Search

Background: Insulin secretion correlates inversely with insulin sensitivity, which may suggest the existence of a crosstalk between peripheral organs and pancreas. Such interaction might be mediated through glucose oxidation that may drive the release of circulating factors with action on insulin secretion., Aim: To evaluate the association between whole-body carbohydrate oxidation and circulating factors with insulin secretion to consecutive oral glucose loading in non-diabetic individuals., Methods: Carbohydrate oxidation was measured after an overnight fast and for 6 hours after two 3-h apart 75-g oral glucose tolerance tests (OGTT) in 53 participants (24/29 males/females; 34±9 y; 27±4 kg/m2). Insulin secretion was estimated by deconvolution of serum C-peptide concentration, β cell function by mathematical modelling and insulin sensitivity from an OGTT. Circulating lactate, free-fatty acids (FFA) and candidate chemokines were assessed before and after OGTT. The effect of recombinant RANTES (regulated on activation, normal T cell expressed and secreted) and IL8 (interleukin 8) on insulin secretion from isolated mice islets was also measured., Results: Carbohydrate oxidation assessed over the 6-h period did not relate with insulin secretion (r = -0.11; p = 0.45) or β cell function indexes. Circulating lactate and FFA showed no association with 6-h insulin secretion. Circulating chemokines concentration increased upon oral glucose stimulation. Insulin secretion associated with plasma IL6 (r = 0.35; p<0.05), RANTES (r = 0.30; p<0.05) and IL8 (r = 0.41; p<0.05) determined at 60 min OGTT. IL8 was independently associated with in vivo insulin secretion; however, it did not affect in vitro insulin secretion., Conclusion: Whole-body carbohydrate oxidation appears to have no influence on insulin secretion or putative circulating mediators. IL8 may be a potential factor influencing insulin secretion., Competing Interests: The authors have declared that no competing interests exist.

Aim of this study was analyzing the time trajectories of the metabolic parameters in European women with former gestational diabetes (fGDM), and determining predictors of type 2 diabetes onset. A group of seventy-six fGDM women were studied at the outpatient department of the University Clinic of Vienna. They were evaluated yearly with a 3 h-oral glucose tolerance test (OGTT) up to 7-years from delivery. At baseline, women also underwent an intravenous glucose tolerance test (IVGTT). Insulin sensitivity and beta-cell function were assessed by both OGTT and IVGTT. Women were divided into progressors (PROG) to diabetes (n = 19) and non-progressors (n = 57). Time trajectories of glycemia and other parameters were analyzed after synchronization to time of diabetes onset or last OGTT. Then, Cox proportional hazard regression analysis was performed to assess the predictive power of studied variables for diabetes onset. We found that, in PROG, time trajectories of glycemia were flat until diabetes onset, when they showed a marked increase (P<0.0001). Insulin sensitivity showed similar marked decrease (P<0.0001) at diabetes onset, together with a tendency to continuous slow decline in the previous years. At contrast, beta-cell function showed only continuous slow decline. Major predictors of diabetes onset were glycemic levels, BMI, insulin resistance, and condition of impaired glucose tolerance. In conclusion, in fGDM, marked deterioration of insulin sensitivity is associated with diabetes onset. Prevention strategies aimed at opposing to the insulin sensitivity derangement may be particularly beneficial.

The incretin effect on insulin secretion was investigated in 8 subjects with type 2 diabetes (T2D) and 8 with normal glucose tolerance (NGT), using 25, 75, and 125 g oral glucose tolerance tests (OGTT) and isoglycemic intravenous glucose infusions (IIGI). The ß-cell response was evaluated using a model embedding a dose-response (slope = glucose sensitivity), an early response (rate sensitivity), and potentiation (time-related secretion increase). The incretin effect, as OGTT/IIGI ratio, was calculated for each parameter. In NGT, the incretin effect on total secretion increased with dose (1.3±0.1, 1.7±0.2, 2.2±0.2 fold of IIGI, P<0.0001), mediated by a dose-dependent increase of the incretin effect on glucose sensitivity (1.9±0.4, 2.4±0.4, 3.1±0.4, P = 0.005), and a dose-independent enhancement of the incretin effect on rate sensitivity (894 [1145], 454 [516], 783 [1259] pmol m−2 L mmol−1 above IIGI; median [interquartile range], P<0.0001). The incretin effect on potentiation also increased (0.97±0.06, 1.45±0.20, 1.24±0.16, P<0.0001). In T2D, the incretin effect on total secretion (1.0±0.1, 1.1±0.1, 1.3±0.1, P = 0.004) and glucose sensitivity (1.2±0.2, 1.3±0.2, 2.0±0.2, P = 0.005) were impaired vs NGT; however, the incretin effect on rate sensitivity increased already at 25 g (269 [169], 284 [301], 193 [465] pmol m−2 L mmol−1 above IIGI; negligible IIGI rate sensitivity in T2D prevented the calculation of the fold increment). OGTT did not stimulate potentiation above IIGI (0.94±0.04, 0.89±0.06, 1.06±0.09; P<0.01 vs NGT). In the whole group, the incretin effect was inversely associated with total secretion during IIGI, although systematically lower in T2D. In conclusion, 1) In NGT, glucose sensitivity and potentiation mediate the dose-dependent incretin effect increase; 2) In T2D, the incretin effect is blunted vs NGT, but rate sensitivity is enhanced at all loads; 3) Relatively lower incretin effect in NGT is associated with higher secretion during IIGI, suggesting that the reduced incretin effect does not result from ß-cell dysfunction. [ABSTRACT FROM AUTHOR]