Association of weight status and the risks of diabetes in adults: a systematic review and meta-analysis of prospective cohort studies

Obesity is a known risk factor for type 2 diabetes mellitus (T2DM); however, the associations between underweight and T2DM and between weight status and prediabetes have not been systematically reviewed. We aimed to estimate the relative risks (RRs) of prediabetes/T2DM in underweight/overweight/obesity relative to normal weight. PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to December 8, 2021. Prospective cohort studies with a minimum 12-month follow-up period reporting the association between baseline body mass index (BMI) categories and risk of prediabetes/T2DM in adults were included. Study quality was assessed using the Newcastle-Ottawa Scale. The main analyses of T2DM risk were performed using the ethnic-specific (Asian/non-Asian) BMI classification and additional analyses of prediabetes/T2DM risk by including all eligible studies. Random-effects models with inverse variance weighting were used. Subgroup analyses and meta-regression were conducted to explore the potential effects of pre-specified modifiers. The study protocol was registered with PROSPERO (CRD42020215957). Eighty-four articles involving over 2.69 million participants from 20 countries were included. The pooled RR of prediabetes risk was 1.24 (95% CI: 1.19-1.28, I-2 = 9.7%, n = 5 studies) for overweight/obesity vs. normal weight. The pooled RRs of T2DM based on the ethnic-specific BMI categories were 0.93 (95% CI: 0.75-1.15, I-2 = 55.5%, n = 12) for underweight, 2.24 (95% CI: 1.95-2.56, I-2 = 92.0%, n = 47) for overweight, 4.56 (95% CI: 3.69-5.64, I-2 = 96%, n = 43) for obesity, and 22.97 (95% CI: 13.58-38.86, I-2 = 92.1%, n = 6) for severe obesity vs. normal weight. Subgroup analyses indicated that underweight is a protective factor against T2DM in non-Asians (RR = 0.68, 95% CI: 0.40-0.99, I-2 = 56.1%, n = 6). The magnitude of the RR of T2DM in overweight/obesity decreased with age and varied by region and the assessment methods for weight and T2DM. Overweight/obesity was associated with an increased prediabetes/T2DM risk. Further studies are required to confirm the association between underweight and prediabetes/T2DM, particularly in Asian populations.