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OBJECTIVE To confirm the presence of subclinical cardiovascular dysfunction in working-age adults with type 2 diabetes (T2D) and determine whether this is improved by a low-energy meal replacement diet (MRP) or exercise training. RESEARCH DESIGN AND METHODS This article reports on a prospective, randomized, open-label, blinded end point trial with nested case-control study. Asymptomatic younger adults with T2D were randomized 1:1:1 to a 12-week intervention of 1) routine care, 2) supervised aerobic exercise training, or 3) a low-energy (∼810 kcal/day) MRP. Participants underwent echocardiography, cardiopulmonary exercise testing, and cardiac magnetic resonance (CMR) at baseline and 12 weeks. The primary outcome was change in left ventricular (LV) peak early diastolic strain rate (PEDSR) as measured by CMR. Healthy volunteers were enrolled for baseline case-control comparison. RESULTS Eighty-seven participants with T2D (age 51 ± 7 years, HbA1c 7.3 ± 1.1%) and 36 matched control participants were included. At baseline, those with T2D had evidence of diastolic dysfunction (PEDSR 1.01 ± 0.19 vs. 1.10 ± 0.16 s−1, P = 0.02) compared with control participants. Seventy-six participants with T2D completed the trial (30 routine care, 22 exercise, and 24 MRP). The MRP arm lost 13 kg in weight and had improved blood pressure, glycemia, 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 (β = 0.132, P = 0.002) but did not improve with the MRP (β = 0.016, P = 0.731). CONCLUSIONS In asymptomatic working-age adults with T2D, exercise training improved diastolic function. Despite beneficial effects of weight loss on glycemic control, concentric LV remodeling, and aortic stiffness, a low-energy MRP did not improve diastolic function.

Background The determinants of exercise capacity in people with type 2 diabetes (T2D), a group at high risk of heart failure, are unknown. Purpose To assess the relationship between subclinical cardiovascular dysfunction and peak VO2 in adults with T2D. Methods We enrolled asymptomatic adults with T2D and no prevalent cardiovascular disease. Matched controls were recruited for comparison. Subjects underwent echocardiography, cardiopulmonary exercise testing and adenosine stress cardiac MRI. Multivariable linear regression analysis was undertaken to identify independent associations between measures of cardiovascular structure and function and peak VO2 (Figure 1). Results 247 adults with T2D (age 52±12y, 55% males, A1c 7.4±1.1%) and 78 controls were included. Subjects with T2D had increased concentric LV remodelling (LV mass/volume 0.84±0.14 vs. 0.76±0.11g/mL, p Conclusions In asymptomatic people with T2D, aortic stiffening, diastolic filling, and myocardial perfusion reserve are key determinants of peak VO2, independent of age, sex, ethnicity, smoking status, or blood pressure. Figure 1 Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): National Institute for Health Research - Career Development Fellowship (G P McCann, CDF-2014-07-045). British Heart Foundation - Clinical Research Training Fellowship (G S Gulsin)

Aim To compare the effects of a glucagon‐like peptide‐1 receptor agonist and a dipeptidyl peptidase‐4 inhibitor on magnetic resonance imaging‐derived measures of cardiovascular function. Materials and methods In a prospective, randomized, open‐label, blinded endpoint trial liraglutide (1.8 mg) and sitagliptin (100 mg) were compared in asymptomatic, non‐insulin treated young (aged 18‐50 years) adults with obesity and type 2 diabetes. The primary outcome was difference in circumferential peak early diastolic strain rate change (PEDSR), a biomarker of cardiac diastolic dysfunction 26 weeks after randomization. Secondary outcomes included other indices of cardiac structure and function, HbA1c and body weight. Results Seventy‐six participants were randomized (54% female, mean ± SD age 44 ± 6 years, diabetes duration 4.4 years, body mass index 35.3 ± 6.1 kg m−2), of whom 65% had ≥1 cardiovascular risk factor. Sixty‐one participants had primary outcome data available. There were no statistically significant between‐group differences (intention‐to‐treat; mean [95% confidence interval]) in PEDSR change (−0.01 [−0.07, +0.06] s−1), left ventricular ejection fraction (−1.98 [−4.90, +0.94]%), left ventricular mass (+1.14 [−5.23, +7.50] g) or aortic distensibility (−0.35 [−0.98, +0.28] mmHg−1 × 10−3) after 26 weeks. Reductions in HbA1c (−4.57 [−9.10, −0.37] mmol mol−1) and body weight (−3.88 [−5.74, −2.01] kg) were greater with liraglutide. Conclusion There were no differences in cardiovascular structure or function after short‐term use of liraglutide and sitagliptin in younger adults with obesity and type 2 diabetes. Longer studies in patients with more severe cardiac dysfunction may be necessary before definitive conclusions can be made about putative pleiotropic properties of incretin‐based therapies.

