Weight strategy in older adults with obesity: calorie restriction or not?

PURPOSE OF REVIEW: Along with the marked increase in the population of older adults with obesity is the need for effective strategies to treat aging- and obesity-related complications. This review highlights recent progress in obesity management in older adults. RECENT FINDINGS: Although calorie restriction is needed to significantly reduce fat mass, an exercise protocol is crucial to ameliorate functional outcomes. The addition of a resistance exercise protocol improves the response of muscle protein synthesis to anabolic stimuli, preventing the calorie restriction-induced reduction in muscle and bone mass. The addition of an aerobic exercise protocol improves cardiorespiratory fitness and cognitive function. However, the addition of both aerobic and resistance exercise protocols to calorie restriction provides the greatest improvements in myocellular quality, frailty, and cardiometabolic and cognitive outcomes, translating into the greatest improvement in quality of life. Such comprehensive lifestyle intervention effectively improves glucometabolic control and age-relevant outcomes in older adults with diabetes. When combined with testosterone therapy, such lifestyle intervention also preserves muscle and bone mass in older, men with obesity and hypogonadism. SUMMARY: We conclude that calorie restriction among older adults with obesity should be prescribed in combination with both aerobic and resistance exercise to maximize benefits on overall health.

Depressive Symptoms are Associated With C-Reactive Protein in Older Adults With Obesity.

OBJECTIVES: To test the hypothesis that depressive symptoms vary with high-sensitivity C-reactive protein (hs-CRP), among older adults with obesity. METHODS: This was a cross-sectional, secondary analysis of baseline data from two related lifestyle intervention trials. The study sample comprises 148 consecutively recruited, community-dwelling older adults (age >=65 years) without severe psychiatric illness and with body mass index >=30 kg/m2. Logarithmically transformed GDS was analyzed as the dependent variable. Independent variables included log-transformed hs-CRP and covariates: sex, age, and concurrent use of antidepressant medication at baseline. An additional analysis was performed using binary conversion of the GDS scores, wherein a cutoff score of 5 was considered positive for depressive symptoms. RESULTS: Sample mean GDS score was 2.7 (SD 3.0, range 0 - 14). A significant multivariate model of GDS scores (R2 = .089, F = 3.5, P = .010) revealed log-transformed hs-CRP (P = .017) and male sex (P = .012) as associated with depressive symptoms. Supplemental analysis demonstrated associations between depressive symptoms and log-transformed hs-CRP (OR 2.17, P = .001) and between depressive symptoms and male sex (OR 3.78, P = .013). Univariate logistic regression found hs-CRP to be associated with depressive symptoms. CONCLUSIONS: In older adults with obese BMI, male sex and higher hs-CRP are associated with depression, even in a group with relatively minimal depressive symptoms. Hs-CRP may offer clinical utility as a biomarker for depression among older adults with obese BMI, even among those with non-severe psychiatric symptomatology.

One-Year Mean A1c of > 7% is Associated with Poor Bone Microarchitecture and Strength in Men with Type 2 Diabetes Mellitus.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is associated with normal or slightly elevated bone mineral density (BMD) but paradoxically increased fracture risk. Although multiple mechanisms have been proposed to explain this observation, one thing is clear from prior studies, T2DM is associated with poor bone quality rather than a defect in bone quantity. The objective of our study is to evaluate the effect of longitudinal glycemic control on bone quality and bone turnover in men with T2DM. METHODS: This was a secondary analysis of baseline data from 169 male participants, aged 35-65 in 3 clinical trials. Participants were grouped according to the average of all their A1C measurements between 9 and 15 months prior to study entry (group 1: no T2DM, group 2: T2DM with A1C ≤ 7%, group 3: T2DM with A1C > 7%). At study entry serum osteocalcin and C-terminal telopeptide of type 1 collagen (CTx) were measured by ELISA, and testosterone and estradiol by liquid-chromatography/mass-spectrometry. Areal BMD, trabecular bone score and body composition were measured by dual-energy X-ray absorptiometry while volumetric BMD, bone microarchitecture, and bone strength were assessed by high-resolution peripheral quantitative computed tomography. RESULTS: At the tibia, trabecular separation was higher and trabecular number was significantly lower in group 3 compared to both groups 2 and 1, even after adjustments for covariates (p = 0.02 for both). Bone strength indices at the tibia such as stiffness and failure load were lowest in group 3, the difference being significant when compared to group 1 (p = 0.01, p = 0.009 respectively) but not to group 2, after adjustments for covariates. Bone turnover markers (osteocalcin and CTx) were significantly lower in group 3 relative to group 1, with CTx also being significantly lower in group 3 compared with group 2 (p < 0.001, p = 0.001 respectively). CONCLUSION: Poor glycemic control over the course of a year in men with T2DM is associated with poorer bone microarchitecture and strength, and reduced bone turnover. Conversely, good glycemic control in the setting of T2DM appears to attenuate this observed impairment in bone quality.

