Natural History of Insulin Sensitivity and Insulin Secretion in the Progression From Normal Glucose Tolerance to Impaired Fasting Glycemia and Impaired Glucose Tolerance: The Inter99 Study

OBJECTIVE—The aim of this study was to describe the natural history of insulin secretion and insulin sensitivity in the development of isolated impaired fasting glycemia (i-IFG), isolated impaired glucose tolerance (i-IGT), and combined IFG/IGT

The Effect of PCSK1 Variants on Waist, Waist-Hip Ratio and Glucose Metabolism Is Modified by Sex and Glucose Tolerance Status

on measures of body fat and glucose homeostasis in Danish individuals and to assess interactions of genotypes with age, sex and glucose tolerance status. Data were included in meta-analyses of additional Europeans. = 0.02) elevated level of acute insulin response for this variant. Finally, we found that the rs6232 G-allele associated with higher levels of GLP-1, GLP-2 and glucagon and that the rs6235 C-allele associated with higher levels of GIP and glucagon during a meal-test. rs6232 G-allele and rs6235 C-allele have an effect on body composition which may be modified by sex, whereas the effect of rs6235 C-allele on fasting and stimulated circulating plasma glucose and hormone levels may be influenced by glucose tolerance status

The effect of FOXA2 rs1209523 on glucose-related phenotypes and risk of type 2 diabetes in Danish individuals

<p>Abstract</p> <p>Background</p> <p>Variations within the <it>FOXA </it>family have been studied for a putative contribution to the risk of type 2 diabetes (T2D), and recently the minor T-allele of <it>FOXA2 </it>rs1209523 was reported to associate with decreased fasting plasma glucose levels in a study using a weighted false discovery rate control procedure to enhance the statistical power of genome wide association studies in detecting associations between low-frequency variants and a given trait.</p> <p>Thus, the primary aim of this study was to investigate whether the minor T-allele of rs1205923 in <it>FOXA2 </it>associated with 1) decreased fasting plasma glucose and 2) a lower risk of developing T2D. Secondly, we investigated whether rs1205923 in <it>FOXA2 </it>associated with other glucose-related phenotypes.</p> <p>Methods</p> <p>The variant was genotyped in Danish individuals from four different study populations using KASPar^®PCR SNP genotyping system. We examined for associations of the <it>FOXA2 </it>genotype with fasting plasma glucose and estimates of insulin release and insulin sensitivity following an oral glucose tolerance test in 6,162 Danish individuals from the population-based Inter99 study while association with T2D risk was assessed in 10,196 Danish individuals including four different study populations.</p> <p>Results</p> <p>The <it>FOXA2 </it>rs1209523 was not associated with fasting plasma glucose (effect size (β) = -0.03 mmol/l (95%CI: -0.07; 0.01), <it>p </it>= 0.2) in glucose-tolerant individuals from the general Danish population. Furthermore, when employing a case-control setting the variant showed no association with T2D (odds ratio (OR) = 0.82 (95%CI: 0.62-1.07), <it>p </it>= 0.1) among Danish individuals. However, when we performed the analysis in a subset of 6,022 non-obese individuals (BMI < 30 kg/m²) an association with T2D was observed (OR = 0.68 (95%CI: 0.49-0.94), <it>p </it>= 0.02). Also, several indices of insulin release and β-cell function were associated with the minor T-allele of <it>FOXA2 </it>rs1209523 in non-obese individuals.</p> <p>Conclusions</p> <p>We failed to replicate association of the minor T-allele of <it>FOXA2 </it>rs1209523 with fasting plasma glucose in a population based sample of glucose tolerant individuals. More extensive studies are needed in order to fully elucidate the potential role of <it>FOXA2 </it>in glucose homeostasis.</p

Habitual physical activity is associated with lower fasting and greater glucose-induced GLP-1 response in men.

RATIONALE: The hormone glucagon-like peptide-1 (GLP-1) decreases blood glucose and appetite. Greater physical activity (PA) is associated with lower incidence of type 2 diabetes. While acute exercise may increase glucose-induced response of GLP-1, it is unknown how habitual PA affects GLP-1 secretion. We hypothesised that habitual PA associates with greater glucose-induced GLP-1 responses in overweight individuals. METHODS: Cross-sectional analysis of habitual PA levels and GLP-1 concentrations in 1326 individuals (mean (s.d.) age 66 (7) years, BMI 27.1 (4.5) kg/m2) from the ADDITION-PRO cohort. Fasting and oral glucose-stimulated GLP-1 responses were measured using validated radioimmunoassay. PA was measured using 7-day combined accelerometry and heart rate monitoring. From this, energy expenditure (PAEE; kJ/kg/day) and fractions of time spent in activity intensities (h/day) were calculated. Cardiorespiratory fitness (CRF; mL O2/kg/min) was calculated using step tests. Age-, BMI- and insulin sensitivity-adjusted associations between PA and GLP-1, stratified by sex, were evaluated by linear regression analysis. RESULTS: In 703 men, fasting GLP-1 concentrations were 20% lower (95% CI: -33; -3%, P = 0.02) for every hour of moderate-intensity PA performed. Higher CRF and PAEE were associated with 1-2% lower fasting GLP-1 (P = 0.01). For every hour of moderate-intensity PA, the glucose-stimulated GLP-1 response was 16% greater at peak 30 min (1; 33%, P rAUC0-30 = 0.04) and 20% greater at full response (3; 40%, P rAUC0-120 = 0.02). No associations were found in women who performed PA 22 min/day vs 32 min/day for men. CONCLUSION: Moderate-intensity PA is associated with lower fasting and greater glucose-induced GLP-1 responses in overweight men, possibly contributing to improved glucose and appetite regulation with increased habitual PA.S B was supported by the UK Medical Research Council (MC_UU_12015/3) and the NIHR Biomedical Research Centre Cambridge (IS-BRC-1215-20014)