Clinical Nutrition 42 (2023) 166e172

Contents lists available at ScienceDirect

Clinical Nutrition
journal homepage: http://www.elsevier.com/locate/clnu

Original article

Prognostic implications of the global leadership initiative on

malnutrition criteria as a routine assessment modality for
malnutrition in hospitalized patients at a university hospital
Naoharu Mori a, *, Keisuke Maeda a, b, Yasushi Fujimoto c, Tomoyuki Nonogaki a, d,
Yuria Ishida a, e, Rie Ohta e, Akio Shimizu a, f, Junko Ueshima a, g, Ayano Nagano a, h,
Ryoji Fukushima i
a
Department of Palliative and Supportive Medicine, Graduate School of Medicine, Aichi Medical University, Nagakute, Aichi, Japan
b
Department of Geriatric Medicine, Hospital, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan
c
Department of Otorhinolaryngology and Head and Neck Surgery, Aichi Medical University, Nagakute, Aichi, Japan
d
Department of Pharmacy, Aichi Medical University Hospital, Nagakute, Aichi, Japan
e
Department of Nutrition, Aichi Medical University Hospital, Nagakute, Aichi, Japan
f
Department of Health Science, Faculty of Health and Human Development, University of Nagano, Nagano City, Nagano, Japan
g
Department of Clinical Nutrition and Food Services, NTT Medical Center Tokyo, Shinagawa-ku, Tokyo, Japan
h
Department of Nursing, Nishinomiya Kyoritsu Neurosurgical Hospital, Nishinomiya, Japan
i
Department of Surgery, Teikyo University School of Medicine/Health and Dietetics Teikyo Heisei University, Tokyo, Japan

a r t i c l e i n f o s u m m a r y

Article history: Background & aims: Few studies have examined the association between mortality and malnutrition
Received 6 April 2022 diagnosed using the Global Leadership Initiative on Malnutrition (GLIM) criteria for routine nutritional
Accepted 11 December 2022 assessment; thus, this association is not well known. We aimed to clarify the association between GLIM-
defined malnutrition and mortality in a large population of hospitalized patients.
Keywords: Methods: In this retrospective cohort study, we enrolled adult patients admitted to Aichi Medical Uni-
GLIM
versity Hospital between April 2019 and March 2021, who underwent nutritional assessment using the
Malnutrition
GLIM criteria. In November 2021, we collected the following data from electronic medical records: de-
Nutritional assessment
Cachexia
mographic, clinical, and laboratory data upon admission; nutritional data assessed using GLIM criteria;
Disease related malnutrition and data on final patient outcomes.
Calf circumference Results: In this study, we included 9372 hospitalized patients who were identified to be at risk by the
validated nutritional screening tools (50.6% men, median age 75.0 [67.0e82.0] years, 69.2% patients aged

70 years). The number of patients with no, moderate, and severe GLIM-defined malnutrition was 4145
(44.2%), 2799 (29.9%), and 2428 (25.9%), respectively. KaplaneMeier survival curve analysis showed a
significant increase in mortality with worsening nutritional status (log-rank test, P < 0.001). After
adjusting for age and sex, multivariable Cox regression analysis revealed that both moderate (Hazard
ratio [HR] 2.0, 95% confidence interval [CI] 1.79e2.23, P < 0.001) and severe malnutrition (HR 3.06, 95% CI
2.74e3.40, P < 0.001) were independent risk factors for mortality. Moreover, multivariable analysis
showed that four of the five GLIM sub-criteria (except low body mass index) were independently
associated with prognosis.
Conclusion: Malnutrition and its severity, routinely assessed using the GLIM criteria, are associated with
high mortality in hospitalized patients at nutritional risk. Further research is needed to evaluate the
usefulness of the GLIM sub-criteria, including low body mass index, in these patients.
© 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/).

1. Introduction

* Corresponding author. Palliative Care Center, Aichi Medical University, 1-1 Malnutrition results from a combination of varying degrees of
Yazakokarimata, Nagakute, Aichi 480-1195, Japan. nutritional deficiencies and inflammatory activity, leading to
E-mail address: [email protected] (N. Mori).

https://doi.org/10.1016/j.clnu.2022.12.008
0261-5614/© 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
N. Mori, K. Maeda, Y. Fujimoto et al. Clinical Nutrition 42 (2023) 166e172

