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The role of aldosterone has yet to be well appreciated in chronic kidney disease (CKD). Two variables define CKD: an estimated glomerular filtration rate of <60 ml/min/1.73 m2 and a spot urine albumin‐creatinine ratio of >30 mg/g. Both are needed for an accurate diagnosis. The presence of CKD at this level is associated with an elevated risk of cardiovascular death and a greater risk of CKD progression to kidney failure and subsequent dialysis. This paper presents an overview of aldosterone's importance in CKD and its contribution to the inflammatory processes involved in CKD development. Data on outcomes, both surrogate and hard, related to outcomes on CKD progression will also be discussed in the context of mineralocorticoid blockade. Based on recent epidemiological data as well as data examining markers of diabetic kidney disease progression, it is clear that use of both renin‐angiotensin system inhibitors and aldosterone receptor antagonists have a significant role in altering the natural history of kidney disease progression itself, as well as reducing the risk of cardiovascular events that generally accompany long‐standing kidney disease. This paper will discuss these issues and the management of consequent hyperkalaemia when both steroidal and non‐steroidal mineralocorticoid receptor antagonists are used in detail. [ABSTRACT FROM AUTHOR]

Aims: To describe the development and report the first‐stage validation of a digital version of the digit symbol substitution test (DSST), for assessment of cognitive function in older people with diabetes. Materials and Methods: A multidisciplinary team of experts was convened to conceptualize and build a digital version of the DSST and develop a machine‐learning (ML) algorithm to analyse the inputs. One hundred individuals with type 2 diabetes (aged ≥ 60 years) were invited to participate in a one‐time meeting in which both the digital and the pencil‐and‐paper (P&P) versions of the DSST were administered. Information pertaining to demographics, laboratory measurements, and diabetes indices was collected. The correlation between the digital and P&P versions of the test was determined. Additionally, as part of the validation process, the performance of the digital version in people with and without known risk factors for cognitive impairment was analysed. Results: The ML model yielded an overall accuracy of 89.1%. A strong correlation was found between the P&P and digital versions (r = 0.76, p < 0.001) of the DSST, as well as between the ML model and the manual reading of the digital DSST (r = 0.99, p < 0.001). Conclusions: This study describes the development of and provides first‐stage validation data for a newly developed digital cognitive assessment tool that may be used for screening and surveillance of cognitive function in older people with diabetes. More studies are needed to further validate this tool, especially when self‐administered and in different clinical settings. [ABSTRACT FROM AUTHOR]

Aims: To perform a systematic review of studies that sought to identify diagnostic biomarkers for the diagnosis of cardiovascular diseases (CVDs) and diabetes mellitus (DM), which could be used in low‐ and middle‐income countries (LMICs) where there is a lack of diagnostic equipment, treatments and training. Materials and Methods: Papers were sourced from six databases: the British Nursing Index, Google Scholar, PubMed, Sage, Science Direct and Scopus. Articles published between January 2002 and January 2023 were systematically reviewed by three reviewers and appropriate search terms and inclusion/exclusion criteria were applied. Results: A total of 18 studies were yielded, as well as 234 diagnostic biomarkers (74 for CVD and 160 for DM). Primary biomarkers for the diagnosis of CVDs included growth differentiation factor 15 and neurogenic locus notch homologue protein 1 (Notch1). For the diagnosis of DM, alpha‐2‐macroglobulin, C‐peptides, isoleucine, glucose, tyrosine, linoleic acid and valine were frequently reported across the included studies. Advanced analytical techniques, such as liquid chromatography mass spectrometry, enzyme‐linked immunosorbent assays and vibrational spectroscopy, were also repeatedly reported in the included studies and were utilized in combination with traditional and alternative matrices such as fingernails, hair and saliva. Conclusions: While advanced analytical techniques are expensive, laboratories in LMICs should carry out a cost–benefit analysis of their use. Alternatively, laboratories may want to explore emerging techniques such as infrared, Fourier transform‐infrared and near‐infrared spectroscopy, which allow sensitive noninvasive analysis. [ABSTRACT FROM AUTHOR]

This article presents the findings of a study on the time spent in the target glucose range (TITR) in children and adolescents with type 1 diabetes using automated insulin delivery (AID) systems. The study found that higher TITR levels were associated with better glycemic control and could be an important marker for optimizing glucose control in children with type 1 diabetes. Another study discussed in the article explored the relationship between time spent in hypoglycemia and the TIR-to-TITR ratio in individuals using AID systems. The study emphasized the importance of using the automatic mode for the majority of time to achieve optimal glycemic outcomes and highlighted the significance of considering factors such as insulin sensitivity and glycemic index values when determining insulin to carbohydrate ratios (ICRs). The article also mentioned the limitations of the study, such as the use of different continuous glucose monitoring (CGM) systems and the lack of raw glucose data. However, the study's primary strength was its large and well-characterized pediatric cohort. The authors of the study provided contributions to the conceptualization and writing of the paper, data collection, and manuscript review. The study was not funded, and the authors declared their conflicts of interest. [Extracted from the article]

Aim: Despite the increasing use of combination treatment with sodium‐glucose cotransporter 2 inhibitors and glucagon‐like peptide‐1 receptor agonists, data are limited on the effects of combination treatment on markers of cardiovascular disease. This study aimed to investigate the effect of empagliflozin, semaglutide, and their combination on vascular function. Materials and Methods: In total, 120 patients with type 2 diabetes were randomized into four groups (n = 30 in each) for 32 weeks: placebo, semaglutide, empagliflozin, and their combination. The study had two co‐primary outcomes: change in arterial stiffness and kidney oxygenation. This paper reports on arterial stiffness assessed as carotid‐femoral pulse wave velocity. Secondary outcomes included 24‐h blood pressure (BP), 24‐h central BP, urinary albumin to creatinine ratio and glycaemic control assessed by both continuous glucose monitoring and glycated haemoglobin. Results: The carotid‐femoral pulse wave velocity did not change significantly in any of the groups compared with placebo. Twenty‐four‐hour systolic BP was reduced by 10 mmHg (95% CI 6–14), p <.001 in the combination group, significantly superior to both placebo and monotherapy (p <.05). Combination treatment increased glycaemic time in range from 72% at baseline to 91% at week 32, p <.001, without increasing time below range. The urinary albumin to creatinine ratio decreased by 36% (95% CI 4–57), p =.03 in the combination group compared with placebo. Conclusions: Empagliflozin, semaglutide, or their combination did not reduce arterial stiffness. Combination treatment showed a substantial and clinically important reduction in 24‐h systolic BP compared with either treatment alone. Combination treatment increased glycaemic time in range without increasing the risk of hypoglycaemia. [ABSTRACT FROM AUTHOR]

