Prevalence of diabetic cardiomyopathy in patients with type 2 diabetes in a large academic medical center.

BACKGROUND: Diabetic cardiomyopathy (DbCM) is characterized by asymptomatic stage B heart failure (SBHF) caused by diabetes-related metabolic alterations. DbCM is associated with an increased risk of progression to overt heart failure (HF). The prevalence of DbCM in patients with type 2 diabetes (T2D) is not well established. This study aims to determine prevalence of DbCM in adult T2D patients in real-world clinical practice. METHODS: Retrospective multi-step review of electronic medical records of patients with the diagnosis of T2D who had echocardiogram at UC San Diego Medical Center (UCSD) within 2010-2019 was conducted to identify T2D patients with SBHF. We defined "pure" DbCM when SBHF is associated solely with T2D and "mixed" SBHF when other medical conditions can contribute to SBHF. "Pure" DbCM was diagnosed in T2D patients with echocardiographic demonstration of SBHF defined as left atrial (LA) enlargement (LAE), as evidenced by LA volume index ≥ 34 mL/m2, in the presence of left ventricular ejection fraction (LVEF) ≥ 45%, while excluding overt HF and comorbidities that can contribute to SBHF. RESULTS: Of 778,314 UCSD patients in 2010-2019, 45,600 (5.9%) had T2D diagnosis. In this group, 15,182 T2D patients (33.3%) had echocardiogram and, among them, 13,680 (90.1%) had LVEF ≥ 45%. Out of 13,680 patients, 4,790 patients had LAE. Of them, 1,070 patients were excluded due to incomplete data and/or a lack of confirmed T2D according to the American Diabetes Association recommendations. Thus, 3,720 T2D patients with LVEF ≥ 45% and LAE were identified, regardless of HF symptoms. In this group, 1,604 patients (43.1%) had overt HF and were excluded. Thus, 2,116 T2D patients (56.9% of T2D patients with LVEF ≥ 45% and LAE) with asymptomatic SBHF were identified. Out of them, 1,773 patients (83.8%) were diagnosed with "mixed" SBHF due to comorbidities such as hypertension (58%), coronary artery disease (36%), and valvular heart disease (17%). Finally, 343 patients met the diagnostic criteria of "pure" DbCM, which represents 16.2% of T2D patients with SBHF, i.e., at least 2.9% of the entire T2D population in this study. CONCLUSIONS: Our findings provide insights into prevalence of DbCM in real-world clinical practice and indicate that DbCM affects a significant portion of T2D patients.

[Impact of smoking on the presence of diabetic cardiomyopathy]. / Impact du tabagisme sur la présence de la cardiomyopathie diabétique.

INTRODUCTION: Type 2 diabetes is associated with an increased risk of coronary disease and is the leading cause of morbidity and mortality in this population. The main objective of our work is to study the correlation of left atrial volume index with coronary disease in type 2 diabetics. MATERIAL AND METHODS: Cross-sectional, analytical, single-center study with prospective recruitment of 330 type 2 diabetic patients carried out at the Constantine Regional Military University Hospital over a period of 03 years (2016-2018) among which 18.8% (62 patients) are smokers. Early cardiac involvement represented by diastolic dysfunction was assessed by two-dimensional transthoracic echocardiography. Data were analyzed using Epi info 7.2.1.0 software to study the impact of smoking on the presence of left ventricular diastolic dysfunction. RESULTS: The average age of our cohort is 52.7 ± 8.4 years, an average of 7.1 ± 1.3% of glycated hemoglobin, an average of 5.3 ± 4.3 years of diabetes duration, a sex ratio to 1.01. 34.8% of patients had left atrial volume index ≥ 34 ml/m2. The prevalence of coronary disease is 27.0%. In multivariate analysis; left atrial volume index is significantly correlated with coronary stenosis (OR = 1.75, 95% CI [1.60 - 2.05], p = 0.02). CONCLUSION: The prevalence of cardiomyopathy is high in type 2 diabetes and smoking is significantly correlated with the presence of this diabetic cardiomyopathy.

