294 © 2003 Diabetes UK. Diabetic Medicine, 20, 294–300 Introduction Type 2 diabetes mellitus (Type 2 DM) is a complex, polygenic disorder usually presenting relatively late in life. While clearly a heterogeneous disorder, the lengthy prediabetic phase is Correspondence to: Dr Adamandia D. Kriketos, Diabetes and Obesity Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst NSW 2010, Australia. E-mail: a.kriketos@garvan.org.au Abstract Aims To examine the relationships between body composition and changes in fasting glycaemia, and in indices of insulin secretion and insulin action over 6 years in females with a family history of Type 2 diabetes with or without prior gestational diabetes (‘at risk’ group, AR) and control females (control group, C). Methods At baseline and at follow-up, an oral glucose tolerance test and dual energy X-ray absorptiometry assessment of body composition were performed. Indices of insulin resistance (HOMA R′) and insulin secretion (HOMA β′) were obtained from fasting insulin and glucose concentrations. Results At baseline, the groups were similar for age, body mass index, fasting levels of plasma glucose and insulin, HOMA R′ and HOMA β′. Despite similar total body fatness, AR had significantly greater waist circumference and central fat (both P < 0.02) compared with C. At follow-up there was a significant increase in central adiposity only in AR, and the fasting plasma glucose (FPG) level was higher in AR compared with C (5.0 ± 0.2 vs. 4.3 ± 0.2 mmol / l, P = 0.02). This rise in plasma glucose in AR was related to a decline in HOMA β′ (r = 0.45, P = 0.0065). Both the baseline and the increments in total and central abdominal fat mass were associated with the time-related decline in HOMA β′. Conclusions Six years after initial assessment, AR showed deterioration in FPG levels due predominantly to a decline in insulin secretion index without major change in insulin resistance index. Importantly, baseline body fatness (especially central adiposity), as well as increases in fatness with time, were the major pre- dictors of the subsequent decline of insulin secretion index and the consequent rise in FPG. Diabet. Med. 20, 294–300 (2003) Keywords Type 2 diabetes mellitus, insulin secretion, HOMA, central fat, glycaemia Abbreviations Type 2 DM, Type 2 diabetes mellitus; GDM, gestational diabetes mellitus; FDR, first degree relative; AR, at risk group; C, control group; PG, plasma glucose; DEXA, dual energy X-ray absorptiometry; WHR, waist–hip ratio; PI, plasma insulin; GIR, glucose infusion rate; ISR, insulin secretory response; HOMA, homeostasis model assessment; FPG, fasting plasma glucose, FPI, fasting plasma insulin; NGT, normal glucose tolerance; IGT, impaired glucose tolerance Blackwell Publishing Ltd. Oxford, UK DME Diabetic Medicine 0742-3071 Blackwell Science Ltd, 2003 20 Original Article Original article Adiposity predicts hyposecretion of insulin A. D. Kriketos et al. Central fat predicts deterioration of insulin secretion index and fasting glycaemia: 6-year follow-up of subjects at varying risk of Type 2 diabetes mellitus A. D. Kriketos, D. G. Carey*, A. B. Jenkins†, D. J. Chisholm, S. M. Furler and L. V. Campbell Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St Vincent’s Hospital, Darlinghurst, *The Wesley Hospital, Auchenflower, and †University of Wollongong, Wollongong, Australia Accepted 17 December 2002