Aerobic or Resistance Exercise, or Both, in Dieting Obese Older Adults.

BACKGROUND: Obesity causes frailty in older adults; however, weight loss might accelerate age-related loss of muscle and bone mass and resultant sarcopenia and osteopenia. METHODS: In this clinical trial involving 160 obese older adults, we evaluated the effectiveness of several exercise modes in reversing frailty and preventing reduction in muscle and bone mass induced by weight loss. Participants were randomly assigned to a weight-management program plus one of three exercise programs - aerobic training, resistance training, or combined aerobic and resistance training - or to a control group (no weight-management or exercise program). The primary outcome was the change in Physical Performance Test score from baseline to 6 months (scores range from 0 to 36 points; higher scores indicate better performance). Secondary outcomes included changes in other frailty measures, body composition, bone mineral density, and physical functions. RESULTS: A total of 141 participants completed the study. The Physical Performance Test score increased more in the combination group than in the aerobic and resistance groups (27.9 to 33.4 points [21% increase] vs. 29.3 to 33.2 points [14% increase] and 28.8 to 32.7 points [14% increase], respectively; P=0.01 and P=0.02 after Bonferroni correction); the scores increased more in all exercise groups than in the control group (P<0.001 for between-group comparisons). Peak oxygen consumption (milliliters per kilogram of body weight per minute) increased more in the combination and aerobic groups (17.2 to 20.3 [17% increase] and 17.6 to 20.9 [18% increase], respectively) than in the resistance group (17.0 to 18.3 [8% increase]) (P<0.001 for both comparisons). Strength increased more in the combination and resistance groups (272 to 320 kg [18% increase] and 288 to 337 kg [19% increase], respectively) than in the aerobic group (265 to 270 kg [4% increase]) (P<0.001 for both comparisons). Body weight decreased by 9% in all exercise groups but did not change significantly in the control group. Lean mass decreased less in the combination and resistance groups than in the aerobic group (56.5 to 54.8 kg [3% decrease] and 58.1 to 57.1 kg [2% decrease], respectively, vs. 55.0 to 52.3 kg [5% decrease]), as did bone mineral density at the total hip (grams per square centimeter; 1.010 to 0.996 [1% decrease] and 1.047 to 1.041 [0.5% decrease], respectively, vs. 1.018 to 0.991 [3% decrease]) (P<0.05 for all comparisons). Exercise-related adverse events included musculoskeletal injuries. CONCLUSIONS: Of the methods tested, weight loss plus combined aerobic and resistance exercise was the most effective in improving functional status of obese older adults. (Funded by the National Institutes of Health; LITOE ClinicalTrials.gov number, NCT01065636 .).

Sex-specific effects of dehydroepiandrosterone (DHEA) on bone mineral density and body composition: A pooled analysis of four clinical trials.

OBJECTIVE: Studies of dehydroepiandrosterone (DHEA) therapy in older adults suggest sex-specific effects on bone mineral density (BMD) and body composition, but the ability of a single study to reach this conclusion was limited. We evaluated the effects of DHEA on sex hormones, BMD, fat mass and fat-free mass in older women and men enrolled in four similar clinical trials. DESIGN: Pooled analyses of data from four double-blinded, randomized controlled trials. PARTICIPANTS: Women (n = 295) and men (n = 290) aged 55 years or older who took DHEA or placebo tablet daily for 12 months. MEASUREMENTS: Twelve-month changes in BMD, fat mass, fat-free mass and serum DHEA sulphate (DHEAS), (17)estradiol, testosterone and insulin-like growth factor-1 (IGF-1). RESULTS: Women on DHEA had increases (mean ± SD; all P < 0.001 vs placebo) in DHEAS (231 ± 164 µg/dL), testosterone (18.6 ± 20.9 µg/dL), (17)estradiol (8.7 ± 11.0 pg/mL) and IGF-1 (25.1 ± 52.3 ng/mL), and men had increases in DHEAS (269.0 ± 177 µg/dL; P < 0.01), (17)estradiol (4.8 ± 12.2 pg/m; P < 0.01) and IGF-1 (6.3 ± 41.4 ng/mL; P < 0.05). Women on DHEA had increases in lumbar spine (1.0% ± 3.4%) and trochanter (0.5% ± 3.8%) BMD and maintained total hip BMD (0.0% ± 2.8%); men had no BMD benefit and a decrease in fat mass (-0.4 ± 2.6 kg; all P < 0.01 vs placebo). CONCLUSIONS: Dehydroepiandrosterone therapy may be an effective approach for preserving bone and muscle mass in women. Key questions are (a) the extent to which longer duration DHEA can attenuate the loss of bone and muscle in women, and (b) whether DHEA has a more favourable benefit-to-risk profile for women than oestrogen therapy.

