There is a growing burden of cardiometabolic disease in many parts of the world. Despite some progress in its prevention, more can be done to tackle risks of its development in the community and in ...different specialty clinics. Currently, the identification and management of those at elevated risk of developing cardiovascular disease or diabetes or with conditions such as fatty liver disease remains fragmented and is not linked to constructive lifestyle advice. In this Perspective, we argue for a more consistent weight-management approach, alongside a holistic assessment of the risk for developing cardiometabolic diseases, offering patients a range of simple or more-intensive evidence-based lifestyle options in an empathetic manner, with encouragement for repeated attempts and a willingness to embrace failure.
Older people have been reported to be at higher risk of COVID-19 mortality. This study explored the factors mediating this association and whether older age was associated with increased mortality ...risk in the absence of other risk factors.
In UK Biobank, a population cohort study, baseline data were linked to COVID-19 deaths. Poisson regression was used to study the association between current age and COVID-19 mortality.
Among eligible participants, 438 (0.09%) died of COVID-19. Current age was associated exponentially with COVID-19 mortality. Overall, participants aged ≥75 years were at 13-fold (95% CI 9.13-17.85) mortality risk compared with those <65 years. Low forced expiratory volume in 1 second, high systolic blood pressure, low handgrip strength, and multiple long-term conditions were significant mediators, and collectively explained 39.3% of their excess risk. The associations between these risk factors and COVID-19 mortality were stronger among older participants. Participants aged ≥75 without additional risk factors were at 4-fold risk (95% CI 1.57-9.96, P = 0.004) compared with all participants aged <65 years.
Higher COVID-19 mortality among older adults was partially explained by other risk factors. 'Healthy' older adults were at much lower risk. Nonetheless, older age was an independent risk factor for COVID-19 mortality.
To compare the relationship between adiposity and prevalent diabetes across ethnic groups in the UK Biobank cohort and to derive ethnic-specific obesity cutoffs that equate to those developed in ...white populations in terms of diabetes prevalence.
UK Biobank recruited 502,682 U.K. residents aged 40-69 years. We used baseline data on the 490,288 participants from the four largest ethnic subgroups: 471,174 (96.1%) white, 9,631 (2.0%) South Asian, 7,949 (1.6%) black, and 1,534 (0.3%) Chinese. Regression models were developed for the association between anthropometric measures (BMI, waist circumference, percentage body fat, and waist-to-hip ratio) and prevalent diabetes, stratified by sex and adjusted for age, physical activity, socioeconomic status, and heart disease.
Nonwhite participants were two- to fourfold more likely to have diabetes. For the equivalent prevalence of diabetes at 30 kg/m(2) in white participants, BMI equated to the following: South Asians, 22.0 kg/m(2); black, 26.0 kg/m(2); Chinese women, 24.0 kg/m(2); and Chinese men, 26.0 kg/m(2). Among women, a waist circumference of 88 cm in the white subgroup equated to the following: South Asians, 70 cm; black, 79 cm; and Chinese, 74 cm. Among men, a waist circumference of 102 cm equated to 79, 88, and 88 cm for South Asian, black, and Chinese participants, respectively.
Obesity should be defined at lower thresholds in nonwhite populations to ensure that interventions are targeted equitably based on equivalent diabetes prevalence. Furthermore, within the Asian population, a substantially lower obesity threshold should be applied to South Asian compared with Chinese groups.
Although obesity and diabetes commonly co-exist, the evidence base to support obesity as the major driver of type 2 diabetes mellitus (T2DM), and the mechanisms by which this occurs, are now better ...appreciated.
This review briefly examines several sources of evidence - epidemiological, genetic, molecular, and clinical trial - to support obesity being a causal risk factor for T2DM. It also summarises the ectopic fat hypothesis for this condition, and lists several pieces of evidence to support this concept, extending from rare conditions and drug effects to sex- and ethnicity-related differences in T2DM prevalence. Ectopic liver fat is the best-studied example of ectopic fat, but more research on pancreatic fat as a potential cause of β-cell dysfunction seems warranted. This ectopic fat concept, in turn, broadly fits with the observation that individuals of similar ages can develop diabetes at markedly different body mass indexes (BMIs). Those with risk factors leading to more rapid ectopic fat gain - for example, men (compared with women), certain ethnicities, and potentially those with a family history of diabetes, as well as others with genes linked to a reduced subcutaneous adiposity - are more likely to develop diabetes at a younger age and/or lower BMI than those without.
Obesity is the major risk factor for T2DM and appears to drive tissue insulin resistance in part via gain of ectopic fat, with the best-studied organ being the liver. However, ectopic fat in the pancreas may contribute to β-cell dysfunction. In line with this observation, rapid resolution of diabetes linked to a preferential and rapid reduction in liver fat has been noted with significant caloric reduction. Whether these observations can help develop better cost-effective and sustainable lifestyle /medical interventions in patients with T2DM requires further study.