Mechanisms of reduced peak oxygen consumption in subjects with uncomplicated type 2 diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2D) increases the risk of incident heart failure (HF), whose earliest fingerprint is effort intolerance (i.e. impaired peak oxygen consumption, or VO2peak). In the uncomplicated T2D population, however, the prevalence of effort intolerance and the underpinning mechanistic bases are uncertain. Leveraging the multiparametric characterization allowed by imaging-cardiopulmonary exercise testing (iCPET), the aim of this study is to quantify effort intolerance in T2D and to dissect the associated cardiopulmonary alterations. METHODS: Eighty-eight adults with well-controlled and uncomplicated T2D and no criteria for HF underwent a maximal iCPET with speckle tracking echocardiography, vascular and endothelial function assessment, as well as a comprehensive biohumoral characterization. Effort intolerance was defined by a VO2peak below 80% of maximal predicted oxygen uptake. RESULTS: Forty-eight patients (55%) had effort intolerance reaching a lower VO2peak than T2D controls (16.5 ± 3.2 mL/min/kg, vs 21.7 ± 5.4 mL/min/kg, p < 0.0001). Despite a comparable cardiac output, patients with effort intolerance showed reduced peak peripheral oxygen extraction (11.3 ± 3.1 vs 12.7 ± 3.3 mL/dL, p = 0.002), lower VO2/work slope (9.9 ± 1.2 vs 11.2 ± 1.4, p < 0.0001), impaired left ventricle systolic reserve (peak S' 13.5 ± 2.8 vs 15.2 ± 3.0, p = 0.009) and global longitudinal strain (peak-rest ΔGLS 1.7 ± 1.5 vs 2.5 ± 1.8, p = 0.03) than subjects with VO2peak above 80%. Diastolic function, vascular resistance, endothelial function, biohumoral exams, right heart and pulmonary function indices did not differ between the two groups. CONCLUSIONS: Effort intolerance and reduced VO2peak is a severe and highly prevalent condition in uncomplicated, otherwise asymptomatic T2D. It results from a major defect in skeletal muscle oxygen extraction coupled with a subtle myocardial systolic dysfunction.

Myocardial glucotoxicity: Mechanisms and potential therapeutic targets.

Besides coronary artery disease, which remains the main cause of heart failure in patients with diabetes, factors independent of coronary artery disease are involved in the development of heart failure in the onset of what is called diabetic cardiomyopathy. Among them, hyperglycaemia - a hallmark of type 2 diabetes - has both acute and chronic deleterious effects on myocardial function, and clearly participates in the establishment of diabetic cardiomyopathy. In the present review, we summarize the cellular and tissular events that occur in a heart exposed to hyperglycaemia, and depict the complex molecular mechanisms proposed to be involved in glucotoxicity. Finally, from a more translational perspective, different therapeutic strategies targeting hyperglycaemia-mediated molecular mechanisms will be detailed.

The Impact of Diabetes Mellitus on Cardiovascular Risk Onset in Children and Adolescents.

The prevalence of diabetes mellitus is rising among children and adolescents worldwide. Cardiovascular diseases are the main cause of morbidity and mortality in diabetic patients. We review the impact of diabetes on establishing, during childhood and adolescence, the premises for cardiovascular diseases later in life. Interestingly, it seems that hyperglycemia is not the only factor that establishes an increased cardiovascular risk in adolescence. Other factors have been recognized to play a role in triggering the onset of latent cardiovascular diseases in the pediatric population. Among these cardiovascular risk factors, some are modifiable: glucose variability, hypoglycemia, obesity, insulin resistance, waist circumference, hypertension, dyslipidemia, smoking alcohol, microalbuminuria and smoking. Others are unmodifiable, such as diabetes duration and family history. Among the etiological factors, subclinical endothelial dysfunction represents one of the earliest key players of atherosclerosis and it can be detected during early ages in patients with diabetes. A better assessment of cardiovascular risk in pediatric population still represents a challenge for clinicians, and thus further efforts are required to properly identify and treat pediatric patients who may suffer from cardiovascular disease later in early adulthood.

Genome-Wide Polygenic Score and the Risk of Ischemic Stroke in a Prospective Cohort: The Hisayama Study.