Therapeutic and lifestyle approaches to obesity in older persons.

PURPOSE OF REVIEW: Obesity rates worldwide continue to increase and will disproportionately affect older adults because of population aging. This review highlights recent progress pertaining to therapeutic approaches to obesity in older adults. RECENT FINDINGS: Caloric restriction alone improves physical function and quality of life in older adults with obesity but is associated with loss of lean mass and increases fracture risk. Adding progressive resistance training to caloric restriction attenuates loss of muscle and bone mass and increasing protein intake enhances this effect. Adding aerobic endurance training to caloric restriction further improves cardiorespiratory fitness but adding both aerobic endurance training and resistance training to caloric restriction results in the greatest improvement in overall physical function while still preserving lean mass. Future promising therapeutic interventions include testosterone, myostatin inhibitors, and bariatric surgery, but there are few studies specific to obese older adults. SUMMARY: The optimal approach toward obesity in older persons is lifestyle intervention incorporating caloric restriction and exercise consisting of aerobic endurance training and resistance training. Maintenance of adequate protein intake, calcium, and vitamin D is advisable. There is insufficient evidence specific to obese older adults to recommend testosterone or bariatric surgery at this time. Myostatin inhibitors may become a future treatment, and clinical trials are ongoing.

Hypogonadal Men with Higher Body Mass Index have Higher Bone Density and Better Bone Quality but Reduced Muscle Density.

Although hypogonadism is a risk factor for bone loss and fractures, the different etiopathophysiology and hormonal profile of classical and obesity-induced hypogonadism may lead to differences in musculoskeletal profile. This is a cross-sectional study of hypogonadal men between 40 and 74 years old. Our outcomes include: areal bone mineral density (aBMD) and body composition by dual-energy X-ray absorptiometry; volumetric BMD (vBMD) and soft tissue composition of the tibia by peripheral quantitative computed tomography. Fracture risk assessment tool (FRAX) scores were evaluated. Testosterone, estradiol, luteinizing hormone, follicle stimulating hormone, sex hormone-binding globulin, C-telopeptide, osteocalcin, and sclerostin were measured. We divided the population into subgroups of BMI: group 1: BMI < 30; group 2: BMI ≥30 to <35 and group 3: BMI ≥ 35 kg/m2. One-hundred five men were enrolled. Spine and hip aBMD, and total and trabecular vBMD at the 4% tibia significantly increased with increasing BMI. Cortical thickness (330.7 ± 53.2, 343.3 ± 35.4, and 358.7 ± 38.2 mm, p = 0.04; groups 1, 2 and 3, respectively) and cortical area (5.3 ± 0.7, 5.5 ± 0.6, and 5.7 ± 0.6 mm, p = 0.01; groups 1, 2 and 3, respectively) at 38% tibia increased with increasing BMI. While absolute lean mass increased with increasing BMI, % lean mass and muscle density (70.2 ± 5.0, 71.3 ± 6.4, and 67.1 ± 5.1 mg/cm3; groups 1, 2 and 3, respectively) were lowest in group 3. Although severely obese hypogondal men have better BMD and bone quality, they have reduced muscle density, the significance of which remains to be determined.

The FTO gene is associated with a paradoxically favorable cardiometabolic risk profile in frail, obese older adults.

