ABSTRACT
Aims/Introduction
Diabetes mellitus (DM) increases postoperative risks and may worsen physical function through muscle loss. Patients undergoing malignancies surgery are aging, and age‐related declines in physical function, particularly sarcopenia, also adversely affects outcomes. As DM and physical decline are interrelated, we aimed to examine how they impact outcomes in older patients undergoing gastrointestinal cancer surgery.
Materials and Methods
This single‐center retrospective cohort study included 1,063 older patients ≥65 years who underwent preoperative evaluation for gastrointestinal cancer between 2012 and 2019. We stratified patients based on current DM and physical function assessed by grip strength. The main outcome was postoperative survival. Cox proportional hazards models examined associated factors.
Results
After exclusions, 655 without DM (non‐DM group) and 257 patients with DM (DM group) were analyzed (mean age: 79.1 ± 4.1 years, 66.8% male). Compared with the non‐DM group, the DM group had higher body mass index (21.5 vs 22.6 kg/m2), higher cardiovascular disease prevalence (26.9 vs 41.2%), and more frequent weak grip strength (53.9 vs 65.8%). Postoperative survival analysis showed no significant difference between the two groups (P = 0.651). Multivariate analysis showed current DM was not an independent risk factor, whereas grip strength remained significantly associated with poor outcomes (HR 0.97 95% CI 0.95–1.00), and no significant interactions were found (P = 0.656).
Conclusions
Current DM did not significantly affect postoperative outcomes; however, lower grip strength was an independent risk factor for poor outcomes. The prognostic impact of reduced physical function was consistent regardless of DM status.
Keywords: Diabetes mellitus, Frail elderly, Neoplasms
INTRODUCTION
In recent years, the incidence of malignant tumors has been increasing as the population ages, and the number of older patients undergoing surgical treatment is consequently also on the rise 1 . Multiple comorbidities and a decline in physical function occur with age, leading to significant individual differences in the overall health status of older patients who require surgery. Diabetes mellitus (DM) is one of the most important factors in perioperative management, increasing the risk of postoperative complications, such as delayed wound healing 2 , 3 , infections 4 , and mortality rates 5 , 6 . However, the impact of DM on postoperative outcomes in older patients may differ from those in younger patients due to age‐related physiological changes and increased prevalence of comorbidities such as hypertension and chronic kidney disease.
The physical function of older patients may decline and sarcopenia, which is the qualitative and quantitative decrease in skeletal muscle mass due to aging may ensue. Older patients with sarcopenia experience more postoperative complications than younger patients and exhibit worse postoperative outcomes than robust older adults 7 , 8 , 9 . Therefore, it is preferable to optimize medical care by conducting a comprehensive geriatric assessment, including physical activity, cognitive function, and physical function assessments, to evaluate risks before surgery 10 , 11 , 12 . To evaluate skeletal muscle mass, muscle strength, and physical function to assess sarcopenia, indicators that can be easily measured in clinical practice are needed. Among these indicators, grip strength is particularly convenient because it can be quickly measured in the examination room and is widely applied for screening and physical function evaluation for sarcopenia.
DM and physical function decline, such as sarcopenia, are often interrelated 13 , 14 . In clinical practice, patients with DM frequently exhibit reduced muscle strength or mass. However, it remains unclear whether diabetes itself independently affects postoperative outcomes or whether its impact is primarily mediated through physical function decline.
This study aimed to elucidate how DM and reduced physical function affect postoperative prognosis in older patients undergoing cancer surgery. We used our hospital's database of older patients with gastrointestinal cancer to examine the effects of DM and physical function, particularly grip strength, on postoperative prognosis.
MATERIAL AND METHODS
Ethics
This study was approved by the hospital's ethics committee (approval number: 13350(T1)‐7) and was conducted by the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study details were published on the hospital's website and informed consent was obtained through an opt‐out method. Participants were free to withdraw their consent at any time.
Design
This retrospective cohort study included older patients who underwent preoperative evaluation for gastrointestinal cancer. Participants were classified into the non‐DM group and the DM group, and survival periods were compared between the groups.
