Thrifty energy phenotype predicts weight regain in postmenopausal women with overweight or obesity and is related to FGFR1 signaling.

BACKGROUND&AIMS: Long term improvement of body weight and metabolism is highly requested in obesity. The specific impact of weight loss associated temporary negative energy balance or modified body composition on metabolism and weight regain is unclear. METHODS: We randomly assigned 80 post-menopausal women (BMI 33.9 (32.2-36.8)kg/m2) to an intervention (IG) or control group (CG). IG underwent a dietary three month-weight loss intervention followed by a four week-weight maintenance period without negative energy balance. The CG was instructed to keep their weight stable. Phenotyping was performed at baseline (M0), after weight loss (M3), the maintenance period (M4) and 24-month follow-up (M24). Co-primary outcomes were changes of insulin sensitivity (ISIClamp) and lean body mass (LBM). Energy metabolism and adipose gene expression were secondary endpoints. RESULTS: Between March 2012 and July 2015, 479 subjects were screened for eligibility. 80 subjects were randomly assigned to IG (n = 40) or CG (n = 40). The total number of dropouts was 18 (IG: n = 13, CG: n = 5). LBM and ISIClamp were stable in the CG between M0 and M3, but were changed in the IG at M3 (LBM: -1.4 (95%CI -2.2-(-0.6)) kg and ISIClamp: +0.020 (95%CI 0.012-0.028) mg·kg-1·min-1/(mU·l-1)) (p < 0.01 and p < 0.05 for IG vs. CG, respectively). Effects on LBM, ISIClamp, FM and BMI were preserved until M4. Lower resting energy expenditure per LBM (REELBM) at M3 and stronger difference of REELBM between M3 and M4 (ΔREELBM-M3M4), which indicates a thrifty phenotype, were positively associated with FM regain at M24 (p = 0.022 and p = 0.044, respectively). Gene set enrichment analysis revealed a relationship of this phenotype to weight loss-induced adaption of adipose FGFR1 signaling. CONCLUSION: Negative energy balance had no additional effect on insulin sensitivity. FGFR1 signaling might be involved in the adaption of energy expenditure to temporary negative energy balance, which indicates a thrifty phenotype susceptible to weight regain. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01105143, https://clinicaltrials.gov/ct2/show/NCT01105143, date of registration: April 16th, 2010.

Weight loss did not modify macronutrient specific response of hormones and satiety in overweight and obese people without metabolic disease - results from a clinical trial.

BACKGROUND & AIMS: Sustained weight loss is highly desirable in obesity. Although the role of incretins in the regulation of body weight is well known, macronutrient specific incretin response and the effects of weight loss on this response have not been investigated before. We aimed to examine GLP-1, GIP, ghrelin, insulin, and satiety response to meals with different macronutrient composition in overweight and obese subjects before and after weight loss. METHODS: 32 overweight and obese participants underwent meal tests before and after weight loss intervention. Test meals were designed to be either carbohydrate (CHO), fat (FAT), or protein (PRO) enriched to test macronutrient specific response. Macronutrient specific response of GLP-1, GIP, and ghrelin before and after weight loss were the primary outcome measures. Response of insulin and satiety were predefined secondary endpoints. RESULTS: There were macronutrient specific response patterns of GLP-1 (PRO>FAT=CHO), GIP (CHO=FAT>PRO), and insulin (CHO>PRO=FAT). Postprandial decline of ghrelin did not differ between the test meals. Hunger, desire to eat, and prospective food consumption were highest after CHO intake (CHO>PRO=FAT) at baseline. After weight loss, fasting and postprandial GLP-1 and insulin were reduced while concomitant ghrelin levels were increased. However, the macronutrient specific hormonal response pattern did not change after weight loss. While weight loss increased hunger and desire to eat, the macronutrient specific differences were lost after weight reduction. Higher weight loss was associated with a stronger decline of PRO induced GLP-1 response (ρ = 0.45, p = 0.024, n = 27). CONCLUSIONS: Both hormones and satiety showed a macronutrient specific response in overweight/obese participants with a possibly favorable role of protein. However, weight loss may cause a partial disruption of this hormone-satiety-connection as macronutrient specific response pattern of satiety scores representing impulse control in particular but not incretins disappeared. TRIAL REGISTRATION: NCT02649907. https://clinicaltrials.gov/ct2/show/NCT02649907.

