Implication of Sex Differences in Visceral Fat for the Assessment of Incidence Risk of Type 2 Diabetes Mellitus

Sang Hyeon Ju; Hyon-Seung Yi

doi:10.4093/dmj.2022.0089

Articles

Page Path: HOME > Diabetes Metab J > Volume 46(3); 2022 > Article

Editorial Implication of Sex Differences in Visceral Fat for the Assessment of Incidence Risk of Type 2 Diabetes Mellitus: Sang Hyeon Ju¹, Hyon-Seung Yi^1,2; Diabetes & Metabolism Journal 2022;46(3):414-416.
DOI: https://doi.org/10.4093/dmj.2022.0089
Published online: May 25, 2022

3,733 Views
172 Download
5 Web of Science
5 Crossref
4 Scopus

¹Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea

²Laboratory of Endocrinology and Immune System, Chungnam National University College of Medicine, Daejeon, Korea

Corresponding author: Hyon-Seung Yi

Laboratory of Endocrinology and Immune System, Chungnam National University College of Medicine, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Korea E-mail: jmpbooks@cnu.ac.kr

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

prev next

Full Article

Download PDF

NOTES
REFERENCES
About this article

Prevalence of type 2 diabetes mellitus (T2DM) in South Korean adults steadily increased from 11.8% in 2012 to 13.8% in 2018 [1]. More than half of these patients were obese (53.2%) and had abdominal obesity (54.0%) determined by abdominal circumference [1]. Moreover, the incidence of T2DM in abdominal obesity is 2.14-fold higher than that in the control group [2]. The strong relationship between T2DM and abdominal obesity originates from visceral adipose tissue (VAT)- mediated insulin resistance [3]. Given that fat distribution is affected by sex hormones, aging, and genetic factors [4], the authors measured visceral fat area (VFA) and visceral-to-subcutaneous fat ratio (VSR) with computed tomography, which is a gold standard for fat mass quantification, and analyzed the sex difference in incidence risk of T2DM.

Body fat composition in humans is sexually dimorphic [4]. For instance, estrogen promotes fat accumulation in gluteofemoral subcutaneous adipose tissue (SAT) rather than in VAT. In a fatty acid kinetic study using radiolabeled triolein, premenopausal women stored a larger percentage of dietary fat in SAT than did men [5], while postmenopausal women store body fat in a more central location than premenopausal women [6,7]. Moreover, estrogen replacement in postmenopausal women reduced VAT and body mass index [8]. Mechanisms promoting estrogen-dependent fat distribution are estrogeninduced inhibition of lipid storage in VAT by suppression of lipoprotein lipase (LPL) activity and lipogenic gene expression [4], estrogen-mediated inhibition of lipolytic activity in gluteofemoral SAT [9], and estrogen-induced gene expression of anti- lipolytic α2A adrenergic receptors in gluteofemoral SAT [9]. The protective effect of estrogen is well documented [10]; the proportion of postmenopausal women who develop incident diabetes (71.0%) is higher than that in the no diabetes group (59.8%). Another sex hormone, testosterone is thought to suppress LPL activity and adipogenesis to inhibit VAT accumulation, though the mechanism is not fully understood, and agedependent decline in testosterone level is associated with visceral obesity. Testosterone therapy upregulated lipolytic activity from VAT but not from gluteofemoral SAT [11]. Another study showed that short-term testosterone suppression increased postprandial fatty acid storage in gluteofemoral SAT and their LPL activity, implying that physiological testosterone level inhibits meal-derived fat storage in gluteofemoral SAT [4]. These findings indicate that imbalance of sex hormones in men and women respectively creates android- and gynoidtype body shapes. Based on this hypothesis, Kim et al. [10] proposed optimal cut-off values of VFA and VSR separately for men and women; as expected, the values were higher in men.

