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Cardiometabolic Risk Factors and Incident Cardiovascular Disease Events in Women vs Men With Type 1 Diabetes.
Braffett, BH, Bebu, I, El Ghormli, L, Cowie, CC, Sivitz, WI, Pop-Busui, R, Larkin, ME, Gubitosi-Klug, RA, Nathan, DM, Lachin, JM, et al
JAMA network open. 2022;5(9):e2230710
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In the general population, women have a lower absolute risk of cardiovascular disease (CVD) compared with men. However, among individuals with type 1 or type 2 diabetes, the relative risk of CVD is similar or higher in women compared with men. The aim of this study was to assess sex differences in achieving recommended CVD risk management targets and associations with CVD events. This is a cohort study which included a total of 1441 (men n= 736) participants with type 1 diabetes. Results show that the prevalence and mean levels of most cardiometabolic risk factors (except for pulse rate and haemoglobin A1c) were consistent with a less atherogenic profile among women compared with men. Furthermore, achieving treatment targets for blood pressure, lipids, and glucose was associated with significantly decreased risk of CVD in both women and men. Authors conclude that their findings argue for a recalibration of CVD risk factor stratification in revised clinical care guidelines and therapeutic recommendations by sex for individuals with type 1 diabetes.
Abstract
IMPORTANCE The lower risk of cardiovascular disease (CVD) among women compared with men in the general population may be diminished among those with diabetes. OBJECTIVE To evaluate cardiometabolic risk factors and their management in association with CVD events in women vs men with type 1 diabetes enrolled in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. DESIGN, SETTING, AND PARTICIPANTS This cohort study used data obtained during the combined DCCT (randomized clinical trial, conducted 1983-1993) and EDIC (observational study, conducted 1994 to present) studies through April 30, 2018 (mean [SD] follow-up, 28.8 [5.8] years), at 27 clinical centers in the US and Canada. Data analyses were performed between July 2021 and April 2022. EXPOSURE During the DCCT phase, patients were randomized to intensive vs conventional diabetes therapy. MAIN OUTCOMES AND MEASURES Cardiometabolic risk factors and CVD events were assessed via detailed medical history and focused physical examinations. Blood and urine samples were assayed centrally. CVD events were adjudicated by a review committee. Linear mixed models and Cox proportional hazards models evaluated sex differences in cardiometabolic risk factors and CVD risk over follow-up. RESULTS A total of 1441 participants with type 1 diabetes (mean [SD] age at DCCT baseline, 26.8 [7.1] years; 761 [52.8%] men; 1390 [96.5%] non-Hispanic White) were included. Over the duration of the study, compared with men, women had significantly lower body mass index (BMI, calculated as weight in kilograms divided by height in meters squared; β = -0.43 [SE, 0.16]; P = .006), waist circumference (β = -10.56 cm [SE, 0.52 cm]; P < .001), blood pressure (systolic: β = -5.77 mm Hg [SE, 0.35 mm Hg]; P < .001; diastolic: β = -3.23 mm Hg [SE, 0.26 mm Hg]; P < .001), and triglyceride levels (β = -10.10 mg/dL [SE, 1.98 mg/dL]; P < .001); higher HDL cholesterol levels (β = 9.36 mg/dL [SE, 0.57 mg/dL]; P < .001); and similar LDL cholesterol levels (β = -0.76 mg/dL [SE, 1.22 mg/dL]; P = .53). Women, compared with men, achieved recommended targets more frequently for blood pressure (ie, <130/80 mm Hg: 90.0% vs 77.4%; P < .001) and triglycerides (ie, <150 mg/dL: 97.3% vs 90.5%; P < .001). However, sex-specific HDL cholesterol targets (ie, ≥50 mg/dL for women, ≥40 mg/dL for men) were achieved less often (74.3% vs 86.6%; P < .001) and cardioprotective medications were used less frequently in women than men (ie, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker: 29.6% [95% CI, 25.7%-33.9%] vs 40.0% [95% CI, 36.1%-44.0%]; P = .001; lipid-lowering medication: 25.3% [95% CI, 22.1%-28.7%] vs 39.6% [95% CI, 36.1%-43.2%]; P < .001). Women also had significantly higher pulse rates (mean [SD], 75.2 [6.8] beats per minute vs 71.8 [6.9] beats per minute; P < .001) and hemoglobin A1c levels (mean [SD], 8.3% [1.0%] vs 8.1% [1.0%]; P = .01) and achieved targets for tighter glycemic control less often than men (ie, hemoglobin A1c <7%: 11.2% [95% CI, 9.3%-13.3%] vs 14.0% [95% CI, 12.0%-16.3%]; P = .03). CONCLUSIONS AND RELEVANCE These findings suggest that despite a more favorable cardiometabolic risk factor profile, women with type 1 diabetes did not have a significantly lower CVD event burden than men, suggesting a greater clinical impact of cardiometabolic risk factors in women vs men with diabetes. These findings call for conscientious optimization of the control of CVD risk factors in women with type 1 diabetes.