Chronic kidney disease is common in the general population and associated with excess cardiovascular disease (CVD), but kidney function does not feature in current CVD risk-prediction models. We ...tested three formulae for estimated glomerular filtration rate (eGFR) to determine which was the most clinically informative for predicting CVD and mortality. Using data from 440,526 participants from UK Biobank, eGFR was calculated using serum creatinine, cystatin C (eGFRcys) and creatinine-cystatin C. Associations of each eGFR with CVD outcome and mortality were compared using Cox models and adjusting for atherosclerotic risk factors (per relevant risk scores), and the predictive utility was determined by the C-statistic and categorical net reclassification index. We show that eGFRcys is most strongly associated with CVD and mortality, and, along with albuminuria, adds predictive discrimination to current CVD risk scores, whilst traditional creatinine-based measures are weakly associated with risk. Clinicians should consider measuring eGFRcys as part of cardiovascular risk assessment.
Abstract The aim of this study was to investigate the effects of very high intensity sprint interval training (SIT) on metabolic and vascular risk factors in overweight/obese sedentary men. Ten men ...(age, 32.1 ± 8.7 years; body mass index, 31.0 ± 3.7 kg m−2 ) participated. After baseline metabolic, anthropometric, and fitness measurements, participants completed a 2-week SIT intervention, comprising 6 sessions of 4 to 6 repeats of 30-second Wingate anaerobic sprints on an electromagnetically braked cycle ergometer, with 4.5-minute recovery between each repetition. Metabolic, anthropometric, and fitness assessments were repeated post-intervention. Both maximal oxygen uptake (2.98 ± 0.15 vs 3.23 ± 0.14 L min−1 , P = .013) and mean Wingate power (579 ± 24 vs 600 ± 19 W, P = .040) significantly increased after 2 weeks of SIT. Insulin sensitivity index (5.35 ± 0.72 vs 4.34 ± 0.72, P = .027) and resting fat oxidation rate in the fasted state (0.13 ± 0.01 vs 0.11 ± 0.01 g min−1 , P = .019) were significantly higher and systolic blood pressure (121 ± 3 vs 127 ± 3 mm Hg, P = .020) and resting carbohydrate oxidation in the fasted state (0.03 ± 0.01 vs 0.08 ± 0.02 g min−1 , P = .037) were significantly lower 24 hours post-intervention compared with baseline, but these changes were no longer significant 72 hours post-intervention. Significant decreases in waist (98.9 ± 3.1 vs 101.3 ± 2.7 cm, P = .004) and hip (109.8 ± 2.2 vs 110.9 ± 2.2 cm, P = .017) circumferences compared with baseline were also observed after the intervention. Thus, 2 weeks of SIT substantially improved a number of metabolic and vascular risk factors in overweight/obese sedentary men, highlighting the potential for this to provide an alternative exercise model for the improvement of vascular and metabolic health in this population.
Wearable devices can capture unexplored movement patterns such as brief bursts of vigorous intermittent lifestyle physical activity (VILPA) that is embedded into everyday life, rather than being done ...as leisure time exercise. Here, we examined the association of VILPA with all-cause, cardiovascular disease (CVD) and cancer mortality in 25,241 nonexercisers (mean age 61.8 years, 14,178 women/11,063 men) in the UK Biobank. Over an average follow-up of 6.9 years, during which 852 deaths occurred, VILPA was inversely associated with all three of these outcomes in a near-linear fashion. Compared with participants who engaged in no VILPA, participants who engaged in VILPA at the sample median VILPA frequency of 3 length-standardized bouts per day (lasting 1 or 2 min each) showed a 38%-40% reduction in all-cause and cancer mortality risk and a 48%-49% reduction in CVD mortality risk. Moreover, the sample median VILPA duration of 4.4 min per day was associated with a 26%-30% reduction in all-cause and cancer mortality risk and a 32%-34% reduction in CVD mortality risk. We obtained similar results when repeating the above analyses for vigorous physical activity (VPA) in 62,344 UK Biobank participants who exercised (1,552 deaths, 35,290 women/27,054 men). These results indicate that small amounts of vigorous nonexercise physical activity are associated with substantially lower mortality. VILPA in nonexercisers appears to elicit similar effects to VPA in exercisers, suggesting that VILPA may be a suitable physical activity target, especially in people not able or willing to exercise.
Imprecise measurement of physical activity variables might attenuate estimates of the beneficial effects of activity on health-related outcomes. We aimed to compare the cardiometabolic risk factor ...dose-response relationships for physical activity and sedentary behaviour between accelerometer- and questionnaire-based activity measures.
