1502-P: Novel Subgroups of Type 2 Diabetes at Diagnosis in a Southern European Cohort

Abstract

In 739 GADA-negative patients of the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) we investigated whether the 4 (severe insulin deficient: SIDD; severe insulin resistant: SIRD; mild obese: MOD; mild age related: MARD) novel subgroups (1) of type 2 diabetes (T2D) were identifiable at diagnosis. Data-driven 4-means cluster analysis of 4 variables [age, BMI, HOMA2 beta cell function (BCF) and insulin resistance] was run as in (1). Two clusters were consistent with SIDD and MARD; the others were labeled obese insulin resistant (OIRD), likely encompassing MOD and SIRD, and early onset diabetes (EOD) (Table). Among 8 diabetes risk alleles tested in (1), HHEX/IDE (rs1111875) and TSPAN8 (rs7961581) had highest prevalence in OIRD (p<0.05). Clamp measured insulin sensitivity (IS), but not modeled BCF (glucose sensitivity) of 5-hour OGTT, was different in all comparisons (Table). OIRD and MARD had lower eGFR than EOD and SIDD (Table). Prevalence of cardiovascular disease (ischemic ECG; plaques at US scans of carotid and peripheral arteries) was higher in MARD (p<0.01), while retinopathy and albuminuric nephropathy were similar in the 4 clusters. At a 14-month follow-up (n=419), SIDD held the highest HbA1c (p<0.01). Thus, in the VNDS, novel subgrouping of T2D is largely confirmed and is associated to significant heterogeneity of genetics, pathophysiology, organ damage and evolution of glucose control.