Gloria Mazzali

Health consequences of obesity in the elderly: a review of four unresolved questions

Obesity prevalence is growing progressively even among older age groups. Controversy exists about the potential harms of obesity in the elderly. Debate persists about the relation between obesity in old age and total or disease-specific mortality, the definition of obesity in the elderly, its clinical relevance, and about the need for its treatment. Knowledge of age-related body composition and fat distribution changes will help us to better understand the relationships between obesity, morbidity and mortality in the elderly. Review of the literature supports that central fat and relative loss of fat-free mass may become relatively more important than BMI in determining the health risk associated with obesity in older ages. Weight gain or fat redistribution in older age may still confer adverse health risks (for earlier mortality, comorbidities conferring independent adverse health risks, or for functional decline). Evaluation of comorbidity and weight history should be performed in the elderly in order to generate a comprehensive assessment of the potential adverse health effects of overweight or obesity. The risks of obesity in the elderly have been underestimated by a number of confounders such as survival effect, competing mortalities, relatively shortened life expectancy in older persons, smoking, weight change and unintentional weight loss. Identification of elderly subjects with sarcopenic obesity is probably clinically relevant, but the definition of sarcopenic obesity, the benefits of its clinical identification, as well as its relation to clinical consequences require further study. Studies on the effect of voluntary weight loss in the elderly are scarce, but they suggest that even small amounts of weight loss (between 5–10% of initial body weight) may be beneficial. In older as well as in younger adults, voluntary weight loss may help to prevent the adverse health consequences of obesity.

Sarcopenic obesity: A new category of obesity in the elderly

BACKGROUND AND AIM In elderly patients, age-related changes in body composition, as well as the increased prevalence of obesity, determine a combination of excess weight and reduced muscle mass or strength, recently defined as sarcopenic obesity (SO). This review examines the main studies regarding sarcopenic obesity in the elderly. DATA SYNTHESIS Definition of SO necessarily combines those of sarcopenia and obesity. The prevalence of sarcopenia and SO increases with age. Muscle and fat mass are strongly interconnected from a pathogenetic point of view. A better understanding of the mechanisms which lead from loss of muscle mass to fat gain or vice versa from fat gain to muscle loss seems to be crucial. Recent data suggest that peptides produced by adipose tissue may play an important role in the pathophysiology of SO, thus more research is needed to better characterize this new area. Obesity and sarcopenia in the elderly may potentiate each other maximizing their effects on disability, morbidity and mortality. Identifying elderly subjects with SO should be mandatory; effective treatment of sarcopenia and SO may attenuate its clinical impact. CONCLUSION The concept of SO may help to clarify the relationship between obesity, morbidity and mortality in the elderly.

Physical disability and muscular strength in relation to obesity and different body composition indexes in a sample of healthy elderly women

OBJECTIVES: The aim of the present study was to test the association between muscular strength, functional limitations, body composition measurements and indexes of sarcopenia in a sample of community-dwelling, elderly women at the high end of the functional spectrum.DESIGN: Cross-sectional.SUBJECTS: In all, 167 women aged 67–78 y were selected from the general population in central Verona. A group of 120 premenopausal healthy women aged 20–50 y represented the young reference group.MEASUREMENTS: Body weight, height, body mass index (BMI) and the presence of acute and chronic conditions were evaluated in each subject. Body composition was measured by dual-energy X-ray absorptiometry (DXA). Physical functioning was assessed using a modified version of the Activities of Daily Living Scale. Dominant leg isometric strength was measured with a Spark Handheld Dynamometer.RESULTS: Elderly women with BMI higher than 30 kg/m2 and in the highest quintile of body fat percent showed a significantly higher prevalence of functional limitation. In our population study, about 40% of sarcopenic elderly women and 50% of elderly women with high body fat and normal muscle mass were functionally limited. The prevalence of functional limitation significantly increased in subjects with class II sarcopenia, defined according to the skeletal muscle mass index (SMI=skeletal muscle mass/body mass × 100). In logistic regression models, after adjusting for age and different chronic health conditions, subjects with BMI higher than 30 kg/m2, in the highest quintile of body fat, or with high body fat and normal muscle mass or class II sarcopenia according to SMI, had a 3–4 times increased risk of functional limitations. Finally, isometric leg strength was significantly lower in subjects in the lowest quintile of relative muscle mass and in sarcopenic and sarcopenic obese women.CONCLUSIONS: High body fat and high BMI values were associated with a greater probability of functional limitation in a population of elderly women at the high end of the functional spectrum. Among the different indexes of sarcopenia used in this study, only SMI predicted functional impairment and disability. Isometric leg strength was significantly lower in subjects with sarcopenia and sarcopenic obesity.

Body composition changes in stable-weight elderly subjects: the effect of sex.

