Body mass index and physical frailty among older Mexican Americans: Findings from an 18-year follow up.

PURPOSES: The relationship between body mass index (BMI) and frailty in older Mexican Americans has not been previously studied. The objective of this study was to examine the relationship between BMI and frailty among non-frail older Mexican Americans at baseline over 18 years of follow up.
METHODS: Longitudinal population-based study of 1,648 non-institutionalized Mexican Americans aged ≥ 67 years from the Hispanic Established Population for the Epidemiologic Study of the Elderly (1995/96-2012/13). Frailty phenotype was defined as meeting three or more of the following: unintentional weight loss of >10 pounds, weakness, self-reported exhaustion, low physical activity, and slow walking speed. BMI (kg/m2) was classified as underweight (<18.5), normal weight (18.5-<25), overweight (25-< 30), obesity category I (30-<35), and obesity category II/morbid obesity (≥35). Covariates included socio-demographics, comorbidities, cognitive function, and depressive symptoms. Generalized Estimating Equation models were performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of frailty as a function of BMI category.
RESULTS: Participants with underweight or obesity category II/ morbid obesity had greater odds of frailty over time compared to those with normal weight (OR = 2.39, 95% CI = 1.29-4.44 and OR = 1.62, 95% CI = 1.07-2.44, respectively) after controlling for all covariates. Participants with BMIs in the overweight or category I obesity were at lower odds of frailty over time.
CONCLUSIONS: Mexican American older adults with BMIs in the underweight or obesity category II/morbid obesity were at higher odds of frailty over time. This indicates that maintaining a healthy weight in this population may prevent future frailty.

Introduction

Frailty is a geriatric condition characterized by decline in multiple systems leading to an impaired ability to respond to stressors [1]. It predisposes individuals to adverse events including hospitalizations, disability, cognitive decline, falls, and mortality [1-4]. There is no universally recognized definition of frailty, but the frailty phenotype described by Fried et al. is the most commonly used definition to study frailty [1]. Weight loss and low body mass index (BMI) are criteria for some definitions of frailty, including the frailty phenotype [1, 5–7]. However, studies have shown that the prevalence of frailty is higher among those malnourished, but the prevalence of malnourished is less than 10% among older adults with frailty [8-10].

The relationship between BMI and frailty has only recently been explored. Cross-sectional studies have shown that there is a U- or J-shaped relationship between BMI and frailty [6, 11–17]. Ferriolli et al. [13], using the Frailty in Brazilian Elderly (FIBRA-BR) Study, found underweight (BMI < 18.5 kg/m2) associated with frailty while obesity (BMI ≥ 30 kg/m2) was associated with prefrailty. Rietman et al. [14] using the Doetinchem Cohort Study found a high prevalence of frailty among those in the underweight (8.2%) and obesity (5.0%) categories compared with those of normal weight. Findings from the EPIdémiologie De I’OStéoporose, Epidmiology of Osteoporisis (EPIDOS) Study showed a J-shaped relationship between BMI and frailty, where the percentage of underweight and obesity women who were frail were 10.8% and 20.3%, respectively [12].

Longitudinal studies have also found that obesity predicts the development of frailty [18-25]. For example, a study by Stenholm et al. [24] concluded that midlife obesity led to a five-fold increase in the risk of frailty over a 22-year follow up compared to those of normal weight among participants in the Mini-Finland Health Examination Survey. Ho et al. [19] found that older adults in the Taiwan Longitudinal Study on Aging with obesity were twice as likely to develop frailty over 8 years of follow up when compared to a group with high-normal weight. Mezuk et al. [23], examining the trajectories of BMI and incident of frailty among participants in the United States Health and Retirement Study, found that older adults with obesity and weight loss class were almost three times more likely to develop frailty over a 10-year follow-up period when compared to a group that was consistently overweight.