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Weight Loss and Exercise Differentially Affect Insulin Sensitivity, Body Composition, Cardiorespiratory Fitness, and Muscle Strength in Older Adults With Obesity: A Randomized Controlled Trial.
Brennan, AM, Standley, RA, Anthony, SJ, Grench, KE, Helbling, NL, DeLany, JP, Cornnell, HH, Yi, F, Stefanovic-Racic, M, Toledo, FGS, et al
The journals of gerontology. Series A, Biological sciences and medical sciences. 2022;77(5):1088-1097
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Aging is marked by increased risk for type 2 diabetes, reduced muscle mass and strength (ie, sarcopenia), decreased physical function and cardiorespiratory fitness, ectopic fat deposition, and insulin resistance all of which increase the risk for physical disability, morbidity, and mortality. These adverse health consequences associated with advanced age are exacerbated with obesity and physical inactivity. The aim of this study was to investigate the effects of weight loss with or without exercise on skeletal muscle insulin sensitivity, exclusively in obese older adults. This study is a 2-site, 6-month randomized controlled trial with a parallel group design. Eighty-six older (60–80 years of age), physically inactive men and women with obesity were randomised into one of the 3 treatments (1:1:1 allocation ratio): control (health education), calorie restriction-induced weight loss, and weight loss with exercise. Results suggest that weight loss via calorie restriction alone is insufficient to significantly improve skeletal muscle insulin sensitivity and requires the addition of exercise to incur benefit, which was also true for clinical measures of insulin resistance including haemoglobin A1C [a blood test that measures the average blood sugar levels over a period of 3 months] and fasting insulin. Authors conclude that regular exercise should be considered as a useful and manageable adjunct to traditional weight loss therapies for older adults with obesity to mitigate risk for chronic disease and maintain functional independence and quality of life.
Abstract
BACKGROUND Aging-related disease risk is exacerbated by obesity and physical inactivity. It is unclear how weight loss and increased activity improve risk in older adults. We aimed to determine the effects of diet-induced weight loss with and without exercise on insulin sensitivity, VO2peak, body composition, and physical function in older obese adults. METHODS Physically inactive older (68.6 ± 4.5 years) obese (body mass index 37.4 ± 4.9 kg/m2) adults were randomized to health education control (HEC; n = 25); diet-induced weight loss (WL; n = 31); or weight loss and exercise (WLEX; n = 28) for 6 months. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp, body composition by dual-energy X-ray absorptiometry and MRI, strength by isokinetic dynamometry, and VO2peak by graded exercise test. RESULTS WLEX improved (p < .05) peripheral insulin sensitivity (+75 ± 103%) versus HEC (+12 ± 67%); WL (+36 ± 47%) versus HEC did not reach statistical significance. WLEX increased VO2peak (+7 ± 12%) versus WL (-2 ± 24%) and prevented reductions in strength and lean mass induced by WL (p < .05). WLEX decreased abdominal adipose tissue (-16 ± 9%) versus HEC (-3 ± 8%) and intermuscular adipose tissue (-15 ± 13%) versus both HEC (+9 ± 15%) and WL (+2 ± 11%; p < .01). CONCLUSIONS Exercise with weight loss improved insulin sensitivity and VO2peak, decreased ectopic fat, and preserved lean mass and strength. Weight loss alone decreased lean mass and strength. Older adults intending to lose weight should perform regular exercise to promote cardiometabolic and functional benefits, which may not occur with calorie restriction-induced weight loss alone.
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The Impact of COVID-19 Stay-At-Home Orders on Health Behaviors in Adults.
