Andrea Palermo

Oral anti-diabetic drugs and fracture risk, cut to the bone: safe or dangerous? A narrative review.

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.

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.

Latent autoimmune diabetes in the adults (LADA) in Asia: from pathogenesis and epidemiology to therapy

Diabetes mellitus is a metabolic disorder resulting from a defect in insulin secretion, insulin action or both. An effect of this process is chronic hyperglycaemia with disorder of carbohydrate, fat and protein metabolism and with long‐term complications of diabetes including retinopathy, nephropathy and neuropathy. Latent autoimmune diabetes in adults (LADA) is a type of autoimmune diabetes that resembles Type 1 diabetes (T1D), however, it shows a later onset and slower progression towards insulin necessity. Epidemiological studies suggest that LADA may account for 2–12% of all cases of diabetes in adult population. The epidemiology and phenotypic characteristics of LADA may vary between Caucasian and Asian diabetic patients as lifestyle, food habits and body mass index differ between these two populations. Data on LADA from population‐based studies in Asia are sparse and only few studies have looked at it.

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.

HLA-dependent autoantibodies against post-translationally modified collagen type II in type 1 diabetes mellitus

Aims/hypothesisIn this study the involvement of oxidative stress in type 1 diabetes mellitus autoimmunity and the possible association with rheumatoid arthritis (RA) was investigated. We tested the hypothesis that oxidative stress induced by chronic hyperglycaemia triggers post-translational modifications and thus the formation of neo-antigens in type 1 diabetes, similar to the ones found in RA.MethodsCollagen type II (CII), a known autoantigen in RA, was treated with ribose and various reactive oxygen species (ROS). Levels of antibodies specific to native and ROS-modified CII (ROS-CII) were compared in type 1 diabetes, type 2 diabetes and healthy controls, and related to the HLA genotype.ResultsSignificantly higher binding to ROS-CII vs native CII was observed in type 1 diabetic patients possessing the HLA-DRB1*04 allele irrespective of variables of glucose control (blood glucose or HbA1c). Type 1 diabetic patients carrying a DRB1*04 allele with the shared epitope showed the highest risk for ROS-CII autoimmunity, while the DRB1*0301 allele was protective. Conversely, native CII autoimmunity was not associated with any specific DRB1 allele. Positive and inverse seroconversion rates of response to ROS-CII were high in DRB1*04-positive type 1 diabetic patients.ConclusionHyperglycaemia and oxidative stress may trigger genetically controlled autoimmunity to ROS-CII and may explain the association between type 1 diabetes mellitus and RA.

PTH(1-34) for Surgical Hypoparathyroidism: A Prospective, Open-Label Investigation of Efficacy and Quality of Life.

CONTEXT Conventional therapy for hypoparathyroidism consists of calcium and calcitriol, but sometimes normal serum calcium cannot be maintained, and/or this approach might lead to nephrocalcinosis, nephrolithiasis, or renal insufficiency. OBJECTIVE The objective of the study was to investigate the effects of 6 months of PTH(1-34) treatment in adult subjects with postoperative hypoparathyroidism and to evaluate quality-of-life changes. DESIGN This was a 2-year prospective, open-label study. At baseline and after 6 months of PTH(1-34) treatment, calcium and vitamin D supplementation requirements, serum calcium, phosphate, creatinine, alkaline phosphatase, uric acid, and 24-hour urinary calcium excretion were evaluated. Quality of life was evaluated by the Rand 36-Item Short Form Health Survey covering eight domains of physical and mental health. SETTING This was an Italian multicentric study. PARTICIPANTS Participants included 42 subjects with surgical hypoparathyroidism (90% females, age range 34-77 y). INTERVENTION The intervention included a twice-daily PTH(1-34) 20 μg sc injection. RESULTS The mean serum calcium levels significantly increased from baseline to 15 days (7.6 ± 0.6 vs 9.1 ± 0.9 mg/dL, P < .001) and remained stable until the end of the observational period, despite a significant reduction in calcium and vitamin D supplementation. Phosphate levels gradually decreased from baseline to the sixth month (P = .005 for the trend), whereas the alkaline phosphatase increased (P < .001). Data from the Rand 36-Item Short Form Health Survey showed a significant improvement in the mean scores of all eight domains (P < .001). CONCLUSION This is the largest study that demonstrates the effectiveness of PTH(1-34) in the treatment of adult patients with postsurgical hypoparathyroidism, and it shows that PTH(1-34) may improve the mental and physical health in hypoparathyroid subjects.