Muscle weakness as an additional criterion for grading sarcopenia-related prognosis in patients with cancer.

BACKGROUND: Low muscle strength has been pointed out as a key characteristic of sarcopenia, but the prognostic significance of muscle function next to reduced skeletal muscle mass (SMM) in patients with cancer has been scantily investigated. METHODS: Data on muscle strength by handgrip (HG) dynamometry and total-body SMM estimated by bioelectrical impedance analysis (BIA) of Italian and German patients with cancer observed prospectively until death or censoring were analysed (N = 1076). Patients were stratified in four risk categories based on low HG (<10th percentiles of age and gender-specific normative values) and low total-body SMM according to SMM index cutoffs (<10.75 and <6.75 kg/m2 in men and women, respectively). RESULTS: During a median follow-up of 58 months [25th-75th percentile, 37-60], 566 patients had died. Patients presenting low HG in combination or not with low SMM were characterised by shorter median survival (12.7 vs. 27.2 months, respectively; p < 0.001) compared to those with low SMM/normal HG and normal SMM/normal HG (>60 months for both). After adjusting for sex, age, body mass index and percentage of weight loss, disease's stage, performance status and type of cancer, compared to reference category (normal HG and SMM; N = 210) the hazard ratios were: low SMM/normal HG (N = 342), 0.83 [95% confidence interval, CI, 0.67-1.02] (p = 0.073); normal SMM/low HG (N = 158), 1.19 [95% CI, 1.07-1.32] (p = 0.002); low SMM/low HG (N = 366), 1.39 [95% CI, 1.27-1.53] (p < 0.001). CONCLUSIONS: Muscle weakness was found to be a more powerful predictor of survival than BIA-estimated SMM and should be considered as an additional key feature of sarcopenia in patients with cancer.

Fetuin-B, a potential link of liver-adipose tissue cross talk during diet-induced weight loss-weight maintenance.

BACKGROUND/OBJECTIVES: Numerous hepatokines are involved in inter-organ cross talk regulating tissue-specific insulin sensitivity. Adipose tissue lipolysis represents a crucial element of adipose insulin sensitivity and is substantially involved in long-term body weight regulation after dietary weight loss. Thus, we aimed to analyze the impact of the hepatokine Fetuin-B in the context of weight loss induced short- and long-term modulation of adipose insulin sensitivity. SUBJECTS/METHODS: 143 subjects (age > 18; BMI ≥ 27 kg/m2) were analyzed before (T-3) and after (T0) a standardized 12-week dietary weight reduction program. Afterward, subjects were randomized to a 12-month lifestyle intervention or a control group. After 12 months (T12) no further intervention was performed until 6 months later (T18) (Maintain-Adults trial). Tissue-specific insulin sensitivity was estimated by HOMA-IR (predominantly liver), ISIClamp (predominantly skeletal muscle), and free fatty acid suppression during hyperinsulinemic-euglycemic clamp (FFASupp) (predominantly adipose tissue). Fetuin-B was measured at all concomitant time points. RESULTS: Circulating Fetuin-B levels correlated significantly with estimates of obesity, hepatic steatosis as well as HOMA-IR, ISIClamp, FFASupp at baseline. Fetuin-B decreased during dietary weight loss (4.2 (3.5-4.9) vs. 3.8 (3.2-4.6) µg/ml; p = 2.1 × 10-5). This change was associated with concomitant improvement of HOMA-IR (r = 0.222; p = 0.008) and FFASupp (r = -0.210; p = 0.013), suggesting a particular relationship to hepatic and adipose tissue insulin sensitivity. Weight loss induced improvements of insulin resistance were almost completely preserved until months 12 and 18 and most interestingly, the short and long-term improvement of FFASupp was partially predicted by baseline level of Fetuin-B. CONCLUSIONS: Our data suggest that Fetuin-B might be a potential mediator of liver-adipose cross talk involved in short- and long-term regulation of adipose insulin sensitivity, especially in the context of diet-induced weight changes. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT00850629, https://clinicaltrials.gov/ct2/show/NCT00850629 , date of registration: February 25, 2009.