Flanagan, EW, Beyl, RA, Fearnbach, SN, Altazan, AD, Martin, CK, Redman, LM
Obesity (Silver Spring, Md.). 2021;29(2):438-445
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In response to the global outbreak of COVID-19, a wave of quarantine and stay-at-home mandates were issued to attenuate the rapid worldwide spread. The aim of this study was to quantify changes in habitual dietary behaviours, physical activity, sleep, sedentary behaviours, and mental health before and during the initial peak of the COVID-19 pandemic. This study is based on an anonymous survey via paid advertisements on the social media platform Facebook. A total of 7,753 completed the first COVID-19 question and were thus included in the analysis. Results indicate that: - declines in healthful eating behaviours were coincident with reductions in physical activity. These negative behaviours were characteristic of individuals reporting weight gain in response to the pandemic outbreak. - anxiety scores nearly doubled in response to the pandemic and 20% of the sample reported that symptoms were severe enough to interfere with daily routines. - home confinement led to shifts in daily work and household responsibilities which resulted in mental health declines alongside some positive and many negative changes to health behaviours. Authors conclude that with increased cases of weight gain and significant declines to mental health, COVID-19 may impact clinical practice for years to come.
Abstract
OBJECTIVE Stay-at-home orders in response to the coronavirus disease 2019 (COVID-19) pandemic have forced abrupt changes to daily routines. This study assessed lifestyle changes across different BMI classifications in response to the global pandemic. METHODS The online survey targeting adults was distributed in April 2020 and collected information on dietary behaviors, physical activity, and mental health. All questions were presented as "before" and "since" the COVID-19 pandemic. RESULTS In total, 7,753 participants were included; 32.2% of the sample were individuals with normal weight, 32.1% had overweight, and 34.0% had obesity. During the pandemic, overall scores for healthy eating increased (P < 0.001), owing to less eating out and increased cooking (P < 0.001). Sedentary leisure behaviors increased, while time spent in physical activity (absolute time and intensity adjusted) declined (P < 0.001). Anxiety scores increased 8.78 ± 0.21 during the pandemic, and the magnitude of increase was significantly greater in people with obesity (P ≤ 0.01). Weight gain was reported in 27.5% of the total sample compared with 33.4% in participants with obesity. CONCLUSIONS The COVID-19 pandemic has produced significant health effects, well beyond the virus itself. Government mandates together with fear of contracting the virus have significantly impacted lifestyle behaviors alongside declines in mental health. These deleterious impacts have disproportionally affected individuals with obesity.
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Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.
Yoshino, M, Yoshino, J, Kayser, BD, Patti, GJ, Franczyk, MP, Mills, KF, Sindelar, M, Pietka, T, Patterson, BW, Imai, SI, et al
Science (New York, N.Y.). 2021;372(6547):1224-1229
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Nicotinamide adenine dinucleotide (NAD+) is a co-substrate for NAD+-consuming enzymes that are essential in the regulation of diverse biological processes. The aim of this study was to determine the effects of nicotinamide mononucleotide (NMN) supplementation on i) body composition, ii) skeletal muscle insulin sensitivity, and insulin signalling; and iii) muscle NAD+ content and global gene expression profile. This study is a 10-week, randomized, placebo-controlled, double-blind trial in postmenopausal women with prediabetes who were overweight or obese. Twenty-five postmenopausal women with prediabetes were randomised to the placebo group (n=12) or the NMN group (n=13). Results show that 10 weeks of NMN supplementation increases muscle insulin signalling and muscle insulin sensitivity in postmenopausal women with prediabetes who are overweight or obese. Authors conclude that the precise mechanism(s) responsible for these metabolic effects and the potential metabolic benefits of NMN supplementation in other patient populations remain to be explored.
Abstract
In rodents, obesity and aging impair nicotinamide adenine dinucleotide (NAD+) biosynthesis, which contributes to metabolic dysfunction. Nicotinamide mononucleotide (NMN) availability is a rate-limiting factor in mammalian NAD+ biosynthesis. We conducted a 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in postmenopausal women with prediabetes who were overweight or obese. Insulin-stimulated glucose disposal, assessed by using the hyperinsulinemic-euglycemic clamp, and skeletal muscle insulin signaling [phosphorylation of protein kinase AKT and mechanistic target of rapamycin (mTOR)] increased after NMN supplementation but did not change after placebo treatment. NMN supplementation up-regulated the expression of platelet-derived growth factor receptor β and other genes related to muscle remodeling. These results demonstrate that NMN increases muscle insulin sensitivity, insulin signaling, and remodeling in women with prediabetes who are overweight or obese (clinicaltrial.gov NCT03151239).
