Erectile dysfunction and its management in patients with diabetes mellitus

Diabetes can be described as a syndrome of multiple closely related conditions induced by a chronic state of hyperglycaemia resulting from defective insulin secretion, insulin action or both. Chronic complications associated with diabetes (including neuropathy, vascular disease, nephropathy and retinopathy) are common, and of these, erectile dysfunction (ED) deserves special attention. ED and its correlation with cardiovascular disease require careful evaluation and appropriate treatment. PDE5 inhibitors (PDE5is) are an important tool for the treatment of ED, with new drugs coming onto the market since the late 90s. This review offers an overview of PDE5is and their use in treating ED in diabetes. We underline the differences between different types of PDE5i, focusing on available doses, duration of action, T ½, side effects and selectivity profiles in relation to patients with diabetes. We also discuss the link between diabetes and ED in presence of various associated cofactors (obesity, hypertension and its pharmacological treatments, atherosclerosis, hyperhomocysteinaemia, neuropathy, nephropathy, hypogonadism and depression). Finally a number of past and ongoing clinical trials on the use of PDE5is in patients with diabetes are presented to offer an overview of the appropriate treatment of ED in this condition

Diabetes and erectile dysfunction. The relationships with health literacy, treatment adherence, unrealistic optimism, and glycaemic control

Purpose: The aim of this study was to evaluate the relationships between health literacy, unrealistic optimism, and adherence to glycometabolic disease management related to erectile dysfunction (ED) in male patients with type 2 diabetes (T2D) or preDM.Materials and Methods: This prospective observational study enroled 167 consecutive patients with T2D and ED. All patients underwent the following examinations: (a) medical history collection; (b) Body Mass Index (BMI) determination; (c) hormonal and biochemical assessment; (d) duration of T2D, complications and treatment; (e) International Index of Erectile Function-5 questionnaire to assess ED; and (f) validated questionnaire to evaluate health literacy, unrealistic optimism, and treatment adherence.Results: Overall, mean age was 62.5 +/- 9.4 years (range: 20-75) and mean BMI was 28.4 +/- 4.8 kg/m(2) (range: 18.4-46.6). The mean IIEF-5 score was 15.4 +/- 5.2 (range: 5-25). The majority of patients showed high health literacy. However, low health literacy was found in patients with higher IIEF-5 scores and high BMI. Unrealistic optimism was low in most patients. Higher adherence to treatment was found in patients who reported regular physical activity, who followed a diet, and in patients with a family history of T2D. Regarding anti-diabetic treatment, patients treated with insulin showed higher health literacy than patients not treated with other medications, whereas higher adherence was found in patients using SGLT2-i.Conclusions: This study highlighted the close relationship between metabolic compensation, BMI, ED, and psychological attitudes, including health literacy and unrealistic optimism

Diabetes and erectile dysfunction: The relationships with health literacy, treatment adherence, unrealistic optimism, and glycaemic control

Purpose: The aim of this study was to evaluate the relationships between health literacy, unrealistic optimism, and adherence to glycometabolic disease management related to erectile dysfunction (ED) in male patients with type 2 diabetes (T2D) or preDM. Materials and methods: This prospective observational study enroled 167 consecutive patients with T2D and ED. All patients underwent the following examinations: (a) medical history collection; (b) Body Mass Index (BMI) determination; (c) hormonal and biochemical assessment; (d) duration of T2D, complications and treatment; (e) International Index of Erectile Function-5 questionnaire to assess ED; and (f) validated questionnaire to evaluate health literacy, unrealistic optimism, and treatment adherence. Results: Overall, mean age was 62.5 ± 9.4 years (range: 20-75) and mean BMI was 28.4 ± 4.8 kg/m2 (range: 18.4-46.6). The mean IIEF-5 score was 15.4 ± 5.2 (range: 5-25). The majority of patients showed high health literacy. However, low health literacy was found in patients with higher IIEF-5 scores and high BMI. Unrealistic optimism was low in most patients. Higher adherence to treatment was found in patients who reported regular physical activity, who followed a diet, and in patients with a family history of T2D. Regarding anti-diabetic treatment, patients treated with insulin showed higher health literacy than patients not treated with other medications, whereas higher adherence was found in patients using SGLT2-i. Conclusions: This study highlighted the close relationship between metabolic compensation, BMI, ED, and psychological attitudes, including health literacy and unrealistic optimism

Women with type 1 diabetes gain more weight during pregnancy compared to age-matched healthy women despite a healthier diet. a prospective case-control observational study

Purpose: Women with type 1 diabetes mellitus (T1D), especially those with suboptimal glucose control, have 3-4 greater chances of having babies with birth defects compared to healthy women. We aimed to evaluate glucose control and insulin regimen modifications during the pregnancy of women with T1D, comparing the offspring's weight and the mother's weight change and diet with those of non-diabetic, normal-weight pregnant women. Methods: Women with T1D and age-matched healthy women controls (CTR) were consecutively enrolled among pregnant women with normal weight visiting our center. All patients underwent physical examination and diabetes and nutritional counseling, and completed lifestyle and food intake questionnaires. Results: A total of 44 women with T1D and 34 healthy controls were enrolled. Women with T1D increased their insulin regimen during pregnancy, going from baseline 0.9 ± 0.3 IU/kg to 1.1 ± 0.4 IU/kg (p = 0.009), with a concomitant significant reduction in HbA1c (p = 0.009). Over 50% of T1D women were on a diet compared to < 20% of healthy women (p < 0.001). Women with T1D reported higher consumption of complex carbohydrates, milk, dairy foods, eggs, fruits, and vegetables, while 20% of healthy women never or rarely consumed them. Despite a better diet, women with T1D gained more weight (p = 0.044) and gave birth to babies with higher mean birth weight (p = 0.043), likely due to the daily increase in insulin regimen. Conclusion: A balance between achieving metabolic control and avoiding weight gain is crucial in the management of pregnant women with T1D, who should be encouraged to further improve lifestyle and eating habits with the aim of limiting upward insulin titration adjustments to a minimum

The importance of evaluating body composition with dual-energy x ray absorptiometry in men: the structure of the aging mens's bones (STRAMBO) study

In recent years, many study groups focused their attention on men's health, such as the Osteoporotic Fractures in Older Men Study (MrOS) (1), the European Male Ageing Study (EMAS) (2), the Hypogonadism in Males (HIM) Study (3), and the Structure of the Aging Men's Bones (STRAMBO) Study (4). Analysis of large cohorts of men allows investigation of various pathophysiological and clinical features of the major diseases, and is even useful for new research and discoveries. This is the case of the article “Age-Related Changes in Fat Mass and Distribution in Men—the Cross-sectional STRAMBO Study,” in which the authors refined their knowledge about fat mass in men, trying to fill a little the lack of knowledge about obesity and its features

Glicometabolic effects on bone metabolism: from new and different pathways to new diagnostic and therapeutic aspects