Prevention of type 2 diabetes mellitus: is it feasible?

The increasing global prevalence of type 2 diabetes mellitus (T2DM) requires the implementation of preventive strategies to halt this trend, tailored to the specific needs of individual regions. Risk factors for T2DM are among the main targets for improving health outcomes and curbing the development of diabetes; excessive weight and obesity are two of the most important risk factors that need to be addressed. A growing body of evidence suggests that subjects with pre‐diabetes who lose body weight and increase physical activity can delay or prevent the onset of T2DM, and in some cases, blood glucose levels may return to normal. Several studies have shown that moderate to intensive levels of exercise are effective in reducing both intra‐abdominal and total adiposity among obese subjects, both improving cardiovascular risk profile and reducing the risk of T2DM development. These consistent observations have given rise to large‐scale randomized controlled trials that use lifestyle intervention (including behavioural strategies for the reinforcement of prescribed changes in nutritional intake, physical activity or both), with or without pharmacological treatment, in populations at high risk of developing T2DM. In this review, large‐scale national trials that have focused on the prevention of T2DM are critically evaluated. Copyright

A Novel Insulin Unit Calculator for the Management of Type 1 Diabetes

BACKGROUND Intensive insulin therapy is the gold standard therapy for type 1 diabetes (T1D) patients. To achieve optimal glycemic control, adjustments of insulin dose at mealtimes must be made taking into account several parameters: blood glucose levels, insulin/carbohydrate ratio, carbohydrate intake, and physical activity. Calsulin (Thorpe Products Ltd., Cambridge, UK) is a new tool for the administration of insulin dose before each meal. The aim of this study was to evaluate the efficacy of Calsulin on metabolic control in T1D patients undergoing intensive insulin therapy. SUBJECTS AND METHODS Forty consecutive patients affected by T1D, 18-65 years old, with disease duration of >1 year, were randomized to Calsulin or to the control group. Hemoglobin A1c (HbA1c) was evaluated at entry into the study and at 3- and 6-month follow-ups. Paired t test (two tailed) and analysis of variance were used to evaluate differences in HbA1c at 3 and 6 months in the two groups. RESULTS HbA1c at entry was 7.9 ± 1.0% (SD) in the Calsulin-treated group and 7.8 ± 1.6% (SD) in control patients (P not significant). Data showed a slight improvement in HbA1c levels at 3 months in the Calsulin-treated group (-0.61% vs. -0.14% difference, respectively; P not significant). At the 6-month follow-up, a significant reduction in HbA1c levels was observed in the Calsulin-treated group versus the control group (-0.85% vs. -0.07% difference, respectively; P < 0.05). CONCLUSIONS Calsulin is an acceptable and practical tool that makes the process of calculating insulin doses easy to use, and, most importantly, it improves metabolic control as shown by a significant reduction of HbA1c levels.

Buccal spray insulin in subjects with impaired glucose tolerance: the prevoral study

Aim: Postprandial hyperglycaemia is a consequence of reduced first phase insulin response and is associated with increased cardiovascular risk and mortality. The aim of this proof‐of‐concept study was to investigate the safety and efficacy of treatment with buccal spray insulin (Oral‐lyn™, Generex Biotechnology Corporation, Toronto, Ontario, Canada) on postprandial plasma glucose and insulin levels in subjects with impaired glucose tolerance (IGT).

Pathophysiology of Bone Fragility in Patients with Diabetes

It has been well established that bone fragility is one of the chronic complications of diabetes mellitus, and both type 1 and type 2 diabetes are risk factors for fragility fractures. Diabetes may negatively affect bone health by unbalancing several pathways: bone formation, bone resorption, collagen formation, inflammatory cytokine, muscular and incretin system, bone marrow adiposity and calcium metabolism. The purpose of this narrative review is to explore the current understanding of pathophysiological pathways underlying bone fragility in diabetics. In particular, the review will focus on the peculiar cellular and molecular system impairment that may lead to increased risk of fracture in type 1 and type 2 diabetes.