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.
1. PMID 29503172
R.C. Bonadonna: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Sanofi-Aventis. Speaker's Bureau; Self; Eli Lilly and Company, Sanofi-Aventis. M. Trombetta: None. C. Zusi: None. M. Dauriz: None. M. Boselli: None. E. Bonora: None.
Italian Ministry of Education, Universities and Research; Italian Scientific Research Programs of Relevant National Interest (2015373Z39_004)