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M-low (mg/kg EMBS per minute)

Fig. 1. The hyperbolic relationship between insulin sensitivity and beta cell function. AIR, acute insulin response to glucose; M-low, low insulin concentration; NGT, normal glucose tolerance; IGT, impaired glucose tolerance; DIA, diabetes; EMBS, estimated metabolic body size or fat free mass. (From Kahn SE. The importance of ß-cell failure in the development and progression of type 2 diabetes. J Clin Endocrinol Metab 2001;86:4051; with permission.)

longitudinal studies in populations at high risk for developing T2DM, such as the Pima Indians of Arizona [45]. In the former study, the progression from normal glucose tolerance (NGT) to IGT was associated with an increase in body weight, worsening in insulin sensitivity, and a decline in the acute insulin secretory response to intravenous glucose. Progression from IGT to diabetes required further increase in body weight, impairment in insulin sensitivity and beta-cell function, and an increase in basal endogenous glucose output [45]. Similar observations were reported in insulin-sensitive and insulin-resistant African-American adults with T2DM who showed a marked decrease in insulin secretion as they progressed from near normoglycemia to frank hypergly-cemia [46].

Metabolic studies of T2DM in youth are scarce in the literature. In a study by Umpaichitra and associates [47], 24 patients who had T2DM and 24 control subjects (aged 9-20 years, matched for body mass index [BMI] and pubertal stage) were evaluated for their insulin and glucagon response to a mixed liquid meal tolerance test. In children who had T2DM, relative hypoinsuline-mia and hyperglucagonemia represented the pancreatic beta- and alpha-cell dysfunctions, and the severity seemed to depend on duration. Insulin deficiency was not expressed relative to the degree of insulin resistance, however, which was not measured.

A Japanese study evaluated obese adolescents who did not have diabetes, obese adolescents who had T2DM, and nonobese control subjects using the minimal model analysis of insulin-modified, frequently sampled intravenous glucose tolerance test [48]. Obese nondiabetic and obese diabetic groups were significantly and equally insulin resistant compared with the nonobese group. The diabetic group had lower first-phase insulin release compared with the nondiabetic group, however, which resulted in lower glucose disposition index (the product of first-phase insulin secretion and insulin sensitivity). Body composition and body fat topography were not evaluated.

Our group recently demonstrated that insulin sensitivity and insulin secretion are impaired in adolescents with T2DM using the glucose clamp technique, which is considered the gold standard for assessment of in vivo insulin sensitivity and secretion [19]. Adolescents who had T2DM were compared with matched (age, BMI, body composition, and pubertal development) obese controls [19]. Insulin sensitivity was evaluated with a 3-hour hyperinsulinemic euglycemic clamp and first- and second-phase insulin secretion with a 2-hour hyperglycemic clamp. Fasting glucose rate of appearance (hepatic glucose production) was determined with the use of [6,6-2H2] glucose. In youth with T2DM compared with obese controls, in vivo insulin sensitivity was approximately 50% lower, first-phase insulin secretion was approximately 74% lower and second-phase insulin secretion was approximately 53% lower, glucose disposition index was approximately 86% lower, and hepatic glucose output was approximately 1.3 times higher [19] (Fig. 2). Our findings were in agreement with the literature in adults with T2DM [41], but we also showed a significant inverse relationship between insulin secretion and HbA1c in T2DM youth (r = —0.61;

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Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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