The prognostic impact of BIA-derived fat-free mass index in patients with cancer.

BACKGROUND & AIMS: Reduced muscle mass represents one of the top ranked phenotypic criteria for malnutrition proposed by the Global Leadership Initiative on Malnutrition. Although height-indexed fat-free mass (FFMI) thresholds have been proposed as useful surrogate measures of reduced muscle mass, the independent prognostic value of BIA-derived FFMI by bioelectric impedance analysis (BIA) in patients with cancer still needs to be fully explored. METHODS: Data on body mass index (BMI), 6-month percentage of weight loss (%WL), FFMI by BIA and quality of life (QoL by EORTC Quality of Life Questionnaire [EORTC QLQ-C30]) of Italian and German patients observed prospectively until death or censoring were used (N = 1217). Patients were stratified in 5 risk categories according to a robustly validated scoring system based on BMI and %WL. Low FFMI was defined as follows: men, <17 kg/m2; women, <15 kg/m2. RESULTS: Reduced FFMI was found in 234 patients (19.2%). After a median follow-up of 57 months [25th-75th, 31-60], 620 patients (50.9%) had died. The study detected differences in survival between patients presenting with and without reduced FFMI (14.0 months vs. 45.1 months; P < 0.001). The fully-adjusted hazard ratio of mortality for low FFMI was 1.46 [95%CI, 1.18-1.81] (P < 0.001). Low FFMI was also independently associated with reduced QoL: fully-adjusted odds ratio, 1.50 [95%CI, 1.00-2.25] (P = 0.050). CONCLUSIONS: Reduced FFMI by BIA independently predicted survival and was associated with impaired QoL. Altered body composition should always be considered in all patients with cancer as additional phenotypic criterion of poor prognosis and BIA offers the possibility of multiple, noninvasive bedside assessments.

Validation of a new prognostic body composition parameter in cancer patients.

BACKGROUND & AIMS: Estimation errors associated with bioelectric impedance evaluation may affect the accuracy of body composition and its prognostic value. We evaluated the prognostic value of a new body composition parameter (Nutrigram®) obtained from bioimpedance vectorial analysis-derived body cell mass and its association with nutritional and functional status. DESIGN: Data of Italian and German cancer patients observed prospectively until death were used. Multivariable models (adjusted for age, gender, hydration status, performance status, and disease's stage) were built in both cohorts to assess the association between body composition outcome parameters (low fat-free mass [FFM], <15 [females] and <17 [males] kg/m2; low standardized phase angle [SPA], <-1.65; low Nutrigram®, <510 [females] and <660 [males] mg/24 h/m) and 1-year all-cause mortality, low body mass index (BMI; <20 [<70 years] and <22 [≥70 years] kg/m2), clinically significant weight loss (WL; ≥10% in 6 months) and low handgrip strength (HG; <20 [females] and <30 [males] kg). RESULTS: Low Nutrigram® was independently associated with mortality in both Italian (HR = 1.84 [95%CI, 1.18-2.86]; P = 0.007) and German cohorts (HR = 1.52 [95%CI, 1.17-2.07]; P = 0.008). Low FFMI and low SPA did not predict survival in the German cohort. In patients with low Nutrigram®, worse nutritional and functional status were observed in both study populations. Performance of models addressing the study endpoints showed substantial consistency with both cohorts, particularly of those including low Nutrigram®. CONCLUSIONS: We validated a new prognostic body composition parameter, which is easier to interpret than standard nutritional parameters and may be useful for identifying cancer patients at nutritional risk, requiring early nutritional support.