OBJECTIVE: Fat mass and obesity-associated (FTO) gene polymorphisms have been reported to be associated with differences in BMI, obesity, and type 2 diabetes. However, previous studies have been predominantly conducted in younger individuals across a spectrum of body weights, whereas little information is available on the older population. We examined the association of FTO gene polymorphisms with cardiometabolic risks among adults who were both obese (BMI≥30 kg/m) and older (age≥65 years). METHODS: A total of 165 frail, obese older adults were genotyped for FTO (rs9939609 and rs8050136) single nucleotide polymorphisms and studied for associations with body weight and body composition, components and prevalence of the metabolic syndrome, insulin response to an oral glucose tolerance test, and levels of adipocytokines (e.g. leptin) and vitamin D. RESULTS: Carriers of the A allele (CA/AA) of the FTO single nucleotide polymorphism rs8050136 had lower body weight, BMI, body fat, and trunk fat than those without the A allele (CC genotype; all P's<0.05). Moreover, genotype CA/AA was associated with lower levels of triglycerides and higher levels of high-density lipoprotein-cholesterol and carriers of this genotype showed a trend toward a lower waist circumference, resulting in a lower prevalence of metabolic syndrome than in CC genotype carriers. The insulin area under the curve during the oral glucose tolerance test was lower for genotype CA/AA. Despite the lower insulin levels, the glucose area under the curve was unchanged, resulting in a higher insulin sensitivity index. Leptin levels were also lower and adiponectin and 25-hydroxyvitamin levels tended to be higher for genotype CA/AA than for genotype CC. No differences were observed for rs9939609. CONCLUSION: Unlike the results from studies in younger individuals, the risk A allele may confer a favorable cardiometabolic risk profile in obese older adults, suggesting selective survival of obese adults into old age. If confirmed in a larger sample of surviving obese older adults, these findings may have implications in the clinical approach to obesity in this population.

Weight loss, exercise, or both and physical function in obese older adults.

BACKGROUND: Obesity exacerbates the age-related decline in physical function and causes frailty in older adults; however, the appropriate treatment for obese older adults is controversial. METHODS: In this 1-year, randomized, controlled trial, we evaluated the independent and combined effects of weight loss and exercise in 107 adults who were 65 years of age or older and obese. Participants were randomly assigned to a control group, a weight-management (diet) group, an exercise group, or a weight-management-plus-exercise (diet-exercise) group. The primary outcome was the change in score on the modified Physical Performance Test. Secondary outcomes included other measures of frailty, body composition, bone mineral density, specific physical functions, and quality of life. RESULTS: A total of 93 participants (87%) completed the study. In the intention-to-treat analysis, the score on the Physical Performance Test, in which higher scores indicate better physical status, increased more in the diet-exercise group than in the diet group or the exercise group (increases from baseline of 21% vs. 12% and 15%, respectively); the scores in all three of those groups increased more than the scores in the control group (in which the score increased by 1%) (P<0.001 for the between-group differences). Moreover, the peak oxygen consumption improved more in the diet-exercise group than in the diet group or the exercise group (increases of 17% vs. 10% and 8%, respectively; P<0.001); the score on the Functional Status Questionnaire, in which higher scores indicate better physical function, increased more in the diet-exercise group than in the diet group (increase of 10% vs. 4%, P<0.001). Body weight decreased by 10% in the diet group and by 9% in the diet-exercise group, but did not decrease in the exercise group or the control group (P<0.001). Lean body mass and bone mineral density at the hip decreased less in the diet-exercise group than in the diet group (reductions of 3% and 1%, respectively, in the diet-exercise group vs. reductions of 5% and 3%, respectively, in the diet group; P<0.05 for both comparisons). Strength, balance, and gait improved consistently in the diet-exercise group (P<0.05 for all comparisons). Adverse events included a small number of exercise-associated musculoskeletal injuries. CONCLUSIONS: These findings suggest that a combination of weight loss and exercise provides greater improvement in physical function than either intervention alone. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00146107.).

Metabolic effects of testosterone added to intensive lifestyle intervention in older men with obesity and hypogonadism.