Participants included 1,063 older individuals who underwent preoperative evaluation for gastrointestinal cancer at a university hospital between April 2012 and March 2019. Gastrointestinal surgeons referred patients to a geriatrician who conducted a comprehensive geriatric assessment and physical function evaluation before surgery. Patients were generally referred if they were ≥70 years. However, there was no fixed age criterion; therefore, non‐older patients were excluded from the analysis.
Data collection
The data collection method was previously reported 8 . Briefly, the following information was retrieved from the electronic medical record system: age, sex, body mass index (BMI), laboratory findings, cancer‐related information, current DM and past cardiovascular disease, and type of surgery. Laboratory findings included hemoglobin, estimated glomerular filtration rate (eGFR), and hemoglobin A1c. The eGFR was calculated by the Japanese formula, using serum creatinine levels and age 15 . Cancer stage was determined according to the tumor–node–metastasis classification of the Union for International Cancer Control 16 , and noninvasive cancers (pTis/M) were categorized as stage 0. Current DM was defined as a current diagnosis of DM under treatment, including the use of oral hypoglycemic agents, insulin, or lifestyle therapy, as documented in the medical records at the time of preoperative evaluation. The following items were obtained from the comprehensive geriatric assessment and physical function evaluation: Barthel Index (basic activities of daily living [ADL]), Lawton's instrumental ADL (IADL), Mini‐Mental State Examination (MMSE) 17 , Geriatric Depression Scale‐15 (GDS‐15), grip strength, walking speed, and limb skeletal muscle mass. Grip strength was measured using a Smedley‐type digital grip strength meter (T‐2177; Toei Light Co., Ltd., Saitama, Japan) and skeletal muscle mass was assessed using a body composition analyzer (MC‐190; TANITA, Tokyo, Japan).
In this study, the sarcopenic score was defined as the number of the following three items: weak grip strength, slow gait speed, and low skeletal muscle mass. The cut‐off values for each component were adopted from the Asian Working Group for Sarcopenia (AWGS) 2019 criteria 18 . Specifically, low grip strength was defined as <28 kg in men and <18 kg in women, slow walking speed as <1.0 m/s, and low skeletal muscle mass as a skeletal muscle index <7.0 kg/m2 in men and <5.7 kg/m2 in women by the bioelectrical impedance analysis method. Although this score was not used as a diagnostic tool, a total score of 3 is consistent with the definition of severe sarcopenia in AWGS2019, and a score of 2 approximately corresponds to sarcopenia.
Evaluation items
The main evaluation item was postoperative survival, which was analyzed using the Kaplan–Meier method with the log‐rank test. Stratification was performed based on the presence or absence of current DM and further by the presence or absence of weak grip strength. Survival was confirmed from the electronic medical records. Weak grip strength was determined according to the AWGS2019 18 (<28 kg in men and <18 kg in women). Cox proportional hazards model analysis was used to examine associated factors with the survival period as the objective variable.
Statistical analysis
Survival curves were compared using the Kaplan–Meier method with the log‐rank test. In Cox proportional hazards model analysis, with the survival period as the dependent variable, age, sex, BMI, cancer stage, current DM, weak grip strength, and sarcopenic score were used as explanatory variables, and we performed univariate and multivariate analyses. Interaction analyses were performed using multivariable Cox models adjusted for age, sex, body mass index, cancer stage, and current DM to evaluate whether the association between physical function (grip strength, weak grip strength, and the sarcopenic score) and survival differed according to DM status. Continuous variables were analyzed using the unpaired t‐test and categorical variables were analyzed using Fisher's exact test. All statistical analyses were performed using EZR 19 version 1.68 (Saitama Medical Center, Jichi Medical University, Saitama, Japan) and R version 4.3.1 (The R Foundation for Statistical Computing, Vienna, Austria).
RESULTS
Of the 1,063 older patients who underwent preoperative comprehensive geriatric assessment for gastrointestinal cancer, four non‐older patients, 56 patients who did not undergo surgery, 56 patients with nonmalignant tumors, one patient with recurrent cancer, and 34 patients with missing data were excluded. A total of 912 patients (mean age: 79.1 ± 4.1 years; men: 609 [66.8%]) were analyzed (Figure 1). The non‐DM group included 655 patients (71.8%), and the DM group included 257 patients (28.2%). Surgical target diseases included esophageal (18.6%), gastric (20.6%), liver (12.8%), biliary tract (2.6%), pancreatic (10.5%), ileocecal (3.1%), colorectal cancers (27.1%), and metastatic liver cancer (2.6%), as well as other malignant tumors (2.0%). In the overall cohort, 60.0% of surgeries were performed using a laparoscopic or thoracoscopic approach, while 40.0% were performed via open thoracic or abdominal surgery.
