Erectile dysfunction (ED) is associated with metabolic and endocrine diseases including obesity, metabolic syndrome (MS), and type 2 diabetes mellitus (DM2). Insulin resistance (IR), present in patients with obesity, MS, and DM2, causes disturbances in the signaling pathways required for nitric oxide production, with subsequent endothelial dysfunction. In addition, IR appears to alter testosterone production. We evaluated in eugonadal patients with ED: 1) the presence of obesity and IR, 2) testosterone levels and their association with obesity and IR, and 3) the degree of ED according to the presence of IR. In a prospective study, 78 eugonadal patients with ED (group P) were recruited and compared with 17 men without ED as a control group (group C). Erectile function was evaluated according to the International Index of Erectile Function 5 (IIEF-5). IR was measured by homeostasis model assessment (HOMA). IR was defined as HOMA of 3 or greater. Patients with ED had significantly higher body mass index (BMI), waist circumference (WC), HOMA values, and prevalence of IR when compared with group C. Total (TT) and bioavailable testosterone (BT) levels were lower in group P compared with group C. There was a significant negative correlation between HOMA and IIEF-5, HOMA and TT, WC and IIEF-5, WC and TT, and WC and BT. Group P patients with IR had higher WCs and lower IIEF-5 scores when compared with patients in group P without IR. In conclusion, patients with ED showed a higher BMI, WC, and HOMA and lower levels of TT and BT. There is a negative correlation between erectile function and IR and abdominal obesity. The TT levels are lower in patients with increased BMI, WC, and IR. However, a negative correlation was shown only between BT (biologically active fraction) and abdominal obesity.

Prolactinomas in men are usually macroprolactinomas and other investigators have attributed bigger size of tumors in men to delay in diagnosis. A retrospective study of 71 macroadenomas (42 men) was carried out. Parameters studied were age, signs and symptoms at presentation, time of onset of symptoms, basal prolactin, estradiol, and total testosterone levels, tumor size and Ki 67 expression in tumor tissue. Male patients were older. Visual defects were significantly more prevalent in men. Hardy 4 stage tumors were found only in men. We found no significant correlation between tumor size and the patients age nor between tumor size and the onset of symptoms. Whereas basal E2 levels (21.2+/-12.9 vs. 33.3+/-43.3 pg/ml, p=n.s.) were very similar in male and female patients, testosterone levels were significantly higher in men (0.6+/-0.5 vs. 1.8+/-1.2 ng/ml, p=0.02). The rate of cell proliferation represented by Ki 67 was significantly higher in tumors in men (3.5+/-1.2 vs. 1.5+/-0.5%, p=0.0001). This is the first study focused in macroprolactinomas that shows that they are clinically and biologically more aggressive in men. Hypogonadism in men could appear later in the progression of prolactinomas and this might explain why men were older at the time of diagnosis. Furthermore, testosterone could be a source for E2 in situ aromatization giving male tumors an advantage in cell proliferation.

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The conversion of differentiated cells into insulin-producing cells is a promising approach for the autologous replacement of pancreatic cells in patients with type 1 diabetes (T1D). At present, cellular reprogramming strategies encompass ethical problems, epigenetic failure or teratoma formation, which has prompted the development of new approaches. Here, we report a novel technique for the conversion of skin fibroblasts from T1D patients into insulin-expressing clusters using only drug-based induction. Our results demonstrate that skin fibroblasts from diabetic patients have pancreatic differentiation capacities and avoid the necessity of using transgenic strategies, stem cell sources or global demethylation steps. These findings open new possibilities for studying diabetes mechanisms, drug screenings and ultimately autologous transgenic-free regenerative medicine therapies in patients with T1D.

We previously showed that children and adolescent offspring of patients with essential hypertension have an increased proximal renal sodium reabsorption as measured by lithium fractional excretion. Insulin has been shown to have antinatriuretic properties and to be increased (hyperinsulinemia) in essential hypertension. The aim of this study was to evaluate the role of insulin on the increased proximal renal sodium reabsorption previously reported. Lithium and sodium fractional excretions were measured 3 hours before and 3 hours after an intravenous glucose tolerance test in 20 normotensive adolescents with a family history of essential hypertension (F+, 14.8 +/- 0.5 years) and 10 normotensive control subjects without a family history of hypertension (F-, 15.2 +/- 0.9 years). Results are mean +/- SEM. Lithium fractional excretion before glucose loading was 16.1 +/- 1.8% in F+ versus 23.5 +/- 2.0% in F- (P < .02) and after glucose loading was 14.7 +/- 1.3% in F+ versus 20.9 +/- 1.7% in F- (P = NS). Lithium fractional excretion did not change after intravenous glucose loading in either group. The insulin area under the curve was 2815 +/- 499 in F+ versus 2290 +/- 418 microU/mL per hour in F- (P = NS). There was no correlation between lithium fractional excretion and insulin area under the curve. Fractional excretion of sodium before glucose loading was 0.99 +/- 0.1% in F+ versus 0.99 +/- 0.1% in F- (P = NS) and after glucose loading was 0.77 +/- 0.1 in F+ versus 0.85 + 0.1% in F- (P < .01 versus values before loading in both groups).(ABSTRACT TRUNCATED AT 250 WORDS)