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OBJECTIVE To quantitate the separate impact of obesity and hyperglycemia on the incretin effect (i.e., the gain in beta-cell function after oral glucose versus intravenous glucose). RESEARCH DESIGN AND METHODS Isoglycemic oral (75 g) and intravenous glucose administration was performed in 51 subjects (24 with normal glucose tolerance [NGT], 17 with(More)
BACKGROUND Insulin resistance is a risk factor for type 2 diabetes and cardiovascular disease progression. Current diagnostic tests, such as glycemic indicators, have limitations in the early detection of insulin resistant individuals. We searched for novel biomarkers identifying these at-risk subjects. METHODS Using mass spectrometry, non-targeted(More)
BACKGROUND Because hyperinsulinemia acutely stimulates adrenergic activity, it has been postulated that chronic hyperinsulinemia may lead to enhanced sympathetic tone and cardiovascular risk. METHODS AND RESULTS In 21 obese (body mass index, 35+/-1 kg/m(2)) and 17 lean subjects, we measured resting cardiac output (by 2-dimensional echocardiography),(More)
In nondiabetic subjects, obesity is associated with a modest expansion of beta-cell mass, possibly amounting-according to the best available estimates-to 10-30% for each 10 kg of weight excess. Whether age of onset and duration of obesity, recent changes in body weight, and body fat distribution have any effect on beta-cell mass in humans is unknown. Both(More)
An increased tissue content of PC-1, an inhibitor of insulin receptor signaling, may play a role in insulin resistance. Large scale prospective studies to test this hypothesis are difficult to carry out because of the need for tissue biopsies. The aim of this study was to investigate whether PC-1 is measurable in human plasma and whether its concentration(More)
Insulin hyperpolarizes plasma membranes; we tested whether insulin affects ventricular repolarization. In 35 healthy volunteers, we measured the Q-T interval during electrocardiographic monitoring in the resting state and in response to hyperinsulinemia (euglycemic 1-mU. min(-1). kg(-1) insulin clamp). A computerized algorithm was used to identify T waves;(More)
First-phase insulin response to intravenous glucose is impaired both in type 2 diabetic patients and in subjects at risk for the disease. Hyperglycemia can modify beta-cell response by either inhibiting or potentiating both first- and second-phase insulin release. In normal subjects, the effect of acute hyperglycemia on insulin secretion is controversial.(More)
Gastric bypass surgery leads to marked improvements in glucose tolerance and insulin sensitivity in obese type 2 diabetes (T2D); the impact on glucose fluxes in response to a physiological stimulus, such as a mixed meal test (MTT), has not been determined. We administered an MTT to 12 obese T2D patients and 15 obese nondiabetic (ND) subjects before and 1(More)
Obesity is a frequent cause of insulin resistance and poses a major risk for diabetes. Abnormal fat deposition within skeletal muscle has been identified as a mechanism of obesity-associated insulin resistance. We tested the hypothesis that dietary lipid deprivation may selectively deplete intramyocellular lipids, thereby reversing insulin resistance.(More)