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Summary Andrologists, cardiologists and diabetologists (and general practitioners) have the great opportunity to collaborate and find shared clinical workup for the benefit of a large number of men. Several evidence established a link between erectile dysfunction (ED), cardiovascular disease (CVD), diabetes, and metabolic syndrome. Not only these conditions share many risk factors and pathophysiological mechanisms but also an emerging paradigm indicates that ED is, in fact, an independent marker of cardiovascular disease risk, CV events and CV mortality. However, there is no consensus on the best cardiologic investigation in men with ED with no known CVD and, on the contrary, on what is the clinical and prognostic role of detecting ED during cardiovascular investigation and CVD risk assessment. Only vasculogenic ED, which represents the most common type of organic ED, indeed represents a harbinger of CVD, especially for younger patients, and might be diagnosed by dynamic penile color doppler ultrasonography, which represents a real cardiovascular imaging technique that give evidence on the presence of systemic endothelial dysfunction and atherosclerosis. Furthermore, assessment of glucose and lipid metabolism is warranted as first step workup in all ED patients, and diabetologists should ask their patients for erectile function, address ED patients to andrologists, and consider vasculogenic ED in the context of the cardiovascular and metabolic workup and in the context of diabetic complications. Sexual symptoms (and testosterone levels) should sound as harbinger for cardiovascular and metabolic investigation and cardiologists and diabetologists have the opportunity to have a symptom (erectile dysfunction) and a vascular test (penile color doppler) that help them in better management of patients, their comorbidities and complications.

BackgroundSome cases of apparently idiopathic GH deficiency (GHD) may be caused by pituitary autoimmunity.ObjectiveTo study the variations in pituitary function and antipituitary antibodies (APA) from childhood to transition age in patients with apparently idiopathic GHD.DesignWe conducted a longitudinal study.Patients and methodsPituitary function and APA detection by immunofluorescence were investigated in 24 childhood patients with isolated GHD before starting recombinant GH therapy and after the stopping of this therapy in transition age. Sera of patients positive for APA were processed by double immunofluorescence to identify their pituitary target.ResultsAt diagnosis, 16 out of 24 patients were APA positive targeting only somatotrophs (group 1), while the remaining eight were APA negative (group 2). When retested off therapy, 12 out of 16 patients in group 1 persisted being APA positive, while the remaining four became negative with recovery of pituitary function. All patients in group 2 persisted being APA negative but still showing GHD. Of the 12 patients persistently APA positive, eight with confirmed GHD showed APA still targeting somatotrophs, whereas four showed APA targeting only gonadotrophs associated with isolated hypogonadotropic hypogonadism (HH).ConclusionPatients with APA at middle but not at high titer in childhood may show a remission of autoimmune GHD in childhood after GH replacement therapy. As APA may shift their target in transition period, an early characterization of APA by double immunofluorescence is advisable in APA positive GHD patients showing delayed puberty, to allow an early diagnosis and an appropriate therapy, thus preventing the progression toward HH.

We assessed the efficacy of eight classes of diabetes medications used in current clinical practice [metformin, sulphonylureas, α-glucosidase inhibitors, thiazolidinediones, glinides, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 (GLP-1) analogues and insulin analogues] to reach the HbA1c target7% in type 2 diabetes.MEDLINE, EMBASE and the Cochrane CENTRAL were searched from inception through April 2011 for randomized controlled trials (RCTs) involving antidiabetic drugs. RCTs had to report the effect of any diabetes medication on the HbA1c levels, to include at least 30 subjects in every arm of the study, and to report the effect of therapy after a minimum of 12 weeks. Data were summarized across studies using random-effects meta-regression.A total of 218 RCTs (339 arms and 77 950 patients) met the inclusion criteria. The proportion of patients who achieved the HbA1c goal ranged from 25.9% (95% CI 18.5-34.9) with α-glucosidase inhibitors to 63.2% (54.1-71.5) with the long-acting GLP-1 analogue. There was a progressive decrease of the proportion of patients at target for each 0.5% increase in baseline HbA1c, ranging from 57.8% for HbA1c ≤7.5% to 20.8% for HbA1c ≥10% (p for trend0.0001), with some difference between insulin and non-insulin drugs: for insulin, the proportion of patients at goal reached a plateau for basal HbA1c value9.0% with no further decrease, whereas for non-insulin drugs the relationship was continuous without any evidence of plateau.There is a considerable variability with regard to attainment of HbA1c goal of7% among the different classes of diabetes medications; baseline HbA1c is an important determinant of observed efficacy.

Background— Postprandial hyperglycemia may be a risk factor for cardiovascular disease. We compared the effects of two insulin secretagogues, repaglinide and glyburide, known to have different efficacy on postprandial hyperglycemia, on carotid intima-media thickness (CIMT) and markers of systemic vascular inflammation in type 2 diabetic patients. Methods and Results— We performed a randomized, single-blind trial on 175 drug-naive patients with type 2 diabetes mellitus (93 men and 82 women), 35 to 70 years of age, selected from a population of 401 patients who participated in an epidemiological analysis assessing the relation of postprandial hyperglycemia to surrogate measures of atherosclerosis. Eighty-eight patients were randomly assigned to receive repaglinide and 87 patients to glyburide, with a titration period of 6 to 8 weeks for optimization of drug dosage and a subsequent 12-month treatment period. The effects of repaglinide (1.5 to 12 mg/d) and glyburide (5 to 20 mg/d) on CIMT were compared by using blinded, serial assessments of the far wall. After 12 months, postprandial glucose peak was 148±28 mg/dL in the repaglinide group and 180±32 mg/dL in the glyburide group ( P 1c showed a similar decrease in both groups (−0.9%). CIMT regression, defined as a decrease of >0.020 mm, was observed in 52% of diabetics receiving repaglinide and in 18% of those receiving glyburide ( P P =0.04) and C-reactive protein ( P =0.02) decreased more in the repaglinide group than in the glyburide group. The reduction in CIMT was associated with changes in postprandial but not fasting hyperglycemia. Conclusions— Reduction of postprandial hyperglycemia in type 2 diabetic patients is associated with CIMT regression.

Despite its prevalence, clinical and prognostic impact, diabetic autonomic neuropathy, is widely under-diagnosed. The need for training and expertise to perform the cardiovascular tests (usually the task of diabetologists) is one possible reason. The availability of computer-assisted systems has allowed a wider diffusion of testing, but has also highlighted the need for an adequate knowledge of physiopathological backgrounds for their correct application and interpretation. The recommendations presented here were developed by the Neuropathy Study Group of the Italian Society of Diabetology and then endorsed by the Italian Association for the Study of Neurovegetative System, to promote the widespread adoption of good clinical practice in diabetic cardiovascular autonomic testing by outlining main evidence-based aspects, i.e. which tests, how to perform them, adequate interpretation of the results and their diagnostic use, confounding conditions that can impact on tests reliability. Therefore, these recommendations include the essential aspects of the physiopathological substrate of the tests, the controversial points in their analysis, their diagnostic characteristics, as well as safety. Detailed information is given on the physiological (age, weight, body position, resting heart rate and blood pressure, respiratory pattern, exercise, meals, acute blood glucose changes) and pathophysiological confounding factors, with emphasis on the effects of drugs. Instructions on how to perform the tests and interpret their results are also considered together with indications of candidate patients and periodicity of testing. A patient instruction sheet on why and how to perform the tests is included. Finally, the specific requirements for computerized systems to perform and evaluate cardiovascular tests are provided.