BACKGROUND: Whether testosterone replacement therapy (TRT) conveys additional cardiometabolic benefit to an intensive lifestyle therapy (LT) in older men with obesity and hypogonadism remains unclear. OBJECTIVE: To determine whether TRT augments the effect of LT on metabolic outcomes in older men with obesity and hypogonadism. DESIGN: Secondary analysis of a randomized, double-blind, placebo-controlled trial. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: 83 older (age ≥ 65 years) men with obesity (BMI ≥ 30 kg/m2) and persistently low AM testosterone (< 10.4 nmol/L) associated with frailty. INTERVENTIONS: LT (weight management and exercise training) plus either testosterone (LT+TRT) or placebo (LT+Pbo) for six months. OUTCOME MEASURES: Primary outcome was change in glycated hemoglobin (HbA1c). Secondary outcomes included changes in other glucometabolic and lipid profile components, liver enzymes, inflammatory markers, adipokines; subcutaneous, visceral, intramuscular, and hepatic fat; blood pressure, and metabolic syndrome score. RESULTS: HbA1c decreased similarly in LT+TRT and LT+Pbo groups (-0.5% vs. -0.6%, respectively; p= 0.35). While TRT showed no synergistic effect with LT on ameliorating secondary outcomes, it eliminated the augmentative effect of LT on high-density lipoprotein cholesterol concentration (5.4 ± 1.0 mg/dL in LT+Pbo group vs. 0.2 ± 1.1 mg/dL in LT+TRT group, p= 0.01) and adiponectin levels (-408 ± 489 ng/mL in TRT+LT group vs 1832 ± 468 ng/mL in LT+Pbo group, p= 0.02). CONCLUSION: In older men with obesity and hypogonadism, adding TRT for six months to LT does not result in further improved cardiometabolic profiles, and could potentially blunt some of the metabolic benefits induced by LT.

Targeting Energy Intake and Circadian Biology to Engage Mechanisms of Aging in Older Adults With Obesity: Calorie Restriction and Time-Restricted Eating.

With the rise in obesity across age groups, it has been a hindrance to engaging in physical activity and mobility in older adults. Daily calorie restriction (CR) up to 25% has been the cornerstone of obesity management even though the safety in older adults remains incompletely understood. Although some adults can follow CR with clinically significant weight loss and improved health metrics, CR faces 2 obstacles-many fail to adopt CR and even among those who can adopt it short term, long-term compliance can be difficult. Furthermore, there is a continuing debate about the net benefits of CR-induced weight loss in older adults because of the concern that CR may worsen sarcopenia, osteopenia, and frailty. The science of circadian rhythm and its plasticity toward the timing of nutrition offer promise to alleviate some challenges of CR. The new concept of Time-Restricted Feeding/Eating (TRF for animal studies and TRE for human studies) can be an actionable approach to sustaining the circadian regulation of physiology, metabolism, and behavior. TRE can often (not always) lead to CR. Hence, the combined effect of TRE through circadian optimization and CR can potentially reduce weight and improve cardiometabolic and functional health while lessening the detrimental effects of CR. However, the science and efficacy of TRE as a sustainable lifestyle in humans are in its infancy, whereas animal studies have offered many desirable outcomes and underlying mechanisms. In this article, we will discuss the scope and opportunities to combine CR, exercise, and TRE to improve functional capacity among older adults with obesity.

Indices of sarcopenic obesity are important predictors of finite element analysis-derived bone strength in older adults with obesity.

Background: The expanding population of older adults with obesity is a public health challenge, in part, because of the increased risk of fractures despite normal or high bone mineral density. Potential factors predisposing to fractures in this group include sarcopenia associated with obesity and impaired bone quality. We aimed to determine the contribution of sarcopenic obesity (SO) indices to bone strength as assessed by microfinite element analysis (µFEA) of high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods: One-hundred eighty-nine older (age ≥ 65 years) adults with obesity (BMI ≥ 30 kg/m2) participated in lifestyle intervention trials at our medical center. All underwent baseline measurements of bone strength (failure load and stiffness) using µFEA from HR-pQCT of the distal radius and tibia. In addition, SO indices [appendicular lean mass/weight (ALM/W) and percent body fat (FM%)] by dual-energy X-ray absorptiometry and handgrip strength (HGS) by dynamometry were assessed. SO was diagnosed and staged based on the 2022 ESPEN and EASO expert consensus statement. Results: Both ALM/W and HGS were positively correlated explaining 28% to 36% of the variance in failure load and stiffness at the distal radius and tibia (all p < 0.001). In contrast, FM% was negatively correlated explaining 22% to 31% of the variance in failure load and stiffness at the distal radius and tibia (all p < 0.001). The associations of SO indices with failure load and stiffness remained significant after controlling for age, sex, race/ethnicity, diabetes, and 25-OH vitamin D (ALM/W: R 2 = 0.301 to 0.448, HGS: R 2 = 0.346 to 0.472, FM%: R 2 = 0.299 to 0.432) (p < 0.001 to 0.011). SO was diagnosed in 75/189 (40%) participants with 66/75 (88%) having functional or metabolic complications (stage II). Participants with SO had lower failure load and stiffness at the distal radius than participants with no SO (both p < 0.05). Conclusion: These findings demonstrate that lower muscle mass and strength and higher fat mass may impair bone quality. Therefore, interventions that focus on preserving muscle mass and strength while reducing fat mass may be important to decrease fracture risk when older adults with obesity undertake lifestyle intervention therapy.