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Proteomic profiles before and during weight loss: Results from randomized trial of dietary intervention.
Figarska, SM, Rigdon, J, Ganna, A, Elmståhl, S, Lind, L, Gardner, CD, Ingelsson, E
Scientific reports. 2020;10(1):7913
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Understanding biological substances, or "biomarkers" that are present in the body of individuals with obesity, could lead to personalised dietary recommendations for weight loss. Current research on biomarkers in individuals with obesity who have undergone a weight loss intervention is lacking. This secondary analysis of a randomised control trial study of 609 healthy and obese adults over 6 months, aimed to identify biomarkers associated with obesity, determine any changes with weight loss and if these could be used to make personalised recommendations. 263 biomarkers were tested and the results showed that 102 were associated with body mass index (BMI). 88 were elevated in individuals with a higher BMI. Upon weight loss, a large number of these decreased and a small number increased. The type of diet had no influence on how these biomarkers changed and only one could be used to predict weight loss. It was concluded that many of the biomarkers were connected to BMI and many changed with weight loss, however none of the biomarkers studied could be used to individualise dietary recommendations. This study could be used by healthcare professionals to understand that the role of biomarkers in personalising recommendations is complex and more research may be needed.
Abstract
Inflammatory and cardiovascular biomarkers have been associated with obesity, but little is known about how they change upon dietary intervention and concomitant weight loss. Further, protein biomarkers might be useful for predicting weight loss in overweight and obese individuals. We performed secondary analyses in the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) randomized intervention trial that included healthy 609 adults (18-50 years old) with BMI 28-40 kg/m2, to evaluate associations between circulating protein biomarkers and BMI at baseline, during a weight loss diet intervention, and to assess predictive potential of baseline blood proteins on weight loss. We analyzed 263 plasma proteins at baseline and 6 months into the intervention using the Olink Proteomics CVD II, CVD III and Inflammation arrays. BMI was assessed at baseline, after 3 and 6 months of dietary intervention. At baseline, 102 of the examined inflammatory and cardiovascular biomarkers were associated with BMI (>90% with successful replication in 1,584 overweight/obese individuals from a community-based cohort study) and 130 tracked with weight loss shedding light into the pathophysiology of obesity. However, out of 263 proteins analyzed at baseline, only fibroblast growth factor 21 (FGF-21) predicted weight loss, and none helped individualize dietary assignment.
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Estimation of Primary Prevention of Gout in Men Through Modification of Obesity and Other Key Lifestyle Factors.
McCormick, N, Rai, SK, Lu, N, Yokose, C, Curhan, GC, Choi, HK
JAMA network open. 2020;3(11):e2027421
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Gout is prevalent in most Western countries. Modifying the contributary factors such as obesity and alcohol intake could prevent gout, however the impact this could have on prevention is unknown. This cohort study of 44,654 men, aimed to estimate the proportion of gout cases that could be prevented through the modification of risk factors. The results showed that the most important risk factor for gout was body mass index (BMI) and modifying other risk factors did not prevent gout. 77% of gout cases could be prevented if all men had been of normal weight, had no alcohol intake, if they adhered to a diet known as the Dietary Approaches to Stop Hypertension (DASH) diet and if they didn't take drugs to increase urine output. It was concluded that weight loss in men determines their ability to prevent gout, regardless of whether they have modified other contributory factors. This study could be used by healthcare professionals to understand that unless weight loss is achieved in individuals who are overweight and have gout, then other interventions may have minimal impact. Recommending the DASH diet to achieve weight loss, may be more successful in the long-term management of gout.
