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      Testosterone level and risk of type 2 diabetes in men: a systematic review and meta-analysis

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          Abstract

          Background

          Type 2 diabetes is a risk factor for testosterone deficiency and impaired sex steroid status. Some studies also investigated the association of testosterone level with diabetes risk in men, but reported controversial findings. To clarify this issue, we conducted a systematic review and meta-analysis.

          Methods

          PubMed, EMBASE and Web of Science were searched for eligible cohort or nested case–control studies published up to August 15, 2017. Meta-analysis was used to calculate the pooled relative risk (RR) of type 2 diabetes associated with higher testosterone level.

          Results

          Thirteen cohort or nested case–control studies with 16,709 participants were included. Meta-analysis showed that higher total testosterone level could significantly decrease the risk of type 2 diabetes in men (RR = 0.65; 95% CI 0.50–0.84; P = 0.001), and higher free testosterone level could also decrease the risk of type 2 diabetes in men (RR = 0.94; 95% CI 0.90–0.99; P = 0.014). After excluding two studies that did not calculate RRs by quartiles of testosterone levels, both higher total testosterone and free testosterone levels could decrease the risk of type 2 diabetes in men, and the pooled RRs were 0.62 (95% CI 0.51–0.76; P < 0.001) and 0.77 (95% CI 0.61–0.98; P = 0.03), respectively.

          Conclusion

          This meta-analysis suggests that higher testosterone level can significantly decrease the risk of type 2 diabetes in men. Therefore, combined with previous researches, the findings above suggest a reverse-causality scenario in the relation between testosterone deficiency and risk of type 2 diabetes in men.

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          Most cited references61

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          Long-term complications of diabetes mellitus.

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            Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men.

            In men, hypoandrogenism is associated with features of the metabolic syndrome, but the role of sex hormones in the pathogenesis of the metabolic syndrome and diabetes is not well understood. We assessed the association of low levels of testosterone and sex hormone-binding globulin (SHBG) with the development of the metabolic syndrome and diabetes in men. Concentrations of SHBG and total and calculated free testosterone and factors related to insulin resistance were determined at baseline in 702 middle-aged Finnish men participating in a population-based cohort study. These men had neither diabetes nor the metabolic syndrome. After 11 years of follow-up, 147 men had developed the metabolic syndrome (National Cholesterol Education Program criteria) and 57 men diabetes. Men with total testosterone, calculated free testosterone, and SHBG levels in the lower fourth had a severalfold increased risk of developing the metabolic syndrome (odds ratio [OR] 2.3, 95% CI 1.5-3.4; 1.7, 1.2-2.5; and 2.8, 1.9-4.1, respectively) and diabetes (2.3, 1.3-4.1; 1.7, 0.9-3.0; and 4.3, 2.4-7.7, respectively) after adjustment for age. Adjustment for potential confounders such as cardiovascular disease, smoking, alcohol intake, and socioeconomic status did not alter the associations. Factors related to insulin resistance attenuated the associations, but they remained significant, except for free testosterone. Low total testosterone and SHBG levels independently predict development of the metabolic syndrome and diabetes in middle-aged men. Thus, hypoandrogenism is an early marker for disturbances in insulin and glucose metabolism that may progress to the metabolic syndrome or frank diabetes and may contribute to their pathogenesis.
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              Testosterone and insulin resistance in the metabolic syndrome and T2DM in men.

              Obesity, type 2 diabetes mellitus and the metabolic syndrome are major risk factors for cardiovascular disease. Studies have demonstrated an association between low levels of testosterone and the above insulin-resistant states, with a prevalence of hypogonadism of up to 50% in men with type 2 diabetes mellitus. Low levels of testosterone are also associated with an increased risk of all-cause and cardiovascular mortality. Hypogonadism and obesity share a bidirectional relationship as a result of the complex interplay between adipocytokines, proinflammatory cytokines and hypothalamic hormones that control the pituitary-testicular axis. Interventional studies have shown beneficial effects of testosterone on components of the metabolic syndrome, type 2 diabetes mellitus and other cardiovascular risk factors, including insulin resistance and high levels of cholesterol. Biochemical evidence indicates that testosterone is involved in promoting glucose utilization by stimulating glucose uptake, glycolysis and mitochondrial oxidative phosphorylation. Testosterone is also involved in lipid homeostasis in major insulin-responsive target tissues, such as liver, adipose tissue and skeletal muscle.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                January 2018
                12 December 2017
                : 7
                : 1
                : 220-231
                Affiliations
                [1 ]Department of Endocrinology Jinshan Hospital of Fudan University, Shanghai, China
                [2 ]Department of Endocrinology Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China
                [3 ]Department of Clinical Laboratory Jinshan Hospital of Fudan University, Shanghai, China
                Author notes
                Correspondence should be addressed to J Zhang or L Ding: zhangjinan@ 123456hotmail.com or dlm196969@ 123456163.com
                Article
                EC170253
                10.1530/EC-17-0253
                5793809
                29233816
                8baca9d0-1229-4e03-89e3-c120702f400e
                © 2018 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 03 December 2017
                : 12 December 2017
                Categories
                Research

                testosterone,type 2 diabetes,meta-analysis
                testosterone, type 2 diabetes, meta-analysis

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