Background and Purpose- Environmental and genetic factors contribute to the development of ischemic stroke (IS). We recently developed a genome-wide polygenic risk score (PRS) for IS using case-control datasets from 4 large-scale observational studies conducted in Japan. Our objective in the present study was to confirm the association between the PRS and the risk of IS with data from an independent prospective cohort recruited from the general Japanese population. Methods- A total of 3038 subjects aged ≥40 years were followed up for 10 years (2002-2012). The genome-wide PRS was calculated using genotype data from >350 000 single-nucleotide polymorphisms. The PRS levels were divided into quintiles. High and low genetic risk groups were defined as top 60% and bottom 40% of PRS, respectively. The hazard ratio (HR) for the development of IS was estimated using a Cox proportional hazards model. Results- During the follow-up period, 91 cases developed first-ever IS. The age- and sex-adjusted HR for IS increased with higher PRS levels (P for trend, 0.03). Subjects with the highest quintile level of PRS had a 2.44-fold (95% CI, 1.16-5.12) greater risk for IS than those with the lowest quintile level after adjusting for age and sex. A similar association was observed after adjusting for environmental risk factors (P for trend, 0.03). As compared with low genetic risk group, the age- and sex-adjusted HR in high genetic risk group was 1.63 (95% CI, 1.04-2.55), which was comparable to the HR of hypertension (HR, 1.41), diabetes mellitus (HR, 1.72), and smoking (HR, 1.54). The age- and sex-adjusted HR increased with the number of environmental risk factors in both high and low genetic risk groups without significant interaction. Conclusions- A high genome-wide PRS was a significant risk factor for IS independent of environmental risk factors in a general Japanese population. This finding suggests that PRS may be useful to identify individuals at a high risk of IS.

Long-term effects of intensive multifactorial therapy in individuals with screen-detected type 2 diabetes in primary care: 10-year follow-up of the ADDITION-Europe cluster-randomised trial.

BACKGROUND: The multicentre, international ADDITION-Europe study investigated the effect of promoting intensive treatment of multiple risk factors among people with screen-detected type 2 diabetes over 5 years. Here we report the results of a post-hoc 10-year follow-up analysis of ADDITION-Europe to establish whether differences in treatment and cardiovascular risk factors have been maintained and to assess effects on cardiovascular outcomes. METHODS: As previously described, general practices from four centres (Denmark, Cambridge [UK], Leicester [UK], and the Netherlands) were randomly assigned by computer-generated list to provide screening followed by routine care of diabetes, or screening followed by intensive multifactorial treatment. Population-based stepwise screening programmes among people aged 40-69 years (50-69 years in the Netherlands), between April, 2001, and December, 2006, identified patients with type 2 diabetes. Allocation was concealed from patients. Following the 5-year follow-up, no attempts were made to maintain differences in treatment between study groups. In this report, we did a post-hoc analysis of cardiovascular and renal outcomes over 10 years following randomisation, including a 5 years post-intervention follow-up. As in the original trial, the primary endpoint was a composite of first cardiovascular event, including cardiovascular mortality, cardiovascular morbidity (non-fatal myocardial infarction and non-fatal stroke), revascularisation, and non-traumatic amputation, up to Dec 31, 2014. Analyses were based on the intention-to-treat principle. ADDITION-Europe is registered with ClinicalTrials.gov, NCT00237549. FINDINGS: 343 general practices were randomly assigned to routine diabetes care (n=176) or intensive multifactorial treatment (n=167). 317 of these general practices (157 in the routine care group, 161 in the intensive treatment group) included eligible patients between April, 2001, and December, 2006. Of the 3233 individuals with screen-detected diabetes, 3057 agreed to participate (1379 in the routine care group, 1678 in the intensive treatment group), but at the 10-year follow-up 14 were lost to follow-up and 12 withdrew, leaving 3031 to enter 10-year follow-up analysis. Mean duration of follow-up was 9·61 years (SD 2·99). Sustained reductions over 10 years following diagnosis were apparent for bodyweight, HbA1c, blood pressure, and cholesterol in both study groups, but between-group differences identified at 1 and 5 years were attenuated at the 10-year follow-up. By 10 years, 443 participants had a first cardiovascular event and 465 died. There was no significant difference between groups in the incidence of the primary composite outcome (16·1 per 1000 person-years in the routine care group vs 14·3 per 1000 person-years in the intensive treatment group; hazard ratio [HR] 0·87, 95% CI 0·73-1·04; p=0·14) or all-cause mortality (15·6 vs 14·3 per 1000 person-years; HR 0·90, 0·76-1·07). INTERPRETATION: Sustained reductions in glycaemia and related cardiovascular risk factors over 10 years among people with screen-detected diabetes managed in primary care are achievable. The differences in prescribed treatment and cardiovascular risk factors in the 5 years following diagnosis were not maintained at 10 years, and the difference in cardiovascular events and mortality remained non-significant. FUNDING: National Health Service Denmark, Danish Council for Strategic Research, Danish Research Foundation for General Practice, Novo Nordisk, Novo Nordisk Foundation, Danish Centre for Evaluation and Health Technology Assessment, Danish National Board of Health, Danish Medical Research Council, Aarhus University Research Foundation, Astra, Pfizer, GlaxoSmithKline, Servier, HemoCue, Wellcome Trust, UK Medical Research Council, UK National Institute for Health Research, UK National Health Service, Merck, Julius Center for Health Sciences and Primary Care, UK Department of Health, and Nuts-OHRA.

