Low Levels of Sex Hormone-binding Globulin and Testosterone Predict the Development of Non-Insulin-dependent Diabetes Mellitus in Men

Haffner, Steven M.; Shaten, Jessica; Stem, Michael P.; Smith, George Davey; Kuller, Lewis H.

doi:10.1093/oxfordjournals.aje.a008832

Cited by 285 publications

(208 citation statements)

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“…We cannot determine the temporality of the associations observed here between androgen levels and diabetes. However, several previous prospective analyses (13,14,16,17) suggest that decreases in testosterone level may precede the development of diabetes, lending support to a temporal if not causal relation. Additionally, including individuals with undiagnosed diabetes, a population at an earlier point in the progression of diabetes, did not change our results.…”

Section: Results -mentioning

confidence: 98%

Androgens and Diabetes in Men

et al. 2007

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OBJECTIVE -Low levels of androgens in men may play a role in the development of diabetes; however, few studies have examined the association between androgen concentration and diabetes in men in the general population. The objective of this study is to test the hypothesis that low normal levels of total, free, and bioavailable testosterone are associated with prevalent diabetes in men.RESEARCH DESIGN AND METHODS -The study sample included 1,413 adult men aged Ն20 years who participated in the morning session of the first phase of the Third National Health and Nutrition Examination Survey, a cross-sectional survey of the civilian, noninstitutionalized population of the U.S. Bioavailable and free testosterone levels were calculated from serum total testosterone, sex hormone-binding globulin, and albumin concentrations.RESULTS -In multivariable models adjusted for age, race/ethnicity, and adiposity, men in the first tertile (lowest) of free testosterone level were four times more likely to have prevalent diabetes compared with men in the third tertile (odds ratio 4.12 [95% CI 1.25-13.55]). Similarly, men in the first tertile of bioavailable testosterone also were approximately four times as likely to have prevalent diabetes compared wth men in the third tertile (3.93 [1.39 -11.13]). These associations persisted even after excluding men with clinically abnormal testosterone concentrations defined as total testosterone Ͻ3.25 ng/ml or free testosterone Ͻ0.07 ng/ml. No clear association was observed for total testosterone after multivariable adjustment (P for trend across tertiles ϭ 0.27).CONCLUSIONS -Low free and bioavailable testosterone concentrations in the normal range were associated with diabetes, independent of adiposity. These data suggest that low androgen levels may be a risk factor for diabetes in men. Diabetes Care 30:234 -238, 2007I t has been suggested that sex steroid hormones may play a causal role in the development of insulin resistance and type 2 diabetes (1,2). There is a growing amount of literature examining the role sex steroid hormones may play in the development of diabetes and cardiovascular disease in women, but there has been relatively less attention paid to this association in men. Men with endocrine disorders that are associated with low testosterone levels (hypogonadism), such as Klinefelter's and Wolfram's syndromes, have an elevated risk of developing insulin resistance and diabetes (3,4). However, the association between sex steroid concentrations within the normal range and diabetes risk in men in the general population has not been well characterized.Obesity, one of the most important underlying causes of insulin resistance, is associated with low testosterone levels in men (5-7) and may partially or wholly mediate the process by which endogenous sex hormones influence diabetes risk. Many previous studies have been conducted in small, highly selected populations or convenience samples and/or did not rigorously measure or control for the possible effects of adiposity. The present st...

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Section: Results -mentioning

confidence: 98%

Androgens and Diabetes in Men

et al. 2007

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“…166,167,170,212,228 ± 233 To some degree, the results from these studies may have been confounded by age, 230,232 which generally correlates negatively with free T but positively with BMI. Nevertheless, the inverse associations of free T with BMI, WHR or insulin remained statistically signi®cant in all studies where an adjustment for age was made 166,167,212,228,229,233 or where all subjects studied were within a very narrow age range. 170,231 …”

