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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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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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A Randomized Placebo-Controlled Trial of Low- Versus Moderate-Dose Vitamin D3 Supplementation on Bone Mineral Density in Postmenopausal Women With HIV.
Yin, MT, RoyChoudhury, A, Bucovsky, M, Colon, I, Ferris, DC, Olender, S, Agarwal, S, Sharma, A, Zeana, C, Zingman, B, et al
Journal of acquired immune deficiency syndromes (1999). 2019;80(3):342-349
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Prevalence of fracture is 2 to 3-fold higher in women with HIV over age 50 than in the general population. The aim of this study was to compare the effects of two doses of vitamin D3 repletion (3000 IU Vs 1000 IU) on bone turnover and change in bone mass and microarchitecture in postmenopausal women with HIV. The study is a randomised placebo-controlled study which recruited women with HIV aged between 40 and 70 years. The participants were randomised to 3000 vs 1000 IU vitamin D3 daily together with 500mg calcium carbonate twice daily. Results indicate that moderate dose vitamin D3 (3000 IU) supplementation in minority postmenopausal women with HIV on established antiretroviral therapy (treatment for HIV) did not appear to have a greater impact on bone mineral density or bone turnover than low dose vitamin D3 supplementation (1000 IU). Authors conclude that further studies are required to determine whether vitamin D3 supplementation is beneficial in this patient population, and if so, what dose provides the maximum benefit in terms of musculoskeletal health in persons aging with HIV.
Abstract
BACKGROUND Prevalence of osteoporosis and fracture is increased among older people with HIV. We compared the effects of low (1000 IU) vs moderate (3000 IU) vitamin D3 (VitD) supplementation on areal bone mineral density (aBMD) and volumetric bone mineral density (vBMD) in African American and Hispanic postmenopausal women with HIV on antiretroviral therapy. METHODS We performed a 12-month prospective, randomized, double-blind, placebo-controlled study with primary outcomes of change in aBMD by dual-energy X-ray absorptiometry (DXA) and secondary outcomes of change in vBMD by quantitative computed tomography and bone turnover markers. An intent-to-treat analysis was performed on 85 randomized subjects (43 low and 42 moderate) for primary DXA outcomes, and complete case analysis was performed for secondary outcomes. RESULTS Mean age was 56 ± 5 years, median CD4 count was 722 cells/mm, and 74% had HIV RNA ≤ 50 copies/mL. Serum 25-OHD was higher in the moderate than low VitD group at 6 months (33.1 ± 10.3 vs 27.8 ± 8.1 ng/mL, P = 0.03) and 12 months, but parathyroid hormone levels remained similar. Percent change in aBMD, vBMD, and bone turnover markers did not differ between low and moderate VitD groups before or after adjustment for baseline aBMD. CONCLUSIONS VitD supplementation at 3000 IU daily increased mean total 25-OHD levels in postmenopausal women with HIV, but we did not find evidence of an effect on BMD beyond those observed with 1000 IU daily. Future studies are necessary to determine whether VitD supplementation is beneficial in this patient population, and if so, what dose is optimal for skeletal health.
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Effective nationwide school-based participatory extramural program on adolescent body mass index, health knowledge and behaviors.
Heo, M, Jimenez, CC, Lim, J, Isasi, CR, Blank, AE, Lounsbury, DW, Fredericks, L, Bouchard, M, Faith, MS, Wylie-Rosett, J
BMC pediatrics. 2018;18(1):7
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Adolescent obesity is a major public health concern that affects health status not only during adolescence but also during adulthood. The aim of this study was to test whether the HealthCorps program would improve weight status represented by body mass index (BMI; kg/m2) z-score and obesity class. A secondary aim was to identify knowledge and health behaviour domains that would be increased with the program. The study design was a two parallel arm quasi-experimental pre-post comparison design. A total of 2279 students from 62 schools participated in the HealthCorps program. Results indicate that HealthCorps program participation resulted in BMI z-score improvement among overweight/obese female students. Participation also resulted in increased knowledge in most domains regardless of sex and improved a few behaviour domains. However, it did not improve weight status among male students. Authors conclude that the HealthCorps was effective for BMI z-score improvements among female students in addition to significant positive effects on knowledge and a few behaviors in both sexes.
