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Purpose Bone formation is impaired in both type 1 diabetes and type 2 diabetes (T2D), whereas sclerostin, an antagonist of bone formation, is increased in T2D only. No data are available on latent autoimmune diabetes in adults (LADA), an autoimmune type of diabetes that may clinically resemble T2D at diagnosis. We evaluated serum sclerostin and bone turnover markers in LADA compared with those in T2D and whether metabolic syndrome (MetS) affects sclerostin in T2D or LADA. Methods This cross-sectional study included 98 patients with T2D and 89 with LADA from the Action LADA and Non Insulin Requiring Autoimmune Diabetes cohorts. Patients were further divided according to MetS status. Nondiabetic participants (n = 53) were used as controls. Serum sclerostin, bone formation (pro-collagen type 1 N-terminal propeptide [P1NP]), and bone resorption (C-terminal telopeptide of type I collagen [CTX]) were analyzed. Results Patients with T2D had higher sclerostin than did those with LADA [P = 0.0008, adjusted for sex and body mass index (BMI)], even when analysis was restricted to patients with MetS (adjusted P = 0.03). Analysis of T2D and LADA groups separately showed that sclerostin was similar between those with and those without MetS. However, a positive trend between sclerostin and number of MetS features was seen with T2D (P for trend = 0.001) but not with LADA. Patients with T2D or LADA had lower CTX than did controls (P = 0.0003) and did not have significantly reduced P1NP. Sclerostin was unrelated to age or hemoglobin A1c but was correlated with BMI (ρ = 0.29; P = 0.0001), high-density lipoprotein (ρ = −0.23; P = 0.003), triglycerides (ρ = 0.19; P = 0.002), and time since diagnosis (ρ = 0.32; P < 0.0001). Conclusions Patients with LADA presented lower bone resorption than did controls, similar to patients with T2D. Sclerostin is increased in T2D but not in LADA, suggesting possible roles on bone metabolism in T2D only.

To evaluate the relationship between wrist circumference, markers of adipose dysfunction, and cardiovascular risk in youths with obesity. In this cross-sectional study, we measured body mass composition by dual-energy X-ray absorptiometry, wrist circumference, waist-to-height ratio, fasting blood insulin, glucose, lipid profile, adiponectin, and leptin in 280 children with overweight/obesity and without diabetes (age: 7–18 years). Cardiovascular risk was estimated by “metabolic syndrome score” (MetS score). Study participants had median [25th–75th percentile] wrist circumference of 17.5 [16.7–18.5] cm and waist-to-height ratio of 0.62 [0.59–0.67]. Lower adiponectin–leptin ratio was found among subjects in the upper 50th percentiles of wrist circumference [0.17 (0.09–0.36) vs. 0.38 (0.16–0.79); p

PurposeIncreased corneal and epidermal Langerhans cells (LCs) have been reported in patients with diabetic neuropathy. The aim of this study was to quantify the density of LCs in relation to corneal nerve morphology and the presence of diabetic neuropathy and to determine if this differed in patients with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and latent autoimmune diabetes of adults (LADA).MethodsPatients with T1DM (n = 25), T2DM (n = 36), or LADA (n = 23) and control subjects (n = 23) underwent detailed assessment of peripheral neuropathy and corneal confocal microscopy. Corneal nerve fiber density (CNFD), branch density (CNBD), length (CNFL) and total, immature and mature LC densities were quantified.ResultsLower CNFD (P < 0.001), CNBD (P < 0.0001), and CNFL (P < 0.0001) and higher LC density (P = 0.03) were detected in patients with T1DM, T2DM, and LADA compared to controls. CNBD was inversely correlated with mature (r = -0.5; P = 0.008), immature (r = -0.4; P = 0.02) and total (r = -0.5; P = 0.01) LC density, and CNFL was inversely correlated with immature LC density (r = -0.4; P = 0.03) in patients with T1DM but not in patients with T2DM and LADA.ConclusionsThis study shows significant corneal nerve loss and an increase in LC density in patients with T1DM, T2DM, and LADA. Furthermore, increased LC density correlated with corneal nerve loss in patients with T1DM.

