Study of genetic factors associated with diabetes at young age

Project Associates
Piyali Dhar Chowdhury (till Dec 2001)

Collaborators
Ravinder Goswami, AIIMS, New Delhi

The project aims to study the genetic factors associated with diabetes of the young, which include insulin dependent diabetes mellitus (IDDM) and ketosis resistant diabetes of the young (KRDY). The ultimate aim of the project is to decipher ways that can be used for the diagnosis of the prediabetics in the high-risk groups e.g. children in the family of patients with either IDDM or KRDY. IDDM has been shown to have autoimmune etiology, however, not much is known about the etiology of KRDY although autoantibodies have been found in KRDY patients, suggesting an autoimmune etiology for this form of the disease as well. The basic problem with the IDDM patients is that by the time they report to the clinic, the insulin producing beta cells of the pancreases are damaged to a considerable extent. So, the treatment of choice is to give insulin which does take care of the daily insulin requirement, however, does not stop autoimmunity. Hence, there is a need to identify these patients earlier in life so that further beta cell damage can be arrested by some kind of immune intervention.

Since the disease has been shown to have genetic predisposition, to be able to identify prediabetics, the project aims to study (i) the HLA-A, B, DRB1, DQA1, DQB1 and DPB1 polymorphism in IDDM and KRDY patients from North India and ethnically matched controls, (ii) the polymorphism of 5’-INS gene (IDDM2) or insulin-linked polymorphic region (ILPR) in IDDM and KRDY patients and controls, (iii) the autoantibody profile to insulin and islet cells and C-peptide levels in IDDM and KRDY patients and controls, and (iv) the association of HLA with the type of autoantibodies found in the patients.

Fifty eight additional (total 103) blood samples from young diabetics and 20 additional samples from normal healthy controls, have been collected and DNAs have been extracted. 80 samples have been studied for HLA class II alleles present in the patients. The results are similar to what was reported last year. However, sample collection is still on since one of the aims of the project is to see whether there are any immunogenetic differences between IDDM and KRDY patients and we may not have enough KRDY patient samples yet. My collaborator Dr R Goswami has sent the samples and we are not aware of their clinical diagnosis as to which samples are from IDDM patients and which are from KRDY patients.

Seventy samples from young diabetics and 40 control samples have been studied for insulin linked polymorphic region. However, the data will be analysed only after the completion of all the patient and control samples to avoid any bias.

Sera samples are being collected as well, at the time of blood collection for autoantibody study. My collaborator is doing this part of the work; the results will be analysed only after the completion of the data collection.