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.
References
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)
