1.
Interaction Between Type 2 Diabetes Prevention Strategies and Genetic Determinants of Coronary Artery Disease on Cardiometabolic Risk Factors.
Merino, J, Jablonski, KA, Mercader, JM, Kahn, SE, Chen, L, Harden, M, Delahanty, LM, Araneta, MRG, Walford, GA, Jacobs, SBR, et al
Diabetes. 2020;69(1):112-120
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Individual risk of Coronary Artery Disease (CAD) and type 2 diabetes reflects the interplay between lifestyle behaviours acting on a backdrop of genetic predisposition. The aim of this study was to examine whether type 2 diabetes prevention strategies, either an intensive lifestyle intervention (ILS) or metformin treatment (MET), modify the association between CAD genetic risk and cardiometabolic risk factors (CRFs) in participants at high risk of type 2 diabetes. The study is a randomised controlled trial were participants were randomly allocated to one of the three groups; ILS (n = 1,079), MET (850 mg twice daily [n = 1,073]), or placebo (n = 1,082). Results indicate that there weren’t major significant differences in baseline characteristics, except for lower high-density lipoprotein and higher triglyceride in the placebo individuals compared with individuals assigned to MET or ILS. In fact, either an ILS or MET has a beneficial effect on 1-year change in different CRFs. Authors conclude that type 2 diabetes–preventive strategies for individuals at high risk of type 2 diabetes provide beneficial effects on CRFs regardless of CAD genetic risk profile.
Abstract
Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with placebo (P < 0.001) irrespective of CAD genetic risk (P interaction > 0.05). We detected nominal significant interactions between PRS and dietary quality and physical activity on 1-year change in BMI, fasting glucose, triglycerides, and HDL cholesterol in individuals randomized to metformin or placebo, but none of them achieved the multiple-testing correction for significance. This study confirms that diabetes preventive interventions improve CRFs regardless of CAD genetic risk and delivers hypothesis-generating data on the varying benefit of increasing physical activity and improving diet on intermediate cardiovascular risk factors depending on individual CAD genetic risk profile.
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Effects of prescribed aerobic exercise volume on physical activity and sedentary time in postmenopausal women: a randomized controlled trial.
McNeil, J, Farris, MS, Ruan, Y, Merry, H, Lynch, BM, Matthews, CE, Courneya, KS, Friedenreich, CM
The international journal of behavioral nutrition and physical activity. 2018;15(1):27
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Physical activity has emerged as an important lifestyle factor for primary prevention of numerous diseases, including postmenopausal breast cancer. The aim of this two-armed randomised controlled study was to examine the effects of a year-long prescribed aerobic exercise programme on physical activity levels and sedentary time in postmenopausal women. A total of 400 postmenopausal women aged between 50 – 74 years were randomised to one of the two groups; moderate (150min of exercise/week) or high (300min of exercise/week) volumes of aerobic exercise interventions. Results showed increased activity time in total and moderate-vigorous intensity/recreational physical activity, coupled with decreased sedentary time, in response to both volumes of prescribed physical activity. However, results also showed that physical activity and sedentary time returned to baseline following study completion. Authors conclude that total physical activity time can be increased with greater volumes of prescribed exercise. Furthermore, additional support and resources may be beneficial to promote the maintenance of increased physical activity and reduced sedentary time in the long-term.
Abstract
BACKGROUND Physical activity has emerged as an important lifestyle factor for primary prevention of numerous diseases, including postmenopausal breast cancer. No study to date has assessed the acute and long-term effects of year-long aerobic exercise programs differing in prescribed exercise volume on physical activity and sedentary time in postmenopausal women. Therefore, we aimed to examine the effects of two moderate-vigorous intensity exercise doses on total, light and moderate-vigorous intensity physical activity times, and sedentary time in postmenopausal women during the year-long intervention and one year later. METHODS The Breast Cancer and Exercise Trial in Alberta (BETA) was a two-center, two-arm, 12-month randomized controlled trial that included 400 previously inactive postmenopausal women randomized to either 150 (MODERATE) or 300 (HIGH) minutes/week of aerobic exercise. Physical activity and sedentary time were assessed at baseline, 6- (intervention mid-point), 12- (prior to end of intervention) and 24-months (follow-up) with waist-mounted accelerometers (Actigraph GTX3®). Self-reported activity and sedentary time at baseline, 12- and 24-months was also assessed (Past Year Total Physical Activity Questionnaire and SIT-Q). Intention-to-treat analyses were conducted using linear mixed models and adjusted for baseline variables. RESULTS Both physical activity interventions led to increases in objective and subjective measures of total and moderate-vigorous intensity/recreational physical activity time, coupled with decreases in sedentary time, at 6- and 12-months compared to baseline. Additionally, greater increases in accelerometry-derived total physical activity time at 6- and 12-months, and self-reported recreational activity time at 12-months, compared to baseline were noted in the HIGH versus MODERATE groups. Decreases in total, light and moderate-vigorous intensity physical activity time, and an increase in sedentary time, in both groups were noted at 24-months compared to 12-months. A decrease in light intensity physical activity time in both groups at 24-months compared to baseline was also noted. CONCLUSION These findings have important health implications, suggesting that total physical activity time can be increased with greater volumes of prescribed exercise, but that additional support and resources could be used to promote the maintenance of these high levels of aerobic exercise participation following study completion. TRIAL REGISTRATION clinicaltrials.gov identifier: NCT01435005 (BETA Trial). Registred September 15th 2011 (retrospectively registered).
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Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty.
Ferrucci, L, Fabbri, E
Nature reviews. Cardiology. 2018;15(9):505-522
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Inflammageing is a term used to describe elevated blood inflammatory markers that leads to frailty and increases an individual’s risk for heart disease, kidney disease and other physical and mental illnesses. Whether inflammageing is causal in heart disease is still uncertain. This large review of 310 papers aimed to understand the causes and role of inflammageing in heart disease and other illnesses associated with ageing. Causes of inflammageing were discussed and mechanisms are not fully understood. Genetic susceptibility, obesity, gut microbiota, gut permeability, when cells can no longer divide, and chronic infections were all implicated. The role of inflammageing in heart disease was a focus and the authors deduced that it was likely to be both causal and a result of heart disease. However, the administration of anti-inflammatories in heart disease has not always proved a successful treatment. Possible causes of inflammageing are likely to be linked and cumulative and although inflammation may cause age related diseases, its role in protecting the body means that its benefits outweigh its consequences. It was concluded that controlling inflammageing may prevent heart disease and other diseases associated with ageing. This study could be used by healthcare professionals to help understand what inflammageing is and its role in age related diseases.
Abstract
Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty - which affect clinical manifestations, prognosis, and response to treatment - and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials.