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Type 2 DM is due to Mitochondrial "fatigue" of the beta cells of pancreas


29 July 2015
India is rapidly becoming the Diabetes capital of the world. 99% of Diabetics are Type 2 (Adult onset), but what triggers Diabetes. Insulin resistance is one common explanation but recently studies at Buck Institute for Research on Ageing, Novato, California, USA has found that it is due to mitochondrial "fatigue" of the beta cells of pancreas, which secrete Insulin. Mitochondiral membrane potential is altered!!
Research is on, why this happens!

Primary prevention of type 2 diabetes in India

Dr A Ramachandran, Chennai
There have been several pioneering prevention programs in the world like the DPP in the US, IDPP in India. The first prevention program was in China.
IDPP screened populations to recruit subjects at risk of developing diabetes with outcome to prevent or postpone onset of type 2 diabetes.
IDPP-1 (Diabetologia 2006;49:289-297) formed the background to do further studies on prevention of diabetes in subjects with IGT among Indians (Diabetologia May 2009; The Lancet Diabetes Sept 2013).
IDPP-1 randomized study subjects into 4 groups: No intervention, lifestyle modification, metformin and lifestyle modification + metformin. We had 95% participation adherence after 3 years. The trial concluded that lifestyle modification significantly reduced conversion to diabetes by 28.5%, metformin by 26.4% and lifestyle modification + metformin by 28.2%.
Difference between Indian study and western studies
Indians develop IGT at least one decade earlier
BMI is much lower
We use metformin at a much lower dose
Moderate lifestyle modification advocated
Weight loss was not significant
The primary prevention trials so far, have proved that lifestyle intervention can reduce incidence of diabetes in high risk subjects. But, such programs are labour intensive, costly and have not been widely implemented, even in high-income countries.
The pilot study in J Assoc Physicians India 2011 Nov;59:711-4 by Shetty AS et al showed that frequent communication via SMS was acceptable to diabetic patients and it helped to improve the health outcomes.
A new study evaluated whether tailored SMSs encouraging lifestyle changes could reduce incidence type 2 diabetes in Indian men with IGT (Lancet Diabetes Endocrinol. 2013 Nov;1(3):191-8). In the study, controls were given standard care advice; intervention group received standard care + motivational text messages, which were tailored according to stage of TTM. There was 36% relative risk reduction in T2DM and 9% absolute risk reduction. HDL-C improved, dietary adherence improved, no sign of improvement in physical activity.
A study published in Nov 2014 issue of Diabetes Care showed that early improvement was associated with a 75% lower incidence of diabetes in 2 years when compared with the remaining dysglycemic persons.
Increased triglycerides and increased waist circumference strongly associated with IR (Diabetes Medicine 2014 Jun 9): hypertriglyceridemic waist phenotype (HTWP): WC =90 cm; serum TG = 1.7 mmol/l. It can be used as a simple proxy for IR.
The oral disposition index is a strong predictor of incident diabetes in Asian Indian prediabetic men (Acta Diabetol. 2015 Feb 12).

Key messages from the SMS study

Mobile messaging could be a practical and affordable strategy to deliver lifestyle advice to delay or prevent onset of T2DM.
The ancillary studies have provided insight into the prediction and pathogenesis of diabetes in the Indian population.

This study is one of the 1st examples of clinical outcome using mobile technology or m-Health.

Diabetes epidemic on the rise in India

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With World Diabetes Day having gone by on November 14, experts give the low-down on one of the biggest lifestyle diseases and how to deal with it

Have a deskbound job that has you sitting for over six hours at a stretch? Have you been leading a very sedentary lifestyle and done nothing about it so far? Well, sit up and smell the proverbial coffee, or in this case, get out and get that adrenalin going. An inactive life, which involves lack of exercise and poor calorie management, is one of the biggest contributors to the dreaded disease of diabetes, today. "India is facing an epidemic of diabetes. At present, confirmed diabetes patients in India are 67 million, with another 30 million in prediabetes group. By 2030, India will have the largest number of patients in the world. Diabetes is not only a blood sugar problem, but brings along other complications as well," warns Dr Arun Bal, diabetic foot surgeon.