Diurnal salivary and plasma cortisol variations are considered valid expression of circadian cortisol rhythmicity. The aim of this study was to assess the reliability of salivary and plasma cortisol evaluating if glycemia and glycemic oscillations may interfere with their concentration.Methods: Forty-seven type 2 diabetic patients and 31 controls were studied for glycemic profile and diurnal salivary and plasma cortisol variations on two contemporary samples taken at 08:00 a.m. and 11:00 p.m (Late Night, LN). Glucose variability was evaluated in diabetic patients by considering the standard deviation of blood glucose (BGSD) readings, by calculating the mean amplitude of glycemic excursions (MAGEs) and continuous overlapping net glycemic action (CONGA).Results: A significant correlation between LN serum cortisol and morning fasting glycemia (r = 0.78; p = 0.004) was observed in T2DM group but not in the control group (r = 0.09; p = 0.74). While LN serum cortisol significantly correlated with CONGA in diabetic patients (r = 0.50; p < 0.001), LN salivary cortisol did not correlate with any indices of glucose variability. Moreover, a highly significant correlation between LN salivary and LN serum cortisol concentrations was found in control group (r = 0.80; p < 0.001) but not in diabetic patients (r = 0.07; p = 0.62) .Conclusions: This study shows for the first time that late night salivary cortisol may give more information than late night plasma cortisol on the dynamic of adrenal function of type 2 diabetic patients, as it is not significantly influenced by glycemic variations.

A meta-analysis of cardiovascular outcome trials (CVOTs) comparing glucagon-like peptide-1 receptor agonists (GLP-1RAs) and placebo concerning cardiorenal outcomes in patients with type 2 diabetes (T2D) is presented. An electronic search without language restrictions up to June 15, 2019 was conducted to determine eligible trials. A meta-analysis of available trial data was undertaken, using a random-effects model to calculate overall hazard ratios (HRs) and 95% confidence intervals (CIs). Data from seven CVOTs, comprising 56 004 patients (68.9% with established cardiovascular disease) were included. GLP-1RA reduced major cardiovascular events (MACE) by 13% (HR, 0.87; 95% CI, 0.80-0.96; P = 0.011) with a non-significant heterogeneity between subgroups of patients with and without cardiovascular disease (CVD) (P = 0.220). GLP-1RA also reduced the risk of cardiovascular death by 12%, of non-fatal stroke by 16%, of hospitalization for heart failure by 9%, of all-cause mortality by 11%, and the broad composite kidney outcome by 17%; the latter appeared to be driven only by a reduction in macroalbuminuria (HR, 0.76 [0.68-0.86]; P = 0.003). GLP-1RAs have moderate benefits concerning MACE, and also reduce hospitalization for heart failure and all-cause mortality; they also robustly reduce the incidence of macroalbuminuria, without affecting the progression of diabetic renal disease.

Background: Abnormal liver blood tests (LBTs) in hyperthyroid patients are not uncommonly encountered. One major adverse event of antithyroid drug (ATD) therapy is drug-induced hepatotoxicity. Abnormal LBT in the hyperthyroidism scenario is a main diagnostic and therapeutic dilemma. We aimed to assess the prevalence and the response to ATD therapy of LBT abnormalities in newly diagnosed and uncomplicated hyperthyroidism through a systematic review and meta-analysis. Methods: A literature search was performed reporting LBTs at presentation and after ATD therapy in hyperthyroid patients. A proportion meta-analysis was performed with random-effects model. Pooled data were presented with 95% confidence intervals (CI). I2 statistic index was used to quantify the heterogeneity. Sensitivity analyses for prevalence of hyperthyroid patients with at least one abnormal LBT were performed. p-Value of

Aim In order to disclose relations between reduction of haemoglobin A1c (HbA1c) levels and risk of major cardiovascular events (MACE), we performed a meta-analysis with metaregression of all cardiovascular outcome trials (CVOTs) so far published in patients with type 2 diabetes (T2D).Materials and Methods An electronic search up to February 10, 2020 was conducted to determine eligible trials. Pooled summary estimates and 95% confidence intervals (CI) were calculated according to the random effects model using the Paule-Mandel method; restricted maximum likelihood estimators were used to estimate model parameters in the metaregression.Results The 15 CVOTs included evaluated 138,250 patients. In the pooled analysis, the risk of MACE was significantly reduced by 9% (hazard ratio, HR = 0.91, 0.87-0.95, P

Metabolic syndrome (MetS) and cancer share many modifiable risk factors including age, genetic factors, obesity, physical inactivity, unhealthy diet, alcohol, smoking, endocrine disruptors exposure, circadian clock disturbances, and air pollution. MetS is closely linked to cancer, as it increases cancer risk and cancer-related mortality; moreover, cancer survivors have an increased risk of MetS. Elucidating the mechanisms linking MetS to cancer is important to prevent or delay these two conditions. Possible mechanisms explaining the relationship between MetS and cancer include hyperinsulinemia and alterations of insulin-like growth factor system, chronic subclinical inflammation, abnormalities in sex hormones metabolism and adipokines, hyperglicemia, alterations in both gene expression and hormonal profile by endocrine disruptors and air pollution, desynchronization of circadian clock. The common soil hypothesis claims that MetS may be considered a surrogate marker for dietary risk factors of cancer, and a warning sign for susceptible individuals exposed to an unhealthy diet. The common soil hypothesis and the clepsydra of foods represent a theoretical substrate to preventive intervention strategies against the pandemics of MetS and cancer: adherence to healthy dietary patterns is associated with a reduced risk of MetS, and improvement of the quality of diet is consistently associated with a reduction in cancer-related mortality.

A meta-analysis is presented of randomized controlled trials (RCTs) comparing free or fixed combinations of a glucagon-like peptide-1 receptor agonist plus basal insulin versus insulin intensification on metabolic control in patients with type 2 diabetes. Electronic databases were searched for RCTs assessing changes in HbA1c, proportion of patients at HbA1c target of 71%, P < 0.001). Results did not differ in either the free or fixed combination subgroups. Combination strategies, either free or fixed, represent a good option for intensifying basal insulin therapy in patients with type 2 diabetes who need amelioration of glycaemic control.

In the past decades, dietary guidelines focused on reducing saturated fat as the primary strategy for cardiovascular disease prevention, neglecting the many other potential effects of diet on health, in particular the harmful effects of sugar. A greater intake of soft drinks (sugar-sweetened beverages), for example, is associated with a 44% increased prevalence of metabolic syndrome, a higher risk of obesity, and a 26% increased risk of developing diabetes mellitus. Carbohydrates comprise around 55% of the typical western diet, ranging from 200 to 350 g/day in relation to a person’s overall caloric intake. For long-term weight gain, food rich in refined grains, starches, and sugar appear to be major culprits. Low-carbohydrate diets restrict daily carbohydrates between 20 and 50 g, as in clinical ketogenic diets. The results of controlled trials show that people on ketogenic diets (a diet with no more than 50 g carbohydrates/day) tend to lose more weight than people on low-fat diets. Moreover, there is no good evidence for recommending low-fat diets, as low-carbohydrate diets lead to significantly greater weight loss (1.15 kg) than did low-fat interventions. However, the magnitude of such a benefit is small. As the quality of ingested carbohydrates seems more important than the quantity for health outcomes, people with metabolic disorders should avoid or substantially reduce low-fiber, rapidly digested, refined grains, starches, and added sugars. So, the consumption of the right carbohydrates (high-fiber, slowly digested, and whole grains), in a moderately lower amount (between 40 and 50% of daily energy content), is compatible with a state of good health and may represent a scientifically-based and palatable choice for people with metabolic disorders.