Abstract
BACKGROUND Adolescent obesity is a major public health concern. Open to all high school students regardless of weight status, HealthCorps is a nationwide program offering a comprehensive high school-based participatory educational program to indirectly address obesity. We tested a hypothesis that the HealthCorps program would decrease BMI z-scores among overweight or obese students, and reduce obesity rates, and evaluated its effects on health knowledge and behaviors. METHODS HealthCorps aimed to improve student knowledge and behaviors regarding nutrition quality, physical activity, sleep, breakfast intake, and mental resilience. Participating students received through HealthCorps coordinators weekly or bi-weekly classroom lessons either for a semester or a year in addition to various during- and after-school health-promoting activities and mentorship. Self-reported height and weight were collected along with questionnaires assessing knowledge and behaviors during 2013-2014 academic year among 14 HealthCorps-participating New York City high schools. This quasi experimental two-arm pre-post trial included 611 HealthCorps and 221 comparison arm students for the analytic sample. Sex-specific analyses stratified by weight status were adjusted for age and Hispanic ethnicity with clustering effects of schools and students taken into account. RESULTS HealthCorps female overweight/obese and obese student had a significant decrease in BMI z-scores (post-pre delta BMI z-score = -0.16 (95%CI = (-0.26, -0.05), p = 0.004 for the former; and = -0.23 (-0.44, -0.03), p = 0.028, for the latter) whereas comparison female counterparts did not. The HealthCorps students, but not the comparison students, had a significant increase for all knowledge domains except for the breakfast realm, and reported a greater number of significant behavior changes including fruit and vegetable intake and physical activities. CONCLUSIONS The HealthCorps program was associated with reduced BMI z-score in overweight/obese and obese female adolescents, with enhanced health knowledge and behavior for both sexes. With its wide reach, this may be a promising program to help combat adolescent obesity in schools. TRIAL REGISTRATION This study is registered as a clinical trial at the ClinicalTrials.gov registry with trial number NCT02277496 on September 10, 2014 (Retrospectively registered).
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Inflammation and glucose homeostasis are associated with specific structural features among adults without knee osteoarthritis: a cross-sectional study from the osteoarthritis initiative.
Stout, AC, Barbe, MF, Eaton, CB, Amin, M, Al-Eid, F, Price, LL, Lu, B, Lo, GH, Zhang, M, Pang, J, et al
BMC musculoskeletal disorders. 2018;19(1):1
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Individuals with osteoarthritis (OA) typically present with greater systemic inflammation and impaired glucose homeostasis. Currently it is unclear whether these factors are associated with early-stage OA, namely bone marrow lesions and swelling. The purpose of this cross-sectional study was to investigate the role of inflammation and glucose homeostasis in early-stage OA. Using baseline data from the Osteoarthritis Initiative, 343 participants were enrolled and tested for markers of inflammation and impaired glucose homeostasis. Bone marrow lesions and swelling were also assessed through imaging results. Results indicate that among individuals without OA, those with greater systemic inflammation were more likely to have bone marrow lesions and knee swelling. According to these results, the authors conclude that systemic inflammation and glucose homeostasis are related to structural features of osteoarthritis. Future studies should explore whether these factors are predictive of OA in order to identify therapeutic targets to prevent or delay the onset of knee OA.
Abstract
BACKGROUND Greater age and body mass index are strong risk factors for osteoarthritis (OA). Older and overweight individuals may be more susceptible to OA because these factors alter tissue turnover in menisci, articular cartilage, and bone via altered glucose homeostasis and inflammation. Understanding the role of inflammation and glucose homeostasis on structural features of early-stage OA may help identify therapeutic targets to delay or prevent the onset of OA among subsets of adults with these features. We examined if serum concentrations of glucose homeostasis (glucose, glycated serum protein [GSP]) or inflammation (C-reactive protein [CRP]) were associated with prevalent knee bone marrow lesions (BMLs) or effusion among adults without knee OA. METHODS We conducted a cross-sectional study using baseline data from the Osteoarthritis Initiative. We selected participants who had no radiographic knee OA but were at high risk for knee OA. Blinded staff conducted assays for CRP, GSP, and glucose. Readers segmented BML volume and effusion using semi-automated programs. Our outcomes were prevalent BML (knee with a BML volume > 1 cm3) and effusion (knee with an effusion volume > 7.5 cm3). We used logistic regression models with CRP, GSP, or glucose concentrations as the predictors. We adjusted for age, sex, body mass index (BMI), and Physical Activity Scale for the Elderly (PASE) scores. RESULTS We included 343 participants: mean age = 59 ± 9 years, BMI = 27.9 ± 4.5 kg/m2, PASE score = 171 ± 82, and 64% female. Only CRP was associated with BML prevalence (odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.09 to 1.87). For effusion, we found an interaction between BMI and CRP: only among adults with a BMI <25 kg/m2 was there a significant trend towards a positive association between CRP and effusion (OR = 1.40, 95% CI = 1.00 to 1.97). We detected a U-shaped relationship between GSP and effusion prevalence. Fasting glucose levels were not significantly associated with the presence of baseline effusion or BML. CONCLUSIONS Among individuals without knee OA, CRP may be related to the presence of BMLs and effusion among normal weight individuals. Abnormal GSP may be associated with effusion. Future studies should explore whether inflammation and glucose homeostasis are predictive of symptomatic knee OA.
