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Aims The glycolysis-derived metabolite methylglyoxal has been linked to clinical microvascular complications, including diabetic nephropathy. We aimed to further investigate the hypothesis that methylglyoxal is involved in decline in renal function by assessing the associations between measures of renal function during a 6-year follow-up in 1481 people with screen-detected Type 2 diabetes, as part of the Danish arm of the ADDITION-Europe trial ( ADDITION- DK). Methods Biobank serum samples collected at ADDITION- DK baseline (2001-2006) and follow-up (2009-2010) were used in the current analysis of methylglyoxal. We assessed cross-sectional baseline and longitudinal associations between methylglyoxal and urinary albumin-to-creatinine ratio ( ACR) or estimated GFR ( eGFR), and between methylglyoxal and categories of albuminuria or reduced eGFR. Results Baseline methylglyoxal was positively associated with ACR at baseline (12% higher ACR per doubling in methylglyoxal levels), and change in methylglyoxal during 6 years of follow-up was inversely associated with change in eGFR (-1.6 ml/min/1.73 m2 per doubling in methylglyoxal change), in models adjusted for age, sex, HbA1c, systolic blood pressure, anti-hypertensive treatment, LDL-cholesterol, lipid-lowering treatment, C-reactive protein and smoking. Conclusions In a population of people with screen-detected Type 2 diabetes, we observed associations between methylglyoxal and markers of renal function: 6-year change in methylglyoxal was inversely associated with 6-year change in eGFR. Also, methylglyoxal at baseline was positively associated with ACR at baseline. Our study lends further support to a role for methylglyoxal in the pathogenesis of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Aims Modulation of dopamine receptor D2 ( DRD2) activity affects insulin secretion in both rodents and isolated pancreatic β-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ ANKK1 locus may affect susceptibility to Type 2 diabetes in humans. Methods Four potentially functional variants in the coding region of the DRD2/ ANKK1 locus (rs1079597, rs6275, rs6277, rs1800497) were genotyped and analysed for Type 2 diabetes susceptibility in up to 25 000 people (8148 with Type 2 diabetes and 17687 control subjects) from two large independent Dutch cohorts and one Danish cohort. In addition, 340 Dutch subjects underwent a 2-h hyperglycaemic clamp to investigate insulin secretion. Since sexual dimorphic associations related to DRD2 polymorphisms have been previously reported, we also performed a gender-stratified analysis. Results rs1800497 at the DRD2/ ANKK1 locus was associated with a significantly increased risk for Type 2 diabetes in women (odds ratio 1.14 (1.06-1.23); P = 4.1*10−4) but not in men (odds ratio 1.00 (95% CI 0.93-1.07); P = 0.92) or the combined group. Although rs1800497 was not associated with insulin secretion, we did find another single nucleotide polymorphism in this locus, rs6275, to be associated with increased first-phase glucose-stimulated insulin secretion in women ( P = 5.5*10−4) but again not in men ( P = 0.34). Conclusion The present data identify DRD2/ ANKK1 as a potential sex-specific Type 2 diabetes susceptibility gene. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, e354-e360 (2012) Abstract Aims Studies suggest that inadequate sleep duration and poor sleep quality increase the risk of impaired glucose regulation and diabetes. However, associations with specific markers of glucose homeostasis are less well explained. The objective of this study was to explore possible associations of sleep duration and sleep quality with markers of glucose homeostasis and glucose tolerance status in a healthy population-based study sample. Methods The study comprised 771 participants from the Danish, population-based cross-sectional 'Health2008' study. Sleep duration and sleep quality were measured by self-report. Markers of glucose homeostasis were derived from a 3-point oral glucose tolerance test and included fasting plasma glucose, 2-h plasma glucose, HbA1c, two measures of insulin sensitivity (the insulin sensitivity index0,120 and homeostasis model assessment of insulin sensitivity), the homeostasis model assessment of β-cell function and glucose tolerance status. Associations of sleep duration and sleep quality with markers of glucose homeostasis and tolerance were