The older Hispanic population is one of the fastest growing ethnic groups in the United States and is projected to rise from 8% in 2018 to 21% in 2060 [26]. This population is characterized by increased risk of diabetes, obesity, and disability, all factors associated with frailty [27, 28]. Research on Mexican Americans has shown an increased risk of frailty in those with older age, female sex, impaired cognitive function, disability, pain, falls, negative affect, and diabetes [3, 4, 28–31]. Previous longitudinal studies examining the relationship between BMI and frailty included mostly non-Hispanic older adults. Therefore, the objective of this study was to examine the relationship between BMI and frailty among non-frail older Mexican Americans at baseline over 18 years of follow up. We hypothesized that Mexican Americans with BMIs in the underweight or obese ranges would have an increased risk of frailty over time compared to Mexican Americans with normal weight.

Materials and methods

Data source and study population

The data were from the Hispanic Established Populations for the Epidemiologic Study of the Elderly (EPESE). This is an ongoing longitudinal study of Mexican Americans 65 years and older who reside in Arizona, California, Colorado, New Mexico, and Texas. The original Hispanic EPESE sample consisted of 3,050 participants interviewed at baseline in 1993–1994 and followed-up every 2 or 3 years thereafter. The present study used data collected from wave 2 (1995/96) to wave 8 (2012/13), allowing for approximately 18 years of follow-up data. Information and data for the Hispanic EPESE are available at the National Archive of Computerized Data on Aging [32]. The baseline interview information was used to assess weight loss (a component of the frailty phenotype) as the difference between weight measured in 1993–94 (baseline) and weight measured in 1995–96 (wave 2). Of the 2,438 participants interviewed at wave 2 (hereafter referred as baseline), 860 were non-frail, 835 were pre-frail, and 170 were frail. We excluded the 170 participants who were frail and the 620 with missing information for any covariate, frailty measure, and BMI. The final sample included 1,648 participants aged 67 years and older. Participants excluded from the study were more likely to be older, to have a lower level of education, lower Mini-Mental State Examination (MMSE) score, and lower BMI; they also reported more strokes, heart attacks, cancer, hip fractures, and high depressive symptoms than included participants. At the end of follow up (2013), 348 participants were re-interviewed in person, 259 were lost to follow up or refused to be re-interviewed, and 1,141 were confirmed dead through the National Death Index and report from relatives (Fig 1). The University’s Institutional Review Board approved the study protocol, and oral informed consent was obtained from each participant at the time of the interview.

Fig 1

Sample flow chart.

Measures

Predictor variable

Body mass index assessment (BMI)

BMI was calculated as weight in kilograms divided by height in meters squared (kg/m2). BMI was grouped according to the National Institutes of Health obesity standards: BMI <18.5 kg/m2, underweight; 18.5–24.9 kg/m2, normal weight; 25–29.9 kg/m2, overweight; 30–34.9 kg/m2, class I obesity, and BMI ≥35 kg/m2, class II/ morbid obesity [33].

Outcome variable

Modified frailty phenotype

Frailty status was determined by a modified version of the frailty phenotype defined by Fried et al. [1]. The criteria were weight loss, weakness, slowness, low physical activity, and exhaustion [1, 34]. Weight loss: >10 pounds, calculated as the difference between weight measured in 1993/94 and in 1995/96. Weakness: unable to perform the handgrip strength test or in the bottom 20% (adjusted for sex and BMI). Slowness: unable to perform a timed 8-foot walk test or in the bottom 20% (height-sex adjusted). Low physical activity: answered “No” to the question “Can you walk half a mile without help?” (sex-adjusted). Exhaustion: positive responses to questions from the Center for Epidemiologic Studies Depression (CES-D) Scale: “Everything I did was an effort” or “I could not get going.” Participants were classified as non-frail if they met none of the criteria, pre-frail if they met 1–2 of the criteria, and frail if they met 3 or more of the criteria. Frailty was assessed at each interview during the 18-year study period.

Covariates

Sociodemographic factors assessed were age, sex, years of formal education, and marital status (married vs. not married). Self-reported medical conditions included hypertension, arthritis, diabetes, heart attack, stroke, cancer, and hip fracture. Cognitive function was assessed with the MMSE [35]. Depressive symptoms were measured with the CES-D Scale [36]. A score of ≥16 was used to determine a clinical range for those with depressive symptoms [37].

