Low levels of androgen may be a risk factor for diabetes in men, according to the findings of a population-based study.
In a sample of 1,413 adult men, concentrations of free and bioavailable testosterone in the low normal range were associated with diabetes independent of adiposity, reported Elizabeth Selvin, Ph.D., of Johns Hopkins Bloomberg School of Public Health, Baltimore, and her colleagues.
“To our knowledge, this is the first study to examine the association between sex steroid hormones and diabetes in a large, nationally representative male population,” the authors wrote (Diabetes Care 2007;30:234–8).
The study sample included multiethnic men aged 20 years or older who participated in the morning session of phase I of the Third National Health and Nutrition Examination Survey (NHANES III), which was conducted between 1988 and 1991.
“Morning session participants were chosen for this hormone study to reduce extraneous variation due to diurnal production of sex hormones,” the authors wrote.
As part of the survey, all of the study participants underwent an interview, an extensive physical examination, and collection of a blood sample.
Height, weight, and waist and hip circumferences were measured as part of the physical examination, and body mass index was calculated.
The information on age, race and ethnicity, and diabetes status was collected by patient self-report. With respect to diabetes specifically, the interviewers asked the participants if they had ever been told by a health professional that they had diabetes or sugar diabetes, the authors noted.
The main hormone measurements of interest in the investigation included serum total testosterone as well as estimated bioavailable and free testosterone levels, which were calculated from serum total testosterone, sex hormone-binding globulin, and albumin concentrations. “Measurements of free and bioavailable testosterone levels more accurately represent concentrations readily available to tissues and metabolic processes,” the authors stated.
In a multivariate model adjusted for age, race/ethnicity, and adiposity, there was no clear association of total testosterone concentration with diabetes; however, men in the lowest tertile (0.09 ng/mL or below) of free testosterone level were more than four times as likely to have prevalent diabetes, compared with men in the highest tertile (higher than 0.14 ng/mL).
Similarly, men in the lowest tertile of bioavailable testosterone (2.11 ng/mL or below) were nearly four times as likely to have prevalent diabetes as were men in the highest tertile (higher than 3.02 ng/mL), the authors reported. They also noted that “these associations persisted even after further adjustment for total cholesterol, triglycerides, and systolic blood pressure.”
In addition, the association with low free testosterone persisted even after the exclusion of men with clinically low levels of total testosterone (less than 3.25 ng/mL) and/or clinically low levels of free testosterone (less than 0.07 ng/mL), suggesting the observed associations were “not entirely driven by hypogonadal men,” the authors wrote.
A sensitivity analysis that included 58 cases of undiagnosed diabetes showed no appreciable alterations in the adjusted models, the authors reported.
“The independent association of low free and bioavailable testosterone levels in our adjusted models suggest[s] that testosterone insufficiency may be a risk factor for diabetes,” the authors wrote.
Despite the fact that the directionality of the associations between low androgen levels and adiposity are unclear based on the analysis, “our data are consistent with the hypothesis that androgens may directly influence glucose metabolism and the development of insulin resistance independently of the effects of adiposity,” they stated.
The study is limited by its cross-sectional design, which precludes evaluation of the temporality of the observed associations between androgen levels and diabetes, the authors wrote.
“However, several previous prospective analyses suggest that decreases in testosterone level may precede the development of diabetes, lending support to a temporal if not causal relation,” they said. “Additionally, including individuals with undiagnosed diabetes, a population at an earlier point in the progression of diabetes, did not change our results.”
Additional studies are needed to investigate the mechanisms by which sex steroid hormones contribute to diabetes as well as other chronic diseases, the authors concluded.
The study is the third from the Hormone Demonstration Program, which is supported by the Maryland Cigarette Restitution Fund Research Grant Program that is based at Johns Hopkins University.