Physical activity and sedentary behaviour were assessed in 317 adults by 7-day accelerometry and International Physical Activity Questionnaire (IPAQ). Fasting blood was taken to determine insulin, glucose, triglyceride and total, LDL and HDL cholesterol concentrations and homeostasis model-estimated insulin resistance (HOMA(IR)). Waist circumference, BMI, body fat percentage and blood pressure were also measured.
For both accelerometer-derived sedentary time (<100 counts.min(-1)) and IPAQ-reported sitting time significant positive (negative for HDL cholesterol) relationships were observed with all measured risk factors--i.e. increased sedentary behaviour was associated with increased risk (all p ≤ 0.01). However, for HOMA(IR) and insulin the regression coefficients were >50% lower for the IPAQ-reported compared to the accelerometer-derived measure (p<0.0001 for both interactions). The relationships for moderate-to-vigorous physical activity (MVPA) and risk factors were less strong than those observed for sedentary behaviours, but significant negative relationships were observed for both accelerometer and IPAQ MVPA measures with glucose, and insulin and HOMA(IR) values (all p<0.05). For accelerometer-derived MVPA only, additional negative relationships were seen with triglyceride, total cholesterol and LDL cholesterol concentrations, BMI, waist circumference and percentage body fat, and a positive relationship was evident with HDL cholesterol (p = 0.0002). Regression coefficients for HOMA(IR), insulin and triglyceride were 43-50% lower for the IPAQ-reported compared to the accelerometer-derived MVPA measure (all p≤0.01).
Using the IPAQ to determine sitting time and MVPA reveals some, but not all, relationships between these activity measures and metabolic and vascular disease risk factors. Using this self-report method to quantify activity can therefore underestimate the strength of some relationships with risk factors.
To determine whether breaking up prolonged sitting with short bouts of standing or walking improves postprandial markers of cardiometabolic health in women at high risk of type 2 diabetes.
Twenty-two ...overweight/obese, dysglycemic, postmenopausal women (mean ± SD age 66.6 ± 4.7 years) each participated in two of the following treatments: prolonged, unbroken sitting (7.5 h) or prolonged sitting broken up with either standing or walking at a self-perceived light intensity (for 5 min every 30 min). Both allocation and treatment order were randomized. The incremental area under the curves (iAUCs) for glucose, insulin, nonesterified fatty acids (NEFA), and triglycerides were calculated for each treatment condition (mean ± SEM). The following day, all participants underwent the 7.5-h sitting protocol.
Compared with a prolonged bout of sitting (iAUC 5.3 ± 0.8 mmol/L ⋅ h), both standing (3.5 ± 0.8 mmol/L ⋅ h) and walking (3.8 ± 0.7 mmol/L ⋅ h) significantly reduced the glucose iAUC (both P < 0.05). When compared with prolonged sitting (548.2 ± 71.8 mU/L ⋅ h), insulin was also reduced for both activity conditions (standing, 437.2 ± 73.5 mU/L ⋅ h; walking, 347.9 ± 78.7 mU/L ⋅ h; both P < 0.05). Both standing (-1.0 ± 0.2 mmol/L ⋅ h) and walking (-0.8 ± 0.2 mmol/L ⋅ h) attenuated the suppression of NEFA compared with prolonged sitting (-1.5 ± 0.2 mmol/L ⋅ h) (both P < 0.05). There was no significant effect on triglyceride iAUC. The effects on glucose (standing and walking) and insulin (walking only) persisted into the following day.
Breaking up prolonged sitting with 5-min bouts of standing or walking at a self-perceived light intensity reduced postprandial glucose, insulin, and NEFA responses in women at high risk of type 2 diabetes. This simple, behavioral approach could inform future public health interventions aimed at improving the metabolic profile of postmenopausal, dysglycemic women.
South Asians, particularly when living in high-income countries, are at a substantially elevated risk of type 2 diabetes compared with white Europeans, and typically develop the disease 5-10 years ...earlier and at a lower BMI. Migrant south Asians seem to be more insulin resistant than white Europeans across the life course and potentially experience β-cell exhaustion at a younger age. Differences in adiposity (high percentage of body fat and high proportion of deep subcutaneous and visceral fat) and skeletal muscle (low percentage of lean mass and low cardiorespiratory fitness) are likely to contribute these factors. No clear evidence is available suggesting genetic factors make a major contribution to the increased risk of diabetes in south Asians, but epigenetic factors might have a role. Irrespective of future mechanistic discoveries, south Asians need to be encouraged and helped-by various culturally appropriate methods--to maintain a high physical activity level and low bodyweight across the life course to prevent diabetes. In clinical terms, cardiovascular risks have attenuated over time in migrant south Asians with diabetes but retinopathy and renal complication risks remain high because of the high levels of glycaemia and rapid glycaemic deterioration noted in this population. We review these aspects and suggest areas for future research.
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