Background Diabetes and bone fragility are rapidly growing diseases, as osteoporosis could be defined as a complication of type 2 diabetes (T2D) (Epstein et al. 2016). Aging of populations worldwide will be responsible for an increased risk in the incidence of these two diseases. There is a pathophysiological link between the high fracture incidence and diabetes if compared with the non-diabetic state, has recently been recognized but not totally clear and understood. In fact, several mechanisms are involved in bone homeostasis by impairing the function of bone cells as osteocytes, as osteoblasts and osteoclasts, and/or modifying the structural characteristics of the bone tissue (Jiang and Xia 2018; Epstein et al. 2016). Furthermore, as osteoblasts and adipocytes both derived from the mesenchymal stem cell (MSC), their physiological differentiation could be modulated by several interacting pathways on which diabetes may shows its influence and disruption. Finally, is well known the alteration of different organs and systems during diabetic disease, involved in bone metabolism, as kidney, gut or vitamin D pathway. In fact, In the last few years, studies are focusing not only to clarify old pathways but also to discover new pathways among diabetes, obesity and bone metabolism, as Wnt signaling and the role of sclerostin, as irisin, as different formulations of vitamin D like calcidiol. Moreover, some complications derived from diabetes, as cardiac neuropathy, were not yet fully evaluated on their link to the axis diabetes-bone, leading a gap of knowledge to fill (Epstein et al. 2016; Napoli, Strollo, et al. 2014). So, many questions remain regarding the underlying mechanisms for greater bone fragility in diabetic patients and the best approach to risk assessment and treatment to prevent fractures. Specific aims 1) to evaluate the role of sclerostin in patients with type 2 diabetes and patients with LADA. 2) to investigate the relationship between irisin and body composition in subjects with osteoporosis and the impact of irisin levels on fragility vertebral fractures. 3) to evaluate the role of calcidiol on metabolic parameters and ß-cell function in subjects with impaired glycaemic control and insufficient vitamin D levels. 4) to evaluate the relationship between cardiac autonomic neuropathy and BMD in patients with diabetes. Materials and Methods 1) This cross-sectional study included 98 T2D and 89 LADA patients from the Action LADA and NIRAD cohorts. Patients were further divided according to MetS status. Non-diabetic subjects (n=53) were used as controls. Serum sclerostin, bone formation (P1NP) and bone resorption (CTX) were analyzed. 2) In this cross-sectional study, 36 overweight subjects affected by at least one vertebral osteoporotic fracture confirmed by a X-ray vertebral morphometry and 36 overweight non-osteoporotic subjects were enrolled. Serum irisin levels were measured using an irisin competitive ELISA. We evaluated lumbar spine and hip BMD and body composition using dual energy X-ray absorptiometry. To measure and monitor daily physical activity, each subject wore an armband for approximately 72 hours. 3) It is a double-blind placebo-controlled clinical trial enrolling subjects with IGT, IFG and T2D (20) and 25(OH)D <20 ng/ml. In this study were enrolled a total of 150 subjects and followed up for 6 months. Subjects were either assigned (50 per group) to 1) daily supplementation of 50 mcg of calcidiol (Arm A); 2) 25 mcg of calcidiol (arm B); 3) placebo (Arm C). Fasting blood glucose and Oral Glucose Tolerance Test (OGTT), HbA1c, 25 (OH) D, calcium, phosphorus, PTH, calciuria, phosphaturia, total cholesterol, HDL cholesterol and triglycerides were measured with laboratory kits used in clinical settings. Measurements of Ox-LDL, Hs-CRP, TNF-α, IL-6, esRAGE, sRAGE were performed at the laboratory. To evaluate insulin resistance were used the ISOGTT index and the evaluation of the model of insulin-resistance homeostasis (HOMA-IR). Beta-cell function was evaluated using the insulin secretion sensitivity index-2 (ISSI-2) 4) Fourty-nine people with T2D were enrolled. Tests to determine heart rate response to deep-breathing (expiratory-to-inspiratory ratio), heart rate response to lying-to-stand test (30:15 ratio) and blood pressure response to standing were performed to detect cardiac autonomic neuropathy, and dual energy X-ray absorptiometry scan of both the lumbar spine and femoral neck were performed to evaluate bone mineral density. Results 1) T2D subjects had higher sclerostin than LADA (p=0.0008, adjusted for sex and BMI), even when analysis was restricted to MetS subjects (adjusted p=0.03). Analyzing T2D and LADA separately, sclerostin was similar between subjects with and without MetS. However, a positive trend between sclerostin and number of MetS features was seen in T2D (p for trend=0.001) but not in LADA. Subjects with either T2D or LADA had lower CTX than controls (p=0.0003), and not significantly reduced P1NP. Sclerostin was unrelated to age or HbA1c but correlated with BMI (ρ=0.29; p=0.0001), HDL (ρ=-0.23; p=0.003), triglycerides (ρ=0.19; p=0.002) and time since diagnosis (ρ=0.32, p<0.0001). 2) No significant correlations were found between irisin and BMD at any site and between irisin with either lean or fat mass. Serum levels of irisin were not correlated with the daily physical activity. Serum irisin levels were lower in subjects with previous osteoporotic fractures than in controls (p= 0.032) and the difference in irisin levels remained significant after adjustment for creatinine (p=0.037), vitamin D (p=0.046), lean mass (p=0.02), lumbar BMD (p=0.023) and femoral BMD (p=0.032). 3) At baseline, subjects were (mean±SD) 63.8± 2.1 y.o., BMI was 27.4±1.2 kg/m2; serum glucose 115.1±8.4 mg/dL, HbA1c 6.4±0.6%, 25OHD 16.3±2.5 ng/mL. There were significant associations of 25OHD with ISOGTT (β=0.35; 95% CI, 0.14, 0.46) and β-cell function (ISSI-2; β = 0.15; 95% CI, 0.02, 0.28). At six months, 25OHD increased up to 48±3 ng/mL in Arm A (P<0.01) and to 36±5 ng/mL in Arm B (P<0.01); no significant changes in the Arm C. Subjects in Arm A had a lower risk of dysglycemia (HR= 0.85, 95% CI, 0.75-0.97 per SD increase) while no significant effects were observed in the Arms B or C. Both ISOGTT and ISSI-2 were improved in Arm A (P<0.05) while no significant changes were observed in Arm B or placebo. Serum levels of sRAGE decreased in Arm A [median 1354 (1069-1680) pg/ml (P<0.01), as compared with levels at study entry, but not in Arms B or C. No significant differences were observed for hsCRP, IL6, TNFα or lipid panel. 4) We analyzed preliminary results among two evaluations of BMD and CAN, not finding any significative difference. In fact, subjects with no CAN showed a normal BMD in 35,7% while the remaining part had osteopenia or osteoporosis (64,3%: osteopenia: 60,7%; osteoporosis: 3,6%). Evaluating BMD in subjects with CAN, 48,1 had a normal BMD while 51,9 had osteopenia (37%) or osteoporosis (14,8%). Conclusions 1) LADA patients present lower bone resorption compared to controls, similarly to T2D. Sclerostin is increased in T2D but not in LADA suggesting possible roles on bone metabolism in T2D only. 2) The data confirm an inverse correlation between irisin levels and vertebral fragility fractures, but no significant correlation was found with BMD or lean mass. Irisin may play a protective role on bone health independent of BMD. 3) Our findings indicate that high doses of calcidiol improved indices of glucose homeostasis in prediabetic subjects and decreased circulating sRAGE levels, suggesting a positive effect also on oxidative stress. 4) No significant correlations were found evaluating BMD in subjects with T2D and CAN

