Risk Of Insulin Resistance Syndrome Research Articles

A historical exploration of Indian diets and a possible link to insulin resistance syndrome

BackgroundInsulin resistance syndrome, especially with diabetes, is becoming increasingly prevalent in India. The increasing consumption of low-fibre and refined carbohydrates is thought to be related to the increased risk of insulin resistance syndrome. AimThe aim was to study the history of eating behaviours in India; the patterns (macronutrients, frequency, and quantity) of food consumption amongst ancient, medieval and modern Indians; and the evolution of a primarily low-fibre and refined-carbohydrate diet. MethodsThe ancient dietary laws of India, historical documents, and ancient and medieval literature and poetry, spanning more than 2000 years, were studied. These data were compared with modern diets among people of different geographical regions, religions and social strata using the National Nutritional Database of the US Department of Agriculture (USDA) for analysis. ConclusionsThe data presented shows a gradual shift over the centuries from the Pastoral Age diet of large quantities of high-fibre carbohydrates, small amounts of digestible carbohydrates, moderate fats, moderate proteins, to an increasing and frequent intake of high-fibre carbohydrates associated with significant drop in protein and fat consumption between 1775 and 1947. From 1947 onwards there has been an increase in the frequency of intake and quantities of low-fibre and refined carbohydrates, and fats with protein intake improving only marginally.

Association of adiponectin gene polymorphism with adiponectin levels and risk for insulin resistance syndrome.

Background:Adiponectin is an abundant adipose tissue–derived protein with anti-atherogenic, anti-inflammatory and antidiabetic properties. Plasma adiponectin levels are decreased in obesity, type 2 diabetes, and coronary artery disease and low adiponectin levels also predict insulin resistance (IR).Methods:Case-control study in which 642 male and female subjects were participated from the North Indian population. Lipid, insulin, leptin and adiponectin level were estimated using standard protocols by commercially available test kits. Single nucleotide polymorphisms +45T>G and +276G>T of the AMP1 (adiponectin) gene was genotyped by polymerase chain reaction restriction fragment length polymorphism method.Results:Levels of adiponectin, insulin, homeostasis model assessment-IR index (HOMA-IR index), systolic blood pressure and fat mass showed significant differences between male and female subjects. Serum adiponectin level showed highly significant association with both the +45 and the +276 genotypes. The common haplotype triglyceride (TG) showed a significantly lower adiponectin value than other haplotypes (P = 0.0001). A clear trend of decreasing adiponectin levels per copy of the common haplotype was observed. Nonobese insulin sensitive subjects showed a higher adiponectin value (P = 0.0006) than nonobese insulin resistant subjects. The values of blood pressure, adiponectin, insulin, HOMA-IR, total-cholesterol, and low-density lipoprotein-cholesterol significantly associated with TG haplotype.Conclusions:We observed the very strong association of the adiponectin 45-276 genotypes and haplotypes with adiponectin levels in healthy north Indian population and TG haplotypes also associated with metabolic parameters of the IR syndrome.

Microarray Evidences the Role of Pathologic Adipose Tissue in Insulin Resistance and Their Clinical Implications

Clustering of insulin resistance and dysmetabolism with obesity is attributed to pathologic adipose tissue. The morphologic hallmarks of this pathology are adipocye hypertrophy and heightened inflammation. However, it's underlying molecular mechanisms remains unknown. Study of gene function in metabolically active tissues like adipose tissue, skeletal muscle and liver is a promising strategy. Microarray is a powerful technique of assessment of gene function by measuring transcription of large number of genes in an array. This technique has several potential applications in understanding pathologic adipose tissue. They are: (1) transcriptomic differences between various depots of adipose tissue, adipose tissue from obese versus lean individuals, high insulin resistant versus low insulin resistance, brown versus white adipose tissue, (2) transcriptomic profiles of various stages of adipogenesis, (3) effect of diet, cytokines, adipokines, hormones, environmental toxins and drugs on transcriptomic profiles, (4) influence of adipokines on transcriptomic profiles in skeletal muscle, hepatocyte, adipose tissue etc., and (5) genetics of gene expression. The microarray evidences of molecular basis of obesity and insulin resistance are presented here. Despite the limitations, microarray has potential clinical applications in finding new molecular targets for treatment of insulin resistance and classification of adipose tissue based on future risk of insulin resistance syndrome.

The insulin resistance epidemic in India: fetal origins, later lifestyle, or both?

In India there is a rapidly escalating epidemic of insulin resistance syndrome (diabetes and coronary heart disease). Contribution of genes and environment is under debate. Small size at birth coupled with subsequent obesity increases risk for insulin resistance syndrome in later life. The tendency of Indians to have higher body fat and central adiposity compared with other races may be programmed in utero. The adipose tissue releases not only fatty acids but also a number of proinflammatory cytokines, which increase insulin resistance and cause endothelial dysfunction. Crowding, infections, and environmental pollution in Indian cities may increase cardiovascular risk by stimulating fat cells. Prevention of diabetes and coronary heart disease in India will have to be approached throughout the life cycle.

