SUMMARY BackgroundNon-alcoholic steatohepatitis (NASH) is a form of progressive fatty liver disease that is strongly associated with insulin resistance, which suggests that insulin sensitizing agents such as metformin may be beneficial for NASH.

Summary Context Morphological characteristics of the glucose curve during an OGTT (time to peak and shape) may reflect different phenotypes of insulin secretion and action, but their ability to predict diabetes risk is uncertain. Objective To compare the ability of time to glucose peak and curve shape to detect prediabetes and β-cell function. Design and participants In a cross-sectional evaluation using an OGTT, 145 adults without diabetes (age 42±9y (mean±SD), range 24–62y, BMI 29.2±5.3 kg/m2, range 19.9–45.2 kg/m2) were characterized by peak (30 mins vs. >30 mins) and shape (biphasic vs. monophasic). Main Outcome Measures Prediabetes and disposition index (DI) – a marker of β-cell function. Results Prediabetes was diagnosed in 36% (52/145) of participants. Peak >30 mins, not monophasic curve, was associated with increased odds of prediabetes (OR: 4.0 vs. 1.1; P<0.001). Both monophasic curve and peak >30 mins were associated with lower DI (P≤0.01). Time to glucose peak and glucose AUC were independent predictors of DI (adjR2=0.45, P<0.001) Conclusion Glucose peak >30 mins was a stronger independent indicator of prediabetes and β-cell function than the monophasic curve. Time to glucose peak may be an important tool that could enhance prediabetes risk stratification.

Periwal V, Chow CC, Bergman RN, Ricks M, Vega GL, Sumner AE. Evaluation of quantitative models of the effect of insulin on lipolysis and glucose disposal. Am J Physiol Regul Integr Comp Physiol 295: R1089 -R1096, 2008. First published August 6, 2008 doi:10.1152/ajpregu.90426.2008.-The effects of insulin on the suppression of lipolysis are neither fully understood nor quantified. We examined a variety of mathematical models analogous to the minimal model of glucose disposal (MMG) to quantify the combined influence of insulin on lipolysis and glucose disposal during an insulin-modified frequently sampled intravenous glucose tolerance test. The tested models, which include two previously published ones, consisted of separate compartments for plasma free fatty acids (FFA), glucose, and insulin. They differed in the number of compartments and in the action of insulin to suppress lipolysis that decreased the plasma FFA level. In one category of models, a single insulin compartment acted on both glucose and FFA simultaneously. In a second category, there were two insulin compartments, each acting on FFA and glucose independently. For each of these two categories, we tested 11 variations of how insulin suppressed lipolysis. We also tested a model with an additional glucose compartment that acted on FFA. These 23 models were fit to the plasma FFA and glucose concentrations of 102 subjects individually. Using Bayesian model comparison methods, we selected the model that best balanced fit and minimized model complexity. In the best model, insulin suppressed lipolysis via a Hill function through a remote compartment that acted on both glucose and FFA simultaneously, and glucose dynamics obeyed the classic MMG. free fatty acids; insulin resistance; mathematical model INSULIN RESISTANCE is a primary risk factor for several common diseases, including diabetes, cardiovascular disease, hypertension, and some forms of cancer. The mechanisms underlying insulin resistance are not completely understood. One important gap in our understanding relates to defects in insulin's ability to regulate lipolysis, leading to relative elevations of plasma free fatty acids (FFA). FFA elevation has been implicated in the modification of insulin action in various tissues as well as altering intermediates in the insulin signaling pathway and mitochondrial enzymes (6, 23). Therefore, methods to quantify insulin's effects on lipolysis and plasma FFA levels in various conditions of insulin resistance would be useful.The pace of development of quantitative methods to assess insulin's effect on FFA has lagged behind that of quantifying insulin's action on glucose disposal. For example, the hyperinsulinemic euglycemic clamp and the minimal model of glucose disposal (MMG) (1, 8) provide a quantitative index of the glucoregulatory action of insulin as a single value, such as glucose infusion rate divided by steady-state insulin concentration (M/I) for the clamp and the insulin sensitivity index (S I ) for the MMG.The current method for quantifying insuli...

Background: The healthy immigrant effect is a phrase that has been used for decades to describe better cardiometabolic health in African immigrants than African Americans. The recent global increase in cardiometabolic diseases raises the possibility that immigrant health may be changing. Therefore, a new assessment of cardiometabolic health in African immigrants is warranted. Methods: Glucose tolerance status, blood pressure, and visceral adipose tissue (VAT) volume were compared in 214 self-identified healthy men comprised of 138 African immigrants, 76 African Americans, mean age 36 -9 years [mean -standard deviation (SD); range 20-64 years]. Insulin resistance was defined by the lowest quartile of the insulin sensitivity index (S I £ 2.28 mU/L