This review will try to elucidate the interconnected pathophysiology of sarcopenia and type 2 diabetes (T2D) and will try to identify a common pathway to explain their development. To this end, the PubMed and Scopus databases were searched for articles published about the underlying pathophysiology, diagnosis and treatment of both sarcopenia and T2D. The medical subject heading (MeSH) terms 'sarcopenia' AND 'diabetes mellitus' AND ('physiopathology' OR 'diagnosis' OR 'therapeutics' OR 'aetiology' OR 'causality') were used. After screening, 32 papers were included. It was evident that sarcopenia and T2D share multiple pathophysiological mechanisms. Common changes in muscle architecture consist of a shift in myocyte composition, increased myosteatosis and a decreased capacity for muscle regeneration. Further, both diseases are linked to an imbalance in myokine and sex hormone production. Chronic low‐grade inflammation and increased levels of oxidative stress are also known pathophysiological contributors. In the future, research efforts should be directed towards discovering common checkpoints in the development of T2D and sarcopenia as possible shared therapeutic targets for both diseases. Current treatment for T2D with biguanides, incretins and insulin may already convey a protective effect on the development of sarcopenia. Furthermore, attention should be given to early diagnosis of sarcopenia within the population of people with T2D, given the sizeable physical and medical burden it encompasses. A combination of simple diagnostic techniques could be used at regular diabetes check‐ups to identify sarcopenia at an early stage and start lifestyle modifications and treatment as soon as possible. [ABSTRACT FROM AUTHOR]

Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) have become agents of choice for people with type 2 diabetes (T2D) with established cardiovascular disease or in high‐risk individuals. With currently available GLP‐1 RAs, 51%‐79% of subjects achieve an HbA1c target of less than 7.0% and 4%‐27% lose 10% of body weight, illustrating the need for more potent agents. Three databases (PubMed, Cochrane, Web of Science) were searched using the MESH terms 'glucagon‐like peptide‐1 receptor agonist', 'glucagon receptor agonist', 'glucose‐dependent insulinotropic peptide', 'dual or co‐agonist', and 'tirzepatide'. Quality of papers was scored using PRISMA guidelines. Risk of bias was evaluated using the Cochrane assessment tool. An HbA1c target of less than 7.0% was attained by up to 80% with high‐dose GLP‐1 RAs and up to 97% with tirzepatide, with even up to 62% of people with T2D reaching an HbA1c of less than 5.7%. A body weight loss of 10% or greater was obtained by up to 50% and up to 69% with high‐dose GLP‐1 RAs or tirzepatide, respectively. The glucose‐ and weight‐lowering effects of the GLP‐1/glucagon RA cotadutide equal those of liraglutide 1.8 mg. Gastrointestinal side effects of high‐dose GLP‐1 RAs and co‐agonists occurred in 30%‐70% of patients, mostly arising within the first 2 weeks of the first dose, being mild or moderate in severity, and transient. The development of high‐dose GLP‐1 RAs and the dual GLP‐1/glucose‐dependent insulinotropic peptide RA tirzepatide resulted in increasing numbers of people reaching HbA1c and body weight targets, with up to 62% attaining normoglycaemia with 15‐mg tirzepatide. Whether this will also translate to better cardiovascular outcomes and affect treatment guidelines remains to be studied. [ABSTRACT FROM AUTHOR]

This document is a correction to a research paper titled "Societal health and economic burden of cardiovascular diseases in the population with type 2 diabetes in Qatar. A 10-year forecasting model." The correction addresses an error in the methods section of the paper, specifically in the description of the model's timeframe. The corrected information states that the model follows individuals for 10 years, until the year 2032, until they die, or until they reach 79 years of age in the model, whichever comes first. The authors apologize for the error. [Extracted from the article]

Background/Aim: Non‐alcoholic fatty liver disease (NAFLD) affects approximately 25% of the global adult population. The aim of this narrative review is to describe the associations between NAFLD and cardiovascular disease (CVD), arrhythmias, cardiac conduction defects, myocardial remodelling and heart failure. We also discuss the potential mechanisms that mediate or attenuate the strength of these associations, and briefly summarize the effect of treatments that both ameliorate NAFLD and decrease risk of CVD. Methods: Searches of PubMed were performed by the two authors using the terms listed in Appendix. We limited the timeframe to the last decade due to the vast amount of research in the field (up to April 2021) for meta‐analyses, reviews and original papers. Only articles published in English were considered. Results: NAFLD is associated with an increased risk of fatal/non‐fatal CVD events and other cardiac and arrhythmic complications (left ventricular hypertrophy, aortic‐valve sclerosis and certain arrhythmias), independently of common CVD risk factors. There are probably several underlying mechanisms, including hepatic/systemic insulin resistance, atherogenic dyslipidaemia, hypertension and pro‐atherogenic, pro‐coagulant and pro‐inflammatory mediators released from the steatotic/inflamed liver that may be involved. Some genetic polymorphisms, such as PNPLA3 (rs738409 C>G) and TM6SF2 (rs58542926 C>T), may worsen the liver disease, but also attenuate the strength of the association between NAFLD and CVD, possibly via their effects on lipoprotein metabolism. Of the currently tested drugs for treating NAFLD that also benefit the vasculature, pioglitazone and GLP‐1 receptor agonists are the most promising. Conclusions: The complex interplay between the liver and cardiometabolic risk factors contributes to CVD, arrhythmias and cardiac disease in NAFLD. There is an urgent need for a multidisciplinary approach to manage both liver disease and cardiometabolic risk, and to test the cardiovascular and cardiac effects of new drugs for NAFLD. [ABSTRACT FROM AUTHOR]

With increasing population aging and prevalence of type 2 diabetes (T2D) worldwide, prevention of diabetic complications remains a major unmet need. While cardiovascular outcomes of diabetes are improving over time, diabetic kidney disease (DKD) still leads to an exceedingly high rate of end‐stage kidney disease (ESKD). A game‐changing opportunity is offered by treatment with sodium‐glucose cotransporter‐2 (SGLT2) inhibitors. Randomized controlled trials (RCTs) have indisputably shown that SGLT2 inhibitors reduce the rate of DKD progression, the decline in estimated glomerular filtration rate (eGFR), and the development of ESKD. In parallel, SGLT2 inhibitors improve cardiovascular outcomes, especially the risk of hospitalization for heart failure. Real‐world studies (RWSs) have largely confirmed the findings of RCTs in broader populations of subjects with T2D followed under routine care. In the present paper, we review RWSs exploring the renal effects of SGLT2 inhibitors and highlight the most critical challenges that can be encountered in designing and conducting such studies. Channelling bias (confounding by indication), time‐lag bias, conditioning on the future, database heterogeneity, linearity of eGFR change over time, and duration of observation are critical issues that may undermine the robustness of RWS findings. We then elaborate on the new opportunities to overcome such limitations by describing the design and objectives of the DARWIN (DApagliflozin Real‐World evIdeNce)‐Renal study, a new RWS promoted by the Italian Diabetes Society. Fine‐tuning of methods for comparative observational research will improve evidence derived from RWSs on the renal effects of SGLT2 inhibitors, aiding the evolving discussion regarding the place of SGLT2 inhibitors in T2D treatment algorithms in different stages of DKD. [ABSTRACT FROM AUTHOR]

First, in table 1 in their paper, Fawzy et al[1] show the baseline characteristics and potential confounding factors in the SGLT2 inhibitor group and the non-SGLT2 inhibitor group, which were used as the covariates for the propensity-score-matching analysis. Sodium-glucose cotransporter-2 inhibitor use was associated with lower risks of stroke and cardiac arrest but not ventricular arrhythmias? We read with great interest the article on the cohort study by Fawzy et al,[1] which aimed to investigate the impact of sodium-glucose cotransporter-2 (SGLT2) inhibitors on the risks of incident heart failure (HF) and adverse cardiovascular outcomes. [Extracted from the article]