Purpose: To describe gender differences concerning glycemic control, cardiovascular risk factors, diabetic complications, concomitant pathologies, and circulating endothelial progenitor cells (EPCs), in a population of young adults with type 1 diabetes. Methods: We collected data from 300 consecutively patients (168 males and 132 females), aged 18–30 years, among those admitted at Diabetes Unit of University of Campania “Luigi Vanvitelli” (Naples, Italy) from March 2012 to January 2017. Circulating levels of seven EPCs phenotypes were determined by flow cytometry. Results: As compared to men, women with type 1 diabetes had a significantly higher HbA1c levels (%, 8.4 ± 1.3 vs. 8.1 ± 1.3, P = 0.020), body mass index (Kg/m2, 24.8 ± 4.2 vs. 23.9 ± 3.9, P = 0.034), HDL-cholesterol (mg/dL, 61.7 ± 13.7 vs. 54.7 ± 13.9, P < 0.001), and a lower count of both CD133+KDR+ and CD34+KDR+CD133+ EPCs (P = 0.022, P < 0.001, respectively). A higher proportion of women had overweight/obesity, and thyroiditis; smoking and sexual dysfunctions were more prevalent in men than in women. Conclusions: Young adults with type 1 diabetes present gender differences with regard to glycemic control, prevalence of some cardiovascular risk factors, sexual dysfunctions and circulating levels of EPCs, most often to the detriment of women.

Exposure to small particulate matter (PM2.5) has become the 5th highest ranking risk factor for death, responsible for 4.2 million deaths worldwide. PM pollution is also associated with cardiovascular disease and type 2 diabetes, and may contribute to deteriorate the already poor cardiometabolic outlook of the diabetic patient. Although most sources of outdoor air pollution are well beyond the control of individuals, there is still room for personal action. Health behaviors (smoking cessation, avoiding obesity, and increasing physical activity) may increase the poor life expectancy of individuals in the lowest income quartile of the Western population; moreover, a favorable lifestyle, (no current smoking, no obesity, physical activity at least once weekly, and a healthy diet pattern), may cut by nearly 50% the risk of coronary heart disease among people at high genetic risk. Things seem not immutable, as individual healthy choices do matter.

Continuous glucose monitoring associated with intensive insulin regimens represents a useful tool to lower HbA1c in selected adults with type 1 diabetes. Recent randomized controlled trials demonstrated greater glycemic benefits in type 1 diabetic patients treated with multiple daily injections of insulin and continuous glucose monitoring over usual care. These positive outcomes, however, are counter-balanced by several limitations that restrict the use of continuous glucose monitoring in the real life, including the apparent lack of benefits in children and pregnant diabetic women, the high cost, the stringent patients’ selection, and the presence of a multi-disciplinary team with specific expertise. Pros and Cons of using continuous glucose monitoring in type 1 diabetic patients with multiple daily injections of insulin are here discussed.

OBJECTIVE The combination of basal insulin plus a glucagon-like peptide 1 receptor agonist (GLP-1RA) has been proposed as a treatment option to intensify insulin therapy in type 2 diabetes. We performed a meta-analysis of randomized controlled trials (RCTs) comparing this combination strategy to other injectable antidiabetes treatments on metabolic control in adult patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted an electronic search until November 2016 on many electronic databases to identify RCTs assessing changes in HbA1c, proportion of patients at HbA1c target ≤7% (53 mmol/mol), hypoglycemia, and weight change. We used a random-effect model to calculate the weighted mean difference (WMD) or relative risk (RR) with the 95% CI. RESULTS We identified 26 RCTs, lasting 12–52 weeks, and involving 11,425 patients. When the combination strategy was compared with other injectable treatments (overall data), there were reductions in HbA1c (WMD = −0.47%, 95% CI −0.59 to −0.35), more patients at HbA1c target (RR = 1.65, 95% CI 1.44–1.88), similar hypoglycemic events (RR = 1.14, 95% CI 0.93–1.39) and a reduction in weight (WMD = −2.5 kg, 95% CI −3.3 to −1.7), with high heterogeneity (I2 > 89%, P < 0.001) and a significant publication bias for three outcomes. In preplanned subgroup analyses, the combination treatment was similar to basal-bolus insulin regimens for glycemic control, with less hypoglycemia (RR = 0.66, 95% CI 0.46–0.93) and reduced weight (WMD = −4.7 kg, 95% CI −6.9 to −2.4). Fixed-ratio combinations yielded results similar to the overall analysis (HbA1c WMD = −0.56%, 95% CI −0.72 to −0.40). CONCLUSIONS GLP-1RAs alone or as titratable fixed-ratio combinations with basal insulin may represent a promising option to advance basal insulin therapy or to initiate injectable therapy in patients with type 2 diabetes inadequately controlled on oral agents. Longer studies are needed to assess durability and tolerability.

BACKGROUND Continuous glucose monitoring (CGM) provides important information to aid in achieving glycemic targets in people with diabetes. PURPOSE We performed a meta-analysis of randomized controlled trials (RCTs) comparing CGM with usual care for parameters of glycemic control in both type 1 and type 2 diabetes. DATA SOURCES Many electronic databases were searched for articles published from inception until 30 June 2019. STUDY SELECTION We selected RCTs that assessed both changes in HbA1c and time in target range (TIR), together with time below range (TBR), time above range (TAR), and glucose variability expressed as coefficient of variation (CV). DATA EXTRACTION Data were extracted from each trial by two investigators. DATA SYNTHESIS All results were analyzed by a random effects model to calculate the weighted mean difference (WMD) with the 95% CI. We identified 15 RCTs, lasting 12–36 weeks and involving 2,461 patients. Compared with the usual care (overall data), CGM was associated with modest reduction in HbA1c (WMD −0.17%, 95% CI −0.29 to −0.06, I2 = 96.2%), increase in TIR (WMD 70.74 min, 95% CI 46.73–94.76, I2 = 66.3%), and lower TAR, TBR, and CV, with heterogeneity between studies. The increase in TIR was significant and robust independently of diabetes type, method of insulin delivery, and reason for CGM use. In preplanned subgroup analyses, real-time CGM led to the higher improvement in mean HbA1c (WMD −0.23%, 95% CI −0.36 to −0.10, P < 0.001), TIR (WMD 83.49 min, 95% CI 52.68–114.30, P < 0.001), and TAR, whereas both intermittently scanned CGM and sensor-augmented pump were associated with the greater decline in TBR. LIMITATIONS Heterogeneity was high for most of the study outcomes; all studies were sponsored by industry, had short duration, and used an open-label design. CONCLUSIONS CGM improves glycemic control by expanding TIR and decreasing TBR, TAR, and glucose variability in both type 1 and type 2 diabetes.

Diabetes is becoming one of the most widespread health burning problems in the elderly. Worldwide prevalence of diabetes among subjects over 65 years was 123 million in 2017, a number that is expected to double in 2045. Old patients with diabetes have a higher risk of common geriatric syndromes, including frailty, cognitive impairment and dementia, urinary incontinence, traumatic falls and fractures, disability, side effects of polypharmacy, which have an important impact on quality of life and may interfere with anti-diabetic treatment. Because of all these factors, clinical management of type 2 diabetes in elderly patients currently represents a real challenge for the physician. Actually, the optimal glycemic target to achieve for elderly diabetic patients is still a matter of debate. The American Diabetes Association suggests a HbA1c goal 6.5%) for patients with concurrent serious illness and at high risk of hypoglycemia. By contrast, the American College of Physicians (ACP) suggests more conservative goals (HbA1c levels between 7 and 8%) for most older patients, and a less intense pharmacotherapy, when HbA1C levels are ≤6.5%. Management of glycemic goals and antihyperglycemic treatment has to be individualized in accordance to medical history and comorbidities, giving preference to drugs that are associated with low risk of hypoglycemia. Antihyperglycemic agents considered safe and effective for type 2 diabetic older patients include: metformin (the first-line agent), pioglitazone, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists. Insulin secretagogue agents have to be used with caution because of their significant hypoglycemic risk; if used, short-acting sulfonylureas, as gliclazide, or glinides as repaglinide, should be preferred. When using complex insulin regimen in old people with diabetes, attention should be paid for the risk of hypoglycemia. In this paper we aim to review and discuss the best glycemic targets as well as the best treatment choices for older people with type 2 diabetes based on current international guidelines.