Statistical analysis

Chi-square, Fisher’s exact, and ANOVA tests were used to describe the sample characteristics by BMI category at baseline. Generalized Estimating Equation using the GENMOD procedure in SAS was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of frailty over 18 years of follow up as a function of BMI category, controlling for socio-demographics, medical conditions, cognitive function, and depressive symptoms. The models used a logit link binomial distribution and autoregressive correlation structure to account for repeated measures of participants. All variables, including BMI categories, were analyzed as time varying (potential to change over time), except for sex and education. Selection bias from missing data is minimizes with the use of GEE models because it allows for the use of all available data from all follow-up interviews while accounting for differences in the follow-up duration. In estimating the working correlation parameters, all non-missing pairs of data taken from the same participants over time are used. Using the GEE procedure, we lose only the observations for which the participant is missing and not all the measurements [38-40]. Participants who died, refused to participate, or were lost to follow up were included until their last follow-up date (last interview date over the 18-year follow up). Additional analyses excluded those who were prefrail or frail at baseline. All analyses were performed using version 9.4 of SAS (SAS Institute, Inc., Cary, NC, USA).

Results

Table 1 shows the baseline descriptive characteristics of the overall sample and by BMI category. The mean age was 74.3 [Standard Deviation (SD) = 5.6] years and the mean BMI was 28.0 (SD = 5.1), with participants classified as 1.0% underweight, 27.4% normal weight, 39.8% overweight, 23.2% obesity category I, and 8.6% obesity category II/morbid obesity. Fifty eight percent were female, 54.9% were married, and the mean years of education was 5.0 (SD = 4.0) years. The mean MMSE score was 24.4 points (SD = 4.2). The most common medical conditions were hypertension, arthritis, and diabetes. Nine percent had high depressive symptoms. Those in the obesity category II/morbid obesity were significantly more likely to be younger (72 years), to be female (84.5%), to be unmarried (54.2%), and to report hypertension (64.1%), arthritis (62.0%), diabetes (34.5%), and high depressive symptoms (15.5%) compared to those in the underweight, normal weight, overweight or obesity category I categories. Participants in the overweight and obesity category II/morbid obesity had the highest scores on the MMSE (24.6).

Table 1

Sample characteristicsof non-frail older Mexican Americans by BMI categories at baseline (N = 1,648).

Variables	Total N (%)	Underweight N (%)	Normal Weight N (%)	Overweight N (%)	Class I Obesity N (%)	Class II/ Morbid Obesity N (%)	p-value
Total	1648 (100)	17 (1.0)	452 (27.4)	655 (39.8)	382 (23.2)	142 (8.6)
Age in years, Mean (SD)	74.3 (5.6)	75.6 (5.2)	75.9 (6.4)	74.3 (5.3)	73.1 (5.2)	72.4 (4.5)	<0.0001
Sex							<0.0001
Male	697 (42.3)	7 (41.2)	204 (45.1)	330 (50.4)	134 (35.1)	22 (15.5)
Female	951 (57.7)	10 (58.8)	248 (54.9)	325 (49.6)	248 (64.9)	120 (84.5)
Education (year)	5.0 (4.0)	4.8 (3.9)	5.0 (3.8)	5.0 (4.1)	5.1 (3.9)	5.0 (3.8)	0.9768
Marital Status							0.0480
Married	905 (54.9)	9 (52.9)	237 (52.3)	384 (58.6)	210 (55.0)	65 (45.8)
Unmarried	743 (45.1)	8 (47.1)	215 (47.7)	271 (41.4)	172 (45.0)	77 (54.2)
BMI (kg/m 2 ), Mean (SD)	28.0 (5.1)	16.8 (1.5)	22.8 (1.6)	27.4 (1.4)	32.0 (1.4)	38.6 (3.9)	<0.0001
MMSE Score	24.4 (4.2)	23.6 (4.6)	23.9 (4.3)	24.6 (4.1)	24.5 (4.1)	24.6 (4.1)	0.0354
Medical conditions
Hypertension	741 (45.0)	5 (29.4)	149 (33.0)	284 (43.4)	212 (55.5)	91 (64.1)	<0.0001
Arthritis	702 (42.6)	2 (11.8)	161 (35.6)	263 (40.2)	188 (49.2)	88 (62.0)	<0.0001
Diabetes	431 (26.2)	3 (17.7)	96 (21.2)	162 (24.7)	121 (31.7)	49 (34.5)	0.0013
Heart attack	136 (8.3)	0 (0.0)	39 (8.7)	57 (8.7)	33 (8.6)	7 (4.9)	0.4888
Stroke	96 (5.8)	2 (11.8)	27 (6.0)	34 (5.2)	27 (7.1)	6 (4.2)	0.4156
Cancer	99 (6.0)	0 (0.0)	33 (7.3)	35 (5.3)	20 (5.2)	11 (7.8)	0.4462
Hip Fracture	12 (0.7)	1 (5.9)	3 (0.7)	3 (0.5)	4 (1.1)	1 (0.7)	0.1686
Depressive Symptoms (CES-D)	151 (9.2)	0 (0.0)	31 (6.9)	54 (8.2)	44 (11.5)	22 (15.5)	0.0065