Another lesson from this study is that visceral fat accumulation in women increases susceptibility to diabetes mellitus compared to that in men. From subgroup analysis by VFA, the odds ratio for incident T2DM was 5- to 10-fold higher in women than in men. Based on this result, VFA in women is a more sensitive and specific measure for predicting T2DM than in men. Although there are differences in degree, previous studies support the susceptibility of women to T2DM related to visceral fat accumulation [12,13]. Thus, as emphasized in many papers, interventions such as exercise and hormone replacement for perimenopausal women should be considered to prevent unfavorable fat distribution [14-16].

The premise of this study is that VAT accumulation induces insulin resistance. The underlying mechanism of VAT-mediated insulin resistance is unclear, but a common pathway of proposed models is inflammation of VAT, possibly from hypoxia [17] or adipocyte cell death [18]. In addition, the immune cells in VAT, including macrophages, dendritic cells, natural killer cells, and T-cells, are dynamically regulated by obesity and participate in obesity-induced VAT inflammation [19,20]. On this basis, a new strategy for predicting T2DM should consider VAT inflammation status. Therefore, it could be helpful to evaluate VAT inflammation using a quantifiable measure of T2 relaxation time using magnetic resonance imaging and by measuring pro-inflammatory cytokines (interleukin 1β [IL-1β], TNF-α, IL-12, and IL-18) derived from M1 macrophages and T-cells.

NOTES

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

REFERENCES

1. Korean Diabetes Association. Diabetes fact sheet 2020. Seoul: Korean Diabetes Association; 2020.
2. Freemantle N, Holmes J, Hockey A, Kumar S. How strong is the association between abdominal obesity and the incidence of type 2 diabetes? Int J Clin Pract 2008;62:1391-6.Article PubMed PMC
3. Zhang M, Hu T, Zhang S, Zhou L. Associations of different adipose tissue depots with insulin resistance: a systematic review and meta-analysis of observational studies. Sci Rep 2015;5:18495.Article PubMed PMC PDF
4. Frank AP, de Souza Santos R, Palmer BF, Clegg DJ. Determinants of body fat distribution in humans may provide insight about obesity-related health risks. J Lipid Res 2019;60:1710-9.Article PubMed PMC
5. Romanski SA, Nelson RM, Jensen MD. Meal fatty acid uptake in adipose tissue: gender effects in nonobese humans. Am J Physiol Endocrinol Metab 2000;279:E455-62.Article PubMed
6. Tremollieres FA, Pouilles JM, Ribot CA. Relative influence of age and menopause on total and regional body composition changes in postmenopausal women. Am J Obstet Gynecol 1996;175:1594-600.Article PubMed
7. Lee YS, Lee HJ, Oh JY, Hong YS, Sung YA. Sex hormone binding globulin, body fat distribution and insulin resistance in premenopausal women. J Korean Diabetes Assoc 2003;27:63-72.
8. Papadakis GE, Hans D, Gonzalez Rodriguez E, Vollenweider P, Waeber G, Marques-Vidal P, et al. Menopausal hormone therapy is associated with reduced total and visceral adiposity: the OsteoLaus Cohort. J Clin Endocrinol Metab 2018;103:1948-57.Article PubMed
9. Pedersen SB, Kristensen K, Hermann PA, Katzenellenbogen JA, Richelsen B. Estrogen controls lipolysis by up-regulating alpha2A-adrenergic receptors directly in human adipose tissue through the estrogen receptor alpha: implications for the female fat distribution. J Clin Endocrinol Metab 2004;89:1869-78.PubMed
10. Kim EH, Kim HK, Lee MJ, Bae SJ, Choe J, Jung CH, et al. Sex differences of visceral fat area and visceral-to-subcutaneous fat ratio for the risk of incident type 2 diabetes mellitus. Diabetes Metab J 2022;46:486-98.Article PubMed PDF
11. Karastergiou K, Smith SR, Greenberg AS, Fried SK. Sex differences in human adipose tissues: the biology of pear shape. Biol Sex Differ 2012;3:13.Article PubMed PMC PDF
12. Hanley AJ, Wagenknecht LE, Norris JM, Bryer-Ash M, Chen YI, Anderson AM, et al. Insulin resistance, beta cell dysfunction and visceral adiposity as predictors of incident diabetes: the Insulin Resistance Atherosclerosis Study (IRAS) Family study. Diabetologia 2009;52:2079-86.Article PubMed PMC PDF
13. Karlsson T, Rask-Andersen M, Pan G, Hoglund J, Wadelius C, Ek WE, et al. Contribution of genetics to visceral adiposity and its relation to cardiovascular and metabolic disease. Nat Med 2019;25:1390-5.Article PubMed PDF
14. Slentz CA, Aiken LB, Houmard JA, Bales CW, Johnson JL, Tanner CJ, et al. Inactivity, exercise, and visceral fat. STRRIDE: a randomized, controlled study of exercise intensity and amount. J Appl Physiol (1985) 2005;99:1613-8.Article PubMed
15. Hunter GR, Brock DW, Byrne NM, Chandler-Laney PC, Del Corral P, Gower BA. Exercise training prevents regain of visceral fat for 1 year following weight loss. Obesity (Silver Spring) 2010;18:690-5.Article PubMed PMC PDF
16. Giannopoulou I, Ploutz-Snyder LL, Carhart R, Weinstock RS, Fernhall B, Goulopoulou S, et al. Exercise is required for visceral fat loss in postmenopausal women with type 2 diabetes. J Clin Endocrinol Metab 2005;90:1511-8.Article PubMed PDF
17. Arcidiacono B, Chiefari E, Foryst-Ludwig A, Curro G, Navarra G, Brunetti FS, et al. Obesity-related hypoxia via miR-128 decreases insulin-receptor expression in human and mouse adipose tissue promoting systemic insulin resistance. EBioMedicine 2020;59:102912.Article PubMed PMC
18. Strissel KJ, Stancheva Z, Miyoshi H, Perfield JW 2nd, DeFuria J, Jick Z, et al. Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes 2007;56:2910-8.Article PubMed PDF
19. Moon JS, Goeminne LJ, Kim JT, Tian JW, Kim SH, Nga HT, et al. Growth differentiation factor 15 protects against the aging-mediated systemic inflammatory response in humans and mice. Aging Cell 2020;19:e13195.Article PubMed PMC PDF
20. Choi MJ, Jung SB, Lee SE, Kang SG, Lee JH, Ryu MJ, et al. An adipocyte-specific defect in oxidative phosphorylation increases systemic energy expenditure and protects against diet-induced obesity in mouse models. Diabetologia 2020;63:837-52.Article PubMed PDF

