Longitudinal decline of β-cell function: Comparison of a direct method vs a fasting surrogate measure: The insulin resistance atherosclerosis study

Context: β-Cell function (BCF) declines overthe course of type 2 diabetes, but little is known about BCF changes across glucose tolerance status (GTS) categories, and comparisons of direct vs surrogate measures. Objective: To assess longitudinal changes in BCF across GTS. Design: The Insulin Resistance Atherosclerosis Study is a multicenter, observational, epidemiologic study. Setting: Four clinical centers in the US that could identify subjects likely to have impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Patients: We compared longitudinal changes in BCF in 1052 subjects over 5 years. Subjects were categorized according to baseline GTS: normal glucose tolerance (NGT: n = 547), impaired fasting glucose or impaired glucose tolerance (IFG/IGT: n = 341), and newly diagnosed type 2 diabetes (n = 164). Interventions: None. Main Outcome Measures: BCF was assessed from a frequently sampled iv glucose tolerance test (AIR, acute insulin response), and the homeostasis model assessment of BCF (HOMA B). Results: NGT and IFG/IGT subjects increased their insulin secretion overtime, whereas those with type 2 diabetes experienced either decline or little change in BCF. After adjustment for demographic variables and change in insulin resistance, change in HOMAB underestimated the magnitude of changes in BCF, as assessed by change in AIR. Relative to NGT, the 5-year change in insulin secretion in IFG/IGT and type 2 diabetes was 31% and 70% lower (by HOMA B) and 50% and 80% lower (by AIR). Conclusions: The decline in BCF overtime in IFG/IGT and type 2 diabetes may be more pronounced than previously estimated; HOMAB may underestimate this decline significantly.