Note: BMI = Body Mass Index; SD = standard deviation; MMSE = Mini Mental State Examination; CES-D = Center for Epidemiologic Studies Depression Scale.

Obesity category I = BMI of 30 to < 35 Kg/m2; Obesity category II/morbid obesity = BMI ≥ 35 Kg/m2

Table 2 presents the results of the generalized estimating equation analysis for frailty over time as a function of BMI category. Participants in the underweight or obesity category II/morbid obesity categories had greater odds of frailty (OR = 2.40, 95% Confidence Interval (CI) = 1.29–4.46 and OR = 1.62, 95% CI = 1.08–2.44, respectively) over time compared to those with normal weight, after controlling for all covariates. Being in overweight or obesity category I did not significantly increase the odds of frailty over time. Older age, arthritis, heart attack, hip fracture, and high depressive symptoms increased the odds of frailty over time. Lower odds of frailty was also observed in those with high MMSE scores. After excluding prefrail or frail participants at baseline (N = 837), those in the underweight or obesity category II/morbid obesity categories had greater odds of frailty over time (OR = 5.09, 95% CI = 1.95–13.32 and OR = 2.80, 95% CI = 1.52–5.14, respectively) compared to those in the normal weight category, after controlling for all covariates. Those in the overweight or obesity category I group were not at increased odds of frailty over time.

Table 2

Generalized estimating equation models for frailty as a function of BMI categories over 18-years of follow up among non-frail older Mexican Americans at baseline (N = 1,648).

Variables	Odds Ratio 95% CI	p-value
Time	1.09 (1.06–1.12)	<0.0001
BMI categories
Underweight	2.40 (1.29–4.46)	0.0056
Normal Weight	Reference	Reference
Overweight	0.86 (0.65–1.13)	0.2706
Obesity Category I	1.09 (0.80–1.50)	0.5804
Obesity Category II/Morbid Obesity	1.62 (1.07–2.44)	0.0211
Age (years)	1.07 (1.05–1.09)	<0.0001
Female Sex	1.10 (0.84–1.43)	0.4843
Years of Education	0.99 (0.96–1.02)	0.5004
Married	1.17 (0.91–1.49)	0.2134
MMSE	0.92 (0.90–0.94)	<0.0001
Hypertension	0.96 (0.76–1.21)	0.7460
Arthritis	1.53 (1.22–1.93)	0.0002
Diabetes	1.20 (0.94–1.55)	0.1507
Heart Attack	1.60 (1.07–2.39)	0.0228
Stroke	0.78 (0.48–1.27)	0.3212
Cancer	1.40 (0.96–2.03)	0.0829
Hip Fracture	2.56 (1.26–5.20)	0.0095
Depressive Symptoms (CES-D ≥ 16)	4.31 (3.38–5.51)	<0.0001

Note: BMI = Body Mass Index; MMSE = Mini Mental State Examination; CES-D = Center for Epidemiologic Studies Depression Scale.

