Pathophysiological Mechanisms Underlying Excess Risk for Diabetes and Cardiovascular Disease in South Asians: The Perfect Storm

Background: South Asians are at a significantly increased risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), are diagnosed at relatively younger ages, and exhibit more severe disease phenotypes as compared with other ethnic groups. The pathophysiological mechanisms underlying T2D and CVD risk in South Asians are multifactorial and intricately related. Methods: A narrative review of the pathophysiology of excess risk of T2D and CVD in South Asians. Results: T2D and CVD have shared risk factors that encompass biological factors (early life influences, impaired glucose metabolism, and adverse body composition) as well as behavioral and environmental risk factors (diet, sedentary behavior, tobacco use, and social determinants of health). Genetics and epigenetics also play a role in explaining the increased risk of T2D and CVD among South Asians. Additionally, South Asians harbor several lipid abnormalities including high concentration of small-dense low-density lipoprotein (LDL) particles, elevated triglycerides, low high-density lipoprotein (HDL)-cholesterol levels, dysfunctional HDL particles, and elevated lipoprotein(a) that predispose them to CVD. Conclusion: In this comprehensive review, we have discussed risk factors that provide insights into the pathophysiology of excess risk of T2D and CVD in South Asians.