Search

Aim Dental caries is one of the most common oral diseases affecting children. The complex multifactorial aetiology of caries involves host (saliva composition and tooth enamel characteristics), oral microflora and substrate (oral hygiene quality and dietary habits composition). Occlusal characteristics may be also a factor in dental caries development. The aim of this aepidemiologic study was to verify the association between DMFT (Decayed, Missed, Filled Teeth) index and occlusal characteristics, dietary habits, oral hygiene habits and parents' education level in a sample of 12-year-old schoolchildren from Southern Italy. Materials and Methods A sample of 536 children was examined to detect dental caries status and several occlusal variables (i.e. molar relationship, overjet and overbite, presence of crossbite, scissor bite, crowding, diastemas and/or midline deviation). A questionnaire to retrieve parents' educational level, patient's dietary and oral hygiene habits was administered. The associations among these variables were assessed statistically through the Χ2 test. Results A positive association was found between caries, parents' social status and some occlusal disorders. va specificato, l'abstract non può essere una caccia al tesoro. In relation to occlusal variables, crossbite (Χ2=3.96, P=0.04) was significantly associated to caries. A significant association was also found between the education level of mothers (Χ2=7.74, P < 0.01) and fathers (Χ2=6.35, P=0.01) and the presence of caries. Dietary habits, oral hygiene and remaining occlusal characteristics were not associated with caries presence (all P > 0.05). Conclusions Of the evaluated occlusal characteristics only posterior crossbite was associated with caries prevalence. Education level of the parents was the other factor significantly associated with caries. Dietary habits, oral hygiene frequency and the remaining occlusal characteristics were not associated with dental caries.

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.

Cushing's disease (CD) is a severe endocrine condition caused by an adrenocorticotropin (ACTH)-pro- ducing pituitary adenoma that chronically stimulates adrenocortical cortisol production and with potentially serious complications if not or inadequately treated. Active CD may produce a fourfold increase in mortality and is associated with significant morbidities. Moreover, excess mortality risk may persist even after CD treatment. Although predictors of risk in treated CD are not fully understood, the importance of early recognition and ade- quate treatment is well established. Surgery with resection of a pituitary adenoma is still the first line therapy, being successful in about 60-70 % of patients; however, recur- rence within 2-4 years may often occur. When surgery fails, medical treatment can reduce cortisol production and ameliorate clinical manifestations while more definitive therapy becomes effective. Compounds that target hypo- thalamic-pituitary axis, glucocorticoid synthesis or adre- nocortical function are currently used to control the deleterious effects of chronic glucocorticoid excess. In this review we describe and analyze the molecular basis of the drugs targeting the disease at central level, suppressing ACTH secretion, as well as at peripheral level, acting as adrenal inhibitors, or glucocorticoid receptor antagonists. Understanding of the underlying molecular mechanisms in CD and of glucocorticoid biology should promote the development of new targeted and more successful therapies in the future. Indeed, most of the drugs discussed have been tested in limited clinical trials, but there is potential ther- apeutic benefit in compounds with better specificity for the class of receptors expressed by ACTH-secreting tumors. However, long-term follow-up with management of per- sistent comorbidities is needed even after successful treatment of CD.

In the management of adrenocorticotropic hormone (ACTH)–dependent Cushing's syndrome, inferior petrosal sinus sampling (IPSS) provides information for the endocrinologist, the neurosurgeon, and the neuroradiologist. To the endocrinologist who performs the etiological diagnosis, results of IPSS confirm or exclude the diagnosis of Cushing's disease with 80%–100% sensitivity and over 95% specificity. Baseline central-peripheral gradients have suboptimal accuracy, and stimulation with corticotropin-releasing hormone (CRH), possibly desmopressin, has to be performed. The rationale for the use of IPSS in this context depends on other diagnostic means, taking availability of CRH and reliability of dynamic testing and pituitary imaging into account. As regards the other specialists, the neuroradiologist may collate results of IPSS with findings at imaging, while IPSS may prove useful to the neurosurgeon to chart a surgical course. The present review illustrates the current standpoint of these 3 specialists on the role of IPSS.

OBJECTIVE - Available evidence supports the emerging hypothesis that metabolic syndrome may be associated with the risk of some common cancers. We did a systematic review and meta-analysis to assess the association between metabolic syndrome and risk of cancer at different sites. RESEARCH DESIGN AND METHODS - We conducted an electronic search for articles published through October 2011 without restrictions and by reviewing reference lists from retrieved articles. Every included study was to report risk estimates with 95% CIs for the association between metabolic syndrome and cancer. RESULTS - We analyzed 116 datasets from 43 articles, including 38,940 cases of cancer. In cohort studies in men, the presence of metabolic syndrome was associated with liver (relative risk 1.43, P < 0.0001), colorectal (1.25, P < 0.001), and bladder cancer (1.10, P = 0.013). In cohort studies in women, the presence of metabolic syndrome was associated with endometrial (1.61, P = 0.001), pancreatic (1.58, P < 0.0001), breast postmenopausal (1.56, P = 0.017), rectal (1.52, P = 0.005), and colorectal (1.34, P = 0.006) cancers. Associations with metabolic syndrome were stronger in women than in men for pancreatic (P = 0.01) and rectal (P = 0.01) cancers. Associations were different between ethnic groups: we recorded stronger associations in Asia populations for liver cancer (P = 0.002), in European populations for colorectal cancer in women (P = 0.004), and in U.S. populations (whites) for prostate cancer (P = 0.001). CONCLUSIONS - Metabolic syndrome is associated with increased risk of common cancers; for some cancers, the risk differs betweens sexes, populations, and de finitions of metabolic syndrome.

