Monogenic diabetes in a Chinese population with young‐onset diabetes: A 17‐year prospective follow‐up study in Hong Kong

Abstract Aims Asians have a high prevalence of young‐onset diabetes, but the pattern of monogenic diabetes is unknown. We aimed to determine the prevalence of monogenic diabetes in Chinese patients with young‐onset diabetes and compare the clinical characteristics and outcome between patients with and without monogenic diabetes. Materials and Methods We sequenced a targeted panel of 33 genes related to monogenic diabetes in 1021 Chinese patients with non‐type 1 diabetes diagnosed at age ≤40 years. Incident complications including cardiovascular disease (CVD), end‐stage kidney disease (ESKD) and all‐cause death were captured since enrolment (1995–2012) until 2019. Results In this cohort (mean ± SD age at diagnosis: 33.0 ± 6.0 years, median[IQR] diabetes duration 7.0[1.0–15.0] years at baseline, 44.9% men), 22(2.2%, 95% confidence interval[CI] 1.4%–3.2%) had monogenic diabetes. Pathogenic (P) or likely pathogenic (LP) variants were detected in GCK ( n = 6), HNF1A ( n = 9), HNF4A ( n = 1), PLIN1 ( n = 1) and PPARG ( n = 2), together with copy number variations in HNF1B ( n = 3). Over a median follow‐up of 17.1 years, 5(22.7%) patients with monogenic diabetes (incidence rate 12.3[95% CI 5.1–29.4] per 1000 person‐years) versus 254(25.4%) without monogenic diabetes (incidence rate 16.7[95% CI 14.8–18.9] per 1000 person‐years) developed the composite outcome of CVD, ESKD and/or death ( p = 0.490). The multivariable Cox model did not show any difference in hazards for composite events between groups. Conclusions In Chinese with young‐onset non‐type 1 diabetes, at least 2% of cases were contributed by monogenic diabetes, over 80% of which were accounted for by P/LP variants in common MODY genes. The incidence of diabetes complications was similar between patients with and without monogenic diabetes.