Impact of sarcopenia on 1-year mortality in older patients with cancer.

OBJECTIVES: sarcopenia is common especially in hospitalised older populations. The aim of this study was to assess the prevalence of sarcopenia, defined as low skeletal mass and muscle strength, and its impact on 1-year mortality in older patients with cancer. METHODS: skeletal muscle mass was estimated using bioelectric impedance analysis and related to height2 (SMI; Janssen et al. 2002). Grip strength was measured with the JAMAR dynamometer and the cut-offs suggested by the European Working Group on Sarcopenia in Older People (EWGSOP) were applied. One-year mortality was assessed by telephone follow-up and the local cancer death registry. RESULTS: of the 439 consecutively recruited cancer patients (60-95 years; 43.5% women), 119 (27.1%) had sarcopenia. Of the patients with sarcopenia, 62 (52.5%) died within 1 year after study entry compared to 108 (35.1%) patients who did not have sarcopenia (P = 0.001). In a stepwise, forward Cox proportional hazards analysis, sarcopenia (HR = 1.53; 95% CI: 1.034-2.250; P < 0.05), advanced disease (HR = 1.87; 95% CI: 1.228-2.847; P < 0.05), number of drugs/day (HR = 1.11; 95% CI: 1.057-1.170; P < 0.001), tumour diagnosis (overall P < 0.05) and Karnofsky index (HR = 0.98, 95% CI: 0.963-0.995; P < 0.05) associated with 1-year mortality risk. The factors sex, age, co-morbidities and involuntary 6-month weight loss ≥5% were insignificant. CONCLUSIONS: sarcopenia was present in 27.1% of older patients with cancer and was independently associated with 1-year mortality. The fact that sarcopenia was nearly as predictive for 1-year mortality as an advanced disease stage underlines the importance of preservation of muscle mass and function as a potential target of intervention in older patients with cancer.

Low Recent Protein Intake Predicts Cancer-Related Fatigue and Increased Mortality in Patients with Advanced Tumor Disease Undergoing Chemotherapy.

Cancer patients, in general, suffer from anorexia hence diminished nutritional intake. In a prospective observational study, we investigated the impact of recent energy and protein intake on cancer-related fatigue and 6-month mortality in patients undergoing chemotherapy. Recent protein and energy intake was assessed by 24-h recall in 285 patients. Cancer-related fatigue was determined by Brief Fatigue Inventory, and fat free mass index (FFMI) was assessed with bioelectrical impedance analysis. Symptoms with the validated German version of European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (30 questions) and 6-month mortality was documented. Risk factors of cancer-related fatigue and predictors of mortality were investigated with logistic regression analysis and stepwise Cox regression analysis, respectively. Low protein intake (<1 g/kg body weight) was found in 66% of patients, who were characterized by higher age, weight, and body mass index. Recent protein intake emerged as the strongest contributor to cancer-related fatigue followed by nausea/vomiting, insomnia, and age. Reduced protein intake, male sex, number of comorbidities, and FFMI were identified as significant predictors for increased 6-month mortality. In conclusion, a low recent protein intake assessed by 24-h recall is associated with a more than twofold higher risk of cancer-related fatigue and 6-month mortality. Every effort should be taken to assess and guarantee proper nutritional intake in patients undergoing chemotherapy.

The bioimpedance phase angle predicts low muscle strength, impaired quality of life, and increased mortality in old patients with cancer.