Diabetic cardiomyopathy - A comprehensive updated review.

Diabetes causes cardiomyopathy and increases the risk of heart failure independent of hypertension and coronary heart disease. This condition called "Diabetic Cardiomyopathy" (DCM) is becoming a well- known clinical entity. Recently, there has been substantial research exploring its molecular mechanisms, structural and functional changes, and possible development of therapeutic approaches for the prevention and treatment of DCM. This review summarizes the recent advancements to better understand fundamental molecular abnormalities that promote this cardiomyopathy and novel therapies for future research. Additionally, different diagnostic modalities, up to date screening tests to guide clinicians with early diagnosis and available current treatment options has been outlined.

Diabetic cardiomyopathy: factual or factoid?

SUMMARY Although long ago described, there is no established consensus regarding the real existence of Diabetic Cardiomyopathy (CMPDM). Due to its complex pathophysiology, it has been difficult for clinical and experimental research to establish clear connections between diabetes mellitus (DM) and heart failure (HF), as well as to solve the mechanisms of the underlying myocardial disease. However, the epidemiological evidence of the relationship of these conditions is undisputed. The interest in understanding this disease has intensified due to the recent results of clinical trials evaluating new glucose-lowering drugs, such as sodium-glucose transporter inhibitors 2, which demonstrated favorable responses considering the prevention and treatment of HF in patients with DM. In this review we cover aspects of the epidemiology of CMPDM and its possible pathogenic mechanisms, as well as, present the main cardiac phenotypes of CMPDM (HF with preserved and reduced ejection fraction) and implications of the therapeutic management of this disease.

RESUMO Apesar de há muito tempo descrita, não existe consenso estabelecido quanto à real existência da cardiomiopatia diabética (CMPDM). Devido à sua complexa fisiopatologia, tem sido árduo à pesquisa clínica e experimental estabelecer conexões claras entre diabetes mellitus (DM) e insuficiência cardíaca (IC), assim como solucionar os mecanismos da doença subjacente do miocárdio. No entanto, as evidências epidemiológicas da relação dessas condições são incontestáveis. O interesse em compreender melhor essa doença tem recrudescido devido aos recentes resultados de ensaios clínicos avaliando novos fármacos hipoglicemiantes, como os inibidores do transportador de sódio-glicose 2, que demonstraram respostas favoráveis, considerando-se a prevenção e tratamento da IC em pacientes portadores de DM. Nesta revisão, percorremos aspectos da epidemiologia da CMPDM e de seus possíveis mecanismos patogênicos, além de apresentarmos os principais fenótipos cardíacos da CMPDM (IC com fração de ejeção preservada e reduzida) e implicações do manejo terapêutico desta doença.

Actinic keratosis and diabetes complications: A nationwide population-based study in South Korea (2009-2015).

