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. 2025 Oct 21;20(10):e0332330. doi: 10.1371/journal.pone.0332330

Frailty and 12-month mortality among older adults with type 2 diabetes in nursing homes: A longitudinal study

Maturin Tabué-Teguo 1,2, Nadine Simo 1,2, Axiane Placide-Francil 3, Moustapha Dramé 1,2, Laurys Letchimy 1,2, Denis Boucaud-Maitre 2,4,*
Editor: Mario Ulises Pérez-Zepeda5
PMCID: PMC12539737  PMID: 41118363

Abstract

Background

Frailty is highly prevalent among older adults with type 2 diabetes mellitus (T2DM) and may contribute to adverse health outcomes, particularly in institutionalized settings. Despite its clinical relevance, the prognostic value of frailty among nursing home residents with T2DM remains underexplored. This study aimed to assess the association between frailty, assessed using the Frailty Index (FI), and 12-month all-cause mortality among older adults with T2DM residing in French Caribbean nursing homes.

Methods

Data were drawn from the KASEHPAD (Karukera Study on Aging in Nursing Homes) study, a prospective, longitudinal cohort conducted across six nursing homes in Martinique and Guadeloupe. Frailty was assessed at baseline using a 30-item deficit accumulation model to compute the FI (range: 0–1). Mortality data were collected over a 12-month follow-up period. Associations between FI and mortality were analyzed using logistic regression and Cox proportional hazards models.

Results

The study included 94 participants with T2DM (mean age: 81.1 ± 10.0 years; 42.6% male). The mean FI was 0.30 ± 0.14. Over the 12-month follow-up, 28 participants (29.8%) died. In unadjusted logistic regression models, each 0.01-point increase in FI was associated with a 6% increase in the odds of death (Odd Ratio (OR) = 1.06; 95% CI: 1.02–1.11; p = 0.002). After adjusting for age and sex, frailty was marginally associated with 1-year mortality (OR = 1.05; 95% CI: 1.00–1.10; p = 0.056), but was not significantly associated with time to death in the Cox model (Hazard Ratio [HR] = 1.03; 95% CI: 0.99–1.07; p = 0.139).

Conclusion

Frailty measured by the FI showed a tendency to be associated with short-term mortality among older adults with type T2DM living in nursing homes. These findings underscore the need for larger studies to further assess the prognostic utility of the FI in informing care planning and clinical management in this vulnerable population.

Introduction

Type 2 diabetes mellitus (T2DM) is highly prevalent among older adults and is frequently associated with multiple comorbidities [1], functional decline, increased frailty measurement and elevated mortality risk [2,3]. In France, data from the GERODIAB cohort—a longitudinal study of nearly 1,000 individuals aged 70 years and older—have highlighted the frequent occurrence of diabetes-related complications, including cardiovascular events, renal impairment, cognitive decline, and high mortality over a five-year follow-up period [4]. In long-term care settings, such as nursing homes, the clinical management of older adults with T2DM is particularly challenging [5]. Residents are often affected by advanced age, polypharmacy, geriatric syndromes, and limited functional reserves [6–9]. In this context, the identification of reliable prognostic markers of major health events is essential to guide individualized and appropriate care strategies in this vulnerable population.

Frailty has emerged as a key determinant of clinical vulnerability in older adults, especially among those living with T2DM [10]. It is defined as a multidimensional syndrome reflecting increased vulnerability to stressors due to cumulative declines across multiple physiological systems [11]. Frailty is highly prevalent among older adults with T2DM [2,12]. The Frailty Index (FI), based on the accumulation of health deficits, is currently one of the most widely used and validated tools for identifying frailty. These deficits encompass a broad spectrum of variables, including clinical signs, symptoms, chronic diseases, functional impairments, psychosocial risk factors, and common geriatric syndromes. The FI is calculated as a ratio of the number of deficits present to the total number of considered variables, thereby providing a continuous score that reflects an individual’s biological vulnerability. Unlike categorical approaches to frailty, the FI captures the multidimensional and progressive nature of the aging process. It has consistently demonstrated strong predictive validity for a range of adverse health outcomes, such as hospitalizations, admission to long-term care facilities, functional decline, and all-cause mortality, particularly among community-dwelling older adults [6,13–17]. Importantly, the FI may serve as a valuable tool to distinguish between chronological age and biological age, offering a more nuanced understanding of heterogeneity in aging trajectories beyond specific diagnostic categories. This capacity to stratify risk at the individual level underscores its potential utility for tailoring prevention strategies, care planning, and resource allocation in geriatric populations. In the French Caribbean, the prevalence of T2DM is higher than in mainland France. Recent findings from nursing homes in the French West Indies [18] report T2DM rates exceeding 28%, well above the national average. In this area, older adults with T2DM residing in French Caribbean nursing homes exhibit a high prevalence of cardiovascular risk factors and are at risk of overtreatment. Despite this high prevalence, little is known about the prognosis value of frailty, as measured by the FI, in predicting mortality among institutionalized older adults with T2DM.

