Subclinical cardiovascular dysfunction in adults with type 2 diabetes: characterisation and lifestyle interventions

BackgroundPeople with type 2 diabetes (T2D) are at increased risk of heart failure. Various measures of subclinical cardiovascular dysfunction have been reported, but it is unclear how these relate to functional limitation or whether they are reversible with lifestyle interventions.ObjectivesTo comprehensively describe cardiovascular function in a multi-ethnic, asymptomatic population with T2D, and determine whether this is improved by a low-energy meal replacement plan (MRP) diet or exercise.MethodsA comparison of adults with and without T2D and no cardiovascular disease was undertaken. A subset undertook a prospective, randomised, open-label, blinded endpoint (PROBE) trial and were assigned a 12-week intervention of: 1) routine care; 2) supervised exercise or 3) MRP. Echocardiography, cardiopulmonary exercise testing and cardiovascular magnetic resonance (CMR) were performed at baseline and post-intervention. The primary outcome was change in left ventricular (LV) peak early diastolic strain rate (PEDSR), measured by CMR.ResultsAt baseline, 247 adults with T2D and 78 controls were compared. Subjects with T2D had concentric LV remodelling, diastolic dysfunction, aortic stiffening, reduced myocardial perfusion, and markedly lower peak VO2. Key clinical determinants of cardiovascular dysfunction were diabetes duration, body mass index (BMI), smoking history, and systolic blood pressure (BP). MPR and diastolic filling were independently associated with peak VO2.Seventy-six T2Ds completed the PROBE trial (30 routine care, 22 exercise, and 24 MRP). The MRP arm lost weight, improved BP, glycaemia, LV mass:volume, and aortic stiffness. The exercise arm had negligible weight loss but increased exercise capacity. PEDSR increased in the exercise arm versus routine care (p=0.002) but did not improve with the MRP compared to routine care.ConclusionsConcentric LV remodelling, diastolic dysfunction, aortic stiffening, and reduced MPR are key components of subclinical cardiovascular dysfunction in T2D. Exercise training improved diastolic function and despite beneficial effects on weight, glycaemic control, concentric LV remodelling and aortic stiffness, an MRP did not improve diastolic function.</div

Diabetic cardiomyopathy: prevalence, determinants and potential treatments.

The prevalence of type 2 diabetes (T2D) has reached a pandemic scale. These patients are at a substantially elevated risk of developing cardiovascular disease, with heart failure (HF) being a leading cause of morbidity and mortality. Even in the absence of traditional risk factors, diabetes still confers up to a twofold increased risk of developing HF. This has led to identifying diabetes as an independent risk factor for HF and recognition of the distinct clinical entity, diabetic cardiomyopathy. Despite a wealth of research interest, the prevalence and determinants of diabetic cardiomyopathy remain uncertain. This limited understanding of the pathophysiology of diabetic heart disease has also hindered development of effective treatments. Tight blood-glucose and blood-pressure control have not convincingly been shown to reduce macrovascular outcomes in T2D. There is, however, emerging evidence that T2D is reversible and that the metabolic abnormalities can be reversed with weight loss. Increased aerobic exercise capacity is associated with significantly lower cardiovascular and overall mortality in diabetes. Whether such lifestyle modifications as weight loss and exercise may ameliorate the structural and functional derangements of the diabetic heart has yet to be established. In this review, the link between T2D and myocardial dysfunction is explored. Insights into the structural and functional perturbations that typify the diabetic heart are first described. This is followed by an examination of the pathophysiological mechanisms that contribute to the development of cardiovascular disease in T2D. Lastly, the current and emerging therapeutic strategies to prevent or ameliorate cardiac dysfunction in T2D are evaluated

Emerging glucose-lowering therapies: a guide for cardiologists

In recent large-scale cardiovascular outcomes trials, two new classes of glucose-lowering medications – sodium glucose co-transporter 2 inhibitors (SGLT2i) and glucagon like peptide-1 receptor agonists (GLP-1RAs) – demonstrated cardiovascular benefits in adults with type 2 diabetes mellitus (T2DM). These findings have prompted growing optimism amongst clinicians regarding the potential for these agents to reduce the burden of cardiovascular disease in people with T2DM. GLP-1RAs and SGLT2i are now advocated as second-line agents in European and U.S. guidelines for management of both hyperglycaemia and for primary prevention of cardiovascular disease in people with T2DM. Given the high prevalence of T2DM in patients with cardiovascular disease, cardiologists will increasingly encounter these agents in routine clinical practice. In this review, we summarise evidence from cardiovascular outcomes trials of GLP-1RAs and SGLT2i, give practical advice on prescribing, and detail safety considerations associated with their use. We also highlight areas where further work is needed, giving details on active clinical trials. The review aims to familiarise cardiologists with these emerging treatments, which will be increasingly encountered in clinical practice, given the expanding representation of T2DM in patients with cardiovascular disease. Whether these drugs will be initiated by cardiologists remains to be determined