IntroductionDespite their young age and relatively short duration of disease, younger adults with type 2 diabetes (T2D) already have diastolic dysfunction and may be at risk of incipient heart failure. Whether weight loss or exercise training improve cardiac dysfunction in people with T2D remains to be established.Methods and analysisProspective, randomised, open-label, blind endpoint trial. The primary aim of the study is to determine if diastolic function can be improved by either a meal replacement plan or a supervised exercise programme, compared with guideline-directed care. A total of 90 obese participants with T2D (aged 18–65 years), diabetes duration Ethics and disseminationThe study has full ethical approval, and data collection was completed in August 2018. The study results will be submitted for publication within 6 months of completion.Trial registration numberNCT02590822; Pre-results.

Individuals with type 2 diabetes have a three- to fivefold increased risk of developing heart failure. Diabetic cardiomyopathy is typified by left ventricular (LV) concentric remodeling, which is a recognized predictor of adverse cardiovascular events. Although the mechanisms underlying LV remodeling in type 2 diabetes are unclear, progressive aortic stiffening may be a key determinant. The aim of this study was to assess the relationship between aortic stiffness and LV geometry in younger adults with type 2 diabetes, using multiparametric cardiovascular MRI. We prospectively recruited 80 adults (aged 18–65 years) with type 2 diabetes and no cardiovascular disease and 20 age- and sex-matched healthy control subjects. All subjects underwent comprehensive bio-anthropometric assessment and cardiac MRI, including measurement of aortic stiffness by aortic distensibility (AD). Type 2 diabetes was associated with increased LV mass, concentric LV remodeling, and lower AD compared with control subjects. On multivariable linear regression, AD was independently associated with concentric LV remodeling in type 2 diabetes. Aortic stiffness may therefore be a potential therapeutic target to prevent the development of heart failure in type 2 diabetes.

Background Late gadolinium enhanced cardiovascular magnetic resonance (LGE-CMR) has excellent specificity, sensitivity and diagnostic accuracy for differentiating between ischemic cardiomyopathy (ICM) and non-ischemic dilated cardiomyopathy (NICM). CMR first-pass myocardial perfusion imaging (perfusion-CMR) may also play role in distinguishing heart failure of ischemic and non-ischemic origins, although the utility of additional of stress perfusion imaging in such patients is unclear. The aim of this retrospective study was to assess whether the addition of adenosine stress perfusion imaging to LGE-CMR is of incremental value for differentiating ICM and NICM in patients with severe left ventricular systolic dysfunction (LVSD) of uncertain etiology. Methods We retrospectively identified 100 consecutive adult patients (median age 69 years (IQR 59–73)) with severe LVSD (mean LV EF 26.6 ± 7.0%) referred for perfusion-CMR to establish the underlying etiology of heart failure. The cause of heart failure was first determined on examination of CMR cine and LGE images in isolation. Subsequent examination of complete adenosine stress perfusion-CMR studies (cine, LGE and perfusion images) was performed to identify whether this altered the initial diagnosis. Results On LGE-CMR, 38 patients were diagnosed with ICM, 46 with NICM and 16 with dual pathology. With perfusion-CMR, there were 39 ICM, 44 NICM and 17 dual pathology diagnoses. There was excellent agreement in diagnoses between LGE-CMR and perfusion-CMR (κ 0.968, p