In this study, we hypothesize that the FI may serve as a useful tool for identifying the most vulnerable individuals—those at greatest risk of negative outcomes, including death—even among a population already characterized by advanced age and chronic illness. The objective of this study is to investigate the association between the FI and 12-month all-cause mortality among older adults with T2DM residing in nursing homes in the French Caribbean.

Methods

Study design

The KASEHPAD study was a prospective, observational study conducted in six nursing homes located in Martinique and Guadeloupe (French West Indies). This study aimed to describe the one-year health trajectories of older adults residing in nursing homes. Details regarding the inclusion criteria and baseline characteristics have been published previously [7]. In brief, participants were interviewed on-site at baseline, after 6 months, and after 12 months. At each visit, various geriatric domains were assessed, including dependency, cognition, malnutrition, neuropsychiatric symptoms, and quality of life. Treatments and comorbidities were extracted from medical records. In addition, phone interviews were conducted twice—at 3 and 9 months after baseline—to collect follow-up data. These phone calls provided updates on vital status and healthcare service utilization (i.e., types and frequency of use). In the event of a participant’s death, the date and cause of death were sought and documented. The study received ethical approval from the EST 1 French Ethics Committee on June 2, 2020, and was registered on ClinicalTrials.gov on October 13, 2020 (NCT04587466). Recruitment of participants began on September 01, 2020 and the end of follow-up was November 30, 2023. The KASEHPAD study is an observational research project involving human participants, with no identified risks to participant safety. In line with this classification, the requirement for written consent was waived by the EST 1 French Ethics Committee (Reference: 2020-A00960-39), in accordance with French regulatory Law No. 2012−300. Participants received a written information leaflet outlining the key elements of the study and provided verbal consent to participate. Verbal consent was documented in the case report form. Participation was entirely voluntary, and individuals were free to decline or withdraw from the study at any time, without any negative consequences. Given the high prevalence of cognitive impairment among nursing home residents, the on-site investigator ensured that participants fully understood the implications of their involvement—namely, responding to medical questionnaires without any impact on their medical care—while explaining the study details and participants’ rights, particularly regarding personal data protection. In instances where a participant was under legal guardianship and/or unable to comprehend the study, the information leaflet was provided to the legal guardian or a designated contact person, and verbal consent was obtained and recorded in the case report form. All procedures were carried out in accordance with relevant ethical guidelines and regulatory requirements.

Frailty index construction

For the present analysis, we constructed a frailty index in accordance with the standard procedure described by Searle and Rockwood [14,19,20]. The FI was derived from baseline data and included 30 variables encompassing a broad range of health domains, including comorbidities, cognitive and psychological status, functional capacity, and clinical signs observed during physical and neurological examinations (Table 1). Each variable (or “deficit”) was dichotomized as 0 (absence of the deficit) or 1 (presence of the deficit). In total, 30 variables were considered for the computation of the FI, thereby ensuring that our model is sufficiently robust [14,19,20]. The FI score was calculated for each participant as the ratio of the number of deficits present to the total number of deficits evaluated. For example, a participant with six deficits had an FI score of 6/30 = 0.2. Thus, FI scores ranged from 0 (no deficits) to 1 (all deficits present), with each additional deficit increasing the score by approximately 0.030.

Table 1. List of variables used to construct the 30-Item KASEHPAD FI. SPPB: Short Physical Performance Battery, MNA: Mini Nutritional Assessment.

1. Atrial fibrillation
2. Arterial Hypertension
3. Coronary heart disease
4. Congestive heart failure
5. Depression
6. Osteoarthritis
7. Osteoporosis
8. Respiratory disease
9. Lung problems
10. Kidney disease
11. Liver disease
12. Thyroid disease
13. Pain
14. Hearing Loss
15. Decreased Visual Acuity
16. Dementia
17. Parkinson’s disease
18. Stroke
19. Cancer
20. Bathing
21. Dressing
22. Toileting
23. Transferring
24. Urinary incontinence
25. Feeding
26. SPPB gait speed
27. SPPB chair stand
28. SPPB balance
29. Weight loss (MNA scale)
30. Neuropsychological problems (MNA scale)

Outcomes

Participants were followed for a 12 months period. Follow-up assessments included two in-person visits at 6 and 12 months, as well as two telephone interviews conducted at 3- and 9-months post-baseline. The primary outcome was all-cause mortality over the 12-month follow-up period.

