‘’There is still a lacuna of research in the area of diabetes in India’’

What is the density estimation of diabetics in India?

Dr Anoop Misra

In 2011, nearly 61.3 million people were suffering from diabetes in India and this figure is expected to reach 101.2 million by the year 2030. At present approximately 63 million people in the age range of 20-79 years are suffering from diabetes in India. However, with a majority of people still remaining undiagnosed, we still cannot comment on the exact figure of diabetes.

Tell us about diabetes due to genetic defects.

The two most common forms of diabetes are Type 1 diabetes and type 2 diabetes. Both these are caused by genetic and environmental factors. In causation of these disorders, multiple genes are involved. However, there are other rare forms of diabetes that are directly related to defect in single gene. These include maturity onset diabetes in the young a (MODY) and diabetes due to mutations in mitochondrial DNA. Further, there are a couple of studies showing that certain genes increase the tendency to develop obesity. In our recent study we found that a particular type of gene (LMNA1908T/T) increases the tendency of obesity therefore people having this particular gene are at 5.6 times higher risk to become obese, further leading to diabetes.

Could you also tell us about cystic fibrosis-related diabetes, steroid diabetes induced by high doses of glucocorticoids, and several forms of monogenic diabetes.

Cystic fibrosis (CF) is a life-threatening genetic disorder that causes severe damage to the lungs and digestive system. It is an inherited condition affecting the cells that produce mucus, sweat and digestive juices. These secreted fluids are normally thin and slippery. But in cystic fibrosis, a defective gene causes the secretions to become thick and sticky. Instead of acting as a lubricant, the secretions plug up tubes, ducts and passageways, especially in the lungs and pancreas.

Cystic fibrosis–related diabetes (CFRD) is the most common co-morbidity in people with cystic fibrosis (CF). It is primarily caused by insulin insufficiency, although fluctuating levels of insulin resistance related to acute and chronic illness also play a role. It is often clinically silent. In CF, the nutritional and pulmonary consequences of diabetes are of greater concern. CFRD is associated with weight loss, protein catabolism, lung function decline, and increased mortality, and thus regular screening is warranted. As per the guidelines of American Diabetes Association, CFRD should be managed by a multidisciplinary team of health professionals with expertise in CF and diabetes.

Steroid diabetes (also known as steroid-induced diabetes) is a medical term referring to prolonged hyperglycaemia (high blood sugar levels) due to glucocorticoid (a steroid) therapy for another medical condition (e.g. severe asthma, organ transplantation, cystic fibrosis, inflammatory bowel disease, and chemotherapy for leukaemia or other cancers). The most common glucocorticoids which cause steroid diabetes are prednisolone and dexamethasone given systemically in ‘pharmacologic doses’ for days or weeks. Typical medical conditions in which steroid diabetes arises during high-dose glucocorticoid treatment include severe asthma, organ transplantation, cystic fibrosis, inflammatory bowel disease, and induction chemotherapy for leukaemia or other cancers.

Monogenic diabetes: Monogenic diabetes is due to defect in a single gene. Different types of monogenic diabetes include neonatal diabetes and MODY (maturity onset diabetes of the young).

What is the incidence of the above forms of diabetes in India?

There is still a lacuna of research in this area in India so far and more studies are required to provide an accurate picture. Overall, combined together these would amount to less than three per cent of cases of diabetes.

Kindly explain thrifty genotype and the thrifty phenotype concept as applicable to diabetes.

Overall Indians have more accumulated fat in their bodies, from the time of birth, nearly 1.5 times more than white race. This can be accumulated in many places, but when it gathers at the abdomen, this interferes with the body’s metabolism and becomes a health problem. As a rule, Indians tend to have greater waist circumference and also waist to hip ratios. Why Indians have higher body fat is not clear, however, it has been suggested that during centuries of famine, body has developed mechanism that enables energy to be stored in the form of fat (best storage form of energy) to be used at times of scarcity of food. Now that food is in excess, this accumulated fat has increased rapidly. We have also researched that this excess fat gets deposited in peculiar places in the body; nape of neck (akin to buffalo hump) and below chin (double chin). In fact these markers could be easily recognised and lend increased risk for development of diabetes.

A ‘thrifty phenotype’ hypothesis emphasises on foetal under-nutrition leading to altered metabolic programming in adult life is an attractive hypothesis but still lacks firm evidence.

• Indian babies born small and with low birth weight had higher systolic blood pressure and adiposity at eight years of age. These data have prompted the concept that the syndrome X originates in mother’s womb and that at this time key metabolic activities may get modulated. Normal weight range in childhood are independent factors, or additive in causation of insulin resistance and the metabolic syndrome has not been investigated.
• Further, the role of micronutrient deficiencies during perinatal period (before birth) in development of chronic diseases later in life has been suggested.

What are the new concepts in Type 2 diabetes management?

The dietary management of Type 2 diabetes has seen a new wave in the area of dietary management. Moving from the conventional dietary approach, a shift towards Mediterranean form of diet has been noticed [laying emphasis on fibre (coming from vegetables, fruits, whole grains and pulses) and monounsaturated fatty acids (coming from nuts and MUFA rich oils; olive, mustard, canola)]. Nearly 70 type of new drugs are being studies for diabetes, which are aimed at pathways other than those targeted by the conventional drugs (sulphonylureas, metformin); including kidneys, liver, cell inflammation, muscle energy pathways etc.

Are there any biologic drug in research for Type 1 diabetes?

There are several researches going on in the field of diabetes, however, it is still too early to comment on these as they still have to successfully complete the trial phase.

What are the most important R&D projects involving diabetes in India?

There are some new projects regarding drug development in India, but the overall contribution to diabetes drug development by India is minuscule.

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