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Low testosterone high estradiol increase diabetes risk in men with obesity
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Men with obesity who have low free testosterone or high estradiol levels are at elevated risk for insulin resistance or developing type 2 diabetes vs. normal-weight men or men with obesity and higher free testosterone levels, according to an analysis of National Health and Nutrition Examination Survey data.
Ji Li, MD, PhD, of the department of pathology at Johns Hopkins School of Medicine, and colleagues analyzed data from 1,461 men aged at least 20 years who participated in NHANES III, conducted between 1988 and 1991 (54.7% with overweight or obesity; 24.9% with central obesity). Researchers assessed serum testosterone, sex hormone-binding globulin, estradiol and androstanediol glucuronide concentrations, as well as HbA1c, serum insulin and fasting plasma glucose, using logistic regression analysis to calculate multiplicative interaction by cross-product interaction terms. Additive interaction was assessed by the relative excess risk due to interaction (RERI).
Among men with overweight or obesity, those in the lowest tertile of free testosterone concentration (OR = 41.66; 95% CI, 14.19-122.31) or in the highest tertile of androstanediol glucuronide concentration (OR = 10.13; 95% CI, 4.2-24.45) had the greatest risk for increased insulin resistance after adjustment for demographic and lifestyle factors. Men with central obesity in the lowest tertile of serum testosterone (OR = 3.35; 95% CI, 1.41-7.95) and lowest tertile of free testosterone (OR = 4.84; 95% CI, 0.92-25.53) had the highest risk for developing type 2 diabetes, according to researchers. Additionally, men with obesity in the lowest tertile of estradiol or men with central obesity in the lowest tertile of free estradiol index were less likely to have a diagnosis of type 2 diabetes vs. other men with obesity (OR = 1.21 vs. 3.31) or central obesity (OR = 3.04 vs. 8.38).
Researchers observed multiplicative interactions between free testosterone, androstanediol glucuronide and overweight or obesity in the risk for insulin resistance, as well as between estradiol and central obesity relating to beta-cell dysfunction (P < .05). For type 2 diabetes, researchers observed multiplicative interactions for total testosterone, free testosterone and free estradiol index with central obesity, and for estradiol with overweight or obesity (P < .05).
Researchers also observed additive interactions with obesity or central obesity for total testosterone (RERI = 2.75; 95% CI, 0.92-4.59), SHBG (RERI = 5.71; 95% CI, 0.77-10.64), and free estradiol index (RERI = –9.96; 95% CI, –19.18 to –0.74) relating to insulin resistance, beta-cell dysfunction and type 2 diabetes.
“Given [the] high prevalence of obesity, increasing incidence of [type 2 diabetes] and high prevalence of low sex steroid hormone concentrations in adult men in the U.S., monitoring and regulating programs on body weight and sex steroid hormone status may become a cost-effective strategy to reduce the risk of [insulin resistance] and [type 2 diabetes] in this country, particularly in adult men,” the researchers wrote. – by Regina Schaffer
Disclosure: The researchers report no relevant financial disclosures.
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