The aim of this real-world study is to evaluate the effect of glucagon-like peptide1 receptor-agonist (GLP1 RA) and sodium-glucose co-transporter2 inhibitor (SGLT2i) on coronary heart disease (CHD) risk, in patients with type 2 diabetes (T2D) in primary cardiovascular prevention.Data from 312 patients with T2D, without CHD history, starting treatment with GLP1 RA (n = 174) or SGLT2i (n = 138), were retrospectively collected. UKPDS-RE score was used to estimate 10-years risk for CHD before and 6, 12 and 24 months after prescription.The 10-year CHD risk significantly decreased over 24 months in both GLP1 RA and SGLT2i groups (p = 0.037 and p 0.001, respectively), with 3% and 7% CHD risk reduction already obtained after the first 6 months of GLP1 RA and SGLT2i therapy respectively (p 0.001 in both groups. Analyses by categories of baseline CHD risk showed significant reductions of CHD risk in the severe risk categories of both groups (p 0.001). CHD risk reduction obtained with SGLT2i was higher than with GLP1 RA at 6 and 12 months but not at 24 months.This real-world study shows that both GLP1 RA and SGLT2i reduce the 10-year risk for cardiovascular disease in patients with T2D in primary cardiovascular prevention.

BACKGROUND Sclerostin (SC) is a monomeric glycoprotein expressed by osteocytes that affects bone formation. Recent studies have suggested a potential role for this protein in the pathophysiology of vascular diseases. The aim of the present study was to investigate SC expression in atherosclerotic plaques of patients affected by severe atherosclerotic disease who underwent carotid endarterectomy. We also evaluated possible differences in SC expression between patients with and without type 2 diabetes (T2D). METHODS This was a cross-sectional study involving 46 patients aged 55 to 80 years (mean, 71.1 ± 6.7 years, 36 men, 15 patients with T2D) who underwent carotid endarterectomy. Immunohistochemical levels of SC were evaluated in the atherosclerotic plaques by double-staining immunochemistry, and serum SC levels were evaluated by enzyme-linked immunosorbent assay. RESULTS Sclerostin was present in the atherosclerotic plaques of all subjects investigated and increased significantly in the media compared with the intima (P

Diabetes is a metabolic disease characterized by high blood glucose levels resulting from impaired insulin production or insulin resistance or both. It has been well established that bone fragility is a new complication of diabetes, particularly of type 1 diabetes (T1D) [1]. Diabetes may negatively affect bone health by unbalancing several processes and systems: bone formation, bone resorption, collagen formation and collagen cross-linking, secretion of inflammatory cytokines, skeletal muscle, incretin system, bone marrow adiposity, calcium metabolism, etc.

The aim of this study was to assess the relation of wrist circumference with changes in left ventricular (LV) structure in a population of overweight/obese children and adolescents. One hundred and six children and adolescents were consecutively enrolled. In all subjects body weight, height, wrist circumference, waist circumference, body mass index-standard deviation score, fasting glucose, insulin, lipid profile, and blood pressure were evaluated. All subjects underwent echocardiographic assessment, and the following parameters were evaluated: LV dimension at end diastole and LV dimension at end systole, LV posterior wall thickness at end diastole and LV posterior wall thickness at end systole, interventricular septal thickness at end diastole and interventricular septal thickness at end systole, LV mass, and epicardial adipose tissue (EAT). LV hypertrophy was defined as LVM Index >=95th percentile. Wrist circumference correlated with all parameters of LV dimensions and LV mass (p