Erectile Dysfunction Severity: The Role of Glycometabolic Compensation and Antihyperglycemic Drugs

Background: The aim of this study was to evaluate the prevalence of DM among patients with ED and the impact of glycometabolic compensation and antihyperglycemic treatment on ED severity. Methods: In total, 1332 patients with ED were enrolled. The diagnosis was performed through the International-Index-of-Erectile-Function questionnaire. ED severity was considered according to presence/absence of spontaneous erections, maintenance/achievement deficiency and response to PDE5-i. DM patients were clustered according to antihyperglycemic treatment: “metformin”/“insulin”/“old antihyperglycemic drugs”/“new antihyperglycemic drugs”. Results: The prevalence of DM patients was 15.8% (Group A, patients with ED and DM). Among these, the prevalence of spontaneous erections (21.0%) was lower than in the remaining patients (Group B, patients with ED without DM) (32.0%, p p p = 0.02). The prevalence of absent response to PDE5-i was higher in patients treated with old antidiabetic drugs than in the population treated with new drugs (p = 0.03). Conclusion: The severity of ED and lower response to PDE5-i were higher in DM patients. A better glycometabolic profile, as well as new antihyperglycemic drugs, seem to have a positive effect on ED

A case of pheochromocytoma with negative MIBG scintigraphy, PET-CT and genetic tests (VHL included) and a rare case of post-operative erectile dysfunction

BACKGROUND: Pheochromocytoma (Ph) is a rare catecholamine-secreting neuroendocrine tumour that arises from the chromaffin cells of the adrenal medulla. Ph usually presents with symptoms including paroxysmal headache, sweating, palpitations, and hypertension. CLINICAL CASE: During a computed tomography (CT) scan in a normotensive 49-year-old man, an incidentaloma of 4.5 cm was detected. Hypercortisolism was excluded after the dexamethasone suppression test, levels of DHEAS all falling within the normal range. After a 24-h urine collection, normal urinary metanephrines and a 4-fold higher level compared to the normal range of urinary normetanephrines were observed. Cortisoluria levels were within the normal range. Multiple endocrine neoplasia type 2 (MEN 2) was also excluded. Before the adrenalectomy, 123I meta-iodobenzylguanidine scintigraphy (MIBG) and 18F-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG PET)/CT were performed and were both negative. Histological examination confirmed the laboratory diagnosis of Ph. Genetic screening to evaluate the SDHB, SDHD, RET, CDKN1B, and VHL genes was requested in order to test for Von Hippel Lindau disease, but unexpectedly all of these were negative. On follow-up after surgery, the patient presented normal urinary catecholamines. However, after Ph removal, he reported frequent episodes of erectile dysfunction (ED) despite non-use of any antihypertensive medications and in the absence of any other precipitating factors, such as hormonal imbalance. CONCLUSIONS: This is a case report in which, in a normotensive patient with Ph, both MIBG and FDG PET-CT were negative, as were also genetic exams, including VHL, this underlining the difficulties in diagnosing this condition; furthermore, a rare case of ED occurred after surgery