OBJECTIVES: We investigated the impact of low phase angle (PhA) values on muscle strength, quality of life, symptom severity, and 1-year mortality in older cancer patients. DESIGN: Prospective study with 1-year follow-up. PARTICIPANTS: Cancer patients aged >60 years. METHODS: PhA was derived from whole body impedance analysis. The fifth percentile of age-, sex-, and body mass index-stratified reference values were used as cut-off. Quality of life was determined with the European Organization of Research and Treatment in Cancer questionnaire, reflecting both several function scales and symptom severity. Muscle strength was assessed by hand grip strength, knee extension strength, and peak expiratory flow. RESULTS: 433 cancer patients, aged 60-95 years, were recruited. Patients with low PhA (n = 197) exhibited decreased muscle strength compared with patients with normal PhA (hand grip strength: 22 ± 8.6 vs 28.9 ± 8.9 kg, knee extension strength: 20.8 ± 11.8 vs 28.1 ± 14.9 kg, and peak expiratory flow: 301.1 ± 118 vs 401.7 ± 142.6 L/min, P < .001). Physical function, global health status, and role function from the European Organization of Research and Treatment in Cancer questionnaire were reduced, and most symptoms (fatigue, anorexia, pain, and dyspnea) increased in patients with low PhA (P < .001). In a risk-factor adjusted regression analysis, PhA emerged as independent predictor of physical function (ß:-0.538, P = .023), hand grip strength (ß:-4.684, P < .0001), knee extension strength (ß:-4.548, P = .035), and peak expiratory flow (ß:-66.836, P < .0001). Low PhA moreover predicted 1-year mortality in the Cox proportional hazards regression model, whereas grip strength was no longer significant. CONCLUSIONS: PhA below the fifth reference percentile is highly predictive of decreased muscle strength, impaired quality of life, and increased mortality in old patients with cancer and should be evaluated in routine assessment.

Discrepancy between body surface area and body composition in cancer.

Calculation of cytostatic dose is typically based on body surface area (BSA) regardless of body composition. The aim of this study was to assess the discrepancy between BSA and low fat-free mass (FFM) by investigating the prevalence of low FFM with regard to BSA in 630 cancer patients. First, BSA was calculated according to DuBois and DuBois. Patients were divided into 6 categories with respect to their BSA. Each BSA category was further divided into 3 groups according to FFM: low (<-1 SD of mean FFM), normal (-0.99 and 0.99 SD of mean FFM) or high (>1 SD of mean FFM), which was derived through bioelectric impedance analysis. FFM was reduced in 15.7% of patients, 69% had normal and 15.2% had high FFM. In patients with low FFM (i.e., more than-1 SD lower than the mean FFM within their BSA group), body mass index and fatigue were higher whereas functional status was reduced. Moreover, in the subcohort of patients receiving chemotherapy, absolute FFM [Hazard ratio (HR) = 0.970, P = 0.026] as well as the allocation to the low FFM group (HR = 1.644, P = 0.025) emerged as predictors of increased 1-yr mortality. In conclusion, there was a large discrepancy between FFM and BSA. Particularly women were affected by low FFM.

Bioelectrical phase angle and impedance vector analysis--clinical relevance and applicability of impedance parameters.

BACKGROUND & AIMS: The use of phase angle (PhA) and raw parameters of bioelectrical impedance analysis (BIA) has gained attention as alternative to conventional error-prone calculation of body composition in disease. This review investigates the clinical relevance and applicability of PhA and Bioelectrical Impedance Vector Analysis (BIVA) which uses the plot of resistance and reactance normalized per height. METHODS: A comprehensive literature search was conducted using Medline identifying studies relevant to this review until March 2011. We included studies on the use of PhA or BIVA derived from tetrapolar BIA in out- and in-patient settings or institutionalized elderly. RESULTS: Numerous studies have proven the prognostic impact of PhA regarding mortality or postoperative complications in different clinical settings. BIVA has been shown to provide information about hydration and body cell mass and therefore allows assessment of patients in whom calculation of body composition fails due to altered hydration. Reference values exist for PhA and BIVA facilitating interpretation of data. CONCLUSION: PhA, a superior prognostic marker, should be considered as a screening tool for the identification of risk patients with impaired nutritional and functional status, BIVA is recommended for further nutritional assessment and monitoring, in particular when calculation of body composition is not feasible.