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A whole-grain diet reduces peripheral insulin resistance and improves glucose kinetics in obese adults: A randomized-controlled trial.
Malin, SK, Kullman, EL, Scelsi, AR, Haus, JM, Filion, J, Pagadala, MR, Godin, JP, Kochhar, S, Ross, AB, Kirwan, JP
Metabolism: clinical and experimental. 2018;82:111-117
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Literature shows that dietary whole-grain intake is associated with a lower incidence of type 2 diabetes. The aim of the study was to investigate the association between a whole-grain diet and insulin resistance and glucose use in individuals at risk for type 2 diabetes. The study was a randomized, double-blind, controlled crossover trial involving fourteen middle-aged, obese adults at risk for diabetes. Randomisation was carried out prior to metabolic testing. Results indicate that whole-grain intake as part of a mixed-meal diet significantly improved post-prandial (after a meal) glucose metabolism in middle-aged obese adults. Furthermore, both whole-grain and refined-grain interventions induced about 3–6% weight and fat loss. Authors conclude that whole-grain intake effectively promotes glycaemic control by improving insulin action.
Abstract
BACKGROUND Whole-grain intake is associated with lower risk of type 2 diabetes but the mechanisms are unclear. PURPOSE We tested the hypothesis that a WG diet reduces insulin resistance and improves glucose use in individuals at risk for type 2 diabetes compared with an isocaloric-matched refined-grain diet. METHODS A double-blind, randomized, controlled, crossover trial of 14 moderately obese adults (Age, 38 ± 2 y; BMI, 34.0 ± 1.1 kg/m2). Insulin resistance and glucose metabolism was assessed using an oral glucose tolerance test combined with isotopic tracers of [6,6-2H2]-glucose and [U-13C]-glucose, and indirect calorimetry. Peripheral and hepatic insulin resistance was assessed as 1/(rate of disposal/insulin), and endogenous glucose rates of appearance (Ra) iAUC60-240 × insulin iAUC60-240, respectively. Both diets met ADA nutritional guidelines and contained either whole-grain (50 g per 1000 kcal) or equivalent refined-grain. All food was provided for 8 wk. with an 8-10 wk. washout period between diets. RESULTS Post-prandial glucose tolerance, peripheral insulin sensitivity, and metabolic flexibility (insulin-stimulated - fasting carbohydrate oxidation) improvements were greater after whole-grain compared to the refined-grain diet (P < 0.05). Compared to baseline, body fat (~2 kg) and hepatic Ra insulin resistance was reduced by both diets, while fasting glucose and exogenous glucose-meal were unchanged after both interventions. Changes in peripheral insulin resistance and metabolic flexibility correlated with improved glucose tolerance (P < 0.05). CONCLUSION Whole-grains reduced diabetes risk and the mechanisms appear to work through reduced post-prandial blood glucose and peripheral insulin resistance that were statistically linked to enhanced metabolic flexibility.
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Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: a 2-y randomized controlled trial of calorie restriction in nonobese humans.
Das, SK, Roberts, SB, Bhapkar, MV, Villareal, DT, Fontana, L, Martin, CK, Racette, SB, Fuss, PJ, Kraus, WE, Wong, WW, et al
The American journal of clinical nutrition. 2017;105(4):913-927
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Aging is associated with a decline in both the quantity and quality of fat-free mass (FFM) in parallel with increases in body weight and adiposity. Calorie restriction (CR) is the only dietary intervention that has shown promise regarding a reduction in the rate of biological aging in many nonhuman species. The aim of this study was to examine differential effects of CR on men and women and in normal-weight compared with overweight individuals. CALERIE-2 was a 2-year, multicentre, parallel-group, randomised controlled trial. The participants were randomly assigned to one of the two groups; CR group or the ad libitum control. Results show that at the end of the 2-year CR period, - body composition was relatively higher in FFM and lower in fat mass (FM) [72% FFM, 28% FM] compared with baseline [67% FFM, 33% FM]. - large improvements were observed in indexes of central adiposity, including smaller waist circumference and reductions in percentage of trunk fat in this nonobese population. Authors conclude that body composition is not adversely affected by CR in the absence of prescribed exercise. In fact, maintaining a sustained level of physical activity during CR may be required to help preserve body-composition profiles commensurate with healthy aging.