Motivated by the success of using graphene oxide (GO) as a nanofiller of composites, there is a drive to search for this new kind of carbon material as a bioactive component in ceramic materials. In the present study, biomineralized GO was prepared by two different approaches, represented by in situ sol-gel synthesis and biomimetic treatment. It was found that in the biocomposites obtained by the sol-gel approach, the spindle-like hydroxyapatite nanoparticles, with a diameter of ca. 5 ± 0.37 nm and a length of ca. 70 ± 2.5 nm, were presented randomly and strongly on the surface. The oxygen-containing functional groups, such as hydroxyl and carbonyl, present on the basal plane and edges of the GO sheets, play an important role in anchoring calcium ions, as demonstrated by FT-IR and TEM investigations. A different result was obtained for biocomposites after biomimetic treatment: an amorphous calcium phosphate on GO sheet was observed after 5 days of treatment. These different approaches resulted in a diverse effect on the proliferation and differentiation of osteogenic mesenchymal stem cells. In fact, in biocomposites prepared by the sol-gel approach the expression of an early marker of osteogenic differentiation, ALP, increases with the amount of GO in the first days of cell culture. Meanwhile, biomimetic materials sustain cell viability and proliferation, even if the expression of alkaline phosphatase activity in a basal medium is delayed. These findings may provide new prospects for utilizing GO-based hydroxyapatite biocomposites in bone repair, bone augmentation and coating of biomedical implants and broaden the application of GO sheets in biological areas. Copyright © 2016 John WileySons, Ltd.

Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers). (C) 2009 Elsevier B.V. All rights reserved.

The use of ozone in the treatment of peripheral vascular disease (PVD) is increasing. The purpose of this study was to evaluate the effect of ozone on haemoglobin oxygen affinity in Type-2 diabetic patients with PVD. Twenty diabetic patients presenting with PVD (Clinical stage II-IV according to Fontaine) and 20 non-diabetic healthy matched subjects were studied. In both groups, aliquots of blood were ozonised with mixtures of oxygen-ozone (O2-O3) to reach end-concentrations of 6.5, 13, 26 and 78 micrograms O3 per ml of substrate. At baseline, diabetic patients presented significantly lower haemoglobin oxygen affinity values but higher plasma levels of free haemoglobin and malonyldialdehyde (MDA) than controls. In both diabetic patients and controls, exposure of blood to ozone reduced haemoglobin oxygen affinity in an "all-or-none" fashion, without changing 2-3, diphosphoglycerate concentrations in erythrocytes. Both free haemoglobin and MDA concentrations showed significant, dose-dependent increases after blood ozonisation. Thus, ozone caused a significant increase in oxygen unloading of haemoglobin in both normal subjects and Type-2 diabetic patients with PVD.

The influence of synthetic salmon calcitonin (CT) on paraphysiological endocrine pancreas was investigated in Man. Large dose (100 U) as well as low dose (1 U) of CT inhibits glucose-induced insulin responses, reduces the suppressive effect of glucose on glucagon secretion and impairs glucose tolerance. These effects are not mediated by hypocalcemia. Studies in which theophylline or calcium were infused in addition to CT suggest that the mode of action of CT is mediated via a change in calcium redistribution in the islet cells. The diabetogenic action of CT is not observed in Paget and osteoporotic patients, after prolonged administration of the hormone.

Since the isolation of enkephalins 7 yr ago, there has been an explosive increase in knowledge and an enormous interest in the action of both exogenous and endogenous opiates. This review deals with the interaction of opiates with the endocrine pancreas. The results of animal studies performed in vitro do not allow any conclusion to be drawn, because the effects of opioid peptides on pancreatic hormone release seem dependent on many variables, including the agent investigated, dose administered, concentration of glucose in the medium, and experimental procedure used. The results of in vivo animal studies suggest that central administration of opiates and opioid peptides acts indirectly via the sympathetic nervous system to cause hyperglycemia and impaired insulin secretion, while peripheral administration tends to stimulate insulin and glucagon secretion. This last statement seems also to be true for studies performed in human beings. The narcotic addict offers a model to evaluate the hormonal and metabolic effects of a chronically administered agent that binds and activates endogenous receptors. In these subjects, it is possible to find increased concentrations of glycosylated hemoglobin A1 and a marked reduction of the acute insulin response to intravenous glucose, but not to arginine, which suggests a state of defective glucose recognition by pancreatic β-cells during narcotic addiction. Thus, the heroin addict, like patients with non-insulin-dependent diabetes, does not respond appropriately to glucose signals. Moreover, naloxone, an opiate-receptor blocking agent, can cause a partial restoration of the acute insulin response to i.v. glucose in some subjects with non-insulin-dependent diabetes. An increased sensitivity to endogenous opiates—enkephalins—might be important in the pathogenesis of non-insulin-dependent diabetes in human beings.

