02662nas a2200229 4500008004100000022001400041245014000055210006900195260001600264300001500280520190800295100002402203700001902227700001802246700001902264700002002283700002402303700002102327700002402348700002402372856003602396 2016 eng d a1945-719700aTestosterone, Dihydrotestosterone, Sex Hormone Binding Globulin and Incident Diabetes among Older Men: the Cardiovascular Health Study.0 aTestosterone Dihydrotestosterone Sex Hormone Binding Globulin an c2016 Oct 12 ajc201626233 a

CONTEXT: Although sex hormone binding globulin (SHBG) and testosterone (T) have been inversely associated with risk of diabetes, few studies have examined dihydrotestosterone (DHT), a more potent androgen than T, or older adults, whose glycemic pathophysiology differs from younger adults.

OBJECTIVE: To determine the associations of SHBG, T, and DHT with insulin resistance and incident diabetes in older adult men.

DESIGN: In a prospective cohort study, we evaluated baseline levels of SHBG, T, and DHT using liquid chromatography-tandem mass spectrometry among 852 men in the Cardiovascular Health Study free of diabetes and cardiovascular disease in 1994.

MAIN OUTCOME: Insulin resistance estimated by HOMA-IR and insulin sensitivity estimated by the Gutt index in 1996, and incident diabetes (n=112) ascertained over a mean follow-up of 9.8 years.

RESULTS: In linear regression models adjusted for demographics, alcohol consumption, current smoking, body-mass index, and other androgens, SHBG (HOMA-IR 0.30 units lower per doubling; 95% confidence interval [CI], 0.08-0.52; p=0.01) and total DHT (HOMA-IR 0.18 units lower per doubling; 95% CI 0.06-0.30; p=0.01), but not free T (p=0.33) were inversely associated with insulin resistance. In corresponding Cox proportional hazards models, total DHT was again inversely associated with risk of diabetes (adjusted hazard ratio per doubling 0.69; 95% CI, 0.52-0.92; p=0.01), but SHBG (hazard ratio 1.09; 95% CI, 0.74-1.59; p=0.66) and free T (hazard ratio 1.15; 95% CI, 0.92-1.43; p=0.23) were not.

CONCLUSIONS: Among older men, higher levels of DHT are inversely associated with insulin resistance and risk of diabetes over the ensuing 10 years, while levels of T are not. Future studies are still needed to clarify the role of SHBG in risk of diabetes in this population.

1 aJoyce, Katherine, E1 aBiggs, Mary, L1 aDjoussé, Luc1 aIx, Joachim, H1 aKizer, Jorge, R1 aSiscovick, David, S1 aShores, Molly, M1 aMatsumoto, Alvin, M1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/7249