Longitudinal Decline of β-Cell Function: Comparison of a Direct Method vs a Fasting Surrogate Measure: The Insulin Resistance Atherosclerosis Study

• Published in: The journal of clinical endocrinology and metabolism Vol. 98; no. 10; pp. 4152 - 4159
• Main Authors: Festa, A., Haffner, S. M., Wagenknecht, L. E., Lorenzo, C., Hanley, A. J. G.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.10.2013; Copyright by The Endocrine Society; Endocrine Society
• Subjects: Adult; Aged; Arteriosclerosis; Atherosclerosis; Atherosclerosis - physiopathology; Beta cells; Biological and medical sciences; Blood Glucose; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - physiopathology; Endocrine Research; Endocrinopathies; Epidemiology; Fasting; Fasting - physiology; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Glucose; Glucose Intolerance - physiopathology; Glucose tolerance; Glucose Tolerance Test; Homeostasis; Humans; Insulin resistance; Insulin Resistance - physiology; Insulin secretion; Insulin-Secreting Cells - physiology; Longitudinal Studies; Male; Medical sciences; Middle Aged; Prediabetic State - physiopathology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Endocrinopathy; Obesity; Pancreatic hormone; Cell function; Fasting; Methodology; Nutrition; Nutrition disorder; Cardiovascular disease; Metabolic diseases; Insulin; Vascular disease; Target tissue resistance; Atherosclerosis; Insulin resistance; β Cell; Fast; Endocrinology; Nutritional status; Comparative study
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2013-1937

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.