Abstract
Importance: The population impact of modifying obesity and other key risk factors for hyperuricemia has been estimated in cross-sectional studies; however, the proportion of incident gout cases (a clinical end point) that could be prevented by modifying such factors has not been evaluated. Objective: To estimate the proportion of incident gout cases that could be avoided through simultaneous modification of obesity and other key risk factors. Design, Setting, and Participants: The Health Professionals Follow-up Study is a US prospective cohort study of 51 529 male health professionals enrolled in 1986 and followed up through questionnaires every 2 years through 2012. Self-reported gout cases were confirmed through June 2015. Clean and complete data used for this analysis were available in June 2016, with statistical analyses performed from July 2016 to July 2019. Exposures: From data collected in the validated questionnaires, men were categorized to low-risk groups according to combinations of the following 4 factors: normal body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]; <25), no alcohol intake, adherence to Dietary Approaches to Stop Hypertension (DASH)-style diet (highest quintile of DASH diet score), and no diuretic use. Main Outcomes and Measures: Population attributable risks (PARs) for incident gout meeting the preliminary American College of Rheumatology survey criteria, overall and stratified by BMI. Results: We analyzed 44 654 men (mean [SD] age, 54.0 [9.8] years) with no history of gout at baseline. During 26 years of follow-up, 1741 (3.9%) developed incident gout. Among all participants, PAR for the 4 risk factors combined (BMI, diet, alcohol use, and diuretic use) was 77% (95% CI, 56%-88%). Among men with normal weight (BMI <25.0) and overweight (BMI 25.0-29.9), we estimated that more than half of incident gout cases (69% [95% CI, 42%-83%] and 59% [95% CI, 30%-75%], respectively) may have been prevented by the combination of DASH-style diet, no alcohol intake, and no diuretic use. However, among men with obesity (BMI ≥30), PAR was substantially lower and not significant (5% [95% CI, 0%-47%]). Conclusions and Relevance: The findings of this cohort study suggest that addressing excess adiposity and other key modifiable factors has the potential to prevent the majority of incident gout cases among men. Men with obesity may not benefit from other modifications unless weight loss is addressed.
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The consequences of exercise-induced weight loss on food reinforcement. A randomized controlled trial.
Flack, KD, Hays, HM, Moreland, J
PloS one. 2020;15(6):e0234692
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Exercise is a long-standing remedy for nearly all of obesity’s comorbidities and often recommended as an economical and health-promoting option for weight loss and weight loss maintenance. The aim of this study was to investigate the effect of exercise on food reinforcement (reward-driven feeding), and to examine whether changes in body composition would be correlated with changes in food reinforcement. This study is randomized controlled trial with a total of 52 participants aged 18 to 40 years. Participants were randomly assigned to one of the three groups (six exercise sessions per week, two sessions per week, and sedentary control). Results indicate that there is great variability in individuals’ change in food reinforcement after a 12-week aerobic exercise intervention. Furthermore, those who did increase their food reinforcement were also those who lost the greatest amount of fat-free mass post-intervention. Authors conclude that preventing the loss of fat-free mass may be a valuable piece to a weight loss programme (with resistance training or dietary protein intake as adjunct therapy).
Abstract
BACKGROUND Obesity remains a primary threat to the health of most Americans, with over 66% considered overweight or obese with a body mass index (BMI) of 25 kg/m2 or greater. A common treatment option many believe to be effective, and therefore turn to, is exercise. However, the amount of weight loss from exercise training is often disappointingly less than expected with greater amounts of exercise not always promoting greater weight loss. Increases in energy intake have been prescribed as the primary reason for this lack of weight loss success with exercise. Research has mostly focused on alterations in hormonal mediators of appetite (e.g.: ghrelin, peptide YY, GLP-1, pancreatic polypeptide, and leptin) that may increase hunger and/or reduce satiety to promote greater energy intake with exercise training. A less understood mechanism that may be working to increase energy intake with exercise is reward-driven feeding, a strong predictor of energy intake and weight status but rarely analyzed in the context of exercise. DESIGN Sedentary men and women (BMI: 25-35 kg/m2, N = 52) were randomized into parallel aerobic exercise training groups partaking in either two or six exercise sessions/week, or sedentary control for 12 weeks. METHODS The reinforcing value of food was measured by an operant responding progressive ratio schedule task (the behavioral choice task) to determine how much work participants were willing to perform for access to a healthy food option relative to a less healthy food option before and after the exercise intervention. Body composition and resting energy expenditure were assessed via DXA and indirect calorimetry, respectively, at baseline and post testing. RESULTS Changes in fat-free mass predicted the change in total amount of operant responding for food (healthy and unhealthy). There were no correlations between changes in the reinforcing value of one type of food (healthy vs unhealthy) to changes in body composition. CONCLUSION In support of previous work, reductions in fat-free mass resulting from an aerobic exercise intervention aimed at weight loss plays an important role in energy balance regulation by increasing operant responding for food.
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Effects of COVID-19 Lockdown on Lifestyle Behaviors in Children with Obesity Living in Verona, Italy: A Longitudinal Study.