changes in body composition and decreased function [1,2]. It is nutritional status of malnourished patients or patients at high risk
associated with increased complication rates, longer hospital stays, of malnutrition in an acute care ward, the team can obtain 200
increased mortality, higher costs, and increased readmission rates points (about 14 USD) per patient per week in reimbursement
[3,4]. In addition, hospitalized patients often experience further (named “Additional Medical Fee for the Nutrition Support Team
deterioration of nutritional status after admission [5]. Therefore, it Activity”). The NST in the study hospital comprised four qualified
is increasingly being considered important to perform early professionals and conducted nutrition assessments. Therefore, the
screening and appropriate nutritional assessments in patients at patients in this study were eligible for the additional medical fee.
risk of malnutrition [2,6]. The NST visited all patients at nutritional risk and attempted to
With the recognition of the importance of nutritional assessment, perform the nutritional assessment. However, during several NST
several diagnostic criteria for malnutrition have been published visits, patients were often absent owing to engagement in other
[1,7]; although, none of them are hitherto well-established. The medical procedures or other reasons, and about one-third of the
Global Leadership Initiative on Malnutrition (GLIM) criteria have patients were discharged without a nutritional assessment, with a
been newly developed by representatives of the world's leading short stay in an acute care hospital. The exclusion criteria for cases
clinical nutrition societies [8]. In diagnosing malnutrition using the with nutritional assessment in this study were missing nutritional
GLIM criteria, the first step is to identify patients at risk for malnu- assessment data related to GLIM criteria, including height and
trition using a validated nutritional screening tool. Nutritional weight. This study was conducted in accordance with the principles
assessment is then performed to diagnose malnutrition and deter- of the Declaration of Helsinki and approved by the Ethics Review
mine its severity [8]. At the time of publication of the GLIM criteria, Committee of Aichi Medical University Hospital (No. 2021e136).
several measurable criteria did not have established reference Owing to the retrospective nature of the study, written informed
values. For example, no reference values were available for body consent could not be obtained. However, the participants were
mass index (BMI) in grading the severity of malnutrition among guaranteed the right to withdraw from the study through an opt-
Asians, and thus, we previously conducted a study to establish BMI out procedure by posting a notice on the hospital's website.
cutoff values in hospitalized patients, shortly after the publication of
the GLIM criteria [9]. Owing to the necessity of validating the GLIM 2.2. Data collection
criteria on a global scale [8,10], validation studies are being con-
ducted in various healthcare facilities and on various patient pop- Data were obtained retrospectively from the patients’ medical
ulations; these validation studies range from prospective studies to records. The variables collected included age, sex, height, weight,
retrospective analyses using existing nutritional data. However, at BMI, calf circumference (CC), hemoglobin levels, serum albumin
present, the findings of these validation studies are insufficient [11]. levels, C-reactive protein (CRP) levels, MUST score, MNA-SF score,
The GLIM criteria are primarily used in hospitalized patients at malnutrition diagnosed using the GLIM criteria and sub-criteria,
high risk for disease-related malnutrition. Nevertheless, most length of hospital stay, patient status on discharge (alive or dead),
validation studies of the GLIM criteria have been conducted in and final outcome as documented in the electronic medical record
patients with specific diseases or elderly patients, and few studies at the end of November 2021. The GLIM sub-criteria included
have been conducted on the general hospitalized patient popula- phenotypic criteria, such as weight loss, low BMI, and reduced
tion in acute-care hospitals [11]. In addition, no study has validated muscle mass, as well as etiologic criteria, such as reduced food
the outcome of malnutrition using the GLIM criteria as a routine intake or assimilation and disease burden/inflammation.
nutritional assessment for hospitalized patients, and the associa-
tion between GLIM-defined malnutrition and mortality in these 2.3. GLIM criteria
patients remains unknown. Therefore, the main objective of this
study was to determine the association between malnutrition, The GLIM criteria consist of three phenotypic and two etiologic
diagnosed using the GLIM criteria as a routine nutritional assess- criteria; at least one phenotypic and one etiologic criterion are
ment, its severity, and overall survival. The secondary objective was required for the diagnosis of malnutrition [8]. Table 1 shows the
to identify the effect of each GLIM criterion on mortality. parameters of the GLIM criteria and their thresholds used in the
present study. To evaluate weight loss, participants were asked to
2. Materials & methods self-report their weight change over the past 3e6 months. BMI was
calculated as body weight (kg) divided by the square of the patient
2.1. Participants height (m). Reduced muscle mass was determined based on the CC
(cm) of the right leg, with the patient in the supine position with 90 
This retrospective cohort study included adult patients aged knee flexion. In this study, we used the validated reduced muscle

18 years who were admitted to the Aichi Medical University mass cutoff values of CC for Japanese patients (30 cm in men and
Hospital between April 2019 and March 2021. The study site was a 29 cm in women), as previously reported [9,14]. The criterion for
900-bed, acute-care university hospital. All newly admitted pa- reduced food intake or assimilation was determined by interviewing
tients were screened for malnutrition on admission in accordance the patient during the nutrition assessment visit and checking the
with the Japanese health insurance system's regulations for basic patient's medical record, and if the reduction in oral intake
hospitalization charges. Nutrition screening was performed using exceeding 50% of the energy requirement lasted more than one
the Malnutrition Universal Screening Tool (MUST) [12] and Mini- week, any reduction exceeding two weeks, or if the patient had a
Nutritional Assessment-Short Form (MNA-SF) [13] for young and chronic gastrointestinal condition that adversely affects food
elderly patients, respectively. Patients with a MUST score
2 were assimilation or absorption, such as short bowel syndrome, pancre-
considered at risk for malnutrition and required referral to a atic insufficiency, esophageal strictures, gastroparesis or chronic
nutrition support team (NST) [12]; an MNA-SF score 11 was also diarrhea, was determined to be applicable. Disease burden/inflam-
recognized as a criterion for subsequent nutritional assessment mation criterion was defined as the presence of acute inflammatory
[13]. Nutritional assessment by the NST was conducted within 5 diseases, such as major infection; burns; trauma or closed head
days of admission of patients at nutritional risk. Under the Japanese injury; comorbidity of chronic or recurrent mild to moderate
health insurance system, when an NST, comprising a qualified inflammation, such as malignant disease, chronic obstructive pul-
physician, nurse, pharmacist, and dietitian, works to improve the monary disease, congestive heart failure, chronic renal disease, or C-
167
N. Mori, K. Maeda, Y. Fujimoto et al. Clinical Nutrition 42 (2023) 166e172

Table 1
Parameters of the GLIM criteria and their thresholds used in the present study.