The management of childhood obesity is a clinical dilemma. Paediatricians will see those children whose weight is at the severe end of the spectrum with obesity-related co-morbidities and for whom more intensive weight loss therapies may be appropriate. A literature review was performed (January 1995-January 2010) of the roles of pharmacotherapy or bariatric surgery in the management of childhood obesity. Three hundred and eighty-three abstracts were reviewed and 76 full-text articles were requested. Of these, 34 were excluded and a total of 21 pharmacotherapy papers and 22 papers on surgery were reviewed in detail. All studies involved adolescents. Pharmacotherapy: Most studies were small and of short duration, the notable exceptions being two large RCTs of sibutramine and orlistat. Sibutramine led to a mean estimated change in BMI from baseline of −3.1 kg/m vs. −0.3 kg/m for placebo over 12 months. Orlistat was also beneficial with a mean reduction in BMI of 0.55 vs. an increase of 0.31 kg/m in the placebo group at 12 months. Bariatric surgery: Most papers presented clinical observations and there were no randomised controlled trials (RCTs). Robust selection criteria were not used and ideal candidate selection remains unclear. Most papers showed a significant benefit of surgery in severely obese adolescents in the short term but long-term data were sparse. There were a surprisingly large number of papers examining the benefits of intensive weight management in obese adolescents. The study design of many was inadequate and the role of pharmacotherapy or surgery in childhood obesity remains unclear. [ABSTRACT FROM AUTHOR]

The Scale Obesity and Prediabetes studies contributed 29% and 33% weight to the analysis (with hazard ratios of 0.85 and 0.88, respectively). Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. First, the SCALE Obesity and Prediabetes Study reported some results after 1 year2 and others after 3 years.3 These are counted twice in the meta-analysis, with total events for drug/placebo being 217/123 after 1 year and 242/142 after 3 years. [Extracted from the article]

In patients with baseline values <=58 mmol/mol, HbA1c levels did not change, but in patients with baseline values >58 mmol/mol, HbA1c levels significantly decreased after 6 (3 mmol/mol; I P i = 0.006), 12 (1.5 mmol/mol; I P i = 0.013) and 24 months (2 mmol/mol; I P i = 0.017). Keywords: continuous glucose monitoring (CGM); CSII; insulin pump therapy; realworld evidence; type 1 diabetes EN continuous glucose monitoring (CGM) CSII insulin pump therapy realworld evidence type 1 diabetes 1101 1105 5 03/08/23 20230401 NES 230401 INTRODUCTION The MiniMed™ 670G insulin pump was the first hybrid closed-loop (HCL) system available for clinical use. A retrospective analysis of 24-month real-world glucose control for children and adolescents with type 1 diabetes using the MiniMed™ 670G insulin pump At baseline, HbA1c was 55 mmol/mol (50-62 mmol/mol), higher than at 6 months (53 mmol/mol [48-60 mmol/mol]; I P i = 0.005) and 12 months (54 mmol/mol [49-63 mmol/mol]; I P i = 0.042), but not different from the values at 18 months (52 mmol/mol [51-64 mmol/mol]) and 24 months (56 mmol/mol [51-64 mmol/mol]; Figure S1). [Extracted from the article]

Hybrid closed‐loop systems are characterized by the coexistence of algorithm‐driven automated insulin delivery combined with manual mealtime boluses. Used correctly, these insulin delivery systems offer better glucose control and reduced risk of hypoglycaemia and represent the most advanced form of insulin delivery available for people with type 1 diabetes. The aim of this paper was to compare the currently available commercial hybrid closed‐loop systems in the UK: the Medtronic 670G/780G, Tandem t:slim X2 Control IQ and CamAPS FX systems. The Medtronic 670G/780G systems use Guardian 3 sensor (7‐day use, two to four calibrations per day), while Tandem and CamAPS systems use the calibration‐free Dexcom G6 sensor (10 days). The CamAPS system is available as an android app, whereas the other two systems have the algorithm embedded in the insulin pump. During pivotal studies, depending on the study population and baseline glycated haemoglobin level, these systems achieve a time spent in the target range 3.9 to 10 mmol/L (70 to 180 mg/dL) of 65% to 76% with low burden of hypoglycaemia. All three systems allow a higher glucose target for announced exercise, while the Tandem system offers an additional night‐time tighter target. The CamAPS system offers fully customizable glucose targets and is the only system licensed for use during pregnancy. Additional education is required for both users and healthcare professionals to harness the best performance from these systems as well as to troubleshoot when "automode exits" occur. We provide consensus recommendations to develop pragmatic pathways to guide patients, clinicians and commissioners in making informed decisions on the appropriate use of the diabetes technology. [ABSTRACT FROM AUTHOR]

Obesity is a chronic multisystem disease associated with increased morbidity and mortality. The increasing prevalence of obesity makes it a major healthcare challenge across both developed and developing countries. Traditional measures such as body mass index do not always identify individuals at increased risk of comorbidities, yet continue to be used in deciding who qualifies for weight loss treatment. A better understanding of how obesity is associated with comorbidities, in particular non‐metabolic conditions, is needed to identify individuals at risk in order to prioritize treatment. For metabolic disorders such as type 2 diabetes (T2D), weight loss can prevent T2D in individuals with prediabetes. It can improve and reverse T2D if weight loss is achieved early in the course of the disease. However, access to effective weight loss treatments is a significant barrier to improved health for people with obesity. In the present paper, we review the rising prevalence of obesity and why it should be classed as a multisystem disease. We will discuss potential mechanisms underlying its association with various comorbidities and how these respond to treatment, with a particular focus on cardiometabolic disease, malignancy and mental health. [ABSTRACT FROM AUTHOR]

With the increasing prevalence of overweight and obesity worldwide, there is a reciprocal increase in the global economic burden and ill‐health from obesity‐related chronic diseases. Primary healthcare services have a role to play in ensuring early detection of weight issues and in directing patients towards evidence‐based care to slow this progression. Research shows that many people with obesity are motivated to lose weight and want their clinician to initiate a conversation about weight management and treatment options. However, this conversation rarely occurs and there is a significant delay in treatment, resulting in an increased burden on the individual, healthcare system and society. In this paper, the components and rationale for the clinical assessment of adult patients with overweight or obesity, including anthropometric measurements and pathology tests, are described. Recommendations to ascertain the potential factors influencing the development of obesity in the patient, such as lifestyle factors (diet and physical activity) and mental health, are also provided. The potential sequelae of obesity that may be present and the necessary assessments for diagnosis are also addressed. These assessments are vital to ensure the patient is referred to the appropriate allied health services and/or specialists. [ABSTRACT FROM AUTHOR]