Figure 1.
Study flowchart illustrating patient selection process. Of the 1,063 older patients who underwent preoperative comprehensive geriatric assessment for gastrointestinal cancer, 912 patients were included in the final analysis after excluding non‐older patients, those who did not undergo surgery, cases with non‐malignant tumors, one recurrent case in whom cancer stage could not be assigned, and those with missing data. The final cohort was categorized into the nondiabetes mellitus (non‐DM) group and the diabetes mellitus (DM) group.
Preoperative patient backgrounds are summarized in Table 1. The DM group had a significantly higher BMI (21.5 ± 3.3 kg/m2 vs 22.6 ± 3.6 kg/m2) and a higher prevalence of cardiovascular disease (26.9% vs 41.2%) compared with the non‐DM group, although age (79.0 ± 4.2 years vs 79.3 ± 3.8 years) and the proportion of men (66.0% vs 68.9%) were similar between the groups. Regarding laboratory findings, hemoglobin levels were similar between groups (11.8 ± 1.8 vs 11.8 ± 1.9 g/dL). However, eGFR was significantly lower in the DM group (64.1 ± 18.5 vs 60.2 ± 19.1 mL/min/1.73m2), and hemoglobin A1c levels were markedly higher (5.7 ± 0.5% vs 6.9 ± 0.9%). In the comprehensive geriatric assessment and physical function evaluation, the DM group did not show significant differences in Barthel Index, MMSE, and GDS compared with the non‐DM group (97.5 ± 9.2 vs 96.5 ± 11.6; 25.2 ± 3.8 vs 25.2 ± 3.7; 3.3 ± 3.0 vs 3.6 ± 3.3, respectively), but had significantly lower IADL scores (6.9 ± 1.6 vs 6.6 ± 1.9) and a higher frequency of weak grip strength (53.9% vs 65.8%). In the DM group, the frequencies of antidiabetic medication use were as follows: sulfonylureas 34.2%, glinides 18.7%, thiazolidinediones 14.0%, biguanides 20.2%, α‐glucosidase inhibitors 23.3%, DPP‐4 inhibitors 62.6%, SGLT2 inhibitors 3.5%, GLP‐1 receptor agonists 3.1%, and insulin 32.3%.
Table 1.
Baseline characteristics of study population
| Variables | Non‐DM group | DM group | P‐value |
|---|---|---|---|
| N | 655 | 257 | |
| Age, years | 79.0 ± 4.2 | 79.3 ± 3.8 | 0.248 |
| Sex (male), % | 66.0 (432) | 68.9 (177) | 0.435 |
| BMI, kg/m2 | 21.5 ± 3.3 | 22.6 ± 3.6 | <0.00001 |
| Cancer Stage, % | 0.291 | ||
| Stage 0 | 0.3 (2) | 0.8 (2) | |
| Stage 1 | 32.7 (214) | 35.0 (90) | |
| Stage 2 | 26.7 (175) | 29.6 (76) | |
| Stage 3 | 25.8 (169) | 19.8 (51) | |
| Stage 4 | 14.5 (95) | 14.8 (38) | |
| Hemoglobin, g/dL | 11.8 ± 1.8 | 11.8 ± 1.9 | 0.928 |
| eGFR, mL/min/m2 | 64.1 ± 18.5 | 60.2 ± 19.1 | 0.00499 |
| Hemoglobin A1c, % | 5.7 ± 0.5 | 6.9 ± 0.9 | <0.00001 |
| Cardiovascular disease, % | 26.9 (176) | 41.2 (106) | <0.00001 |
| Barthel index | 97.5 ± 9.2 | 96.5 ± 11.6 | 0.146 |
| IADL (Lawton) | 6.9 ± 1.6 | 6.6 ± 1.9 | 0.00822 |
| MMSE | 25.2 ± 3.8 | 25.2 ± 3.7 | 0.943 |
| GDS‐15 | 3.3 ± 3.0 | 3.6 ± 3.3 | 0.209 |
| Grip strength | |||
| Men | 27.4 ± 6.4 | 25.9 ± 6.4 | 0.00765 |
| Women, kg | 17.1 ± 5.0 | 16.1 ± 5.0 | 0.113 |
| Weak grip strength, % | 53.9 (353) | 65.8 (169) | 0.00135 |
| Gait speed meter/s | 1.13 ± 0.27 | 1.06 ± 0.32 | 0.0260 |
| SMI kg/m2 | |||
| Men | 7.3 ± 1.1 | 7.4 ± 1.2 | 0.260 |
| Women | 5.9 ± 1.0 | 6.2 ± 1.0 | 0.0361 |
| Sarcopenic score | 1.1 ± 1.0 | 1.3 ± 1.0 | 0.112 |