Section: Physiological Mechanismsmentioning

confidence: 87%

Plasma androgens, IGF-1, body size, and prostate cancer risk: a synthetic review

Kaaks

Lukanova

Sommersberg

2000

Prostate Cancer Prostatic Dis

103

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We present a review of the epidemiological evidence for relations of prostate cancer risk to circulating total and bioavailable androgens, to alterations in the metabolism of insulin-like growth factor-1 (IGF-1), and to anthropometric indices of longitudinal growth (body stature) and overweight. In addition, we review the physiological inter-relationships between insulin, growth hormone/IGF-1 axis, and sex steroid metabolism, as well as the associations of bioavailable sex steroid levels with overweight and obesity. A ®rst conclusion of this review is that, taken together, epidemiological studies have provided little support for the hypothesis that prostate cancer risk is increased in men with elevated total or biovailable testosterone (T). Although one prospective study showed an increased risk in men with low plasma sex hormone-binding globulin (SHBG) and with elevated plasma T for given levels of SHBG, this was not con®rmed by results from other cohort studies. A second conclusion is that overweight, which is generally associated with moderate reductions in both total and bioavailable plasma T, appears to be unrelated to any signi®cant increase or decrease in prostate cancer risk. However, signi®cant increases in risk have been observed for men with a taller body stature, or with elevated plasma IGF-1. IGF-1 may directly enhance prostate tumorigenesis by inhibiting apoptosis and by stimulating cell proliferation. In addition, IGF-1 downregulates the synthesis of SHBG, and enhances sex steroid synthesis. Therefore, we do not entirely rule out that due to an elevation of plasma IGF-1 levels, men at increased risk of prostate cancer also have mildly elevated plasma bioavailable T, which epidemiological studies may have failed to demonstrate because of methodological problems. Prostate Cancer and Prostatic Diseases (2000) 3, 157±172.

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“…Prolactin has been found to inhibit production of sex hormone–binding globulin in vitro 34. Low sex hormone–binding globulin has been prospectively associated with increased odds of incident diabetes 33, 35, 36. Although the mechanism and causality of this association has not been fully characterized, it is possible that elevated prolactin may influence diabetes risk by inhibiting production of sex hormone–binding globulin.…”

Section: Discussionmentioning

confidence: 99%

Association Between Prolactin and Incidence of Cardiovascular Risk Factors in the Framingham Heart Study

Therkelsen

Abraham

Pedley

et al. 2016

JAHA

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BackgroundProlactin is an anterior pituitary hormone that may modulate the adverse effects of obesity. Prolactin has been associated with cardiovascular disease mortality, but less is known about whether prolactin predicts incidence of cardiovascular disease risk factors.Methods and ResultsOur sample (n=3232, mean age 40.4 years, 52.1% women) was drawn from Framingham Heart Study participants who attended 2 examinations an average of 6.1 years apart. After excluding those with elevated prolactin (>30 mg/dL for women, >20 mg/dL for men), multivariable‐adjusted regressions modeled the associations between baseline prolactin and changes in cardiovascular disease risk factors. Models were adjusted for age, sex, baseline value of the risk factor, smoking status, hormone replacement therapy, and menopausal status and additionally for body mass index. Mean prolactin levels were 11.9 mg/dL (SD 5.2) in women and 8.0 mg/dL (SD 2.9) in men. No associations were observed for change in weight, body composition, total cholesterol, triglycerides, or fasting glucose. In women, for example, for each 5‐mg/dL increment in prolactin, odds of incident hypercholesterolemia were 1.06, which was not significant (95% CI 0.91–1.23, P=0.46). Some exceptions were of note. In women, for each 5‐mg/dL increment in prolactin, we observed increased odds of low high‐density lipoprotein cholesterol at follow‐up (odds ratio 1.50, 95% CI 1.18–1.91, P=0.001) that persisted after adjustment for body mass index (P=0.001). In men, a 5‐mg/dL increment in prolactin was associated with increased odds of incident hypertension (odds ratio 1.61, 95% CI 1.18–2.20 P=0.002) and incident diabetes (odds ratio 1.70, 95% CI 1.04–2.78, P=0.03).ConclusionsProlactin is not associated with a comprehensive panel of incident cardiovascular disease risk factors. Measurement of circulating prolactin levels in the community likely does not provide substantial insight into cardiometabolic risk.

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Low Levels of Sex Hormone-binding Globulin and Testosterone Predict the Development of Non-Insulin-dependent Diabetes Mellitus in Men

Cited by 285 publications

References 0 publications

Androgens and Diabetes in Men

Androgens and Diabetes in Men

Plasma androgens, IGF-1, body size, and prostate cancer risk: a synthetic review

Association Between Prolactin and Incidence of Cardiovascular Risk Factors in the Framingham Heart Study

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