Against the backdrop of obesity as a major public health problem, we examined three questions: How much weight loss is needed to benefit patients with obesity? How well do current therapies do in producing weight loss? What strategies can be used to improve patient outcomes using evidence‐based studies. This paper reviews literature on the outcomes of lifestyle, diet, medications and surgical treatments for obesity using literature searches for obesity treatments. Current treatments, including lifestyle, diet and exercise, produce a weight loss of 5% to 7% on average. Despite continued attempts to identify superior dietary approaches, most careful comparisons find that low carbohydrate diets are not significantly better than low fat diets for weight loss. The four medications currently approved by the US Food and Drug Administration for long‐term management of obesity are not as effective as surgery, adding about 5% on average to lifestyle approaches to weight loss. Two new medications that are under investigation, semaglutide and tirzepatide, significantly improve on this. For all treatments for weight loss, including lifestyle, medications and surgery, there is enormous variability in the amount of weight lost. Examination of this literature has yielded evidence supporting baseline and process predictors, but the effect sizes associated with these predictors are small and there are no prospective studies showing that a personalized approach based on genotype or phenotype will yield uniform success. Because obesity is a chronic disease it requires a 'continuous treatment model' across the lifespan. [ABSTRACT FROM AUTHOR]

The large number of pharmacological agents available to treat type 2 diabetes (T2D) makes choosing the optimal drug for any given patient a complex task. Because newer agents offer several advantages, whether and when sulphonylureas (SUs) should still be used to treat T2D is controversial. Published treatment guidelines and recommendations should govern the general approach to diabetes management. However, expert opinions can aid in better understanding local practices and in formulating individual choices. The current consensus paper aims to provide additional guidance on the use of SUs in T2D. We summarize current local treatment guidelines in European countries, showing that SUs are still widely proposed as second‐line treatment after metformin and are often ranked at the same level as newer glucose‐lowering medications. Strong evidence now shows that sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2is) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are associated with low hypoglycaemia risk, promote weight loss, and exert a positive impact on vascular, cardiac and renal endpoints. Thus, using SUs in place of SGLT‐2is and GLP‐1RAs may deprive patients of key advantages and potentially important cardiorenal benefits. In subjects with ascertained cardiovascular disease or at very high cardiovascular risk, SGLT‐2is and/or GLP‐1RAs should be used as part of diabetes management, in the absence of contraindications. Routine utilization of SUs as second‐line agents continues to be acceptable in resource‐constrained settings. [ABSTRACT FROM AUTHOR]

Understanding the benefits and risks of treatments to be used by older individuals (≥65 years old) is critical for informed therapeutic decisions. Glucose‐lowering therapy for older patients with diabetes should be tailored to suit their clinical condition, comorbidities and impaired functional status, including varying degrees of frailty. However, despite the rapidly growing population of older adults with diabetes, there are few dedicated clinical trials evaluating glucose‐lowering treatment in older people. Conducting clinical trials in the older population poses multiple significant challenges. Despite the general agreement that individualizing treatment goals and avoiding hypoglycaemia is paramount for the therapy of older people with diabetes, there are conflicting perspectives on specific glycaemic targets that should be adopted and on use of specific drugs and treatment strategies. Assessment of functional status, frailty and comorbidities is not routinely performed in diabetes trials, contributing to insufficient characterization of older study participants. Moreover, significant operational barriers and problems make successful enrolment and completion of such studies difficult. In this review paper, we summarize the current guidelines and literature on conducting such trials, as well as the learnings from our own clinical trial (IMPERIUM) that assessed different glucose‐lowering strategies in older people with type 2 diabetes. We discuss the importance of strategies to improve study design, enrolment and attrition. Apart from summarizing some practical advice to facilitate the successful conduct of studies, we highlight key gaps and needs that warrant further research. [ABSTRACT FROM AUTHOR]

Transparency of real‐world evidence (RWE) studies is critical to understanding how findings of a specific study were derived and is a necessary foundation to assessing validity and determination of whether decisions should be informed by the findings. In the present paper, we lay out strategies to improve clarity in the reporting of comparative effectiveness studies using real‐world data that were generated by the routine operation of a healthcare system. This may include claims data, electronic health records, wearable devices, patient‐reported outcomes or patient registries. These recommendations were discussed with multiple stakeholders, including regulators, payers, academics and journal editors, and endorsed by two professional societies that focus on RWE. We remind readers interested in diabetes research of the utility of conceptualizing a target trial that is then emulated by a RWE study when planning and communicating about RWE study implementation. We recommend the use of a graphical representation showcasing temporality of key longitudinal study design choices. We highlight study elements that should be reported to provide the clarity necessary to make a study reproducible. Finally, we suggest registering study protocols to increase process transparency. With these tools the readership of diabetes RWE studies will be able to more efficiently understand each study and be more able to assess a study's validity with reasonably high confidence before making decisions based on its findings. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is the major cause of kidney failure in the world and the combination of DKD and diabetes mellitus contributes to an additive incidence of worsening cardiovascular mortality rates. Angiotensin‐converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) remain the mainstay of therapy and have reduced kidney function decline in DKD from 8 to 10 to ~4 mL/min/y. Sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors, in the presence of ACE inhibitors or ARB agents, further slowdown DKD progression by an additional 58% to 1.8 mL/min/y. Moreover, SGLT2 inhibitors reduce heart failure risk. However, the normal rate of kidney function decline in humans is between 0.7 and 0.9 mL/min/y, hence, there is still room for improvement. Mineralocorticoid receptor antagonists (MRAs) already have a track record of benefit in heart failure risk reduction, and efficacy in reducing albuminuria and treating resistant hypertension; however hyperkalaemia and other adverse effects preclude their routine use in DKD. Novel non‐steroidal MRAs offer a reduced risk of hyperkalaemia, and yet have many benefits that they share with their steroidal cousins. This paper reviews the data for both steroidal and non‐steroidal MRAs in DKD and presents some data from soon‐to‐be‐completed ongoing renal and cardiovascular outcome trials in DKD. [ABSTRACT FROM AUTHOR]

Type 1 diabetes mellitus (T1DM) remains one of the most challenging long‐term conditions to manage. Despite robust evidence to demonstrate that near normoglycaemia minimizes, but does not completely eliminate, the risk of complications, its achievement has proved almost impossible in a real‐world setting. HbA1c to date has been used as the gold standard marker of glucose control and has been shown to reflect directly the risk of diabetes complications. However, it has been recognized that HbA1c is a crude marker of glucose control. Continuous glucose monitoring (CGM) provides the ability to measure and observe inter‐ and intraday glycaemic variability (GV), a more meaningful measure of glycaemic control, more relevant to daily living for those with T1DM. This paper reviews the relationship between GV and hypoglycaemia, and micro‐ and macrovascular complications. It also explores the impact on GV of CGM, insulin pumps, closed‐loop technologies, and newer insulins and adjunctive therapies. Looking to the future, there is an argument that GV should become a key determinant of therapeutic success. Further studies are required to investigate the pathological and psychological benefits of reducing GV. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) and obesity constitute interwoven pandemics challenging healthcare systems in developed countries, where diabetic kidney disease (DKD) is the most common cause of end‐stage renal disease. Obesity accelerates renal functional decline in people with T2DM. Intentional weight loss (IWL) strategies in this population hold promise as a means of arresting DKD progression. In the present paper, we summarize the impact of IWL strategies (stratified by lifestyle intervention, medications, and metabolic surgery) on renal outcomes in obese people with DKD. We reviewed the Medline, EMBASE and Cochrane databases for relevant randomized control trials and observational studies published between August 1, 2018 and April 15, 2019. We found that IWL improves renal outcomes in the setting of DKD and obesity. Rate of progression of DKD slows with IWL, but varying outcome measures among studies makes direct comparison difficult. Furthermore, established means of estimating renal function are imperfect owing to loss of lean muscle mass with IWL strategies. The choice of optimal IWL strategy needs to be individualized; future work should establish the comparative efficacy of IWL strategies in obese people with DKD to better inform such decisions. [ABSTRACT FROM AUTHOR]

