Prevalence and risk factors of diabetes in patients with Klinefelter syndrome: a longitudinal observational study.

OBJECTIVE: To evaluate the prevalence and risk factors of diabetes in patients with Klinefelter syndrome. DESIGN: Retrospective longitudinal study. SETTING: Medical college hospital. PATIENT(S): Klinefelter group (n = 39) and idiopathic hypogonadotropic hypogonadism (IHH) group (n = 40). INTERVENTION(S): Testosterone replacement therapy. MAIN OUTCOME MEASURE(S): The metabolic parameters, lipid profiles, and sex hormones were compared before and after T replacement therapy. The median duration of follow-up was 4 years in the Klinefelter group and 5.2 years in the IHH group. RESULT(S): The prevalence of diabetes was 20.5% (8 of 39) in the Klinefelter group and 5% in the IHH group. In the Klinefelter group, the incidence of diabetes was 12.5% in patients with 47,XXY karyotype and 57.1% in patients with other atypical karyotypes, such as 46XY/47XXY chimera. In the Klinefelter group, the average (± SD) age at diagnosis of diabetes was 27.1 ± 4.5 years. Four subjects had diabetes before T therapy, and their blood glucose did not improve after T replacement. One patient had a history of acute pancreatitis. Two other subjects had very high triglyceride levels. During the follow-up, body weight increased more in Klinefelter patients than in IHH patients. CONCLUSION(S): The prevalence of diabetes is higher in Klinefelter patients than in IHH patients, possibly owing to abnormal karyotypes. Other risk factors, such as low T level, high body weight, acute pancreatitis, and high triglyceride levels, may also contribute to the development of diabetes.

Clinical values of single or repeated triptorelin stimulating test in the differential diagnosis between idiopathic hypogonadotropic hypogonadism and constitutional delayed puberty / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the values of single or repeated luteinizing hormone (LH) releasing hormone analogue (triptorelin) stimulating test in the differential diagnosis between idiopathic hypogonadotropic hypogonadism (IHH) and constitutional delayed puberty (CDP).</p><p><b>METHODS</b>Male patients (n = 133) without puberty onset after the age of 14 were recruited for triptorelin stimulating test and were followed up for 24 - 48 months until the diagnosis were confirmed: 86 were IHH and the other 47 were CDP. Repeated triptorelin stimulating tests were conducted in 9 IHH patients and 13 CDP patients one year after the first stimulating tests with an attempt to evaluate the dynamic change of hypothalamus-pituitary-testis axis function. The relationship between the final diagnosis and the peak LH value (LH(max)), and the changes of repeated LH(max) were investigated.</p><p><b>RESULTS</b>In the single triptorelin stimulating test, LH(max) was (1.9 +/- 1.2) U/L in IHH group, which was significantly lower than that in CDP group [(13.7 +/- 8.3) U/L] (P < 0.01); 75 IHH patients (87.2%) had a LH(max) lower than 4 U/L, while only 2 CDP patients (4.3%) had a LH(max) lower than 4 U/L. When LH(max) < 4U/L was used as a criteria for the diagnosis of IHH, the single triptorelin stimulating test had a sensitivity of 87.2%, a specificity of 95.7%, and a positive predictive value of 97.4%. The repeated triptorelin stimulating tests performed one year later showed that the LH(max) in the 9 IHH patients increased from (4.7 +/- 2.5) U/L to (5.1 +/- 3.3) U/L (P = 0.78), while that in the 13 CDP patients increased from (10.7 +/- 3.3) U/L to (24.5 +/- 5.7) U/L (P < 0.05).</p><p><b>CONCLUSIONS</b>A single triptorelin stimulating test is highly effective in differentiating IHH from CDP. For some patients without definitive diagnosis, a repeated triptorelin stimulating test performed one year later may provide more valuable information on the dynamic change of the hypothalamus-pituitary-testis axis function.</p>

Testosterone replacement therapy improves insulin sensitivity and decreases high sensitivity C-reactive protein levels in hypogonadotropic hypogonadal young male patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Many clinical studies suggest the inverse relationship between testosterone levels and insulin sensitivity in men, however the causative relationship of these two events is still not determined. The purpose of this study was to investigate the effects of testosterone replacement therapy (TRT) on insulin sensitivity, body composition, serum lipid profiles and high sensitivity C-reactive protein (hsCRP) in hypogonadotropic hypogonadal (HH) puberty undeveloped male patients.</p><p><b>METHODS</b>In this prospectively designed study, we compared homeostasis model assessment of insulin resistance (HOMA-IR), insulin areas under the curves (AUC) of 3-hour oral glucose tolerance test (OGTT) and other metabolic parameters between 26 HH patients and 26 healthy men. The patients' HOMA-IR, insulin AUC, body composition, lipid profiles, hsCRP and other parameters were compared before and after nine-month TRT.</p><p><b>RESULTS</b>The average levels of total testosterone (TT) in HH and healthy group were (0.9 +/- 0.6) nmol/L and (18.8 +/- 3.4) nmol/L, respectively. HOMA-IR in HH group was significantly higher than the healthy group (5.14 +/- 5.16 vs 2.00 +/- 1.38, P < 0.005). Insulin AUC in 3-hour OGTT in HH group was significantly higher than the healthy group (698.6 +/- 414.7 vs 414.2 +/- 267.5, P < 0.01). Fasting glucose level in HH group was significantly higher than control group ((5.1 +/- 0.6) mmol/L vs (4.7 +/- 0.3) mmol/l, P < 0.005). Height, weight and grasp strength of the patients were significantly increased after 9-month TRT. Significant reductions in HOMA-IR (from 5.14 +/- 5.16 to 2.97 +/- 2.16, P < 0.01), insulin AUC (from 698.6 +/- 414.7 to 511.7 +/- 253.9, P < 0.01) and hsCRP (from (1.49 +/- 1.18) mg/L to (0.70 +/- 0.56) mg/L, P < 0.05) were found after TRT. Serum total cholesterol, LDL-C, HDL-C and triglyceride were all decreased, albeit with no significant difference compared to the level prior to TRT.</p><p><b>CONCLUSIONS</b>HOMA-IR, insulin AUC and fasting glucose level in HH young male patients were significantly higher than those of the control group, which suggests that low level of testosterone in male adolescents might be a risk factor for insulin resistance. TRT can significantly improve patients' insulin sensitivity and suppress serum hsCRP, which in return suggests that TRT may prevent the HH patients from developing diabetes mellitus and cardiovascular diseases (CVD) in future.</p>