Other Variables

Sociodemographic data included age, sex, and education level. Clinical data, including medical diagnoses and current medications, were extracted from participants’ medical records and healthcare documentation. Global cognitive function was assessed using the 30-item Mini-Mental State Examination (MMSE) [21]. Physical function were evaluated using the Activities of Daily Living (ADL) score [22], while nutritional status was measured using the short form of the Mini Nutritional Assessment [23].

Statistical Analysis

Quantitative variables were expressed as means ± standard deviations (SD), and categorical variables were presented as frequencies and percentages. Group comparisons were performed using chi-square tests for categorical variables and Student’s t-tests for continuous variables. The primary outcome was 12-month all-cause mortality, treated as a binary dependent variable. To assess the association between FI and mortality, logistic regression models were employed. Both unadjusted and adjusted models were estimated, with adjustments made for age and sex. The strength of association was expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Additionally, Cox proportional hazard models were performed to study the relationship between the FI and the risk of mortality over the follow-up. Missing data were not imputed. All statistical analyses were conducted using R software (R Foundation for Statistical Computing, Vienna, Austria).

Result

In total, 94 older adults with T2DM were included in the study and 91 were analyzed at 12 months follow-up (Fig 1). The mean age of participants was 81.1 ± 10.0 years, and 42.6% were male. During the 12-month follow-up period, 28 (29.8%) older adults died. Compared to survivors, those who died were significantly older (88.0 ± 9.9 vs 78.2 ± 8.6 years; p < 0.001) and had a lower body mass index (20.8 ± 4.5 vs 25.5 ± 5.2; p < 0.001). Dementia was more frequent among those who died (75.0% vs 44.4%; p = 0.007), and they exhibited significantly poorer functional and cognitive performance, as reflected by lower ADL score (1.3 ± 1.6 vs 2.5 ± 2.1; p = 0.003) and MMSE score (6.7 ± 6.5 vs 12.3 ± 9.3; p = 0.002). The FI was not significantly higher in participants who died compared to those who survived (0.37 ± 0.13 vs 0.27 ± 0.14; p = 0.346). (Table 2).

Fig 1. Flow-chart of the KASEHPAD study regarding older adults with T2DM.

Fig 1

Table 2. Baseline Characteristics of Nursing Home Residents According to Death Events (n = 94).

Characteristics Mean ± CI or n (%) Death Event (=yes) (n = 28) Death Event (=no) (n = 63) p
Age 81.1 ± 10.0 88.0 ± 9.9 78.2 ± 8.6 <0.001
Gender (men) 40 (42.6%) 10 (35.7%) 30 (47.6%) 0.291
BMI 24.4 ± 5.3 20.8 ± 4.5 25.5 ± 5.2 <0.001
Hypertension 80 (85.1%) 24 (85.7%) 54 (85.7%) 1
Cardiac failure 16 (17.0%) 4 (14.3%) 12 (19.0%) 0.768
Myocardial infarction 5 (5.3%) 2 (7.1%) 3 (4.5%) 0.641
Stroke 23 (24.5%) 6 (21.4%) 17 (27.0%) 0.573
Dementia 50(53.2%) 21 (75.0%) 28 (44.4%) 0.007
Parkinson’s disease 6 (6.4%) 4 (14.3%) 2 (3.2%) 0.070
Depression 15 (16.0%) 4 (14.3%) 10 (15.9%) 1
Kidney disease 21 (22.3%) 4 (14.3%) 17 (27.0%) 0.184
ADL score 2.1 ± 2.0 1.3 ± 1.6 2.5 ± 2.1 0.003
MMSE score 10.4 ± 8.9 6.7 ± 6.5 12.3 ± 9.3 0.002
FI score 0.30 ± 0.14 0.37 ± 0.13 0.27 ± 0.14 0.346

BMI: Body Mass Index; ADL: Activities of Daily Living; MMSE: Mini-Mental State Examination; FI: Frailty Index

In unadjusted logistic regression models, each 0.01-point increase in the FI was associated with a 6% increase in the odds of death (OR = 1.06; 95% CI: 1.02–1.11; p = 0.002). After adjusting for age, sex, the association remained marginally significant (adjusted OR = 1.05; 95% CI: 1.00–1.10; p = 0.056) (Table 3). In unadjusted Cox proportional hazard models, FI was also associated with increased risk of mortality (HR:1.04, 95%CI: 1.01–1.11; p = 0.009). After adjusting for age and sex, this association was not significant (HR: 1.03, 95%CI: 0.99–1.07; p = 0.139).

Table 3. Relationship of Frailty Index (FI) and Mortality over 1 year of follow-up.

