Can Vitamin D Replacement Reduce Insulin Resistance In South Asians With Vitamin D Deficiency?

Cardio metabolic risk in South Asians

Incident Cardiovascular Disease (CVD) within the South Asian Diaspora has failed to decline in parallel with other migrant groups. Rates of coronary disease in middle-aged South Asians, 50% higher than UK background, are concerning and place a growing socio-economic burden on communities and health-care providers. Concerted efforts to recognise and manage early CVD-risk within this highly susceptible group are essential if persistent health inequalities are to be adequately addressed. Significant variation in CVD implies differential interaction of risk factors across populations or the presence of additional factors accounting for increased risk. Metabolic conditions prevalent in South Asians and characterised by insulin resistance, glucose disorders and dyslipidaemia may be key to addressing observed CVD differences. Type 2 Diabetes Mellitus (T2DM) develops early in South Asians and once established carries a high risk of vascular mortality. Prediabetes is more common in South Asians and associate independently with vascular and diabetes-risk. Ethnic pre-disposition to central obesity and its metabolic consequences is clearly important in determining CVD risk, but even when combined with other factors (e.g. social-economic deprivation, smoking, blood pressure) fails to entirely account for observed variation in vascular events between groups. Assumptions that cultural incompatibility and medication compliance influence CVD outcomes are largely unsubstantiated, implying unidentified factors contribute to increased risk in South Asians.

Vitamin D Deficiency (VDD)

There has been a resurgence of interest in the recognition and treatment of VDD beyond established roles in metabolic bone disease. Epidemiological studies implicate vitamin D and calcium homeostasis in a plethora of non-skeletal immune-based chronic diseases. Proposed mechanisms accounting for these pleiotropic actions focus upon well-characterised in-vitro immuno-modulatory effects, intracellular calcium signalling and the recent finding that the Vitamin D receptor is ubiquitous. The emerging science connecting biochemical deficiency, molecular or cytokine responses and disease pathogenesis is well-reviewed. VDD appears to predispose to vascular, rheumatic and neuropathic inflammation, hypertension, metabolic syndrome and atherosclerosis.

Data from large observational cohorts and trials designed for bone-related outcomes consistently demonstrate inverse relationships between (1) serum 25-hydroxy-cholecalciferol (25(OH)VitD) and prevalent T2DM/CVD or conversely, (2) supplementation and incident all cause mortality. Baseline serum 25(OH)VitD predicts future glycaemic status, whilst VDD associates with markers of insulin resistance, coronary calcification, aortic stiffness, left ventricular mass, endothelial dysfunction, and hypertension. Diabetes-related micro and macro-vascular complications may be exacerbated by VDD.