Background and aims: Although cross-sectional and longitudinal studies have shown age-related changes in body composition and fat distribution, they may be related to body weight changes. The aim of this study was to evaluate yearly age-related changes in body composition and fat distribution, over a two-year period, in 101 women and 60 men (age range: 68 to 78 years at baseline). Methods: Body composition was evaluated by dual energy X-ray absorptiometry (DXA), and fat distribution by waist and hip circumferences and waist-to-hip circumference ratio. Baseline free testosterone, IGF-1 and serum albumin were evaluated in all subjects, as well as physical activity. Clinical evaluation was performed at baseline and yearly in order to exclude subjects with any condition inducing pathological changes in body composition or fat distribution. Subjects with a weight change >5% of their baseline body weight during the study period, were excluded. Results: Significant increases occurred in Body Mass Index (BMI) (1.18% in women, 1.13% in men), waist (1.75% in women, 1.39% in men), and hip circumference (1.06% in women, 1.31% in men), whereas height decreased significantly in both men (0A2%) and women (0.55%). Significant increases in total body fat (1.31%) and percent body fat (1.27%) were observed in women but not in men. Lean body mass did not change significantly throughout the study in either sex. Significant losses in leg muscle mass and appendicular skeletal muscle mass (ASM), calculated as the sum of arm and leg fat-free soft tissue, were observed in men (respectively 3.56 and 2.77%) and women (respectively 2A1 and 1.59%). A significant decrease in ASM adjusted by stature (ASM/height2), a proposed proxy for sarcopenia, was found in men only (1.97%). The rates of loss in leg muscle mass and appendicular muscle mass were significantly higher in men than in women, even after adjusting for free testosterone, IGF-1, physical activity and serum albumin. Conclusions: These data demonstrate significant changes in body composition and fat distribution in independently living, weight-stable elderly men and women. These changes are dependent on sex and independent of physical activity, hormones or serum albumin.

Predictors of Ectopic Fat Accumulation in Liver and Pancreas in Obese Men and Women

The aim of the present study was to determine the relationship between body fat distribution, adipocytokines, inflammatory markers, fat intake and ectopic fat content of liver and pancreas in obese men and women. A total of 12 lean subjects (mean age 47.25 ± 14.88 years and mean BMI 22.85 ± 2), 38 obese subjects (18 men and 20 women) with mean age 49.1 ± 13.0 years and mean BMI 34.96 ± 4.21 kg/m2 were studied. Measurements: weight, height, BMI, waist circumference, as well as glucose, insulin, HOMA (homeostasis model assessment of insulin resistance), cholesterol, triglycerides, high‐density lipoprotein cholesterol, high sensitivity C‐reactive protein, daily energy intake, leptin, and adiponectin. Magnetic resonance was used to evaluate visceral, subcutaneous adipose tissue (SCAT) as well as liver and pancreas lipid content using in‐phase and out‐of‐phase magnetic resonance imaging (MRI) sequence. Obese subjects had significantly higher weight, waist circumference, SCAT, deep SCAT, visceral adipose tissue (VAT), liver and pancreatic lipid content than lean subjects. Obese women had significantly lower VAT, liver and pancreas lipid content regardless of same BMI. In multiple regression analyses, the variance of liver lipid content explained by gender and VAT was 46%. When HOMA was added into a multiple regression, a small increase in the proportion of variance explained was observed. A 59.2% of the variance of pancreas lipid content was explained by gender and VAT. In conclusion, obese men show higher VAT and ectopic fat deposition in liver and pancreas than obese women despite same BMI. Independent of overall adiposity, insulin resistance, adiponectin and fat intake, VAT, measured with MRI, is the main predictor of ectopic fat deposition in both liver and pancreas.

Relationship between leptin levels and bone mineral density in the elderly

objective To assess the relationship between circulating leptin levels, bone mineral content and density in the elderly.

Relation between adiponectin and bone mineral density in elderly post-menopausal women: role of body composition, leptin, insulin resistance, and dehydroepiandrosterone sulfate.

Introduction: Adipocytokines have been proposed as new mediators of the protective effects of fat mass on the skeleton. The aim of this study was to test the relationship between adiponectin, leptin, and bone mineral density (BMD), independently of body composition, insulin resistance, and other factors known to affect bone metabolism. Methods: Thirty-six post-menopausal non-diabetic elderly women, with ages ranging from 66 to 77 yr took part in the study. In all subjects we evaluated body weight, height, body mass index (BMI), waist circumference, adiponectin, leptin, insulin, DHEAS, and homeostasis model assessment of insulin resistance (HOMA), as well as yr since menopause. Total body fat mass (FM) and BMD at whole body and femoral level were measured with Dual energy X-ray Absorptiometry (DXA). Volumetric BMD was defined as the ratio between total body BMD and height. Results: Leptin was positively and adiponectin negatively related with whole body and femoral BMD. Positive associations between insulin, HOMA, DHEAS, and BMD measures were also found. After adjusting for FM, only adiponectin maintained a significant relation with whole body and femoral BMD; the strength of this association was reduced after adjustment for insulin resistance, estimated by HOMA. In stepwise multiple linear regression analyses adiponectin explained 11.7% of total BMD variance, 17.4% of femoral neck BMD variance, and 30.7% of volumetric BMD variance, independently of BMI, FM, leptin, HOMA, and DHEAS. Conclusions: The present study may suggest possible involvement of adiponectin in bone metabolism, independently of FM and insulin resistance even in elderly post-menopausal women.

