End-stage renal disease (ESRD) is a significant global public health concern that affects people in both wealthy and developing nations (1). Renal replacement therapy is currently provided to more than 1.9 million patients with ESRD worldwide (2). Patients on hemodialysis (HD) encounter a variety of health-related stressors, significantly increasing their susceptibility to depression (3). Of particular concern is the high prevalence of depression among patients receiving HD. A recent study reported that 74.6% of patients on HD had clinically significant depressive symptoms (4). Among patients with HD, depression adversely affects clinical outcomes, manifesting as diminished quality of life, compromised medication adherence, heightened hospital readmission rates, and elevated risks of both suicidal behavior and mortality (5–7).

Type 2 diabetes mellitus (T2DM) is characterized by chronic hyperglycemia, while depression is a prevalent comorbidity of the condition, probably as a result of overlapping risk factors (8). Studies have indicated that individuals with diabetes have a higher prevalence of depression (9). Biological pathways, including chronic hyperglycemia, low-grade inflammation, and microvascular dysfunction, are implicated in the pathogenesis of both T2DM and depression (10). Subclinical inflammation, dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, and the sympathetic nervous system are linked to molecular alterations in depression and T2DM (11). Depression predicts suboptimal glycemic control, more frequent hospitalizations, accelerated diabetic complications, and increased diabetes-related mortality (12). Individuals with diabetes mellitus who exhibit poor glycemic control are at an increased risk of incident depression and other associated health complications (13). Depression can significantly impact daily behaviors, including sleep patterns, dietary intake, appetite, fatigue levels, and physical activity. These symptoms are also closely associated with diabetes management. Patients diagnosed with comorbidities may derive clinical benefit from enhanced surveillance protocols and individualized therapeutic interventions (14–16).

Malnutrition represents a significant public health concern, particularly among elderly individuals residing in long-term care facilities, hospitalized patients, or those living independently at home (17–19). Previous research has demonstrated that 27.3% of HD patients exhibit moderate to severe malnutrition (20). The Geriatric Nutritional Risk Index (GNRI), introduced by Bouillanne et al. in 2005, is an objective nutritional screening tool based on height, weight, ideal body weight, and serum albumin concentration. This tool has been validated as a reliable instrument for assessing patients’ nutritional status and identifying individuals at risk of malnutrition (21, 22). Existing literature has established an association between dehydration and depression, with evidence indicating that malnutrition tends to be more pronounced among dialysis patients experiencing depressive symptoms (23). Malnutrition is also one of the most common complications in older people with T2DM. Studies on the connection between GNRI and depression in older adults with T2DM are limited, particularly in the settings of Chinese community dialysis patients.

The purpose of this study was to examine the association between GNRI and depression in older Chinese community-dwelling dialysis patients, stratified by the presence or absence of T2DM. Diabetes stratification is crucial for identifying and managing high-risk patients susceptible to complications, particularly within the dialysis population. Accurate risk stratification enables the customization of treatment plans, thereby enhancing the overall care provided to patients. We hypothesized that lower GNRI scores would be associated with an increased prevalence of depression among patients with T2DM on dialysis. By examining the relationship between depression and GNRI, dialysis patients can be provided with more personalized nutritional and psychological interventions, thereby enhancing their overall quality of life and treatment satisfaction.

Figure 1 shows the flow of hemodialysis participants with subgroups. Baseline characteristics of the subjects were presented in Table 1 . Among 684 participants (431 men, 253 women; mean age 69.60 ± 6.65 years), there were 240 (35.1%) patients with depression. Table 1 shows the socioeconomic and health-related characteristics of patients with MHD stratified by depression. Hyperlipidemia, diabetes, heart disease, and PTH significantly differed between groups (P<0.05, Table 1 ).

In participants with T2DM, we classified them again according to whether they are defined as depressed ( Table 2 ). Individuals with T2DM who concurrently had depression showed reduced GNRI scores (P =0.017). Individuals without T2DM who suffered from depression required lengthier dialysis sessions (P =0.005). Heart disease (P =0.004) and hyperlipidemia (P =0.018) were also more common in people with depression. Additionally, individuals with depression had higher levels of laboratory markers such as hemoglobin (P =0.037), albumin (P =0.049), and PTH (P =0.002). Table 2 shows the difference in characteristics of older adults classified by depression and T2DM.As shown in Figure 2 , it is noteworthy that in the diabetes group, depression patients’ GNRI scores was significantly associated with depression and it is a protective factor for depression.

We further analyzed the relationship between depression and GNRI in T2DM participants ( Table 3 ). Before adjustment for covariates, there were significant differences between baseline depression and GNRI (OR=0.983, 95% CI 0.969–0.996, P =0.013). After adjusting for covariates, significant differences between baseline depression and GNRI during follow-up (OR=0.984, 95% CI 0.969–1.000, P =0.046).

Our study delineates the association between GNRI and depression in older dialysis patients with and without T2DM. We found that, among patients with T2DM, those with depression had significantly lower GNRI scores than their non-depressed counterparts; however, no such association was observed in patients without T2DM.

