Dario Tuccinardi

Irisin is associated with osteoporotic fractures independently of bone mineral density, body composition or daily physical activity.

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.

BMI and BMD: The Potential Interplay between Obesity and Bone Fragility

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.

DiaPep277 peptide therapy in the context of other immune intervention trials in type 1 diabetes

Introduction: Type 1 diabetes (T1D) is characterized by the autoimmune destruction of pancreatic β-cells. The aim of immune intervention is to arrest this autoimmune attack. DiaPep277, a major T-cell epitope of heat shock protein 60 (hsp60), has been shown to be effective in the modulation of the immune response in recent onset T1D and is the main focus of this review in the context of other ongoing trials using different approaches. Areas covered: The authors performed a literature search of Pubmed listed publications (from the last 10 years) and a website search of the company licensing DiaPep277. DiaPep277 has been investigated in Phase I – III trials in humans. Phase II trials showed a significant preservation of β-cell function in adult T1D patients (but not children) with an absence of adverse effects and not accompanied by lower glycosylated haemoglobin (HbA1c) levels or reduced daily insulin requirement compared with placebo-treated patients. Expert opinion: Administration of DiaPep277 is safe and represents a promising therapeutic strategy in patients with recent-onset T1D. The results of two large Phase III trials will tell us whether this therapy may change our current approach to treating T1D patients at diagnosis.

Low-risk HLA genotype in Type 1 diabetes is associated with less destruction of pancreatic B-cells 12 months after diagnosis.

Aims  The role of human leukocyte antigen (HLA) genes in the susceptibility to Type 1 diabetes (T1DM) is well known. However, we do not know whether the degree of pancreatic B‐cell destruction depends on different HLA genetic risk. The aim of this study was to analyse the influence of DRB1* and DQB1* genes on the rate of pancreatic B‐cell loss in a prospective series of 120 consecutive newly diagnosed T1DM subjects in the first 12 months after diagnosis.

Erectile dysfunction and its management in patients with diabetes mellitus

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

Vitamin K and osteoporosis: Myth or reality?

Vitamin K is a liposoluble vitamin. The predominant dietary form, phylloquinone or vitamin K1, is found in plants and green vegetables; whereas menaquinone, or vitamin K2, is endogenously synthesized by intestinal bacteria and includes several subtypes that differ in side chain length. Aside from its established role in blood clotting, several studies now support a critical function of vitamin K in improving bone health. Vitamin K is in fact required for osteocalcin carboxylation that in turn regulates bone mineral accretion; it seems to promote the transition of osteoblasts to osteocytes and also limits the process of osteoclastogenesis. Several observational and interventional studies have examined the relationship between vitamin K and bone metabolism, but findings are conflicting and unclear. This systematic review aims to investigate the impact of vitamin K (plasma levels, dietary intake, and oral supplementation) on bone health with a particular interest in bone remodeling, mineral density and fragility fractures.

Glycemic variability in the development of cardiovascular complications in diabetes

Diabetes mellitus represents a major risk factor for the development of coronary artery disease and other vascular complications. Glycated haemoglobin, fructosamine, and fasting blood glucose levels are partial parameters to exhaustively describe patient dysglycemic status. Thus, recently the new concept of glycemic variability has emerged, including information about two major aspects: the magnitude of blood glucose excursions (from nadir to peak, thus lower and higher spikes) and the time intervals in which these fluctuations occur. Despite the lack of consensus regarding the most appropriate definition and tools for its assessment, glycemic variability seems to have more deleterious effects than sustained hyperglycemia in the pathogenesis of diabetic cardiovascular complications. This manuscript aimed to review the most recent evidence on glycemic variability and its potential use in everyday clinical practice to identify diabetic patients at higher risk of cardiovascular complications and thus needing stricter monitoring and treatment.

