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The Thin-Fat Man: Pilgrim's Progress



Prof. C. S. Yajnik
Director, Diabetes Unit


The idea of setting up a Diabetes Unit occurred to me when I was a student at the BJ Medical College and saw an increasing number of diabetic patients in the wards and the outpatients. Our patients showed obvious differences from the text book descriptions, and I thought we needed to study and document them properly. I was lucky to train in Oxford with Dr Hockaday and Dr Edwin Gale. The atmosphere and the training in Oxford was instrumental in shaping my career. On my return from the UK, I worked at the Sassoon Hospital as a Pool Officer of the CSIR, but soon realised the limitations of the place. My plans to transfer to the KEM Hospital materialized only when the then Prime Minister Shri Rajiv Gandhi intervened! Mrs Banoo Coyaji helped me set up a Diabetes Clinic and Dr V N Rao supported my research ambitions.

The Inception

Our first break came when the Wellcome Trust awarded a grant to 'Characterise Indian diabetic Patients'. Dr Shelgikar and Dr SS Naik helped to set up the study with help from Oxford. The Wellcome Diabetes Study highlighted that the Indian diabetic patients were younger, shorter and thinner compared to the patients in the UK but were centrally more obese (higher waist-hip ratio), had larger subcutaneous fat and were more insulin resistant. This was the beginning of the 'thin-fat insulin resistant Indian' concept which became the focus of our future research. There was a considerable resistance to such a paradoxical idea but over years it has established itself and is one of our most frequently quoted research finding. My photograph (‘a thin-fat Indian’) with Dr John Yudkin, published in the Lancet is shown in many meetings.

Fetal Origins and a Lifelong Partnership

We thought that childhood under-nutrition contributed to adult diabetes (the so-called 'malnutrition-related Diabetes' (MRDM)). This idea was purely speculative, and there was little expertise in setting up long term prospective studies in the community. The big boost came in 1991 when Prof David Barker and Caroline Fall visited us to 'sell’ the idea of 'fetal origins of adult disease’. We were quickly convinced that intrauterine life may be the most important period in life to determine future health. Dr Barker and Dr Fall have been partners in our research since then. We set up the first 'fetal origins' study in India with Dr Anand Pandit (Pune Childrens' Study) and found that low birth weight predicted insulin resistance in Indian children. Children who were born small but grew big were the most affected. The next logical step was to study the factors which influenced the growth of Indian babies, and the Pune Maternal Nutrition Study was born.

PMNS and Onwards

Around this time we had our second lucky break, Shri HK Firodiya and Shri Rahul Bajaj donated generously for the construction and equipment of the Diabetes Centre. The Pune Maternal Nutrition Study was set up in six villages near Vadu. KEM Hospital's rapport with the community was a crucial factor in the success of this study. This is the first prospective study in India to investigate the effect of maternal factors (from before conception) on the risk of diabetes and cardiovascular disease in the baby. Dr Kurus Coyaji supervised obstetric aspects, Dr Siddhi Hirve and a team of social workers (MSWs) supervised the field work, Dr Shobha Rao and her team helped with nutritional measurements, Dr Arun Kinare and colleagues helped with ultrasonographic measurements and Mrs Punam Gupta and Charu Jogalekar helped with data management. Laboratory measurements were supervised by Dr SS Naik and Dattatray Bhat. We described that the 'small and thin' Indian babies are in fact 'fatter' compared to the Europid babies and that the metabolic and endocrine risk of future Diabetes was already present at birth. The study highlighted the important role of maternal micronutrient nutrition for baby's growth. These babies are regularly followed up for measurement of risk factors for future disease.

Dr Helga Refsum visited Pune on a Rotary fellowship. She introduced us to the world of homocysteine. Working with her we found that Indians have very high levels of homocysteine in blood. Unlike in Europeans (in whom it is related to folate deficiency), in Indians it is related to vit B12 deficiency (common in vegetarians). We soon extended our studies to demonstrate that maternal vitamin B12 and folate nutrition is important for foetal growth, development and future risk of diabetes. Low maternal vitamin B12 but high folate status predisposes the baby to adiposity and insulin resistance, risk factors for type 2 Diabetes. These findings may have important implications for controlling the diabetes and heart disease epidemic in India. We are in the process of setting up an intervention to improve vitamin status of adolescents to improve the health of the next generation.

Working with Prof John Yudkin we investigated the risk of diabetes and heart disease in rural and urban men (CRISIS study). Urbanization is associated with substantial increase in body fat, an inflammatory state, and insulin resistance which contribute to higher risk of type 2 diabetes and heart disease.

The role of genetics in diabetes is now becoming clear. Our main advisor for genetic studies is Prof Andrew Hattersley (Exeter, UK) who is a dear friend from Oxford days. We have teamed up with Dr Giriraj Chandak (CCMB, Hyderabad) for genetic investigations. We published the first Indian papers on the new exciting markers- TCF7L2 and FTO and are in the process of completing the genome wide study (GWAS) for type 2 diabetes. One new development is to use genetic markers to prove causality of lifestyle exposures. Recently we have used a genetic marker of 1C metabolism (MTHFR) to confirm the causality of the associations of folate and homocysteine with fetal growth. The new excitement is to study genetic regulation by nutritional factors (epigenetics) which is at the root of ‘Developmental Origins of Health and Disease (DOHaD)’. Our findings of the role of vitamin B12 and folate in fetal growth and programming of adiposity and insulin resistance have opened a new door in this branch.

We are also investigating the role of environment (atmospheric pollution) on human health. In an exciting study we have found a relation between exposure to particulate matter and levels of inflammation.

Our progress in research is matched by Patient Care in the Pankuwar Firodiya Day Care Centre. We provide a quality service to diabetic patients through services of many consultants and specialists. Patient education is one of our strengths and we have many educators to do this difficult job.

Finally, we also conduct many clinical trials. Over years we have participated in over 30 clinical trials of antidiabetic medication and devices.

Administering a large unit with multifarious activities is not an easy task. This has been possible because of Pallavi's untiring efforts. She has devoted lot of time to keep things in order.

Our journey in the field of diabetes has been exciting and enjoyable. Hopefully the future will be even more so. Our hope is that our contribution will help reduce the problem of diabetes in India.


Top
Year Event
1986 Beginning of Diabetes OPD at KEM Hospital
1987 First Wellcome Grant
1993 Inauguration of Diabetes Unit
1995 First outdoor camp for type 1 Diabetes children
1997 Official visit by Wellcome Trust (Mary Phillips)
2001 Foot Clinic Established
2006 RSSDI Conference hosted
2006 Vitamin B12 Brainstorming Meeting' (DBT)
2007

'Newer Paradigms in Vitamin B12 Research' An international work-shop