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OBJECTIVE Sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) reduce body weight and improve cardiometabolic health, but their effect on physical activity is unknown. RESEARCH DESIGN AND METHODS We pooled data (n = 148) from three randomized trials to investigate the effect of empagliflozin (SGLT2i) and liraglutide (GLP-1RA), in comparison with sitagliptin (dipeptidyl peptidase 4 inhibitor) and dietary therapies, on accelerometer-assessed physical activity. RESULTS Liraglutide (mean −1,144 steps/day; 95% CI −2,069 to −220), empagliflozin (−1,132 steps/day; −1,739, −524), and sitagliptin (−852 steps/day; −1,625, −78) resulted in reduced total daily physical activity after 6 months (P < 0.01 vs. control). Moderate- to vigorous-intensity physical activity was also reduced. Dietary interventions led to no change or an increase in physical activity. CONCLUSIONS The initiation of all glucose-lowering therapies was associated with reduced physical activity, warranting further investigation.

OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1RA) reduce body weight and improve cardiometabolic health, but their effect on physical activity is unknown. RESEARCH DESIGN AND METHODS. We pooled data (n = 148) from three randomised trials to investigate the effect of empagliflozin (SGLT2i) and liraglutide (GLP-1RA), in comparison to sitagliptin (dipeptidyl peptidase 4 inhibitor) and dietary therapies on accelerometer-assessed physical activity. RESULTS: Liraglutide (-1144 steps/day; 95% CI -2069, -220), empagliflozin (-1132 steps/day; -1739, -524) and sitagliptin (-852 steps/day; -1625, -78) resulted in reduced total daily physical activity after 6 months (p< 0.01 vs. control). Moderate-to-vigorous intensity physical activity was also reduced. Dietary interventions led to no change or an increase in physical activity. CONCLUSIONS: The initiation of all glucose lowering therapies was associated with reduced physical activity, warranting further investigation.

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.

Objective: People with T2D have increased risk of heart failure, with fibro-inflammatory pathways implicated in the pathogenesis. This secondary analysis assessed the relationship between multiple fibro-inflammatory biomarkers and cardiovascular (CV) structure and function in patients with T2D and asymptomatic nondiabetic controls and the impact of two lifestyle interventions, exercise training or meal replacement plan (MRP). Methods: Data was derived from a randomised controlled trial (RCT), including a nested case-control study. Adults with T2D and no CV disease were randomized (1:1:1) to a 12-week intervention of 1) supervised aerobic exercise training, 2) a low-energy (∼810 kcal/day) MRP or 3) standard care. Fasting bloods for fibro-inflammatory biomarkers and cardiac MRI (CMR) were undertaken pre- and post-intervention. Principal component analysis (PCA) was performed to visualise this multivariate dataset in a 3D space to understand the relationship between CMR outcomes of interest (e.g., cardiac geometry, systolic and diastolic function), key demographic variables (age, sex, ethnicity and smoking status) and the fibro-inflammatory biomarkers (total of 68 variables) between cases and controls and pre-post intervention. Results: At baseline 36 controls and 83 T2D were compared of which 76 participants completed the RCT. People with T2D had an adverse fibro-inflammatory profile compared to controls’. The PCA 3D-visulisation containing demographics, biomarkers and CMR data shows almost complete separation between controls and those with T2D. Following MRP there was a marked shift in the PCA but not for the exercise intervention. Conclusion: Alterations in fibro-inflammatory pathways impact CV structure and function before the onset of symptomatic heart failure in people with T2D. The MRP improved this fibro-inflammatory profile but not exercise. Longer term studies are required to determine whether the MRP can reduce symptomatic heart failure. Disclosure E. M. Brady: Other Relationship; Self; Bristol Myers Squibb Pharmaceutical company. E. Mirkes: None. K. Parke: None. G. S. Gulsin: None. L. Athithan: None. J. Henson: None. T. Yates: None. M. J. Davies: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Boehringer Ingelheim Limited (UK), Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi, Other Relationship; Self; AstraZeneca, NIHR Leicester Biomedical Research Centre, Novo Nordisk, Speaker's Bureau; Self; Astra Zeneca Pharma India Ltd, Boehringer Ingelheim (China), Boehringer Ingelheim (Philippines), Inc., Boehringer Ingelheim International GmbH, Boehringer Ingelheim Limited (UK), Boehringer Ingelheim Saudi Arabia Trading, Boehringer Ingelheim Singapore Pte. Ltd, Boehringer Ingelheim Sp. Z o. o., Eli Lilly and Company, Napp Pharmaceuticals, Novo Nordisk, Novo Nordisk A/S, S. C. Sanofi Romania SRL, Sanofi K. K. G. P. Mccann: None. P. Kanagala: None. L. Ng: None. Funding National Institute for Health Research (CDF2014-07-045 to G.P.M.)