AIM: As the associations between actinic keratosis (AK) and diabetes complications in patients with diabetes mellitus (DM) have never been investigated, this study aimed to evaluate any such associations in patients with DM. METHODS: This retrospective cohort study analyzed clinical data for DM patients aged>40 years who had undergone the health examination recommended by the South Korea National Health Insurance Program between 2009 and 2012 (n=2,056,580). All of these patients were classified according to the presence of diabetic retinopathy (DR), end-stage renal disease (ESRD) and history of DVD; myocardial infarction, stroke, transient ischaemic attacks. Newly diagnosed AK was identified using claims data from baseline to the date of diagnosis or 31 December 2015, whichever came first. RESULTS: Of the 2,056,580 patients with DM, 6404 (0.31%) developed AK. Those patients in the DR, ESRD and CVD groups were more likely to be diagnosed with AK (P<0.001, by log-rank test). After adjusting for age and gender, the risks for AK were significantly higher in the DR, ESRD and CVD groups: HR (95% CI): 1.29 (1.21-1.39), HR: 4.24 (3.28-5.47) and HR: 1.22 (1.13-1.31), respectively. CONCLUSION: This study has revealed that the incidence of AK is higher in diabetes patients with ocular, renal and cardiovascular complications.

Decreases in neprilysin and vasoconstrictors and increases in vasodilators following bariatric surgery.

The aim of this study was to determine if weight loss following Roux-en-Y gastric bypass (RYGB) surgery in morbidly obese patients is associated with a decrease in plasma concentrations of neprilysin, mediators of the renin angiotensin system (RAS), catecholamines and endothelin-1, and also with an increase in the concentrations of vasodilators. Fasting blood samples were obtained from 15 patients with morbid obesity and diabetes prior to and 6 months after RYGB surgery. Circulating levels of neprilysin, vasoconstrictors, vasodilators, and the mRNA expression of related genes in circulating mononuclear cells (MNC) were measured. Six months after RYGB surgery the concentrations of neprilysin, angiotensinogen, angiotensin II, renin and endothelin-1 fell significantly by 27 ±16%, 22 ±10%, 22 ±8%, 35 ±13% and 17 ±6% (P < .05 for all), respectively, while ANP concentrations increased significantly by 24 ±13%. There was no significant change in aldosterone, BNP, cAMP or cGMP concentrations, or angiotensin converting enzyme (ACE) expression. These changes may contribute to the reduction of congestive cardiac failure and blood pressure risks after RYGB surgery.

Mortality risk remains higher in individuals with type 1 diabetes: A population-based cohort study (the Ayrshire diabetes follow-up cohort [ADOC]).

AIMS: Type 1 diabetes is associated with an increased risk of cardiovascular disease and all-cause mortality. Numerous studies have demonstrated that outcomes for diabetes are improved by intensive glycaemic control, blood pressure control, and treatment of dyslipidaemia in addition to cessation of smoking. The aim of this study was to compare mortalities in individuals with type 1 diabetes with that in non-diabetic individuals, and to investigate the effects of age, gender, glycaemic control, socio-economic status, hypertension, ischaemic heart disease (IHD), smoking status, body mass index (BMI) and dyslipidaemia. METHODS: A population-based analysis in Ayrshire and Arran, Scotland included 253 304 non-diabetic individuals and 1324 individuals with type 1 diabetes who were tracked from 2009 to 2014. RESULTS: Patients with type 1 diabetes had higher mortality rates than non-diabetic individuals (HR, 3.20; P < .01), with relative mortality in female individuals with type 1 diabetes being higher than that in males (OR, 2.38 vs 1.52; P < .01). Increasing age (HR, 2.37), smoking (HR, 1.85), IHD (HR, 1.62) and hypertension (HR, 1.21) (all P < .01) increased mortality risk. A hypertensive female with type 1 diabetes and IHD who smoked had an HR of 11.6 compared with a non-smoking, normotensive non-diabetic female without IHD. For a hypertensive male with type 1 diabetes and IHD who smoked, HR was 6.96. BMI > 30 kg/m2 was associated with reduced mortality risk in both non-diabetic (HR, 0.61) and diabetic subjects (HR, 0.40). CONCLUSIONS: This study confirmed that the risk of mortality in individuals with type 1 diabetes remains elevated. Further studies are required to understand how gender affects the disparity in mortality and why obesity appears to be protective.

