The role of testosterone in type 2 diabetes and metabolic syndrome in men

Abstract

Over the last three decades, it has become apparent that testosterone plays a significant role in glucose homeostasis and lipid metabolism. The metabolic syndrome is a clustering of risk factors predisposing to diabetes mellitus type 2, atherosclerosis and cardiovascular morbidity and mortality. The main components of the syndrome are visceral obesity, insulin resistance, glucose intolerance, raised blood pressure and dyslipidemia (elevated triglycerides, low levels of high-density lipoprotein cholesterol), and a pro-inflammatory and thrombogenic state. Crosssectional epidemiological studies have reported a direct correlation between plasma testosterone and insulin sensitivity, and low testosterone levels are associated with an increased risk of type 2 diabetes mellitus, dramatically illustrated by androgen deprivation in men with prostate carcinoma. Lower total testosterone and sex hormone-binding globulin (SHBG) predict a higher incidence of the metabolic syndrome. There is evidence that hypotestosteronemia should be an element in the definition of the metabolic syndrome since low levels of testosterone are associated with or predict the development of the metabolic syndrome and of diabetes mellitus. Administration of testosterone to hypogonadal men reverses part of the unfavorable risk profile for the development of diabetes and atherosclerosis. So far, studies on the effects of normalization of testosterone in hypogonadal men on glucose homeostasis are limited, but convincing, and if diabetes mellitus is viewed in the context of the metabolic syndrome, the present results of testosterone treatment are very encouraging. Arq Bras Endocrinol Metab. 2009;53(8):901-7 Keywords Testosterone; metabolic syndrome; cardiovascular risk factors; insulin sensitivity; diabetes mellitus resumo Ao longo das últimas três décadas, tornou-se evidente que a testosterona desempenha um papel significativo na homeostase da glicose no metabolismo lipídico. A síndrome metabólica é um agrupamento de fatores de risco que predispõem ao diabetes melito tipo 2, aterosclerose e morbidade e mortalidade cardiovasculares. Os principais componentes da síndrome são: obesidade visceral, resistência insulínica, intolerância à glicose, hipertensão arterial e dislipidemia (triglicerídeos elevados, baixos níveis de HDL-colesterol), além de um estado pró-inflamatório e trombogênico. Estudos epidemiológicos transversais relataram uma correlação direta entre testosterona plasmática e sensibilidade à insulina, e níveis baixos de testosterona se associam com risco aumentado de diabetes tipo 2, ilustrado dramaticamente pela privação androgênica em homens com carcinoma de próstata. Baixos níveis de testosterona total e globulina transportadora de hormônios sexuais (SHBG) predizem maior incidência de síndrome metabólica. Existem agora evidências de que a hipotestosteronemia deveria ser um elemento na definição da síndro-me metabólica, uma vez que baixos níveis de testosterona estão associados ou predizem o desenvolvimento de síndrome metabólica e de...

Evaluation of Serum Testosterone Level in Men with Type 2 Diabetes Mellitus

“…However, the present study demonstrated negative correlation between the serum testosterone and HbA1c levels, possibly indicating reduction in HbA1c levels in diabetic patients with administration of testosterone. Low levels of testosterone has been reported to be associated with type II diabetes and insulin resistance along with inappropriately low levels of hematocrit values [19,22,23] . The decrease in hormone level is slow and constant over all decades and starts early in life, probably after the third or fourth decade.…”

“…Studies have reported inverse relationship between blood sugar and testosterone [24] . The treatment of hypogonadism by means of testosterone replacement therapy often leads to reduction in blood sugar level along with reduction in the resistance to insulin among the diabetic patients [22,25] .…”

Distúrbios metabólicos em doenças infecciosas emergentes e negligenciadas

“…Cirurgias para excisão do tecido adiposo ou lipossucção das áreas com acúmulo anormal de gordura têm sido realizadas em pacientes com importante "corcova de búfalo"; no entanto, a recorrência do acúmulo pode ocorrer (24). A reposição de testosterona em homens hipogoná-dicos parece resultar em melhora da lipo-hipertrofia visceral, menor risco para desenvolvimento de DM2 e SM (25,26). No entanto, o papel da administração de testosterona sobre o risco cardiovascular permanece incerto (27).…”

Vitamin D and biomarkers of sex steroid hormones are non-linearly and inversely related to all-cause mortality: results from NHANES III

“…Besides the well-known function of vitamin D in promoting in vitro bone mineralization and prevention of osteoporosis and bone fracture through intestinal calcium absorption [3,4], mounting evidence has linked hypovitaminosis D to musculoskeletal diseases [5], cancer [6], autoimmune diseases, type 2 diabetes, cardiovascular disease [6,7] and all-cause mortality [5]. The main source of vitamin D is cholecalciferol (vitamin D3), synthesized in the skin by ultraviolet radiation [2]; pro-vitamin D3 (7-dehydrocholesterol) is converted to pre-vitamin D3, which isomerizes into cholecalciferol and is later converted to calcitriol (1,25(OH) 2 D 3 ) through a two-step enzymatic pathway involving liver 25-hydroxylase (CYP2R1) andkidney 1-α-hydroxylase (CYP27B1) [2,8,9]. Vitamin D status is assessed by measuring 25(OH)D 3 [8].…”

“…Similarly, when administered at high doses, exogenous testosterone has been correlated with sudden cardiac death and liver disease [16,23,24]. However, perceived health benefits of low dose exogenous testosterone may have contributed to its widespread use without approved change in indication [16,22,[25][26][27].…”