Long-Term Effects of Lifestyle Intervention and Metformin during DPP on Appendicular Lean Mass

Abstract

Weight loss prevents progression to diabetes but long term effects on lean mass are unknown. We determined if intensive lifestyle modification (ILS), metformin (MET) or placebo (PLB) treatment in the Diabetes Prevention Program (DPP) had differential effects on appendicular lean mass (ALM) and sarcopenic-obesity (SO) ∼16 years after DPP randomization in the DPP Outcome Study (DPPOS). During DPP, 3234 participants at high risk for diabetes were randomized to ILS, MET or PLB; 2779 continued in DPPOS and were offered modified group ILS. During DPPOS, ILS was offered additional lifestyle reinforcement semi-annually and MET received unmasked metformin. This analysis includes 1374 DPPOS participants who had dual-energy X-ray absorptiometry scans at year 12 for ALM (sum of lean mass in arms and legs). Low ALM was defined as ALM/BMI <0.789 for men or <0.512 for women. SO was defined as low ALM with BMI>30. Prevalence of low ALM and SO was compared across the 3 groups using Pearson’s chi-squared test. Logistic regression models determined the associations between treatment and low ALM or SO and between weight loss and low ALM or SO. Mean age at Y12 was 66.5 (±9.5) years. Mean time since DPP baseline was 15.6 (±0.7) years. Weight loss (DPP baseline to DPPOS Y12) did not differ by group (-4.4 kg ILS; -3.5 kg MET; -3.1 kg PLB; p=0.114). Prevalence of low ALM differed by group in men (35.7% ILS, 28.3% MET, 22.5% PLB; p=0.049) but not women (20.9% ILS, 24.8% MET, 24.1% PLB; p=0.482). In men, low ALM prevalence was higher in ILS compared with PLB (P=0.024) but not in MET vs. PLB. Prevalence of SO did not differ across groups in men (23.1% ISL, 22.0% MET, 14.1% PLB; p=0.112) or women (17.3% ILS, 20.9% MET, 20.3% PLB; p=0.492). SO prevalence was not different in ILS vs. PLB or in MET vs. PLB in men or women. More weight loss was associated with higher risk of low ALM and SO in women and men (p<0.001) independent of group. In men but not women at high risk of diabetes, lifestyle intervention to prevent diabetes may contribute to lower ALM. Disclosure A.V. Schwartz: None. Q. Pan: None. H.P. Hazuda: None. E. Horton: Advisory Panel; Self; PTS Diagnostics, Merck & Co., Inc., Theracos, Inc.. M.A. Hoskin: None. R. Rastogi Kalyani: None. W.C. Knowler: None. A. Kriska: None. M. Schlögl: None. H. Florez: Advisory Panel; Self; Sanofi. D. Research Group: None.