Traumatic brain injury (TBI) is one of the most common causes of mortality and long-term disability and it is associated with an increased prevalence of neuroendocrine dysfunctions. Post-traumatic hypopituitarism (PTHP) results in major physical, psychological and social consequences leading to impaired quality of life. PTHP can occur at any time after traumatic event, evolving through various ways and degrees of deficit, requiring appropriate screening for early detection and treatment. Although the PTHP pathophysiology remains to be elucitated, on the basis of proposed hypotheses it seems to be the result of combined pathological processes, with a possible role played by hypothalamic-pituitary autoimmunity (HPA). This review is aimed at focusing on this possible role in the development of PTHP and its potential clinical consequences, on the basis of the data so far appeared in the literature and of some results of personal studies on this issue. Purpose: Traumatic brain injury (TBI) is one of the most common causes of mortality and long-term disability and it is associated with an increased prevalence of neuroendocrine dysfunctions. Post-traumatic hypopituitarism (PTHP) results in major physical, psychological and social consequences leading to impaired quality of life. PTHP can occur at any time after traumatic event, evolving through various ways and degrees of deficit, requiring appropriate screening for early detection and treatment. Although the PTHP pathophysiology remains to be elucitated, on the basis of proposed hypotheses it seems to be the result of combined pathological processes, with a possible role played by hypothalamic–pituitary autoimmunity (HPA). This review is aimed at focusing on this possible role in the development of PTHP and its potential clinical consequences, on the basis of the data so far appeared in the literature and of some results of personal studies on this issue. Methods: Scrutinizing the data so far appeared in literature on this topic, we have found only few studies evaluating the autoimmune pattern in affected patients, searching in particular for antipituitary and antihypothalamus autoantibodies (APA and AHA, respectively) by simple indirect immunofluorescence. Results: The presence of APA and/or AHA at high titers was associated with an increased risk of onset/persistence of PTHP. Conclusions: HPA seems to contribute to TBI-induced pituitary damage and related PTHP. However, further prospective studies in a larger cohort of patients are needed to define etiopathogenic and diagnostic role of APA/AHA in development of post-traumatic hypothalamic/pituitary dysfunctions after a TBI.

Diabetic kidney disease (DKD) still remains a progressive condition that is associated with higher risk of end-stage kidney disease and significant cardiovascular morbidity and mortality. Twelve cardiovascular outcome trials in type 2 diabetes (T2D) have been published to date. Most trials with dipeptidyl-peptidase inhibitors (SAVOR-TIMI 53 with saxagliptin, EXAMINE with alogliptin, TECOS with sitagliptin, and CARMELINA with linagliptin) and with glucagon-like peptide-1 receptor agonists (GLP-1RAs) (ELIXA with lixisenatide, LEADER with liraglutide, SUSTAIN-6 with semaglutide, EXCSEL with exenatide once-weekly, and HARMONY with albiglutide) pointed towards reduced albuminuria, which is a surrogate endpoint possibly heralding renal function preservation. The three trials with sodium-glucose co-transporter-2 inhibitors (SGLT-2is) (empagliflozin, canagliflozin and dapagliflozin) also showed a salutary effect on long-term estimated glomerular filtration rate, suggesting that SGLT-2is are more effective at mitigating loss of kidney function than incretin-based therapies; moreover, SGLT-2is also have the advantage of plausible haemodynamic mechanisms for improved renal outcomes. Despite some residual limitations linked to differences in study populations and patient characteristics, the cardiorenal protective actions of SGLT-2is, and to a lesser extent some GLP-1RAs, make them favourable medications for patients with T2D at increased cardiorenal risk. There is room for optimism that their use may change the paradigm of the ineluctable progression of DKD.

Therapy of hypothyroidism is based on the administration of appropriate doses of L-thyroxine (L-T4). A failure to achieve the TSH target may be due to poor compliance with the L-T4 therapy in about 60% of cases or to malabsorption in about 40% of cases. No tools are available for detecting malabsorption disorders before the choice of the most appropriate therapy. The aim of this study is to validate the EMPATHY questionnaire and to demonstrate its usefulness in indicating the most appropriate therapy.

Aims To assess the long-term effect of Mediterranean diet, as compared with low-fat diet, on sexual function in patients with newly diagnosed type 2 diabetes. Methods In a randomized clinical trial, with a total follow-up of 8.1years, 215 men and women with newly diagnosed type 2 diabetes were assigned to Mediterranean diet (n=108) or a low-fat diet (n=107). The primary outcome measures were changes of erectile function (IIEF) in diabetic men and of female sexual function (FSFI) in diabetic women. Results There was no difference in baseline sexual function in men (n=54 vs 52) or women (n=54 vs 55) randomized to Mediterranean diet or low-fat diet, respectively ( P =0.287, P =0.815). Over the entire follow-up, the changes of the primary outcomes were significantly lower in the Mediterranean diet group compared with the low-fat group: IIEF and FSFI showed a significantly lesser decrease (1.22 and 1.18, respectively, P =0.024 and 0.019) with the Mediterranean diet. Baseline C-reactive protein levels predicted erectile dysfunction in men but not female sexual dysfunction in women. Conclusions Among persons with newly diagnosed type 2 diabetes, a Mediterranean diet reduced the deterioration of sexual function over time in both sexes.

Purpose: This publication reviews the accepted knowledges and the findings still discussed on several features of autoimmune hypophysitis, including the most recently described forms, such as IgG4 and cancer immunotherapy- related hypophysitis. Methods: The most characteristic findings and the pending controversies were derived from a literature review and previous personal experiences. A single paragraph focused on some atypical examples of the disease presenting under confounding pretences. Results: Headache, visual field alterations and impaired pituitary secretion are the most frequent clinical findings of the disease. Pituitary biopsy, still considered the gold diagnostic standard, does not always receive consent from the patients. The role of magnetic resonance imaging is limited, as this disease may generate images similar to those of other diseases. The role of antipituitary and antihypothalamus antibodies is still discussed owing to methodological difficulties and also because the findings on the true pituitary antigen(s) are still debated. However, the low sensitivity and specificity of immunofluorescence, one of the more widely employed methods to detect these antibodies, may be improved, considering a predetermined cut-off titre and a particular kind of immunostaining. Conclusion: Autoimmune hypophysitis is a multifaceted disease, which may certainly be diagnosed by pituitary biopsy. However, the possible different clinical, laboratory and imaging features must be considered by the physician to avoid a misdiagnosis when examining a possibly affected patient. Therapeutic choice has to be made taking into account the clinical conditions and the degree of hypothalamic-pituitary involvement, but also considering that spontaneous remissions can occur.

