jfa journal

AND option

OR option

LETTER TO THE EDITOR: OBESITY DEFINITION FOR MUSCLE OUTCOMES IN SARCOPENIC OBESITY: UTILITY OF WAIST CIRCUMFERENCE REVISITED

 

J.P. Lim1,2, J. Chew1,2, N.H. Ismail2,3, W.S. Lim1,2

 

1. Department of Geriatric Medicine, Tan Tock Seng Hospital, Singapore; 2. Institute of Geriatrics and Active Ageing, Tan Tock Seng Hospital, Singapore; 3. Department of Continuing and Community Care, Tan Tock Seng Hospital, Singapore

Corresponding Author: Jun Pei Lim, Department of Geriatric Medicine, Institute of Geriatrics and Active Aging, Tan Tock Seng Hospital, Annex 2 Level 3, 11 Jalan Tan Tock Seng, Singapore 308433, Email: Jun_Pei_LIM@ttsh.com.sg, Telephone: +65-6359 6474, Fax: +65-6359 6294

J Frailty Aging 2021;in press
Published online June 23, 2021, http://dx.doi.org/10.14283/jfa.2021.28


 

Dear Editor,

Sarcopenic obesity (SO) is defined as the concomitant presence of sarcopenia and obesity (1). Studies have employed different obesity definitions to understand the relation of SO to cardiometabolic outcomes, with more recent studies examining muscle-related outcomes (2, 3). The leading candidates amongst obesity definitions are waist circumference (WC), percentage fat mass (FM%), and fat mass index (FMI). The last two measures are derived from dual energy X-ray absorptiometry (DXA) or bioelectrical impedance (BIA), and adjust for fat quantity irrespective of distribution (4).
The emergence of abdominal adiposity as significant in the pathogenesis of SO reinforces the importance of incorporating fat distribution when considering obesity definitions (5). Abdominal adiposity is associated with adipose tissue inflammation, which in turn predisposes to the systemic pro-inflammatory milieu implicated in ectopic fat accumulation in skeletal muscle. Using WC as a surrogate of abdominal adiposity to define obesity, we previously demonstrated in obese and SO subjects elevated levels of Monocyte Chemoattractant Protein-1 (MCP-1), a pro-inflammatory cytokine secreted by adipocytes and adipose tissue leukocytes, to support the theory of chronic inflammation underpinned by abdominal adiposity (6, 7). Moreover, WC-defined SO was associated with intermuscular adipose tissue (8) and performed the worst amongst body composition phenotypes in handgrip strength, gait speed and Short Physical Performance Battery (SPPB) (9). In a study that compared ten different anatomical locations for measuring waist circumference (including six using bony landmarks and four involving the umbilicus), WC measured at 2.5cm above umbilicus was found to have the highest correlate with abdominal adiposity in older adults (8), suggesting that the different measurement protocols are not equivalent. This is an important consideration, as the umbilicus provides a useful landmark for optimal differentiation of the putative deep subcutaneous adipose tissue (vis-à-vis the protective superficial subcutaneous adipose tissue) in the abdominal wall (10).
Using an alternative WC protocol that measures narrowest point of the waist, the Yishun study in Singapore reported that SO was associated with Short Physical Performance Battery (SPPB) only with FMI but not WC or FM% definitions for obesity (3). Moreover, this WC protocol yielded prevalence of obesity and SO at 64.5% and 16.1% respectively, which was higher than the 52% and 10.5% prevalence observed using 2.5cm above umbilicus landmark (9). There was also a lack of biomarkers to explicate the findings. To ascertain if the observed lack of utility of WC obesity definition of SO can be attributed to the measurement protocol, we conducted the current study using 2.5cm above umbilicus landmark. We used WC, FM% and FMI definitions to compare prevalence of obese and SO; and the association with SPPB and blood inflammatory biomarkers across body composition phenotypes.
We studied 200 community-dwelling older adults (mean age 67.4, Supplementary table 1) from the GERILABS study.9 WC was measured 2.5cm above the umbilicus (Cut-offs: ≥90 cm men, ≥80 cm women, as per the International Diabetes Federation 2006 (IDF 2006) cut-offs for South Asians) (11). Body composition measurements were obtained using DXA. To facilitate comparisons, cut-offs for FM% and FMI [calculated as fat mass(kg) divided by height(m) squared] were referenced to the Yishun study – 31.0% and 7.63 kg/m2 for men, and 41.4% and 9.93 kg/m2 for women. Using the Asian Working Group for Sarcopenia 2014 consensus for sarcopenia, and WC, FM% or FMI definitions for obesity, we classified participants as normal, obese, sarcopenic and sarcopenic obesity (SO). We assessed overall physical performance using SPPB, and measured C-reactive protein (CRP), interlukin-6 (IL-1), tumour necrosis factor-α (TNF-α) and MCP-1 as inflammatory biomarkers. Using the 3 obesity definitions, we compared prevalence and inflammatory biomarkers across body composition phenotypes. We performed linear regression to examine the association with SPPB, adjusting for age, gender, history of diabetes mellitus and stroke disease.
We found that WC definition identified the highest prevalence of obese and SO, followed by FM% and FMI; our figures for WC were, however, lower than the Yishun study (53% vs 64.5%, and 9.5% vs 16,1%, respectively) (3). Moreover, WC definition of SO was most predictive for poor SPPB scores (coefficient -2.169, p <.0005) and had the highest model fit compared to FMI or FM% (table 1). For blood biomarkers, significant trends in both CRP and MCP-1 levels across body composition were observed for WC, FMI and FM% (p<.01), with MCP-1 levels highest in SO defined by WC. Interestingly, using WC definition, SO had higher levels of IL-6 than sarcopenia, whereas SO had higher levels of TNF-α than obese using FMI definition.