Background:Type 2 diabetes (T2D) is associated with an increased risk of heart failure (HF) and cardiovascular mortality. A large-scale meta-analysis on HF found that diabetes was more frequent in women than men, and diabetes appeared to have attenuated the otherwise protective effect of female sex on progression of cardiomyopathy. The exact underlying mechanisms for this remain unclear. Here, we aimed to determine the effect of sex on the phenotypic expression of diabetic heart disease in patients with T2D.Methods:A total of 62 male [mean age 44 ± 8 years, body mass index (BMI) 33 ± 5 kg/m2, mean HBA1c of 7.8 ± 1.8%] and 67 female (44 ± 10 years, BMI 35 ± 6 kg/m2, HBA1c 7.6 ± 1.2%) T2D patients on oral glucose-lowering treatment, and 16 male (48 ± 17 years, BMI 25 ± 3 kg/m2) and 14 female (50 ± 10 years, BMI 25 ± 4 kg/m2) controls were recruited. Left ventricular (LV) volumes, mass, function and deformation, and left atrial (LA) volumes and function were assessed using cardiac magnetic resonance imaging (CMR).Results:Participants in all groups were of similar age, and there were no significant differences in blood pressure (BP), diabetes duration or metabolic profile between the two diabetes groups. Concentric remodeling was present in both sexes ( p Conclusion:Male sex adversely affects the phenotypic expression of diabetic heart disease. The striking differences in the cardiac phenotype between male and female patients with T2D promote awareness of gender-specific risk factors in search of treatment and prevention of diabetes-associated HF.Condensed Abstract:We aimed to determine the effect of sex on the phenotypic expression of diabetic heart disease in patients with T2D. While our findings support the notion that in T2D, male sex adversely affects the phenotypic expression of diabetic heart disease, this is in apparent conflict with the previous large-scale study showing diabetes attenuates the otherwise protective effect of female sex on progression of cardiomyopathy. Further longitudinal studies looking at gender differences in clinical outcomes in T2D patients are needed. These sex-related differences promote awareness of sex-specific risk factors in search of treatment and prevention of diabetes-associated HF.

Background The prevalence of type 2 diabetes (T2DM) in younger adults is growing. Compared to the late onset T2DM, it is well recognized that the disease tends to behave more aggressively in the younger age group with evidence of premature micro and macrovasular diseases and shorter life span. This increased mortality is largely attributed to cardiovascular complications. In a recent pilot study, young adults with T2DM were found to have significantly lower peak diastolic strain rate (PEDSR) on cardiac MRI (CMR), a forerunner of diabetic cardiomyopathy. Liraglutide, a glucagon like peptide-1 (GLP-1) analogue, is one of the new classes of glucose lowering therapies licensed to be used in management of T2DM. In randomised controlled trials, liraglutide improves glycaemic control by 1–1.5 % with an added benefit of weight loss of 2–3 kg. In addition, there is emerging evidence elucidating the cardioprotective effects of GLP-1 analogues independent of glycaemic control. In a small study, liraglutide has also been shown to improve cardiac function in patients with coronary ischaemia or congestive heart failure. Methods and aims This is a prospective, randomised, open-label, blind end-point (PROBE) active-comparator trial. A total of 90 obese eligible participants with T2DM (18–50 years) will be randomised to either liraglutide 1.8 mg once daily or sitagliptin 100 mg once daily for 26 weeks. The primary aim is to assess whether liraglutide improves diastolic function compared to sitagliptin as measured by PEDSR using CMR. Discussion Although newer classes of GLP-1 analogues are made available in recent years, there are very few published studies demonstrating the beneficial effect of GLP-1 analogues on cardiovascular endpoints. In a recently published LEADER study, liraglutide has shown superiority to placebo in a population of type 2 diabetes with high risk of cardiovascular disease. To the best of our knowledge, there are no published studies establishing the effect of liraglutide on cardiac function in younger patients with T2DM on a larger scale. The LYDIA study will comprehensively describe changes in various parameters of cardiac structure and function in patients treated with liraglutide aiming to provide new evidence on effect of liraglutide on diastolic function in young obese people with T2DM. Trial Registration ClinicalTrials.gov identifier: NCT02043054 Electronic supplementary material The online version of this article (doi:10.1186/s12933-016-0421-6) contains supplementary material, which is available to authorized users.