Regulatory guidelines describe the use of estimands in designing and conducting clinical trials. Estimands ensure alignment of the objectives with the design, conduct and analysis of a trial. An estimand is defined by four inter‐related attributes: the population of interest, the variable (endpoint) of interest, the way intercurrent events are handled and the population level summary. A trial may employ multiple estimands to evaluate treatment effects from different perspectives in order to address different scientific questions. As estimands may be an unfamiliar concept for many clinicians treating diabetes, this paper reviews the estimand concept and uses the PIONEER 1 phase 3a clinical trial, which investigated the efficacy and safety of oral semaglutide vs placebo, as an example of the way in which estimands can be implemented and interpreted. In the PIONEER 1 trial, two estimands were employed for each efficacy endpoint and were labelled as: (a) the treatment policy estimand, used to assess the treatment effect regardless of use of rescue medication or discontinuation of trial product, and provides a broad perspective of the treatment effect in the population of patients with type 2 diabetes in clinical practice; and (b) the trial product estimand, used to assess the treatment effect if all patients had continued to use trial product for the planned duration of the trial without rescue medication, thereby providing information on the anticipated treatment effect of the medication. Both approaches are complementary to understanding the effect of the studied treatments. [ABSTRACT FROM AUTHOR]

Moreover, as the Clinical Events Committee adjudicated new-onset diabetes, patients in whom review of possible incident cases revealed the diabetes was, in fact, prevalent, could not logically be at risk of new-onset diabetes. The correct calculation is that, of the 10 081 patients with a clinical diagnosis of diabetes per the local site investigator listed in Table 1, 10 065 patients were in the safety analysis population of 27 525 patients, and another 784 patients in the safety population were identified by the Clinical Events Committee as having prevalent diabetes and thus were not at-risk of incident diabetes. The correct calculation is that, of the 11 031 patients with diabetes identified through all means in the intention-to-treat cohort, 11 015 were in the safety cohort of 27 525 patients, leaving 16 510 (the sum of 8256 and 8254) as eligible for new-onset diabetes, just as we correctly reported. [Extracted from the article]

We also re-ran the analysis considering the adverse events reported in ClinicalTrials.gov with SCALE Obesity and Prediabetes divided into arms 1 and 2 (no prediabetes) and arms 3 and 4 (prediabetes). Leite, A.R., Angélico-Gonçalves, A., Vasques-Nóvoa, F., Borges-Canha, M., Leite-Moreira, A., Neves, J.S. and Ferreira, J.P. (2022), Effect of GLP-1 receptor agonists on cardiovascular events in overweight or obese adults without diabetes: a meta-analysis of placebo-controlled randomized trials. Effect of GLP-1 receptor agonists on cardiovascular events in overweight or obese adults without diabetes: a meta-analysis of placebo-controlled randomized trials. [Extracted from the article]

The U-500R insulin protocol was consistently applied by the NPs/PA so that variations in HbA1c levels would be mainly influenced by changes in patient lifestyles (as is usually the case for patients receiving less concentrated insulins). Following this simplified, straightforward U-500R insulin protocol, based on the principles underlying the use of NPH and regular insulin in self-mixed/split-insulin regimens, should enable PCPs to treat and improve diabetes control in these challenging, markedly insulin-resistant patients. In 2016, 3.3% of insulin-requiring people with diabetes received >200 units per day.[1] Because 30%[2] of the 28.5 million adults known to have diabetes[3] take insulin, there are >250 000 patients receiving an amount of insulin for which substituting U-500 regular insulin (U-500R) has been recommended. Human regular U-500 insulin via continuous insulin infusion versus multiple daily injections in adults with type 2 diabetes: the VIVID study. [Extracted from the article]

Aims: To compare the safety and efficacy of fast‐acting insulin aspart (faster aspart) with conventional insulin aspart (IAsp) in adults with type 1 diabetes (T1D). Materials and methods: onset 1 was a randomized, multicentre, treat‐to‐target, phase III, 52‐week (initial 26 weeks + additional 26 weeks) trial conducted at 165 sites across 9 countries. Adults with T1D were randomly allocated to double‐blind mealtime faster aspart or IAsp, each with once‐ or twice‐daily insulin detemir. The primary endpoint, change in glycated haemoglobin (HbA1c) from baseline after the initial 26 weeks, has been reported previously. In the present paper, we report data from the full 52‐week study period. Results: Between August 2013 and June 2015, 381 participants were assigned to double‐blind faster aspart and 380 participants to IAsp. After 52 weeks, estimated mean changes from baseline in HbA1c levels were −0.08% (faster aspart) and +0.01% (IAsp); estimated treatment difference significantly favoured faster aspart (−0.10% [95% confidence interval {CI} −0.19;−0.00]; P = .0424). Changes from baseline in 1‐hour postprandial plasma glucose (PPG) increment (meal test; faster aspart −1.05 mmol/L; IAsp −0.14 mmol/L) also significantly favoured faster aspart (estimated treatment difference −0.91 mmol/L [95% CI −1.40;−0.43]; −16.48 mg/dL [95% CI −25.17;−7.80]; P = .0002). There was no difference in overall severe or blood glucose‐confirmed hypoglycaemic episodes or treatment‐emergent adverse events between treatments. Conclusions: At 52 weeks, overall glycaemic control had significantly improved with faster aspart vs IAsp, consistent with the 26‐week study findings. Achieving an insulin profile closer to physiological insulin secretion with faster aspart translates into lower PPG and HbA1c levels compared with those achieved with IAsp in people with T1D. [ABSTRACT FROM AUTHOR]

The Restoring Insulin Secretion ( RISE) study was initiated to evaluate interventions to slow or reverse the progression of β-cell failure in type 2 diabetes ( T2D). To design the RISE study, we undertook an evaluation of methods for measurement of β-cell function and changes in β-cell function in response to interventions. In the present paper, we review approaches for measurement of β-cell function, focusing on methodologic and feasibility considerations. Methodologic considerations included: (1) the utility of each technique for evaluating key aspects of β-cell function (first- and second-phase insulin secretion, maximum insulin secretion, glucose sensitivity, incretin effects) and (2) tactics for incorporating a measurement of insulin sensitivity in order to adjust insulin secretion measures for insulin sensitivity appropriately. Of particular concern were the capacity to measure β-cell function accurately in those with poor function, as is seen in established T2D, and the capacity of each method for demonstrating treatment-induced changes in β-cell function. Feasibility considerations included: staff burden, including time and required methodological expertise; participant burden, including time and number of study visits; and ease of standardizing methods across a multicentre consortium. After this evaluation, we selected a 2-day measurement procedure, combining a 3-hour 75-g oral glucose tolerance test and a 2-stage hyperglycaemic clamp procedure, augmented with arginine. [ABSTRACT FROM AUTHOR]