Grade Phenotypic criteria Etiologic criteria

Non-volitional Low BMI Reduced muscle Reduced food intake or Disease burden/
weight loss mass assimilation inflammation

Moderate 5%e10% within the BMI <18.5 kg/m2 for CC < 30.0 cm for 50% of energy requirements >1 Acute disease/injury
malnutrition past 6 months, age <70 years, men, week or
or BMI <20 kg/m2 for age CC < 29.0 cm for or Chronic inflammatory
10%e20% beyond
70 years women any reduction in energy disease
6 months requirement for >2 weeks or
Severe >10% within the BMI <17.0 kg/m2 for CC < 27.0 cm for or CRP level >5 mg/L
malnutrition past 6 months, age <70 years, men, any chronic gastrointestinal
or BMI <17.8 kg/m2 for CC < 26.0 cm for condition that adversely
>20% beyond age
70 years women impacts food assimilation or
6 months absorption

GLIM, The Global Leadership Initiative on Malnutrition; BMI, body mass index; CC, calf circumference; CRP, C-reactive protein.

reactive protein levels >5 mg/L. For patients diagnosed with Nutritional assessment was performed by the nutrition support
malnutrition, three phenotypic criteria were used to assess the team in 9520 patients. We included 9372 patients in the final
severity of malnutrition, in accordance with the diagnostic flow of analysis, after excluding patients who did not undergo nutritional
the GLIM criteria [8]: (i) weight loss >10%, (ii) severely low BMI, or assessment using the GLIM criteria or who did not have related
(iii) a severe deficit in muscle mass. The GLIM criteria do not provide documented data. Of these, 50.6% (n ¼ 4746) were men. The me-
specific cutoff values for BMI that distinguish between moderate dian age of the patients was 75.0 [67.0e82.0] years, and 69.2%
and severe malnutrition in Asians [8]. We identified and used 17.0 (n ¼ 6485) of patients were aged
70 years. Major reasons for
and 17.8 kg/m2 as cutoff values for severely low BMI in the younger hospital admission, based on the ICD-10, were neoplasms
and older adult populations, respectively, as previously reported in (n ¼ 2604, 27.8%) as well as cardiovascular (n ¼ 1403, 15.0%),
our institution [9]. Additionally, specific reference values for CC, digestive (n ¼ 1275, 13.6%), and respiratory (n ¼ 842, 9.0%) diseases.
which assesses severe loss of muscle mass, are not provided in the Table 2 shows the characteristics of patients by GLIM-defined
GLIM criteria. In our institution, the CC values indicating severe nutritional status. The number of patients with no, moderate, and
muscle mass loss were defined as < 27 cm for men and <26 cm for severe malnutrition was 4145 (44.2%), 2799 (29.9%), and 2428
women; these values are >10% lower than the corresponding values (25.9%), respectively. Compared with patients without malnutri-
indicating muscle mass loss in the sarcopenia diagnostic criteria [9]. tion, those with moderate and severe malnutrition were older;
Using these cutoff values, we conducted aa study in our institution predominantly women; had significantly lower BMIs, CCs, and
to investigate the prevalence of GLIM-defined malnutrition that hemoglobin levels; and had higher CRP levels.
showed similar frequencies of patients with severely reduced In-hospital mortality increased with worsening nutritional
muscle mass and other phenotypic criteria [9]. Therefore, these status (P < 0.001); the mortality rates were 2.1%, 4.9%, and 9.2% for
values were considered reasonable as cutoff values for severely patients with no, moderate, and severe malnutrition, respectively.
reduced muscle mass and continued to be employed. During the follow-up period, 2085 patients (22.2%) were confirmed
dead. The median observation period for surviving patients was
2.4. Statistical analysis 345 [72e599] days. The KaplaneMeier survival curves shown in
Fig. 1 differed significantly by GLIM-defined nutritional status (log-
Continuous data are presented as medians [interquartile ranges] rank test; P < 0.001). The 1-year survival rates for patients with no,
and categorical data as numbers and percentages. Differences in moderate, and severe malnutrition were 85.9% (95% CI, 84.6e87.1),
continuous variables were analyzed using the ManneWhitney U 72.6% (95% CI, 70.6e74.4), and 62.1% (95% CI, 59.8e64.4), respec-
test. Categorical data were expressed as numbers and percentages, tively; moreover, the 2-year survival rates were 78.1% (95% CI,
and differences were analyzed using the chi-square test. Multi- 46.2e79.9), 63.8% (95% CI, 61.3e66.2), and 51.5% (95% CI,
group comparisons were performed using the Bonferroni method. 48.6e54.2), respectively.
KaplaneMeier survival curves were used to evaluate malnutrition- Table 3 shows the results of the Cox regression analysis of the
related mortality. Differences were confirmed using the log-rank relationship between GLIM-defined malnutrition and mortality.
test, followed by crude and adjusted Cox regression analysis. Age After adjusting for age and sex, multivariable Cox regression anal-
and sex, which are clinical factors that are not included in the GLIM ysis showed that both moderate (HR 2.0, 95% CI 1.79e2.23,
criteria and sub-criteria, were included as covariates in the Cox P < 0.001) and severe malnutrition (HR 3.06, 95% CI 2.74e3.40,
regression model. Age was stratified (<70 or
70 years) according P < 0.001) were independent risk factors for mortality.
to the characteristics of the GLIM criteria. Multivariable analysis Table 4 shows the results of the Cox regression analysis for
was also performed to identify the effect of each GLIM criterion on mortality associated with six combinations of three phenotypic and
mortality, and hazard ratios (HRs) and 95% confidence intervals two etiologic criteria. After adjusting for age, all six combinations
(CIs) were calculated. For all statistical tests, a p-value <0.05 was were associated with mortality.
considered statistically significant. All statistical analyses were Results of the multivariable analysis of the relationship between
performed using R (version 4.0.4; The R Foundation for Statistical each GLIM sub-criterion and mortality are presented in
Computing, Vienna, Austria). Supplementary Table S1. After adjusting for age, four sub-criteria
(except low BMI) were independently associated with mortality.
3. Results The disease burden/inflammation criterion showed the highest HR
among all sub-criteria (HR 4.32, 95% CI 3.65e5.12).
During the study period, 14,934 patients were found to be at risk Figure 2 shows KaplaneMeier curves for the nutritional status
for malnutrition via nutritional screening performed on admission. for different age groups. The median age of patients aged <70 years