Logistic model Cox model
Unadjusted OR p Adjusted OR p Unadjusted HR p Adjusted HR p
FI 1.06 (1.02-1.11) 0.002 1.05 (1.00-1.10) 0.056 1.04 (1.01-1.11) 0.009 1.03 (0.99-1.07) 0.139

OR: odd-Ratio. HR: Hazard Ratio

Discussion

In this prospective cohort study of older adults with T2DM residing in nursing homes in the French Caribbean, our findings suggest that FI mays serve as a predictor of 12-month all-cause mortality. Individuals with higher frailty levels were significantly more likely to die within one year in univariates analysis. In multivariable models adjusted for age and gender, frailty was marginally associated with 1-year mortality when using logistic regression but was not significantly associated with time to death in the Cox proportional hazards model. This discrepancy likely reflect the different nature of the models, with logistic regression capturing the overall likelihood of death at one year, and Cox regression focusing on the instantaneous hazard over time. conceptual frameworks of the two models: logistic regression estimates the overall probability of death within a fixed period, whereas Cox regression evaluates the instantaneous hazard of death over time. While we hypothesized that frailty would be associated with increased overall mortality among residents with T2DM, it may not significantly influence the timing of death over the 12-month follow-up period. Nevertheless, this observation warrants further validation through large-scale studies.

Our results are consistent with previous studies of the relationship between FI and adverse health outcomes in older adults [24,25]. These studies have demonstrated that FI is a strong predictor of death [6,26], functional decline [27], and hospitalization in both community-dwelling and institutionalized older adults [28]. However, the strength of this association may be attenuated in nursing home populations, likely due to the high baseline prevalence of deficits and proximity to end-of-life. This “ceiling effect” suggests a reduced discriminatory capacity of the FI in highly frail populations, as previously reported by Tabue-Teguo and colleagues [6]. Importantly, while frailty has been widely studied in general geriatric cohorts, few investigations have specifically targeted diabetic nursing home residents—a group characterized by advanced age, high levels of multimorbidity, and complex clinical needs [12,29,30]. Our study addresses this gap and provides evidence that frailty, as measured by the FI, could be a clinically meaningful predictor of short-term mortality in this high-risk subgroup. The observed 12-month mortality rate of nearly 30% among frail residents with T2DM is concerning but consistent with their known vulnerability. Frailty likely reflects the cumulative impact of physiological decline across multiple systems, impairing resilience to common acute stressors such as infections, cardiovascular events, or exacerbations of chronic diseases [31,32]. The FI, as a quantitative and scalable tool, may offer clinicians a practical approach to stratifying risk and guiding care decisions, including advance care planning and prioritization of interventions [33]. Notably, in our analysis, the FI outperformed several individual comorbidities (e.g., hypertension, chronic kidney disease) in predicting mortality, emphasizing the added prognostic value of comprehensive geriatric assessment over disease-specific indicators alone. Although longitudinal assessment of FI could be of interest, the relatively short 12-month follow-up period in our study limits the potential added value of measuring changes over time. Previous research using the same set of FI variables [6] demonstrated that the baseline FI reliably predicted 1-year mortality in nursing home residents. Given the deficit accumulation approach used to construct the FI [34], it tends to remain stable over short intervals, which may reduce the utility of repeated assessments within a 6-month timeframe. Furthermore, our relatively small sample size (94 participants with T2DM) and the limited number of events (28 deaths) reduce the statistical power to detect additional predictive value from mid-point FI measurements.

This study has several strengths, including a longitudinal design, the use of validated frailty assessment methodology, and a focus on an underrepresented and particularly vulnerable population. From a clinical standpoint, findings from the KASEHPAD cohort offer valuable real-world insights into the prognostic significance of frailty in diabetic older adults living in long-term care facilities in the French West Indies. Nonetheless, some limitations should be acknowledged. The relatively small sample size may have limited the statistical power to detect subgroup differences or explore interactions. Notably, a more detailed analysis of macrovascular and microvascular complications and treatments could provide valuable insights into the relationship between these complications and mortality. The magnitude of the association between frailty and mortality was low. This association is likely to be weaker in nursing home populations because residents generally present with a high burden of health deficits and are, therefore, closer to the outcome of interest—namely, mortality—compared to community-dwelling older adults. Moreover, while the FI was constructed according to established principles, it was adapted to the available dataset, which could affect its reproducibility. Finally, the absence of cause-specific mortality data limits our ability to elucidate the specific pathways linking frailty and death.

Conclusion

In this study, frailty measured by the FI showed a tendency to be associated with short-term mortality among older adults with type T2DM living in nursing homes. While these findings did not reach strong statistical significance, the observed trend suggests that frailty may play an important prognostic role in this vulnerable population. Incorporating frailty assessment into routine care may contribute to more personalized and appropriate management strategies. Nevertheless, these findings warrant larger-scale studies to further support the prognostic utility of the Frailty Index in guiding the management and care planning of institutionalized older adults with T2DM.

Supporting information

S1 Data. Data Set.

