Effects of Low-Energy Diet or Exercise on Cardiovascular Function in Working-Age Adults With Type 2 Diabetes: A Prospective, Randomized, Open-Label, Blinded End Point Trial

Gulsin, Gaurav S.; Swarbrick, Daniel; Athithan, Lavanya; Brady, Emer M; Henson, Joseph; Baldry, Emma; Argyridou, Stavroula; Jaicim, Nishal Bhupendra; Squire, Gareth; Walters, Yvette; Marsh, Anna-Marie; McAdam, John; Parke, Kelly; Biglands, John; Yates, Thomas; Khunti, Kamlesh; Davies, Melanie J.; McCann, Gerry P

doi:10.2337/dc20-0129

Cited by 58 publications

(68 citation statements)

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“…30 Imaging studies demonstrate reduced contractility in the atria of people with severe obesity, with remodeling and improved contractility following weight loss interventions. 31 These observations support the further evaluation of pre-surgery weight loss as an organ protection strategy in people with severe obesity.…”

Section: Clinical Importancesupporting

confidence: 53%

Gene and metabolite expression dependence on body mass index in human myocardium

Roman

Yusoff

et al. 2021

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We hypothesized that body mass index (BMI) dependent changes in myocardial gene expression and energy-related metabolites underlie the biphasic association between BMI and mortality (the obesity paradox) in cardiac surgery. We performed transcriptome profiling and measured a panel of 144 metabolites in 53 and 55, respectively, myocardial biopsies from a cohort of sixty-seven adult patients undergoing coronary artery bypass grafting (registration: NCT02908009). The initial analysis identified 239 transcripts with biphasic BMI dependence. 120 displayed u-shape and 119 n-shape expression patterns. The identified local minima or maxima peaked at BMI 28-29. Based on these results and to best fit the WHO classification, we grouped the patients into three groups: BMI<25, 25≤BMI≤32, and BMI>32. The group analysis indicated that protein translation-related pathways were downregulated in 25≤BMI≥32 compared with BMI<25 patients. Muscle contraction transcripts were upregulated in 25≤BMI≥32 patients, and cholesterol synthesis and innate immunity transcripts were upregulated in the BMI>32 group. Transcripts involved in translation, muscle contraction and lipid metabolism also formed distinct correlation networks with biphasic dependence on BMI. Metabolite analysis identified acylcarnitines and ribose-5-phosphate increasing in the BMI>32 group and α-ketoglutarate increasing in the BMI<25 group. Molecular differences in the myocardium mirror the biphasic relationship between BMI and mortality.

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Section: Clinical Importancesupporting

confidence: 53%

Gene and metabolite expression dependence on body mass index in human myocardium

Roman

Yusoff

et al. 2021

Preprint

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“…Interventions to improve diastolic function and myocardial blood flow in asymptomatic people with T2D could therefore attenuate progression from stage B HF to overt HFpEF. For example, we have recently shown in a randomized trial that improvements in diastolic function occurred with exercise but not dietary weight loss ( 35 ). Limited and conflicting data exist regarding the impact of newer glucose-lowering therapies (sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists) on diastolic function ( 36 – 38 ) in people with T2D, and these warrant further investigation.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Determinants of Aerobic Exercise Capacity in Adults With Type 2 Diabetes

et al. 2020

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To assess the relationship between subclinical cardiac dysfunction and aerobic exercise capacity (peak VO 2) in adults with type 2 diabetes (T2D), a group at high risk of developing heart failure. RESEARCH DESIGN AND METHODS Cross-sectional study. We prospectively enrolled a multiethnic cohort of asymptomatic adults with T2D and no history, signs, or symptoms of cardiovascular disease. Age-, sex-, and ethnicity-matched control subjects were recruited for comparison. Participants underwent bioanthropometric profiling, cardiopulmonary exercise testing, and cardiovascular magnetic resonance with adenosine stress perfusion imaging. Multivariable linear regression analysis was undertaken to identify independent associations between measures of cardiovascular structure and function and peak VO 2. RESULTS A total of 247 adults with T2D (aged 51.8 6 11.9 years, 55% males, 37% black or south Asian ethnicity, HbA 1c 7.4 6 1.1% [57 6 12 mmol/mol], and duration of diabetes 61 [32-120] months) and 78 control subjects were included. Subjects with T2D had increased concentric left ventricular remodeling, reduced myocardial perfusion reserve (MPR), and markedly lower aerobic exercise capacity (peak VO 2 18.0 6 6.6 vs. 27.8 6 9.0 mL/kg/min; P < 0.001) compared with control subjects. In a multivariable linear regression model containing age, sex, ethnicity, smoking status, and systolic blood pressure, only MPR (b 5 0.822; P 5 0.006) and left ventricular diastolic filling pressure (E/e9) (b 5 20.388; P 5 0.001) were independently associated with peak VO 2 in subjects with T2D. CONCLUSIONS In a multiethnic cohort of asymptomatic people with T2D, MPR and diastolic function are key determinants of aerobic exercise capacity, independent of age, sex, ethnicity, smoking status, or blood pressure. Heart failure (HF) has emerged as one of the commonest and deadliest complications of type 2 diabetes (T2D) (1). Even in asymptomatic individuals with T2D, there is a high prevalence of left ventricular (LV) systolic and diastolic dysfunction and/or cardiac remodeling (2,3). The American Heart Association has classified such individuals as having stage B HF (4), and this group is at high risk of developing clinical symptoms. Earlier identification of the cardiovascular manifestations of stage B HF may permit earlier diagnosis and treatment of those patients most at risk (5).