The detection rate of depressive symptoms in the PHQ-9 in our study was 35.1%, which is consistent with the results of other studies: King-Wing Ma et al. reported the prevalence of depressive symptoms in hemodialysis patients to be 22.8%–39.3% (7). However, several studies have shown a higher prevalence of depression in hemodialysis patients, as high as 85% (32). Heterogeneity across studies can be attributed to variations in patient characteristics, time since dialysis initiation, and the screening instruments employed.

Some studies suggest that serum hemoglobin (33, 34), albumin (34, 35), lipid levels (36), and heart disease (37) are associated with depression. In contrast, we did not observe an independent association between serum albumin and depressive symptoms. This discrepancy may partly reflect heterogeneity in patients’ metabolic status, body composition, physical-activity levels, environmental factors, and the severity spectrum of depression.

Older adults with diabetes are more likely to suffer from depression. Additionally, our investigation revealed that T2DM patients exhibited a significantly higher prevalence of depression compared to non-T2DM patients (P<0.05). This result is consistent with prior research (38, 39). Additionally, our previous study demonstrated notable nutritional disparities associated with depressive status (40). Malnutrition not only contributes to adverse health outcomes in individuals with diabetes but also serves as a risk factor for chronic kidney disease (CKD) (41, 42). Thus, in this study, we examined the link between the GNRI and depression in diabetic and non-diabetic hemodialysis patients as well as the nutritional status as assessed by the GNRI in the depressed and diabetic subgroups of the population receiving hemodialysis.

Potential mechanisms underlying the association between the GNRI and depression are outlined below. Depression is well-documented to be immune-modulated. Elevated levels of inflammatory markers, such as C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), and soluble IL-2 receptor (43–45), are consistently associated with depression in cross-sectional study meta-analyses. Additionally, gene expression studies have discovered that depression is associated with an upregulation of inflammatory pathways (46–48). IL-6 and CRP represent the most extensively studied inflammatory biomarkers in this context. Both are easy to measure in serum and are related. Consequently, CRP and IL-6 are among the most frequently scrutinized serological indicators for depression.

Association between the GNRI and systemic inflammation have been documented in prior research (49, 50). A previous study has found that patients with lower GNRI scores had lower serum albumin concentrations and lean body mass and higher levels of inflammatory markers, including CRP, TNF-α, and IL-6 (49). These findings indicate that the GNRI—an accessible, validated nutritional screening tool—not only assesses nutritional status but also serves as a proxy for underlying inflammatory processes, particularly in patients with chronic kidney disease (CKD).

Diabetes is a chronic medical condition with a well-established bidirectional association with depression. The burden of diabetes management, along with diabetes-related complications and psychosocial stressors, such as stigma and the psychological impact of diagnosis, may trigger or exacerbate depressive disorders (51, 52). The onset of diabetes exacerbates concerns regarding protein–energy balance by accelerating the loss of muscle mass, strength (53), and serum albumin, while also adversely affecting overall nutritional intake. Hypoalbuminemia is associated with both acute and chronic inflammation, a key pathophysiological mechanism contributing to the development of long-term diabetic complications. Furthermore, prolonged chronic inflammation increases the risk of hypoalbuminemia, suggesting that as patients with diabetes accumulate chronic complications (54), systemic inflammatory activity is also heightened. Since GNRI is primarily influenced by serum albumin, height, and body weight objective factors, the index of GNRI decreases when these variables remain constant.

In the present study, the GNRI, when analyzed as a continuous variable, was significantly associated with depression in the diabetic population. Depressed patients exhibited lower GNRI scores compared to their non-depressed counterparts. Notably, the GNRI was not employed as a dichotomous indicator in this analysis, as such categorization may oversimplify the assessment of nutritional status and fail to capture subtle but clinically relevant changes that could influence patient prognosis. Furthermore, the observed associations may be influenced by sample selection and specific population characteristics. Therefore, further well-designed prospective cohort studies are warranted to validate the relationship between GNRI and depression in individuals with diabetes.

While this study offers novel insights into the relationship between nutrition and depression in dialysis patients, both with and without diabetes, several limitations must be acknowledged. First, since this was a cross-sectional study, it was not possible to determine the existence of a causal link. Second, it is possible that the study sample cannot be applied to other populations because it was restricted to Chinese dialysis patients. Third, even after adjusting for a number of variables, we continue to take into account certain variables, such as residency status and marital status. Furthermore, the GNRI was only used as a continuous variable in this study and was not classified using the traditional methods. Consequently, large-scale multicenter studies with increased sample diversity are imperative to enhance statistical power and generalizability. Furthermore, longitudinal designs are essential for establishing temporal relationships, tracking GNRI-depression trajectories, and validating causality in this understudied population.

In conclusion, this study demonstrated the relationship between depression and the GNRI in older Chinese community dialysis patients, both with and without T2DM. Notably, a significant correlation was observed between depression and GNRI within the diabetic cohort, highlighting the potential impact of nutritional status on the onset of depression. These findings provide valuable insights for clinical practice and future research, potentially leading to improved mental health treatment for dialysis patients.