(CSV)

pone.0332330.s001.csv (6.5KB, csv)

Acknowledgments

We would like to thank the ACTIVE Team from Bordeaux for their precious methodological support, as well as Valérie Soter, and Mélanie Petapermal for their regulatory support. We thank the following nursing homes for participating in the study: EHPAD Les Flamboyants (Gourbeyre, Guadeloupe), EHPAD Kalana (Bouillante, Guadeloupe), EHPAD Nou Grand Moun (Capesterre-Belle-Eau, Guadeloupe), EHPAD les Jardins de Belost (Saint-Claude, Guadeloupe), Centre Hospitalier Gerontologique Palais Royal (Les Abymes, Guadeloupe) and Centre Emma Ventura (Fort-de-France, Martinique).

Declaration of generative AI: During the preparation of this work the author(s) used ChatGPT in order to improve readability and language. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication.

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

This study was supported by a grant from the Conseil Départemental de la Guadeloupe and ARS de la Guadeloupe, Saint-Martin, and Saint-Barthélemy (grant 2020/DPAPH/DRM) and ARS Martinique. The funding body had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

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Decision Letter 0

Mario Pérez-Zepeda

18 Jul 2025

PONE-D-25-31998 Frailty and 12-Month Mortality Among Older Adults with Type 2 Diabetes in Nursing Homes. A longitudinal study. PLOS ONE

Dear Dr. Boucaud-Maitre,

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Reviewer #1: No

Reviewer #2: No

**********

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Reviewer #1: No

Reviewer #2: N/A

**********

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Reviewer #1: Yes

Reviewer #2: No

**********

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Reviewer #2: Yes

**********

5. Review Comments to the Author

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Reviewer #1: Considering that this is a mortality study, the authors should have done a survival analysis including log rank test and Cox regression. They seem to have the data, so in my opinion they should perform it in order to publish their results.

Reviewer #2: Thank you for the opportunity to review this manuscript addressing the prognostic role of frailty in older adults with type 2 diabetes mellitus (T2DM) residing in nursing homes. The topic is highly relevant given the growing interest in frailty and risk stratification in institutionalized older adults with multimorbidity. However, I believe that the manuscript requires substantial revision before it can be considered for publication. Below, I provide detailed comments intended to help the authors strengthen their work.

Major Comments:

1.Lack of Stratification by Diabetes Treatment and Complications

The manuscript does not distinguish between participants treated with insulin and those on oral antidiabetic medications, nor does it stratify for the presence or absence of macrovascular complications. This is a significant limitation, as the severity and management of diabetes (including history of cardiovascular events, renal impairment, or diabetic foot) are likely to influence both frailty and mortality.

2.Absence of a Comparison Group Without Diabetes

The study would have benefitted from including a comparator group of non-diabetic nursing home residents to evaluate whether frailty carries a different prognostic weight in diabetic versus non-diabetic older adults. Without this comparison, it is difficult to assess the specificity of the observed associations to the diabetic population.

3.Unclear Follow-Up Design and Methodology

Although the manuscript mentions follow-up through in-person and telephone interviews, it does not detail the content or structure of these follow-up interactions—particularly the telephone assessments. Clarifying what clinical, functional, or survival data were captured at each time point (3, 6, 9, and 12 months) is crucial for evaluating the robustness of the outcome ascertainment.

4.Frailty Index Temporal Dynamics Not Reported

5.Overlap Between FI and ADL Measures

Several items included in the FI (e.g., bathing, dressing, toileting) are also captured separately using the ADL scale. The potential redundancy and statistical collinearity should be addressed. It would be important to clarify whether the predictive value of the FI is independent of the ADL score.

6.Inconsistency Between Results and Conclusions

In the results section, the adjusted analysis shows that FI is not a statistically significant predictor of mortality (p = 0.056), and yet the conclusions emphasize its utility for care planning and management. This discrepancy should be reconciled. A more nuanced interpretation is required, especially given the marginal statistical significance and the possible confounding role of age.

7.Impact on Clinical Management Not Substantiated

The authors suggest that FI assessment may guide care planning and improve prognosis, but they do not explain what specific changes in management would follow FI stratification, nor do they provide any evidence that such changes would alter outcomes. In particular, the authors should clarify how they envision the FI influencing decision-making in patients whose outcomes are predominantly driven by age and baseline functional impairment.

8.Definition of Frailty Needs Clarification

The manuscript adopts the deficit accumulation approach, but it does not adequately define or justify the conceptual framework of frailty being used. A clearer explanation of how frailty is operationalized and how it differs from disability or comorbidity would benefit readers unfamiliar with the field.

9.Underdeveloped Discussion and Conclusion

The discussion could be strengthened by a more critical interpretation of the limitations, especially regarding the sample size, generalizability, and the ceiling effect in highly frail populations. The conclusions would also benefit from being more concise and aligned with the actual findings. Currently, they overstate the prognostic utility of FI despite the lack of a significant adjusted effect and the absence of intervention data.

