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© 2005 by the American Diabetes Association, Inc.
Pathophysiology/Complications |
Youth Type 2 Diabetes
Insulin resistance, ß-cell failure, or both?
1 Division of Pediatric Endocrinology, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania
2 Division of Biostatistics, Department of Family Medicine and Clinical Epidemiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Address correspondence and reprint requests to Silva A. Arslanian, MD, Children’s Hospital of Pittsburgh, 3705 Fifth Ave. at DeSoto St., Pittsburgh, PA 15213. E-mail: silva.arslanian{at}chp.edu
OBJECTIVE—This study evaluates insulin sensitivity, pancreatic ß-cell function (BCF), and the balance between the two in youth with type 2 diabetes and assesses the relationship of diabetes duration and HbA1c to insulin sensitivity and BCF.
RESEARCH DESIGN AND METHODS—The subjects were 14 adolescents with type 2 diabetes and 20 obese control subjects of comparable age, BMI, body composition, and puberty. Insulin sensitivity was evaluated with a 3-h hyperinsulinemic (80 mU · m–2 · min–1) euglycemic clamp. First-phase insulin secretion (FPIS) and second-phase insulin secretion (SPIS) were evaluated with a 2-h hyperglycemic (12.5 mmol/l) clamp. Fasting glucose rate of appearance was determined with the use of [6,6-2H2]glucose.
RESULTS—Fasting glucose rate of appearance was higher in type 2 diabetic patients than in obese control subjects (16.5 ± 1.1 vs. 12.3 ± 0.5 µmol · kg–1 · min–1; P = 0.002). Insulin sensitivity was lower in type 2 diabetic patients than in obese control subjects (1.0 ± 0.1 vs. 2.0 ± 0.2 µmol · kg–1 · min–1 per pmol/l; P = 0.001). Fasting insulin was higher in type 2 diabetic patients than in obese control subjects (289.8 ± 24.6 vs. 220.2 ± 18.0 pmol/l; P = 0.007), and FPIS and SPIS were lower (FPIS: 357.6 ± 42.0 vs. 1,365.0 ± 111.0 pmol/l; SPIS: 652.2 ± 88.8 vs. 1,376.4 ± 88.8 pmol/l; P < 0.001 for both). The glucose disposition index (GDI = insulin sensitivity x FPIS) was 
86% lower in type 2 diabetic patients than in obese control subjects. HbA1c correlated with FPIS (r = –0.61, P = 0.025) with no relationship to insulin sensitivity.
CONCLUSIONS—Despite the impairment in both insulin sensitivity and BCF in youth with type 2 diabetes, the magnitude of the derangement is greater in BCF than insulin sensitivity when compared with that in obese control subjects. The inverse relationship between BCF and HbA1c may either reflect the impact of deteriorating BCF on glycemic control or be a manifestation of a glucotoxic phenomenon on BCF. Future studies in youth type 2 diabetes should target the natural course of ß-cell failure and means of retarding and/or preventing it.
Abbreviations: BCF, ß-cell function • DEXA, dual-energy X-ray absorptiometry • FPIS, first-phase insulin secretion • GDI, glucose disposition index • HOMA, homeostasis model assessment • ICA, islet cell antibody • IGT, impaired glucose tolerance • NGT, normal glucose tolerance • PCOS, polycystic ovary syndrome • SPIS, second-phase insulin secretion
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