Comparison of baseline characteristics between the non‐DM (nondiabetic) and the diabetes mellitus (DM) groups. The DM group had a significantly higher BMI and prevalence of cardiovascular disease. The distribution of cancer stage (0–4) was comparable between the two groups. Laboratory tests showed significantly lower eGFR and higher HbA1c in the DM group, while hemoglobin levels were similar between groups. In addition, the DM group had lower IADL scores and a higher frequency of weak grip strength. Data are presented as mean ± standard deviation or percentage (%), with p‐values indicating statistical significance. BMI, body mass index; DM, diabetes mellitus; GDS‐15, Geriatric Depression Scale‐15; IADL, instrumental activities of daily living; MMSE, Mini‐Mental State Examination; SMI, skeletal muscle mass index.
The median follow‐up period was 726 days (interquartile range 435–1,227 days). A total of 211 (23.1%) patients died during the follow‐up period and 701 (76.9%) survived. The postoperative survival analysis stratified by the presence or absence of current DM showed no significant difference between the two groups (P = 0.651) (Figure 2a). When further stratified by the presence or absence of weak grip strength, postoperative outcomes were worse in the groups with weak grip strength, regardless of current DM (P = 0.000635) (Figure 2b).
Figure 2.
Postoperative survival analysis. (a) Kaplan–Meier survival curves stratified by the absence or presence of diabetes mellitus. No significant difference in postoperative survival was observed between the diabetes mellitus (DM) and the non‐DM groups (p = 0.651). (b) Kaplan–Meier survival curves were further stratified according to the absence or presence of weak grip strength. Patients with weak grip strength had significantly worse postoperative survival outcomes, regardless of their diabetes mellitus status (p = 0.000635).
We subsequently performed Cox proportional hazards model analysis, with postoperative survival days as the dependent variable and age, sex, BMI, cancer stage, current DM, grip strength, and sarcopenic score as explanatory variables. To evaluate the associations of DM and physical function with postoperative survival, we constructed three Cox proportional hazards models. All models retained age, sex, BMI, cancer stage, and current DM. Model 1 also included continuous grip strength to assess the effect of muscle strength. Model 2 replaced continuous grip strength with weak grip strength as a binary variable based on AWGS criteria, given that values below this cutoff are considered clinically meaningful. Model 3 incorporated the sarcopenic score to explore the association between postoperative outcomes and broader physical frailty, including low muscle mass and gait speed, in addition to muscle strength. Results of the univariate analysis are shown in Table 2. Age, male sex, BMI, and cancer stage were positively correlated with postoperative risk (hazard ratio [HR] 1.03 95% confidence interval [CI] 1.00–1.07; HR 1.52 95% CI: 1.11–2.08; HR 0.92 95% CI: 0.88–0.95; HR 1.87 95% CI: 1.67–2.10, respectively). Current DM was not a significant risk factor (hazard ratio [HR], 1.07; 95% CI: 0.80–1.44). Grip strength was negatively correlated with postoperative risk (HR 0.98 95% CI: 0.97–1.00), and weak grip strength and sarcopenic score were positively correlated with postoperative risk (HR 1.79 95% CI: 1.34–2.39; HR 1.49 95% CI: 1.10–2.03, respectively).
Table 2.