Additional Suggestions

Consider including a flow diagram of participant recruitment and follow-up.

Indicate how missing data were handled.

Ensure statistical results are consistently reported (e.g., precise p-values and confidence intervals).

Conclusion

In its current form, the manuscript raises important questions but does not provide sufficient methodological or interpretive clarity to support its conclusions. I recommend major revision, with careful attention to the points outlined above. I appreciate the authors’ effort in addressing a timely and clinically significant topic and hope these comments are helpful in improving the manuscript.

**********

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Reviewer #1: No

Reviewer #2: No

**********

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PLoS One. 2025 Oct 21;20(10):e0332330. doi: 10.1371/journal.pone.0332330.r002

Author response to Decision Letter 1


18 Aug 2025

Reviewer #1:

1. Considering that this is a mortality study, the authors should have done a survival analysis including log rank test and Cox regression. They seem to have the data, so in my opinion they should perform it in order to publish their results.

Authors response : We thank the reviewer for their comments. First of all, we would like to clarify our decision to use a logistic regression model rather than a Cox proportional hazards model to analyze one-year mortality. Given the short and clearly defined follow-up period, the relatively low sample size, with vital status assessed precisely at 12 months, we considered logistic regression to be an appropriate and interpretable approach. Indeed, the study population consisted of older adults living in nursing homes, a setting associated with high short-term mortality (approximately 30%). In this context, the proportional hazards assumption required for Cox modeling may not have been appropriate, and analyzing mortality as a binary outcome at a fixed time point provided a clearer interpretation of the event of interest. If frail patients die at approximately the same rate as non-frail patients over time — that is, if their survival curves are similar — the Cox proportional hazards model may not detect a significant association, even if the overall mortality is slightly higher in the frail group. This is because the Cox model estimates the hazard ratio, which reflects the instantaneous risk of death at any given time point, rather than the cumulative probability of death over the entire follow-up period. Therefore, if the excess mortality among frail individuals is spread evenly over time without a clear difference in the timing of deaths, the hazard ratio may be close to 1 and non-significant, despite a potentially meaningful difference in overall mortality. In contrast, logistic regression — which compares the final mortality status at a fixed time point (e.g., 1 year) — may be more sensitive to such cumulative effects, particularly in studies with relatively short follow-up periods as observed in KASEHPAD study or when most events occur late during follow-up (more than half of death occur between six and twelwe months in our study). Therefore, we considered the logistic model to be more appropriate for addressing our research question.

Nevertheless, we acknowledge that a Cox model can provide complementary insights, and we have performed this additional analysis. Using the Cox model (n = 91), we found that higher FI scores were significantly associated with increased mortality risk: each 0.01-point increase in the FI was associated with a 4.3% increase in the hazard of death (HR = 1.04; 95% CI: 1.01–1.11; p = 0.0089). This result is similar to those obtained using logistic regression. However, after adjustment for age and sex, the association between FI and mortality was no longer significant (adjusted HR = 1.03; 95% CI: 0.99–1.07; p = 0.139), while age remained significantly associated with mortality (HR = 1.08; 95% CI: 1.03–1.13; p < 0.001). This suggests that while frailty may be associated with increased overall mortality, it may not significantly influence the timing of death during the 12 months follow-up.

We propose to include the Cox analysis in the Methods and Results sections, and to add the following paragraph to the Discussion: “ In multivariable models adjusted for age and gender, frailty was marginally associated with 1-year mortality when using logistic regression but was not significantly associated with time to death in the Cox proportional hazards model. This discrepancy likely reflect the different nature of the models, with logistic regression capturing the overall likelihood of death at one year, and Cox regression focusing on the instantaneous hazard over time. conceptual frameworks of the two models: logistic regression estimates the overall probability of death within a fixed period, whereas Cox regression evaluates the instantaneous hazard of death over time. While we hypothesized that frailty would be associated with increased overall mortality among residents with T2DM, it may not significantly influence the timing of death over the 12-month follow-up period. Nevertheless, this finding warrants confirmation through large-scale studies.”

Reviewer #2: Thank you for the opportunity to review this manuscript addressing the prognostic role of frailty in older adults with type 2 diabetes mellitus (T2DM) residing in nursing homes. The topic is highly relevant given the growing interest in frailty and risk stratification in institutionalized older adults with multimorbidity. However, I believe that the manuscript requires substantial revision before it can be considered for publication. Below, I provide detailed comments intended to help the authors strengthen their work.

Authors comment : We thank the reviewer for their encouraging comments.

Major comments

1. Lack of Stratification by Diabetes Treatment and Complications

The manuscript does not distinguish between participants treated with insulin and those on oral antidiabetic medications, nor does it stratify for the presence or absence of macrovascular complications. This is a significant limitation, as the severity and management of diabetes (including history of cardiovascular events, renal impairment, or diabetic foot) are likely to influence both frailty and mortality.