Cancer may impair sexual function in women. We provide an overview of studies that address Female Sexual Dysfunction (FSD) in women with cancer with a meta-analysis of observational studies that used a validated diagnostic tool. Searches included MEDLINE, Scopus, and Google Scholar for studies published from January 2000 to 31 December 2014. Every included study had to involve at least 30 cancer patients, to investigate FSD based on the Female Sexual Function Index (FSFI), and to have been published in peer-review journals. Duplicate independent data extraction and quality assessment were performed. Data were pooled using a random effects model if statistical heterogeneity was present. The main outcomes were FSFI total score and FSD prevalence. FSFI is a 19-item self-report instrument for assessing key dimensions of female sexual function. A value less than 26.55 is consistent with FSD. Thirty-five studies met the inclusion criteria. Among these, 27 reported FSFI scores, and 16 FSD prevalence. Most studies (56 %) had low to moderate quality. The mean value of FSFI was lower than 20 at all cancer sites: 16.25 (pooled random effect, 95 % CI 14.91-17.58, I (2) = 14.5 %) for colorectal cancer, 18.11 (95 % CI 14.45-21.77, I (2) = 97.8 %) for gynecological cancer, and 19.58 (95 % CI 17.64-21.53, I (2) = 90.9 %) for breast cancer. FSD prevalence was higher than 60 % at all cancer sites, with the highest value for gynecological cancer (78.44 %, 95 % CI 68.36-88.52 %, I (2) = 94.1 %). Women with cancer showed low FSFI scores with a high prevalence of FSD. Cancer may impair sexual function in women. We provide an overview of studies that address Female Sexual Dysfunction (FSD) in women with cancer with a meta-analysis of observational studies that used a validated diagnostic tool. Searches included MEDLINE, Scopus, and Google Scholar for studies published from January 2000 to 31 December 2014. Every included study had to involve at least 30 cancer patients, to investigate FSD based on the Female Sexual Function Index (FSFI), and to have been published in peer-review journals. Duplicate independent data extraction and quality assessment were performed. Data were pooled using a random effects model if statistical heterogeneity was present. The main outcomes were FSFI total score and FSD prevalence. FSFI is a 19-item self-report instrument for assessing key dimensions of female sexual function. A value less than 26.55 is consistent with FSD. Thirty-five studies met the inclusion criteria. Among these, 27 reported FSFI scores, and 16 FSD prevalence. Most studies (56 %) had low to moderate quality. The mean value of FSFI was lower than 20 at all cancer sites: 16.25 (pooled random effect, 95 % CI 14.91–17.58, I2 = 14.5 %) for colorectal cancer, 18.11 (95 % CI 14.45–21.77, I2 = 97.8 %) for gynecological cancer, and 19.58 (95 % CI 17.64–21.53, I2 = 90.9 %) for breast cancer. FSD prevalence was higher than 60 % at all cancer sites, with the highest value for gynecological cancer (78.44 %, 95 % CI 68.36–88.52 %, I2 = 94.1 %). Women with cancer showed low FSFI scores with a high prevalence of FSD.

We read with interest the article by Makimattila et al. (1) reporting the prevalence of autoimmune diseases (ADs) in patients with type 1 diabetes (T1D) from the Finnish Diabetic Nephropathy (FinnDiane) Study, an ongoing, nationwide, multicenter study aimed at identifying genetic and environmental risk factors for complications of diabetes (1). ADs were identified by linking the data of the FinnDiane cohort (4,758 T1D patients, with a median age of 51.4 years and a median duration of disease of 35.5 years) with those from the nationwide health registries. Makimattila et al. (1) report that 22.8% of their T1D patients had at …

Edelman and Polonsky (1) suggest that poor adherence to pharmacotherapy is largely (∼75%) responsible for the gap between clinical efficacy from randomized controlled trials and real-world effectiveness of antihyperglycemic drugs. As no single strategy can be applied successfully to all patients with type 2 diabetes in order to improve medication adherence, other approaches are suggested, including innovation in delivery methods and reduction of the number of daily pills, shared strategies between clinicians and patients, and easier access to medications. Only 11 years ago, the first newer diabetes drug (sitagliptin) was …

Breast cancer patients (BCP) are at risk of female sexual dysfunction (FSD). Our aim was to clarify the effects of treatment strategies, and steroid hormones levels on FSD. We enrolled 136 BCP (46.9 ± 0.8 years), and 122 completed questionnaires. BCP were divided into four groups: 22 women with advanced breast cancer on neoadjuvant therapy (NAT), 48 on adjuvant therapy (AT), 30 taking hormonal therapy (HT) and 22 with metastatic cancer on first line chemotherapy (FLT). Fifty-eight healthy women (43 ± 2.8 years) were enrolled as controls. FSD was evaluated by FSFI, and sexual distress was assessed with FSDS-R. We have collected demographic data, laboratory values, and LH, FSH, total testosterone (T), and estradiol (E2) levels. BCP showed a prevalence of FSD of 69%, total FSFI score was 17. FSDS-R was 8.3. FSD had a prevalence of 72 % in NAT, 65% in AT, 77% in metastatic BCP under FLT, 67% in HT, compared with a prevalence of 20% in controls. BCP showed lower E2 than normal values, as well as T. LH and FSH were significantly elevated than normal values. Total FSFI score was positively correlated with T in 122 BCP, no significant correlation was found between E2 and FSFI. Significant differences were found between NAT and HT in lubrication, pain domains and total FSDS-R score, AT and HT in pain domain, AT and NAT in lubrication domain. BCP are at high risk of developing FSD both for treatment choice and hormonal status, but they have not sexually related personal distress.

Background: Type 1 diabetic patients have high instability of daily glucose levels. The aim of this study was to evaluate the long-term effects of continuous subcutaneous insulin infusion (CSII) therapy, compared with multiple daily injections of insulin (MDI), on glucose variability, in young type 1 diabetic patients transitioned to the adult diabetes care. Methods: Patients aged 18-30 years and considered eligible for insulin pump therapy were included in the study. Ninety-eight patients who started CSII therapy and 125 who remained in MDI completed a 2-year follow-up. Glucose variability was assessed with continuous glucose monitoring using blood glucose standard deviation (BGSD), mean amplitude of glycemic excursion (MAGE), continuous overall net glycemic action (CONGA-2 h), low blood glucose index, high blood glucose index, and average daily risk range. Results: MAGE and BGSD decreased in both groups, with adjusted differences at 2 years of -0.74 mM (95% confidence interval [CI] -1.22 to -0.26, P = 0.003) and -0.3 (CI -0.52 to -0.1, P = 0.005) favoring the pump-therapy group. No significant differences between groups in the other variability indexes were observed. HbA1c decreased in both groups without significant difference (0.05%, -0.26, 0.35, P = 0.77); fasting glucose, insulin dose, and overall hypoglycemia (daily, nocturnal, and severe) decreased more in patients with CSII, compared with those with MDI. Conclusions: Among young adults with type 1 diabetes transitioning from the pediatric care, the use of CSII is associated with lower glucose variability, fasting glycemia, and overall hypoglycemic events than MDI during a 2-year period of follow-up.

