Migrant South Asian populations in Europe, North America the Westernised countries have a greater cardiovascular disease (CVD) risk than their respective indigenous populations. Both overall and premature CVD morbidity and mortality is significantly higher in migrant South Asians than in white populations in the UK and globally. Despite this, the role of ultrasound as a screening tool for CVD risk assessment in South Asians has not been studied extensively. Data also suggest that increased susceptibility to the adverse effects of insulin resistance and type 2 diabetes mellitus (T2DM) may contribute to the increased CVD risk.South Asians living in the United Kingdom also have a 3-5 fold increased prevalence of T2DM, developing the disease around a decade earlier and at a lower body mass index (BMI) compared to white Europeans. Furthermore, non-diabetic South Asians have higher fasting glycaemia and are more insulin resistant than Europeans. Liver fat is also associated with insulin resistance and T2DM risk and is considered to play a causal role in diabetes. Limited data suggest that South Asians have higher liver fat content than age- and BMI-matched Europeans, but it is not currently clear whether this contributes to the observed ethnic difference in insulin resistance.The first aim was to determine the extent to which increased insulin resistance and fasting glycaemia in South Asian, compared to white European men, living in the UK, was due to lower cardiorespiratory fitness (maximal oxygen uptake [VO2max]) and physical activity. The second aim was to determine whether South Asians have increased liver fat compared to Europeans and the extent to which any such differences can explain the increased insulin resistance observed between these groups. The final aim was to determine whether South Asians had a difference in carotid intima-media thickness (cIMT) or carotid plaque presence compared to Europeans; and if so, whether any measured risk factors (if any) could account for any such observed differences in cIMT and/or carotid plaque disease.100 SA and 100 age and BMI-matched European men without diagnosed diabetes, aged 40-70 years, had fasting blood taken for glucose concentration, insulin, plus other risk factors, and underwent 2-dimensional carotid ultrasound for measurement of intima-media thickness and carotid plaque analysis, assessment of physical activity (using accelerometry), VO2max, body size and composition, and demographic and other lifestyle factors. For addressing the first aim of this thesis, 13 South Asian and 1 European man had HbA1c levels >6.5% indicating potential undiagnosed diabetes and were excluded from the analyses relating. Linear regression models were used to determine the extent to which body size and composition, fitness and physical activity variables explained differences in insulin resistance (assessed by Homeostasis Assessment Model of Insulin Resistance, HOMAIR) and fasting glucose between SA and Europeans. For the second aim, 28 South Asian and 24 European participants were chosen at random (but matched for age) within 4 months of their original main study visit to undergo magnetic resonance spectroscopy for quantification of liver fat.HOMAIR and fasting glucose were 67% (p<0.001) and 3% (p<0.018) higher, respectively, in South Asians than Europeans. Lower VO2max, lower physical activity and greater total adiposity in SA individually explained 68% (95% confidence interval [CI], 45-91%), 29% (95% CI, 11-46%) and 52% (95% CI, 30-80%), respectively, and together explained 83% (95% CI, 50-119%) (all p<0.001), of the ethnic difference in HOMAIR. Lower VO2max and greater total adiposity respectively explained 61% (95% CI, 9-111%) and 39% (95% CI; 9-76%) (combined effect 63% (95% CI 8-115%); all p<0.05)) of the ethnic difference in fasting glucose. Unadjusted mean liver fat content did not differ significantly between South Asians compared to Europeans (5.28 (standard deviation [SD], 2.11)% vs 5.41 (SD,2.35)%, p=0.913), but following adjustment for alcohol consumption was significantly lower in South Asians than Europeans (5.30 (SD, 2.10)% vs 9.03 (SD, 2.22)% p=0.017). Adjustment for alcohol-adjusted liver fat did not attenuate the difference in HOMAIR between ethnic groups. There were no significant differences in unadjusted or age-adjusted in mean cIMT between South Asians and Europeans. There was an increased odds ratio for the presence of plaque disease in South Asians compared to Europeans, however this was not significant (OR 1.57, 95% CI 0.89-2.77, p=0.13).Lower cardiorespiratory fitness is a key factor associated with the excess insulin resistance and fasting glycaemia in middle-aged South Asian compared to European men living in the UK. Also, whilst clear associations between liver fat and insulin resistance were observed in South Asians and Europeans, these results challenge the notion that excess liver fat per se explains the greater insulin resistance observed in South Asians. Finally, cIMT is similar between South Asian and European men and there is also currently no clear evidence for more carotid plaques in South Asian compared to European men living in the UK. This important negative finding highlights the need for further studies on carotid plaque or research in alternative screening methods for CVD which are more sensitive in identifying subclinical CVD.
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The cardiometabolic phenotype of UK South Asian Men
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