Univariate analyses of factors associated with postoperative survival
| (Univariate analysis) Variables | HR | 95% CI | P‐value |
|---|---|---|---|
| Age | 1.03 | 1.00–1.07 | 0.0478 |
| Sex (male) | 1.52 | 1.11–2.08 | 0.00836 |
| BMI | 0.92 | 0.88–0.95 | <0.0001 |
| Cancer stage | 1.87 | 1.67–2.10 | <0.0001 |
| Current DM | 1.07 | 0.80–1.44 | 0.651 |
| Grip strength | 0.98 | 0.97–1.00 | 0.0511 |
| Weak grip strength | 1.79 | 1.34–2.39 | <0.0001 |
| Sarcopenic score | 1.49 | 1.10–2.03 | 0.0108 |
Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for each variable. Cox proportional hazards model was used to examine the association between variables and postoperative survival. Variables included demographic characteristics (age, sex, BMI), cancer stage, current DM status, and measures of physical function (grip strength, weak grip strength, sarcopenic score). BMI, body mass index; CI, confidence interval; DM, diabetes mellitus; HR, hazard ratio.
Results of the multivariate analysis are given in Table 3. Current DM was not a significant risk factor in any model, and age was not a significant risk factor. However, after adjustment, grip strength remained a significant risk factor with a lower HR in Model 1 (HR 0.96 95% CI: 0.93–0.98). In Model 2, weak grip strength was not significantly associated with postoperative survival (HR 1.27 95% CI: 0.93–1.74). In Model 3, sarcopenic score was not a significant risk factor along with BMI (HR 1.36 95% CI: 0.94–1.96).
Table 3.
Multivariate analyses of factors associated with postoperative survival
| (Multivariate analysis) | Model 1 | Model 2 | Model 3 | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Variables | HR | 95% CI | P‐value | HR | 95% CI | P‐value | HR | 95% CI | P‐value |
| Age | 1.03 | 1.00–1.07 | 0.0817 | 1.03 | 1.00–1.07 | 0.0728 | 1.02 | 0.95–1.09 | 0.672 |
| Sex (male) | 1.99 | 1.34–2.94 | <0.000608 | 1.53 | 1.11–2.10 | 0.00899 | 2.09 | 0.99–4.42 | 0.0530 |
| BMI | 0.93 | 0.89–0.98 | <0.00398 | 0.93 | 0.89–0.97 | 0.00188 | 0.97 | 0.86–1.09 | 0.602 |
| Cancer stage | 1.79 | 1.57–2.04 | <0.0001 | 1.80 | 1.58–2.05 | <0.0001 | 2.10 | 1.52–2.89 | <0.0001 |
| Current DM | 1.11 | 0.82–1.50 | 0.506 | 1.12 | 0.83–1.51 | 0.476 | 1.17 | 0.59–2.32 | 0.654 |
| Grip strength | 0.97 | 0.95–1.00 | 0.0392 | ||||||
| Weak grip strength | 1.27 | 0.93–1.74 | 0.135 | ||||||
| Sarcopenic score | 1.35 | 0.94–1.95 | 0.105 | ||||||
Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using three Cox proportional hazards models. All models included age, sex, BMI, cancer stage, and current DM. Model 1 incorporated continuous grip strength. Model 2 replaced it with weak grip strength as a binary variable based on AWGS criteria. Model 3 used the sarcopenic score to reflect broader physical frailty, including muscle mass and gait speed in addition to grip strength. BMI, body mass index; CI, confidence interval; DM, diabetes mellitus; HR, hazard ratio.
Multivariable interaction analyses corresponding to the three multivariate models are presented in Table 4. No significant interactions were observed between DM and grip strength in Model 1, between DM and weak grip strength in Model 2, or between diabetes mellitus and the sarcopenic score in Model 3. These results indicate that the association between reduced physical function and postoperative survival was consistent regardless of DM status.
Table 4.