Despite the availability of many new treatment options for type 2 diabetes, the proportion of patients achieving the HbA1c target < 7.0% remains around 50%. We put forward the hypothesis that the unchanged HbA1c results, observed in the last decade in type 2 diabetes patients, are also a consequence of medication nonadherence and clinical inertia. Poor medication-taking behavior is usually defined as medication nonadherence and is responsible for uncontrolled hemoglobin A1c level in 23% of cases. Medication nonadherence may also affect clinical outcomes, as diabetic patients with good adherence (≥80%) had a significant 10% lower rate of hospitalization events and a significant 28% lower rate of all-cause mortality when compared with patients with poor adherence (

The purpose of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the effect of intensified insulin regimens (basal-bolus versus premixed) on glycemic control in patients with type 2 diabetes. We conducted an electronic search until March 2015 on many electronic databases including online registries of ongoing trials. All RCTs comparing basal-bolus with premixed insulin regimens, with a duration of >12 weeks and with >30 patients per arm, were included. Investigators extracted data on study characteristics, outcome measures, and methodological quality. We found thirteen RCTs lasting 16-60 weeks and involving 5255 patients assessed for the primary endpoint (reduction of HbA1c from baseline). Meta-analysis of change in HbA1c level between basal-bolus and premixed insulin regimens resulted in a small and non-significant difference of 0.09% (95% CI -0.03 to 0.21), with substantial heterogeneity between studies (I(2) = 74.4%). There was no statistically significant difference in the event rate for overall hypoglycemia (0.16 episode/patient/year, 95%CI -2.07 to 2.3), weight change (-0.21 kg, -0.164 to 0.185), and daily insulin dose (-0.54 U/day, -2.7 to 1.6). The likelihood for reaching the HbA1c

Quality of care monitoring is a key strategy for health policy. In Italy, the AMD Annals continuous monitoring and quality improvement initiative has been in place since 2006. Results after 8 years are now available.Quality of diabetes care indicators during the years 2004-2011 were extracted from electronic medical records of 300 diabetes clinics. From 200,000 to 500,000 patients with type 2 diabetes were analyzed per year. Six process indicators, eight intermediate outcome indicators, seven indicators of treatment intensity/appropriateness, and a quality of care summary score (Q score) were evaluated. Previous studies documented that the risk of developing a new cardiovascular event was 80 % higher in patients with a Q score15 and 20 % higher in those with a score between 15 and 25, as compared to those with a score25.The proportion of patients with HbA1c ≤7 %, LDL cholesterol100 mg/dl, and blood pressure ≥140/90 mmHg increased by 4.8, 21.9, and 10.0 %, respectively. Process and treatment intensity/appropriateness indicators consistently improved. The proportion of patients with a Q score15 decreased from 13.5 to 6.5 %, while those with a Q score25 increased from 22.9 to 38.5 %.AMD Annals document the progress in quality of diabetes care. Longitudinal improvements in Q score can translate into less cardiovascular events, with evident clinical and economic implications. AMD Annals represent a physician-led effort not requiring allocation of extra-economic resources, which is easy to implement and deeply rooted in routine clinical practice. They are a potential case model for other healthcare systems.

In randomized controlled trials (RCTs), more intensive glucose control in patients with type 2 diabetes leads to a modest (9%) reduction in major cardiovascular events (MACE), associated with a 20% reduction of kidney events and 13% reduction of eye events. The FDA issued guidance in 2008 led to the conduct of numerous cardiovascular outcomes (CVOT) trials to assess cardiovascular safety of new antihyperglycemic therapies in patients with type 2 diabetes. The results of these trials show that insulin glargine, three different dipeptidyl peptidase-4 (DPP-4) inhibitors (saxagliptin, alogliptin, and sitagliptin) and lixisenatide (a glucagon like peptide-1 receptor agonist) produce no significant difference in CVOT when compared with usual care or placebo. Other trials with newer diabetes drugs, including empagliflozin and canagliflozin (two sodium-glucose co-transporter-2 inhibitors), liraglutide and semaglutide (two GLP-1 receptor agonists) succeeded in demonstrating CV benefit in people with type 2 diabetes. In the last two decades, the equation “diabetes equals myocardial infarction” have contributed to the development of preventive therapy for risk factors in diabetes. In both primary and secondary prevention, the diabetic patients with high rates of statin and aspirin treatment have improved CV outcome, as compared with non-users. The drugs used to reduce glucose levels in patients with type 2 diabetes seem important for the ultimate cardiovascular outcome: the combination of intensive glycemic control, when safely attainable, with newer diabetes drugs (empagliflozin, canagliflozin, liraglutide, and semaglutide) may decrease the incidence of MACE, nephropathy and retinopathy. Moreover, depending on the drug used, CV mortality and heart failure may also be reduced.

Background We assessed the long-term effects of a Mediterranean diet on circulating levels of endothelial progenitor cells (EPCs) and the carotid intima-media thickness (CIMT) in patients with type 2 diabetes. Design This was a parallel, two-arm, single-centre trial. Methods Two hundred and fifteen men and women with newly diagnosed type 2 diabetes were randomized to a Mediterranean diet (n = 108) or a low-fat diet (n = 107). The primary outcome measures were changes in the EPC count and the CIMT of the common carotid artery after the treatment period defined as the end of trial (EOT). Results At the EOT, both the CD34+KDR+ and CD34+KDR+CD133+ counts had increased with the Mediterranean diet compared with the low-fat diet (p < 0.05 for both). At the EOT evaluation, there was a significant (p = 0.024) difference of -0.025 mm in the CIMT favouring the Mediterranean diet. Compared with the low-fat diet, the rate of regression in the CIMT was higher in the Mediterranean diet group (51 vs. 26%), whereas the rate of progression was lower (25 vs. 50%) (p = 0.032 for both). Changes in the CIMT were inversely correlated with the changes in EPC levels (CD34+KDR+, r = -0.24, p = 0.020; CD34+KDR+CD133+, r = -0.28, p = 0.014). At the EOT, changes in levels of HbA1c, HOMA, total cholesterol, high-density lipoprotein cholesterol and systolic blood pressure were significantly greater with the Mediterranean diet than with the low-fat diet. Conclusion Compared with a low-fat diet, a long-term trial with Mediterranean diet was associated with an increase in circulating EPCs levels and prevention of the progression of subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes.

Purpose: The aim of this study was to evaluate the prevalence and risk factors associated with female sexual dysfunction (FSD) in young women with type 1 diabetes treated with different intensive insulin regimens. Methods: Type 1 diabetic women aged 18–35 years were included in this study if they had stable couple relationship and no oral contraceptive use. All women were asked to complete the Female Sexual Function Index (FSFI) and other validated multiple-choice questionnaires assessing sexual-related distress (Female Sexual Distress Scale, FSDS), quality of life (SF-36 Health Survey), physical activity (International Physical Activity Questionnaire), depressive symptoms (Zung Self-Rating Depression Scale, SRDS) and diabetes-related problems (Diabetes Integration Scale ATT-19). FSD was diagnosed according to a FSFI score higher than 26.55 and a FSDS score lower than 15. Results: The overall prevalence of FSD in diabetic and control women was 20 and 15 %, respectively (P = 0.446). Compared with the continuous subcutaneous insulin infusion group and control women, diabetic women on multiple daily injections (MDI) had lower global FSFI score (P = 0.007), FSDS score (P = 0.045) and domains such as arousal (P = 0.006), lubrication and satisfaction scores (P

The importance of metabolic syndrome (MetS) lies in its associated risk of cardiovascular disease and type 2 diabetes, as well as other harmful conditions such as nonalcoholic fatty liver disease. In this report, the available scientific evidence on the associations between lifestyle changes and MetS and its components is reviewed to derive recommendations for MetS prevention and management. Weight loss through an energy-restricted diet together with increased energy expenditure through physical activity contribute to the prevention and treatment of MetS. A Mediterranean-type diet, with or without energy restriction, is an effective treatment component. This dietary pattern should be built upon an increased intake of unsaturated fat, primarily from olive oil, and emphasize the consumption of legumes, cereals (whole grains), fruits, vegetables, nuts, fish, and low-fat dairy products, as well as moderate consumption of alcohol. Other dietary patterns (Dietary Approaches to Stop Hypertension, new Nordic, and vegetarian diets) have also been proposed as alternatives for preventing MetS. Quitting smoking and reducing intake of sugar-sweetened beverages and meat and meat products are mandatory. Nevertheless, there are inconsistencies and gaps in the evidence, and additional research is needed to define the most appropriate therapies for MetS. In conclusion, a healthy lifestyle is critical to prevent or delay the onset of MetS in susceptible individuals and to prevent cardiovascular disease and type 2 diabetes in those with existing MetS. The recommendations provided in this article should help patients and clinicians understand and implement the most effective approaches for lifestyle change to prevent MetS and improve cardiometabolic health.

