Effects of Nonglucose Nutrients on Insulin Secretion and Action in People With Pre-Diabetes

Abstract

To determine whether nonglucose nutrient-induced insulin secretion is impaired in pre-diabetes, subjects with impaired or normal fasting glucose were studied after ingesting either a mixed meal containing 75 g glucose or 75 g glucose alone. Despite comparable glucose areas above basal, glucose-induced insulin secretion was higher (P < 0.05) and insulin action lower (P < 0.05) during the meal than the oral glucose tolerance test (OGTT) in all subgroups regardless of whether they had abnormal or normal glucose tolerance (NGT). However, the nutrientinduced ␦ (meal minus OGTT) in insulin secretion and glucagon concentrations did not differ among groups. Furthermore, the decrease in insulin action after meal ingestion was compensated in all groups by an appropriate increase in insulin secretion resulting in disposition indexes during meals that were equal to or greater than those present during the OGTT. In contrast, disposition indexes were reduced (P < 0.01) during the OGTT in the impaired glucose tolerance groups, indicating that reduced glucose induced insulin secretion. We conclude that, whereas glucose-induced insulin secretion is impaired in people with abnormal glucose tolerance, nonglucose nutrient-induced secretion is intact, suggesting that a glucosespecific defect in the insulin secretory pathway is an early event in the evolution of type 2 diabetes.

Synergism by individual macronutrients explains the marked early GLP-1 and islet hormone responses to mixed meal challenge in mice

“…The first main finding of the current study is that the mixed meal significantly exaggerated early insulin secretion compared to an isocaloric glucose challenge, in spite of lower plasma glucose levels after mixed meal. This is similar as previously inferred from studies in rats [14] and humans [15,16].…”

Mechanisms through which a small protein and lipid preload improves glucose tolerance

“…Similarly, the ingestion of a small amount of whey protein was able to blunt the glycaemic excursion to a greater extent when given before rather than mixed with a highcarbohydrate meal [2]. Although the effects of protein and fat on glucose tolerance are expected to be synergistic, being the involved mechanisms partially different, the available evidence does not fully support this hypothesis [24], possibly because the nutrients were co-ingested with glucose and not given as a preload.…”

Contribution of Hepatic and Extrahepatic Insulin Resistance to the Pathogenesis of Impaired Fasting Glucose

“…Even if it did, several arguments still favor decreased glucose uptake as the primary cause of postprandial hyperglycemia in people with IFG. First, insulin-induced stimulation of glucose disposal was markedly reduced at insulin concentrations of ϳ150 pmol/l, levels similar to those observed in the same subjects within 30 -60 min of eating a mixed meal or drinking 75 g glucose (12,27). Second, insulin action measured in the same individuals on a separate occasion using the labeled "minimal" meal model was lower in IFG than in NFG subjects during the 6 h after meal ingestion, indicating that there was not a late compensatory increase in glucose disposal (12).…”

“…The subjects were selected by using the Mayo Clinic electronic medical record system to search for all individuals who had fasting glucose levels between 100 and 126 mg/dl, BMI between 20 and 40 kg/m 2 , and age between and 40 and 70 years and were otherwise healthy. As previously reported (12,27), subjects were studied on three occasions in random order at which time they ingested either a mixed meal or 75 g glucose or underwent a hyperinsulinemic-euglycemic clamp during which they received either a 0.25 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 (preprandial) or 0.5 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 (prandial) insulin infusions. The study was approved by the Mayo Institutional Review Board, and all subjects gave informed written consent to participate in the study.…”

“…Subjects were Caucasian, in good health, at a stable weight, and did not engage in vigorous physical exercise. Subjects were part of a larger study examining mechanisms of postprandial hyperglycemia, results of which have been reported in part elsewhere (12,27). The subjects were selected by using the Mayo Clinic electronic medical record system to search for all individuals who had fasting glucose levels between 100 and 126 mg/dl, BMI between 20 and 40 kg/m 2 , and age between and 40 and 70 years and were otherwise healthy.…”