Pietrobelli, A, Pecoraro, L, Ferruzzi, A, Heo, M, Faith, M, Zoller, T, Antoniazzi, F, Piacentini, G, Fearnbach, SN, Heymsfield, SB
Obesity (Silver Spring, Md.). 2020;28(8):1382-1385
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The coronavirus disease 2019 (COVID-19) pandemic has had far reaching health, social, and economic implications. Among them is the abrupt cessation of school programs for children and adolescents in Italy. The aim of this study was to test the hypothesis that factors contributing to weight gain among children and adolescents with overweight and obesity are exacerbated during a pandemic-associated lockdown. This study is a longitudinal clinical trial which enrolled non-adult participants (n=41) with obesity as controls in the ongoing longitudinal observational OBELIX Study in Verona, Italy. Results indicate that eating, activity, and sleeping behaviours changed in an unfavourable direction just after three weeks into their confinement during the national lockdown. Thus, findings support the hypothesis that lockdown appears to create an unfavourable environment for maintaining healthy lifestyle behaviours Authors conclude that recognition of the lockdown phenomenon is the first step in taking preventive measures.
Abstract
OBJECTIVE The aim of this study was to test the hypothesis that youths with obesity, when removed from structured school activities and confined to their homes during the coronavirus disease 2019 pandemic, will display unfavorable trends in lifestyle behaviors. METHODS The sample included 41 children and adolescents with obesity participating in a longitudinal observational study located in Verona, Italy. Lifestyle information including diet, activity, and sleep behaviors was collected at baseline and 3 weeks into the national lockdown during which home confinement was mandatory. Changes in outcomes over the two study time points were evaluated for significance using paired t tests. RESULTS There were no changes in reported vegetable intake; fruit intake increased (P = 0.055) during the lockdown. By contrast, potato chip, red meat, and sugary drink intakes increased significantly during the lockdown (P value range, 0.005 to < 0.001). Time spent in sports activities decreased by 2.30 (SD 4.60) h/wk (P = 0.003), and sleep time increased by 0.65 (SD 1.29) h/d (P = 0.003). Screen time increased by 4.85 (SD 2.40) h/d (P < 0.001). CONCLUSIONS Recognizing these adverse collateral effects of the coronavirus disease 2019 pandemic lockdown is critical in avoiding depreciation of weight control efforts among youths afflicted with excess adiposity. Depending on duration, these untoward lockdown effects may have a lasting impact on a child's or adolescent's adult adiposity level.
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Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease.
Smith, GI, Shankaran, M, Yoshino, M, Schweitzer, GG, Chondronikola, M, Beals, JW, Okunade, AL, Patterson, BW, Nyangau, E, Field, T, et al
The Journal of clinical investigation. 2020;130(3):1453-1460
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Non-alcoholic fatty liver disease (NAFLD) is a common complication of obesity and is associated with multiorgan insulin resistance, dyslipidaemia and an increased risk of diabetes and coronary heart disease. The aims of this study were to (a) determine hepatic de novo lipogenesis (DNL) [the liver’s biochemical process of synthesising fatty acids] in 3 distinct cohorts, (b) determine the relationships among hepatic DNL and intrahepatic [within the liver] triglyceride (IHTG) content, and (c) determine the effect of moderate (10%) weight loss. This study is a cross-sectional study which included a total of 67 men and women (mean age: 39 ± 1 years; 14 men and 53 women). Results highlight the importance of DNL in the pathogenesis of hepatic steatosis [build up of fats in the liver] and suggest that increases in daily 24-hour plasma glucose and insulin concentrations are major drivers of increased DNL in individuals with obesity and NAFLD. Additionally, moderate (10%) weight loss caused a marked decrease in both hepatic DNL and IHTG content. Authors conclude that increases in circulating glucose and insulin promote hepatic DNL in individuals with NAFLD. Whereas an improvement in insulin sensitivity and a decrease in hepatic DNL, are potentially important contributors to the decline in IHTG content associated with moderate weight loss.