Background: Sclerostin (SC) is a circulating glycoprotein secreted by osteocytes that exerts its inhibitory role on osteoblasts by the Wnt canonical pathway. This results in a reduced bone formation. SC serum levels are increased in patients affected by Chronic Kidney Disease (CKD) being positive correlated with vascular calcification. SC serum levels and vascular calcification show a positive correlation also in patients with atherosclerotic vascular disease mainly in Type 2 Diabetes (T2D) patients. Aims:The aim of the present study was to investigate the SC expression in the atherosclerotic plaques of patients who underwent carotid endarterectomy. The secondary aims were to verify whether there were differences between T2D and non T2D patients in terms of SC expression and if there was a correlation between SC serum level and expression in the atherosclerotic plaques. Methods: This was a cross-sectional study involving 46 subjects (age = 71.1 u00b1 6.7 years, 36 men), 15 T2D patients (disease duration 7.2 u00b1 5.0 yrs), that underwent to surgical carotid endarterectomy in order to remove critical atherosclerotic plaques (>70%). We have excluded patients affected by Type 1 diabetes mellitus, autoimmune disease, osteoporosis, end stage renal disease, sclerostosis, hyperparathyroidism, cirrhosis, previous bone fractures. Serum levels of SC were also measured. Thereafter the plaques were collected, decalcified in osteodec and processed for paraffin embedding. The presence of SC was detected by immunohistochemistry using SC monoclonal antibodies (rabbit polyclonal, 1:25, ABCAM). We compared intima and media tunica, subdividing the plaque into three parts: core, shoulder and peri-calcification; finally, we evaluated the different cells: lymphocytes, macrophages and Vascular Smooth Muscle Cells (VSMC), the level of SC was defined considering five levels (absent, focal, mild, moderate and diffused) following the SIAPeC-IAP study group criteria. McNemar test was used to compare SC expression into plaque components. Results: SC expression was detected in all atherosclerotic plaques. SC was more significantly expressed in the media compared to the intima (p

Recent evidence demonstrating an increased fracture risk among obese individuals suggests that adipose tissue may negatively impact bone health, challenging the traditional paradigm of fat mass playing a protective role towards bone health. White adipose tissue, far from being a mere energy depot, is a dynamic tissue actively implicated in metabolic reactions, and in fact secretes several hormones called adipokines and inflammatory factors that may in turn promote bone resorption. More specifically, Visceral Adipose Tissue (VAT) may potentially prove detrimental. It is widely acknowledged that obesity is positively associated to many chronic disorders such as metabolic syndrome, dyslipidemia and type 2 diabetes, conditions that could themselves affect bone health. Although aging is largely known to decrease bone strength, little is yet known on the mechanisms via which obesity and its comorbidities may contribute to such damage. Given the exponentially growing obesity rate in recent years and the increased life expectancy of western countries it appears of utmost importance to timely focus on this topic.

On the road towards personalized treatments for type 2 diabetes, we suggest here that two parameters could be added to the ABCDE algorithm, 'F' for frailty and 'G' for geography. Indeed, the progressive ageing of population is causing a simultaneous increase of frailty worldwide. The identification of the optimal therapeutic approach is often difficult in frail subjects because of the complexity of 'frailty syndrome'. Nevertheless, given the relevance of diabetes in the development and progression of frailty, a safe and effective cure of diabetes is extremely important to guarantee a good medical outcome. There are few data about diabetes treatment in this delicate category of patients, and the choice of the appropriate therapy mostly remains a challenge. Moreover, type 2 diabetes affects more than 382 million people of different countries, races and ethnicities. To face the lack of solid evidence-based medicine for the treatment of diabetes in different ethnic groups, it is extremely important to increase knowledge about the different pathophysiology of diabetes according to ethnicity. In this way, a tailored approach to treatment of various ethnic groups living in the same or different regions can eventually be developed. Copyright © 2016 John WileySons, Ltd.

Fracture risk is higher in older adults with type 2 diabetes and may be influenced by treatments for diabetes. Oral anti-diabetic drugs have different effects on bone metabolism. The purpose of this review is to describe the effects of these drugs on bone metabolism and fracture risk. Osteoporosis is a progressive skeletal disorder that is characterized by compromised bone strength and increased risk of fracture. This condition has become an important global health problem, affecting approximately 200 million people worldwide. Another chronic and highly prevalent condition is diabetes mellitus, which affects more than 380 million people; both type 1 and type 2 diabetes are risk factors for fracture. Type 2 diabetes, in particular, is associated with impaired bone strength, although it is characterized by normal or elevated bone mineral density. Several therapeutic strategies are available to achieve the best outcomes in the management of diabetes mellitus but these have different effects on bone metabolism. The purpose of this narrative review is to describe the effects of oral hypoglycemic agents (metformin, sulfonylureas, thiazolidinediones, meglitinides, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-dependent glucose transporter 2 inhibitors) on bone metabolism and on the risk of developing fragility fractures in patients with type 2 diabetes. Both diabetes and osteoporosis represent a significant burden in terms of healthcare costs and quality of life. It is very important to choose therapies for diabetes that ensure good metabolic control whilst preserving skeletal health.