Acid–base balance may influence risk for insulin resistance syndrome by modulating cortisol output

Frank metabolic acidosis is known to promote renal excretion of hydrogen ion by induction of glutaminase and other enzymes in the renal tubules. This induction, at least in part, reflects an increase in pituitary output of ACTH and a consequent increased production of cortisol and aldosterone; these latter hormones act on the renal tubules to promote generation of ammonia, which expedites renal acid excretion. Recent evidence suggests that the moderate metabolic acidosis associated with a protein-rich diet low in organic potassium salts – quantifiable by net acid output in daily urine – can likewise evoke a modest increase in cortisol production. Since cortisol promotes development of visceral obesity, and has a direct negative impact on insulin function throughout the body, even a modest sustained up-regulation of cortisol production may have the potential to increase risk for insulin resistance syndrome and type 2 diabetes. This thesis appears to be consistent with previous epidemiological reports correlating high potassium consumption, or a high intake of fruits and vegetables, with reduced risk for diabetes and coronary disease. Future prospective epidemiology should assess whether the estimated acid–base balance of habitual diets – calculated from the ratio of dietary protein and potassium – correlates with risk for insulin resistance syndrome and diabetes.

Elevated sympathetic activity may promote insulin resistance syndrome by activating alpha-1 adrenergic receptors on adipocytes

An excess of free intracellular calcium can reduce the efficiency of insulin-mediated glucose transport by blocking the dephosphorylation of GLUT-4. Classical isoforms of protein kinase C (PKC) can interfere with insulin signalling via serine phosphorylation of IRS-1 and the insulin receptor. Parathyroid hormone (PTH), by activating phospholipase C-β in adipocytes, can promote a sustained increase in intracellular free calcium in these cells, while also activating classical PKCs. This may rationalize the fact that insulin resistance is a typical feature of hyperparathyroidism, as well as epidemiological evidence that regular ingestion of dairy products or of ethanol – which down-regulates PTH secretion – reduces risk for insulin resistance syndrome and diabetes. Alpha-1 adrenergic receptors of adipocytes – like PTH receptors – also activate phospholipase C-β, and thus have an effect analogous to PTH on intracellular free calcium and PKC activity in adipocytes. This suggests that, via activation of alpha-1 adrenergic receptors, increased sympathetic activity in adipose tissue may promote insulin resistance syndrome. In fact, measures which provoke increased sympathetic output – such as diuretic use and severe salt restriction – are known to compromise insulin sensitivity, whereas alpha-1 antagonist drugs, as well as drugs that act centrally to suppress sympathetic activity, typically have a favorable effect on insulin function. When insulin resistance syndrome is associated with elevated sympathetic activity – for example, in hypertensives who are obese or on diuretic therapy – measures which down-regulate sympathetic activity, or, more specifically, alpha-1 adrenergic activity, may be warranted. These include centrally acting imidazoline analogs (moxonidine, rilmenidine) and alpha-1 antagonists (doxazosin, prazosin). Taurine and high-dose pyridoxine may represent practical nutritional strategies for moderating elevated sympathetic activity, and exercise training and low-insulin-response diets may be useful in this regard as well.

Weight gain and the risk of developing insulin resistance syndrome.

Obesity and weight gain have been associated independently with hypertension, hyperinsulinemia, and dyslipidemia; however, prior research has not looked at the relation between weight gain from early adulthood to middle age and the development of this cluster of risk factors, known as insulin resistance syndrome. The association between weight gain over 30 years (defined as the difference between measured weight in middle age and participant recall of their weight at age 20) and the odds of developing insulin resistance syndrome at middle age was examined in a population-based sample of 2,272 eastern Finnish men. Each 5% increase in weight over the reported weight at age 20 was associated with nearly a 20% greater risk of insulin resistance syndrome by middle age, after adjustment for age and height. Moreover, there was a strong graded association between categories of weight gain and risk of insulin resistance syndrome. Men with weight increases of 10-19%, 20-29%, or > or =30% since age 20 were 3.0, 4.7, or 10.6 times more likely to have insulin resistance syndrome, respectively, by middle age, compared with men within 10% of their weight at age 20. Adjustments for age, height, physical activity, smoking, education, and parental history of diabetes did not alter these findings. The odds of having developed the hemodynamic and metabolic abnormalities that characterize insulin resistance syndrome by middle adulthood were increasingly higher the greater the weight gain over the preceding 30 years. This study adds to the literature identifying deleterious effects of weight gain from young to middle adulthood.