Interaction analyses between diabetes mellitus and physical function measures for postoperative survival
| Model | Variable | HR (95% CI) | P‐value |
|---|---|---|---|
| Model 1 | Grip strength (per 1 kg) | 0.97 (0.96–1.05) | 0.0651 |
| Current DM | 1.08 (0.38–3.08) | 0.883 | |
| Grip strength × Current DM | 1.00 (0.96–1.05) | 0.962 | |
| Model 2 | Weak grip strength | 1.30 (0.91–1.85) | 0.156 |
| Current DM | 1.18 (0.67–2.08) | 0.564 | |
| Weak grip strength × Current DM | 0.93 (0.48–1.80) | 0.818 | |
| Model 3 | Sarcopenic score | 1.37 (0.88–2.14) | 0.162 |
| Current DM | 1.23 (0.37–4.13) | 0.737 | |
| Sarcopenic score × Current DM | 0.97 (0.51–1.84) | 0.921 |
Hazard ratios (HR) and 95% confidence intervals (CI) are shown for multivariable interaction analyses between diabetes mellitus (DM) and three physical function measures corresponding to Models 1–3 in Table 3: continuous grip strength, weak grip strength, and sarcopenic score. All models were adjusted for age, sex, body mass index, cancer stage, and current DM.
DISCUSSION
This study examined the impact of DM and reduced physical function on postoperative outcomes in older patients who underwent gastrointestinal cancer surgery. Compared with the non‐DM group, patients with DM exhibited a higher BMI but lower grip strength. In older patients with DM, insulin resistance increases due to decreased skeletal muscle mass 20 , and weakened insulin signaling leads to a shift toward protein catabolism, further decreasing skeletal muscle mass 21 , 22 , creating a vicious cycle of DM and sarcopenia 13 , 14 . Similarly, DM and dementia are mutually risk‐related 23 , 24 , 25 , 26 , but in this study, there was no significant between‐group difference in MMSE scores. As cognitive function was only evaluated using the MMSE, the evaluation may have lacked sensitivity to detect dementia. DM is also a well‐established risk factor for both renal function decline and cardiovascular disease 27 , 28 , 29 , 30 . In the present study, the DM group exhibited significantly lower eGFR values and a higher prevalence of cardiovascular disease, suggesting a greater burden of both microvascular and macrovascular complications.
Postoperative survival analysis stratified by the presence or absence of current DM showed no significant differences between the groups. With the development of new treatments for DM and its complications, including chronic kidney disease and cardiovascular disease, and improvements in treatment quality, the mortality rate of patients has been decreasing 31 . Therefore, the impact of current DM on postoperative outcomes may have been mitigated. In contrast, postoperative outcomes were worse in patients with weak grip strength, regardless of current DM. This is consistent with previous reports showing that decreased physical function worsens postoperative outcomes 7 , 14 . Decreased physical function leads to inactivity and confinement, which, in turn, causes decreased appetite and malnutrition, creating a cycle that promotes further physical function decline 32 . This state of physiological decline is known as frailty 33 .
We subsequently conducted a multivariate analysis with postoperative survival days as the objective variable. In the univariate analysis, age, male sex, cancer stage, weak grip strength, and the sarcopenic score were positively correlated with postoperative risk, while grip strength was negatively correlated. The finding that advanced age predicts shorter survival and females generally have longer life expectancy is consistent with existing literature 34 . In the multivariate analysis, current DM did not emerge as a significant risk factor, whereas grip strength remained an independent predictor. Weak grip strength in Model 2 and the sarcopenic score in Model 3 were not significantly associated with postoperative outcomes after adjustment. These results suggest that current DM per se is not a major determinant of postoperative survival and that physical function, particularly muscle strength, plays a more important role. Grip strength, which physiologically varies between men and women and declines with age, was identified as a stronger predictor of postoperative outcomes than age in the multivariate analysis. These findings underscore the concept that overall health status, including physical function, is a more crucial determinant of postoperative outcomes than age 35 . In this study, when the sarcopenic score was included as an explanatory variable in Model 3, it did not emerge as a significant risk factor, similar to BMI. This is potentially because skeletal muscle mass is included in the calculation of the sarcopenic score, and body weight is included in the calculation of BMI, making them highly confounding factors.
