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Research Achievements |
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| Epidemiology & Clinical Research |
Epidemiology is the study of the way disease occurs in a population. By meticulously counting and defining the characteristics of members of a particular group, region, or country, and applying statistical calculations, epidemiologists can track events such as the spread of disease or the influence of different risk factors, and draw the conclusions can lead to preventive action and treatment. We have been closely interacting with leading scientists in this area of research as Dr. Nick Wareham from UK , Dr. Knut Borsch Johensen of Denmark for appropriate statistical design and software development. This led to the now internationally known Chennai Urban Population Study (CUPS).
The epidemiology team of MDRF has been involved in developing new ways to obtain accurate prevalence data on diabetes and its various complications. This department has facilities for handling huge data sets. The major project under progress is the Chennai Urban Rural Epidemiology Study (CURES) currently following 26,000 subjects in urban Chennai and will follow 25,000 in the rural areas near Chennai. ‘CURES' is one of the largest studies of its kind to determine the prevalence of diabetic complications undertaken in India .
The other prominent studies under progress include Prospective Urban Rural Evaluation (PURE) study, ICMR- WHO Stepwise approach to N on-communicable diseases (NCDs), Chunampet Rural Diabetes Project and Heglina study. |
| Diabetic Retinopathy |
In view of the high prevalence of diabetes in Indians, a large number of patients would have a high risk of developing diabetic eye disease at diagnosis or even before diagnosis of diabetes is made. A series of studies are in progress to obtain accurate estimation of prevalence of diabetic retinopathy in Indians and the research priorities include determining the causative factors for retinopathy, to identify the role of growth factors, adhesion molecules and other second messengers in the pathogenesis of diabetes and its progression to diabetic retinopathy.
To assess the prevalence of diabetic retinopathy, a cohort of consecutive 6792 type 2 diabetes patients attending Dr.Mohans' MVDSC, were screened using a combination of retinal photography and clinical examination by retinal specialists. This study proved that a total of 2319 patients (34.1%) had evidence of retinopathy, this appears to be lower than that reported among Europeans. Preliminary studies on risk factors indicate that diabetic retinopathy appears to be more related to levels of haptoglobulin and C reactive protein but does not show association with serum sialic acid levels.
Familial clustering of diabetic retinopathy was studied in 322 families with atleast two diabetic siblings who were registered at Dr.Mohans' M.V.Diabetes Specialities Centre and had undergone a retinal examination. The study results revealed that familial clustering of diabetic retinopathy was three times higher in siblings of Type 2 diabetic subjects with diabetic retinopathy
Association of preclinical atherosclerotic markers with diabetic retinopathy was studied in the Chennai Urban Rural Epidemiological Study [CURES] population, which suggested a strong association of pre-clinical atherosclerotic markers (IMT & AI) with diabetic retinopathy. |
| Risk factors for coronary artery disease in diabetes |
Indians appear to be more genetically susceptible to Coronary Artery Disease (CAD) and this may be linked to high Lp(a) levels. Increased plasma fibrinogen, plasminogen activator inhibitor 1 (PAI-1) and an excess of diabetes combined with insulin resistance appear to increase the thrombogenic risk of Indians as a race. Haemostatic factors, which increase the risk of thrombosis may play a role in coronary artery disease. One haemostatic factor that has not been tested to date is platelet activation among Indians. In collaboration with Dr.Jerome Markovitz of University of Alabama at Birmingham, we have been currently involved in a project looking at platelet activation by flowcytometry detection. |
| Calcium turnover studies |
Since intracellular Calcium (Cai) is a main regulator of vascular tone, (-cell insulin secretion, platelet activation and a strong modulator of enzymes involved in oxidative phosphorylation, glucose transport, protein kinase C-(, several transcription factors and gene expression, studying its cellular and sub-cellular distribution has become an active area of research. We have utilized peripheral blood lymphocytes and platelets from type 2 diabetes patients to delineate different mechanisms of Calcium turnover that determine the level of Cai . When compared to age-and weight matched control subjects, cells from type 2 diabetes patients exhibited higher (P<0.05) basal Cai and reduced plasma membrane Calcium-ATPase activity. There exist a positive correlation of Cai levels with the plasma glucose and HbA1c values. While cells from patients show a defective Calcium extrusion kinetics mediated by Na+/Calcium exchanger, they also exhibit higher rates of store-operated Calcium entry determined by the depletion of intracellular Calcium stores. |
| Genetics of Diabetes |
The application of DNA science to diabetes is one of the most exciting research developments ahead within a relatively short time scale. The genetic determinants of Type I disease reside in the HLA region to a significant extent. The objective of the work is to define the relationship of the genetic and immunological markers and their utility for the prediction of Type I diabetes in the siblings. Our lab is involved in a collaborative research with Prof. Pitchappan, Professor of Immunology, Unit of Immunogenetics, School of Biological Sciences, Madurai Kamraj University. Our future programmes will include the studies related to regulation of gene and role of Single Nucleotide Polymorphism's (SNPs) and susceptibility to Type 2 diabetes. |
| Islet cell transplantation and islet cell cloning |
Islet cells in the pancreas secretes the hormone Insulin that controls blood sugar. In Insulin dependent diabetes mellitus, the islet cells are degenerated and these patients require Insulin throughout their life for survival. Islet cell transplantation has been a hot subject of research worldwide and always require infusion of steroids. Currently we are involved in islet cell transplantation in animal models in collaboration with Prof.S.Gunasekaran of Christian Medical College, Vellore.
Development of an effective cell line could become a unlimited source of beta cells. This will also enable to produce limitless widespread use of successful transplantation techniques. We are presently undertaken a collaborative project with Prof. V.Thyagarajan of Animal Biotechnology (ABT), Tamil Nadu Veternary and Animal Sciences University (TANUVAS), Chennai to clone islet cells from the mice model using hybridoma techniques.
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