CHARACTERIZATION OF LATENT AUTOIMMUNE DIABETES IN ADULTS IN A REGION OF INDIA

Abstract

Introduction: A significant proportion of diabetic patients with adult‐onset diabetes, initially non requiring insulin treatment, have glutamic decarboxylase autoantibodies (GADA) in their sera and display a different clinical phenotype from classical type 2 diabetes (DM2) without GADA. A new subclass of diabetes with the designation of latent autoimmune diabetes of adult‐onset (LADA) has been proposed for this category of subjects. _x000D_ Research Objectives: Adult-onset autoimmune diabetes is heterogeneous consisting of various groups. This observation has been intensively investigated in Europe and needs a comprehensive search in India. Epidemiological studies have reported varied prevalence of LADA. In South Asia, data on LADA are sparse. Significant discrepancy in the frequency of LADA has been observed in earlier studies on Indian population ranging from 2.6% to 58%. Such variation in the results may be attributed to local differences and conflicting methodology adopted by various authors. Diagnosing LADA early in the disease process is important as it may have therapeutic implications. In order to assess the true prevalence and characterize LADA in various populations, a standardised diagnostic criterion is required. The adoption of standard criterion and valid methods to define LADA would facilitate the rational comparison of the disease between different populations and a more efficient management for all health providers._x000D_ Methods: We performed a cross-sectional investigation in the Northern region of India that included 139 subjects. Inclusion criteria were: a) diagnosis of diabetes by standard criteria; b) age at diagnosis of diabetes, 30 – 70 years; c) duration of disease between 6 months to 5 years. The concentrations of glucose, glycosylated hemoglobin, lipid profile, creatinine, C-peptide, and GADA were measured in serum/plasma samples after fasting for more than 10 hours. Subjects with GADA in whom insulin was started at diagnosis or within one month of diagnosis were defined as DM1. All antibody negative subjects were diagnosed as DM2. LADA patients were defined as patients who did not require insulin for at least 6 months after diagnosis and depicted GADA at their sera._x000D_ Results and Conclusions:_x000D_ 1- LADA represents 6.5% of cases among all adult-onset diabetes in a region of Northern India, considerably a higher frequency than reported in two previous studies. In diabetic subjects diagnosed at 31-40 years of age, the frequency of LADA was 13.9%. A decreasing trend of LADA with increasing age was suggested, similar to reports from Chinese and European publications._x000D_ 2- In our study, LADA was the prevalent subtype of adult-onset autoimmune diabetes, in agreement with earlier reports showing lower prevalence of DM-1A among children and adolescents in Northern India. In this investigated population, the prevalence of LADA was much lower than previously reported in Southern India._x000D_ 3- The group of subjects with diagnosis of LADA were younger, and presented lower abdominal circumference, serum C-peptide and triglycerides levels at fasting than the group of subjects with DM2 from the same area of Northern India._x000D_ 4- In our study, LADA patients depicting high titers of GADA in their sera at the time of diagnosis were more likely to be male, leaner, and insulin- treated, and less likely to display systolic hypertension and the metabolic syndrome._x000D_ 5- In the same investigated population, LADA patients depicting low titers of GADA in their sera were mostly females, and they did not show phenotypic differences than DM-2 patients, similar to data reported for Asian Chinese population, in contradiction to the data reported for European population._x000D_ 6- In comparison to subjects with DM2, serum C-peptide levels at fasting at the time of diagnosis were lower in LADA patients in the current study. This difference remained after 36 months, contrary to data of Spanish LADA Study.

Date of Award	30 May 2018
Original language	English
Supervisor	Alberto de Leiva Hidalgo (Director)