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“…Interventions to improve diastolic function and myocardial blood flow in asymptomatic people with T2D could therefore attenuate progression from stage B HF to overt HFpEF. For example, we have recently shown in a randomised trial that improvements in diastolic function occurred with exercise but not dietary weight loss (35). Limited and conflicting data exist regarding the impact of newer glucose-lowering therapies (sodium glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists) on diastolic function (36)(37)(38) in people with T2D, and these warrant further investigation.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular determinants of aerobic exercise capacity in adults with type 2 diabetes

Gulsin¹,

Henson²,

Brady³

et al. 2020

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<div><b>Objective</b></div><div><b><br></b></div> <p>To assess the relationship between subclinical cardiac dysfunction and aerobic exercise capacity (peak VO<sub>2</sub>) in adults with type 2 diabetes (T2D), a group at high risk of developing heart failure.</p> <h3>Research design and methods</h3> <p>Cross-sectional study. We prospectively enrolled a multi-ethnic cohort of asymptomatic adults with T2D and no history, signs or symptoms of cardiovascular disease. Age-, sex-, and ethnicity-matched controls were recruited for comparison. Participants underwent bio-anthropometric profiling, cardiopulmonary exercise testing and cardiovascular magnetic resonance with adenosine stress perfusion imaging. Multivariable linear regression analysis was undertaken to identify independent associations between measures of cardiovascular structure and function and peak VO<sub>2</sub>.</p> <h3>Results</h3> <p>Two hundred and forty seven adults with T2D (age 51.8±11.9 years, 55% males, 37% black or south Asian ethnicity, HbA1c 7.4±1.1% (57±12 mmol/mol), duration of diabetes 61 (32 – 120) months and 78 controls were included. Subjects with T2D had increased concentric left ventricular (LV) remodelling, reduced myocardial perfusion reserve, and markedly lower aerobic exercise capacity (peak VO<sub>2 </sub>18.0±6.6 vs. 27.8±9.0mL/kg/min, p<0.001) compared with controls. In a multivariable linear regression model containing age, sex, ethnicity, smoking status and systolic blood pressure, only myocardial perfusion reserve (β=0.822, p=0.006) and E/e’ (β= -0.388, p=0.001) were independently associated with peak VO<sub>2</sub> in subjects with T2D.</p> <h3>Conclusions</h3> <p>In a multi-ethnic cohort of asymptomatic people with T2D, myocardial perfusion reserve and diastolic function are key determinants of aerobic exercise capacity, independent of age, sex, ethnicity, smoking status, or blood pressure. </p> <br>

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Effects of Low-Energy Diet or Exercise on Cardiovascular Function in Working-Age Adults With Type 2 Diabetes: A Prospective, Randomized, Open-Label, Blinded End Point Trial

Abstract: including the URL of the record and the reason for the withdrawal request. Effects of low-energy diet or exercise on cardiovascular function in working-age adults with type 2 diabetes: a prospective, randomized, open-label, blinded endpoint trial

Cited by 58 publications

References 43 publications

Gene and metabolite expression dependence on body mass index in human myocardium

Gene and metabolite expression dependence on body mass index in human myocardium

Cardiovascular Determinants of Aerobic Exercise Capacity in Adults With Type 2 Diabetes

Cardiovascular determinants of aerobic exercise capacity in adults with type 2 diabetes

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