The assessment of coronary artery disease in patients with end-stage renal disease.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality among patients with end-stage renal disease (ESRD). Clustering of traditional atherosclerotic and non-traditional risk factors drive the excess rates of coronary and non-coronary CVD in patients with ESRD. Coronary artery disease (CAD) is a key disease process, present in ∼50% of the haemodialysis population ≥65 years of age. Patients with ESRD are more likely to be asymptomatic, posing a challenge to the correct identification of CAD, which is essential for appropriate risk stratification and management. Given the lack of randomized clinical trial evidence in this population, current practice is informed by observational data with a significant potential for bias. For this reason, the most appropriate approach to the investigation of CAD is the subject of considerable discussion, with practice patterns largely varying between different centres. Traditional imaging modalities are limited in their diagnostic accuracy and prognostic value for cardiac events and survival in patients with ESRD, demonstrated by the large number of adverse cardiac outcomes among patients with negative test results. This review focuses on the current understanding of CAD screening in the ESRD population, discussing the available evidence for the use of various imaging techniques to refine risk prediction, with an emphasis on their strengths and limitations

Physical activity and structured exercise in patients with type 2 diabetes mellitus and heart failure

Patients with type 2 diabetes mellitus (T2DM) or heart failure (HF) are encouraged to adopt a physically active lifestyle and participation in structured exercise is endorsed as a safe and effective adjunct to medical therapy in both conditions. This article aims to provide health care professionals with the information required to tailor guidance relating to physical activity and exercise for individuals with T2DM and HF by: (1) presenting an overview of current guidelines, and (2) providing practical suggestions for their implementation. ‘Traditional’ forms of exercise training include moderate to vigorous-intensity aerobic exercise and dynamic resistance exercise. Benefits of exercise training include improved cardiorespiratory fitness and physical function, more favourable body composition, lower metabolic risk and enhanced quality of life. Before engaging in structured exercise, medical clearance may be required for certain types of activities, and precautions should be taken to minimise the risk of hypoglycaemia and left-ventricular overload in patients with T2DM and HF. Importantly, patients with HF should be educated to distinguish severe adverse symptoms during exercise from expected feelings of breathlessness and fatigue. The latter should not be a reason to discourage patients from engaging in as much physical activity and structured exercise as possible. In order to optimise adherence, exercise prescription should be driven by patient preferences, motivations and individual circumstances. Consideration should also be given to more novel approaches, such as reducing sedentary behaviour and high-intensity interval training. Copyright © 2018 John Wiley & Sons

sj-docx-1-tae-10.1177_20420188231193231 – Supplemental material for Response to a low-energy meal replacement plan on glycometabolic profile and reverse cardiac remodelling in type 2 diabetes: a comparison between South Asians and White Europeans

Supplemental material, sj-docx-1-tae-10.1177_20420188231193231 for Response to a low-energy meal replacement plan on glycometabolic profile and reverse cardiac remodelling in type 2 diabetes: a comparison between South Asians and White Europeans by Lavanya Athithan, Gaurav S. Gulsin, Joseph Henson, Loai Althagafi, Emma Redman, Stavroula Argyridou, Kelly S. Parke, Jian Yeo, Thomas Yates, Kamlesh Khunti, Melanie J. Davies, Gerry P. McCann and Emer M. Brady in Therapeutic Advances in Endocrinology and Metabolism</p

Biochemical Screening for Nonadherence Is Associated With Blood Pressure Reduction and Improvement in Adherence.

We hypothesized that screening for nonadherence to antihypertensive treatment using liquid chromatography-tandem mass spectrometry-based biochemical analysis of urine/serum has therapeutic applications in nonadherent hypertensive patients. A retrospective analysis of hypertensive patients attending specialist tertiary care centers was conducted in 2 European countries (United Kingdom and Czech Republic). Nonadherence to antihypertensive treatment was diagnosed using biochemical analysis of urine (United Kingdom) or serum (Czech Republic). These results were subsequently discussed with each patient, and data on follow-up clinic blood pressure (BP) measurements were collected from clinical files. Of 238 UK patients who underwent biochemical urine analysis, 73 were nonadherent to antihypertensive treatment. Their initial urinary adherence ratio (the ratio of detected to prescribed antihypertensive medications) increased from 0.33 (0-0.67) to 1 (0.67-1) between the first and the last clinic appointments. The observed increase in the urinary adherence ratio in initially nonadherent UK patients was associated with the improved BP control; by the last clinic appointment, systolic and diastolic BPs were ≈19.5 and 7.5 mm Hg lower than at baseline (P=0.001 and 0.009, respectively). These findings were further corroborated in 93 nonadherent hypertensive patients from Czech Republic-their average systolic and diastolic BPs dropped by ≈32.6 and 17.4 mm Hg, respectively (P<0.001), on appointments after the biochemical analysis. Our data show that nonadherent hypertensive patients respond to liquid chromatography-tandem mass spectrometry-based biochemical analysis with improved adherence and significant BP drop. Such repeated biochemical analyses should be considered as a therapeutic approach in nonadherent hypertensive patients