Obesity category I = BMI of 30 to < 35 Kg/m2; Obesity category II/morbid obesity = BMI ≥35 Kg/m2

Table 3 presents the results of the generalized estimating equation analysis for each frailty criterion over time as a function of BMI category. After controlling for all covariates, underweight participants had greater odds of weight loss (OR = 2.71, 95% CI = 1.71–4.28), overweight or obesity category I participants had greater odds of weakness (OR = 1.44, 95% CI = 1.20–1.71 and OR = 1.62, 95% CI = 1.31–2.01, respectively), those in obesity category I also had greater odds of exhaustion (OR = 1.1, 95% CI = 1.02–1.68), and those in the obesity category II/morbid obesity had greater odds of weakness, slowness, low physical activity, and exhaustion. Those in the overweight, obesity category I or obesity category II/morbid obesity had lower odds of weight loss over time.

Table 3

Generalized estimating equation models for each frailty criterion as a function of BMI categories over 18-years of follow up among non-frail older Mexican Americans at baseline (N = 1,648).

BMI category	Weight Loss OR (95% CI)	Weakness OR (95% CI)	Slowness OR (95% CI)	Low Physical Activity OR (95% CI)	Exhaustion OR (95% CI)
Underweight	2.71 (1.71–4.28)	1.12 (0.59–2.10)	0.78 (0.44–1.37)	1.10 (0.63–1.91)	1.86 (0.99–3.50)
Normal Weight	Reference	Reference	Reference	Reference	Reference
Overweight	0.60 (0.52–0.70)	1.44 (1.20–1.71)	0.90 (0.75–1.09)	1.11 (0.93–1.33)	1.20 (0.96–1.50)
Obesity Category I	0.54 (0.45–0.64)	1.62 (1.31–2.01)	1.03 (0.82–1.29)	1.22 (0.99–1.51)	1.31 (1.02–1.68)
Obesity Category II /Morbid Obesity	0.45 (0.34–0.58)	1.96 (1.47–2.63)	1.42 (1.06–1.89)	2.36 (1.80–3.10)	1.65 (1.17–2.33)

Note: Controlled for time (years) age (years), gender, marital status, years of education, comorbid conditions (hypertension, arthritis, diabetes, heart attack, stroke, cancer, and hip fracture), cognitive function, and depressive symptoms.

BMI = Body Mass Index; OR = odds ratio; CI = confidence interval.

Fig 2 shows the participants’ frailty status at each wave as a function of BMI category over 18-years of follow up among those who were non-frail at baseline. Frailty increased from 22.2% to 75% for those in the underweight category, 12.2% to 34.6% for those in the normal weight category, 8.7% to 28.8% for those in the overweight category, 6.9% to 37.5% for those in the obesity category I, and 14.9% to 83.3% for those in the obesity category II/morbid obesity.

Fig 2

Percent of non-frail, pre-frail, and frailty by BMI categories over time among non-frail older Mexican Americans at baseline (N = 1,648).

Fig 3 presents the percent of each frailty criterion by BMI category over time among those who were non-frail at baseline. Weight loss was more prevalent among those who were in the underweight and normal weight categories during the early years of follow up and less prevalent among those who were in the obesity categories. Weakness was consistently more prevalent among those who were in the underweight category or obesity categories during the whole follow up. Slowness was more prevalent among those who were in the underweight or morbid obesity category. Exhaustion was more prevalent among those with morbid obesity consistently during the whole follow up and among those who were in the underweight category in the first 10 years of follow up. Low physical activity was more prevalent among those with morbidity obesity.

Fig 3

Percent of each frailty criterion by BMI categories over time among non-frail older Mexican Americans at baseline (N = 1,648).

Discussion

This study examined the relationship between BMI and frailty among non-frail older Mexican Americans at baseline who were followed over 18 years. This study showed a U-shaped relationship between BMI and frailty. Participants in the underweight category or obesity category II/morbid obesity were at 2 and 1.6 times, respectively, greater risk of frailty over time than those in the normal weight category, after controlling for all covariates. Results were similar after excluding pre-frail and frail participants at baseline. When we examined the relationship between BMI category and each frailty criterion, we found that underweight participants were at higher risk of weight loss, while the overweight or obese were at lower risk of weight loss. Those in the overweight or obesity categories were at higher risk for weakness, slowness, exhaustion, and low physical activity.

