BAFFLING UNKNOWNS IN OUR UNDERSTANDING OF TYPE 2 DIABETES

Type 2 diabetes is a global public health crisis that has grown in parallel with the worldwide rise in obesity, particularly in developing countries like India. Rapid urbanization coupled with reduced physical activity, high carbohydrate diet, poor nutrition in utero combined with overnutrition in later life and the characteristic special Indian phenotype have major role in diabetes epidemic. However, our understanding of diabetes does not stop here as there are several lesser-known factors contributing to diabetes waiting to be precisely unraveled through further research.

Air pollution

Much has been written that pollution sets up chronic inflammatory process resulting in long term health effects that include diabetes and many other lifestyle disorders. It is however, not clear if different sources of pollution exert the same magnitude of damaging health effect. There is also no concerted health policy against these individual sources of pollution. Aged and poor persons from low-income countries are particularly vulnerable to various sources of pollution. Indoor pollution is lesser known than the outdoor pollution. The former for example results from fuel burning, smoking, deteriorating building material, newly installed flooring and upholstery, personal care and household cleaning products, air conditioning devices etc. Sources of outdoor pollution include automobiles, smog, persistent organic pollutants (POPs) etc. Higher serum concentrations of certain POPs have been linked with higher prevalence of diabetes.

Endocrine disruptors

Walking into a modern mall can take you to numerous fragrance rich personal care products (like perfumes, soaps, after shaves and nail polish), packaged foods in plastic containers, edibles and drinks in metal cans, plastic microwave wares and plastic toys etc. Numerous chemicals involved in the manufacture, transport and storage of these products act as endocrine disrupting chemicals (EDCs) and disturb our endocrine or hormonal balance. EDCs can leach out into foods and drinks from their containers and can also add to indoor pollution. Long term use of such products has been attributed to diabetes and other disorders like cardiovascular, respiratory, reproductive, and thyroid disorders, and to obesity. Not much research has been done in this direction and no organized programs exit in India to combat this menace.

Climate extremes

Climate extreme, both hot and cold negatively affects diabetes. Humidity and moisture are also offending factors. Impaired thermoregulation due to autonomic disturbance specially in older diabetics make them more vulnerable to electrolyte imbalances and kidney dysfunction in the face of heat waves while exposure to cold temperatures is associated with poor glycemic control and increased rates of acute myocardial infarction. In addition to extremes of temperature, air pollution as a consequence of the climate crisis has also been implicated in the increased prevalence and incidence of diabetes, particularly gestational diabetes (GDM).

Gut microbiota

Gut microbiome composition may influence the development of type 2 diabetes. An increased gut microbial diversity, along with specifically more butyrate-producing bacteria and decrease in 2 pathogens may benefit insulin resistance and risk of type 2 diabetes. Gut microbiota are known to influence glucose homeostasis and insulin resistance in major metabolic organs such as liver, muscle and fat. Probiotic supplementation as beneficial in type 2 diabetes mellitus is reported.

Role of stress

Chronic stress is a contributory factor for diabetes while episodic stressful events can make it more difficult to control your diabetes as the hormones from stress can cause blood sugar to rise

Race and ethnicity

Reasons for higher prevalence of diabetes (e. g. among Asian Indians, Pacific Islanders, American Indians, African-Americans and Asian-Americans) versus lower prevalence (e. g. among Alaska Natives and others) are not entirely clear. Increased belly fat and to some extent, potassium deficiency have been cited as some of the reasons.

Miscellaneous factors

Hypothetical pathogen linked to NCDs have been described, e. g. obesity (Ad-36 human adenovirus), dyslipidemia (Covid 19, HIV), metabolic syndrome (HCV, gut microbiota). Non-infectious approach is also being pursued to achieve vaccine preparation. For instance, our immune system can be made to see fat cells of an obese person as a threat and attack them with our leucocytes. All this needs more investigation and the role of Vitamin D deficiency and uranium toxicity in diabetes likewise requires more clarity.

Concluding comments

Type 2 diabetes is complex and multifactorial. Obesity and an inactive lifestyle are the two most important factors responsible for 90% of cases but complete understanding of its etiogenesis requires a deep peep for other factors as well. Moreover, prevention and/or amelioration of obesity and inactive lifestyle does not offer one hundred percent guarantees against diabetes. Equally perplexing is the situation when full blown vascular complications develop despite good control of diabetes or there are no such complications even after long drawn poorly controlled diabetes. So far, the battle has been won only partially and much still needs to be done. Cure of diabetes is still elusive and we are nowhere near to the brink of its eradication. It is however sincerely hoped someday the intelligent and diligent minds will reach a breakthrough