Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity.

Patients with established type 2 diabetes display both β-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci, and indices of proinsulin processing, insulin secretion, and insulin sensitivity. We included data from up to 58,614 nondiabetic subjects with basal measures and 17,327 with dynamic measures.

Beyond fasting plasma glucose: the association between coronary heart disease risk and postprandial glucose, postprandial insulin and insulin resistance in healthy, nondiabetic adults.

Objective: Prediabetes is defined by elevations of plasma glucose concentration, and is aimed at identifying individuals at increased risk of type 2 diabetes and coronary heart disease (CHD). However, since these individuals are also insulin resistant and hyperinsulinemic, we evaluated the association between several facets of carbohydrate metabolism and CHD risk profile in apparently healthy, nondiabetic individuals.

Methods: Plasma glucose and insulin concentrations were measured before and at hourly intervals for eight hours after two test meals in 281 nondiabetic individuals.

Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans.

OBJECTIVE Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084).

Metabolic impact of switching antipsychotic therapy to aripiprazole after weight gain: a pilot study.

Switching antipsychotic regimen to agents with low weight gain potential has been suggested in patients who gain excessive weight on their antipsychotic therapy. In an open-label pilot study, we evaluated the metabolic and psychiatric efficacy of switching to aripiprazole in 15 (9 men, 6 women) outpatients with schizophrenia who had gained at least 10 kg on their previous antipsychotic regimen. Individuals had evaluation of glucose tolerance, insulin resistance (insulin suppression test), lipid concentrations, and psychiatric status before and after switching to aripiprazole for 4 months.