Impact of testosterone treatment on circulating irisin in men with late-onset hypogonadism and metabolic syndrome.

OBJECTIVES: The beneficial effects of testosterone replacement therapy (TRT) in men with late-onset hypogonadism (LOH) on the body composition and metabolic outcomes are well-established. A potential explanation might lie in the hormones, secreted from skeletal muscles, named "myokines". The aim of this study was to evaluate the effects of TRT on the levels of serum irisin in subjects with LOH. STUDY DESIGN: A total 40 men with metabolic syndrome (MS) and LOH (measured serum testosterone concentration < 12 nmol/l). TRT with Testosterone Undecanoate (Nebido™) was performed at baseline and at week 6. Irisin serum concentration was determined at baseline and at week 18 by means of ELISA. RESULTS: Circulating irisin was positively associated with serum testosterone (r = 0.283, p < 0.05). TRT has led to a statistically significant rise in circulating serum irisin levels (7.12 ± 0.76 mcg/ml versus 7.76 ± 0.75 mcg/ml; paired-samples t-test p < 0.001). ROC-analyses determined irisin to be predictive of treatment response (AUC = 0.741, p = 0.014). CONCLUSIONS: Irisin is positively associated with serum testosterone in a population of men with MS and LOH. TRT in these subjects has led to a significant improvement in associated clinical symptoms as well as to a significant rise in serum irisin levels.

Comparison of the first intake of vardenafil and tadalafil in patients with diabetic neuropathy and diabetic erectile dysfunction.

INTRODUCTION: Diabetic neuropathy (DN) is one of the key pathogenetic factors for diabetic erectile dysfunction (DED). AIM: The aim of this study was to compare the effect of the first intake of tadalafil and vardenafil in men with DN and DED. METHODS: In this comparative prospective randomized study were included 49 phosphodiesterase type 5 (PDE5) inhibitor-naïve men (80% type 2 diabetes). DN was assessed by a modified Neuropathy Disability Score (NDS ≥ 3). Each patient received two pills containing 20 mg of either tadalafil (N = 24) or vardenafil (N = 25). They had to be taken after discharge from the hospital at a time interval of at least 3 and 1 day, respectively, and 1 to 6 hours before the intended sexual activity. MAIN OUTCOME MEASURES: The treatment efficacy was evaluated by the changes in the erectile domain of International Index of Erectile Function (IIEF), Sexual Encounter Profile Question 2 (SEP2) and 3 (SEP3), and the Global Assessment Question (GAQ). RESULTS: For all patients, IIEF increased from 12.6 ± 6.8 to 19.6 ± 9.0 (P < 0.001) points after treatment. The number of men with positive answers on SEP2 increased from 27 (55.1%) to 38 (77.6%), on SEP3 from 7 (14.3%) to 30 (61.2%). Thirty-one (63.3%) evaluated the effect of the drugs as beneficial (GAQ). No significant efficacy difference between tadalafil and vardenafil was observed. The initial indicators for DED, as well as the treatment efficacy, correlated highly significant with NDS. Both PDE5 inhibitors were well tolerated. Before entering the study, 28% of men have seen a physician, but only 57.1% of them have started treatment. CONCLUSIONS: In this study design, tadalafil and vardenafil are equally effective with the first intake in patients with diabetes and DN. Baseline indicators of erectile dysfunction and the ones verifying the effect of the treatment show significant correlation with the DN indicator-NDS. Tadalafil and vardenafil are well tolerated with no serious side effects.

Prevalence of Positive Diabetes-Associated Autoantibodies among Type 2 Diabetes and Related Metabolic and Inflammatory Differences in a Sample of the Bulgarian Population.

