OR22-1 TESTOSTERONE REPLACEMENT DECREASES INSULIN RESISTANCE IN HYPOGONADAL MEN WITH TYPE 2 DIABETES

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR22-Male Reproductive Hormones: Effects on Fertility and Beyond
Translational
Sunday, June 16, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 11:15 AM
Room 104 (Moscone Center)
Sandeep S Dhindsa*1, Manav Batra2, Nitesh D Kuhadiya3, Sartaj Sandhu2, Ajay Chaudhuri4, Antoine Makdissi5, Husam Ghanim6 and Paresh Dandona7
1SUNY at Buffalo, Amherst, NY, 2SUNY at Buffalo, 3University at Buffalo, Buffalo, NY, 4SUNY at Buffalo, Williamsville, NY, 5State Univ of New York at Buffal, Buffalo, NY, 6SUNY at Buffalo, Buffalo, NY, 7State Univ of NY, Buffalo, NY
One third of men with type 2 diabetes(T2D) have hypogonadotropic hypogonadism(HH). Testosterone(T) concentrations are inversely related to BMI. We conducted a randomized placebo controlled trial to evaluate the effect of T replacement on insulin resistance in T2D men with HH.

50 men with T2D were recruited into the study. HH was defined as free T concentrations <5 ng/dl with normal or low LH and FSH. 26 men had HH(mean total T 247±82ng/dl; free T 4.2±1.1ng/dl) and 24 men had normal total and free T concentrations(means 527±205 and 7.3±2.0ng/dl). Insulin sensitivity was calculated from the glucose infusion rate(GIR) during the last 30 min of a 4 hour hyperinsulinemic-euglycemic clamp(80mU/m2/min) and expressed as mg/kg body weight/min. Lean mass and fat mass were measured by DEXA. Men with HH were randomized to receive intramuscular T(250 mg) or placebo(1ml saline) every 2 weeks for 6 months(n=13 in each group). Clamps and DEXA were repeated at 6 months.

Men with HH had similar age(54±8 vs. 53±10years, p=0.56) but higher BMI(40±9 vs. 34±7kg/m2, p=0.02) than eugonadal men. Men with HH had higher fat mass(45±15 vs. 34±15kg, p=0.02) but similar lean mass(73±21 vs. 66±9kg, p=0.12) than eugonadal men. Mean GIR was lower in men with HH than in eugonadal men(4.1±2.4 vs. 6.9±3.6 mg/kg/min, p=0.003) even after adjustment for fat mass, lean mass and age(4.6±2.7 vs. 6.4±2.7 mg/kg/min, p=0.05). Total and free T increased after 6 months of T therapy(273±96 vs 561±249 ng/dl, p=0.01; 4.2±1.1 vs. 11.8±7.1 ng/dl, p=0.007; blood sample drawn 1 week after the final T injection) but did not change in placebo group(271±40 vs 349±215 ng/dl, p=0.23; 4.0±0.8 vs. 4.8±2.1 ng/dl, p=0.3). There was no change in weight(123±23 vs 122±24kg, p=0.37) or fat mass(46±15 vs 43±13kg, p=0.24) but lean mass(71±9 vs 72±10kg, p=0.03) increased slightly but significantly after 6 months of T therapy. There was no change in weight(111±38 vs 112±38kg, p=0.85), fat mass(37±16 vs 36±14kg, p=0.19) or lean mass(67±14 vs 67±13kg, p=0.57) in placebo group. GIR increased by 30% after 6 months (4.1±2.0 vs 5.3±2.3 mg/kg/min, p=0.005) of T therapy but did not change in placebo group(3.4±1.5 vs 3.5±1.8 mg/kg/min, p=0.88). Change in GIR did not relate to increase in free T(r=-0.16, p=0.68) or to change in lean mass(r=-0.13, p=0.73) in T group.

Our data show for the first time that 1) men with T2D and HH are more insulin resistant than those with normal T; 2) insulin resistance is reversed following T replacement.

Sources of support: NIH

Nothing to Disclose: SSD, MB, NDK, SS, AC, AM, HG, PD

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: NIH
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