A large proportion of patients with type 1 diabetes do not reach their glycaemic target of glycated hemoglobin ( HbA1c) <7.0% (53 mmol/mol) and, furthermore, an increasing number of patients with type 1 diabetes are overweight and obese. Treatment of type 1 diabetes is based on insulin therapy, which is associated with well-described and unfortunate adverse effects such as hypoglycaemia and increased body weight. Glucagon-like peptide-1 ( GLP-1) receptor agonists ( RAs) are the focus of increasing interest as a possible adjunctive treatment to insulin in type 1 diabetes because of their glucagonostatic and extrapancreatic effects. So far, the focus has mainly been on the long-acting GLP-1RAs, but the risk-benefit ratio emerging from studies evaluating the effect of long-acting GLP-1RAs as adjunctive therapy to insulin therapy in patients with type 1 diabetes has been disappointing. This might be attributable to a lack of glucagonostatic effect of these long-acting GLP-1RAs in type 1 diabetes, alongside development of tachyphylaxis to GLP-1-induced retardation of gastric emptying. In contrast, the short-acting GLP-1RAs seem to have a preserved and sustained effect on glucagon secretion and gastric emptying in patients with type 1 diabetes, which could translate into effective lowering of postprandial glucose excursions; however, these observations regarding short-acting GLP-1RAs are all derived from small open-label trials and should thus be interpreted with caution. In the present paper we review the potential role of GLP-1RAs, in particular short-acting GLP-1RAs, as add-on to insulin in the treatment of type 1 diabetes. [ABSTRACT FROM AUTHOR]

Aims To conduct a phase III study to evaluate the efficacy and safety of ertugliflozin monotherapy in people with type 2 diabetes. Materials and methods This was a 52-week, double-blind, multicentre, randomized, parallel-group study with a 26-week, placebo-controlled treatment period (phase A), followed by a 26-week active-controlled treatment period (phase B) in 461 men and women, aged ≥18 years with inadequate glycaemic control (glycated haemoglobin [HbA1c] concentration 7.0% to 10.5% [53-91 mmol/mol], inclusive) despite diet and exercise. Results from phase A are reported in the present paper. The primary endpoint was the change in HbA1c from baseline to week 26. Results At week 26, the placebo-adjusted least squares mean HbA1c changes from baseline were −0.99% and −1.16% for the ertugliflozin 5 and 15 mg doses, respectively ( P < .001 for both doses). The odds of having HbA1c <7.0% (53 mmol/mol) were significantly greater in the ertugliflozin 5 and 15 mg groups compared with the placebo group. Both doses of ertugliflozin significantly lowered fasting plasma glucose and 2-hour postprandial glucose levels and body weight. The placebo-adjusted differences in changes from baseline in systolic blood pressure were not statistically significant. A higher incidence of genital mycotic infections occurred in men and women treated with ertugliflozin compared with placebo. There was no significant difference between treatments in the proportion of participants with symptomatic hypoglycaemia or adverse events associated with urinary tract infection or hypovolaemia. Conclusions Ertugliflozin 5 and 15 mg treatment for 26 weeks provides effective glycaemic control, reduces body weight and is generally well tolerated, when used as monotherapy. [ABSTRACT FROM AUTHOR]

Gut bacteria are involved in a number of host metabolic processes and have been implicated in the development of obesity and type 2 diabetes in humans. The use of antibiotics changes the composition of the gut microbiota and there is accumulating evidence from observational studies for an association between exposure to antibiotics and development of obesity and type 2 diabetes. In the present paper, we review human studies examining the effects of antibiotics on body weight regulation and glucose metabolism and discuss whether the observed findings may relate to alterations in the composition and function of the gut microbiota. [ABSTRACT FROM AUTHOR]

The recently completed EMPA-REG study showed that empagliflozin significantly decreased the major adverse cardiac events ( MACE) endpoint, which comprised cardiovascular death, non-fatal myocardial infarction ( MI) and stroke, in patients with high-risk type 2 diabetes ( T2DM), primarily through a reduction in cardiovascular death, without a significant decrease in either MI or stroke. In the PROactive study, pioglitazone decreased the MACE endpoint by a similar degree to that observed in the EMPA-REG study, through a marked reduction in both recurrent MI and stroke and a modest reduction in cardiovascular death. These observations suggest that pioglitazone might be an ideal agent to combine with empagliflozin to further reduce cardiovascular events in patients with high-risk diabetes as empagliflozin also promotes salt/water loss and would be expected to offset any fluid retention associated with pioglitazone therapy. In the present paper, we provide an overview of the potential benefits of combined pioglitazone/empagliflozin therapy to prevent cardiovascular events in patients with T2DM. [ABSTRACT FROM AUTHOR]

Aims To examine the efficacy and safety of once-weekly dulaglutide 0.75 mg monotherapy compared with once-daily liraglutide 0.9 mg in Japanese patients with type 2 diabetes ( T2D) for 52 weeks. Methods We conducted a phase III, randomized, 52-week (26-week primary endpoint), active- and placebo-controlled trial comparing 492 Japanese patients (dulaglutide, n = 281; liraglutide, n = 141; and placebo, n = 70). Participants and investigators were blinded to treatment assignment for dulaglutide and placebo but not for liraglutide (open-label comparator); after 26 weeks, patients randomized to placebo were switched to once-weekly dulaglutide 0.75 mg (open-label). The present paper reports results for patients treated with dulaglutide and patients treated with liraglutide for 52 weeks. Results At week 52, dulaglutide decreased HbA1c significantly from baseline compared with liraglutide [least squares mean difference: −0.20; 95% confidence interval ( CI) −0.39, −0.01; p = 0.04]. At week 52 (last observation carried forward), dulaglutide significantly decreased pre- and post-dinner blood glucose ( BG) levels, the mean of seven-point self-monitored BG profiles, the mean of all postprandial BG levels and circadian variation compared with liraglutide. Body weight was generally stable in both groups through 52 weeks. The most frequently reported adverse events were nasopharyngitis, constipation, nausea and diarrhoea. Eight dulaglutide-treated (2.9%) and four liraglutide-treated (2.9%) patients reported hypoglycaemia, with no event being severe. Conclusions Monotherapy with once-weekly dulaglutide 0.75 mg was effective and safe in Japanese patients with T2D, with better glycaemic control compared with once-daily liraglutide 0.9 mg. [ABSTRACT FROM AUTHOR]

Obesity predisposes an individual to develop numerous comorbidities, including type 2 diabetes, and represents a major healthcare issue inmany countries worldwide. Bariatric surgery can be an effective treatment option, resulting in profound weight loss and improvements in metabolic health; however, not all patients achieve similar weight loss or metabolic improvements. Exercise is an excellent way to improve health, with well-characterized physiological and psychological benefits. In the present paper we review the evidence to determine whether there may be a role for exercise as a complementary adjunct therapy to bariatric surgery. Objectively measured physical activity data indicate that most patients who undergo bariatric surgery do not exercise enough to reap the health benefits of exercise. While there is a dearth of data on the effects of exercise on weight loss and weight loss maintenance after surgery, evidence from studies of caloric restriction and exercise suggest that similar adjunctive benefits may be extended to patients who perform exercise after bariatric surgery. Recent evidence from exercise interventions after bariatric surgery suggests that exercise may provide further improvements in metabolic health compared with surgery-induced weight loss alone. Additional randomized controlled exercise trials are now needed as the next step to more clearly define the potential for exercise to provide additional health benefits after bariatric surgery. This valuable evidence will inform clinical practice regarding much-needed guidelines for exercise after bariatric surgery. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor discussing the article "Effects of a natural extract of hydroxycitric acid and a combination of HCA-SX plus niacin-bound chromium and Gymnema sylvestre extract on weight loss," by H.G. Preuss and colleagues. Criticism over the absence of primary endpoints or suggestions on the conduction of a priori power calculations; Failure of statistical analysis strategy to clarify confusing outcome conclusions; Absence on adjustments for multiple comparisons in multiple t-tests; Data inconsistencies leading to questionable data results interpretation.