Our findings are similar to those from previous cross-sectional [6, 11–16] and longitudinal [18-25] studies that demonstrated a U-or J-shaped relationship between BMI and frailty. Gajic-Veljanoski et al. [41], using the Canadian Multi-Centre Osteoporosis Study, found that baseline BMIs ≥25 kg/m2 was associated with faster frailty progression over 5-years with the greatest effect among those with BMI ≥40 kg/m2 when compared to those with normal weight. Landré et al. [21] examined the relationship between weight history during adulthood and frailty among participants from the GAZEL (GAZ and ELectricité) Cohort and found that long term obesity and onset of obesity in late adulthood were associated with frailty over 25 years of follow up when compared with those with normal weight. In another study, Strandberg et al. [25] used the Helsinki Businessmen Study to determine whether midlife obesity could be a predictor of frailty over a 26-year follow up among the initially health. They found that those who were overweight or obese in midlife were twice as likely to develop frailty compared to those of normal weight. The studies of Landré [21] and Strandberg [25] considered normal weight as BMIs <25 kg/m2. A recent systematic review and meta-analysis conducted by Yuan et al. [42] found that underweight and obesity both increased the risk of frailty over time.

Some mechanisms can explain our findings. The increased risk of frailty over time among those in the underweight category may be related to the weight loss criterion for frailty used in our study; however, weight loss can be seen in any of the BMI categories, not just in those who are underweight. Another explanation is the loss of muscle mass seen in older adults with undernutrition which is accompanied by low BMI [43, 44]. The increased risk of frailty over time among those in the obesity category II/morbid obesity may be related to the association of obesity with multiple conditions like insulin resistance, diabetes, cardiovascular disease, and increased inflammation, all of which are risk factors for frailty [45, 46]. Another explanation is related to the decreased muscle mass seen in older adults with obesity, known as “sarcopenia obesity”[47, 48].

Our study has some limitations. First, comorbid conditions were assessed through self-reports. This may lead to recall bias as compared to physician assessment. Second, participants excluded from the study were less healthy than those included, which might have led to underestimating the relationship between BMI and frailty. Third, participants who died before wave 2 may have produced a survival bias. Fourth, we do not have the measure of waist circumference (WC) assessed in all study waves. In older adults, WC has been suggested to be a better predictor than weight alone of whole-body fat percent and visceral adipose tissue [49, 50]. Fifth, our measure of frailty phenotype does not consider cognitive function or psychosocial measures [51]. Finally, our findings are not generalizable to the larger Hispanic population in the United States. This study has several strengths, including its large community-based sample of older Mexican Americans, a disadvantaged and underserved population, the length of follow up, and the use of generalized estimating equation models, an analytical approach that allows using all available data on socio-demographics, comorbidities, and BMI as time varying.

Conclusions

This study shows that older Mexican Americans in the underweight or obesity type II/morbid obesity categories are at increased risk of frailty over an 18-year follow up when compared to those of normal weight. Overweight or obese older Mexican Americans were at higher risk of weakness, slowness, exhaustion, and low physical activity. Interventions should be implemented to improve body weight among the underweight and morbid obesity to enhance physical function, increase muscle strength, and increase levels of physical activity to prevent pre-frailty or frailty in this population.

20 Jun 2022

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Reviewer #1: The Study evaluate the relationship between BMI and frailty among non-frail older Mexican Americans in a Longitudinal population-based study of 1,648 non-institutionalized Mexican Americans aged ≥ 67 years from the Hispanic Established Population for the Epidemiologic Study of the Elderly (1995/96-2012/13). Frailty phenotype was defined as meeting three or more of the following: unintentional weight loss of >10 pounds, weakness, self-reported exhaustion, low physical activity, and slow walking speed.

