vegetable oil, butter and nuts and seeds were unrelated to T2D.Conclusions:Fatty foods were generally not associated with T2D, apart from weak positive association for margarine. The higher risk among nonconsumers of cakes and cookies needs further explanation.European Journal of Clinical Nutrition advance online publication, 26 November 2014; doi:10.1038/ejcn.2014.249.
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| 22. |
- Burger, Koert N. J., et al.
(författare)
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Dietary Fiber, Carbohydrate Quality and Quantity, and Mortality Risk of Individuals with Diabetes Mellitus
- 2012
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Ingår i: PLoS ONE. - San Fransisco : Public Library of Science (PLoS). - 1932-6203. ; 7:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dietary fiber, carbohydrate quality and quantity are associated with mortality risk in the general population. Whether this is also the case among diabetes patients is unknown. Objective: To assess the associations of dietary fiber, glycemic load, glycemic index, carbohydrate, sugar, and starch intake with mortality risk in individuals with diabetes. Methods: This study was a prospective cohort study among 6,192 individuals with confirmed diabetes mellitus (mean age of 57.4 years, and median diabetes duration of 4.4 years at baseline) from the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary intake was assessed at baseline (1992-2000) with validated dietary questionnaires. Cox proportional hazards analysis was performed to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality, while adjusting for CVD-related, diabetes-related, and nutritional factors. Results: During a median follow-up of 9.2 y, 791 deaths were recorded, 306 due to CVD. Dietary fiber was inversely associated with all-cause mortality risk (adjusted HR per SD increase, 0.83 [95% CI, 0.75-0.91]) and CVD mortality risk (0.76[0.64-0.89]). No significant associations were observed for glycemic load, glycemic index, carbohydrate, sugar, or starch. Glycemic load (1.42[1.07-1.88]), carbohydrate (1.67[1.18-2.37]) and sugar intake (1.53[1.12-2.09]) were associated with an increased total mortality risk among normal weight individuals (BMI <= 25 kg/m(2); 22% of study population) but not among overweight individuals (P interaction <= 0.04). These associations became stronger after exclusion of energy misreporters. Conclusions: High fiber intake was associated with a decreased mortality risk. High glycemic load, carbohydrate and sugar intake were associated with an increased mortality risk in normal weight individuals with diabetes.
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| 23. |
- Cai, Lina, et al.
(författare)
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Genome-wide association analysis of type 2 diabetes in the EPIC-InterAct study
- 2020
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Ingår i: Scientific Data. - : Nature Publishing Group. - 2052-4463. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes (T2D) is a global public health challenge. Whilst the advent of genome-wide association studies has identified >400 genetic variants associated with T2D, our understanding of its biological mechanisms and translational insights is still limited. The EPIC-InterAct project, centred in 8 countries in the European Prospective Investigations into Cancer and Nutrition study, is one of the largest prospective studies of T2D. Established as a nested case-cohort study to investigate the interplay between genetic and lifestyle behavioural factors on the risk of T2D, a total of 12,403 individuals were identified as incident T2D cases, and a representative sub-cohort of 16,154 individuals was selected from a larger cohort of 340,234 participants with a follow-up time of 3.99 million person-years. We describe the results from a genome-wide association analysis between more than 8.9 million SNPs and T2D risk among 22,326 individuals (9,978 cases and 12,348 non-cases) from the EPIC-InterAct study. The summary statistics to be shared provide a valuable resource to facilitate further investigations into the genetics of T2D.
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| 24. |
- Cooper, A. J., et al.
(författare)
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Fruit and vegetable intake and type 2 diabetes : EPIC-InterAct prospective study and meta-analysis
- 2012
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Ingår i: European Journal of Clinical Nutrition. - London : Nature Publishing Group. - 0954-3007 .- 1476-5640. ; 66:10, s. 1082-1092
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Forskningsöversikt (refereegranskat)abstract
- Fruit and vegetable intake (FVI) may reduce the risk of type 2 diabetes (T2D), but the epidemiological evidence is inconclusive. The aim of this study is to examine the prospective association of FVI with T2D and conduct an updated meta-analysis. In the European Prospective Investigation into Cancer-InterAct (EPIC-InterAct) prospective case-cohort study nested within eight European countries, a representative sample of 16 154 participants and 12 403 incident cases of T2D were identified from 340 234 individuals with 3.99 million person-years of follow-up. For the meta-analysis we identified prospective studies on FVI and T2D risk by systematic searches of MEDLINE and EMBASE until April 2011. In EPIC-InterAct, estimated FVI by dietary questionnaires varied more than twofold between countries. In adjusted analyses the hazard ratio (95% confidence interval) comparing the highest with lowest quartile of reported intake was 0.90 (0.80-1.01) for FVI; 0.89 (0.76-1.04) for fruit and 0.94 (0.84-1.05) for vegetables. Among FV subtypes, only root vegetables were inversely associated with diabetes 0.87 (0.77-0.99). In meta-analysis using pooled data from five studies including EPIC-InterAct, comparing the highest with lowest category for FVI was associated with a lower relative risk of diabetes (0.93 (0.87-1.00)). Fruit or vegetables separately were not associated with diabetes. Among FV subtypes, only green leafy vegetable (GLV) intake (relative risk: 0.84 (0.74-0.94)) was inversely associated with diabetes. Subtypes of vegetables, such as root vegetables or GLVs may be beneficial for the prevention of diabetes, while total FVI may exert a weaker overall effect.
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| 25. |
- Dahlin, Lars, et al.
(författare)
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Disturbed vibrotactile sense in finger pulps in patients with Type 1 diabetes-correlations with glycaemic level, clinical examination and electrophysiology
- 2011
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 28:9, s. 1045-1052
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Tidskriftsartikel (refereegranskat)abstract
- Aims In a cohort of men and women with Type 1 diabetes, prospectively followed for > 20 years, vibrotactile sense in fingers was investigated and related to neurophysiological tests, glycaemic level and clinical score. Methods Out of 58 patients, diagnosed at the age of 15-25 years and recruited 1984-1985, 32 patients (13 women, median age 52 years, range 44-75 years; 19 men, median age 52 years, range 39-69 years; median duration 33.5 years, range 21-52 years) accepted follow-up in 2006. Vibration thresholds were measured in finger pulps of index and little fingers bilaterally at seven frequencies and related to results of touch (monofilaments), tactile discrimination (two-point discrimination test), electrophysiology (median nerve function), glycaemic level (HbA(1c) levels since 1984-1985) and a clinical score. Results Vibrotactile sense was reduced in finger pulps, mainly in men, compared with an age-and gender-matched healthy control group with normal HbA(1c). Vibration thresholds were increased, particularly at 250 and 500 Hz, in both index and little finger pulps. Touch and tactile discrimination correlated with vibration thresholds, but not with each other or with electrophysiology. HbA(1c) levels (at follow-up or mean values from five follow-ups since recruitment) did not correlate with any nerve function variables. Clinical scores correlated with vibrotactile sense, particularly at higher frequencies (> 125 Hz), but not with total Z-scores of electrophysiology. Duration of disease did not correlate with any variables. Conclusions Examination of vibration thresholds in index and little finger pulps may be valuable to detect neuropathy, where thresholds correlate with symptoms and tests.
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