Table 1. Prevalence, Regression Coefficients, Blood Biomarkers across different SO definitions

* p values for regression coefficients <0.05; †Adjusted for age, gender, history of diabetes mellitus and stroke disease; ‡Adjusted R-squared 0.246; §Adjusted R-squared 0.163; ||Adjusted R-squared 0.168; { Difference between SO and N (p<0.05); #Difference between SO and O (p<0.05); **Difference between SO and S (p<0.05); †† Difference between S and N (p<0.05); ‡‡ Difference between S and O (p<0.05); §§ Difference between O and N (p<0.05)

 

Using the 2.5cm above umbilicus landmark, our results support the superiority of the WC definition in the associations of body compositions with physical performance. Other strengths vis-à-vis FMI/FM% definitions include ease of performance without requirement for specialized equipment; higher case detection; and selection for MCP-1 mediated inflammatory pathways associated with abdominal adiposity. Blood biomarker results implicate different pro-inflammatory pathways depending on obesity definitions. IL-6 is secondarily elevated due to MCP-1 induction of mononuclear cells and endothelial cells to express adhesion molecules with release of IL-6.12 In contrast, for FMI definition, CRP and TNF-alpha levels are elevated consistent with an overall increase in adjusted total adiposity. Although MCP-1 is also elevated for FMI/FM% definitions, the difference between SO and obese is lower, suggesting a greater contribution of overall as opposed to abdominal adiposity.
Taken together, our study corroborates the utility of WC obesity definition for muscle outcomes in SO, provided we employ standardized measurements protocols which correlate with abdominal adiposity. Study limitations include the cross-sectional design limiting conclusions of causality and use of a single WC measurement protocol precluding direct comparisons with other protocols. Usage of abdominal callipers by trained personnel may have provided more reliable estimates of abdominal visceral adiposity instead of WC. In addition, the WC cut-offs in our study are from established guidelines for Asian populations and have not been locally validated. Future outcome studies specifically evaluating different WC protocols in relation to SO may be useful to ascertain the optimal protocol.

 

Acknowledgement: This study was approved by the National Healthcare Group Institutional Research Board and funded by the Lee Foundation Grant 2013. We would like to extend our thanks to Ms Suzanne Yew, Ms Tan Cai Ning and Ms Audrey Yeo for their assistance in data collection.

Conflict of interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest

Author contribution statement: JPL drafted the manuscript. All authors critically appraised and contributed to manuscript revision, approved the final version of the letter, and agree to be accountable for all aspects of the work.

 

SUPPLEMENTARY MATERIAL

 

References

1. Roubenoff R. Sarcopenic obesity: The confluence of two epidemics. Obes Res. 2004;12(6):887-888. doi:10.1038/oby.2004.107
2. Yoshimura Y, Wakabayashi H, Nagano F, et al. Sarcopenic Obesity Is Associated With Activities of Daily Living and Home Discharge in Post-Acute Rehabilitation. J Am Med Dir Assoc. 2020;21(10):1475-1480. doi:10.1016/j.jamda.2020.03.029
3. Pang BWJ, Wee S-L, Lau LK, et al. Obesity Measures and Definitions of Sarcopenic Obesity in Singaporean Adults — The Yishun Study. J Frailty Aging. Published online 2020. doi:10.14283/jfa.2020.65
4. Donini LM, Busetto L, Bauer JM, et al. Critical appraisal of definitions and diagnostic criteria for sarcopenic obesity based on a systematic review. Clin Nutr. 2020;39(8):2368-2388. doi:10.1016/j.clnu.2019.11.024
5. Zoico E, Rossi A, Di Francesco V, et al. Adipose tissue infiltration in skeletal muscle of healthy elderly men: Relationships with body composition, insulin resistance, and inflammation at the systemic and tissue level. Journals Gerontol – Ser A Biol Sci Med Sci. 2010;65 A(3):295-299. doi:10.1093/gerona/glp155
6. Lim JP, Leung BP, Ding YY, et al. Monocyte chemoattractant protein-1: A proinflammatory cytokine elevated in sarcopenic obesity. Clin Interv Aging. 2015;10(March):605-609. doi:10.2147/CIA.S78901
7. Afandy NO, Lock HS, Tay L, et al. Association of Monocyte Chemotactic Protein-1 and Dickkopf-1 with Body Composition and Physical Performance in Community-Dwelling Older Adults in Singapore. J Frailty, Sarcopenia Falls. 2021;06(01):25-31. doi:10.22540/jfsf-06-025
8. Lim JP, Chong MS, Tay L, et al. Inter-muscular adipose tissue is associated with adipose tissue inflammation and poorer functional performance in central adiposity. Arch Gerontol Geriatr. 2019;81(November 2018):1-7. doi:10.1016/j.archger.2018.11.006
9. Khor EQ, Lim JP, Tay L, et al. Obesity Definitions in Sarcopenic Obesity: Differences in Prevalence, Agreement and Association with Muscle Function. J frailty aging. 2020;9(1):37-43. doi:10.14283/jfa.2019.28
10. Golan R, Shelef I, Rudich A, et al. Abdominal superficial subcutaneous fat: A putative distinct protective fat subdepot in type 2 diabetes. Diabetes Care. 2012;35(3):640-647. doi:10.2337/dc11-1583
11. IDF. The IDF consensus worldwide definition of the metabolic syndrome Part 1 : Worldwide definition for use in clinical practice. International Diabetes Federation. Published 2006. Accessed May 13, 2021. https://www.idf.org/component/attachments/attachments.html?id=705&task=download
12. Dong B, Sun B. Inflammatory Markers and Disability in Chinese Older Adults. J Gerontol Geriatr Res. 2016;05(01):1-6. doi:10.4172/2167-7182.1000275