Participants with underweight or obesity category II/ morbid obesity had greater odds of frailty over time compared to those with normal weight after controlling for all covariates. Participants with BMIs in the overweight or category I obesity were at lower odds of frailty over time.

I found the study of interest conducted on a large cohort data. Data support conclusion. Figures and table are exhaustive. The statistical analysis is correct.

Reviewer #2: The authors examined the relationship between BMI and frailty among non-frail older Mexican Americans at baseline over 18 years of follow up in longitudinal population-based study of 1,648 non-institutionalized Mexican Americans aged ≥ 67 years from the Hispanic Established Population for the Epidemiologic Study of the Elderly (1995/96-2012/13). Frailty phenotype was defined as meeting three or more of the following: unintentional weight loss of >10 pounds, weakness, self-reported exhaustion, low physical activity, and slow walking speed. BMI (kg/m 2) was classified as underweight (<18.5), normal weight (18.5-<25), overweight (25-< 30), obesity category I (30-<35), and obesity category II/morbid obesity (≥35). Covariates included socio-demographics, comorbidities, cognitive function, and depressive symptoms. Generalized Estimating Equation models were performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of frailty as a function of BMI category. Participants with underweight or obesity category II/ morbid obesity had greater odds of frailty over time compared to those with normal weight (OR 2.39, 95% CI 1.29-4.44 and OR 1.62, 95% CI 1.07-2.44, respectively) after controlling for all covariates. Participants with BMIs in the overweight or category I obesity were at lower odds of frailty over time.

The manuscript is interesting but I have some concerns that should be addressed. Firstly, frailty is actually considered as a “multidimensional” condition. The authors consider only the “physical” domain of the frailty. Please see and discuss “Abete P et al. The Italian version of the "frailty index" based on deficits in health: a validation study. Aging Clin Exp Res. 2017;29:913-926”. I suggest to add in the title “physical” before frailty.

Secondly, you have to consider the presence of “sarcopenic obesity” in your patients. Please see and discuss “Remelli F et al. Prevalence of obesity and diabetes in older people with sarcopenia defined according to EWGSOP2 and FNHI criteria. Aging Clin Exp Res. 2022 Jan;34(1):113-120.

**********

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13 Jul 2022

Response to Reviewers' comments

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Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

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Reviewer #1: Yes

Reviewer #2: Yes

Thank you.

________________________________________

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Thank you.

________________________________________

3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: Yes

Reviewer #2: Yes

Thank you.

________________________________________

4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #2: Yes

Thank you.

________________________________________

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The Study evaluate the relationship between BMI and frailty among non-frail older Mexican Americans in a Longitudinal population-based study of 1,648 non-institutionalized Mexican Americans aged ≥ 67 years from the Hispanic Established Population for the Epidemiologic Study of the Elderly (1995/96-2012/13). Frailty phenotype was defined as meeting three or more of the following: unintentional weight loss of >10 pounds, weakness, self-reported exhaustion, low physical activity, and slow walking speed.

Participants with underweight or obesity category II/ morbid obesity had greater odds of frailty over time compared to those with normal weight after controlling for all covariates. Participants with BMIs in the overweight or category I obesity were at lower odds of frailty over time.

I found the study of interest conducted on a large cohort data. Data support conclusion. Figures and table are exhaustive. The statistical analysis is correct.

Response: Thank you!

Reviewer #2: The authors examined the relationship between BMI and frailty among non-frail older Mexican Americans at baseline over 18 years of follow up in longitudinal population-based study of 1,648 non-institutionalized Mexican Americans aged ≥ 67 years from the Hispanic Established Population for the Epidemiologic Study of the Elderly (1995/96-2012/13). Frailty phenotype was defined as meeting three or more of the following: unintentional weight loss of >10 pounds, weakness, self-reported exhaustion, low physical activity, and slow walking speed. BMI (kg/m 2) was classified as underweight (<18.5), normal weight (18.5-<25), overweight (25-< 30), obesity category I (30-<35), and obesity category II/morbid obesity (≥35). Covariates included socio-demographics, comorbidities, cognitive function, and depressive symptoms. Generalized Estimating Equation models were performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of frailty as a function of BMI category. Participants with underweight or obesity category II/ morbid obesity had greater odds of frailty over time compared to those with normal weight (OR 2.39, 95% CI 1.29-4.44 and OR 1.62, 95% CI 1.07-2.44, respectively) after controlling for all covariates. Participants with BMIs in the overweight or category I obesity were at lower odds of frailty over time.