Life's Essential 8: Optimizing Health in Older Adults.

The population worldwide is getting older as a result of advances in public health, medicine, and technology. Older individuals are living longer with a higher prevalence of subclinical and clinical cardiovascular disease (CVD). In 2010, the American Heart Association introduced a list of key prevention targets, known as "Life's Simple 7" to increase CVD-free survival, longevity, and quality of life. In 2022, sleep health was added to expand the recommendations to "Life's Essential 8" (eat better, be more active, stop smoking, get adequate sleep, manage weight, manage cholesterol, manage blood pressure, and manage diabetes). These prevention targets are intended to apply regardless of chronologic age. During this same time, the understanding of aging biology and goals of care for older adults further enhanced the relevance of prevention across the range of functions. From a biological perspective, aging is a complex cellular process characterized by genomic instability, telomere attrition, loss of proteostasis, inflammation, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. These aging hallmarks are triggered by and enhanced by traditional CVD risk factors leading to geriatric syndromes (eg, frailty, sarcopenia, functional limitation, and cognitive impairment) which complicate efforts toward prevention. Therefore, we review Life's Essential 8 through the lens of aging biology, geroscience, and geriatric precepts to guide clinicians taking care of older adults.

Sarcopenic obesity research perspectives outlined by the sarcopenic obesity global leadership initiative (SOGLI) - Proceedings from the SOGLI consortium meeting in rome November 2022.

The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched the Sarcopenic Obesity Global Leadership Initiative (SOGLI) to reach expert consensus on a definition and diagnostic criteria for Sarcopenic Obesity (SO). The present paper describes the proceeding of the Sarcopenic Obesity Global Leadership Initiative (SOGLI) meeting that was held on November 25th and 26th, 2022 in Rome, Italy. This consortium involved the participation of 50 researchers from different geographic regions and countries. The document outlines an agenda advocated by the SOGLI expert panel regarding the pathophysiology, screening, diagnosis, staging and treatment of SO that needs to be prioritized for future research in the field.

Cognitive and neural correlates of aerobic fitness in obese older adults.

UNLABELLED: BacKGROUND/STUDY CONTEXT: Aerobic fitness is associated with preserved cognition and brain volume in older adulthood. The current study investigated whether the benefits of aerobic fitness extend to obese older adults, a segment of the population that is rapidly growing and who exhibit compromised cognition and brain structure relative to their nonobese counterparts. METHODS: Measures of obesity, aerobic fitness, cognition (processing speed, executive function, spatial ability, memory), and regional brain volumes (prefrontal gray, prefrontal white, hippocampus) were obtained from 19 obese older adults aged 65 to 75. Hierarchical linear regression analyses were conducted to examine the proportion of unique variance in cognitive and volumetric measures accounted for by aerobic fitness after controlling for covariates (age, gender, and waist circumference). RESULTS: Aerobic fitness accounted for a significant amount of unique variance in processing speed (adjusted R (2) = .44), executive function (adjusted R (2) = .34), and hippocampal volume (adjusted R (2) = .27). CONCLUSION: This novel pattern of results suggests that obesity does not preclude the benefits of fitness for cognition and brain volume in older adults. Fitness appears to be a beneficial factor for maintenance of processing speed, executive function, and hippocampal volume, which are vulnerable to age- and/or obesity-related decline.

Baseline Testosterone Predicts Body Composition and Metabolic Response to Testosterone Therapy.

