OBJECTIVE -We have previously shown that hypogonadotrophic hypogonadism is common in middle-aged patients with type 2, but not with type 1, diabetes. We have now investigated the total and free testosterone concentrations in young (aged 18 -35 years) type 1 and type 2 diabetic patients.RESEARCH DESIGN AND METHODS -In this study carried out in a tertiary referral center, serum concentrations of total and free testosterone were measured in 38 type 1 diabetic (mean age 26.45 Ϯ 0.89 years) and 24 type 2 diabetic (mean age 27.87 Ϯ 0.97 years) subjects. The mean BMI of type 1 and type 2 diabetic patients was 27.41 Ϯ 1.18 and 38.55 Ϯ 2.04 kg/m 2 , respectively (P Ͻ 0.001).RESULTS -The mean total testosterone concentration of type 1 and type 2 diabetic patients was 22.89 Ϯ 1.23 and 11.14 Ϯ 0.99 nmol/l, respectively (P Ͻ 0.001). The mean free testosterone concentration of type 1 and type 2 diabetic patients was 0.489 Ϯ 0.030 and 0.296 Ϯ 0.022 nmol/l, respectively (P Ͻ 0.001). Eight of 24 (33%) type 2 diabetic patients had subnormal free testosterone concentrations (Ͻ0.225 nmol/l). Using an age-based reference range, 14 of 24 (58%) type 2 diabetic patients had low free testosterone concentrations (Ͻ0.278 nmol/l). Three of 38 (8%) type 1 diabetic patients had free testosterone concentrations below the lower limit of normal (P ϭ 0.02 when compared with type 2 diabetes). Luteinizing hormone (LH) and folliclestimulating hormone (FSH) concentrations in type 2 diabetic patients with low free testosterone concentrations were in the normal range and were similar to those in type 1 diabetic patients.CONCLUSIONS -Young type 2 diabetic patients have significantly lower plasma concentrations of total and free testosterone and inappropriately low LH and FSH concentrations with a very high prevalence of hypogonadotrophic hypogonadism, when compared with type 1 diabetic patients of a comparable age. The potential implications for their sexual and reproductive function during prime reproductive years are profound. Diabetes Care 31

It has recently been demonstrated that > or = one-third of men with type 2 diabetes mellitus have low testosterone concentrations associated with inappropriately low luteinizing hormone and follicle-stimulating hormone concentrations. Hypogonadotropic hypogonadism in men with type 2 diabetes is associated with obesity but not duration of diabetes, elevated glycosylated hemoglobin, or the presence of microvascular complications of diabetes. Recent data show that hypogonadotropic hypogonadism is also observed frequently in nondiabetics with the metabolic syndrome or obesity, but it is not associated with type 1 diabetes. Low testosterone concentrations in men with type 2 diabetes have also been related to a higher C-reactive protein concentrations, lower hematocrit, increased total and regional adiposity, lower bone mineral density, and erectile dysfunction. This article discusses the pathophysiology of hypogonadotropic hypogonadism in men with type 2 diabetes and its signs and symptoms. Clinical trials are required to determine whether testosterone replacement therapy alleviates insulin resistance, inflammation, and symptoms related to sexual dysfunction care.

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