BACKGROUND: The study aimed to estimate the prevalence of unrecognized cases with positive autoantibodies among type 2 diabetes (T2D) in a sample of the Bulgarian population and to compare some metabolic and inflammatory markers to those of patients having negative autoantibodies and subjects with latent autoimmune diabetes (LADA). METHODS: Patients with T2D, patients with LADA, and control participants were enrolled. Antiglutamic acid decarboxylase, anti-insulinoma-associated 2, and antizinc transporter 8 autoantibodies were assayed through ELISA. C-reactive protein and interleukin 6 (IL-6) and tumor necrosis factor alpha were assessed. RESULTS: Ten percent of patients with T2D had positive autoantibodies. They had lower body mass index (p = 0.014), worse glycemic control (HbA1c, p = 0.033), and better HDL cholesterol (p = 0.026) than those in negative autoantibodies cases. Compared to LADA, glycemia and anthropometric data did not differ significantly but metabolic syndrome was more prevalent among newly found cases with positive autoantibodies (p = 0.046). Their level of inflammatory markers was similar to that of patients having negative autoantibodies (p > 0.05), but IL-6 was higher when compared to LADA (p = 0.002). CONCLUSION: Prevalence of patients having positive autoantibodies within T2D in the analyzed sample of the Bulgarian population was 10%. They shared common metabolic features with subjects with LADA, but inflammatory phenotype was closer to that of T2D.

Markers of visceral obesity and cardiovascular risk in patients with polycystic ovarian syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of most common endocrine disturbances in women of reproductive age. Besides its well known effects on reproductive health, it is also linked to increased cardiovascular risk in later life. OBJECTIVES: The aim of this study was to investigate the link between some anthropometric indices of visceral obesity and surrogate markers of cardiovascular risk according to the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society consensus. STUDY DESIGN: The study included 36 normal weight (BMI<25 kg/m²) and 19 obese PCOS subjects (BMI ≥ 30 kg/m²), aged between 18 and 40 years. Different anthropometric markers were compared as predictors for an adverse cardiometabolic profile and composite cardiovascular risk factors as defined by the AE-PCOS consensus. RESULTS: Both waist-to-stature ratio (WSR) (area under the curve 0.75, p=0.002) and waist circumference (WC) (area under the curve 0.77, p=0.001) but not waist-to-hip ratio (WHR) (area under the curve 0.62, p=0.143) were shown to be good markers of increased cardiovascular risk, insulin resistance and dislipidemia in PCOS patients. The cut-off point for WSR of 0.50 is useful and the cut-off of 80 cm for WC is more appropriate than 88 cm in detecting cardiovascular risk in PCOS patients. Androgen levels and immunoreactive insulin during an oral glucose tolerance test had lower power for predicting increased cardiovascular risk than WC and WSR. CONCLUSION: The study indicates that WSR and WC are better associated with composite cardiovascular risk factors as defined by the AE-PCOS consensus than WHR, and that the commonly used cut-off for WSR of 0.5 is useful for detecting cardiovascular risk in PCOS patients.

Earlier development of diabetic neuropathy in men than in women with type 2 diabetes mellitus.

BACKGROUND: Data about the prevalence of diabetic neuropathy (DN) differ substantially, depending on the population and diagnostic methods. Sex-specific differences in DN are rarely discussed. OBJECTIVES: The aims of the present study were to assess the prevalence of, and analyze sex differences in, DN in a hospital population with type 2 diabetes mellitus (T2DM) over a period of 18 years. METHODS: In this retrospective study performed at a university hospital endocrinology clinic in Sofia, patient clinical records from 1990-2007 were examined. Patients were included in the database only at their first admission. RESULTS: Data from 1705 patients with T2DM were analyzed (961 women, 744 men; mean [SD] age, 60.0 [11.9] years; diabetes duration, 9.9 [8.4] years; glycosylated hemoglobin, 9.0% [2.2%]; and body mass index, 29.4 [6.0] kg/m²). Obesity (46.3% vs 32.0%; P < 0.001), hypertension (86.7% vs 77.8%; P < 0.001), and dyslipidemia (61.2% vs 55.0%; P < 0.05) were significantly more common in women than in men, respectively. The prevalence of DN was 78.8%, with no significant sex differences. However, prevalence differed with time, corresponding to the frequency of application of electrophysiologic (electromyograms) or semiquantitative instrumental diagnostic methods. In men, the median (25th-75th percentiles) interval between diagnosis of T2DM and diagnosis of DN was 6 (1-12) years; in women, the interval was 8 (4-13) years (P < 0.01). CONCLUSIONS: In this study of Bulgarian patients with T2DM, women were at higher macrovascular risk than were men. A high prevalence of DN was observed among these patients. The period from the diagnosis of T2DM to DN was shorter in men than in women-this necessitates earlier screening and therapeutic intervention for DN in men. Reasons for this sex difference may include differences in lifestyle and the testosterone deficiency that is common in men with diabetes, leading to a more pronounced deficit of neurosteroids.