Authors response : We concur with the reviewer’s comment, which should be considered alongside a more descriptive study of KASEHPAD of older adults residing in nursing homes that we recently conducted and published (Tabué-Teguo M, Simo N, Rambhojan C, Letchimy L, Bonnet M, Vélayoudom FL, Boucaud-Maitre D. Prevalence and characteristics of older adults with type 2 diabetes mellitus living in French Caribbean nursing homes: results from the baseline KASEHPAD study. Aging Clin Exp Res. 2025 Mar 24;37(1):103. doi: 10.1007/s40520-025-03008-5. PMID: 40128462; PMCID: PMC11933193). In this study, the mean HbA1c was 7.32% ± 1.5%, with 35 participants (42.7%) exhibiting an HbA1c level of <7%. Among the residents, 37.2% were not receiving any antidiabetic treatment, 43% were on insulin (n=41), and 25% were receiving oral antidiabetic agents.

However, we acknowledge that the sample size may be too small to perform robust additional analyses. Moreover, we observed in our study that, in multivariate analysis (n = 71) adjusted for age, sex, BMI, hypertension, hypercholesterolemia, dementia, MNA score, ADL score, and HbA1c, only HbA1c was significantly associated with antidiabetic treatment (OR: 1.76; 95% CI: 1.12–3.04). This suggests that antidiabetic treatment may not be a reliable marker of clinical severity when comorbidities are taken into account.

Regarding comorbidities, we used a frailty index based on the model proposed by Rockwood, which includes atrial fibrillation, hypertension, coronary heart disease, heart failure, and kidney disease. We agree with the reviewer that a more detailed analysis of macrovascular and microvascular complications could provide valuable insights into the relationship between these complications and mortality. We acknowledge this as a major limitation of our study and propose to explicitly address it in the discussion section.

2. Absence of a Comparison Group Without Diabetes.

The study would have benefitted from including a comparator group of non-diabetic nursing home residents to evaluate whether frailty carries a different prognostic weight in diabetic versus non-diabetic older adults. Without this comparison, it is difficult to assess the specificity of the observed associations to the diabetic population.

Authors response: This is an interesting point. As the KASEHPAD cohort also included non-diabetic participants (n=224), we conducted an additional analysis to examine the association between the frailty index and one-year mortality in non-diabetic residents—a relationship that has already been demonstrated in previous studies. In our logistic regression model (n=208), the frailty index was indeed associated with one-year mortality: OR = 1.06 (95% CI: 1.03–1.09), as was male sex (OR = 2.24; 95% CI: 1.05–4.95), while age was not significantly associated (OR = 1.03; 95% CI: 0.99–1.07).

This additional analysis reinforces the external validity of our study, as it confirms findings already reported in the literature. However, we would like to emphasize that this analysis among non-diabetic individuals lies outside the primary scope of our study focused on older adults with T2DM residing in nursing homes. Given that this association has been well-documented previously, we do not consider it necessary to include these additional findings in the main manuscript.

3.Unclear Follow-Up Design and Methodology. Although the manuscript mentions follow-up through in-person and telephone interviews, it does not detail the content or structure of these follow-up interactions—particularly the telephone assessments. Clarifying what clinical, functional, or survival data were captured at each time point (3, 6, 9, and 12 months) is crucial for evaluating the robustness of the outcome ascertainment.

Author’s response : We agree with the reviewer’s comment. The methodology of this study has already been described in several publications (Boucaud-Maitre D et al., Front Med (Lausanne). 2024 Sep 17;11:1428443; Boucaud-Maitre D et al., Sci Rep. 2025 Feb 20;15(1):6170; Boucaud-Maitre D et al., Sci Rep. 2025 Mar 6;15(1):7918). Nevertheless, we acknowledge the importance of providing sufficient methodological detail for readers of the present article. We therefore propose to expand the Methods section as follows:

“The KASEHPAD study was a prospective, observational study conducted in six nursing homes located in Martinique and Guadeloupe (French West Indies). The aim of the study was to describe the one-year health trajectories of older adults residing in nursing homes. Details regarding the inclusion criteria and baseline characteristics have been published previously (7). In brief, participants were interviewed on-site at baseline, after 6 months, and after 12 months. At each visit, various geriatric domains were assessed, including dependency, cognition, malnutrition, neuropsychiatric symptoms, and quality of life. Treatments and comorbidities were extracted from medical records. In addition, phone interviews were conducted twice—at 3 and 9 months after baseline—to collect follow-up data. These phone calls provided updates on vital status and healthcare service utilization (i.e., types and frequency of use). In the event of a participant’s death, the date and cause of death were sought and documented.”

