Low sex hormones may increase likelihood for transition to diabetes among Hispanic adults
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Low testosterone among men and low sex hormone-binding globulin among women are associated with progression from prediabetes to diabetes, according to a study published in The Journal of Clinical Endocrinology & Metabolism.
“A novel aspect of this study was the ability to examine associations at different stages of development of diabetes, including transition from normoglycemia to prediabetes and from prediabetes to diabetes,” Victoria Persky, MD, professor of epidemiology and biostatistics in the School of Public Health at the University of Illinois at Chicago, and colleagues wrote. “The stronger associations of testosterone among men and SHBG among women with transition from prediabetes to diabetes than from normoglycemia to prediabetes, suggest that testosterone and SHBG are operative later in the stages of diabetes development.”
Researchers examined data from adults aged 45 to 74 years participating in the Hispanic Community Health Study/Study of Latinos from March 2008 to June 2011. Demographics, medical history, two 24-hour dietary recalls, blood pressure, height, weight, waist-to-hip ratio and fasting serum and plasma samples were collected at baseline. A repeat assessment was conducted during a 6-year follow-up from 2014 to 2017. Researchers randomly chose 1,621 adults with prediabetes or normal glucose at baseline who had all hormonal measurements to include in a longitudinal analysis.
Low testosterone linked to diabetes for men
The cohort included 964 men, of whom 517 had normal glucose levels at baseline and 498 had prediabetes. Of those with normoglycemia, 274 progressed to prediabetes at 6 years and 10 progressed to diabetes. Of those with prediabetes at baseline, 219 still had prediabetes at 6 years while 236 progressed to diabetes. After adjusting for confounders, low testosterone (incidence rate ratio [IRR] = 1.75; 95% CI, 1.18-2.59; P = .005) and estradiol-to-testosterone-ratio (IRR = 2.36; 95% CI, 1.02-5.45; P = .044) were associated with conversion from prediabetes to diabetes. Low testosterone was also associated with conversion from normoglycemia at baseline to prediabetes at follow-up (IRR = 1.54; 95% CI, 1.04-2.27; P = .031).
“In longitudinal analyses in this study, testosterone was inversely, while low testosterone and the ratio of estradiol-to-testosterone were positively, associated with conversion from prediabetes to diabetes,” the researchers wrote. “Low testosterone, however, was also positively associated with conversion from normoglycemia to prediabetes. The longitudinal associations in this study suggest that the results are not due to reverse causation with insulin decreasing testosterone.”
Among men, estradiol was associated with change in fasting insulin (beta = 1.17; 95% CI, 0.31-2.02; P = .008) and change in homeostasis model assessment of insulin resistance (beta = 0.39; 95% CI, 0.06-0.72; P = .02). Bioavailable estradiol was associated with change in fasting insulin (beta = 0.75; 95% CI, 0.16-1.33; P = .012) and change in HOMA-IR (beta = 0.23; 95% CI, 0.03-0.44; P = .027). Testosterone was not associated with change in fasting glucose alone, but it was inversely associated with change in fasting glucose when controlling for SHBG.
Low SHBG associated with transition to diabetes for women
Among 657 women, 305 had normoglycemia at baseline, and 388 had prediabetes. Of the normoglycemia group, 157 progressed to prediabetes at follow-up and seven progressed to diabetes. Of those with prediabetes at baseline, 174 still had prediabetes at follow-up and 189 progressed to diabetes. SHBG was inversely associated with a transition from prediabetes to diabetes (IRR = 0.62; 95% CI, 0.44-0.86; P = .005). There were no associations with conversion from normoglycemia to prediabetes.
Among women, SHBG was inversely associate with change in HbA1c (beta = –0.04; 95% CI, –0.06 to –0.01; P = .002) and post-load glucose (beta = –6.58; 95% CI, –9.9 to –3.27; P < .0001). Luteinizing hormone (beta = –1.05; 95% CI, –1.92 to –0.19; P = .017) and follicle-stimulating hormone (beta = –1.13; 95% CI, –1.99 to –0.27; P = .011) were inversely associated with change in fasting glucose, and follicle-stimulating hormone was also associated with change in HOMA-IR (beta = –0.3; 95% CI, –0.56 to –0.03; P = .027).
“The stronger associations with transition from prediabetes to diabetes than from normoglycemic to prediabetes suggest that testosterone and SHBG are operative at later stages of the development of diabetes,” the researchers wrote. “There are some suggestions that estradiol in men may increase risk of insulin resistance; however, biologic pathways by which endogenous sex hormones affect glucose homeostasis await future studies.”
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