Abstract

The aging process is accompanied by high risk of malnutrition. Low-grade SCI and acute inflammation may drive anorexia of aging which may cause or exacerbate loss of muscle mass and malnutrition. For the diagnosis of malnutrition, inflammation and muscle mass must be assessed according to the GLIM criteria. Firstly, inflammation is assessed with disease-based indicators with CRP as a supportive inflammatory biomarker, but concerns have been raised about the appropriateness of the current approach. GDF15 has emerged as a potential inflammatory biomarker for malnutrition in old age and as an important regulator of appetite. Secondly, muscle mass is sparsely estimated with BIA or DXA in older adults, instead proxies for muscle mass are often used. Therefore, more research is needed to investigate how inflammation and muscle mass can be assessed in the GLIM criteria in older adults. In the first part of this thesis (Study 1 and Study 2), we investigated the association between GDF15 with nutritional status, appetite, and physical function in acutely admitted older adults (Study 1). Secondly, we investigated the performance of MF-BIA to estimate reduced muscle mass compared to DXA and explored the association between muscle mass, dehydration, poor appetite, and malnutrition in older adults (Study 2). In Study 1, 302 patients were included. The adjusted (age, sex, and CRP) logistic regression analysis found that higher GDF15 levels were associated with malnutrition, poor appetite, and low physical function (P = 0.004). In Study 2, 42 patients were included. The analysis of sensitivity and PPV revealed that ASM was superior in detecting reduced muscle mass compared to ASMI and FFMI. Sensitivity for ASM, ASMI, and FFMI were 86%, 22%, and 23%, respectively. PPV for ASM, ASMI, and FFMI were 75%, 67%, and 75%, respectively. The results indicated that patients with dehydration had higher median muscle mass values; this was the opposite for patients with malnutrition. Median muscle mass values appeared similar regardless of appetite status.

Anorexia of aging is a key driver for the development of malnutrition, and it appears closely related to low-grade SCI and acute inflammation. However, to date current treatment strategies are limited, and no pharmacologic agents have proven to effectively treat anorexia of aging. In the second part of the thesis (Study 3), we investigated the effect of CBM when administered at two time points on caloric intake during a controlled feeding study with a homogenous ad-libitum lunch test meal and safety parameters compared to placebo in older adults with poor appetite. In Study 3, 17 patients were included. A paired t-test found no difference in caloric intake during CBM and placebo conditions (mean difference in caloric intake favoring CBM: 10 kcal, 95% CI: -55-75 kcal, P = 0.75). Evaluation of safety parameters including blood pressure and heart rate, tiredness, vertigo, nausea, and euphoria suggests that CBM is generally tolerated.

The results from this thesis show that higher GDF15 levels were associated with malnutrition and risk factors for malnutrition in acutely admitted older adults. GDF15 may hold promise as an objective inflammatory biomarker for malnutrition assessment and as a biomarker for appetite. However, its utility within nutritional care is unclear since the exact biological functions of GDF15 remain to be determined. Furthermore, MF-BIA appeared reasonable for identifying reduced muscle when compared to DXA in older adults. Larger cohorts are needed to increase the understanding of the effects of subject-related factors (fluid shifts, fasting, and hydration) on muscle mass estimates. Lastly, our trial did not find an increase in caloric intake or safety concerns when CBM was administered during a controlled feeding study in older adults with poor appetite.

More research on the utility of GDF15 and MF-BIA in the GLIM criteria in older adults and optimization of treatment strategies for anorexia of aging is highly needed to improve the identification and treatment of malnutrition in older adults characterized by low-grade SCI and recurrent acute inflammation.