Longitudinal relationships between glycemic status and body mass index in a multiethnic study: evidence from observational and genetic epidemiology

We investigated the relationship between glycemic status and BMI and its interaction with obesity single-nucleotide polymorphisms (SNPs) in a multi-ethnic longitudinal cohort at high-risk for dysglycemia. We studied 17 394 participants from six ethnicities followed-up for 3.3 years. Twenty-three obesity SNPs were genotyped and an unweighted genotype risk score (GRS) was calculated. Glycemic status was defined using an oral glucose tolerance test. Linear regression models were adjusted for age, sex and population stratification. Normal glucose tolerance (NGT) to dysglycemia transition was associated with baseline BMI and BMI change. Impaired fasting glucose/impaired glucose tolerance to type 2 diabetes transition was associated with baseline BMI but not BMI change. No simultaneous significant main genetic effects and interactions between SNPs/GRS and glycemic status or transition on BMI level and BMI change were observed. Our data suggests that the interplay between glycemic status and BMI trajectory may be independent of the effects of obesity genes. This implies that individuals with different glycemic statuses may be combined together in genetic association studies on obesity traits, if appropriate adjustments for glycemic status are performed. Implementation of population-wide weight management programs may be more beneficial towards individuals with NGT than those at a later disease stage.