Diabetes and cardio 
It's not just the vision, diabetes takes a severe toll on the heart too. "The incidence of heart disease is increasing at a rapid rate. It was 1.09% in the 1950s, increased to 9.7 % in 1990, and 11% by 2000. This rising trend will make India the heart disease capital of the world," warns interventional cardiologist, Dr Suresh Vijan. "Indians face a dual risk of heart disease and diabetes. The risk of death due to myocardial infarction is three times higher in diabetics as compared with non-diabetics. Life expectancy too is reduced by 30% in diabetics as compared to non diabetics; this translates into a loss of eight years of life." The culprit? "Increased consumption of dense-rich foods along with increasing sedentary lifestyle has increased the incidence of diabetes and heart disease," he says.
How it's treated: Adopting a healthy lifestyle with more activity will reduce the incidence of diabetes and heart disease. Try walking each day or do some cardio activity, after consulting your doctor.

Diabetic foot ulcers 
One of the most dreaded complications of diabetes is foot ulcer and gangrene. Deaths due to foot gangrene are only second to cancer deaths. "People with diabetes are at an increased risk of complications from wound healing. Due to the decreased blood flow, injuries heal slowly than in people who do not have the disease. It occurs in 15% of all patients with diabetes and precedes 84% of all lower leg amputations. Many people with diabetes also have Neuropathy — loss of sensation in their hands or feet," adds Dr Bal.
How it's treated: He says 85% of these amputations can be easily prevented by patient education and proper and early wound care. The cornerstone of prevention of diabetes is regular exercise, managing stress and healthy food habits.

Gestational diabetes 
Gestational diabetes is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy. "In developing countries Including India, the prevalence is almost 16-17%. Those who are overweight and have a family history of diabetes, are at the risk of developing GDM," says Dr Deepak Chaturvedi, endocrinologist and diabetologist. Is there any way to avoid it? "Control weight through calorie intake for one. Have small, frequent meals during pregnancy (balanced diet), avoid obesity before conception and stay active throughout your pregnancy," he advises.
How it's treated: Split the daily meals in 5-6 portions. Use insulin therapy, whenever needed. Follow normal physical activity plus graduated daily exercise like walking. Monitor bodyweight, blood pressure, haemoglobin, glysolytated haemoglobin, blood sugar etc. Foetal development assessment by ultra sonography.

How it affects the eyes 
Diabetes can cause the loss of vision when it starts affecting your retina, warns surgical head, Dr Keiki Mehta. "Diabetic retinopathy often has no early warning signs. In the early stages, virtually no changes occur in vision. As the fluid gathers in the macular area, the vision gets blurry. In the early stages, small fine blood clots develop on the retina, with hazy white spots. In later stages, the vessels leak and fibrous fine bands like cobwebs develop on the retina and as they heal, the fibrous bands pull off the retina causing retinal detachment and loss of vision," he says.

Who are at risk?
All people with diabetes are at risk — those with Type 1 diabetes (juvenile onset) and those with Type 2 diabetes (adult onset).

How it's treated: Treatment involves sealing off leaking blood vessels using laser. Sometimes, an injection is given in the eye to stabilise the retina. In severe cases, Vitrectomy is done whereby the liquid at the back of the eye is removed.

Obesity: Is surgery the answer? 
Bariatric and Metabolic surgery can be recommended as an early intervention in the management of several obese subjects with Type 2 diabetes if intensive lifestyle interventions fail to achieve and maintain significant weight loss, says bariatric surgeon, Dr Abhay Agrawal. "Recent publications have confirmed that substantial and durable weight loss is achieved by current surgical procedures (Stapling of Stomach and Gastric Bypass and DJB) in subjects with Type 2 diabetes," he states.