Abstract
BACKGROUNDAn increase in intrahepatic triglyceride (IHTG) is the hallmark feature of nonalcoholic fatty liver disease (NAFLD) and is decreased by weight loss. Hepatic de novo lipogenesis (DNL) contributes to steatosis in individuals with NAFLD. The physiological factors that stimulate hepatic DNL and the effect of weight loss on hepatic DNL are not clear.METHODSHepatic DNL, 24-hour integrated plasma insulin and glucose concentrations, and both liver and whole-body insulin sensitivity were determined in individuals who were lean (n = 14), obese with normal IHTG content (n = 26), or obese with NAFLD (n = 27). Hepatic DNL was assessed using the deuterated water method corrected for the potential confounding contribution of adipose tissue DNL. Liver and whole-body insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp procedure in conjunction with glucose tracer infusion. Six subjects in the obese-NAFLD group were also evaluated before and after a diet-induced weight loss of 10%.RESULTSThe contribution of hepatic DNL to IHTG-palmitate was 11%, 19%, and 38% in the lean, obese, and obese-NAFLD groups, respectively. Hepatic DNL was inversely correlated with hepatic and whole-body insulin sensitivity, but directly correlated with 24-hour plasma glucose and insulin concentrations. Weight loss decreased IHTG content, in conjunction with a decrease in hepatic DNL and 24-hour plasma glucose and insulin concentrations.CONCLUSIONSThese data suggest hepatic DNL is an important regulator of IHTG content and that increases in circulating glucose and insulin stimulate hepatic DNL in individuals with NAFLD. Weight loss decreased IHTG content, at least in part, by decreasing hepatic DNL.TRIAL REGISTRATIONClinicalTrials.gov NCT02706262.FUNDINGThis study was supported by NIH grants DK56341 (Nutrition Obesity Research Center), DK20579 (Diabetes Research Center), DK52574 (Digestive Disease Research Center), and RR024992 (Clinical and Translational Science Award), and by grants from the Academy of Nutrition and Dietetics Foundation, the College of Natural Resources of UCB, and the Pershing Square Foundation.
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The Risks of Cardiovascular Disease and Mortality Following Weight Change in Adults with Diabetes: Results from ADVANCE.
Lee, AK, Woodward, M, Wang, D, Ohkuma, T, Warren, B, Sharrett, AR, Williams, B, Marre, M, Hamet, P, Harrap, S, et al
The Journal of clinical endocrinology and metabolism. 2020;105(1)
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Type 2 diabetes is characterized by metabolic dysregulation resulting in an increased risk of cardiovascular disease The objectives of this study were: a. to determine whether weight change over 2 years was associated with subsequent cardiovascular outcomes and death in adults with diabetes, and b. to examine whether this association was modified by baseline body mass index (BMI), age, or type of glucose-lowering medications. This study is a large prospective study of adults with type 2 diabetes. One arm tested the effects of intensive glucose lowering versus standard glucose control. Whereas the second arm tested the effects of blood pressure-lowering medication versus a placebo. Results showed that that >10% weight loss was associated with >2 times higher risk of cardiovascular and all-cause mortality and was associated with 75% greater risk of major macrovascular events, compared with adults with stable weight. These associations were not significantly modified by metformin use, age, or baseline BMI. Authors conclude that unless patients specifically report lifestyle changes to lose weight, even modest weight loss may be a marker of declining health for which further clinical investigation is merited.
Abstract
CONTEXT Weight loss is strongly recommended for overweight and obese adults with type 2 diabetes. Unintentional weight loss is associated with increased risk of all-cause mortality, but few studies have examined its association with cardiovascular outcomes in patients with diabetes. OBJECTIVE To evaluate 2-year weight change and subsequent risk of cardiovascular events and mortality in established type 2 diabetes. DESIGN AND SETTING The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation was an international, multisite 2×2 factorial trial of intensive glucose control and blood pressure control. We examined 5 categories of 2-year weight change: >10% loss, 4% to 10% loss, stable (±<4%), 4% to 10% gain, and >10% gain. We used Cox regression with follow-up time starting at 2 years, adjusting for intervention arm, demographics, cardiovascular risk factors, and diabetes medication use from the 2-year visit. RESULTS Among 10 081 participants with valid weight measurements, average age was 66 years. By the 2-year examination, 4.3% had >10% weight loss, 18.4% had 4% to 10% weight loss, and 5.3% had >10% weight gain. Over the following 3 years of the trial, >10% weight loss was strongly associated with major macrovascular events (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.26-2.44), cardiovascular mortality (HR, 2.76; 95% CI, 1.87-4.09), all-cause mortality (HR, 2.79; 95% CI, 2.10-3.71), but not major microvascular events (HR, 0.91; 95% CI, 0.61-1.36), compared with stable weight. There was no evidence of effect modification by baseline body mass index, age, or type of diabetes medication. CONCLUSIONS In the absence of substantial lifestyle changes, weight loss may be a warning sign of poor health meriting further workup in patients with type 2 diabetes.