In a previous study it was shown that adiponectin concentrations were significantly lower in the South-Asians when compared to Caucasians . In recent study, subjects with type 2 diabetes and impaired glucose tolerance test showed significantly decreased serum adiponectin concentrations. Although serum adiponectin levels were negatively correlated with BMI, diabetic subjects had lower values of serum adiponectin than did non-diabetic subjects, independent of the BMI [8, 22, 23]. Weyer et al, showed that serum adiponectin concentrations were more closely related to fasting insulinemia and to the rate of insulin-stimulated glucose disposal, a direct measure of insulin sensitivity, than to percent body fat and the 2-hr glucose concentration suggesting that hyperinsulinaemia and/or insulin resistance might be a major determinants of the hypoadiponectinemia in obesity and type 2 diabetes. One of possible mechanisms for this that has been suggested is, overproduction of TNF-αby adipose tissue [24–26]. Also in the recent study showed AdipoR1/R2 appears to be inversely regulated by insulin in physiological and pathophysiological states such as fasting/refeeding, insulin deficiency, and hyper-insulinemia models via the insulin/phosphoinositide 3-kinase/Foxo1 pathway and is correlated with adiponectin sensitivity. Adiponectin interferes with TNF-α signalling in endothelial cells . Decreased serum adiponectin may play a causative role in the development of insulin resistance.
In the present study in BMI matched South-Asian subjects, we found that adiponectin concentration decrease across the glycaemic spectrum, with NGT subjects having the highest and subjects with type 2 diabetes the lowest concentrations. There is a significant decrease in the adiponectin concentrations even at the stage of IGT. In a different study it was found that serum adiponectin concentrations are lower in nondiabetic Pima Indians than in Caucasians and in subjects with IGT and diabetes compared with those with NGT, this indicates that factors other than adiposity must play a role in determining adiponectinemia . In our study serum adiponectin levels were negatively correlated with 2-hr plasma insulin concentration, though there was no relation with percentage body fat. Circulating adiponectin levels have been shown to decrease in parallel with progression of insulin resistance during development of type 2 diabetes in rhesus monkeys genetically predisposed to develop insulin resistance . In this study, there was a negative correlation of adiponectin levels with body weight and fasting insulin levels and a positive correlation with insulin-stimulated glucose up-take (a marker of insulin sensitivity). In these monkeys, the decline in adiponectin levels preceded overt hyperglycaemia. Development of hyperinsulinaemia is one possible mechanism for the suppression of adiponectin levels seen in this study. However, hyperinsulinaemia per se seems unlikely as a mediator of low adiponectin levels, since adiponectin levels remain low in the later stage of type 2 diabetes in association with decreased insulin levels. Adipocyte insulin action or signal transduction rather than absolute levels of insulin may regulate adiponectin concentration. In support of this contention, Bogan and Lodish  have shown that secretion of adiponectin by 3T3-L1 adipocytes requires phospatidylinositol 3-kinase (PI-3K), a major intermediate of insulin signalling activity. Insulin stimulated insulin receptor substrate 1 (IRS-1) associated PI-3K activity has been shown to be decreased in adipocytes of type 2 diabetic subjects . Thus it is possible that the decreased adipocyte PI-3K activity in type 2 diabetic patients may contribute to the decreased adiponectin levels. Other investigators have presented data on the potential inverse relationship between adiponectin and insulin action. Euglycemic hyperinsulinaemia clamp studies both in human and rats  have shown that insulin infusion leads to decreased circulating adiponectin levels, consistent with the interpretation that insulin exerts an acute effect on adipocytes to decrease production and/or secretion of this adipocytokines. Also some studies showed a relation between the adiponectin and Coronary heart disease risk factors, these results collectively indicate that plasma HDL cholesterol levels and visceral fat masses are independently associated with plasma adiponectin concentrations. In another study a reduction in serum adiponectin level is associated with the prevalence and magnitude of systemic atherosclerosis including IHD and ASO which confirmed our finding in the South Asian subjects.
In our study there was a significant increase in the resistin levels between NGT and IGT subjects though there was no statistically significant difference between NGT and DM subjects. The negative correlation between serum resistin and adiponectin levels may also suggest that, resistin could be a marker for TNF-α which has been shown to be associated with chronic inflammation and insulin resistance. Previous studies have provided evidence for the association of leptin with key variables of the metabolic syndrome and with insulin sensitivity, independently of obesity . Several recent studies have documented a relationship between leptin and insulin levels or insulin sensitivity [36–38]. However, given the close correlation of leptin with indices of adipose tissue mass, no studies were able to investigate if leptin relates to those variables through obesity and/or hyperinsulinaemia, or independent of them. In our study we could not elucidate any relationship between leptin levels according to glucose tolerance.
Taken together, our findings indicate that the observed changes in adiponectin are likely to be related to metabolic changes associated with progression to diabetes. In this study in a British South-Asian population with a high incidence of type 2 diabetes, cardiovascular disease, central obesity and metabolic syndrome, we have demonstrated that serum adiponectin levels are inversely correlated across the glycaemic spectrum with patients of type 2 diabetes having the lowest levels. Even in patients with IGT the serum adiponectin levels were lower than BMI matched NGT subjects. Adiponectin concentration was also negatively correlated with 2-hr plasma insulin levels; these are consistent with the interpretation that insulin exerts an acute effect on adipocytes to decrease production and/or secretion of this adipocytokines.