Comment: The manuscript is interesting, but I have some concerns that should be addressed. Firstly, frailty is actually considered as a “multidimensional” condition. The authors consider only the “physical” domain of the frailty. Please see and discuss “Abete P et al. The Italian version of the "frailty index" based on deficits in health: a validation study. Aging Clin Exp Res. 2017;29:913-926”. I suggest to add in the title “physical” before frailty.

Response: We agree with the reviewer comment. We have now added in the discussion under the study limitation section the following “Fifth, our measure of frailty phenotype does not consider cognitive function or psychosocial measures (52)” on page 15, lines 297-298.

Comment: Secondly, you have to consider the presence of “sarcopenic obesity” in your patients. Please see and discuss “Remelli F et al. Prevalence of obesity and diabetes in older people with sarcopenia defined according to EWGSOP2 and FNHI criteria. Aging Clin Exp Res. 2022 Jan;34(1):113-120.

Response: We have added the following sentence in the discussion section “Another explanation is related to the decreased muscle mass seen in older adults with obesity, known as “sarcopenia obesity”(48, 49)” on page 14, lines 287-289.

Submitted filename: Response-to-reviewer-comments-BMI-Frailty-07-08-2022.docx

Click here for additional data file.

16 Aug 2022

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Pasquale Abete

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

According to Reviewer's comments the manuscript needs a major revision.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: No

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: I did not found in the revised manuscript:

1) the modification of title: "I suggest to add in the title “physical” before frailty"

2) the references:

- #49: Remelli F et al. Prevalence of obesity and diabetes in older people with sarcopenia defined according to EWGSOP2 and FNHI criteria. Aging Clin Exp Res. 2022 Jan;34(1):113-120.

- #50: Abete P et al. The Italian version of the "frailty index" based on deficits in health: a

validation study. Aging Clin Exp Res. 2017;29:913-926”

**********

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Reviewer #2: No

**********

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24 Aug 2022

Response to Reviewers' comments

Reviewer #2:

Comment # 1: The modification of title: "I suggest to add in the title “physical” before frailty".

Response: The title now reads “Body mass index and physical frailty among older Mexican Americans: Findings from an 18-year follow up”

Comment # 2: The references:

- #49: Remelli F et al. Prevalence of obesity and diabetes in older people with sarcopenia defined according to EWGSOP2 and FNHI criteria. Aging Clin Exp Res. 2022 Jan;34(1):113-120.

- #50: Abete P et al. The Italian version of the "frailty index" based on deficits in health: a validation study. Aging Clin Exp Res. 2017;29:913-926”

Response: We have added the references. Reference number 48 correspond to “Remelli F et al. Prevalence of obesity and diabetes in older people with sarcopenia defined according to EWGSOP2 and FNHI criteria. Aging Clin Exp Res. 2022 Jan;34(1):113-120; and reference number 51 correspond to “Abete P et al. The Italian version of the "frailty index" based on deficits in health: a validation study. Aging Clin Exp Res. 2017;29:913-926”.

Thank you for noticing the absence of the references.

Submitted filename: Response-to-reviewer-comments-BMI-Frailty-08-22-2022.docx

Click here for additional data file.

26 Aug 2022

Body mass index and physical frailty among older Mexican Americans: Findings from an 18-year follow up.

PONE-D-22-13598R2

Dear Dr. SNIH,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Pasquale Abete

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

No further comments.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

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Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The manuscript is really improves and all questions arised have been aswered. The manuscript is now acceptable to be published in PONE.

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Reviewer #2: No

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31 Aug 2022

PONE-D-22-13598R2

Body mass index and physical frailty among older Mexican Americans: Findings from an 18-year follow up.

Dear Dr. Al Snih:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

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