Subtle changes in glucocorticoid levels, including a flattening of the diurnal rhythm with raised nadir, are prevalent, being characteristic of both aging and major depression. Both these conditions are also associated with deficits in hippocampally mediated cognitive functions. We hypothesized that this profile of glucocorticoid levels causes structural and functional changes in the hippocampus, which in turn may engender cognitive deficits. We implanted slow-release corticosterone pellets into adrenally intact adult male rats to produce a flattened glucocorticoid rhythm with levels clamped midway between the normal nadir and zenith. Using density profile analysis we measured hippocampal expression of messenger RNAs encoding structural and functional proteins. In rats with a flattened glucocorticoid rhythm, the expression of the mRNA coding for microtubule associated protein-2b (MAP2b) was reduced in CA3 relative to sham-operated controls, but unchanged in dentate gyrus and CA1. In contrast, the expression of the mRNA coding the alpha subunit of calcium-calmodulin dependent kinase (CAMKIIalpha) was reduced in dentate gyrus in animals with a flattened glucocorticoid rhythm, but unchanged in CA3. The expression of the mRNA coding the synaptic vesicle protein synaptophysin was unchanged in both CA3 and dentate gyrus. The data indicate that a flattening of the normal diurnal glucocorticoid rhythm decreases the hippocampal expression of mRNAs coding key structural and functional proteins, and does so in a regionally selective manner. The data may have relevance for cognitive deficits characteristic of aging and depression.

Cardiac imaging is essential for the diagnosis and follow-up individuals with congenital heart disease (CHD). Currently echocardiography is the first-line investigation, although no single imaging technique is sufficient for complete evaluation of cardiac anatomy and physiology in these patients. Increasingly, adults with CHD are referred for cardiac magnetic resonance (CMR) imaging. The high spatial resolution, functional assessment capabilities and excellent reproducibility of CMR make it a desirable investigation for CHD [1]. Ebstein's anomaly is a rare (incidence ≈1 in 200 000 live births) congenital heart disorder characterized by malformations of the tricuspid valve (TV) and right ventricle (RV). The hallmark features are clearly demonstrated in this CMR study. They are: Malposition of the posterior and septal TV leaflets in the walls of the RV with enlargement, fenestration and/or tethering of the anterior leaflet. Dilatation of the true atrio-ventricular junction and downward displacement of the functional TV annulus. Atrialization of the RV [2]. In the four-chamber view (Fig. 1A), the grossly dilated right heart is clearly evident, with an atrialized RV and dilated tricuspid annulus. The enlarged anterior TV leaflet is well visualized (red arrow), as is the hypoplastic septal leaflet (yellow arrow). The LA and LV are small, owing to compression from the volume-overloaded right heart. Figure 1: (A) CMR four-chamber cine view. Seen here is the grossly dilated right heart, with an atrialized RV and dilated tricuspid annulus. The enlarged anterior TV leaflet is well visualized (red arrow), as is the mislaid and hypoplastic septal leaflet (yellow ... The massively dilated atrial and ventricular portions of right heart are visualized in the short-axis cine view (Fig. 1B). Again the tricuspid valve septal leaflet is seen (red arrow) and the pale jet of tricuspid regurgitation is notable during systole. The intraventricular septum flattened during diastole consistent with right-sided volume overload and there is slow filling of the LV consistent with ventricular–ventricular interaction.