Context: β-Cell function (BCF) declines over the 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 over time, 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 HOMA B 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 over time in IFG/IGT and type 2 diabetes may be more pronounced than previously estimated; HOMA B may underestimate this decline significantly.