The role of ubiquitin-proteasome system in the accelerated atherosclerotic progression of diabetic patients is unclear. We evaluated ubiquitin-proteasome activity in carotid plaques of asymptomatic diabetic and nondiabetic patients, as well as the effect of rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-γ activator, in diabetic plaques. Plaques were obtained from 46 type 2 diabetic and 30 nondiabetic patients undergoing carotid endarterectomy. Diabetic patients received 8 mg rosiglitazone (n = 23) or placebo (n = 23) for 4 months before scheduled endarterectomy. Plaques were analyzed for macrophages (CD68), T-cells (CD3), inflammatory cells (HLA-DR), ubiquitin, proteasome 20S activity, nuclear factor (NF)-κB, inhibitor of κB (IκB)-β, tumor necrosis factor (TNF)-α, nitrotyrosine, matrix metalloproteinase (MMP)-9, and collagen content (immunohistochemistry and enzyme-linked immunosorbent assay). Compared with nondiabetic plaques, diabetic plaques had more macrophages, T-cells, and HLA-DR cells (P < 0.001); more ubiquitin, proteasome 20S activity (TNF-α), and NF-κB (P < 0.001); and more markers of oxidative stress (nitrotyrosine and O 2- production) and MMP-9 (P < 0.01), along with a lesser collagen content and IκB-β levels (P < 0.001). Compared with placebo-treated plaques, rosiglitazone-treated diabetic plaques presented less inflammatory cells (P < 0.01); less ubiquitin, proteasome 20S, TNF-α, and NF-κB (P < 0.01); less nitrotyrosine and superoxide anion production (P < 0.01); and greater collagen content (P < 0.01), indicating a more stable plaque phenotype. Similar findings were obtained in circulating monocytes obtained from the two groups of diabetic patients and cultured in the presence or absence of rosiglitazone (7.0 μmol/l). Ubiquitin-proteasome over-activity is associated with enhanced inflammatory reaction and NF-κB expression in diabetic plaques. The inhibition of ubiquitin-proteasome activity in atherosclerotic lesions of diabetic patients by rosiglitazone is associated with morphological and compositional characteristics of a potential stable plaque phenotype, possibly by downregulating NF-κB-mediated inflammatory pathways. © 2006 by the American Diabetes Association.

Human plasma albumin was incubated in 25 mM/l glucose at 37 degrees C for up to sevent days. Aliquots of this mixture were also incubated with alpha-tocopherol (Vitamin E) at 2 mg/dl, 4 mg/dl and 8 mg/dl, respectively. Vitamin E inhibited protein glycation and, furthermore, shows a dose-dependent effect. This report suggests the possibility of using Vitamin E, at therapeutic doses, to obtain the inhibition of non-enzymatic glycation.

The serum concentrations of different glycosaminoglycan fractions have been studied in diabetic subjects without evidence of vascular complications and compared with those of age-and sex-matched normal subjects. Electrophoretic analysis of the various glycosaminoglycan fractions showed an increase in hyalunoric acid and heparin, and a decrease in heparan sulfate, chondroitin-4-sulfate and chondroitin-6-sulfate. Furthermore, the levels of glycosylated haemoglobin A1 were positively correlated with those of hyaluronic acid (r = 0.96, p. less than 0.001) and heparin (r = 0.45, p less than 0.01) in the diabetic group. The present data suggest thah a) in diabetics there is a shift in the metabolism of glycosaminoglycans towards a decreased sulfated glycosaminoglycans/hyaluronic acid ratio; and b) long-lasting hyperglycemia is correlated with the disturbances in the metabolism of glycosaminoglycans.

