Trajectories of changes in glucose tolerance in a multiethnic cohort of obese youths: an observational prospective analysis

Summary Background Type 2 diabetes is preceded by a prediabetic stage of impaired glucose tolerance that affects 10–23% of youth and is expected to double over the next decade. The natural history of impaired glucose tolerance and the determinants of β-cell dynamic response have never been investigated longitudinally in young people. We aimed to investigate the clinical and metabolic determinants of longitudinal glucose tolerance changes and β-cell function in a multiethnic cohort of obese youth. Methods We followed up prospectively a multiethnic cohort of overweight and obese (body-mass index >85th percentile) adolescents with baseline normal glucose tolerance (plasma glucose Findings Between January, 2010, and December, 2016, 526 adolescents (mean age 12·7 years, range 10·6–14·2) were enrolled to our study. At baseline, 364 had normal and 162 had impaired glucose tolerance. Median follow-up was 2·9 years (IQR 2·7–3·1). 105 (65%) of 162 with impaired glucose tolerance at baseline reverted to normal glucose tolerance at follow-up, 44 (27%) had persistent impaired glucose tolerance, and 13 (8%) progressed to type 2 diabetes. A feature of reversion to normal glucose tolerance was a roughly four-fold increase in the oral disposition index (from median 0·94 [IQR 0·68–1·35] at baseline to 3·90 [2·58–6·08] at follow-up; p vs 1·59 [1·12–2·23]; p Interpretation Impaired glucose tolerance is highly reversible in obese adolescents. Ethnic origin is the main clinical modifier of the dynamic β-cell response to prediabetic hyperglycaemia and, thus, determines the reversibility of impaired glucose tolerance, or its persistence. Therapeutic interventions for impaired glucose tolerance should target the specific mechanisms underpinning glucose tolerance changes in high-risk ethnic groups. Funding National Institutes of Health (National Institute of Child Health and Human Development, National Center for Research Resources, and National Institute of Diabetes and Digestive and Kidney Diseases), American Diabetes Association, International Society for Pediatric and Adolescent Diabetes, Robert Leet Patterson and Clara Guthrie Patterson Trust, European Society for Pediatric Endocrinology, American Heart Association, and the Allen Foundation.