Although there is an evidence of correlation between irisin and osteoporotic fractures, previous studies have not elucidated the relationship between irisin and either lean or fat mass. The main aim of this study is to investigate the relationship between irisin and body composition in postmenopausal women with osteoporosis and the impact of irisin levels on fragility vertebral fractures.In this cross-sectional study, 36 overweight subjects affected by at least one vertebral osteoporotic fracture confirmed by an X-ray vertebral morphometry and 36 overweight nonosteoporotic subjects were enrolled. Serum irisin levels were measured using an irisin competitive ELISA. We evaluated lumbar spine and hip BMD and body composition using dual energy X-ray absorptiometry. To measure and monitor daily physical activity, each subject wore an armband for approximately 72 h.No significant correlations were found between irisin and BMD at any site and between irisin with either lean or fat mass. Serum levels of irisin were not correlated with the daily physical activity. Serum irisin levels were lower in subjects with previous osteoporotic fractures than in controls (P = 0·032), and the difference in irisin levels remained significant after adjustment for creatinine (P = 0·037), vitamin D (P = 0·046), lean mass (P = 0·02), lumbar BMD (P = 0·023) and femoral BMD (P = 0·032).Our data confirm an inverse correlation between irisin levels and vertebral fragility fractures, but no significant correlation was found with BMD or lean mass. Irisin may play a protective role on bone health independent of BMD but further studies are needed to clarify the relationship between irisin and bone metabolism.

Diabetic osteopathy is an upcoming complication of diabetes characterized by osteoporosis, increased risk for bone fractures and alterations in bone metabolism. Osteocalcin (OC) is a bone-specific protein produced by osteoblasts involved in the regulation of glucose and energy metabolism. The aim of this study is to determine whether OC serum levels are correlated with metabolic control in adult subjects with type one diabetes mellitus (T1DM). A cross-sectional study was conducted on 93 subjects (51 men) with mean age, disease duration and body mass index (BMI) of 39.9 ± 12.3, 17.2 ± 12.6 years and 24.5 ± 3.4 kg/m2, respectively. Blood samples were drawn to measure levels of hemoglobin A1c (HbA1c), OC, 25-OH vitamin D and PTH. Significant inverse correlations were found between OC and HbA1c (r = −0.295, P = 0.004) and between OC and BMI (r = −0.218, P = 0.037). These correlations were confirmed also among men in the analyses by gender [HbA1c vs OC: r = −0.363, P = 0.009; BMI vs OC: r = −0.291, P = 0.043], and similar but nonsignificant trends were confirmed among women. A significant difference in mean OC was also found between the lowest and the highest HbA1c tertile (22.3 ± 10.0 vs 16.9 ± 8.0 ng/mL, P = 0.025). These data show that in T1DM of long duration, OC serum levels are inversely associated with HbA1c and BMI, supporting the hypothesis that a poor glycemic control can affect osteoblast function.

One of the main open issues in the development of applications for sensor network management is the definition of interoperability mechanisms among the several monitoring systems and heterogeneous data. Interesting researches related to integration techniques have taken place; they are primary based on the adoption of sharing data mechanisms; furthermore in the last years, the service-oriented architecture (SOA) approach has become predominant in many sensor networks projects as it enables the cooperation and interoperability of different sensor platforms at a higher abstraction level.

Imbalance of bone resorption and bone formation is responsible for osteoporosis that is characterized by decreased bone mass and mineral density. The aim of this study was to evaluate the available data that could clarify the effectiveness and safety of supplementations with calcium and vitamin D, alone or in combination, to slow down bone loss in postmenopausal and elderly women. Using search key words, we performed a research both in the PubMed and Cochrane Library in order to find all meta-analysis, prospective and randomized clinical studies published from 2000 to 2014 that had investigated the effectiveness of calcium and vitamin D in the treatment of osteoporosis. At the moment it is not possible either to provide reassurance that calcium supplements given with vitamin D do not cause adverse cardiovascular events or to link them with certainty to increased cardiovascular risk. According to the data now available, vitamin D, at dosage of at least 800 IU/day, alone or in combination with antiresorptive drugs, should be administered in osteoporotic and osteopenic patients for a primary and secondary prevention. Further studies are needed and the debate remains ongoing. However, every administration needs the calculation of the absolute fracture risk of the patient. Especially considering the high cost of osteoporosis prevention, more studies are mandatory to clarify indications and contraindications.