The simultaneous assessment of quantitative indexes of insulin secretion and action in a single individual is important when quantifying their relative role in the evolution of glucose tolerance in different physiopathological states. Available methods quantify these indexes in relatively nonphysiological conditions, e.g., during glucose clamps or intravenous glucose tolerance tests. Here, we present a method based on a physiological test applicable to large-scale genetic and epidemiologic studies-the oral glucose tolerance test (OGTT). Plasma C-peptide, insulin, and glucose data from a frequently sampled OGTT with 22 samples throughout 300 min (FSOGTT 300-22 ) were analyzed in 11 subjects with various degrees of glucose tolerance. T he simultaneous assessment of ␤-cell function and insulin sensitivity in a single individual is of primary importance when quantifying their relative role in the evolution of glucose tolerance in different physiopathological states. Two methods are available for this purpose: the clamp technique, which uses a euglycemichyperinsulinemic and a hyperglycemic-euinsulinemic clamp in the same individual (1), and the intravenous glucose tolerance test (IVGTT) interpreted by the minimal models of glucose disposal (2) and C-peptide kinetics and secretion (3). Both these approaches give accurate and precise estimates of insulin sensitivity and ␤-cell function in a single individual, but plasma glucose, C-peptide, and insulin concentrations achieved during these studies are relatively nonphysiological. Recently, the need to quantify ␤-cell function and insulin sensitivity under more normal life conditions has encouraged many investigators to use more physiological protocols, including meal-like studies (4), graded up and down glucose infusions (5), meals (6,7), and oral glucose tolerance tests (OGTTs) (8,9). However, an approach to measure indexes of ␤-cell function and insulin action in a single individual based on a physiological test such as the OGTT is not available. The ability to derive in a single individual important information such as the clinical classification of oral glucose tolerance while simultaneously quantifying his or her ␤-cell function and insulin sensitivity could provide a unique tool potentially applicable to large-scale genetic and epidemiologic studies.Therefore, the aim of the present study was to investigate whether indexes of ␤-cell function and insulin sensitivity could be simultaneously assessed in a single individual from OGTT data by extending to the OGTT the up and down C-peptide minimal model (5) and the insulin sensitivity formula recently derived for a meal (7). The database consisted of a frequently sampled 300-min OGTT performed on 11 subjects with various degrees of glucose tolerance. Indexes of insulin sensitivity and ␤-cell function based on OGTTs with reduced number of samples were also calculated and compared with those derived from the frequently sampled OGTT to arrive at a robust clinical protocol. RESEARCH DESIGN AND METHODSSubjects. Studies were ...

Glucose tolerance decreases with age. For determining the cause of this decrease, 67 elderly and 21 young (70.1 ؎ 0.7 vs. 23.7 ؎ 0.8 years) participants ingested a mixed meal and received an intravenous injection of glucose. Fasting glucose and the glycemic response above basal were higher in the elderly than in the young participants after either meal ingestion (P < 0.001) or glucose injection (P < 0.01). Insulin action (Si), measured with the meal and intravenous glucose tolerance test models, was highly correlated (r ‫؍‬ 0.72; P < 0.001) and lower (P < 0.002) in the elderly than in the young participants. However, when adjusted for differences in percentage body fat and visceral fat, Si no longer differed between groups. When considered in light of the degree of insulin resistance, all indexes of insulin secretion were lower (P < 0.01) in the elderly participants, indicating impaired ␤-cell function. Hepatic insulin clearance was increased (P < 0.002), whereas total insulin clearance was decreased (P < 0.002) in the elderly subjects. Multivariate analysis (r ‫؍‬ 0.70; P < 0.001) indicated that indexes of insulin action (Si) and secretion (Phi total ) but not age, peak oxygen uptake, fasting glucose, degree of fatness, or hepatic insulin clearance predicted the postprandial glycemic response. We conclude that the deterioration in glucose tolerance that occurs in healthy elderly subjects is due to a decrease in both insulin secretion and action with the severity of the defect in insulin action being explained by the degree of fatness rather than age per se. Diabetes

Neither DHEA nor low-dose testosterone replacement in elderly people has physiologically relevant beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life. (ClinicalTrials.gov number, NCT00254371 [ClinicalTrials.gov].).

Assessment of insulin secretion in humans under physiological conditions has been a challenge because of its complex interplay with insulin action and hepatic insulin extraction. The possibility of simultaneously assessing beta-cell function, insulin sensitivity, and hepatic insulin extraction under physiological conditions using a simple protocol is appealing, since it has the potential to provide novel insights regarding the regulation of fasting and postprandial glucose metabolism in diabetic and nondiabetic humans. In this Perspective, we review data indicating that an oral glucose tolerance test (OGTT) or a meal test is able to accomplish this goal when interpreted with the oral beta-cell minimal model. We begin by using the well-established intravenous minimal model to highlight how the oral minimal model was developed and how the oral assessment parallels that of an intravenous glucose tolerance test (IVGTT). We also point out the unique aspects of both approaches in relation to their ability to assess different aspects of the beta-cell secretory cascade. We review the ability of the oral model to concurrently measure insulin sensitivity and hepatic insulin extraction, thereby enabling it to quantitatively portray the complex relationship among beta-cell function, hepatic insulin extraction, and insulin action. In addition, data from 204 individuals (54 young and 159 elderly) who underwent both IVGTT and meal tolerance tests are used to illustrate how these different approaches provide complementary but differing insights regarding the regulation of beta-cell function in humans.