Burden of cardio-renal-metabolic conditions in adults with type 2 diabetes within the Diabetes Collaborative Registry.

We examined the prevalence of cardio-renal-metabolic (CaReMe) conditions and their combinations among 530 747 adults with type 2 diabetes in a USA-based outpatient registry of 271 primary care, cardiology and endocrinology offices. We evaluated the following CaReMe conditions: hypertension, hyperlipidaemia, coronary artery disease (CAD), chronic kidney disease (CKD), cerebrovascular disease, peripheral artery disease, atrial fibrillation, heart failure, and gout or hyperuricaemia; prevalence estimates were adjusted based on the distribution of diabetes by age in the US population in 2015. We found that it was uncommon for patients to have isolated type 2 diabetes without other CaReMe conditions, with only 6.4% having no other CaReMe conditions and 51% having ≥3 other CaReMe conditions. The most prevalent individual conditions were hypertension (83%), hyperlipidemia (81%), CAD (32%) and CKD (20%), and the most common combinations included various groupings of hypertension, hyperlipidaemia, atherosclerotic cardiovascular disease and CKD. Older age, male sex and tobacco use were each associated with increased numbers of CaReMe conditions. These findings highlight the clinical need for novel treatment strategies for diabetes that address both glycaemia and coexisting disease states.

Perspectives on diabetes mortality as the result of residual confounding and reverse causality by common disease.

Type 2 diabetes (T2D) is associated with major global health burdens, including 2 to 4 times increased rates of morbidity and mortality from cardiovascular disease. However, T2D remains an exclusion diagnosis in individuals with arbitrarily elevated blood-glucose levels. While it is well-established that diabetes is associated with an elevated risk of cardiovascular disease and cancer, it has recently been shown that heart failure and cancer may precede, and even contribute to, the development of T2D. In the present review, we have summarized these findings and discuss their potential implications for our understanding of the T2D disease entity, including its treatment and associated increased mortality. We suggest that the existence of a hitherto unrecognized distinct T2D subtype, secondary to heart failure and/or cancer, may substantially contribute to the excess mortality reported in T2D patients with mild disease. Treatment and clinical care of this subtype needs to be defined separately from the general T2D phenotype.

DECLARE-TIMI 58: Participants' baseline characteristics.

AIM: To describe the baseline characteristics of participants randomized in the Dapagliflozin Effect on CardiovascuLAR Events (DECLARE-TIMI 58) trial, the pivotal study conducted to assess cardiovascular (CV) outcomes with dapagliflozin. METHODS: The DECLARE-TIMI 58 trial will analyse 17 160 patients with type 2 diabetes randomized to treatment with dapagliflozin (10 mg/d) or matching placebo. We analysed their baseline characteristics. RESULTS: The participants' mean ± SD age was 63.8 ± 6.8 years, 62.6% were male, and their mean ± SD diabetes duration was 11.8 ± 7.8 years, glycated haemoglobin 8.3% ± 1.2% (67 mmol/mol ± 9.7 mmol/mol) and body mass index 32.1 ± 6.0 kg/m2 . Randomization included 6971 (40.6%) patients with atherosclerotic CV disease (CVD), and 10 189 (59.4%) patients with multiple risk factors (MRF) for CVD (defined as men age ≥ 55 years or women ≥60 years, with at least one of dyslipidaemia, hypertension or smoking). Patients with CVD compared with patients with MRF were younger (62.5 ± 8.1 vs 64.7 ± 5.6 years), more frequently male (72.1% vs 56.1%), less often used metformin (74.6% vs 81.2%), more often used insulin (44.2% vs 36.4%), and more frequently used statins, aspirin, clopidogrel and ß-blockers (82.2%, 71.1%, 24.7% and 66.6% vs 63.7%, 39.1%, 1.5% and 32.3%, respectively). CONCLUSION: The DECLARE-TIMI 58 trial is expected to provide conclusive data on the effect of treatment with dapagliflozin in addition to standard of care, on CV outcomes in a broad patient population with type 2 diabetes and CVD or MRF for CVD.

Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes.

AIMS: To simplify administration of aqueous exenatide once weekly, which requires reconstitution, the exenatide microspheres have been reformulated in a ready-to-use autoinjector with a Miglyol diluent (exenatide QWS-AI). This study compared the efficacy and safety of exenatide QWS-AI with the first-in-class glucagon-like peptide-1 receptor agonist exenatide twice daily (BID). MATERIALS AND METHODS: This randomized, open-label, controlled study in patients with type 2 diabetes using diet and exercise or taking stable oral glucose-lowering medication randomized patients 3:2 to either exenatide QWS-AI (2 mg) or exenatide BID (10 µg) for 28 weeks. The primary outcome was the 28-week change in glycated haemoglobin (HbA1c). A subset of patients completed a standardized meal test for postprandial and pharmacokinetic assessments. RESULTS: A total of 375 patients (mean HbA1c, 8.5% [69 mmol/mol]; body mass index, 33.2 kg/m2 ; diabetes duration, 8.5 years) received either exenatide QWS-AI (n = 229) or exenatide BID (n = 146); HbA1c was reduced by -1.4% and -1.0%, respectively (least-squares mean difference, -0.37%; P = .0072). More patients achieved HbA1c <7.0% with exenatide QWS-AI (49.3%) than with exenatide BID (43.2%; P = .225). Body weight was reduced in both groups (P = .37 for difference). Gastrointestinal adverse events (AEs) were reported in 22.7% (exenatide QWS-AI) and 35.6% (exenatide BID) of patients; fewer patients in the exenatide QWS-AI group withdrew because of AEs than in the exenatide BID group. Minor hypoglycaemia occurred most often with concomitant sulfonylurea use. CONCLUSIONS: Exenatide QWS-AI was associated with a greater reduction in HbA1c, similar weight loss and a favorable gastrointestinal AE profile compared with exenatide BID.

Development of a cardiovascular diseases risk prediction model and tools for Chinese patients with type 2 diabetes mellitus: A population-based retrospective cohort study.

AIMS: Evidence-based cardiovascular diseases (CVD) risk prediction models and tools specific for Chinese patients with type 2 diabetes mellitus (T2DM) are currently unavailable. This study aimed to develop and validate a CVD risk prediction model for Chinese T2DM patients. METHODS: A retrospective cohort study was conducted with 137 935 Chinese patients aged 18 to 79 years with T2DM and without prior history of CVD, who had received public primary care services between January 1, 2010 and December 31, 2010. Using the derivation cohort over a median follow-up of 5 years, the interaction effect between predictors and age were derived using Cox proportional hazards regression with a forward stepwise approach. Harrell's C statistic and calibration plot were used on the validation cohort to assess the discrimination and calibration of the models. The web calculator and chart were developed based on the developed models. RESULTS: For both genders, predictors for higher risk of CVD were older age, smoking, longer diabetes duration, usage of anti-hypertensive drug and insulin, higher body mass index, haemoglobin A1c (HbA1c), systolic and diastolic blood pressure, a total cholesterol to high-density lipoprotein-cholesterol (TC/HDL-C) ratio and urine albumin to creatinine ratio, and lower estimated glomerular filtration rate. Interaction factors with age demonstrated a greater weighting of TC/HDL-C ratio in both younger females and males, and smoking status and HbA1c in younger males. CONCLUSION: The developed models, translated into a web calculator and color-coded chart, served as evidence-based visual aids that facilitate clinicians to estimate quickly the 5-year CVD risk for Chinese T2DM patients and to guide intervention.

Effect of obesity and type 2 diabetes, and glucose ingestion on circulating spexin concentration in adolescents.

