Long-term risk of incident type 2 diabetes and measures of overall and regional obesity: the EPIC-InterAct case-cohort study

BACKGROUND Waist circumference (WC) is a simple and reliable measure of fat distribution that may add to the prediction of type 2 diabetes (T2D), but previous studies have been too small to reliably quantify the relative and absolute risk of future diabetes by WC at different levels of body mass index (BMI). METHODS AND FINDINGS The prospective InterAct case-cohort study was conducted in 26 centres in eight European countries and consists of 12,403 incident T2D cases and a stratified subcohort of 16,154 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. We used Prentice-weighted Cox regression and random effects meta-analysis methods to estimate hazard ratios for T2D. Kaplan-Meier estimates of the cumulative incidence of T2D were calculated. BMI and WC were each independently associated with T2D, with WC being a stronger risk factor in women than in men. Risk increased across groups defined by BMI and WC; compared to low normal weight individuals (BMI 18.5-22.4 kg/m(2)) with a low WC (<94/80 cm in men/women), the hazard ratio of T2D was 22.0 (95% confidence interval 14.3; 33.8) in men and 31.8 (25.2; 40.2) in women with grade 2 obesity (BMI≥35 kg/m(2)) and a high WC (>102/88 cm). Among the large group of overweight individuals, WC measurement was highly informative and facilitated the identification of a subgroup of overweight people with high WC whose 10-y T2D cumulative incidence (men, 70 per 1,000 person-years; women, 44 per 1,000 person-years) was comparable to that of the obese group (50-103 per 1,000 person-years in men and 28-74 per 1,000 person-years in women). CONCLUSIONS WC is independently and strongly associated with T2D, particularly in women, and should be more widely measured for risk stratification. If targeted measurement is necessary for reasons of resource scarcity, measuring WC in overweight individuals may be an effective strategy, since it identifies a high-risk subgroup of individuals who could benefit from individualised preventive action.

Journal Article; Research Support, Non-U.S. Gov't;

Funding: EU Integrated Project LSHM-CT-2006-037197. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. InterAct investigators acknowledge funding from the following agencies: KO: Danish Cancer Society; JS: ‘Heisenberg-Professorship (SP716/2-1), clinical research group (KFO218/1), and a research group (Molecular Nutrition to JS) support of the Bundesministerium fu¨ r Bildung und Forschung (BMBF); MJT: Health Research Fund (FIS) of the Spanish Ministry of Health; the CIBER en Epidemiologı´a y Salud Pu´ blica (CIBERESP), Spain, Murcia Regional Government (Nu 6236); JWJB, HBBdM, IS, AMWS, DLvdA, YTvdS: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands; verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht; FLC: Cancer Research UK; PWF: Swedish Research Council, Novo Nordisk, Swedish Diabetes Association, Swedish Heart-Lung Foundation; GH: The county of Va¨sterbotten; RK: German Cancer Aid, Federal Ministry of Education and Research; TJK: Cancer Research UK; KK: Medical Research Council UK, Cancer Research UK; PN: Swedish Research Council; JRQ: Asturias Regional Government; BT: German Cancer Aid; Federal Ministry of Education and Research; AT: Danish Cancer Society; RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government.