Although patients with current DM exhibited a higher prevalence of weak grip strength, the multivariate models showed that only grip strength as a continuous measure remained independently associated with postoperative survival. Furthermore, the interaction analyses indicated that the adverse prognostic impact of reduced physical function was consistent regardless of DM status. Taken together, these findings suggest that while patients with DM tend to have lower muscle strength, current DM does not modify the relationship between muscle strength and postoperative survival. It is also important to consider racial and ethnic differences in the pathophysiology and complications of DM. Compared with Western populations, Japanese individuals tend to have lower BMI and are more prone to β‐cell dysfunction rather than insulin resistance 36 . Moreover, the prevalence and impact of DM‐related complications such as chronic kidney disease and cardiovascular disease may differ across ethnic groups 37 , 38 . These differences may partially explain why current DM was not an independent predictor of postoperative survival in our cohort of older Japanese patients.
This study highlights the importance of comprehensive preoperative evaluation of older patients. Future efforts should focus on perioperative interventions to maintain and improve physical function in patients with cancer, based on preoperative assessments. However, the effect of preoperative exercise and nutritional interventions on improving outcomes remains uncertain 39 , 40 , 41 , indicating a need for optimization of intervention strategies. Preoperative interventions targeting patients with DM and decreased physical function may improve postoperative outcomes through better perioperative blood glucose management and frailty improvement.
This study has several limitations. First, there is a potential for selection bias. As this study exclusively targeted older patients undergoing gastrointestinal cancer surgery at a single university hospital, the results cannot be generalized. Furthermore, gastrointestinal cancers were analyzed collectively, despite differences in prognosis and complication profiles across cancer types. However, we limited the study population to gastrointestinal cancers to reduce heterogeneity in surgical invasiveness and postoperative complication patterns. Inclusion of other cancer types, such as thoracic malignancies, could have introduced substantial variability in surgical risk and complication profiles and confounded the interpretation of the impact of DM and physical function, which was the primary focus of this study. Second, the assessment of DM in this study was limited to its presence or absence. Neither the duration of DM nor the degree of glycemic control was considered. Although HbA1c levels were significantly higher in the DM group compared with the non‐DM group, most patients did not have poorly controlled DM, and stratification based on glycemic control was not performed. These limitations may hinder the interpretation of the qualitative impact of DM severity on postoperative outcomes. Nevertheless, proper glycemic management remains clinically important, particularly given the higher prevalence of renal and cardiovascular complications observed in the DM group. Third, antidiabetic medication patterns in this cohort reflect the clinical practice of 2012–2019, during which the use of sulfonylureas, glinides, and insulin was more common and the use of GLP‐1 receptor agonists and SGLT2 inhibitors was limited. Therefore, the drug profile may differ from current practice.
In older patients undergoing gastrointestinal cancer surgery, current DM did not significantly affect postoperative outcomes. Lower grip strength was associated with poorer postoperative survival, and the prevalence of weak grip strength was higher in patients with DM. However, the prognostic impact of reduced physical function was consistent regardless of DM status. These findings highlight the importance of assessing and addressing physical function in the perioperative management of older adults with DM.
AUTHOR CONTRIBUTIONS
TF, HA, YY, SY, YO, YA, KS, and MI conducted preoperative assessments. KY, NM, TN, HT, HE, and YD managed perioperative care based on preoperative evaluations. TF, KU, YY, and TM performed the data analysis. TF, KU, HA, and KY drafted the manuscript. All authors reviewed and approved the final version of the manuscript.
FUNDING
This research received no external funding.
DISCLOSURE
The authors declare no conflicts of interest.
Research protocol approval: The protocol for this research project was approved by the Ethics Committee of the University of Osaka Hospital (approval number: 13350(T1)‐7), and the study conforms to the provisions of the Declaration of Helsinki (as revised in Fortaleza, Brazil, October 2013).
Informed consent: Informed consent was obtained from participants through an opt‐out approach, as approved by the Ethics Committee. Details of the study were disclosed on the hospital website, and participants were given the opportunity to refuse participation.
Approval date and registration number: Approved on October 26, 2020 (No. 13350(T1)‐7).
Animal experiments: N/A.
ACKNOWLEDGMENT
We thank Ms. Mari Shirai and the staff members who helped us recruit subjects. We also express our sincere gratitude to the medical staff of our department for their cooperation with this study. This research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors. We would like to thank Editage (www.editage.jp) for English language editing.
[“Correction added on 08 January 2026, after first online publication: The article type was incorrectly published as “Special Research Report” and has now been corrected to “Original Article”.]
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.