The current state of diabetes mellitus in India

Diabetes is fast gaining the status of a potential epidemic in India with more than 62 million diabetic individuals currently diagnosed with the disease., In 2000, India (31.7 million) topped the world with the highest number of people with diabetes mellitus followed by China (20.8 million) with the United States (17.7 million) in second and third place respectively. According to Wild et al. the prevalence of diabetes is predicted to double globally from 171 million in 2000 to 366 million in 2030 with a maximum increase in India. It is predicted that by 2030 diabetes mellitus may afflict up to 79.4 million individuals in India, while China (42.3 million) and the United States (30.3 million) will also see significant increases in those affected by the disease., India currently faces an uncertain future in relation to the potential burden that diabetes may impose upon the country. Many influences affect the prevalence of disease throughout a country, and identification of those factors is necessary to facilitate change when facing health challenges. So what are the factors currently affecting diabetes in India that are making this problem so extreme?
From :
The aetiology of diabetes in India is multifactorial and includes genetic factors coupled with environmental influences such as obesity associated with rising living standards, steady urban migration, and lifestyle changes. Yet despite the incidence of diabetes within India, there are no nationwide and few multi-centric studies conducted on the prevalence of diabetes and its complications. The studies that have been undertaken are also prone to potential error as the heterogeneity of the Indian population with respect to culture, ethnicity, socio- economic conditions, mean that the extrapolation of regional results may give inaccurate estimates for the whole country.
There are, however, patterns of diabetes incidence that are related to the geographical distribution of diabetes in India. Rough estimates show that the prevalence of diabetes in rural populations is one-quarter that of urban population for India and other Indian sub-continent countries such as Bangladesh, Nepal, Bhutan, and Sri Lanka., Preliminary results from a large community study conducted by the Indian Council of Medical research (ICMR) revealed that a lower proportion of the population is affected in states of Northern India (Chandigarh 0.12 million, Jharkhand 0.96 million) as compared to Maharashtra (9.2 million) and Tamil Nadu (4.8 million). The National Urban Survey conducted across the metropolitan cities of India reported similar trend: 11.7 per cent in Kolkata (Eastern India), 6.1 per cent in Kashmir Valley (Northern India), 11.6 per cent in New Delhi (Northern India), and 9.3 per cent in West India (Mumbai) compared with (13.5 per cent in Chennai (South India), 16.6 per cent in Hyderabad (south India), and 12.4 per cent Bangalore (South India). A suggested explanation for this difference is that the north Indians are migrant Asian populations and south Indians are the host populations, however this possible cause-and-effect has not been corroborated through further research. Similar ethnographic disparities have been observed in indigenous and non-indigenous populations in countries colonised by the Great Britain: indigenous people from New Zealand and Australia have been shown to suffer from diabetes and cardio-metabolic disorders more than the non-indigenous people., Further studies are required in India to highlight cultural and ethnic trends and provide a more complete understanding of the differences in diabetes aetiology between Indian and other ethnic groups within India.
Although the Indian urban population has access to reliable screening methods and anti-diabetic-medications, such health benefits are not often available to the rural patients. There is a disproportionate allocation of health resources between urban and rural areas, and in addition poverty in rural areas may be multi-faceted. Food insecurity, illiteracy, poor sanitation, and dominance of communicable diseases may all contribute, which suggests that both policy makers and local governments may be undermining and under-prioritising the looming threat of diabetes. Such inadequacies contribute to an infrastructure that may result in poor diabetes screening and preventive services, non-adherence to diabetic management guidelines, lack of available counselling, and long distance travel to health services. Aged care facilities in rural areas report disparity in the diabetes management compared with their urban counterparts, with these populations more likely to suffer from diabetic complications compared to their urban counterparts. More needs to be done to address the rural-urban inequality in diabetes intervention.
Obesity is one of the major risk factors for diabetes, yet there has been little research focusing on this risk factor across India. Despite having lower overweight and obesity rates, India has a higher prevalence of diabetes compared to western countries suggesting that diabetes may occur at a much lower body mass index (BMI) in Indians compared with Europeans., Therefore, relatively lean Indian adults with a lower BMI may be at equal risk as those who are obese. Furthermore, Indians are genetically predisposed to the development of coronary artery disease due to dyslipidaemia and low levels of high density lipoproteins;these determinants make Indians more prone to development of the complications of diabetes at an early age (20-40 years) compared with Caucasians (>50 years) and indicate that diabetes must be carefully screened and monitored regardless of patient age within India.
An upsurge in number of early-onset diabetes cases is also responsible for the development of various diabetic complications due to longer disease duration, however data on the prevalence on diabetic complications across the whole of India is scarce., A recent international study reported that diabetes control in individuals worsened with longer duration of the disease (9.9±5.5 years), with neuropathy the most common complication (24.6 per cent) followed by cardiovascular complications (23.6 per cent), renal issues (21.1 per cent), retinopathy (16.6 per cent) and foot ulcers (5.5 per cent). These results were closely in line with other results from the South Indian population,- however further data from different sections of India is required to be able to assess whether patterns of complications rates vary across the country. Poor glycaemic control, a factor that has been observed in the Indian diabetic population, is responsible for micro- and macrovascular changes that present with diabetes, and can predispose diabetic patients to other complications such as diabetic myonecrosis and muscle infarction. Developing countries like sub-Saharan African countries have noted rise in Plasmodium falciparum cases in patients with diabetes mellitus, and the convergence of two such diseases provides for complications that not only limit the available treatment options but also increase the morbidity, mortality and financial burden on a resource limited country like India.
There are a number of challenges that plague diabetes care in India. While HbA1c is the gold standard test around the world for insulin initiation and intensification, it is not easily available to a large section of Indian population. Furthermore, there is a lack of “clinical inertia” for the commencement of insulin therapy in both the clinical and patient communities. The most common apprehensions are related to the complexities of the insulin regimen and concerns about weight gain, hypoglycaemic events, and fear of insulin prick. An inadequacy in Indian guidelines is also responsible for wide variation in treatment preferences across the country; the creation of simple and practical insulin guidelines that can be incorporated into routine clinical practice by primary health care physicians are desperately required to facilitate treatment and the initiation of insulin therapy throughout the country.
To reduce the disease burden that diabetes creates in India, appropriate government interventions and combined efforts from all the stakeholders of the society are required. Clinicians may be targeted to facilitate the implementation of screening and early detection programmes, diabetes prevention, self-management counselling, and therapeutic management of diabetes in accordance with the appropriate local guidelines form the backbone of controlling the predicted diabetes epidemic. Early screening and detection of pre-diabetes (especially in pregnant women, children and adults with BMI ≥25) may yield positive health outcomes in society. Continuing education programmes for general practitioners may provide the “clinical inertia” required to initiate programme adherence, and may be a major step in achieving target glycaemic levels and the prevention of disease complications. Aggressive clinical measures in terms of early insulin initiation combined with optimal doses of oral hypoglycaemic agents and appropriate lifestyle modification could also have long-term positive effects in disease management.
Government policies may help in creating guidelines on diabetes management, funding community programmes for public awareness about the diabetes risk reduction, availability of medicines and diagnostic services to all sections of community. Efforts by various governments and agencies around the world to intervene in diabetes management have resulted in positive health outcomes for their communities. In the United States there are number of public and private funded programmes to prevent and manage diabetes that have been successful., Similarly, the Australian government runs programmes such as the “National Health Priority Areas initiative” that is dedicated to provide focussed and continuum of care and attention on chronic disease like diabetes., The United Kingdom government places special emphasis on diabetes care in patients, with the National Health Service conducting various patient education programs and trials to improve quality of life of patients such as the “Dose Adjustment for Normal Eating” (DAFNE) study and “Diabetes Education & Self-Management for Ongoing & Newly Diagnosed” (DESMOND) study to provide patient education. Similarly, a government initiative in the United Arab Emirates has set up an expert panel to form guidelines for diabetes management and public awareness programmes. This has resulted in positive health effects which may arrest rising trend in diabetes cases in that country. In India, similar efforts and services are required at ‘grass roots’ level to contain the new-age diabetes pandemic.