Adiponectin gene expression and adipocyte NF-κB transcriptional activity in elderly overweight and obese women : inter-relationships with fat distribution, hs-CRP, leptin and insulin resistance

Objective:The regulatory processes that modulate adiponectin production and the mechanisms involved in nuclear factor kB (NF-kB) transcriptional activity in human adipocytes are not yet fully known. The aim of our study was to evaluate the inter-relationships between body fat, fat distribution, systemic inflammation, insulin resistance, leptin and the serum and subcutaneous adipose tissue gene expression levels of tumor necrosis factor-alpha (TNF-α), adiponectin and the inhibitor kappa B-alpha (IkB-α), in subjects with a wide range of body mass index (BMI). We also wanted to determine which of these variables was most closely related to adiponectin gene expression and adipocyte NF-kB transcriptional power.Methods:A total of 27 women aged between 50 and 80 years, with BMI ranging from 22.1 to 53.3 kg/m2, were studied. In all subjects BMI, waist circumference, body composition by dual X-ray absorptometry, triglycerides, cholesterol, high-density lipoprotein cholesterol (HDL-Ch), glucose, insulin, homeostasis model assessment of insulin resistance (HOMA), high-sensitive C-reactive protein (hs-CRP), serum adiponectin, leptin and TNF-α were evaluated. Subcutaneous adipose tissue biopsies were taken from the abdomen of all subjects and the mRNA levels of adiponectin, TNF-α and IkB-α were determined.Results:BMI and waist circumference were associated positively with leptin, HOMA, and hs-CRP, and negatively with HDL-Ch; waist was also associated with adiponectin and IkB-α mRNA. HOMA was negatively associated with serum adiponectin and adiponectin mRNA. Hs-CRP was negatively associated with IkB-α mRNA, and was positively associated with HOMA. Step-down multiple regression analysis was performed to determine the joint effects of BMI, waist circumference, triglycerides, HDL-Ch, HOMA, hs-CRP, leptin, serum and TNF-α mRNA on adiponectin gene expression: waist circumference and leptin were both included in the best fitting regression equation for predicting adiponectin gene expression (R 2=0.403, P=0.006). Stepwise multiple regression analysis was performed, considering IkB-α mRNA as a dependent variable and BMI, waist, HDL-Ch, HOMA, hs-CRP and adiponectin mRNA as independent variables. Adiponectin mRNA was the only variable to enter the regression (R2=0.406, P<0.001).Conclusion:Our results suggest that abdominal adiposity and leptin are independent predictors of adiponectin gene expression and that in human adipocytes, adiponectin gene expression is strongly related to IkB-α mRNA.

Sarcopenia, Cachexia and Congestive Heart Failure in the Elderly

Skeletal muscle abnormalities and loss are frequently present in patients with mild or moderate cardiac heart failure (CHF) and may contribute to fatigue and dyspnea. These muscle abnormalities may be associated with age related body composition changes, such as sarcopenia. Muscle damage has also been observed in subjects with cardiac cahexia, a serious CHF complication, associated with poor prognosis independently of functional disease severity, age, and measures of exercise capacity and cardiac function. Loss of muscle mass is a feature of cachexia, whereas most sarcopenic subjects are not cachectic. Individuals with no weight loss, no anorexia, and no measurable systemic inflammatory response may be sarcopenic. Patients with severe CHF show multiple marked histological abnormalities of skeletal muscle, such as muscle fiber atrophy. These abnormalities are different in sarcopenia and cachexia. The majority of mechanisms involved in sarcopenia play a role even in the determination of cachexia and they are amplified in cachexia where they may induce both muscle damage as well as other abnormalities, such as fat and weight loss, through activation of lypolisis or anorexia. To distinguish cachexia and sarcopenia in CHF patients, even if not easy, should be clinically relevant, because no specific treatment is available for cachectic patients whereas treatment options are possible for sarcopenia.

Adipose tissue, diet and aging

Age related increase in body fat mass, visceral adipose tissue (AT), and ectopic fat deposition are strongly related to worse health conditions in the elderly. Moreover, with aging higher inflammation in adipose tissue may be observed and may contribute to inflammaging. Aging may significantly affect AT function by modifying the profile of adipokines produced by adipose cells, reducing preadipocytes number and their function and increasing AT macrophages infiltration. The initiating events of the inflammatory cascade promoting a greater AT inflammatory profile are not completely understood. Nutrients may determine changes in the amount of body fat, in its distribution as well as in AT function with some nutrients showing a pro-inflammatory effect on AT. Evidences are sparse and quite controversial with only a few studies performed in older subjects. Different dietary patterns are the result of the complex interaction of foods and nutrients, thus more studies are needed to evaluate the association between dietary patterns and changes in adipose tissue structure, distribution and function in the elderly.