ContextWomen with autoimmune Addison’s disease with normal ovulatory cycles but positive for steroid cell antibodies (StCA) have been considered at risk of premature ovarian insufficiency (POI).DesignThirty-three women younger than 40 years, with subclinical-clinical autoimmune Addison’s disease but with normally ovulatory menses, were followed up for 10 years to evaluate the long-term time-related variations of StCA, ovarian function and follicular reserve. All patients and 27 control women were investigated at the start and every year for the presence and titre of StCA (by indirect immunofluorescence), serum concentrations of anti-Mullerian hormone (AMH) and ovarian function at four consecutive menses every year.ResultsAt the start of the study StCA were present in 16 women (group 1), at low/middle titres (≤1:32) in seven of them (43.8%, group 1A), at high titres (>1:32) in the remaining nine patients (group 1B, 56.2%), while they were absent from 17 patients (group 2). During the follow-up period, all women in group 1A remained StCA-positive at low/middle titres with normal ovulatory menses and normal gonadotrophin and AMH levels, while all patients in group 1B showed a further increase of StCA titres (1:128–1:256) and progressed through three stages of ovarian function. None of the patients in group 2 and controls showed the appearance of StCA or ovarian dysfunction during the follow-up.ConclusionsThe presence of StCA at high titres can be considered a good predictive marker of subsequent development of autoimmune POI. To single out the stages of autoimmune POI may allow a timely therapeutic choice in the subclinical and early clinical stages.

No specific diet is recommended to prevent type 2 diabetes. We did a meta-analysis of prospective cohort studies to assess the association between different diets and prevention of type 2 diabetes. We did a comprehensive search of multiple electronic databases (Medline, Scopus, EMBASE, and ISI web of knowledge) until August 2013 using predefined criteria. We included prospective cohort studies that evaluated the role of different diets in type 2 diabetes prevention. Studies were selected by 2 independent reviewers. We did random-effects meta-analyses to determine the relative risk (RR) of incident diabetes associated with healthful dietary patterns. A total of 21,372 cases of incident diabetes, from 18 prospective studies, with 20 cohorts, in 4 world regions were identified. In the random-effect meta-analysis of the 20 cohorts, RR was 0.80 (95 % confidence interval (CI) = 0.74-0.86, P < 0.001), with high heterogeneity (I 2 = 57 %, P = 0.001) and no evidence of publication bias (Egger's test, P = 0.653). Exclusion of two cohorts produced identical RR (0.80, 95 % CI 0.76-0.84), with nonsignificant heterogeneity (I 2 = 9 %). The risk of incident diabetes did not appreciably change considering the geography (USA, Europe, and Asia), the duration of follow-up (10 years), and type of diets (Mediterranean and DASH, Dietary Approaches to Stop Hypertension, diets). There was a difference between at risk and general population (P = 0.0487), but the evidence was limited to two studies only. The results of our study demonstrate that several healthy diets are equally and consistently associated with a 20 % reduced risk of future type 2 diabetes.

Both type 2 diabetes and secondary hypogonadism may be associated with low vitamin D levels.The aim of this study was to evaluate 25-hydroxyvitamin D (25(OH)D) concentrations in type 2 diabetic males with and without hypogonadism.We performed a case-control study among 122 male adults with type 2 diabetes, 51 with associated hypogonadism (Group 1) and 71 with normal gonadal function (Group 2). One hundred age-matched nondiabetic males with normal gonadal function served as a control group.Levels of 25(OH)D were assessed by a chemiluminescent immunoassay in all patients. Morning testosterone, pituitary, thyroid, parathyroid hormones, fasting glucose, and hemoglobin A1c were also evaluated.The overall diabetic population showed a mean 25(OH)D concentration (22.3 ± 6.09 ng/mL) significantly lower than the control group (34.3 ± 7.2, P0.001), with 81% of diabetic patients presenting 25(OH)D deficiency (20 ng/mL) or insufficiency (20-29.9 ng/mL). The lowest 25(OH)D concentration was found in Group 1 (20.1 ± 6.58 ng/mL). Concentration of 25(OH)D was significantly lower in the 42 patients with hypogonadotropic hypogonadism as compared with the 9 patients with hypergonadotropic hypogonadism (19.4 ± 7.06 vs. 23.8 ± 6.11 ng/mL, P0.001). No difference in erectile dysfunction (ED) prevalence between Group 1 and Group 2 was found, nor was there a correlation between the severity of ED and vitamin D levels (r = -0.10, P = 0.39).These results show that type 2 diabetic patients with hypogonadism present lower 25(OH)D concentration and higher prevalence of vitamin D deficiency, compared with patients without hypogonadism. The finding that 25(OH)D concentrations were similar between type 2 diabetic patients with hypergonadotropic hypogonadism and those with normal gonadal function deserves further study.

Background: The risk of bone fractures in subjects with the metabolic syndrome is unknown. We did a meta-analysis to assess the association between metabolic syndrome, risk of fractures, and bone mineral density (BMD). Materials and Methods: We did searches on electronic databases (Medline, Scopus, and ISI Web of Knowledge) until December 2012 and searched reports to identify studies in humans on bone fractures and BMD at different sites. Two independent reviewers collected the relevant reports. We did random-effects meta-analyses to determine the risk of fractures and BMD values associated with metabolic syndrome. Results: A total of 17 studies, with 35 datasets, were included. In 10 articles (14 datasets) including 1350 incident and 1628 prevalent fractures, metabolic syndrome was associated with a reduced fracture risk (risk ratio = 0.85, 95% confidence interval, 0.71 - 1.00; high heterogeneity: I-2 = 55%, P = .006). Omission of 2 outlier studies resulted in a significant negative association (risk ratio = 0.85, P = .012; I-2 = 34%, P = .130). Most of the reduced fracture risk was seen in cohort studies (18% reduced risk), suggesting a direction of causality; sex, site of fracture, and definition of the syndrome did not affect the estimates. In 16 articles, including 29 341 subjects, there was no difference in spine, femoral neck, or calcaneus BMD values between subjects with or without metabolic syndrome; mean differences ranged from 0.001 to 0.012 g/cm(2) (P > .10). Conclusions: This article shows a reduced risk of bone fractures associated with metabolic syndrome, without modification of BMD. The clinical significance of these findings remains uncertain and should be addressed in future prospective studies.

We performed a systematic review and meta-analysis of the empirical evidence on the association of metabolic syndrome and its components with colorectal cancer incidence and mortality. A systematic literature search of multiple electronic databases was conducted and complemented by cross-referencing to identify studies published before 31 October 2012. Every included study was to report risk estimates with 95 % confidence intervals for the association between metabolic syndrome and colorectal cancer (incidence or mortality). Core items of identified studies were independently extracted by two reviewers, and results were summarized by standard methods of meta-analysis. We identified 17 studies, which reported on 49 data sets with 11,462 cancer cases. Metabolic syndrome was associated with an increased risk of colorectal cancer incidence and mortality in both men (RR: 1.33, 95 % CI 1.18-1.50, and 1.36, 1.25-1.48, respectively) and women (RR: 1.41, 1.18-1.70, and 1.16, 1.03-1.30, respectively). The risk estimates changed little depending on type of study (cohort vs non cohort), populations (US, Europe, Asia), cancer site (colon and rectum), or definition of the syndrome. The risk estimates for any single factor of the syndrome were significant for higher values of BMI/waist (RR: 1.19, 95 % CI 1.10-1.28), dysglycemia (RR: 1.29, 1.11-1.49), and higher blood pressure (RR: 1.09, 1.01-1.18). Dysglycemia and/or higher BMI/waist explained most of the risk associated with metabolic syndrome. Metabolic syndrome is associated with an increased risk of colorectal cancer incidence and mortality in both sexes. The risk conveyed by the full syndrome is not superior to the sum of its parts.