Effect of sexual dimorphism on muscle strength in cachexia.

BACKGROUND: Reduced muscle strength is a cardinal feature in cachexia. We investigated whether weight loss is associated differently with muscle strength in men and women in a large cohort of hospitalized patients. METHODS: One thousand five hundred hospitalized patients (whereof 718 men, mean age 57.6 ± 16.0 years, mean body mass index (BMI) 24.6 ± 4.8 kg/m²) were included in the study. Non-edematous involuntary weight loss was determined with Subjective Global Assessment; isometric maximal muscle strength was evaluated by hand grip strength. Mid-upper arm circumference and triceps skinfold were used to calculate arm muscle area. Interrelationship between sex and weight loss was evaluated by regression analysis performed with the general linear model (GLM) allowing adjustment for continuous and categorical variables and corrected for age, arm muscle area (AMA), BMI, and diagnosis category (benign/malignant disease) as potentially confounding covariates. RESULTS: Both men and women exhibited a significant stepwise decrease of hand grip strength with increasing weight loss. Age, sex, moderate and severe weight loss, BMI, and AMA were significant predictors of hand grip strength. The GLM moreover revealed a significant sex × weight loss effect, since grip strength was similarly decreased in moderate weight loss in men and women when compared to control patients without weight loss (8.5% in men and 10.5% in women, not significant (n.s.)), but the further reduction of grip strength in severe weight loss was significantly different between men and women (10.6% vs. 4.1%, P = 0.033). CONCLUSIONS: Our findings indicate sex-specific differences in muscle strength response to weight loss.

Determinants of bioelectrical phase angle in disease.

Phase angle (PhA), a parameter of bioelectrical impedance analysis, is a well-known predictor of morbidity and mortality in various diseases. The causes of decreased PhA are, however, not yet completely understood. We therefore investigated determinants of PhA in 777 hospitalised patients in a retrospective analysis. PhA was assessed by bioelectrical impedance analysis at 50 KHz. Subjective global assessment (SGA) was used to evaluate nutritional status. Age, sex, BMI as well as nutritional status (SGA), benign or malignant disease and C-reactive protein (CRP) were investigated as potential determinants of PhA and standardised PhA (SPhA) = (observed PhA - mean PhA of reference values)/standard deviation of reference values in a general linear model regression analysis. Next to age (estimated effect size, 46·6%; P<0·0001), malnutrition (39·1%; P<0·0001) emerged as a major PhA determinant in our study population. Moreover, sex (6·4%; P<0·0001), CRP (4·4%; P<0·0001) and BMI (3·5%; P < 0·0001) exhibited a significant influence on PhA, whereas malignant disease showed no significant effect in this model. The only significant determinants of SPhA were malnutrition (85·4%; P<0·0001) and inflammation (9·6 %; P<0·0001). In conclusion, next to the established predictors, malnutrition and inflammation have a strong impact on PhA in sick individuals, which partly explains its prognostic power. When investigating the SPhA, only malnutrition and inflammation were found to be significant predictors, as a result of which the SPhA is considered a more suitable indicator of nutritional and health status.

Hand grip strength: outcome predictor and marker of nutritional status.

