Role of Sex Hormones in Mediating Adiposity Changes From Weight Loss in People With Type 2 Diabetes: Look AHEAD Sex Hormone Study.

Abstract

In people with type 2 diabetes (T2D), weight loss affects sex hormones (testosterone [T], estradiol [E2], sex hormone-binding globulin [SHBG]) and reduces fat and lean mass differently in women vs men, but the relationship between sex hormones and adiposity changes due to weight loss is not clear. This paper aims to examine the relationships between sex hormones and adiposity changes due to an intensive lifestyle intervention (ILI). We analyzed data from 2334 participants (50% female) in the Look AHEAD Sex Hormone Ancillary Study, including a subset of 822 (47.4% female) with dual-energy x-ray absorptiometry scans. Using structural equation modeling, we assessed how changes in E2, T, and SHBG at year 1 (Y1) mediated the effects of ILI on adiposity measures at year 4 (Y4). We stratified by sex to explore sex differences. In men, a 14.4% ILI-associated increase in total T at Y1 mediated increases in weight (189 g; 95% CI, 65-317) and waist circumference (0.135 cm; 95% CI, 0.19-0.248) at Y4. Additionally, a 24.6% increase in SHBG at Y1 mediated increases both in percentage trunk fat (0.082%; 95% CI, 0.003%-0.174%) and percentage whole-body fat (0.068%; 95% CI, 0.001%-0.146%) at Y4. In women, a 21.8% decrease in bioavailable T (BioT) at Y1 mediated decreases in whole-body fat mass (-164; 95% CI, -326 to -29.3), whole-body lean mass (-115 g; 95% CI, -203.4 to -40), and trunk lean mass (-97.2 g; 95% CI, -156 to -45.5) at Y4. This study revealed sex-specific mediating effects of sex hormones due to weight loss from ILI on body composition changes in people with T2D. Further research is needed to explore long-term health outcomes related to sex differences in recommendations for weight loss in people with T2D.