Samay Boorgu, Florence High School, Florence, Alabama, USA
SUMMARY
According to a 2020 report of the International Diabetes Federation, 88 million people from South Asian countries are living with diabetes, with 77 million people from India alone. Globally, the South Asian diaspora reports a high prevalence of hyperglycemia at a much younger age than other ethnic or immigrant populations. The increasing burden of diabetes is prevalent in India compared to European populations, even though India witnesses higher rates of malnutrition compared to other regions. To better understand how diabetes in Indians could develop from a young age, characteristics are interpreted using a ‘capacity-load’ model of glucose homeostasis. The glycemic control depends on the body’s metabolic capacity. The body has a metabolic capacity to produce insulin and allow muscle glucose clearance. Furthermore, elevated diabetic risk could result from a high metabolic load, which can be attributed to a certain lifestyle that is consistent among the Indian population. This article explores the etiological factors that place South Asian populations at a high risk of developing Type 2 diabetes. Multiple sociodemographic, biological, lifestyle, and metabolic factors contribute to this phenomenon. Foremost among them are reduced beta-cell function and impaired insulin action owing to decreased lean muscle mass and ectopic fat deposition in the liver and muscle.
The susceptibility to diabetes in South Asian populations is rising. With rapid urbanization and lifestyle changes, India has become the “diabetes capital” of the world (Wells, Pomeroy, Walimbe, Popkin, & Yajnik, 2016). The likelihood of South Asians developing Type 2 diabetes can be up to six times higher than the general population (Editor, 2019). Neighboring countries such as Pakistan, Bangladesh, and Sri Lanka are also seeing enormous numbers of cases of diabetes in patients in their twenties through seventies.
Figure 1. A comparison between the prevalence of diabetes in India in 1966-1975 and in 2014. Note: According to the source, “these figures do not differentiate between different types of diabetes mellitus; however, according to the International Diabetes Foundation Atlas ∼95% of adult individuals with the disease have type 2 diabetes mellitus” (Unnikrishnan, Ranjit, & Mohan, 2016).
South Asian populations have a specific phenotype characterized by high levels of intra-abdominal fat and insulin resistance, which predisposes them to Type 2 diabetes (Unnikrishnan, Ranjit, & Mohan, 2016). Susceptibility to diabetes can be understood using a metabolic model of diabetes, characterized by “metabolic capacity” that maintains glycemic control and “metabolic load” attributed to factors such as obesity, diet, and a sedentary lifestyle. An increase in metabolic load can overwhelm the metabolic capacity, putting South Asian populations at higher risk even at a lower Body Mass Index (BMI).
Insulin resistance, along with impaired insulin secretion, is central to the pathophysiology of Type 2 diabetes. Research shows that insulin resistance in muscle tissue and the inability of the beta-cells in the pancreas to secrete sufficient insulin are equal contributors to diabetes. Adverse lifestyle conditions can affect ectopic fat deposition in the liver and muscles leading to insulin resistance. In South Asians, isolated impaired fasting glucose (iIFG) level is highly prevalent, which results from hepatic insulin resistance with an early phase, stationary impairment in beta-cell function (Narayan & Kanaya, 2020).
Figure 2. Proposed pathophysiological pathways for type 2 diabetes (Narayan & Kanaya, 2020).
Another contributor to the high incidence of diabetes in South Asians is abdominal visceral and hepatic fat that causes insulin resistance and other metabolic consequences. This is important because greater body adiposity and higher waist circumference are prevalent among South Asians. On the one hand, visceral fat (excess weight that develops over time around the center of the body) stores have been found to secrete a protein called retinol-binding protein 4 (RBP4), which has been proven to increase resistance to insulin (Klöting et al., 2007). South Asians also have greater hepatic fat content, attributable to the higher saturated fat content of traditional South Asian diets. A study conducted on South Asians living in America indicated that hepatic fat was closely linked to progression from prediabetes to diabetes. Another study demonstrated that there was a high incidence of prediabetes and diabetes (29.5 and 22.2 per 1000 person respectively) among residents of Chennai, India (Narayan & Kanaya, 2020). Additionally, at the mitochondrial level, South Asians have a higher oxidative capacity which provokes insulin resistance (Narayan & Kanaya, 2020).
Researchers have also hypothesized that fetal and infant under-nutrition reduces the growth of the pancreas and muscle tissue that impacts the body’s glucose tolerance in adulthood. On top of that, maternal malnutrition can be a direct contributor to beta-cell dysfunction in offspring, and infants born undernourished have been shown to have higher levels of adiposity. Some babies may also gain adipose weight after two years of age, causing impaired glucose tolerance in adolescence. Maternal vitamin B12 deficiency can also lead to adiposity and insulin resistance in offspring (Narayan & Kanaya, 2020).
Although South Asian countries are an epicenter, a diabetes epidemic is a looming threat to developing countries worldwide. As described in the World Health Organization Global Report on Diabetes, the prevalence of diabetes in the South East Asia region doubled from 4.1% to 8.6%, and absolute numbers increased from 17 million to 96 million between 1980 and 2014. However, a more dramatic change was demonstrated in the Western Pacific region, where the number of affected individuals increased from 29 million to 131 million in the same time period (World Health Organization, 2016). Although all WHO regions demonstrated an increase in diabetes in this time period, the greatest increases have been seen in developing or recently developed countries such as China, Cambodia, and Malaysia.
To conclude, many factors that cause insulin resistance predispose South Asians to a high risk of developing type 2 diabetes. Obesity, lifestyle, genetic factors, and maternal undernourishment can affect the functioning of the pancreatic cells, and in turn, promote insulin resistance. The need to further unravel the biological reasons that put South Asians at a higher risk of getting diabetes, such as mitochondrial metabolism, poor insulin secretion, and adiposity, is pressing.
References
Editor. (2019, January 15). Diabetes in South Asians. Retrieved from https://www.diabetes.co.uk: https://www.diabetes.co.uk/south-asian/
Klöting, N., Graham, T. E., Berndt, J., Kralisch, S., Kovacs, P., Wason, C. J., Fasshauer, M., Schön, M. R., Stumvoll, M., Blüher, M., & Kahn, B. B. (2007). Serum retinol-binding protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass. Cell metabolism, 6(1), 79–87. https://doi.org/10.1016/j.cmet.2007.06.002
Narayan, K. M., & Kanaya, A. M. (2020). Why are South Asians prone to type 2 diabetes? A hypothesis based on underexplored pathways. Diabetologia, 63(6), 1103–1109. https://doi.org/10.1007/s00125-020-05132-5
Unnikrishnan, R., Anjana, R. M., & Mohan, V. (2016, April 15). Diabetes mellitus and its complications in India. Nature News. Retrieved October 14, 2021, from https://www.nature.com/articles/nrendo.2016.53.
Wells, J. C., Pomeroy, E., Walimbe, S. R., Popkin, B. M., & Yajnik, C. S. (2016). The elevated susceptibility to diabetes in India: An evolutionary perspective. Frontiers in Public Health, 4. https://doi.org/10.3389/fpubh.2016.00145
World Health Organization. (2016, April 21). Global report on diabetes. World Health Organization. Retrieved November 12, 2021, from https://www.who.int/publications-detail-redirect/9789241565257.