Describe Insulin resistance in Non-conventional Factors ?

Insulin resistance refers to a generalized metabolic disorder in which various tissues are resistant to normal levels of plasma insulin. Metabolic abnormalities include defective glucose uptake by skeletal muscle, increased release of free fatty acids by adipose tissue, overproduction of glucose by the liver, and hy per secretion of insulin by pancreatic B-cells. On the basis of studies comparing South Asian immigrants in Britain and the native European population, McKeigue and co-workers have suggested that a pattern of insulin resistance and associated metabolic abnormalities might be the reason for the high rates of CAD and type two diabetes among South Asian people. In a subsequent study by the same group, it was found that major Q waves with or without a history of CAD were more common in South Asian patients with glucose intolerance and hy perinsulinemia than in those with normal glucose and insulin levels (6 per cent v. 1.9 per cent). The population attributable risk fraction (this is the proportion by which prevalence of disease would be expected to fall in the population if the risk factor was removed, assuming the association to be causal) in South Asian men aged between 40 and 54 years was 73 per cent.

Abdominal obesity is an important component of the insulin resistance syndrome. Again, it was found that the average waist-hip ratio (WHR) was higher in South Asian men than in the Europeans studied. A WHR'>0.92 had an adjusted odds ratio of 3.1 for AM1 in the case-control study by Pais et al. Although Mohan and others did not find any difference in the WHR between the subjects with and without CAD in their community-based study, there was a significant association of obesity as measured by BMI and another estimate of abdominal obesity, the waist-height ratio. The prevalence of an 'apple' shaped body habitus (high WHR) was as high as 71 per cent in an urban population sample from Delhi. Urban Indians in this study were just as centrally obese as the South Asians in the Southall study. Although the average WHR of the rural population sampled was less than that of the urban population, they were more centrally obese than the Europeans in the Southall study.

Several studies have documented the clustering of other metabolic abnormalities associated with the insulin resistance syndrome. In immigrant South Asians in the UK, the average fasting and post-load serum insulin, blood pressure and plasma TG levels were higher than the levels in the native European population. The HDL cholesterol was also significantly lower. High serum TG levels and low HDL levels have also been seen in studies of native Indians with CAD. Although there is substantial evidence for an association between the metabolic syndrome and CAD in Indians, the mechanism by which atherosclerosis is caused by these syndromes as been extensively debated. The most plausible explanation is that the risk of CAD is increased by the associated alteration in the lipid profile leading to atherogenic dyslipidaemia, Hypertension, a thrombotic tendency evidenced by elevated levels of plasminogen activator inhibitor-1 (PAI-1) and by the presence of IGT or diabetes.

The question whether this South Asian predilection for insulin resistance is a genetic or acquired trait requires elucidation. In their comparison of Punjabi immigrants in London and their siblings in rural Punjab, Bhatnagar et a1 had showed that the former had a greater BMI, higher systolic blood pressure, raised serum total cholesterol, apolipoprotein (Apo) B, FBG, and lower HDL cholesterol than the latter. However, the insulin sensitivity of the native Punjabi population was also impaired, suggesting a genetically determined propensity for insulin resistance. In another study, Shaukatetal analyzed the risk factor profiles of young siblings of UK-based Asians. When compared to their European

Counter parts the young Asians (mean age 22 years) were more sedentary, centrally obese, insulin resistant and had higher lipoprotein (a) [Lp(a)] levels. They also showed evidence of a prothrombotic tendency with elevated levels of PAI-1 and reduced tissue plasminogen activator (tPA) activity. The divergence from the European population diminished but did not disappear after adjustment for level of physical activity. Significantly, both the studies showed higher concentrations of Lp(a) in Asians irrespective of their place of residence. These facts point to an interplay between genetic predisposition and lifestyle changes in determining the increased risk of CAD.