Natural History of Insulin Sensitivity and Insulin Secretion in the Progression From Normal Glucose Tolerance to Impaired Fasting Glycemia and Impaired Glucose Tolerance: The Inter99 Study

• Published in: Diabetes care Vol. 32; no. 3; pp. 439 - 444
• Main Authors: Færch, Kristine, Vaag, Allan, Holst, Jens J, Hansen, Torben, Jørgensen, Torben, Borch-Johnsen, Knut
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01-03-2009
• Subjects: Blood Glucose - analysis; Blood Glucose - metabolism; Dextrose; Diabetes; Fasting - blood; Female; Follow-Up Studies; Glucose; Glucose Intolerance - blood; Glucose Intolerance - physiopathology; Glucose tolerance tests; Humans; Hyperglycemia; Insulin; Insulin - metabolism; Insulin Secretion; Male; Middle Aged; Natural history; Pathophysiology/Complications; Prediabetic State - blood; Prediabetic State - physiopathology; Studies
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc08-1195

OBJECTIVE:--The aim of this study was to describe the natural history of insulin secretion and insulin sensitivity in the development of isolated impaired fasting glycemia (i-IFG), isolated impaired glucose tolerance (i-IGT), and combined IFG/IGT. RESEARCH DESIGN AND METHODS--Baseline and 5-year follow-up data from the Inter99 study were used. Individuals with normal glucose tolerance (NGT) at baseline and i-IFG, i-IGT, combined IFG/IGT, or NGT at the 5-year follow-up were examined with an oral glucose tolerance test (n = 3,145). Insulin sensitivity index (ISI), homeostasis model assessment of insulin sensitivity (HOMA-IS), early-phase insulin release (EPIR), and insulin secretion relative to insulin action (disposition index) were estimated. RESULTS:--Five years before the pre-diabetes diagnoses (i-IFG, i-IGT, and IFG/IGT), ISI, HOMA-IS, EPIR, and disposition index were lower than in individuals who maintained NGT. During the 5-year follow-up, individuals developing i-IFG experienced a significant decline only in HOMA-IS, whereas individuals developing i-IGT experienced significant declines in ISI, EPIR, and disposition index. Individuals with IFG/IGT exhibited pronounced declines in ISI, HOMA-IS, EPIR, and disposition index during the 5-year follow-up. CONCLUSIONS:--A stationary reduced insulin secretion followed by a decline in primarily hepatic insulin sensitivity characterizes the transition from NGT to i-IFG. In contrast, low whole-body insulin sensitivity with a secondary lack of β-cell compensation is associated with the development of i-IGT. Thereby, i-IFG and i-IGT appear to result from different underlying mechanisms, which may have implications for the prevention and treatment of the diabetes that succeeds them.