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/m(2)) 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 (FFA(Supp)) (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, FFA(Supp) at baseline. Fetuin-B decreased during dietary weight loss (4.2 (3.5-4.9) vs. 3.8 (3.2-4.6) mu g/ml; p = 2.1 x 10(-5)). This change was associated with concomitant improvement of HOMA-IR (r = 0.222; p = 0.008) and FFA(Supp) (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 FFA(Supp) 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

Impact of body composition and dietary intake as risk factors for an impaired clinical outcome in cancer patients

Onkologische Patienten entwickeln im Laufe ihrer Erkrankung häufig Begleiterscheinungen, die mit einer beeinträchtigten Lebensqualität, reduzierten Verträglichkeit der Therapie und einer verschlechterten Prognose einhergehen. Zu diesen Beschwerden gehören die Kachexie und tumorassoziierte Fatigue, die mit einer verringerten Nahrungsaufnahme, verschlechterten Körperzusammensetzung sowie verringerten Leistungsfähigkeit assoziiert sind. Die frühe Erfassung dieser Risikofaktoren ist in der Behandlung von Tumorpatienten somit von großer Bedeutung. Der Phasenwinkel, ein direkt gemessener Rohwert der Bioelektrischen Impedanzanalyse (BIA), hat als Indikator der Körperzusammensetzung zunehmend an wissenschaftlichem Interesse gewonnen. In einem Kollektiv an stationär behandelten, onkologischen Patienten wurde erstmals die prognostische Bedeutung des Phasenwinkels unter Berücksichtigung der alters-, geschlechts- und BMI-stratifizierten Referenzwerte untersucht. Der Phasenwinkel unter der fünften Referenzperzentile war mit einem schlechteren Ernährungs- und funktionellen Status, einer verschlechterten Lebensqualität und gesteigerten Mortalität assoziiert. Der anhand der Referenzwerte standardisierte Phasenwinkel erwies sich nicht nur als signifikanter Prädiktor einer Kachexie und verschlechterten Muskelkraft, sondern hatte auch eine höhere prognostische Aussagekraft in Bezug auf die 6-Monats-Mortalität als Kachexie oder Krankheitsschwere. Die Ergebnisse zeigen, dass der Phasenwinkel zur Identifikation von Risikopatienten herangezogen werden kann, die von einer intensiveren medizinischen und ernährungsmedizinischen Therapie profitieren könnten. Da die Körperzusammensetzung auch für die Therapieverträglichkeit der Chemotherapie von Bedeutung ist, wurde die Variabilität der anhand der BIA berechneten fettfreien Masse (FFM) im Vergleich zur Körperoberfläche bei onkologischen Patienten analysiert. Bei mehr als 30% der untersuchten Patienten wurde eine signifikante Abweichung der FFM von der jeweiligen Norm festgestellt, wobei besonders Frauen häufig davon betroffen waren. Eine verringerte FFM war mit einem verschlechterten funktionellen Status und einer stärker ausgeprägten Fatigue assoziiert. Zudem war eine niedrige FFM, neben Alter und Tumorstadium, ein unabhängiger Prädiktor der 1-Jahres-Mortalität. Des Weiteren entwickeln viele Patienten im Zuge ihrer Tumorerkrankung und Behandlung eine Anorexie, die mit einer verringerten Nahrungsaufnahme einhergeht. Im Rahmen einer Studie an chemotherapierten Patienten mit einer hohen Prävalenz der Fatigue, wurde die Bedeutung einer verringerten Protein- bzw. Energieaufnahme untersucht. Die Mehrheit der Studienpatienten wies eine inadäquate Proteinaufnahme unter 1 g/Kilogramm Körpergewicht auf. Die zu geringe Proteinzufuhr galt neben Übelkeit/Erbrechen, Schlaflosigkeit und Alter als stärkste Determinante der Fatigue. Außerdem waren eine verringerte Proteinaufnahme, das Geschlecht, die Anzahl an Komorbiditäten und der FFM-Index signifikante Prädiktoren einer gesteigerten 6-Monats-Mortalität. Die Ergebnisse der drei Publikationen zeigen, dass ein verringerter Phasenwinkel, eine verschlechtere Körperzusammensetzung sowie eine verminderte Proteinaufnahme einen entscheidenden Einfluss auf Leistungsfähigkeit, Fatigue und Mortalität bei onkologischen Patienten nimmt. Die Erfassung dieser Risikofaktoren sollte daher im Rahmen der Behandlung eine besondere Beachtung finden.Cancer patients often develop problems which are accompanied by impaired quality of life, tolerability of therapy or even clinical outcome. These problems can include cachexia and cancer-related fatigue, which are associated with decreased nutritional intake, impaired body composition and function. The early assessment of these risk factors is important for the treatment of cancer patients. The phase angle, a raw parameter of the bioelectrical impedance analysis (BIA), has gained much attention in the last years. We investigated the prognostic value of phase angle considering the age-, sex- and BMI-stratified reference values in hospitalised cancer patients. A phase angle below the fifth percentile of the reference values was associated with impaired nutritional and functional status, quality of life and increased mortality. Based on the reference values standardised phase angle was identified as a predictor of cachexia and impaired muscle function. Furthermore, it was a stronger indicator of 6-month mortality than cachexia or disease severity. These results indicate that the phase angle is a useful parameter for the identification of patients at risk and who would profit from a more intensive medical and nutritional therapy. Body composition is likely a factor which influences therapy tolerability. We therefore investigated the variability of fat-free mass (FFM) using the BIA, while considering the body surface area. More than 30% of the patients had a FFM differing from the respective norm and especially women were affected by low FFM. Low FFM was associated with impaired functional status and increased fatigue. Furthermore, next to age and advanced disease, low FFM was an independent predictor of increased 1-year mortality. Cancer patients often suffer from anorexia, which is accompanied by reduced nutritional intake. The impact of low protein and energy intake was investigated in patients with high prevalence of cancer- related fatigue and undergoing chemotherapy. The majority of the patients showed low recent protein intake below 1g/kilogram body weight, which was shown to be the strongest impact factor on cancer-related fatigue, next to nausea/vomiting, insomnia and age. Moreover, reduced protein intake, male sex, number of comorbidities as well as FFM-Index were significant predictors of increased 6-month mortality. The results of the three papers suggest that impaired phase angle, body composition and protein intake are relevant factors for the functionality, fatigue and mortality in oncological patients. Therefore, particular attention should be given to the assessment of these risk factors in the treatment of cancer patients

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 Sarcopenia and 1-year mortality in cancer 413 Downloaded from https://academic.oup.com/ageing/article-abstract/48/3/413/5272750 by Université de Genève user on 26 November 2019 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