BACKGROUND & AIMS: Among all muscle function tests, measurement of hand grip strength has gained attention as a simple, non-invasive marker of muscle strength of upper extremities, well suitable for clinical use. This review outlines the prognostic relevance of grip strength in various clinical and epidemiologic settings and investigates its suitability as marker of nutritional status in cross-sectional as well as intervention studies. METHODS: Studies investigating grip strength as prognostic marker or nutritional parameter in cross-sectional or intervention studies were summarized. RESULTS AND CONCLUSIONS: Numerous clinical and epidemiological studies have shown the predictive potential of hand grip strength regarding short and long-term mortality and morbidity. In patients, impaired grip strength is an indicator of increased postoperative complications, increased length of hospitalization, higher rehospitalisation rate and decreased physical status. In elderly in particular, loss of grip strength implies loss of independence. Epidemiological studies have moreover demonstrated that low grip strength in healthy adults predicts increased risk of functional limitations and disability in higher age as well as all-cause mortality. As muscle function reacts early to nutritional deprivation, hand grip strength has also become a popular marker of nutritional status and is increasingly being employed as outcome variable in nutritional intervention studies.

Cutoff percentiles of bioelectrical phase angle predict functionality, quality of life, and mortality in patients with cancer.

BACKGROUND: The bioelectrical phase angle has shown predictive potential in various diseases, but general cutoffs are lacking in the clinical setting. OBJECTIVES: This study evaluated the prognostic value of the fifth percentile of sex-, age-, and body mass index-stratified phase angle reference values in patients with cancer with respect to nutritional and functional status, quality of life, and 6-mo mortality. In a second step, we also studied the effect of the standardized phase angle (with a z score to determine individual deviations from the population average) on these variables. DESIGN: A total of 399 patients with cancer were studied. Phase angle was obtained with bioelectrical impedance analysis; muscle function was assessed by handgrip strength and peak expiratory flow. Quality of life was determined by the European Organization for Research and Treatment of Cancer questionnaire. Nutritional status was assessed by using Subjective Global Assessment. Survival of patients was documented after 6 mo. RESULTS: Patients with a phase angle of less than the fifth reference percentile had significantly lower nutritional and functional status, impaired quality of life (P lt 0.0001), and increased mortality (P lt 0.001). The standardized phase angle emerged as a significant predictor for malnutrition and impaired functional status in generalized linear model regression analyses. It was also a stronger indicator of 6-mo survival than were malnutrition and disease severity in the Cox regression model (P lt 0.0001) and according to the receiver operating characteristic curve. CONCLUSIONS: The standardized phase angle is an independent predictor for impaired nutritional and functional status and survival. The fifth phase angle reference percentile is a simple and prognostically relevant cutoff for detection of patients with cancer at risk for these factors.

Determinants of hand grip strength, knee extension strength and functional status in cancer patients.

BACKGROUND & AIMS: Decreased functionality and muscle weakness are prominent features in cancer patients. We investigated determinants of muscle function assessed by hand grip and knee extension strength as well as functional status in cancer patients. METHODS: 189 consecutively admitted cancer patients (age 60.8 ± 12.7 years, 96 male) were recruited. Muscle function was assessed by hand grip and knee extension strength, and percentage of anticipated peak expiratory flow (%PEF). Functional status was determined by the EORTC questionnaire of quality of life. Nutritional status was assessed with Subjective Global Assessment (SGA). Age, gender, SGA, body mass index, clinical variables such as cancer location, presence of distant metastases, tumour burden according to TNM stage, UICC stage, number of drugs per day, number of comorbidities, type of treatment and depression were investigated as potential risk factors for muscle weakness and impaired functional status in a multiple regression analysis. RESULTS: 80 patients (39 male) were classified moderately or severely malnourished. Malnutrition also emerged as an independent determinant for hand grip (estimated effect size 11%, p < 0.01), knee extension strength (estimated effect size 12%, p < 0.001), and peak expiratory flow (estimated effect size 30%, p < 0.008) and functional status (estimated effect size 19.4%, p < 0.001) next to age and gender, which were the strongest predictors. Among the disease parameters, only amount of daily medication exhibited a significant influence on knee extension strength. CONCLUSIONS: Malnutrition is a disease independent risk factor for reduced muscle strength and functional status in cancer patients. Treatment of malnutrition might therefore also restore muscle strength.