168
N. Mori, K. Maeda, Y. Fujimoto et al. Clinical Nutrition 42 (2023) 166e172

Table 2
Characteristics of patients classified based on the GLIM criteria.

No malnutrition n ¼ 4145 Moderate malnutrition n ¼ 2799 Severe malnutrition n ¼ 2428 P-value

Age, years median [IQR] 73.0 [65.0e80.0] 76.0 [68.0e82.0] 77.0 [69.0e84.0] <0.001
Age
70 years, n (%) 2652 (64.0) 2016 (72.0) 1817 (74.8) <0.001
Men, n (%) 2202 (53.1) 1390 (49.7) 1154 (47.5) <0.001
Body mass index, kg/m2, median [IQR] 21.9 [19.8e24.2] 19.5 [18.3e21.4] 17.2 [16.0e19.1] <0.001
Calf circumference, cm, median [IQR]
Men 33.0 [31.1e35.0] 29.8 [28.5e31.8] 27.0 [25.0e29.6] <0.001
Women 31.2 [29.7e33.2] 28.7 [27.4e30.6] 26.0 [24.0e28.2] <0.001
Hemoglobin level, g/dL, median [IQR] 12.4 [10.8e13.7] 11.4 [9.8e12.9] 11.0 [9.5e12.3] <0.001
Albumin level, g/dL, median [IQR] 3.6 [3.2e4.1] 3.4 [2.9e3.8] 3.2 [2.7e3.7] <0.001
C-reactive protein level, mg/L, median [IQR] 3.8 [1.0e34.4] 13.3 [2.3e57.7] 15.4 [2.7e57.2] <0.001

GLIM, The Global Leadership Initiative on Malnutrition; IQR, interquartile range.

Table 4
Cox regression analysis of each combination of GLIM sub-criteria for mortality.

Factors HR 95% CI P-value

Non-volitional weight loss

þReduced food intake/Assimilation 2.10 1.89e2.32 <0.001
þDisease burden/Inflammation 2.27 2.08e2.48 <0.001
Low body mass index
þReduced food intake/Assimilation 1.88 1.71e2.07 <0.001
þDisease burden/Inflammation 1.86 1.71e2.03 <0.001
Reduced muscle mass
þReduced food intake/Assimilation 2.30 2.10e2.52 <0.001
þDisease burden/Inflammation 2.35 2.15e2.56 <0.001

Each combination of GLIM sub-criteria was adjusted for age group (
70 or <70
years).
GLIM, The Global Leadership Initiative on Malnutrition; HR, hazard ratio; CI, con-
fidence interval.

Supplementary Fig. S1 shows KaplaneMeier curves for the

abovementioned four conditions having the highest disease bur-
dens. In all disease subgroups, mortality tended to worsen with
Fig. 1. KaplaneMeier curves for overall survival based on GLIM-defined nutritional
worsening GLIM-defined nutritional status (all log-rank trend tests,
status. GLIM, Global Leadership Initiative on Malnutrition. P < 0.001).

was 57.0 [44.0e66.0] years, and the median age of patients aged 4. Discussion

70 years was 79.0 [74.0e84.0] years. Patients aged <70 years and

70 years showed increased mortality with an increase in In this study, we examined participant nutritional status and its
malnutrition severity. Based on the Cox regression analysis find- association with all-cause mortality in a university hospital that
ings, the HRs for moderate and severe malnutrition were 2.0 (95% uses the GLIM criteria as a routine nutritional assessment modality
CI 2.35e3.71) and 3.97 (95% CI 3.17e4.97), respectively, in patients for the diagnosis of malnutrition in hospitalized patients with
<70 years, and 1.73 (95% CI 1.52e1.96) and 2.70 (95% CI 2.39e3.05), nutritional risks; we obtained the following findings. First, GLIM-
respectively, in patients
70 years. defined malnutrition was associated with high mortality in hospi-
Supplementary Table S2 shows the frequency of phenotypic and talized patients, and the mortality increased with the severity of
etiologic criteria in patients with different GLIM-defined nutritional malnutrition. Second, of the three phenotypic criteria and two
statuses. The frequency of each sub-criterion increased with etiologic criteria used in the GLIM criteria, four criteria (except low
worsening nutritional status. Cancer was found to impose the BMI) were independently associated with mortality. A trend toward
highest disease burden in all the different nutritional status cate- an increase in mortality with the severity of GLIM-defined
gories, followed by chronic kidney disease (CKD), congestive heart malnutrition was observed in different age groups and patients
failure, and major infections. with conditions constituting major burden diseases. Although this

Table 3
Cox regression analysis of the association between GLIM-defined malnutrition and mortality.

