Abstract P2014: Baseline Sex Hormone Binding Globulin Level Modifies Intensive Lifestyle Intervention Effect on Blood Pressure in Post-Menopausal Females

Background: The Look AHEAD (Action for Health in Diabetes) randomized controlled trial showed that Intensive Lifestyle Intervention (ILI) targeting weight loss caused greater reductions in systolic and diastolic blood pressure (SBP and DBP) than Diabetes Support and Education (DSE) in patients with body mass index (BMI) 25 kg/m 2 and type 2 diabetes (T2D). Nonetheless, treatment assignment alone did not explain the individual variations in BP improvement. We hypothesize that baseline sex hormone binding globulin (SHBG), which is inversely associated with hypertension in both males and females, might modify the effect of ILI on BP. Methods: We selected a random sample of 1167 post-menopausal females and 1167 males from the Look AHEAD trial in our analysis. We retained the randomized design and created sex-stratified linear mixed models to examine whether log-transformed baseline SHBG levels modify the treatment effects (i.e., absolute difference between ILI and DSE) on SBP and DBP reduction after 1 year, adjusting for age, race, study site, baseline BMI and use of anti-hypertensive medications. Results: In our study sample (age: 60.0 [SD, 6.2] years; 14.8% black; 50% female), median [IQI] baseline SHBG levels were 32.9 [22.2-54.0] nmol/L in females and 29.0 [19.9-44.8] nmol/L in males. Mean (SD) baseline SBP and DBP were 130 (17.3) and 67.6 (9.2) mmHg for females, 128.6 (16.3) and 73.1 (8.9) mmHg for males. Females with 2-fold higher baseline SHBG had 3.0 (95%CI: 1.0, 5.0) mmHg and 1.3 (95%CI: 0.3, 2.2) mmHg greater reduction in SBP (Figure, panel A) and DBP (panel B), respectively, due to ILI compared to DSE. However, treatment effects in males did not vary significantly with baseline SHBG (heterogeneity p-values: 0.81 SBP, 0.98 DBP). Conclusion: Females with higher baseline SHBG had more BP lowering due to ILI, compared to DSE, but this effect was not seen in males. Future research is needed to confirm if baseline SHBG can identify female patients with T2D who benefit most from ILI, and to determine whether those with low SHBG levels need more aggressive BP management in combination with ILI.