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Background /purpose: Leptin—a protein hormone that plays vital role in the regulation of glucose homeostasis and insulin sensitivity, involved in regulating the circadian rhythms of gonadotropic, thyrotropic and adrenal axes in the endocrine system. This cross-sectional study was undertaken to correlate serum leptin levels and other demographic and biochemical parameters between prediabetic cases and control subjects of Kashmiri population. Furthermore, association of serum leptin levels with various demographic and biochemical parameters along with insulin resistance in pre-diabetic subjects was elucidated. In our study, pre-diabetic cases (n = 212) and healthy controls (n = 196) were enrolled. Methods: All study subjects underwent anthropometric assessment. Serum samples of all study subjects were analysed for biochemical parameters employing the principle of spectrophotometry and leptin levels using sandwich enzyme-linked immunosorbent assay (ELISA). Insulin levels of prediabetic cases were deduced by chemiluminescent micro particle immunoassay (CMIA) technology and thereby calculating their insulin resistance. Results: The cases had statistically increased leptin levels, lipid profile and obesity as compared to controls (p ≤ 0.05). Our study, showed a positive correlation between elevated leptin levels and increased lipid levels (total cholesterol, triglycerides; TG and very low density lipoproteins-cholesterol; VLDL-C) in prediabetics (p < 0.001). Conclusion: Beyond adiposity, leptin levels may increase the risk of pre-diabetes in Kashmiri population. Since the secretion, estimation and measurements of leptins are modest in contrast to insulin levels; therefore, leptin levels can also be included in the routine measurement as an indicator of metabolic syndrome and/or T2DM. [ABSTRACT FROM AUTHOR]

The potential lipotoxic effect of intramyocellular triglyceride (IMTG) accumulation has been suggested to be a major component in the development of insulin resistance. Increased levels of IMTGs correlate with insulin resistance in both obese and diabetic patients, but this relationship does not exist in endurance trained (ETr) subjects. This may be, in part, related to differences in the gene expression and activities of key enzymes involved in fatty acid transport and oxidation as well as in the perodixation status of the IMTGs in obese/diabetic patients as compared with ETr subjects. Disruptions in fat and lipid homeostasis in skeletal muscle have been shown to activate protein kinase C (PKC), which acts on several downstream signalling pathways, including the insulin and the I?B kinase (IKK)/NF?B signalling pathways. Additionally, an increased peroxidation of IMTGs may reduce insulin sensitivity by increasing TNFa, which is known to increase the expression of suppressor of cytokine signalling proteins (SOCS). A common characteristic observed when activating both PKC and TNFa/SOCS3 is the inhibition of tyrosine phosphorylation of IRS-1 and subsequently an inhibition of its activation of downstream signalling molecules. These may be important players in the development of insulin resistance and understanding their activation and expression in both obese and ETr humans should assist in understanding how and why IMTGs become lipotoxic.International Journal of Obesity (2004) 28, S66-S71. doi:10.1038/sj.ijo.0802859 [ABSTRACT FROM AUTHOR]