Univariable analysis Multivariable analysis

HR 95% CI P-value HR 95% CI P-value

Age
70 years 1.56 1.41e1.73 <0.001 1.41 1.27e1.56 <0.001

Sex, Male 1.38 1.26e1.50 <0.001 1.41 1.29e1.54 <0.001
GLIM-defined malnutrition
No malnutrition 1.00 (reference) 1.00 (reference)
Moderate malnutrition 2.02 1.81e2.26 <0.001 2.00 1.79e2.23 <0.001
Severe malnutrition 3.04 2.73e3.39 <0.001 3.06 2.74e3.40 <0.001

GLIM, The Global Leadership Initiative on Malnutrition; HR, hazard ratio; CI, confidence interval.

169
N. Mori, K. Maeda, Y. Fujimoto et al. Clinical Nutrition 42 (2023) 166e172

Fig. 2. KaplaneMeier curves based on GLIM-defined nutritional status for different age groups. P values for overall log-rank tests examine whether the three different
KaplaneMeier curves differ. P values for log-rank trend tests examine whether increased severity of malnutrition is associated with worsening of overall survival. GLIM, Global
Leadership Initiative on Malnutrition.

was a retrospective cohort study, the assessment of the three association in a larger sample population and over a relatively
phenotypic and two etiologic GLIM sub-criteria and the diagnosis longer observation period for adult hospitalized patients with
of malnutrition based on these sub-criteria were performed by the nutritional risks; we also demonstrated the association between
nutrition support team at admission. Therefore, data on the the severity of malnutrition and mortality in hospitalized patients.
assessment of nutritional status and the presence of each sub- The effects on mortality associated with the six combinations of
criterion were available in the medical records, unlike in many three phenotypic and two etiologic criteria used to diagnose
other large-scale retrospective studies wherein the GLIM criteria malnutrition in GLIM generally did not appear to be markedly
were retrospectively applied for malnutrition diagnosis. To the best different, although the two with low BMI had slightly lower hazard
of our knowledge, this is the first study to examine the association ratios. Contrarily, in examining the association of each of the five
between nutritional status and all-cause mortality in a large sample sub-criteria with mortality, with the exception of low BMI, the four
population, using the GLIM criteria for routine nutritional GLIM sub-criteria of non-volitional weight loss, loss of muscle
assessment. mass, decreased food intake/assimilation, and disease burden/
GLIM-defined malnutrition was associated with high mortality inflammation were independently associated with mortality. The
in hospitalized patients, and the mortality increased with malnu- combination and importance of the GLIM sub-criteria for the
trition severity. Compared with nutritionally at-risk patients diagnosis of malnutrition have not been adequately examined in
without malnutrition, the HRs for mortality were approximately previous studies [11]. Among the aforementioned studies exam-
twice and thrice as high as those of patients with moderate and ining the association between each sub-criterion and mortality in
severe malnutrition, respectively. The association between GLIM- acute-care hospitalized patients, only Martín et al. reported that
defined malnutrition and mortality in the general adult popula- reduced muscle mass and the presence of inflammation were
tion in acute-care hospitals was examined in four previous studies. independently associated with in-hospital mortality [16]. Among
In a prospective cohort study of 601 adult hospitalized patients, the four sub-criteria found to be associated with mortality in our
Brito et al. reported that GLIM-defined malnutrition was associated study, disease burden/inflammation was an independent factor
with a 5.1-fold increased risk of in-hospital mortality and high 6- with a HR more than twice as high as that of the other sub-criteria.
month mortality [15]. Moreover, Martín et al., in a prospective This may suggest the importance of this sub-criterion on the
observational study of 1015 adult patients admitted to the general outcome of disease-related malnutrition, which is common in
ward of a university hospital, reported that in-hospital mortality hospitalized patients. In contrast, low BMI was not an independent
increased with the severity of GLIM-defined malnutrition [16]. In prognostic factor in our study. Some studies have questioned the
addition, IJmker-Hemink et al. conducted a post hoc analysis of a adoption of BMI for nutritional diagnosis as it may not reflect
prospective cohort study of 574 patients admitted in an academic muscle mass; therefore, depleted muscle mass may be missed us-
hospital and found that GLIM-defined malnutrition showed good ing BMI alone [19]. In recent years, several problems have been
predictive power for 1-year mortality [17]. Furthermore, Balci et al., encountered with the use of BMI for the diagnosis of malnutrition
in a retrospective analysis of 231 patients admitted to a medical or [20,21]. Chaar et al. recently conducted a single-center prospective
surgical ward, showed that moderate or severe GLIM-defined study of 121 patients that met the GLIM criteria and reported that
malnutrition effectively predicted 5-year mortality [18]. These the use of low BMI may not be effective in diagnosing malnutrition
previous study findings corroborated with our findings that GLIM- in a hospital setting [22]. Our findings may also prompt a recon-
defined malnutrition was associated with worse prognosis in hos- sideration of the use of the low BMI sub-criterion in the diagnosis of
pitalized patients. Our study revealed the abovementioned malnutrition among hospitalized patients.

