Spotlight

Paradise for Diabetes Research

The state-of-the-art research lab of Madras Diabetes Research Foundation in the outskirts of Chennai is conducting various path-breaking studies in diabetes, says Rita Dutta

Research has always been an indomitable passion for him, almost his alter ego and his motive to be a diabetologist. We are talking about Dr V Mohan, renowned diabetologist and Founder-Chairman of Dr Mohan's Diabetes Specialities Centre, Chennai. And the proof of his zeal and dedication to diabetes research lies not in the multiple research projects that he has immersed himself into over the last four decades, not even in the hundreds of research papers that he has diligently published, but in creating a state-of-the-art research centre where he is engaging and nurturing bright minds to unveil unknown facets on diabetes and thus helping the nation cope with a killer disease that 50.8 million Indians are grappling with today.

The Lab cocooned in verdant greenery and away from the din and bustle of the city is the new research centre of Madras Diabetes Research Foundation (MDRF), located at Siruseri (in the outskirts of Chennai). Spread over a sprawling 6.5 acres, the main research unit is called Kallam Anji Reddy Centre as a mark of recognition to Dr Anji Reddy, who donated a substantial amount to build the centre. One would realise that one has entered the hallowed world of diabetes research, as the entrance of the main building houses a gallery that is dotted with pictures of leading diabetologists. The lab, located at Women‘s Biotech Park, could be constructed as the land was given to Dr Reema Mohan, Vice President, MDRF, for being woman entrepreneur.

Though everything looks grandiose today, the seeds for starting this centre were sown when MDRF was founded way back in 1996 at Gopalapuram research wing of Dr Mohan's Diabetes Specialitites Centre with only one room and one scientist.

It is no wonder that the research activities have multiplied manifold in the last decade, as even in 1971 Dr Mohan was reclined towards research. Recollects Dr V Mohan, President and Chief of Diabetes Research, MDRF, "When my father asked me to join him at his centre in the 70s, I agreed on the condition that he would allow me to conduct research. However, at that time it was an uphill task to conduct research as the Government did not provide any funding to us. Our research grants were refused on the ground that research was the prerogative of Government institutes and not private ones." Fortunately, such inimical attitude of the Government has now completely altered for centres involved in serious research and indeed the Government now supports MDRF and similar research centres.

The Siruseri unit, which was started in 2007, has conducted over 85 research projects. The facility provides opportunities for pre-clinical safety studies for cell-based therapies, proteins and new chemical entities. The research unit of MDRF has 13 departments, fifteen faculty and 25 research students. A cent per cent non-profit organisation, MDRF depends largely on private donors and Government research support for its growth and activities.

Inside the tele-opthalmology mobile van of MDRF

A technician at the cell and molecular biology lab

Some Key Departments & Studies

Cell & Molecular Biology: The department is involved in studying cell and molecular signatures with special reference to insulin secretion, insulin action and vascular function. Says Dr M Balasubramanyam, Head, Cell & Molecular Biology, "Our research integrates physiological and pharmacological approaches with biochemical, molecular biological and proteomics techniques to study mechanisms underlying development and progression of diabetes, its complications and cardiovascular diseases." As of now, the department is working on exploring novel mechanisms of insulin resistance and type II diabetes using miRNA and RNAi technologies, search for susceptibility genes for type II diabetes in Indians, role of NF-E2-related factor-2/ Hemoxygenase-1 (Nrf2/HO-1) signalling in the retinal vasculature, exploring a role of 'hyperglycemic memory'and activation of Nrf2 and/or HO-1 induction to identify novel drug targets for insulin resistance and type II diabetes.

Ocular Research: This department aims to determine the prevalence/incidence of diabetes related eye problems in the population and in the clinical population and to assess the impact of therapy for diabetic retinopathy and to study molecular mechanisms using post-mortem retinal endothelial cells. It is engaged in conducting a population-based prospective cohort study to assess the incidence of diabetic retinopathy.

This department is also involved in MDRF Rural Tele-ophthalmology Project at Chunampet Village in Kancheepuram district. Supported by World Diabetes Foundation (WDF), Denmark, this project uses a mobile van, equipped with an ECG monitor, a doppler imaging system, a biothesiometer and a digital retinal camera, to provide tele-consultation from the Gopalapuram centre to patients inside the van, with the help of ISRO satellite. Says Dr Rema Mohan, Vice President and Chief of Ocular Research, MDRF, "This project is also aimed to encourage community participation by empowering local people to become spokespersons to adopt a healthy lifestyle and thereby play a significant role in preventing diabetes related eye disorders in the family and in the community at large."

Molecular Genetics: To find genes that cause/ predispose individuals to diabetes using genetic techniques and to understand the molecular basis of diabetes and its related traits in order to form a rational platform for improved diagnosis treatment of patients, the department of molecular genetics is involved in some key projects. Says Dr Radha Venkatesan, Head, Molecular Genetics, MDRF, which is an ICMR Advanced Centre for Genomics of type II diabetes, "We were able to show a novel association of an intronic polymorphism in the adiponectin gene to type II diabetes, obesity and adiponectin level. Further, we have identified a novel MODY 3 gene mutation which we have shown to co-segregate with the disease in the family which is not seen in normal glucose tolerant subjects. Additionally, we have shown the Ala 98Val polymorphism of the MODY 3 gene to be associated with younger age at onset of type II diabetes."