Diabetes mellitus is reaching potentially epidemic proportions in India. The level of morbidity and mortality due to diabetes and its potential complications are enormous, and pose significant healthcare burdens on both families and society. Worryingly, diabetes is now being shown to be associated with a spectrum of complications and to be occurring at a relatively younger age within the country. In India, the steady migration of people from rural to urban areas, the economic boom, and corresponding change in life-style are all affecting the level of diabetes. Yet despite the increase in diabetes there remains a paucity of studies investigating the precise status of the disease because of the geographical, socio-economic, and ethnic nature of such a large and diverse country. Given the disease is now highly visible across all sections of society within India, there is now the demand for urgent research and intervention - at regional and national levels - to try to mitigate the potentially catastrophic increase in diabetes that is predicted for the upcoming years.

Epidemiology of type 2 diabetes: Indian scenario

India leads the world with largest number of diabetic subjects earning the dubious distinction of being termed the “diabetes capital of the world”. According to the Diabetes Atlas 2006 published by the International Diabetes Federation, the number of people with diabetes in India currently around 40.9 million is expected to rise to 69.9 million by 2025 unless urgent preventive steps are taken. The so called “Asian Indian Phenotype” refers to certain unique clinical and biochemical abnormalities in Indians which include increased insulin resistance, greater abdominal adiposity i.e., higher waist circumference despite lower body mass index, lower adiponectin and higher high sensitive C-reactive protein levels. This phenotype makes Asian Indians more prone to diabetes and premature coronary artery disease. At least a part of this is due to genetic factors. However, the primary driver of the epidemic of diabetes is the rapid epidemiological transition associated with changes in dietary patterns and decreased physical activity as evident from the higher prevalence of diabetes in the urban population. Even though the prevalence of microvascular complications of diabetes like retinopathy and nephropathy are comparatively lower in Indians, the prevalence of premature coronary artery disease is much higher in Indians compared to other ethnic groups. The most disturbing trend is the shift in age of onset of diabetes to a younger age in the recent years. This could have long lasting adverse effects on nation’s health and economy. Early identification of at-risk individuals using simple screening tools like the Indian Diabetes Risk Score (IDRS) and appropriate lifestyle intervention would greatly help in preventing or postponing the onset of diabetes and thus reducing the burden on the community and the nation as a whole

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