170
N. Mori, K. Maeda, Y. Fujimoto et al. Clinical Nutrition 42 (2023) 166e172

GLIM-defined malnutrition was significantly associated with assessment implementation rate of less than 70%. Therefore, if all
mortality in both younger (<70 years) and older adults (
70 years). cases had undergone nutritional assessment, it could have influ-
Several studies have reported an association between GLIM- enced the outcome.
defined malnutrition and mortality in older adults. Xu et al. re-
ported that GLIM-defined malnutrition increased the odds of in- 5. Conclusions
hospital mortality in hospitalized patients aged
70 years [23].
Sobestiansky examined 56 geriatric inpatients and reported that We examined the prognostic impact of malnutrition diagnosed
GLIM-defined malnutrition was associated with increased 1-year using the GLIM criteria as a routine nutritional assessment of a
mortality [24]. These findings are generally consistent with our large sample of patients hospitalized in a university hospital; we
study findings. Nevertheless, to our knowledge, no previous study found that GLIM-defined malnutrition and its severity were asso-
has investigated mortality-related outcomes in the hospitalized ciated with a worse prognosis. We found similar trends in patients
non-elderly adult population, such as those aged under 70 years. of different age groups as well as in patients with conditions
We found that malnutrition in hospitalized patients was signifi- constituting major disease burdens. Further research is needed to
cantly associated with mortality, even in patients aged <70 years, investigate the abovementioned association in different healthcare
although HRs differed by age group. The exacerbation of the HR due settings, for the universal standardization of the GLIM criteria for
to malnutrition may have been greater in patients aged <70 years malnutrition diagnosis. In addition, future studies should evaluate
because of the longer life expectancy of non-malnourished patients the reference values and combinations of each GLIM criterion.
aged <70 years compared to that of patients aged
70 years.
In a subgroup analysis of patients with cancer, CKD, heart failure Funding statement
(HF), and major infectionsdthe most frequent diseases in the dis-
ease burden criteriada trend toward increased mortality was also This research did not receive any specific grant from funding
observed with worsening GLIM-defined nutritional status. Previous agencies in the public, commercial, or not-for-profit sectors.
studies have reported the association between GLIM-defined
malnutrition and mortality in disease-specific cohorts, especially Author contributions
in patients with cancer, HF, and severe infections, as well as in
patients undergoing dialysis [25e29]. Of the four diseases exam- NM, KM, and RF contributed to the conception of the study. YF,
ined in this study, three were classified as chronic wasting diseases YI, RO, NM, and KM contributed to the acquisition of data. NM, KM,
and one as acute disease, which clearly demonstrates that the as- AS, JU, and AN contributed to the analysis and interpretation of
sociation between GLIM-defined malnutrition and high mortality is data. NM, KM, and AS drafted the manuscript. All authors critically
maintained in patients with each of these inflammation-inducing revised the manuscript, provided their final approval, and agreed to
diseases. be accountable for all aspects of the work, ensuring its integrity and
The present study had several limitations. First, this was a accuracy.
single-center retrospective study; hence, the findings may not be
generalizable to patients in different healthcare settings. Second, Conflicts of interest
although the patient prognosis was evaluated over an observation
period of
6 months, approximately 20% of the included patients Naoharu Mori: Grants outside the submitted work and speaking
had an actual observation period of <3 months. This is because our honoraria from Daichi Sankyo Co., LTD, Otsuka Pharmaceutical
study was a large-scale retrospective cohort study, and therefore, it Factory, Inc., Abbott Nutrition and Shionogi & Co., Ltd., and
was difficult to contact each patient for prognosis assessment. We speaking honoraria from Ono Pharmaceutical Co., LTD, and Kyowa
took advantage of the characteristics of the study hospital, wherein Kirin Co., Ltd.
most inpatients continue to receive follow-up after discharge; thus, Ryoji Fukushima: Grants outside the submitted work from Ono
we obtained data on patient outcomes from the last medical ex- Pharmaceutical Co., LTD, and Taiho Pharmaceutical Co., LTD, and
amination findings available in the electronic medical records. Due speaking honoraria from Otsuka Pharmaceutical Factory, Inc., Ter-
to the nature of this study, it was also not possible to retrospectively umo Corporation, and EA Pharma Co., Ltd.
collect data on the severity of individual cases. Therefore, this study The other authors declare that they have no conflicts of interest.
could not be adjusted for disease severity, which may affect mor-
tality. Third, the assessment of skeletal muscle mass was not based Acknowledgement
on an accurate and reproducible method using validated methods
of body composition assessment. The GLIM criteria state that The authors wish to express appreciation to the doctors, nurses,
physical measurements, such as the CC measurement employed in pharmacists, and all other professionals working at Aichi Medical
this study, are acceptable and feasible in clinical practice [8]. A University Hospital for all the time and attention they have devoted
recent study reviewed the findings of GLIM-related studies and to our study.
reported that almost half of the tools used for assessing low muscle
mass in the literature were based on anthropometry, with CC
Appendix A. Supplementary data
measurement performed in most of the studies [11]. In the evalu-
ation of muscle mass during routine nutritional assessment, the
Supplementary data to this article can be found online at
measurement of CC is more acceptable in clinical practice, and our
https://doi.org/10.1016/j.clnu.2022.12.008.
results may support its usefulness. Finally, one-third of the patients
at nutritional risk were discharged without having undergone a
References
nutritional assessment. The NST visited all patients at nutritional
risk and attempted to perform the nutritional assessment. How- [1] White JV, Guenter P, Jensen G, Malone A, Schofield M, Academy Malnutrition
ever, because the study hospital was an acute care hospital and Work Group, A.S.P.E.N. Board of Directors. Consensus statement of the acad-
many patients had a short hospital stay, patients were often not emy of nutrition and dietetics/American society for parenteral and enteral
nutrition: characteristics recommended for the identification and documen-
present at the time of the NST visit as they were receiving other tation of adult malnutrition (undernutrition). J Acad Nutr Diet 2012;112:
medical treatment or due to other reasons, resulting in a nutrition 730e8. https://doi.org/10.1016/j.jand.2012.03.012.

