Association between serum leptin and adiponectin levels with risk of insulin resistance and impaired glucose tolerance in non-diabetic women.

Obesity is a well known risk factor for insulin resistance and type 2 diabetes. Recently discovered adipocyte-derived proteins (leptin and adiponectin) might contribute to the pathologic mechanism linking obesity and insulin resistance. A total of 190 non-diabetic women were recruited from the Obesity Clinic of Kaohsiung Municipal Hsiao-Kang Hospital, Taiwan, between February 2003 and February 2004. All participants completed a simple questionnaire. Blood pressure and body mass index were measured; blood samples for fasting glucose, total cholesterol, high-density lipoprotein cholesterol, triglyceride, leptin, adiponectin, and fasting insulin level were collected after an overnight fast. Two-hour glucose level after a 75-g glucose tolerance test was determined. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as the index of insulin resistance. Multivariate linear regression analyses were used to analyze the relationship between adipocytokines and insulin resistance after adjusting for possible confounding factors. Leptin and adiponectin were found to be independently associated with HOMA-IR and fasting insulin concentration, but in divergent directions, after adjusting for potential confounding factors. Adiponectin, but not leptin, was associated with impaired glucose tolerance after adjusting for potential confounding factors. The results suggest that leptin and adiponectin may be involved in the pathophysiologic link between obesity and insulin resistance independently. Low levels of adiponectin may increase the risks of developing impaired glucose metabolism and type 2 diabetes.

Demethylation within the proximal promoter region of human estrogen receptor alpha gene correlates with its enhanced expression: Implications for female bias in lupus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease primarily affecting women. Previous studies have indicated that sex hormone estrogens contribute to the female predilection of SLE. Estrogen regulates gene expression by translocating estrogen receptors (ER) α and ß into the nucleus where they induce transcription by binding to estrogen response elements of target genes. We have previously observed that expression of ERα gene and protein in lupus patients is significantly higher than in healthy controls and that estradiol up-regulates calcineurin expression via over-expression of ERα gene in SLE. However, the pathogenesis of over-expression of ERα gene is unknown. Here we report that enhanced expression of ERα mRNA and protein in SLE and rheumatoid arthritis is associated with DNA demethylation within the proximal promoter region located between -232 and +81 base pair relative to transcription start site of human ERα gene (GenBank Accession no. AL356311.6). The frequency of DNA demethylation was comparable between male and female. These findings suggest that estrogen and demethylated ERα promoter associated up-regulated ERα genes are two critical factors in the gender biased development of autoimmune diseases besides genetic factor.