Overweight and obesity currently constitute a major threat to human well-being. Almost half of the female population are currently overweight. Pregnant overweight women are at risk of gestational diabetes affecting the health of the mother and the child, in both the short and long term. Notwithstanding the extensive scientific interest centred on the problem, research efforts have thus far been unable to devise preventive strategies. Recent scientific advances point to a gut microbiota dysbiosis, with ensuing low-grade inflammation as a contributing element, in obesity and its comorbidities. Such findings would suggest a role for specific probiotics in the search for preventive and therapeutic adjunct applications in gestational diabetes. The aim of the present paper was to critically review recent demonstrations of the role of intestinal microbes in immune and metabolic regulation, which could be exploited in nutritional management of pregnant women by probiotic bacteria. By modulating specific target functions, probiotic dietary intervention may exert clinical effects beyond the nutritional impact of food. As this approach in pregnancy is new, an overview of the role of gut microbiota in shaping host metabolism, together with the definition of probiotics are presented, and finally, specific targets and potential mechanisms for probiotics in pregnancy are discussed. Pregnancy appears to be the most critical stage for interventions aiming to reduce the risk of non-communicable disease in future generations, beyond the immediate dangers attributable to the health of the mother, labour and the neonate. Specific probiotic interventions during pregnancy provide an opportunity, therefore, to promote the health not only of the mother but also of the child. [ABSTRACT FROM AUTHOR]

Aims To investigate the efficacy and tolerability of albiglutide, a weekly glucagon-like peptide-1 receptor agonist, when added to metformin and glimepiride in a triple therapy regimen in people with type 2 diabetes mellitus. Methods This was a 156-week, randomized, double-blind, parallel-group, multicentre study. In the present paper we describe the primary results, namely those at 52 weeks. Adult participants (n = 685) were randomly assigned to albiglutide (30 mg/week), pioglitazone (30 mg/day) or placebo. If needed, blinded uptitration of albiglutide (to 50 mg/week) and pioglitazone (to 45 mg/day) was allowed. The participant's current dose of metformin (>1500 mg/day) was maintained throughout. The glimepiride dose (4 mg/day), standardized before randomization, could be decreased if persistent hypoglycaemia occurred. Results The week 52 model-adjusted difference in change of glycated haemoglobin (primary endpoint) for albiglutide versus placebo was -0.87 [95% confidence interval ( CI) -1.07, -0.68]%-units (p < 0.001), and for albiglutide versus pioglitazone it was 0.25 (95% CI 0.10, 0.40)%-units; therefore, not non-inferior. In the albiglutide group only, fasting plasma glucose reduced rapidly in the first 2 weeks. Confirmed hypoglycaemia occurred in 14% of participants on albiglutide, 25% on pioglitazone and 14% on placebo. The mean (± standard error) weight change was −0.42 (±0.2) kg with albiglutide, +4.4 (±0.2) kg (p < 0.001) with pioglitazone, and −0.40 (±0.4) kg with placebo and serious adverse events occurred in 6.3, 9.0 and 6.1% of participants in the respective groups. Injection site reactions occurred in 13% of participants on albiglutide and resulted in treatment discontinuation for four participants (1.4%). Conclusions Albiglutide, as part of triple therapy, provided effective glucose-lowering and was generally well tolerated. [ABSTRACT FROM AUTHOR]

Aim Different intervention strategies can prevent type 2 diabetes ( T2DM). Aim of the present systematic review and meta-analysis was to evaluate the effectiveness of different strategies. Methods Studies were grouped into 15 different strategies: 1: diet plus physical activity; 2: physical activity; 3-6: anti-diabetic drugs [glitazones, metformin, beta-cell stimulating drugs (sulphanylureas, glinides), alfa-glucosidase inhibitors]; 7-8: cardiovascular drugs ( ACE inhibitors, ARB, calcium antagonists); 9-14 [diets, lipid-affecting drugs (orlistat, bezafibrate), vitamins, micronutrients, estrogens, alcohol, coffee]; 15: bariatric surgery. Only controlled studies were included in the analysis, whether randomized, non-randomized, observational studies, whether primarily designed to assess incident cases of diabetes, or performed with other purposes, such as control of hypertension, of ischemic heart disease or prevention of cardiovascular events. Appropriate methodology [preferred reporting items for systematic reviews and meta-analyses ( PRISMA) statement] was used. Seventy-one studies (490 813 subjects), published as full papers, were analysed to identify predictors of new cases of T2DM, and were included in a meta-analysis (random-effects model) to study the effect of different strategies. Intervention effect (new cases of diabetes) was expressed as odds ratio ( OR), with 95% confidence intervals ( C.I.s). Publication bias was formally assessed. Results Body mass index was in the overweight range for 13 groups, obese or morbidly obese in lipid-affecting drugs and in bariatric surgery. Non-surgical strategies, except for beta-cell stimulating drugs, estrogens and vitamins, were able to prevent T2DM, with different effectiveness, from 0.37 (C.I. 0.26-0.52) to 0.85 (C.I. 0.77-0.93); the most effective strategy was bariatric surgery in morbidly obese subjects [0.16 (C.I. 0.11,0.24)]. At meta-regression analysis, age of subjects and amount of weight lost were associated with effectiveness of intervention. Conclusions These data indicate that several strategies prevent T2DM, making it possible to make a choice for the individual subject. [ABSTRACT FROM AUTHOR]

A recently published study by Butler et al. concluded that incretin treatment had adverse effects on the human type 2 diabetic pancreas including 'a marked expansion of the exocrine and endocrine pancreatic compartments, the former being accompanied by increased proliferation and dysplasia and the latter by α-cell hyperplasia with the potential for evolution into neuroendocrine tumours'. Incretin therapy has become widely used for type 2 diabetes, so these conclusions have instigated major concerns with regard to patient safety. We reassessed both the clinical case information and virtual microscopy images of the same 34 cases that were used in the Butler study as well as Network for Pancreatic Organ Donation ( nPOD) cases that were not included. Whereas we would like to stress that it is important to investigate in depth any indication that incretin treatment may lead to inflammation or dysplasia in the pancreas, we find that the data presented in the Butler paper have serious methodological deficiencies that preclude any meaningful conclusions. [ABSTRACT FROM AUTHOR]

