Inflammation as a diagnostic criterion in the GLIM definition of malnutrition—what CRP-threshold relates to reduced food intake in older patients with acute disease?

Malnutrition with weight and muscle loss is common in older patients and often multifactorial. Disease-related inflammation is a key contributor to diminished appetite and reduced food intake, increasing the risk of malnutrition. The GLIM diagnostic framework requires at least one phenotypic criterion (e.g., weight loss, low BMI, reduced muscle mass) and one etiologic criterion (e.g., reduced food intake/malabsorption or inflammation). While thresholds for weight loss, BMI, and low intake are defined, how to classify inflammation remains unclear. Given that inflammation can fulfill the etiologic criterion in lieu of low food intake, it is important to identify an inflammation level associated with increased risk of reduced intake. CRP is an unspecific biomarker of systemic inflammation, typically <0.5 mg/dl in healthy persons. Prior work suggests higher CRP is associated with lower intake in older hospitalized patients. This study aimed to determine the CRP level at which the risk of low food intake increases in acutely ill older hospitalized patients.

Prior studies have shown that inflammation diminishes appetite and food intake in older patients and is associated with adverse functional and clinical outcomes. CRP is commonly elevated in both acute and chronic inflammatory states and correlates with reduced intake in hospitalized older adults. Earlier reports found that a substantial proportion of patients with CRP >3.0 mg/dl had intake <75%, and that elevated CRP (>1 mg/dl) was associated with lower energy intake in older inpatients. However, specific CRP thresholds linked to impaired intake were not previously established. The GLIM criteria include inflammation as an etiologic factor but lack explicit thresholds and a distinction between acute high-grade and chronic low-grade inflammation; some community-based studies have applied relatively low inflammatory biomarker cut-offs within normal ranges to meet the GLIM inflammation criterion, underscoring the need for clearer, clinically relevant thresholds.

Design and setting: Cross-sectional post hoc analysis of two previous studies conducted at two acute care geriatric hospital departments in Germany (Marien-Hospital Herne, MHH; St. Marien-Hospital Borken, MHB). Participants: 377 consecutively admitted patients (200 from MHH, 177 from MHB), aged 63–100 years; inclusion required age >60 years and ability to cooperate. All measurements were conducted within the first days after hospital admission. Ethics: Approved by the Ruhr-University Bochum ethics committee (no. 16-5956, 4 April 2017) and Friedrich-Alexander-University Erlangen-Nürnberg (no. 16_16 Bc, 1 February 2016). Written informed consent was obtained from all participants. Nutritional status and intake: Nutritional status was assessed by the Mini Nutritional Assessment Short Form (MNA-SF); classified as normal (12–14), at risk (8–11), or malnourished (0–7). Nutritional intake was assessed using the NRS-2002 food intake item in MHB and the plate diagram method in MHH; intake categorized as >75%, 50–75%, and ≤50% of requirements. Geriatric assessments: Functional status via Barthel Index (0–100); cognitive function via MoCA (MHH) or MMSE (MHB), with scores <26 indicating cognitive impairment; depressive symptoms via DIA-S (MHH) or GDS-15 (MHB). CRP measurement: Serum CRP analyzed at admission or the following day per standard procedures. Inflammation categories: no inflammation 0.0–0.49 mg/dl, mild 0.5–3.0 mg/dl, moderate to severe ≥3.0 mg/dl. For intake comparisons across inflammation levels, CRP groups were 0.0–0.99, 1.0–1.99, 2.0–2.99, 3.0–4.99, 5.0–9.99, and ≥10.0 mg/dl. Statistical analysis: Continuous variables reported as mean ± SD or median (IQR) as appropriate; categorical variables as n (%). Differences in CRP across intake levels and MNA-SF categories tested by Kruskal–Wallis with pairwise comparisons. Proportions with intake <50% and <75% across CRP groups compared using one-way ANOVA with Tukey post hoc or Chi-square test, as appropriate. Significance threshold P < 0.05.

- Sample characteristics: n=377; mean age 82.2 ± 6.6 years; 64% female. By MNA-SF, 23% malnourished and 53% at risk. Inflammation distribution: 27% no inflammation, 40% mild (0.5–3.0 mg/dl), 33% moderate to severe (≥3.0 mg/dl). - Food intake: 22% (82/377) had intake <50% of requirements; among these, 45% had moderate to severe inflammation, 35% mild, and 20% no inflammation. - CRP and intake: Median CRP was significantly higher in patients with intake <50% versus >75% of requirements (2.3 vs 0.7 mg/dl, P < 0.001). - Threshold behavior: Proportions with intake <50% were similar across CRP groups 0.0–0.99, 1.0–1.99, and 2.0–2.99 mg/dl, but increased with CRP ≥3.0 mg/dl (from 19% at 2.0–2.99 mg/dl to 28% at 3.0–4.99 mg/dl; P = 0.062). Groups with CRP ≥3.0 mg/dl showed a markedly higher proportion of patients with low intake (<50% and <75%). - No significant differences in median CRP across MNA-SF categories (malnourished: 1.4 mg/dl [IQR 0.4–4.3]; at risk: 1.4 mg/dl [0.5–4.6]; normal: 1.1 mg/dl [0.4–4.1]). - Overall inference: A CRP level around 3.0 mg/dl is associated with notably increased risk of reduced food intake in acutely ill older inpatients.

The study directly addresses the research question by linking graded CRP categories to contemporaneously assessed food intake among acutely ill older inpatients. Findings show a clear increase in the proportion of patients with reduced intake at CRP levels ≥3.0 mg/dl, while levels below 3.0 mg/dl showed similar proportions, suggesting a pragmatic threshold for clinically relevant inflammation-related anorexia in this population. This aligns with prior observations that elevated CRP is associated with lower intake and that substantial fractions of patients with CRP >3.0 mg/dl have intake <75%. The results support using CRP ≥3.0 mg/dl as an orientation for fulfilling the GLIM etiologic criterion of inflammation in hospitalized older adults when assessing malnutrition risk. The discussion emphasizes the need to distinguish between acute high-grade and chronic low-grade inflammation in GLIM operationalization, as both degree and duration of inflammation contribute to anorexia and catabolism. Clearer guidance may prevent over- or underestimation of malnutrition when inflammation is used as an etiologic criterion and could facilitate clinical implementation.

A serum CRP threshold of approximately 3.0 mg/dl appears reasonable to indicate acute inflammation associated with reduced food intake in acutely ill older hospitalized patients and may guide application of the GLIM inflammation criterion in this setting. Future research should define clinically relevant thresholds for both acute and chronic inflammation, clarify duration effects, and validate these thresholds prospectively in populations where disease-related inflammation is the primary driver of malnutrition.

- Post hoc cross-sectional analysis of two primary studies, limiting causal inference. - Two different methods were used to assess food intake (NRS-2002 item and plate diagram); no gold standard exists, though both are clinically relevant/validated in context. - Very old, acutely ill patients with multiple comorbidities were included; effects of acute versus chronic inflammation could not be disentangled. - Malnutrition is multifactorial; residual confounding is likely and cannot be excluded. - Results are most applicable to acutely ill older inpatients; generalizability to other settings requires further study.