LAUSR

Abstract Background: Altered profiles of subcutaneous adipose tissue gene expression have been independently associated with insulin sensitivity. T2DM has been associated with higher levels of adipokines, inflammatory cytokines and lower plasma sex steroid concentrations. We sought to examine the interplay between these factors, specifically with respect to their associations with mRNA transcript levels in subcutaneous adipose tissue. Methods: Cross-sectional assessment of 162 men with T2DM not treated with insulin (Median age 57 [51 - 61]). Basic anthropometric parameters (including body fat by bioimpedance) were measured. Testosterone, DHT, A4, 17-OHP, E2 and E1 measured by LCMS; TNFα, IL-6, IL-8, IL-1ß, MCP-1, leptin, FSH, LH, SHBG and insulin by ELISA (all fasting) and RT-PCR assessed a panel of 23 gene transcripts in adipose tissue (n = 115). Results: Testosterone (R -.273) & DHT (R -.352) were associated with HOMA-IR independent of BMI but not after adjustment for SHBG. No other biochemical parameters were independently associated with HOMA-IR. Waist circumference (R .351) and HbA1c (R .284) but not IL-6 (R .315) were independently associated with CYP19 expression. HbA1c (R -.222) and A4 (R .207) were independently associated with estrogen receptor α expression. FSH (R -.229) was independently associated with androgen receptor expression. Insulin (R .274) and IL-6 (R .245) were independently associated with adipose leptin expression. Associations with BMI (R .275), DHT (R -.208) and FSH (R -.211) were not significant after adjustment for confounders. Insulin receptor expression was only independently associated with fat mass (R -.378). PPARγ expression was only significantly correlated with HbA1c (R -.204) whilst, after adjustment, MCP-1 expression was only independently associated with percentage fat (R .332). Retinol binding protein 4 expression was independently associated with HbA1c (-.323), MCP-1 (R .297) and FSH (-.254). Conclusion: Circulating sex steroids were not associated with insulin resistance or differences across a wide range of adipose mRNA transcript levels in men with T2DM. Insulin or HbA1c appeared to be a stronger correlate for adipose transcript profiles than circulating adipokines or cytokines. Recent evidence suggests FSH may exert direct effects upon adipose tissue and these findings potentially support this hypothesis.