Charcot arthropathy is a major complication of diabetes and it poses management challenges to health care professionals. Early diagnosis and timely intervention are essential for improved outlook of these patients. Casting therapy has been accepted as the mainstay treatment of the acute Charcot foot, although there are still controversies regarding its duration, the choice of removable and non-removable device and weight-bearing casts vs. non-weight-bearing casts. Two groups of antiresorptive therapies have been evaluated in the treatment of the acute Charcot foot, bisphosphonates (intravenous and oral) and calcitonin. These therapies have clearly shown a reduction of bone turnover, although, they have not shown a significant effect on temperature reduction. Current evidence to support their use is weak. An anabolic agent to speed up clinical resolution and fracture healing may be helpful and a clinical trial to evaluate the possible benefit of 1-84 recombinant human parathyroid hormone on fracture healing in the acute Charcot foot is in progress. This paper summarises the current approach to medical management of acute Charcot arthropathy with specific emphasis on casting and pharmacological therapy. Emerging new studies of the pathogenesis of this condition are also discussed. [ABSTRACT FROM AUTHOR]

Aim: Aim of this study was to analyse clinical correlates of HbA1c, and of overall, nocturnal, and severe hypoglycaemia, through direct-weighted regressions, as well as the effect of different insulin regimens and insulin analogues, through meta-analysis. Methods: Appropriate methodology (PRISMA statement) was used. Sixty-seven randomized studies, published as full papers were analysed to identify predictors of both HbA1c and hypoglycaemia; studies were included in a meta-analysis to study the effect of different insulin regimens or insulin analogues on HbA1c and hypoglycaemia during the first year of insulin treatment in type 2 diabetes patients. Results: Final HbA1c, change of HbA1c, hypoglycaemia, nocturnal hypoglycaemia and severe hypoglycaemia were associated with intensity of treatment. Final HbA1c was higher with basal than with twice-a-day or prandial, and with twice-a-day than with prandial regimen, with opposite figures for hypoglycaemia. Within basal regimens, detemir and glargine were similar to NPH insulin on HbA1c, with less hypoglycaemia and nocturnal hypoglycaemia; within prandial regimens, new analogues were more effective than regular insulin on HbA1c, and induced less hypoglycaemia. The effect of glargine on HbA1c and on hypoglycaemia vanished with increasing number of insulin injections. Conclusion: Metabolic control and hypoglycaemia are associated with intensity of treatment. Basal regimens have a reduced effect on metabolic control, but are associated with lower frequency of hypoglycaemia. Newer analogues, short- and long-acting, yield better control and less hypoglycaemia than older analogues. [ABSTRACT FROM AUTHOR]

An estimated 72.5 million American adults are obese, and the growing US obesity epidemic is responsible for substantial increase in morbidity and mortality, as well as increased health care costs. Obesity results from a combination of personal and societal factors, but is often viewed as a character flaw rather than a medical condition. This leads to stigma and discrimination towards obese individuals and decreases the likelihood of effective intervention. Conditions related to obesity are increasingly common, such as metabolic syndrome, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), all of which indicate high risk for type 2 diabetes (T2DM). This paper reviews the progression from obesity to diabetes, identifying physiological changes that occur along this path as well as opportunities for patient identification and disease prevention. Patients with prediabetes (defined as having IFG, IGT or both) and/or metabolic syndrome require interventions designed to preserve insulin sensitivity and β-cell function, both of which start to deteriorate prior to T2DM diagnosis. Lifestyle modification, including both healthy eating choices and increased physical activity, is essential for weight management and diabetes prevention. Although sustained weight loss is often considered by patients and physicians as being impossible to achieve, effective interventions do exist. Specifically, the Diabetes Prevention Program (DPP) and programs modelled along its parameters have shown repeated successes, even with long-term maintenance. Recent setbacks in the development of medications for weight loss further stress the importance of lifestyle management. By viewing obesity as a metabolic disorder rather than a personal weakness, we can work with patients to address this increasingly prevalent condition and improve long-term health outcomes. [ABSTRACT FROM AUTHOR]

Pregnancy is now considered to be an important risk factor for new or persistent obesity among women during the childbearing years. High gestational weight gain is the strongest predictor of maternal overweight or obesity following pregnancy. A growing body of evidence also suggests that both high and low gestational weight gains are independently associated with an increased risk of childhood obesity, suggesting that influences occurring very early in life are contributing to obesity onset. In response to these data, the US Institute of Medicine (IOM) revised gestational weight gain guidelines in 2009 for the first time in nearly two decades. However, less than one third of pregnant women achieve guideline-recommended gains, with the majority gaining above IOM recommended levels. To date, interventions to optimize pregnancy weight gains have had mixed success. In this paper, we summarize the evidence from human and animal studies linking over-nutrition and under-nutrition in pregnancy to maternal and child obesity. In addition, we discuss published trials and ongoing interventions to achieve appropriate gestational weight gain as a strategy for obesity prevention in women and their children. [ABSTRACT FROM AUTHOR]

This paper reviews the evidence in relation to the optimal target for HbA1c and outlines a global treatment algorithm for people with type 2 diabetes. While most guidelines recommend a general HbA1c target of 7%, recent large scale intervention studies have examined the potential benefits of lower targets. These studies have generally shown that lower HbA1c targets provide no macrovascular benefits and limited effects on microvascular complications while increasing rates of hypoglycaemia. Overall these studies do not support a general HbA1c target lower than 7.0%. However an individual's HbA1c target should be set and reviewed taking into account treatment benefits, safety, and tolerability. This may mean that an HbA1c target lower than 7% is appropriate for some when it can be easily and safely achieved but equally a higher HbA1c target may be appropriate in others. Clinicians and consumers are fortunate in having a wide range of pharmacological agents available to treat hyperglycaemia, however access to many of these options is limited in many middle and low income countries. Developing treatment algorithms is complex for several reasons. The major limitation is the limited evidence base for choosing particular treatment options or combinations of medications. However it is possible to derive a generic evidence-informed consensus algorithm which considers availability, access and cost of medications which can be adapted for local country use. [ABSTRACT FROM AUTHOR]

Aim: This systematic review and meta-analysis was to evaluate the body weight increase and its clinical correlates, through direct weighted regressions, as well as the effect of different insulin regimens and insulin analogues, through meta-analysis. Methods: Appropriate methodology according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was adhered to. Forty-six randomized studies, published as full papers, reporting the effect of insulin treatment on change in body weight were identified, and used to identify predictors of weight change; studies were included in a meta-analysis to study the effect of different insulin regimens or insulin analogues on weight change. Results: Intensity of treatment [aim of study (fasting blood glucose, mg/dl), dose of insulin, final HbA1c, change of HbA1c and frequency of hypoglycaemia] was significantly associated with body weight increase, with small differences between basal versus twice-a-day and prandial regimen. At meta-analysis, body weight increase was lower with basal regimen than with twice-a-day regimen and than with a prandial regimen. Within all regimens, body weight increase was lower with detemir than with NPH, with no difference between glargine and NPH; only two studies directly compared detemir and glargine, indicating lower weight gain with the former insulin. Within twice-a-day regimens and within prandial regimens, comparison was between newer analogues and older drugs, with no significant difference in body weight increase. Conclusion: Body weight increase during the first year of insulin treatment is associated with the intensity of treatment; body weight increase also depends on the insulin regimen applied. [ABSTRACT FROM AUTHOR]

As an introduction to the Symposium, we have reviewed the early steps in glucagon research from its discovery in 1923 to the establishment of the basics of the physiology and pathophysiology of the hormone after the description of a sensitive and specific radioimmunoassay by Unger and his co-workers in 1959. [ABSTRACT FROM AUTHOR]