Context: Male hypogonadism adversely affects body composition, bone mineral density (BMD), and metabolic health. A previous report showed that pre-treatment testosterone (T) levels of <200 ng/dl is associated with greater improvement in spine BMD with T therapy. However, to date, there is no study that investigates whether baseline T levels also influence body composition and metabolic response to T therapy. Objective: The aim of this study is to determine if there are differences in the changes in body composition, metabolic profile, and bone turnover markers, in addition to BMD, in response to T therapy in men with a baseline T level of <264 ng/dl compared to those with levels ≥264 ng/dl. Methods: This is a secondary analysis of a single-arm, open-label clinical trial (NCT01378299) on pharmacogenetics of response to T therapy conducted between 2011 and 2016 involving 105 men (40-74 years old), with average morning T < 300 ng/dl, given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subjects were divided into those with baseline T levels of <264 ng/dl (N = 43) and those with ≥264 ng/dl (N = 57). T and estradiol (E2) were measured by liquid chromatography/mass spectrometry; serum bone turnover markers (C-telopeptide [CTX], osteocalcin, and sclerostin), adiponectin, and leptin were measured by enzyme-linked immunosorbent assay; glycated hemoglobin (HbA1c) was measured by high-performance liquid chromatography; and areal BMD and body composition was measured by dual-energy x-ray absorptiometry (DXA). Results: Men with T < 264 ng/dl showed greater increases in total fat-free mass (FFM) at 18 months compared to those with T ≥ 264 ng/dl (4.2 ± 4.1 vs. 2.7 ± 3.8%; p = 0.047) and unadjusted appendicular FFM at 6 and 18 months (8.7 ± 11.5 vs. 4.4 ± 4.3%, 7.3 ± 11.6 vs. 2.4 ± 6.8%; p = 0.033 and p = 0.043, respectively). Men with T ≥ 264 ng/dl showed significant decreases in HbA1c at 12 months (-3.1 ± 9.2 vs. 3.2 ± 13.9%; p = 0.005), fasting glucose at 18 months (-4.2 ± 31.9 vs. 13.0 ± 57.3%; p = 0.040), LDL at 6 months (-6.4 ± 27.5 vs. 12.8 ± 44.1%; p = 0.034), and leptin at 18 months (-40.2 ± 35.1 vs. -27.6 ± 31.0%; p = 0.034) compared to those with T < 264 ng/dl. No significant differences in BMD and bone turnover markers were observed. Conclusion: T therapy results in improvement in body composition irrespective of baseline T levels but T < 264 ng/dl is associated with greater improvement in FFM, whereas a T level of ≥264 ng/dl favors improvement in metabolic profile.

Lifestyle Intervention Strategy to Treat Diabetes in Older Adults: A Randomized Controlled Trial.

OBJECTIVE: Lifestyle intervention is recommended as first-line treatment of diabetes at all ages; however, little is known about the efficacy of lifestyle intervention in older adults with diabetes. We aimed to determine whether lifestyle intervention would improve glycemic control and age-relevant outcomes in older adults with diabetes and comorbidities. RESEARCH DESIGN AND METHODS: A total of 100 older adults with diabetes were randomly assigned to 1-year intensive lifestyle intervention (ILI) (diet and exercise at a facility transitioned into community-fitness centers and homes) or healthy lifestyle (HL) group. The primary outcome was change in HbA1c. Secondary outcomes included glucoregulation, body composition, physical function, and quality of life. Changes between groups were analyzed with mixed-model repeated-measures ANCOVA following the intention-to-treat principle. RESULTS: HbA1c improved more in the ILI than the HL group (mean ± SE -0.8 ± 0.1 vs. 0.1 ± 0.1%), associated with improved insulin sensitivity (1.2 ± 0.2 vs. -0.4 ± 0.2) and disposition (26.0 ± 8.9 vs. -13.0 ± 8.4 109 min-1) indices (between-group P < 0.001 to 0.04). Body weight and visceral fat decreased more in the ILI than HL group (-8.4 ± 0.6 vs. -0.3 ± 0.6 kg, P < 0.001, and -261 ± 29 vs. -30 ± 27 cm3, P < 0.001, respectively). Physical Performance Test score increased more in the ILI than HL group (2.9 ± 0.6 vs. -0.1 ± 0.4, P < 0.001) as did VO2peak (2.2 ± 0.3 vs. -1.2 ± 0.2 mL/kg/min, P < 0.001). Strength, gait, and 36-Item Short Form Survey (SF-36) Physical Component Summary score also improved more in the ILI group (all P < 0.001). Total insulin dose decreased in the ILI group by 19.8 ± 4.4 units/day. Adverse events included increased episodes of mild hypoglycemia in the ILI group. CONCLUSIONS: A lifestyle intervention strategy is highly successful in improving metabolic and functional health of older adults with diabetes.