Dear Sir The hyperglycaemic effect of morphine has been a well recognized phenomenon throughout this century [1], but the mechanism of its action still remains unclear. Recent studies in the dog [2] and in man [3] suggest that both morphine and beta-endorphin increase the plasma levels of glucose, insulin and glucagon. These observations have led to the suggestion that the interference of the opioid peptides on carbohydrate metabolism may be through modifications of pancreatic hormone release. We have studied the effect of protracted morphine administration on carbohydrate metabolism in 27 male addicts (age range: 18-34 years, mean + SEM: 24 _+ 2.2 years) before narcotic withdrawal. The results were compared with those obtained in 46 healthy males matched for age (mean _+ SEM: 25 _+ 1.8 years) and weight. Carbohydrate metabolism was assessed by determining fasting plasma glucose (mean of three samples on three consecutive days) and glycosylated haemoglobin A1 (HbA0 (mean of two sampies) which represents a very useful index of the glycaemic control of the last 3-4 weeks [4]. Glycosylated haemoglobin A1 was determined according to the method of Welch and Boucher [5]. The intra- and inter-assay coefficients of variation for this method are 1.5% and 3%, respectively. The mean _+ SEM HbA1 level was 7.18 + 0.17% in addicts and 6.11 _+ 0.06% in control subjects, a difference which is statistically significant (p < 0.001). No significant difference was found in fasting plasma glucose (5.08 + 0.13 retool/1 in addicts versus 4.72 + 0.19 mmol/1 in control subjects). No significant correlation was found between fasting plasma glucose and HbA1 in addicts. Total haemoglobin was 15 _+ 0.2 g/dl in addicts and 14.3 + 0.4 g/dl in controls (NS) (Fig. 1).

A functional arterial spasm, revealed by reduced post-ischemic response, is present in diabetic subjects with no overt evidence of vascular damage. The administration of three different antioxidant agents, vitamin C, thiopronine and glutathione, produces an increase of basal blood flow in both diabetic and normal subjects, and ameliorates significantly the vascular functional response in diabetes. These data suggest that free radicals may play a role in the regulation of arterial resistance in humans, and that a de-regulation of their action may be involved in the development of arterial dysfunction in diabetes.

Data on fibrinolysis in diabetes mellitus are still unclear, as is the role of hyperglycaemia on this topic and the possibility of any therapeutic intervention. In this study we examined fibrinopeptide A, tissue plasminogen activator and plasminogen activator inhibitor plasma levels in Type 1 diabetic patients compared to matched healthy normal controls, and the effect of induced hyperglycaemia on these parameters. At the same time the effect of a glycosaminoglycan, Sulodexide, administration during hyperglycaemia was evaluated. Fibrinopeptide A and plasminogen activator inhibitor were increased while tissue plasminogen activator was decreased in Type 1 diabetic patients, in the basal state. Induced hyperglycaemia increases fibrinopeptide A formation and tissue plasminogen activator concentrations, while it decreases plasminogen activator inhibitor levels more in normal subjects than in diabetic patients. Sulodexide consistently reduces this phenomenon. This study shows an altered fibrinolytic response to increased thrombin activation in Type 1 diabetic patients and suggests that the administration of the glycosaminoglycan, Sulodexide, may help to reduce this phenomenon.

Alteration of antithrombin III (ATIII) activity, glycemia level dependent, exists in diabetes mellitus. In this study the ability of a low molecular weight heparin (LMWH) (Fluxum, Alfa-Wassermann S.p.A., Bologna, Italy), as well as unfractioned héparin, to preserve ATIII activity from glucose-induced alterations, both in vitro and in vivo, is reported. The subcutaneous and intravenous LMWH and heparin administration increases basal depressed ATIII activity in diabetic patients. Heparin shows an equivalent effect on both anti-IIa and anti-Xa activity of ATIII, while LMWH is more effective in preserving the anti-Xa activity. Similarity, heparin preserves ATIII activity from hyperglycemia-induced alterations, during hyperglycemic clamp, and LMWH infusion is able to preserve a significant amount of anti-Xa activity from glucose-induced alterations. Since diabetic patients show a high incidence of thrombotic accidents, LMWH appears to be a promising innovation for the prevention of diabetic thrombophylia.

To evaluate the status of ano-rectal complex in diabetic patients, 20 patients with no fecal incontinence and/or local ano-rectal disorders and 18 normal subjects underwent to: 1) ano-rectal manometry; 2) defecography; and 3) rectal sensation tests. In all subjects, the five classic cardiovascular reflexes tests were performed to detect autonomic neuropathy. No significant difference between diabetic patients and controls was found in length, maximum resting pressure and strength of phasic external anal sphincter or anal canal at ano-rectal manometry; similarly, no significant difference between diabetic and normal subjects was found by the same technique in threshold and amplitude of ano-rectal inhibitory reflex. Ano-rectal angle of diabetic patients was not significantly different from normals both at resting and during straining at defecographic study. By rectal sensation testing, it was possible to demonstrate a significant difference between diabetic and normal subjects in perception of rectal distension (87.5 +/- 27.5 vs 39.2 +/- 6.5 ml, p less than 0.05; mean +/- SEM) and of stimulus of defecation (147.0 +/- 56.3 vs 52.9 +/- 18.5 ml, p less than 0.001) but not in perception of maximum tolerable volume (343.5 +/- 69.9 vs 322.0 +/- 48.5 ml, p = NS). No relationship was found between these results and the score of autonomic neuropathy and/or duration of diabetic disease. These data suggest that an early involvement of only sensory parasympathetic fibers of ano-rectal complex occurs in diabetic patients without gastrointestinal symptoms.

