Endocrine Abstracts

Background & objective: In contrast to Caucasians of European origin, the aetiology of diabetes mellitus (DM) in young adults in other ethnic groups, including Indians is likely to be heterogeneous and difficult to determine. This study was undertaken to determine the aetiology of DM in the young South Indian population.

Methods: In this ambispective study, 144 South Indian young-onset diabetes (age at onset 12-35 years; duration <5 years) were studied. Diabetes secondary to steroid intake, gestational diabetes and secondary to endocrine diseases like acromegaly, and Cushing’s disease were excluded. Fasting and post-prandial plasma glucose, fasting lipid profile, fasting and stimulated C-peptide, islet cell antibodies ICAs [glutamic acid decarboxylase 65 (GADA), tyrosine phosphatase (IA-2Ab) and zinc transporter-8 (ZnT8Ab)] and pancreatic imaging using abdominal radiography was performed in all patients. Clinically suspected MODY subjects were subjected to targeted next generation sequencing for 13 MODY genes.

Results: The prevalence of type 2 diabetes (T2DM) and type 1 diabetes (T1DM) was 59.02% (85/144) and 29.16% (42/144) respectively, followed by fibrocalculous pancreatic diabetes (2.77%). Other rare types included MODY (2.08%), ketosis-prone type 2 DM (2.08%), diabetes secondary to lipodystrophy (1.38%), syndromic diabetes (1.38%), diabetes secondary to pancreatic disease (2.08%). The median (IQR) fasting c-peptide was 1.83(1.3, 2.62) vs 0.27(0.023, 0.66) ng/ml [P<0.0001] while stimulated C-peptide was 4.38(2.82, 5.95) vs 0.43(0.093, 1.55) ng/ml[P<0.0001] in T2DM and T1DM respectively. ICA was positive in 73.80% of T1DM and 5.8% of T2DM. Among T1DM subjects, the ICA positivity for GADA, IA-2Ab and ZnT8Ab was 61.90% (26/42), 21.42% (9/42) and 1.66% (7/42) respectively. GADA+ IA-2Ab positivity was found in 7.14%, and GADA+ZnT8Ab positivity was found in 9.52%. and only one T1DM subject was found to be positive for IA-2Ab+ZnT8Ab. For diagnosis of T1DM, the addition of IA-2Ab increased the yield in three subjects, while ZnT8 didn’t add to the yield. MODY was diagnosed in 2.08% (3/144) subjects, one subject was positive for a novel heterozygous ABCC8 (NM_000352.6): c.1591A>G. P (Thr531Ala) gene missense variant with unknown significance. Other two MODY subjects were positive for heterozygous ABCC8 (NM_000352.6): c.917G>A p. (Arg306His) gene missense mutation and a rare heterozygous PDX1 (NM_00209.4): c.670G>A P (Glu224Lys) gene variant with unknown significance respectively.

Conclusion: The aetiology of diabetes in young adults was heterogeneous, with T2DM more common than T1DM. Testing for islet antibodies and C-peptide along with targeted genetic testing in this age group helps in the correct etiological diagnosis of diabetes.