Francesco Fantin

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.

Chronic Plaque Psoriasis Is Associated with Increased Arterial Stiffness

Background: Patients with moderate to severe chronic plaque psoriasis have a higher prevalence of cardiovascular risk factors and atherosclerosis. Arterial stiffness is a measure of endothelial dysfunction and an independent predictor of cardiovascular events. Objectives: To investigate whether chronic plaque psoriasis is associated with an increased arterial stiffness. Methods: A cross-sectional study on 39 adult patients with moderate to severe chronic plaque psoriasis and 38 control patients with skin diseases other than psoriasis was conducted. Arterial stiffness was assessed by carotid-femoral and carotid-radial pulse wave velocity (PWVcf, PWVcr). Results: PWVcf was significantly higher in patients with psoriasis than in controls (means ± SD; 8.88 ± 1.96 vs. 7.57 ± 1.34 m/s; p = 0.001). Difference was still significant after adjustment for age, gender, smoking status, hypertension and body mass index (8.78 ± 1.98 vs. 7.78 ± 2.0 m/s; p = 0.03). There was a positive correlation between PWVcf and years of psoriasis duration (r = 0.58; p = 0.0001), but not with disease severity. Conclusion: Moderate to severe chronic plaque psoriasis may be independently associated with increased arterial stiffness. Psoriasis duration could be a risk factor for arterial stiffness and atherosclerosis.

The Anorexia of Aging

Malnutrition in the elderly is one of the greatest threats to health, well-being and autonomy, it is therefore crucial to understand and to contrast the causal factors of inadequate energy intake. This review focuses on the mechanisms of the so-called ‘anorexia of aging’. In recent years, it has been shown that elderly subjects have abnormal peripheral signal patterns and alterations in central hypothalamic control relays. Negative feedback from impaired gastric motility, exaggerated long-term adiposity signals (leptin, insulin) and postprandial anorexigenic signals (CCK, PYY) seem to prevail over the central feeding drive. If nutritional strategies of intervention are to be improved, these data need to be taken into account.

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.

Body composition and pulmonary function in the elderly: a 7-year longitudinal study.

Objective:To evaluate over a 7-year follow-up period the relationships between changes in body composition, fat distribution and pulmonary function in a sample of elderly men and women.Design:Longitudinal clinical study.Subjects:A total of 47 women and 30 men aged 71.6±2.3 and 71.7±2.2 years, respectively, at baseline with body mass index (BMI) values of 24.96±3.28 and 27.04±3.35 kg m−2 were followed for 7 years.Measurements:Body weight, waist circumference, sagittal abdominal diameter (SAD), fat-free mass (FFM) and fat mass as measured by dual energy X-ray absorptiometry (DXA) and forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) by spirometry were evaluated at baseline and after a 7-year mean follow-up.Results:In women as in men there were no significant changes in weight, SAD and BMI. A significant decrease in height and FFM was observed in both women and men. Height-adjusted FEV1 and FVC decreased significantly in women and men over the 7-year follow-up. Changes in SAD were the most powerful predictors of 7-year follow-up of FEV1 and FVC after taking into account, respectively, baseline FEV1 and FVC. Linear regression analysis, performed by using 7-year follow-up lung function variables as dependent variables and changes in body composition variables as independent variables, showed that 1 cm SAD increase predicted a decrease in FEV1 and FVC of 31 and 46 ml, respectively, and 1 kg FFM decrease predicted a decrease in FVC of 38 ml. After subdividing our study population into four categories of change in FFM and SAD, patients with decreased FFM and increased SAD showed the highest probability of having a worsening in FEV1 and FVC.Conclusion:Increase in abdominal fat and FFM decline are significant predictors of lung function decline in the elderly. Old subjects developing both abdominal fat gain and FFM loss show the highest probability of developing worsening in lung function.

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.

Identifying sarcopenia in acute care setting patients.

OBJECTIVES To evaluate the prevalence of sarcopenia by applying European Working Group on Sarcopenia in Older People (EWGSOP) flow chart in an acute care geriatric unit as well as to test a modified version of the EWGSOP diagnostic algorithm combining handgrip and gait speed test to identify subjects with low muscle mass. DESIGN Observational cohort study. SETTING Geriatric unit in an academic medical department. PARTICIPANTS One hundred nineteen acutely ill persons (34.4% female), with mean age 80.4 ± 6.9 years and body mass index 26.3 ± 4.9 kg/m(2). MEASUREMENTS Assessment of muscle mass by bioimpedence analysis, muscle strength by handheld dynamometer, and gait speed with the 4-meter walking test. RESULTS Using the EWGSOP classification for sarcopenia, 5.0% presented with sarcopenia and 21.0% with severe sarcopenia. Combining gait speed test and handgrip strength measurement, the highest predictive power in detecting subjects with low muscle mass was observed (sensitivity and specificity, 80.6% and 62.5%, respectively). Subjects presenting with both normal gait speed and handgrip showed normal values of muscle mass as assessed with bioimpedence analysis. By using the ROC method, when the 2 tests were combined, the AUC was statistically higher than when using each test separately (0.740; P = .018). CONCLUSIONS Our study shows that 1 of 4 patients admitted to the acute care department were recognized to be sarcopenic. When a modifived version of the EWGSOP flow chart, obtained combining both gait speed and handgrip was used, sensitivity and specificity of algorithm to identify subjects with low muscle mass was improved.

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.

Quantification of Intermuscular Adipose Tissue in the Erector Spinae Muscle by MRI: Agreement With Histological Evaluation

Deposition of fat between skeletal muscle bundles and beneath the muscle fascia, recently called intermuscular adipose tissue (IMAT), is gaining attention as potential contributor to insulin resistance, metabolic syndrome, muscle function impairment, and disability. The aim of this study was to compare IMAT as measured at the erector spinae level by magnetic resonance imaging (MRI), a well‐recognized gold standard method to evaluate fat content inside muscles, and histology estimates. In 18 healthy elderly men and women with a wide range of BMI (25.05–35.58 kg/m2), undergoing elective vertebral surgery, IMAT within the erector spinae muscle was evaluated by MRI, by body composition using dual‐energy X‐ray absorptiometry and histological evaluation of intraoperative biopsy sample. The concordance between IMAT/total area (TA) ratio evaluated by MRI and histological examination was analyzed employing Lins concordance correlation coefficient and the procedure proposed by Bland and Altman. Two thresholds to distinguish between muscle and IMAT calculated, respectively, by 20 and 10% reduction of the gray‐level intensity evaluated by MRI from surrounding subcutaneous adipose tissue (SAT) were used. With a 20% reduction, calculated IMAT/TA as evaluated by MRI on average exceeds histological evaluation by 21.79%, whereas by reducing the threshold by 10% agreement between MRI and histology improved with a 12.42% difference. Our data show a good degree of concordance between IMAT assessment by MRI and histology and seems to show that agreement between the two methods could be improved by using a more restrictive threshold between muscle and fat.