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 Use and Effectiveness of Selected Alternative Markers for Insulin Sensitivity and Secretion Compared with Gold Standard Markers in Dietary Intervention Studies in Individuals without Diabetes: Results of a Systematic Review

Background: The gold‐standard techniques for measuring insulin sensitivity and secretion are well established. However, they may be perceived as invasive and expensive for use in dietary intervention studies. Thus, surrogate markers have been proposed as alternative markers for insulin sensitivity and secretion. This systematic review aimed to identify markers of insulin sensitivity and secretion in response to dietary intervention and assess their suitability as surrogates for the gold‐standard method-ology. Methods: Three databases, PubMed, Scopus, and Cochrane were searched, intervention studies and randomised controlled trials reporting data on dietary intake, a gold standard of analysis of insulin sensitivity (either euglycaemic‐hyperinsulinaemic clamp or intravenous glucose tolerance test and secretion (acute insulin response to glucose), as well as surrogate markers for insulin sensitivity (either fasting insulin, area under the curve oral glucose tolerance tests and HOMA‐IR) and insulin secretion (disposi-tion index), were selected. Results: We identified thirty‐five studies that were eligible for inclusion. We found insufficient evidence to predict insulin sensitivity and secretion with surrogate markers when compared to gold standards in nutritional intervention studies. Conclusions: Future research is needed to investigate if surrogate measures of insulin sensitivity and secretion can be repeatable and reproduci-ble in the same way as gold standards

Relationship between retinal vessel diameters and retinopathy in the Inter99 Eye Study

Purpose: To examine the association between retinal vessel diameters and retinopathy in participants with and without type 2 diabetes in a Danish population-based cohort. Methods: The study included 878 persons aged 30 to 60 years from the Inter99 Eye Study. Retinopathy was defined as a presence of one or more retinal hemorrhages or one or more microaneurysms. Vessel diameters were expressed as central retinal artery equivalent diameter (CRAE) and central retinal vein equivalent diameter (CRVE). Multiple linear regression analyses were performed. Results: Among participants with diabetes, CRAE was 6.3 µm (CI 95%: 1.0 to 11.6, p = 0.020) wider and CRVE was 7.9 µm (CI 95%: 0.7 to 15.2, p = 0.030) wider in those with retinopathy compared to those without retinopathy, after adjusting for age, gender, HbA1c, blood pressure, smoking, serum total and HDL cholesterol. In all participants, CRAE increased with presence of retinopathy (p = 0.005) and with smoking (p = 0.001), and CRAE decreased with hypertension (p < 0.001), high HDL cholesterol (p = 0.016) and age (p < 0.001). Central retinal vein equivalent diameter increased with presence of retinopathy (p = 0.022) and with smoking (p < 0.001), and decreased with higher HDL cholesterol (p < 0.001) and age (p = 0.015). Female gender was associated with wider CRVE (p = 0.029). Conclusions: Wider retinal vessel diameters were associated with the presence of retinopathy in participants with diabetes, but not in participants without diabetes. The associations between retinal vessel diameters and known retinopathy risk factors were confirmed. These results suggest that information obtained by non-invasive imaging of the interior of the eye can contribute to a better understanding of systemic disease processes

Associations between postprandial gut hormones and markers of bone remodeling

Gut-derived hormones have been suggested to play a role in bone homeostasis following food intake, although the associations are highly complex and not fully understood. In a randomized, two-day cross-over study on 14 healthy individuals, we performed postprandial time-course studies to examine the associations of the bone remodeling markers carboxyl-terminal collagen type I crosslinks (CTX) and procollagen type 1 N-terminal propeptide (P1NP) with the gut hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) using two different meal types—a standardized mixed meal (498 kcal) or a granola bar (260 kcal). Plasma concentrations of total GIP, total GLP-1, total PYY, CTX, and P1NP were measured up to 240 min after meal intake, and the incremental area under the curve (iAUC) for each marker was calculated. The iAUC of CTX and P1NP were used to assess associations with the iAUC of GIP, GLP-1, and PYY in linear mixed effect models adjusted for meal type. CTX was positively associated with GIP and GLP-1, and it was inversely associated with PYY (all p < 0.001). No associations of P1NP with GIP or GLP-1 and PYY were found. In conclusion, the postprandial responses of the gut hormones GIP, GLP-1, and PYY are associated with the bone resorption marker CTX, supporting a link between gut hormones and bone homeostasis following food intake

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)