4. Frailty Index Temporal Dynamics Not Reported.

Author’s response : We thank the reviewer for this pertinent comment. We agree that analyzing the evolution of the Frailty Index (FI) over time is of interest. However, in our study, the 6-month follow-up period is relatively short and does not provide additional relevant information regarding the association between FI and mortality.

The Rockwood FI measured at baseline has been well established in the literature as a robust predictor of short- and medium-term mortality (Mitnitski et al., 2001; Rockwood et al., 2005) even to nursing home. In a previous study (Tabue Teguo et al., JAMDA 2015), we also demonstrated that the baseline FI constructed using the same variables as in the present work accurately predicted 1-year mortality in nursing home residents. Its short-term stability (over 6 months), partly due to its deficit accumulation based methodology (Searle et al.), limits the added value of 6 months measurements. Finally, given the sample size (90 T2DM participants) and the relatively low number of events (30 deaths) in our study, including the 6-month FI measurement would be unlikely to improve the predictive performance or provide clinically meaningful additional insights.We have added a corresponding paragraph in the discussion section.

5. Overlap Between FI and ADL Measures. Several items included in the FI (e.g., bathing, dressing, toileting) are also captured separately using the ADL scale. The potential redundancy and statistical collinearity should be addressed. It would be important to clarify whether the predictive value of the FI is independent of the ADL score.

Author’s response : There was no collinearity in our multivariate analysis, as we adjusted for age and sex, but not for ADL, which are already included in the frailty index.

6. Inconsistency Between Results and Conclusions. In the results section, the adjusted analysis shows that FI is not a statistically significant predictor of mortality (p = 0.056), and yet the conclusions emphasize its utility for care planning and management. This discrepancy should be reconciled. A more nuanced interpretation is required, especially given the marginal statistical significance and the possible confounding role of age.

Author’s response : We fully agree with the reviewer’s objection. Our study raises a scientifically relevant question that deserves to be explored in larger-scale studies, in order to determine whether the assessment of frailty in nursing home settings is indeed essential. We have revised both the abstract, the discussion and the conclusion to reflect this more nuanced interpretation.

7. Impact on Clinical Management Not Substantiated

The authors suggest that FI assessment may guide care planning and improve prognosis, but they do not explain what specific changes in management would follow FI stratification, nor do they provide any evidence that such changes would alter outcomes. In particular, the authors should clarify how they envision the FI influencing decision-making in patients whose outcomes are predominantly driven by age and baseline functional impairment.

Author’s response: We agree with the reviewer. At this stage, it is necessary to confirm (or refute) these findings before recommending the widespread implementation of the Frailty Index in nursing homes for T2DM adults. See discussion and conclusion.

8. Definition of Frailty Needs Clarification. The manuscript adopts the deficit accumulation approach, but it does not adequately define or justify the conceptual framework of frailty being used. A clearer explanation of how frailty is operationalized and how it differs from disability or comorbidity would benefit readers unfamiliar with the field.

Author’s response : We agree with the reviewer’s comment. The Frailty Index (FI), developed by Rockwood and colleagues, is grounded in a theoretical framework that conceptualizes frailty as the result of an age-related accumulation of health deficits. We propose to develop this point in the introduction section : « These deficits encompass a broad spectrum of variables, including clinical signs, symptoms, chronic diseases, functional impairments, psychosocial risk factors, and common geriatric syndromes. The FI is calculated as a ratio of the number of deficits present to the total number of considered variables, thereby providing a continuous score that reflects an individual's biological vulnerability. Unlike categorical approaches to frailty, the FI captures the multidimensional and progressive nature of the aging process. It has consistently demonstrated strong predictive validity for a range of adverse health outcomes, such as hospitalizations, admission to long-term care facilities, functional decline, and all-cause mortality, particularly among community-dwelling older adults. Importantly, the FI may serve as a valuable tool to distinguish between chronological age and biological age, offering a more nuanced understanding of heterogeneity in aging trajectories beyond specific diagnostic categories. This capacity to stratify risk at the individual level underscores its potential utility for tailoring prevention strategies, care planning, and resource allocation in geriatric populations. »

9. Underdeveloped Discussion and Conclusion. The discussion could be strengthened by a more critical interpretation of the limitations, especially regarding the sample size, generalizability, and the ceiling effect in highly frail populations. The conclusions would also benefit from being more concise and aligned with the actual findings. Currently, t

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pone.0332330.s003.docx (35.1KB, docx)

Decision Letter 1

Mario Pérez-Zepeda

29 Aug 2025

<p>Frailty and 12-Month Mortality Among Older Adults with Type 2 Diabetes in Nursing Homes. A longitudinal study.

PONE-D-25-31998R1

Dear Dr. Boucaud-Maitre,

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Acceptance letter

Mario Pérez-Zepeda

PONE-D-25-31998R1

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