Effect of Aerobic or Resistance Exercise, or Both, on Intermuscular and Visceral Fat and Physical and Metabolic Function in Older Adults With Obesity While Dieting.

BACKGROUND: Obesity exacerbates age-related effects on body composition and physical and metabolic function. Which exercise mode is most effective in mitigating these deleterious changes in dieting older adults with obesity is unknown. METHODS: In a randomized controlled trial, we performed a head-to-head comparison of aerobic (AEX), resistance (REX), or combination (COMB) exercise during matched ~10% weight loss in 160 obese older adults. Prespecified analyses compared 6-month changes in intermuscular adipose tissue (IMAT) and visceral adipose tissue (VAT) assessed using MRI, insulin sensitivity index (ISI) by oral glucose tolerance test, physical function using Modified Physical Performance Test (PPT), VO2peak, gait speed, and knee strength by dynamometry. RESULTS: IMAT and VAT decreased more in COMB than AEX and REX groups (IMAT; -41% vs -28% and -23% and VAT: -36% vs -19% and -21%; p = .003 to .01); IMAT and VAT decreased in all groups more than control (between-group p < .001). ISI increased more in COMB than AEX and REX groups (86% vs 50% and 39%; p = .005 to .03). PPT improved more in COMB than AEX and REX groups, while VO2peak improved more in COMB and AEX than REX group (all p < .05). Knee strength improved more in COMB and REX than AEX group (all p < .05). Changes in IMAT and VAT correlated with PPT (r = -0.28 and -0.39), VO2peak (r = -0.49 and -0.52), gait speed (r = -0.25 and -0.36), and ISI (r = -0.49 and -0.52; all p < .05). CONCLUSIONS: Weight loss plus combination aerobic and resistance exercise was most effective in improving ectopic fat deposition and physical and metabolic function in older adults with obesity.

Circulating osteogenic progenitors and osteoclast precursors are associated with long-term glycemic control, sex steroids, and visceral adipose tissue in men with type 2 diabetes mellitus.

Introduction: Type 2 diabetes mellitus (T2DM) is well-known to be associated with normal bone density but, concurrently, low bone turnover and increased risk for fracture. One of the proposed mechanisms is possible derangement in bone precursor cells, which could be represented by deficiencies in circulating osteogenic progenitor (COP) cells and osteoclast precursors (OCP). The objective of our study is to understand whether extent of glycemic control has an impact on these cells, and to identify other factors that may as well. Methods: This was a secondary analysis of baseline data from 51 male participants, aged 37-65 in an ongoing clinical trial at Michael E. DeBakey VA Medical Center, Houston, Texas, USA. At study entry serum Hemoglobin A1c was measured by high-performance liquid chromatography osteocalcin (OCN) and C-terminal telopeptide of type 1 collagen (CTx) were measured by ELISA, and testosterone and estradiol by liquid-chromatography/mass-spectrometry. Areal bone mineral density (BMD), trabecular bone score and body composition were measured by dual energy x-ray absorptiometry, while COP and OCP were measured by flow cytometry. Results: When adjusted for serum testosterone, parathyroid hormone, and 25-hydroxyvitamin D, those with poor long-term glycemic control had significantly higher percentage of COP (p = 0.04). COP correlated positively with visceral adipose tissue (VAT) volume (r = 0.37, p = 0.01) and negatively with free testosterone (r = -0.28, p = 0.05) and OCN (r = -0.28, p = 0.07), although only borderline for the latter. OCP correlated positively with age, FSH, lumbar spine BMD, and COP levels, and negatively with glucose, triglycerides, and free estradiol. Multivariable regression analyses revealed that, in addition to being predictors for each other, another independent predictor for COP was VAT volume while age, glucose, and vitamin D for OCP. Conclusion: Our results suggest that high COP could be a marker of poor metabolic control. However, given the complex nature and the multitude of factors influencing osteoblastogenesis/adipogenesis, it is possible that the increase in COP is a physiologic response of the bone marrow to increased osteoblast apoptosis from poor glycemic control. Alternatively, it is also likely that a metabolically unhealthy profile may retard the development of osteogenic precursors to fully mature osteoblastic cells.