"It is established that polished white rice leads to diabetes. Can we reverse diabetes if we have brown rice?" - Dr V Mohan President and Chief of Diabetes Research MDRF

"The tele-pathology project is also aimed at empowering the local people to become spokespersons to adopt a healthy lifestyle" - Dr Rema Mohan Vice President and Chief of Ocular Research MDRF

Epidemiology: With the objective of studying the distribution and determinants of diabetes in the population, this department has pioneered some key studies in the country. The first study, the Chennai Urban Population Study (CUPS) carried out by MDRF between 1996 and 1998, looked at intra urban differences in diabetes with respect to socio-economic status. Explains Dr Mohan, "This study reported on the prevalence of diabetes, impaired glucose tolerance (IGT) and other features of the metabolic syndrome like insulin resistance, hyperlipidemia, hypertension and obesity in two socio economically different sections of society within an urban environment and also reported on the differences in risk factor profiles within these two strata of society."

The Chennai Urban Rural Epidemiology Study (CURES), started in 2001, is an epidemiologic study involving 26,001 individuals of a representative population of Chennai to estimate the prevalence of diabetes and its complications in urban Indians and to identify the risk factors for non-communicable diseases (NCDs).

Another key study—the Prospective Urban and Rural Epidemiological (PURE) study, is a prospective cohort study that will track changing lifestyles, risk factors and chronic disease using periodic standardised data collection in urban and rural areas of 14 countries. The WHO stepwise approach for NCDs is a large multi centric cross-sectional survey conducted in five centres in India using standardised protocol. Other studies include Integrated Disease Surveillance Project, Indian Diabetes Risk Score Validation Study, sentinel surveillance System for cardiovascular disease in Indian industrial population, influence of heritability on glucose intolerance and metabolic syndrome in adolescents, family genetic study, schizophrenia, diabetes, etc.

However, the most important epidemiological study is the ICMR-INDIAB study, a three-year study which MDRF is conducting in collaboration with ICMR for determining the nationwide and state-wise prevalence of diabetes. This study is coordinated by Dr V Mohan and Dr RM Anjana, Diabetologist and Research Officer, MDRF. Adds Dr Anjana, "This will be the largest epidemiological study on diabetes in India till date."

Clinical Trials: With the attached hospital having close to 2,00,000 diabetic patients (one of the largest in the world), MDRF is a pioneer in clinical trials. The department has conducted over 80 GCP trials.

Foods, Nutrition & Dietetics: This department was formed with the objective of studying and evaluating the nutrition determinants of chronic diseases such as diabetes and also to popularise lifestyle modification by increasing awareness on the variety of food choices for individuals with diabetes. Elaborates Sudha Vasudevan, Head, Foods, Nutrition & Dietetics, "We are conducting rural nutritional epidemiological studies which would estimate of the dietary intake of the rural population, determination of risk factor association and comparison of urban rural dietary intake. Others include cooking oils and HDL-Cholesterol levels, development of the visual food atlas to estimate portion size and tools". For Foods Research, the department is focussed at food quality analysis and product development, sensory evaluation and nutrient estimation of rice samples, popularly consumed by Chennaites with different degree of milling, estimation of proximate and dietary fibre among nine rice varieties, testing of newly processed rice using post harvest technology.

Molecular Immunology and Transcriptomics: Even as diabetes is a major risk factor for tuberculosis, the 'DM-TB nexus' is not well studied. Says Dr Aravindhan Vivekanandhan, Head, Molecular Immunology and Transcriptomics, "Several studies indicate that patients with TB who have diabetes present a higher bacillary load in sputum, delayed mycobacterial clearance, and higher rates of multidrug-resistant infection.” A project has been initiated in the department to address the impact of diabetes on the 'protective immune correlates' of TB. Other studies include immune system in diabetes and filariasis coexistence, in silico prediction and in vitro validation of putative T and B cell epitopes in diabetes associated autoantigens.

Translational Research: The department approaches diabetes and NCDs prevention in the community through prevention—primordial, primary, secondary and tertiary. Says Dr Ranjani Harish, Head, Translational Research, "One of the community projects that we are involved in is obesity reduction and awareness of NCDs through group education, which is aimed at screening children in schools and colonies to determine the prevalence of obesity, diabetes, pre-diabetes, hypertension, dyslipidemias, metabolic syndrome and MODY.”

The Significance

Amongst the innumerable research results, two studies that have had a major impact are the Indian Diabetes Risk Score that helps indicate diabetes in three easy steps and findings that have shown that PPAR gamma gene 12 Ala polymorphism does not protect the Indians from diabetes; rather coactivator of PPAR gamma is associated with type II diabetes. New research projects that MDRF is keen on taking on now include large-scale study on why Asian Indians are prone to diabetes, to find out new genes responsible for diabetes, and also to focus on lifestyle changes for diabetes. "It is established that polished white rice leads to diabetes. Can we reverse diabetes if we have brown rice?" quips Dr Mohan. Such a curious mind and a vision to make a long-term difference would continue to break new grounds in prevention, diagnosis and treatment of diabetes.

rita.dutta@expressindia.com