Overweight and obese patients with nickel allergy have a worse metabolic profile compared to weight matched non-allergic individuals

Background A lack of balance between energy intake and expenditure due to overeating or reduced physical activity does not seem to explain entirely the obesity epidemic we are facing, and further factors are therefore being evaluated. Nickel (Ni) is a ubiquitous heavy metal implied in several health conditions. Regarding this, the European Food Safety Authority has recently released an alert on the possible deleterious effects of dietary Ni on human health given the current levels of Ni dietary intake in some countries. Pre-clinical studies have also suggested its role as an endocrine disruptor and have linked its exposure to energy metabolism and glucose homeostasis dysregulation. Ni allergy is common in the general population, but preliminary data suggest it being even more widespread among overweight patients. Objectives The aim of this study has been to evaluate the presence of Ni allergy and its association with the metabolic and endocrine profile in overweight and obese individuals. Methods We have evaluated 1128 consecutive overweight and obese outpatients. 784 were suspected of being allergic to Ni and 666 were assessed for it. Presence of Ni allergy and correlation with body mass index (BMI), body composition, metabolic parameters and hormonal levels were evaluated. Results We report that Ni allergy is more frequent in presence of weight excess and is associated with worse metabolic parameters and impaired Growth Hormone secretion. Conclusions We confirm that Ni allergy is more common in obese patients, and we report for the first time its association with worse metabolic parameters and impaired function of the GH-IGF1 axis in human subjects.

Mangosteen Extract Shows a Potent Insulin Sensitizing Effect in Obese Female Patients: A Prospective Randomized Controlled Pilot Study

There is a widely acknowledged association between insulin resistance and obesity/type 2 diabetes (T2DM), and insulin sensitizing treatments have proved effective in preventing diabetes and inducing weight loss. Obesity and T2DM are also associated with increased inflammation. Mangosteen is a tropical tree, whose fruits—known for their antioxidant properties—have been recently suggested having a possible further role in the treatment of obesity and T2DM. The objective of this pilot study has been to evaluate safety and efficacy of treatment with mangosteen extract on insulin resistance, weight management, and inflammatory status in obese female patients with insulin resistance. Twenty-two patients were randomized 1:1 to behavioral therapy alone or behavioral therapy and mangosteen and 20 completed the 26-week study. The mangosteen group reported a significant improvement in insulin sensitivity (homeostatic model assessment-insulin resistance, HOMA-IR −53.22% vs. −15.23%, p = 0.004), and no side effect attributable to treatment was reported. Given the positive preliminary results we report and the excellent safety profile, we suggest a possible supplementary role of mangosteen extracts in the treatment of obesity, insulin resistance, and inflammation.

A 6-month follow-up study of the randomized controlled Ma-Pi macrobiotic dietary intervention (MADIAB trial) in type 2 diabetes

Background:In the MADIAB trial (a 21-day randomized, controlled trial in patients with type 2 diabetes (T2D)), intervention with the Ma-Pi 2 macrobiotic diet resulted in significantly greater improvements in metabolic control compared with a standard recommended diet for patients with T2D. We report on a 6-month follow-up study, which investigated, whether these benefits extended beyond the 21-day intensive dietary intervention, in real-world conditions.Subjects:At the end of the MADIAB trial (baseline of this follow-up study), all participants continued their assigned diet (Ma-Pi or control) for 6 months. The Ma-Pi 2 group followed the Ma-Pi 4 diet during this follow-up study. Forty of the original 51 subjects (78.4%) participated in the follow-up (body mass index, 27–45 kg m−2; age, 40–75 years). Primary outcome was percentage change from baseline in HbA1c; secondary outcomes were anthropometric data and lipid panel.Results:A significantly greater median percentage reduction was observed for HbA1c in the Ma-Pi group (−11.27% (95% confidence interval (CI): −10.17; −12.36)) compared with the control group (−5.88% (95% CI: −3.79; −7.98)) (P < 0.001). Total and low-density lipoprotein (LDL) cholesterol increased in both groups with no differences between groups (P=0.331 and P=0.082, respectively). After correcting for age and gender, the Ma-Pi diet was associated with a higher percentage reduction in HbA1c (95% CI: 2.56; 7.61) and body weight (95% CI: 0.40; 3.99), and a higher percentage increase in LDL cholesterol (95% CI: −1.52; −33.16). However, all participants’ total and LDL cholesterol levels remained within recommended ranges (<200 mg dl−1 and <100 mg dl−1, respectively). The Ma-Pi diet group achieved the target median HbA1c value (<5.7% (39 mmol mol−1)) at 6 months.Conclusions:Both the Ma-Pi and control diets maintained their benefits beyond the 21-day intensive monitored intervention over a 6-month follow-up in real-world conditions. The Ma-Pi diet resulted in greater improvement in glycemic control.