Background Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose co-transporter-2 (SGLT-2) inhibitors reduce cardiorenal outcomes. We performed a network meta-analysis to compare the effect on cardiorenal outcomes among GLP-1 RAs, SGLT-2 inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. Methods We searched the PUBMED, Embase and Cochrane databases for relevant studies published up until 10 December 2021. Cardiovascular and renal outcome trials reporting outcomes on GLP-1RA, SGLT-2 inhibitors and DPP-4 inhibitors in patients with or without type 2 diabetes mellitus were included. The primary outcome was major adverse cardiovascular events (MACE); other outcomes were cardiovascular and total death, nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure (HHF), and renal outcome. Results Twenty-three trials enrolling a total number of 181,143 participants were included. DPP-4 inhibitors did not lower the risk of any cardiorenal outcome when compared with placebo and were associated with higher risks of MACE, HHF, and renal outcome when compared with the other two drug classes. SGLT-2 inhibitors significantly reduced cardiovascular (RR = 0.88) and total (RR = 0.87) death, as compared with DPP-4 inhibitors, while GLP-1 RA reduced total death only (RR = 0.87). The comparison between GLP-1RA and SGLT-2 inhibitors showed no difference in their risks of MACE, nonfatal MI, nonfatal stroke, CV and total death; SGLT-2 inhibitors were superior to GLP-1RA in reducing the risk of HHF and the renal outcome (24% and 22% lower risk, respectively). Only GLP-1RA reduced the risk of nonfatal stroke (RR = 0.84), as compared with placebo. There was no head-to-head trial directly comparing these antidiabetic drug classes. Conclusions SGLT-2 inhibitors and GLP-1RA are superior to DPP-4 inhibitors in reducing the risk of most cardiorenal outcomes; SGLT-2 inhibitors are superior to GLP-1RA in reducing the risk of HHF and renal events; GLP-1RA only reduced the risk of nonfatal stroke. Both SGLT-2 inhibitors and GLP-1RA should be the preferred treatment for type 2 diabetes and cardiorenal diseases.

Background A meta-analysis is presented of cardiovascular outcome trials (CVOTs) comparing glucagon-like peptide-1 receptor agonists (GLP-1RA) versus placebo on cardiorenal outcomes in patients with type 2 diabetes mellitus (T2DM). Methods We did an electronic search up to June 30, 2021, for eligible trials. We did a meta-analysis of available trial data using a random-effects model to calculate overall hazard ratios (HRs) and 95% CI (confidence intervals). We included data from 8 CVOTs and 60,080 patients (72.4% with established cardiovascular disease). Results GLP-1RA reduced major cardiovascular events (MACE) by 14% (HR = 0.86, 95% CI 0.79–0.94, P = 0.006) with a non-significant heterogeneity between subgroups of patients with and without cardiovascular disease (P = 0.127). GLP-1RA also reduced the risk of cardiovascular death by 13% (P = 0.016), nonfatal stroke by 16% (P = 0.007), hospitalization for heart failure by 10% (P = 0.023), all-cause mortality by 12% (P = 0.012), and the broad composite kidney outcome by 17% (P = 0.012), which was driven by a reduction in macroalbuminuria only (HR = 0.74, 0.67–0.82, P Conclusions GLP-1RA have moderate benefits on MACE, and also reduce hospitalization for heart failure and all-cause mortality; they also have robust benefits on reducing the incidence of macroalbuminuria.

Lower extremity amputations (LEA) are associated with a high mortality and medical expenditure. Diabetes accounts for 45% to 70% of LEA and is one of the most potent risk factors for peripheral artery diseases (PAD). The existence of a link between the recent relaxation of glycemic targets and the resurgence of LEA is suggested from the analysis of adult participants in the National Health and Nutrition Examination Survey (NHANES) between 2010 and 2015, when diabetes-related LEA increased by more than 25% associated with a decline in glycemic control. Indeed, in “the perfect wave” of NHANES, including the years 2007–2010, there was the highest number of diabetic people with hemoglobin A1c (HbA1c), non-high-density lipoprotein (HDL) cholesterol and blood pressure levels at their respective targets, associated with the lowest number of LEA. Until now, the ACCORD study, testing the role of aggressive vs conventional glucose control, and the LEADER trial, evaluating the effects of liraglutide versus placebo, have shown a reduced incidence of LEA in people with type 2 diabetes. The results of ongoing clinical trials involving glucagon-like peptide-1 receptor agonists (GLP-1RA, liraglutide or semaglutide) hopefully will tell us whether the wider use of these drugs may provide additional vascular benefits for diabetic people affected by PAD to decrease their risk of LEA.

