Malipatil Nagaraj S, Yadegarfar Ghasem, Lunt Mark, Keevil Brian, Siddals Kirk, Livingston Mark, Roberts Siriol, Narayanan Prakash, Rutter Martin, Gibson J Martin, Donn Rachelle, Hackett Geoff, Jones T Hugh, Heald Adrian
The School of Medicine and Manchester Academic Health Sciences Centre University of Manchester Manchester UK.
Department of Diabetes and Endocrinology Salford Royal Hospital Salford UK.
Endocrinol Diabetes Metab. 2019 Mar 27;2(3):e00064. doi: 10.1002/edm2.64. eCollection 2019 Jul.
Hypogonadism is more prevalent in men with type 2 diabetes (T2DM) (25%-40%) than in men without T2DM. Hypogonadism has been associated with poorer glycaemic outcomes and increased cardiovascular morbidity/mortality. We report a 14-year follow-up study to evaluate the influence of baseline testosterone level on T2DM outcomes.
A total of 550 men with T2DM underwent baseline total testosterone and dihydrotestosterone measurement by tandem mass spectrometry. Mean age of the men was 59.7 ± 12 (mean ± SD) years. Sex hormone-binding globulin (SHBG) was measured and free testosterone estimated. Patients were followed up between 2002 and 2016. Mean follow-up period was 12.2 ± 4 years using the Salford (UK) Integrated Health Records system.
Mean baseline total testosterone was 13.7 ± 5.8 nmol/L, and mean free testosterone was 245.7 ± 88.0 pmol/L. Mean for low total testosterone (<10 nmol/L) was 7.6 ± 2.0 nmol/L (n = 154) and 142 men had a free testosterone <190 pmol/L. During the 14-year duration follow-up, 22% of men experienced a myocardial infarction, 18% experienced a stroke, 11% developed angina, 14% underwent coronary revascularization. About 38% of the men initially recruited died. A lower total testosterone was associated with a higher body mass index (kg/m) at follow-up: regression coefficient -0.30 (95% CI -0.445 to -0.157), = 0.0001. The mortality rate was higher in patients with lower total testosterone compared to normal baseline total testosterone (5.0% vs 2.8% per year, < 0.0001). A similar phenomenon was seen for dihydrotestosterone (4.3% vs 2.9% per year, = 0.002) for normal vs low dihydrotestosterone) and for lower SHBG. Over the whole follow-up period 36.1% (143/396), men with normal baseline testosterone died vs 55.8% (86/154) of hypogonadal men at baseline. In Cox regression, the age-adjusted hazard ratio (HR) for higher mortality associated with low total testosterone was 1.54 (95% CI: 1.2-2.0, < 0.002), corresponding to a 3.2 year reduced life expectancy for hypogonadal T2DM men.
Low testosterone and dihydrotestosterone levels are associated with higher all-cause mortality in T2DM men. Hypogonadal men with T2DM should be considered as very high risk for cardiovascular events/death.
性腺功能减退在2型糖尿病（T2DM）男性中（25%-40%）比在无T2DM的男性中更为普遍。性腺功能减退与较差的血糖结果以及心血管发病率/死亡率增加有关。我们报告一项为期14年的随访研究，以评估基线睾酮水平对T2DM结局的影响。
共有550名T2DM男性通过串联质谱法进行了基线总睾酮和双氢睾酮测量。这些男性的平均年龄为59.7±12（平均±标准差）岁。测量了性激素结合球蛋白（SHBG）并估算了游离睾酮。患者在2002年至2016年期间接受随访。使用索尔福德（英国）综合健康记录系统，平均随访期为12.2±4年。
平均基线总睾酮为13.7±5.8nmol/L，平均游离睾酮为245.7±88.0pmol/L。总睾酮低（<10nmol/L）者的平均值为7.6±2.0nmol/L（n = 154），142名男性的游离睾酮<190pmol/L。在14年的随访期间，22%的男性发生心肌梗死，18%的男性发生中风，11%的男性患心绞痛，14%的男性接受了冠状动脉血运重建。最初招募的男性中约38%死亡。随访时较低的总睾酮与较高的体重指数（kg/m）相关：回归系数-0.30（95%CI -0.445至-0.157），P = 0.0001。与正常基线总睾酮相比，总睾酮较低的患者死亡率更高（每年5.0%对2.8%，P<0.0001）。双氢睾酮（正常与低双氢睾酮相比，每年4.3%对2.9%，P = 0.002）和较低的SHBG也出现类似现象。在整个随访期间，基线睾酮正常的男性中有36.1%（143/396）死亡，而基线性腺功能减退的男性中有55.8%（86/154）死亡。在Cox回归中，与低总睾酮相关的较高死亡率的年龄调整风险比（HR）为1.54（95%CI：1.2-2.0，P<0.002），这相当于性腺功能减退的T2DM男性预期寿命缩短3.2年。
低睾酮和双氢睾酮水平与T2DM男性的全因死亡率较高相关。患有T2DM的性腺功能减退男性应被视为心血管事件/死亡的极高风险人群。