analysed by multiple linear and logistic regression. Results A 1-h increment in sleep duration was associated with a 0.3 mmol/mol (0.3%) decrement in HbA1c and a 25% reduction in the risk of having impaired glucose regulation. Further, a 1-point increment in sleep quality was associated with a 2% increase in both the insulin sensitivity index0,120 and homeostasis model assessment of insulin sensitivity, as well as a 1% decrease in homeostasis model assessment of β-cell function. Conclusions In the present study, shorter sleep duration was mainly associated with later alterations in glucose homeostasis, whereas poorer sleep quality was mainly associated with earlier alterations in glucose homeostasis. Thus, adopting healthy sleep habits may benefit glucose metabolism in healthy populations. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, 755-760 (2012) Abstract Background and aim Most studies show that diabetes increases with migration and urbanization. Previous studies from Greenland have shown inconsistent associations between cardiovascular risk and urbanization. Thus, the aim was to study the association between diabetes and urbanization among Greenland Inuit. Methods A total of 3089 adult Inuit aged 18 years and older participated in a geographically representative, population-based study 'Inuit Health in Transition Study'. The examination included a 75 g oral glucose tolerance test and anthropometric measurements. Information on socio-demographic characteristic and health behaviour was obtained by interview or questionnaire. The participants were categorized according to degree of urbanization into three groups based on current place of residence: (1) participants living in towns (> 2000 inhabitants), (2) participants living in small towns (< 2000 inhabitants) and (3) participants living in villages (< 500 inhabitants). Results The total prevalence of diabetes was 9% of which 79% were previously unknown. Nine per cent had impaired glucose tolerance and 19% had impaired fasting glycaemia (IFG). Compared with towns, odds rations (ORs) for diabetes and impaired fasting glycaemia were higher in small towns [ORdiabetes = 1.5 (1.0-2.3), ORIFG = 1.9 (1.2-2.3)] and villages [ORdiabetes = 1.2 (0.8-1.9), ORIFG = 1.3 (0.9-2.0)], whereas no association was seen for impaired glucose tolerance. The inverse association between urbanization and diabetes and impaired fasting glycaemia persisted after adjustment for relevant confounders. Conclusion Diabetes and impaired fasting glycaemia decreased with urbanization contrary to the results of most studies. It appears that Greenland Inuit follow the pattern usually observed in industrialized countries with the highest risk of diabetes in the lower socio-economic groups. [ABSTRACT FROM AUTHOR]

Diabet. Med. 27, 906–910 (2010) Aims Glycated haemoglobin (HbA1c) has been proposed as an alternative to the oral glucose tolerance test for diagnosing diabetes. We compared the cardiovascular risk profile of individuals identified by these two alternative methods. Methods We assessed the prevalence of cardiovascular risk factors in individuals with undiagnosed diabetes according to the World Health Organization classification or by the newly proposed HbA1c level ≥ 6.5% among 6258 participants of the Danish Inter99 study. Receiver operating curve analysis assessed the ability of fasting: 2-h plasma glucose and HbA1c to distinguish between individuals at high and low risk of ischemic heart disease, predicted by the PRECARD program. Results Prevalence of undiagnosed diabetes was 4.1% [95% confidence interval (CI) 3.7–4.7%] by the current oral glucose tolerance test definition, whereas 6.6% (95% CI 6.0–7.2%) had diabetes by HbA1c levels. HbA1c-defined individuals were relatively older with higher proportions of men, smokers, lipid abnormalities and macro-albuminuria, but they were leaner and had lower blood pressure. HbA1c was better than fasting- and 2-h plasma glucose at distinguishing between individuals of high and low predicted risk of ischaemic heart disease; however, the difference between HbA1c and fasting- and 2-h plasma glucose was not statistically significant. Conclusions Compared with the current oral glucose tolerance test definition, more individuals were classified as having diabetes based on the HbA1c criteria. This group had as unfavourable a risk profile as those identified by the oral glucose tolerance test. [ABSTRACT FROM AUTHOR]