171
N. Mori, K. Maeda, Y. Fujimoto et al. Clinical Nutrition 42 (2023) 166e172

[2] Cederholm T, Barazzoni R, Austin P, Ballmer P, Biolo G, Bischoff SC, et al. ESPEN malnutrition and its relation with adverse outcomes, a prospective observa-
guidelines on definitions and terminology of clinical nutrition. Clin Nutr tional study. Clin Nutr ESPEN 2020;38:67e73. https://doi.org/10.1016/j.
2017;36:49e64. https://doi.org/10.1016/j.clnu.2016.09.004. clnesp.2020.06.015.
[3] Sorensen J, Kondrup J, Prokopowicz J, Schiesser M, Kra €henbühl L, Meier R, et al. [17] Ijmker-Hemink V, Heerschop S, Wanten G, Berg van den M. Evaluation of the
EuroOOPS: an international, multicentre study to implement nutritional risk validity and feasibility of the GLIM criteria compared with PG-SGA to diagnose
screening and evaluate clinical outcome. Clin Nutr 2008;27:340e9. https:// malnutrition in relation to one-year mortality in hospitalized patients. J Acad
doi.org/10.1016/j.clnu.2008.03.012. Nutr Diet 2022;122:595e601. https://doi.org/10.1016/j.jand.2021.07.011.
[4] Lim SL, Ong KCB, Chan YH, Loke WC, Ferguson M, Daniels L. Malnutrition and its [18] Balci C, Bolayir B, Eşme M, Arik G, Kuyumcu ME, Yesil Y, et al. Comparison of
impact on cost of hospitalization, length of stay, readmission and 3-year mor- the efficacy of the global leadership initiative on malnutrition criteria, sub-
tality. Clin Nutr 2012;31:345e50. https://doi.org/10.1016/j.clnu.2011.11.001. jective global assessment, and nutrition risk screening 2002 in diagnosing
[5] Dupertuis YM, Kossovsky MP, Kyle UG, Raguso CA, Genton L, Pichard C. Food malnutrition and predicting 5-year mortality in patients hospitalized for acute
intake in 1707 hospitalised patients: a prospective comprehensive hospital illnesses. JPEN - J Parenter Enter Nutr 2021;45:1172e80. https://doi.org/
survey. Clin Nutr 2003;22:115e23. https://doi.org/10.1054/clnu.2002.0623. 10.1002/jpen.2016.
[6] Kondrup J, Allison SP, Elia M, Vellas B, Plauth M, Educational and Clinical [19] Cederholm T, Bosaeus I, Barazzoni R, Bauer J, Van Gossum A, Klek S, et al.
Practice Committee, European Society of Parenteral and Enteral Nutrition Diagnostic criteria for malnutrition e an ESPEN consensus statement. Clin
(ESPEN). ESPEN guidelines for nutrition Screening. Clin Nutr 2003;22:415e21. Nutr 2015;34:335e40. https://doi.org/10.1016/j.clnu.2015.03.001.
https://doi.org/10.1016/s0261-5614(03)00098-0. [20] Barone M. Is the use of the BMI alone sufficient to diagnose malnutrition in
[7] Cederholm T, Bosaeus I, Barazzoni R, Bauer J, Van Gossum A, Klek S, et al. both male and female adults? Clin Nutr 2018;37:1771. https://doi.org/
Diagnostic criteria for malnutrition e an ESPEN consensus statement. Clin 10.1016/j.clnu.2018.07.003.
Nutr 2015;34:335e40. https://doi.org/10.1016/j.clnu.2015.03.001. [21] Ng WL, Collins PF, Hickling DF, Bell JJ. Evaluating the concurrent validity of body
[8] Cederholm T, Jensen GL, Correia MITD, Gonzalez MC, Fukushima R, mass index (BMI) in the identification of malnutrition in older hospital inpatients.
Higashiguchi T, et al. GLIM criteria for the diagnosis of malnutrition e a Clin Nutr 2019;38:2417e22. https://doi.org/10.1016/j.clnu.2018.10.025.
consensus report from the global clinical nutrition community. Clin Nutr [22] Chaar DE, Mattar L, Khoury CFE. AND/ASPEN and the GLIM malnutrition
2019;38:1e9. https://doi.org/10.1016/j.clnu.2018.08.002. diagnostic criteria have a high degree of criterion validity and reliability for
[9] Maeda K, Ishida Y, Nonogaki T, Mori N. Reference body mass index values and the identification of malnutrition in a hospital setting: a single-center
the prevalence of malnutrition according to the Global Leadership Initiative prospective study. JPEN-Parenter Enter 2022. https://doi.org/10.1002/
on Malnutrition criteria. Clin Nutr 2020;39:180e4. https://doi.org/10.1016/ jpen.2347.
j.clnu.2019.01.011. [23] Xu JY, Zhu MW, Zhang H, Li L, Tang PX, Chen W, et al. A cross-sectional study