Cardiovascular outcome trials (CVOTs) have demonstrated a significant reduction of major adverse cardiovascular events (MACE) in patients with type 2 diabetes (T2D) treated by SGLT-2 inhibitors. This holds true in the presence of background therapy with statins in most patients. Noteworthy, this SGLT-2 inhibitors effect is unique because, at variance with other components of cardiorenal protection, MACE prevention does not appear to be a class effect. Here, we present meta-analysis of the four key CVOTs indicating a major role of renal function in determining the extent of MACE prevention, with the benefit increasing in more severe kidney disease, that is, a high-risk condition where effectiveness of the traditional approach with statins is reduced.

The combination of rapid-acting plus long-acting insulins has been the cornerstone of therapy of patients with type 1 diabetes mellitus (T1DM) and has also become the gold standard of insulin therapy in type 2 diabetes (T2DM). A significant proportion of T2DM patients are overtreated, with potential harms of insulin therapy exceeding its benefits. Treatment simplification aims to decrease the complexity of insulin regimens, including, but not limited to fewer administration times and fewer blood glucose checks. Few small studies in T2DM patients with good glycemic control have shown that glucagon-like peptide-1 receptor agonists (GLP-1RA) or sodium-glucose cotrasporter-2 (SGLT-2) inhibitors can be a safe and effective alternative to bolus insulin, if basal insulin administration is continued. Two larger and controlled trials have thrown some light about simplification of complex insulin regimens in patients with T2DM and poor glycemic control. Although different in their design (randomized controlled trial versus pragmatic trial), their results provide evidence that it is possible to switch from a basal bolus insulin regimen to a combination of basal insulin plus either a GLP-1RA or a daily gliflozin pill, with same or better glycemic control, less injections, less insulin doses, less hypoglycemia and increased satisfaction of therapy. The dogma about the untouchability of basal bolus insulin regimen has been confuted.

Purpose: A relationship between thyroid dysfunction and diabetes mellitus has been described by several authors but the role of glycemic variability is still unclear. We planned the present study to evaluate the influence of glycemic variability on thyroid hormones and TSH concentrations in patients with type 1 diabetes mellitus (T1DM).Methods: Seventy-seven young patients with T1DM were enrolled and evaluated for basal glucose concentrations, HbA1c, thyroid hormones and TSH concentrations. Glucose variability was investigated by considering the standard deviation of blood glucose readings and by calculating the mean amplitude of glycemic excursions and continuous overlapping net glycemic action (CONGA). The low (LBGI) and high (HBGI) blood glucose indices were also calculated. The correlations between TSH, thyroid hormones, glycemia and HbA1c were studied in patients and in controls, whereas those between TSH, thyroid hormones and indices of glucose variability only in patients.Results: No correlations were observed in T1DM patients between free thyroid hormones and glycemic values, HbA1c and indices of glucose variability, while an inverse correlation was observed between TSH levels and glycemic values (r = −0.27; p = 0.01), CONGA index (r = −0.35; p = 0.001) and HBGI (r = −0.28; p = 0.01) but not with HbA1c (r = −0.1; p = 0.47). Conclusions: Our results suggest a direct action of glycemic excursions on TSH secretion, regardless of variations of thyroid hormone concentrations. Thus, the evaluation of thyroid function through the assay of TSH concentrations in these patients should be made, if possible, by multiple samples on patients in euglycemic state to avoid underestimation or overestimation of thyroid dysfunction due to a wrong diagnosis of euthyroidism or dysthyroidism with consequent inappropriate choice of therapeutic options.

As a consequence of the coronavirus disease 2019 (COVID-19) pandemic, profound changes in daily lives have occurred. In Italy, the exponential spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection required extraordinary measures to limit viral transmission, leading to an almost complete lockdown of the country (1). The mandatory lockdown significantly affected patients with chronic diseases, including people with diabetes and diabetic foot ulceration (DFU), which represents a heavy burden for health care systems in terms of mortality and reduced quality of life (1,2). The interruption of preventive education, early treatment, and diagnosis may have led to increased hospitalization of patients with severe DFU at high amputation risk (3). The aim of this study was to evaluate clinical features and amputation risk of individuals with diabetes and DFU admitted to a tertiary care center during the COVID-19 lockdown compared with a population admitted in the first 5 months of 2019. Patients with diabetes and DFU admitted to the Division of Endocrinology and Metabolic Diseases at the Teaching Hospital of University of Campania “Luigi Vanvitelli” (Naples, Italy) from 9 March 2020 to 18 May 2020 were included in this study. This cohort was compared with a population of patients admitted …

