Session: OR48-Insulin Resistance & Metabolic Syndrome: From Clinical Physiology to Clinical Care
Room 304 (Moscone Center)
Methods: We measured fat and lean body mass (LBM) by DEXA; fasting FFA and lipids in a CTSA lab; central and peripheral Si using a 2-stage, hyperinsulinemic euglycemic clamp (whole body [WB] Si, HGO, Rd); liver and intramyocellular (IMCL, soleus) lipid by 1H-MR spectroscopy.
Results: 20 men (68 years old, range=62-78) weighing 105kg (85-137) lost a median of 1.4kg (-7.4 to 2.0; p=0.002) total fat, 0.9kg (-4.6 to 0.2; p=0.0007) trunk fat and 0.7kg (-3.0 to 2.3, p=0.01) extremity (ext) fat, and gained 1.4kg of total LBM (-0.8 to 7.1; p=0.0002) and 1.2kg of ext LBM (-1.1 to 4.8; p=0.0006) during T treatment (Rx). WB Si improved by 1.05 (-2.44 to 3.73; dL/min per μU/mL, p=0.04) and Rd by 1.16 (-3.08 to 3.85, p=0.03). Ds in WB Si and Rd only occurred with declines in trunk and ext fat larger than the median declines, whereby Si WB improved (+1.59, p=0.04; +1.56, p=0.06, respectively) as did Rd (+2.08, p=0.04; +2.11, p=0.05). At wk20, HGO was related to trunk fat (ρ=-0.57, p=0.009) and % total fat (ρ=-0.65, p=0.002) but not to D in fat. Liver fat/H2O declined in 14 (by 44%) of 19 persons with associated Ds in Si WB (+1.36, p=0.09) and Rd (+1.23, p=0.08). IMCL/Cr declined in 12 (by 41%) of 15 with Ds in Si WB (+0.57, p=0.06) and Rd (+0.61, p=0.04). In these subjects, baseline FFA correlated with WB Si, HGO, and Rd (ρ=-0.63, -0.58, -0.59, p≤0.02). By multi-linear regression, Ds in total fat and FFA during the clamp (wk20-wk0) accounted for 55% and 15% of D in WB Si (p≤0.03), and 74% (p<0.0001) and 8% (p=0.06) of D in Rd. Triglycerides decreased by 35mg/dL (-239 to 38; p=0.02), LDL-C by 14mg/dL (-56 to 27; p=0.02), and HDL-C by 5mg/dL (-23 to 2; p=0.004). No serious AEs occurred.
Conclusions: In older obese men with IR, T Rx significantly reduced fat mass and improved WB Si and glucose disposal if there were large reductions in regional adiposity. T improved LDL-C and triglycerides but reduced HDL-C. Physiologic factors (e.g. D in fat, FFA, tissue lipid) that predict the most favorable cardiometabolic responses to T in older men should be confirmed.
Disclosure: FRS: Study Investigator, Solvay Pharmaceuticals. Nothing to Disclose: JH, JC, HWK, PC, TAB, KEY
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