Background: Literature data examining the role of metabolic syndrome and its components in prostate cancer risk are limited and contradictory. Aim: We did a meta-analysis of studies that evaluated the association between metabolic syndrome, its components, and risk of prostate cancer. Subjects and methods: We conducted an electronic search for articles published through September 2012 without restrictions. Every included study was to report risk estimates with 95% confidence intervals for the association between metabolic syndrome and prostate cancer. Results: The final number of papers included in the meta-analysis was 14, all published in English, with 4728 prostate cancer cases. Metabolic syndrome was associated with a 12% increase in prostate cancer risk (p=0.231), that was lower in cohort studies (7 studies, RR=1.04, p=0.791) than other studies (RR=1.23, p=0.125). The association was significant in the 8 European studies (RR=1.30, p=0.034), but not in the 4 U.S. or 2 Asiatic studies. The risk estimates of prostate cancer for higher values of body mass index, dysglycemia or dyslipidemia (high triglycerides, low HDL-cholesterol) were not significant; on the contrary, hypertension and waist circumference >102 cm were associated with a significant 15% (p=0.035) and 56% (p=0.007) greater risk of prostate cancer, respectively. Conclusions: Metabolic syndrome is weakly and non significantly associated with prostate cancer risk, but associations vary with geography. Among single components of the syndrome, hypertension and higher waist circumference are significantly associated with increased risk of prostate cancer.

Introduction: Attaining optimal glycemic targets in patients with type 2 diabetes is often hard and compromised by the shortcomings of the several treatments. Areas covered: When glycemic levels are not adequately controlled, an association of GLP-1 receptor agonists and insulin therapy can be adopted. In order to assess the benefit/risk profile of this combination therapy, a literature search of randomized clinical trials was performed.Eighteen trials matched the inclusion criteria. In 10 studies, GLP-1 receptor agonists were added on to an existing regimen, whereas insulin added to an existing GLP-1 receptor agonists regimen occurred in 2 studies. Six studies compared GLP-1 receptor agonists with short acting insulin as a treatment strategy to intensify basal insulin therapy. Expert opinion: Clinical trials herein reviewed demonstrated the safety and the efficacy of combining GLP-1 receptor agonists with basal insulin, with most studies showing equal or slightly superior efficacy, as compared with the addition of prandial insulin, associated with weight loss and less hypoglycemia.

Diabetes mellitus and cancer are two growing health problems. They have in common many modifiable risk factors including sex, age, obesity, physical activity, diet, alcohol, and smoking, and have a long latency before overtly manifesting. Patients with diabetes experience a roughly 20–25% higher cancer incidence compared to individuals without diabetes, and it depends on cancer site. Moreover, patients with diabetes who further develop cancer have increased early and late mortality in comparison with cancer patients without diabetes. Prediabetes and metabolic syndrome are also related to an increased risk of developing and die from cancer. Possible mechanisms linking diabetes and prediabetes with cancer include hyperglycemia (endogenous or exogenous), hyperinsulinemia, and alterations of insulin-like growth factor system, chronic subclinical inflammation, abnormalities in sex hormone metabolism, and adipokines. It becomes crucial to define the right orientation of the associations between diabetes and cancer in order to identify the modifiable pathogenic mechanisms. The common soil hypothesis claims that prediabetes and diabetes, as well as metabolic syndrome, may be considered a surrogate sign for dietary risk factors of cancer. The clepsydra of foods may help choose foods associated with healthy benefit while avoiding foods associated with harm, including cancer.

The clinical benefits of real time continuous glucose monitoring (rtCGM) use have been well demonstrated in both CSII- and MDI-treated individuals in large clinical trials. However, recommendations for patient use of rtCGM in everyday life situations are lacking. This article provides guidance to clinicians and patients with type 1 diabetes (T1D) in effective use of rtCGM data, including glucose rate of change (ROC) arrows, for insulin dosing adjustments and other treatment decisions. The recommendations presented here are based on our own clinical experiences as endocrinologists, our personal experiences living with T1D using rtCGM, and findings from a recent survey of T1D patients who have successfully used rtCGM in their self-management. It is important that both clinicians and people with diabetes understand the utility and limitations of rtCGM. Maintaining a collaborative clinician-user relationship remains an important factor in safe, successful rtCGM use.

Erectile dysfunction (ED) is a common comorbidity of diabetes mellitus, but few studies investigated its prevalence in type 1 diabetes. The objective of this study was to evaluate the prevalence and correlates of ED in young men with type 1 diabetes treated with different intensive insulin regimens. The study population included 151 type 1 diabetic men, aged 18-35 years, and 60 healthy age-matched controls. Ninety-four men were treated with multiple daily injections of insulin (MDI), and the remaining 71 with continuous subcutaneous insulin infusion (CSII). All participants in the study completed the International Index of Erectile function (IIEF-5), and other validated multiple-choice questionnaires assessing quality of life, physical activity, depressive symptoms and diabetes-related problems. The overall prevalence of ED was higher in diabetic men (37%), as compared with controls (6%, P

Type 2 diabetes has been associated with sexual dysfunction in men and women (1). Erectile dysfunction (ED) is a marker of significantly increased risk of cardiovascular disease and all-cause mortality in men with diabetes and the general population; however, no data support a clear role for female sexual dysfunction (FSD) as a predictor of future cardiovascular events in women with diabetes. There is some evidence from clinical trials that sexual dysfunction is amenable to amelioration with interventions based on diet and lifestyle modification in men and women (2). Using the data of the MEditerranean DIet and Type 2 diAbetes (MEDITA) randomized trial (3), we investigated the long-term effect of Mediterranean diet on 1 ) incident ED and FSD in people with type 2 diabetes and 2 ) combined incidence of sexual dysfunction (men or women) with worsening of sexual function in those participants with sexual dysfunction at baseline. Participants in the two-arm, single-center MEDITA trial were randomly assigned to a Mediterranean diet ( n = 108) or a low-fat …

Because of the increasing prevalence of type 2 diabetes, the need to intensify treatment to manage hyperglycemia is expanding. Premixed insulin regimens were designed to maximize patient convenience and reduce the number of daily injections required by providing both rapid-acting and intermediate-acting components in one formulation. Although the basal bolus insulin regimen is considered by many as “the golden standard” in reaching goals of glycemic control, proper use of intensified insulin regimens, such as basal bolus or premixed, will result in similar HbA1c reduction, hypoglycemic events, and weight gain. At the same number of daily insulin injections (2 shots/day), the premixed regimen is associated with a significant 0.2 % HbA1c decrease, as compared with the basal plus regimen (one shot of long-acting plus one shot of short-acting insulin). The choice of insulin regimen should consider the preferences, and resources of the individual and the family for adapting treatment to the patient needs. At last, the process of insulin initiation and intensification in type 2 diabetes must be carried out in the context of patient safety, minimizing the risk of hypoglycemia, weight gain, and injection burden.