Aims GIOIA is an ongoing prospective multicentre study aiming to assess the vascular and metabolic effects of SGLT-2 inhibitors (gliflozins) and DPP-4 inhibitors (gliptins) in the routine clinical practice of patients with type 2 diabetes (T2D). Herein we describe the preliminary effectiveness data at 6 months. Methods SGLT-2i and DPP-4i-naive adult patients with T2D (N = 301 and 260, respectively), with glycated haemoglobin A1c (A1C) >7%, an estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2, on background therapy with metformin, insulin or both, are being followed to evaluate markers of vascular (carotid intima-media thickness), myocardial (myocardial diastolic function) and renal (urinary albumin/creatinine ratio) damage during treatment with SGLT-2i or DPP-4i for a period of 24 months. Result At baseline, patients initiated on SGLT-2i are younger (about 6 years) and more heavy (about 7.5 kg), have higher A1C level (0.5% more), a longer diabetes duration and more CV events (20% more) than patients initiated on DPP‐4i. At 6 months, patients on SGLT-2i (N = 298) and DPP-4i (N = 258) exhibit significant ameliorations in A1C (−1.% and −0.7%, respectively), which were greater (−1.2% and −0.81%) in those on a background metformin treatment only. The composite endpoint (A1C ≤ 7.0% + weight loss ≥ 3 kg) was achieved by 24% and 16% of patients receiving SGLT-2i or DPP-4i, respectively. No unexpected adverse events were reported. Conclusions Both SGLT-2i and DPP-4i provide substantial improvements in metabolic parameters in the usual clinical practice of T2D, especially when used as second-line treatment.

We provided an updated systematic review with meta-analysis of randomized controlled trials (RCTs) assessing the metabolic effects of combination therapy of insulin and GLP-1RA (combo) in comparison with other injectable therapy. We searched PubMed, Cochrane Register of Controlled Trials, Scholar, and ClinicalTrials.gov for RCTs evaluating changes in HbA1c (primary outcome), proportion of patients at HbA1c target

Aims: Sodium–glucose cotransporter-2 inhibitors (gliflozins) and statins are oral drugs that may have beneficial cardiovascular effects in patients with type 2 diabetes, especially in those with known cardiovascular disease. We planned a systematic review and meta-analysis of cardiovascular outcome trials (CVOTs) that evaluated the effect of gliflozins on MACE risk in patients with T2D stratified by age and by statin use. Methods: The electronic search was carried out until 20 January 2020. RCTs were included if they were CVOTs performed in adults with T2D, compared add-on therapy with any gliflozin versus placebo, and had major cardiovascular events (MACE) as primary outcome. We limited the evaluation to MACE in order to minimize the statistical impact of post-hoc analyses. We used a random-effect model to calculate hazard ratio (HR) and 95% CI. Results: The hazard ratio for MACE was 0.95 (95% CI, 0.86–1.05) in people

Metabolic diseases are associated with chronic low-grade inflammation, which has been indicated as a potential mediator of endothelial dysfunction and cardiovascular disease. Visceral adiposity is thought to be the starting condition of the inflammatory state through the release of inflammatory cytokines, including TNF-alpha, CRP, and IL-6, which in turn promote endothelial dysfunction, endothelial expression of chemokines (IL-1) and adhesion molecules (ICAM-1, VCAM-1, and P-selectin), and the inhibition of anti-atherogenic factors (adiponectin). Obesity, metabolic diseases, and diabetes, all conditions characterized by abdominal fat, are well-recognized risk factors for sexual dysfunction in both sexes. Evidence from randomized-controlled trials supports the association between inflammatory milieau and erectile dysfunction in men suffering from metabolic diseases, whereas, in women, this has to be confirmed in further studies. A healthy lifestyle based on dietary pattern with high content of whole grain, fruit, nuts and seeds, and vegetables and low in sodium and saturated fatty acids plus regular physical activity may help to modulate the pro-inflammatory state associated with metabolic diseases and the related burden of sexual dysfunctions.

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.

Background: The real efficacy of selenium supplementation in Hashimoto’s thyroiditis (HT) is still an unresolved issue. Objectives: We studied the short-term effect of l-selenomethionine on the thyroid function in euthyroid patients with HT. Our primary outcome measures were TSH, thyroid hormones, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb) levels and thyroid echogenicity after 6months of l-selenomethionine treatment. The secondary outcome measure was serum CXCL10 levels. Methods: In a placebo-controlled randomized prospective study, we have enrolled untreated euthyroid patients with HT. Seventy-six patients were randomly assigned to receive l-selenomethionine 166µg/die (SE n=38) or placebo (controls n=38) for 6months. TSH, free T 4 (FT 4 ), free T 3 (FT 3 ), TPOAb and CXCL10 serum levels were assayed at time 0, after 3 and 6months. An ultrasound examination of the left and right thyroid lobe in transverse and longitudinal sections was performed. A rectangular region, the region of interest, was selected for analysis. Results: TSH, FT4, FT3, TPOAb, thyroid echogenicity and CXCL10 were not statistically different between SE and control groups at time 0, after 3 and 6months. In the SE group, FT 4 levels were significantly decreased (P&nbsp

Objective: To evaluate the effect of surgical menopause and estrogen replacement therapy on atrio–ventricular conduction and ventricular repolarization in women. Methods: In a prospective, randomized, double-blind, placebo-controlled clinical trial 50 women underwent hystero–salpingo–oophorectomy. Twenty-five women were treated with 50 μg/die of transdermal estradiol and the other 25 were treated with placebo patches. The duration of the treatment was 12 cycles. Before surgery and after 12 cycles of treatment, a standard electrocardiogram was performed to evaluate atrio–ventricular conduction time and cardiac repolarization time. Results: No significant variations in atrio–ventricuar conduction time and cardiac repolarization time were detected between the two groups at entry, nor was there any difference in both groups after 12 cycles of treatment with transdermal estradiol. Conclusions: Surgical menopause and estrogen replacement therapy do not modify atrio–ventricular conduction and ventricular repolarization in women.