Abstract
Background: Calorie restriction (CR) retards aging and increases longevity in many animal models. However, it is unclear whether CR can be implemented in humans without adverse effects on body composition.Objective: We evaluated the effect of a 2-y CR regimen on body composition including the influence of sex and body mass index (BMI; in kg/m2) among participants enrolled in CALERIE-2 (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), a multicenter, randomized controlled trial.Design: Participants were 218 nonobese (BMI: 21.9-28.0) adults aged 21-51 y who were randomly assigned to 25% CR (CR, n = 143) or ad libitum control (AL, n = 75) in a 2:1 ratio. Measures at baseline and 12 and 24 mo included body weight, waist circumference, fat mass (FM), fat-free mass (FFM), and appendicular mass by dual-energy X-ray absorptiometry; activity-related energy expenditure (AREE) by doubly labeled water; and dietary protein intake by self-report. Values are expressed as means ± SDs.Results: The CR group achieved 11.9% ± 0.7% CR over 2-y and had significant decreases in weight (-7.6 ± 0.3 compared with 0.4 ± 0.5 kg), waist circumference (-6.2 ± 0.4 compared with 0.9 ± 0.5 cm), FM (-5.4 ± 0.3 compared with 0.5 ± 0.4 kg), and FFM (-2.0 ± 0.2 compared with -0.0 ± 0.2 kg) at 24 mo relative to the AL group (all between-group P < 0.001). Moreover, FFM as a percentage of body weight at 24 mo was higher, and percentage of FM was lower in the CR group than in the AL. AREE, but not protein intake, predicted preservation of FFM during CR (P < 0.01). Men in the CR group lost significantly more trunk fat (P = 0.03) and FFM expressed as a percentage of weight loss (P < 0.001) than women in the CR group.Conclusions: Two years of CR had broadly favorable effects on both whole-body and regional adiposity that could facilitate health span in humans. The decrements in FFM were commensurate with the reduced body mass; although men in the CR group lost more FFM than the women did, the percentage of FFM in the men in the CR group was higher than at baseline. CALERIE was registered at clinicaltrials.gov as NCT00427193.
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In a randomized trial in prostate cancer patients, dietary protein restriction modifies markers of leptin and insulin signaling in plasma extracellular vesicles.
Eitan, E, Tosti, V, Suire, CN, Cava, E, Berkowitz, S, Bertozzi, B, Raefsky, SM, Veronese, N, Spangler, R, Spelta, F, et al
Aging cell. 2017;16(6):1430-1433
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Obesity and insulin resistance are associated with accelerated aging and increased risk of many age-related diseases. The risk of many cancers, including prostate cancer, increases with age and being overweight further increases the risk. The aim of the study is to investigate the inhibition of tumour growth through the effect of protein restriction diets and hence, levels of circulating amino acids. The participants of the study were men (n=38) with prostate cancer awaiting prostatectomy surgery. Most of the subjects were overweight with a BMI of 30.45 ± 5.8. They were randomly assigned to either a control diet or a protein restricted diet. In comparison to the control diet, results show that protein restriction increased the levels of receptors (a protein molecule that receives chemical signals from outside a cell) responsible of leptin, the hormone that controls hunger. The results also show that protein restriction can improve the body’s sensitivity to the effects of the insulin in neurons (a nerve cell specialised to transmit information throughout the body). Authors conclude that protein restriction can counteract major age-related diseases.
Abstract
Obesity, metabolic syndrome, and hyperleptinemia are associated with aging and age-associated diseases including prostate cancer. One experimental approach to inhibit tumor growth is to reduce dietary protein intake and hence levels of circulating amino acids. Dietary protein restriction (PR) increases insulin sensitivity and suppresses prostate cancer cell tumor growth in animal models, providing a rationale for clinical trials. We sought to demonstrate that biomarkers derived from plasma extracellular vesicles (EVs) reflect systemic leptin and insulin signaling and respond to dietary interventions. We studied plasma samples from men with prostate cancer awaiting prostatectomy who participated in a randomized trial of one month of PR or control diet. We found increased levels of leptin receptor in the PR group in total plasma EVs and in a subpopulation of plasma EVs expressing the neuronal marker L1CAM. Protein restriction also shifted the phosphorylation status of the insulin receptor signal transducer protein IRS1 in L1CAM+ EVs in a manner suggestive of improved insulin sensitivity. Dietary PR modifies indicators of leptin and insulin signaling in circulating EVs. These findings are consistent with improved insulin and leptin sensitivity in response to PR and open a new window for following physiologic responses to dietary interventions in humans.