Spexin is a novel peptide that has been reported to be down regulated in obese adults and children and in normoglycemic adults following glucose ingestion. Spexin may therefore have a role in metabolic regulation. The purpose of the current study was to determine the effect of obesity and type 2 diabetes (T2DM), and the effect of glucose ingestion on circulating spexin concentration in adolescents. Boys and girls (mean age 16 years old) classified as healthy normal weight (NW, n = 22), obese (Ob, n = 10), or obese with T2DM (n = 12) completed measurements of body composition, blood pressure, cardiorespiratory fitness, and blood concentrations of glucose, insulin, and lipids. The median fasting serum spexin concentration did not differ between groups (NW: 0.35; Ob: 0.38, T2DM: 0.34 ng/mL, respectively). In 10 NW participants who completed a standard oral glucose tolerance test, spexin concentration was unchanged at 30 and 120 minutes relative to the fasting baseline. Finally, spexin was not significantly correlated with any of the body composition, fitness, or blood biochemical measurements. These data do not support the proposed role of spexin as a metabolic regulator or biomarker of glucose control in adolescents.

Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide.

The aim was to determine the effects of dulaglutide, a synthetic once-weekly, injectable human glucagon-like peptide 1 analogue that lowers blood glucose, body weight, appetite and blood pressure, on cardiovascular outcomes. People with type 2 diabetes, aged ≥50 years, with glycated haemoglobin (HbA1c) ≤9.5%, and either a previous cardiovascular event, evidence of cardiovascular disease or ≥2 cardiovascular risk factors were randomly allocated to a weekly subcutaneous injection of either dulaglutide (1.5 mg) or placebo and followed within the ongoing Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial every 3 to 6 months. The primary cardiovascular outcome is the first occurrence of the composite of cardiovascular death or non-fatal myocardial infarction or non-fatal stroke. Secondary outcomes include each component of the primary composite cardiovascular outcome, a composite clinical microvascular outcome comprising retinal or renal disease, hospitalization for unstable angina, heart failure requiring hospitalization or an urgent heart failure visit, and all-cause mortality. Follow-up will continue until the accrual of 1200 confirmed primary outcomes. Recruitment of 9901 participants (mean age 66 years, 46% women) occurred in 370 sites located in 24 countries over a period of 2 years. The mean duration of diabetes was 10 years, mean baseline HbA1c was 7.3%, and 31% had prior cardiovascular disease. The REWIND trial's international scope, high proportion of women, high proportion of people without prior cardiovascular disease and inclusion of participants whose mean baseline HbA1c was 7.3% suggests that its cardiovascular and safety findings will be directly relevant to the typical middle-aged patient seen in general practice throughout the world.

Favourable changes in mortality in people with diabetes: US NHANES 1999-2010.

AIMS: Diabetes-related complications have declined during the past two decades. We aimed to examine whether mortality in people with diabetes improved over time in the 1999 to 2010 National Health and Nutrition Examination Survey (NHANES). METHODS: We conducted a prospective cohort study using 1999 to 2004 and 2005 to 2010 data from the NHANES. For primary analyses, we compared the unadjusted, age-adjusted and multivariable-adjusted hazard ratios (HR) for mortality outcomes (total, cardiovascular, cardiac and cancer deaths) of the participants with diabetes with those without diabetes using Cox proportional hazard models. RESULTS: For each mortality outcome, HR (95% confidence interval) in diabetic participants during the period 2005 to 2010 was lower than that during the period 1999 to 2004 (all-cause death, 2.76 [1.87-4.08] vs 4.23 [2.57-6.98]; cardiovascular death, 2.70 [1.20-6.04] vs 8.82 [3.28-23.70]; cardiac death, 2.45 [0.98-6.09] vs 15.55 [7.01-34.50]; cancer death, 2.33 [0.87-6.23] vs 3.03 [1.20-7.65]). Compared with mortality outcome during the period 1999 to 2004, greater declines in mortality during the period 2005 to 2010 were observed for cardiovascular (-54.0%) and cardiac deaths (-64.8%). In age-adjusted and multivariable-adjusted models, the cumulative event rates for total, cardiovascular and cardiac deaths were not significantly different between participants with and without diabetes during the period 2005-2010; this was not the case during the period 1999-2004. The leading cause of death was malignant neoplasm during the period 2005-2010. CONCLUSION: Considerably improved outcomes for total, cardiovascular and cardiac deaths were observed in people with diabetes during the 2005 to 2010 NHANES compared to the 1999 to 2004 NHANES.