The association between 25(OH)D levels, frailty status and adiposity indices in older adults

Background Vitamin D deficiency is common in older adults and has been linked with frailty and obesity, but it remains to be studied whether frail obese older adults are at higher risk of vitamin D deficiency. Therefore, the aim of this study is to explore the association between frailty, adiposity indices and serum 25(OH)D concentrations. Methods 1447 individuals with 65 years or older, participating in a cross-sectional study (Nutrition UP 65). Frailty, according to Fried et al., body mass index (BMI), waist circumference (WC), body roundness index (BRI) and body shape index (ABSI) were evaluated. A stepwise multinomial logistic regression was carried out to quantify the association between 25(OH)D quartiles and independent variables. Results Median 25(OH)D levels were lower in individuals presenting both frailty and obesity (p<0.001). In the multivariate analysis, pre-frailty (OR 2.65; 95% CI 1.63-4.32) and frailty (OR 3.76; 95% CI 2.08-6.81) were associated with increased odds of lower 25(OH)D serum levels (first quartile). Regarding adiposity indices, obesity (OR 1.75; 95% CI 1.07-2.87) and the highest categories of WC (OR 3.46; 95% CI 1.95-6.15), BRI (OR 4.35; 95% CI 2.60-7.29) and ABSI (OR 3.17 95% CI 1.86-5.38) were directly associated with lower 25(OH)D serum levels (first quartile). Conclusions A positive association between frailty or obesity and lower levels of vitamin D was found. Moreover, besides BMI and WC, other indicators of body adiposity, such as BRI and ABSI, were associated with lower 25(OH)D serum concentrations.


Introduction 40
Vitamin D is fat-soluble vitamin mainly obtained from sun exposure of the skin and in lesser amounts 41 from diet and supplements (1-3). It is stored mainly in adipose tissue and muscle and, to a lesser extent, in 42 other tissues (4). Vitamin D deficiency is a public health problem of growing concern (5-7), common in older 43 adults (5,7,8) and it has been linked to adverse health outcomes such as falls (9), poorer cognitive function 44 (10) and cancer (11). 25(OH)D concentrations decrease with age, due to a reduction in cutaneous vitamin D 45 synthesis (12), to the possible decline in the ability of the kidney to synthesize 1,25(OH) 2 D (4).

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Despite the well-known consequences of vitamin D deficiency in bone health (13), this hormone seems to also have a key-role in skeletal muscle (14), namely influencing its function and performance (14,15). Frailty

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increases with age and its prevalence in the community ranges from 4.0-59.1%, depending on the definition 49 adopted (16). It is associated with an increased risk of adverse health outcomes, such as falls, disability, 50 hospitalization and even mortality (17). Evidence has shown a link between frailty and vitamin D status, with 51 frailty being associated with lower levels of serum 25(OH)D (18). However, the impact of vitamin D 52 deficiency in frailty status in later life is still unknown.

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Obesity has also increased appreciably worldwide and older adults are no exception (19). Several 54 meta-analyses reported a significant association with lower serum 25(OH)D concentrations (20)(21)(22), although 55 the mechanisms underlying this association are not yet fully understood. Furthermore, obesity has also been 56 positively associated with frailty status in older adults (23,24), but it remains to be studied whether frail obese 57 older adults are at higher risk of vitamin D deficiency and if the presence of these conditions could 58 simultaneously lead to worse health outcomes. According to the previously described in literature, obese older 59 adults may be predisposed to vitamin D deficiency, which is in turn associated with worse physical function 60 and frailty (18,25). Conversely, frailty may impact the amount of sun exposure and, consequently, predispose 61 to vitamin D deficiency. Even though several studies have evaluated the association of frailty status and obesity 62 on vitamin D levels separately (18,20,21), to our knowledge, literature regarding the study of all three 63 conditions is absent. It will be relevant to know if frail obese older adults are more likely to present low vitamin 64 D levels. Besides body mass index (BMI), other adiposity indicators such as waist circumference (WC), body roundness index (BRI) and body shape index (ABSI) may be used (26,27). While previous studies have Physical activity, assessed by the short form of the International Physical Activity Questionnaire (36)

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The association between obesity and frailty status and 25(OH)D quartiles was further investigated 254 through multivariate multinomial regression (

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Additionally, when an interaction effect between frailty status and adiposity indices was tested 280 statistical differences were not found. 281

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Waist circumference was further adjusted for height. Bold text indicates a statistically significant difference with a p-value less than 0.05.

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⁕Missing data in 10 individuals.

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In this cross-sectional study an inverse association between frailty and obesity with serum

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When we compared vitamin D levels between frailty and obesity groups we found decreasing

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All adiposity indicators evaluated were inversely associated with 25(OH)D serum 306 concentrations. Regarding BMI, an inverse association between 25(OH)D levels and obesity, but not for 307 pre-obesity was found. Moreover, being at the fourth quartile of BRI was associated with a four-fold 308 increased risk of presenting 25(OH)D levels in the first quartile, and it was more strongly associated 309 than the other studied adiposity indicators. It was also observed that the odds of being in the first quartile 310 of 25(OH)D increased significantly across BRI quartiles.

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Physiological changes that occur with ageing predispose older adults to lower levels of serum

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Body mass index and WC are traditionally chosen as anthropometric indicators of general and 346 abdominal adiposity, respectively. Nevertheless, in the present study, the other adiposity indices 347 evaluated (BRI and ABSI), were positively associated with lower vitamin D levels, showing that these 348 may also be used as alternative obesity indicators to identify older adults at risk of low 25(OH)D levels.

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Despite the lack of positive correlation between ABSI and BMI, our study also demonstrated the link 350 between these indices and lower vitamin D levels, which reinforces their utility.

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The present study has some limitations. Firstly, this was a cross-sectional study, therefore the 352 possibility of reverse causation should not be excluded. Secondly, although we have adjusted for 353 multiple covariates, the possible occurrence of residual confounding cannot be ruled out. Thirdly, serum 354 25(OH)D concentrations were measured using electrochemiluminescence immunoassay, when liquid 355 chromatography-tandem mass spectrometry is considered the golden standard, which can introduce 356 variability in the results (58). And, lastly, participants´ sun exposure levels were not assessed.

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In contrast, some strengths can also be pointed out. To our knowledge, this is the first study to concentrations, allowed to study this association.

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In summary, present results show that besides BMI and WC, other measures of adiposity such 364 as BRI and ABSI are inversely associated with 25(OH)D serum concentrations. As discussed above, 365 several studies reported conflicting results, however present results reinforce the positive relationship 366 between vitamin D deficiency and both frailty and obesity. Plus, they emphasize the need to target obese 367 and frail elderly people and monitoring their serum vitamin D levels with special care. However,

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longitudinal studies are necessary to fully elucidate these associations.