OBJECTIVE To assess the relationship between subclinical cardiac dysfunction and aerobic exercise capacity (peak VO2) 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 VO2. RESULTS A total of 247 adults with T2D (aged 51.8 ± 11.9 years, 55% males, 37% black or south Asian ethnicity, HbA1c 7.4 ± 1.1% [57 ± 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 VO2 18.0 ± 6.6 vs. 27.8 ± 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 (β = 0.822; P = 0.006) and left ventricular diastolic filling pressure (E/e′) (β = −0.388; P = 0.001) were independently associated with peak VO2 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.

Aim: Evaluate the PRE-STARt intervention in five European countries (UK, Portugal, Spain, Germany and Greece). Methods: The 8 family based interactive workshops aimed to elicit positive lifestyle behavior change in 12-14 year olds. The written curriculum was underpinned by specific learning theories and philosophy. Demographic, biomedical, anthropometric and lifestyle behavior measures were collected at baseline, 3 and 6 months. Due to design differences across countries, the analysis assesses changes within each country. Results: 318 participants were recruited (50% male, 69% Caucasian ethnicity). Control group were more overweight than the intervention group (10%). Average time spent doing moderate-vigorous physical activity (MVPA) was 45 minutes/day. A trend towards increased MVPA at 6 months in the UK was observed (8 mins/day). The attendance data for change in MVPA at 6 months indicate a dose response. Those attending at least 4 workshops had significantly higher MVPA compared to those who attended less than 4 (OR:12.64 (3.63 to 21.66), 18.92 (5.74 to 32.09)). A trend towards clinical and statistical significant reduction in both BMI and weight for all countries was observed. The UK observed a non-significant reduction in self-reported sitting time on weekdays (1 hour/day). Eating behaviors improved in each country at 6 months; in Greece increased frequency of eating breakfast; a reduction in the number of days snacks eaten in the UK; a trend across all countries for increased fruit and vegetable consumption. Conclusion: The intervention is accepted by the target population. The data point to positive emerging trends in changes in health behaviors (both eating and activity) in addition to health outcomes namely a reduction in body weight and BMI. A definitive randomized controlled trial is required to test effectiveness and cost effectiveness of the intervention. Disclosure E.M. Brady: None. L.J. Gray: None. S. Weihrauch-Blüher: None. C. Edwardson: None. D. Harrington: None. R.T. Ribeiro: None. A. Vazeou: None. A.L. Northern: None. E. Alustiza: None. M. Davies: Advisory Panel; Self; AstraZeneca. Board Member; Self; AstraZeneca. Consultant; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Board Member; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Eli Lilly and Company. Board Member; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Board Member; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Novo Nordisk Inc.. Board Member; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Board Member; Self; Sanofi-Aventis. Consultant; Self; Sanofi-Aventis. Research Support; Self; Sanofi-Aventis. Advisory Panel; Self; Sanofi-Aventis. Speaker's Bureau; Self; Sanofi-Aventis. Advisory Panel; Self; Servier. Consultant; Self; Intarcia Therapeutics, Inc.. Speaker's Bureau; Self; Mitsubishi Tanabe Pharma Corporation.