[10] De van der Schueren MAE, Keller H, Cederholm T, Barazzoni R, Compher C, of GLIM-defined malnutrition based on new validated calf circumference cut-
Correia M, et al. Global Leadership Initiative on Malnutrition (GLIM): guidance off values and different screening tools in hospitalised patients over 70 years
on validation of the operational criteria for the diagnosis of protein-energy old. J Nutr Health Aging 2020;24:832e8. https://doi.org/10.1007/s12603-020-
malnutrition in adults. Clin Nutr 2020;39:2872e80. https://doi.org/10.1016/ 1386-4.
j.clnu.2019.12.022. [24] Sobestiansky S, Åberg AC, Cederholm T. Sarcopenia and malnutrition in
[11] Correia MITD, Tappenden KA, Malone A, Prado CM, Evans DC, Sauer AC, et al. relation to mortality in hospitalised patients in geriatric care e predictive
Utilization and validation of the global leadership initiative on malnutrition validity of updated diagnoses. Clin Nutr ESPEN 2021;45:442e8. https://
(GLIM): a scoping review. Clin Nutr 2022;41:687e97. https://doi.org/10.1016/ doi.org/10.1016/j.clnesp.2021.07.002.
j.clnu.2022.01.018. [25] Sanchez-Torralvo FJ, Ruiz-García I, Contreras-Bolívar V, Gonzalez-Almendros I,
[12] Stratton RJ, Hackston A, Longmore D, Dixon R, Price S, Stroud M, et al. Ruiz-Vico M, Abuin-Fernandez J, et al. CT-determined sarcopenia in GLIM-
Malnutrition in hospital outpatients and inpatients: prevalence, concurrent defined malnutrition and prediction of 6-month mortality in cancer in-
validity and ease of use of the ‘malnutrition universal screening tool’ patients. Nutrients 2021;13:2647. https://doi.org/10.3390/nu13082647.
(“MUST”) for adults. Br J Nutr 2004;92:799e808. https://doi.org/10.1079/ [26] Liu C, Lu Z, Li Z, Xu J, Cui H, Zhu M. Influence of malnutrition according to the
bjn20041258. GLIM criteria on the clinical outcomes of hospitalized patients with cancer.
[13] Rubenstein LZ, Harker JO, Salva  A, Guigoz Y, Vellas B. Screening for under- Front Nutr 2021;8:774636. https://doi.org/10.3389/fnut.2021.774636.
nutrition in geriatric Practice Developing the short-form mini-nutritional [27] Avesani CM, Sabatino A, Guerra A, Rodrigues J, Carrero JJ. A comparative analysis
assessment (MNA-SF). Journals Gerontology Ser J Gerontol A Biol Sci Med Sci of nutritional assessment using global leadership initiative on malnutrition
2001;56:M366e72. https://doi.org/10.1093/gerona/56.6.m366. versus subjective global assessment and malnutrition inflammation score in
[14] Maeda K, Koga T, Nasu T, Takaki M, Akagi J. Predictive accuracy of calf maintenance hemodialysis patients. J Ren Nutr 2021. https://doi.org/10.1053/
circumference measurements to detect decreased skeletal muscle mass and j.jrn.2021.06.008.
European Society for Clinical Nutrition and Metabolism-defined malnutrition [28] Oguri M, Ishii H, Yasuda K, Sumi T, Takahashi H, Murohara T. Combined
in hospitalized older patients. Ann Nutr Metab 2017;71:10e5. https://doi.org/ prognostic value of malnutrition using GLIM criteria and renal insufficiency in
10.1159/000478707. elderly heart failure. Escola Hear Fail 2021. https://doi.org/10.1002/ehf2.
[15] Brito JE, Burgel CF, Lima J, Chites VS, Saragiotto CB, Rabito EI, et al. GLIM criteria 13685.
for malnutrition diagnosis of hospitalized patients presents satisfactory criterion [29] Shahbazi S, Hajimohammadebrahim-Ketabforoush M, Vahdat Shariatpanahi M,
validity: a prospective cohort study. Clin Nutr 2021;40:4366e72. https:// Shahbazi E, Vahdat Shariatpanahi Z. The validity of the global leadership
doi.org/10.1016/j.clnu.2021.01.009. initiative on malnutrition criteria for diagnosing malnutrition in critically ill
[16] Galindo Martín CA, Aportela Va zquez VA, Becerril Herna ndez F, Aguilar patients with COVID-19: a prospective cohort study. Clin Nutr ESPEN 2021;43:
Medina CR, Ayala Carrillo SL, Chavez Flores A, et al. The GLIM criteria for adult 377e82. https://doi.org/10.1016/j.clnesp.2021.03.020.

172