Detection of antipituitary antibodies (APA) at high levels and with a particular immunofluorescence pattern in patients with autoimmune polyendocrine syndromes may indicate a possible future autoimmune pituitary involvement. This longitudinal study was aimed at characterizing in patients with a single organ-specific autoimmune disease the pituitary cells targeted by APA at start, verifying whether this characterization allows to foresee the kind of possible subsequent hypopituitarism.Thirty-six APA positive and 40 APA negative patients with isolated autoimmune diseases participated in the study. None of them had pituitary dysfunction at entry. Characterization by four-layer immunofluorescence of pituitary cells targeted by APA in APA positive patients at entry and study of pituitary function in all patients were performed every 6 months during a 5 year follow-up.Antipituitary antibodies immunostained selectively one type of pituitary-secreting cells in 21 patients (58.3 %, group 1), and several types of pituitary cells in the remaining 15 (41.7 %, group 2). All patients in group 1 showed subsequently a pituitary insufficiency, corresponding to the type of cells targeted by APA in 18 of them (85.7 %). Only 8 out of 15 patients in group 2 (53.3 %) showed a hypopituitarism, isolated in 7 and combined in the other one. None of APA negative patients showed hypopituitarism.The characterization of pituitary cells targeted by APA in patients with isolated autoimmune diseases, when the pituitary function is still normal, may help to foresee the kind of subsequent hypopituitarism, especially when APA immunostained selectively only one type of pituitary cells. A careful follow-up of pituitary function in these patients is advisable to allow an early diagnosis of hypopituitarism, even in subclinical phase and a consequent timely replacement therapy.

Osteoporosis increases dramatically with age. About 40 % of women in developed countries will experience an osteoporosis-related fracture in the course of their lifetime, with men experiencing approximately one-third to one-half the risk of women. The “lipid hypothesis of osteoporosis” claims for a role of oxidized lipids as a contributing factor in osteoporosis. On the other hand, statins are supposed to exert anabolic effects on the bone, either through their lipid-lowering action or signal pathways that are independent of their effects on lipid levels. The epidemiological evidence seems to suggest that higher triglycerides may give some protection against fracture, although no association with reduced fracture risk has been reported between lipid-lowering drug (except statins) users and non-users. The epidemiological evidence for a role of statins in osteoporosis is strong, with a lower fracture risk ranging from 30 to 40 % in statin users versus non-users. However, some pitfalls inherent to observational studies (high heterogeneity, residual confounding, potential publication bias) and the lack of association in randomized trials suggest caution. At the moment, the evidence for a role of statins in prevention of osteoporosis is insufficient to recommend starting statin therapy with the aim to prevent osteoporosis.

Introduction. Limited data are available supporting the notion that treatment of lifestyle risk factors may improve erectile dysfunction (ED). Aim. In the present study, we analyzed the effect of a program of changing in lifestyle designed to improve erectile function in subjects with ED or at increasing risk for ED. Methods. Men were identified in our database of subjects participating in randomized controlled trials evaluating the effect of lifestyle changes. A total of 209 subjects were randomly assigned to one of the two treatment groups. The 104 men randomly assigned to the intervention program received detailed advice about how to reduce body weight, improve quality of diet, and increase physical activity. The 105 subjects in the control group were given general information about healthy food choices and general guidance on increasing their level of physical activity. Main Outcome Measures. Changes in erectile function score (International Index of Erectile Function-5 (IIEF-5); items 5, 15, 4, 2, and 7 from the full-scale IIEF-15) and dependence of the restoration of erectile function on the changes in lifestyle that were achieved. Results. Erectile function score improved in the intervention group. At baseline, 35 subjects in the intervention group and 38 subjects in the control group had normal erectile function (34% and 36%, respectively). After 2 years, these figures were 58 subjects in the intervention group and 40 subjects in the control group, respectively (56% and 38%, P = 0.015). There was a strong correlation between the success score and restoration of erectile function. Conclusions. It is possible to achieve an improvement of erectile function in men at risk by means of nonpharma- cological intervention aiming at weight loss and increasing physical activity. Esposito K, Ciotola M, Giugliano F, Maiorino MI, Autorino R, De Sio M, Giugliano G, Nicoletti G, D'Andrea F, and Giugliano D. Effects of intensive lifestyle changes on erectile dysfunction in men. J Sex Med 2009;6:243-250.