Figure & Data

References

Citations

Citations to this article as recorded by

Prediction of high visceral adipose tissue for sex‐specific community residents in Taiwan
Yu‐Hsuan Chang, Chin‐Sung Chang, Chieh‐Yu Liu, Yin‐Fan Chang, Shiow‐Ching Shun
Nursing & Health Sciences.2024;[Epub] CrossRef
Association of triglyceride glucose index and triglyceride glucose-body mass index with sudden cardiac arrest in the general population
Shuijing Zhang, Wenbing Liu, Bin Xu, Shuguang Wang, Zhongyan Du, Wenke Cheng
Cardiovascular Diabetology.2024;[Epub] CrossRef
Determination of SRPA and adiposity measures and its association with glycemic status in type 2 diabetics having high mean HbA1c in a private clinic of a city in west India
Jayesh D. Solanki, Rahul Vaghasiya, Isha Sharma, Jagdish B. Patel
Journal of Family Medicine and Primary Care.2024; 13(9): 3897. CrossRef
Visceral fat and attribute-based medicine in chronic kidney disease
Hiroshi Kataoka, Kosaku Nitta, Junichi Hoshino
Frontiers in Endocrinology.2023;[Epub] CrossRef
The predictive significance of lipid accumulation products for future diabetes in a non-diabetic population from a gender perspective: an analysis using time-dependent receiver operating characteristics
Jiajun Qiu, Maobin Kuang, Yang Zou, Ruijuan Yang, Qing Shangguan, Dingyang Liu, Guotai Sheng, Wei Wang
Frontiers in Endocrinology.2023;[Epub] CrossRef

PubReader
ePub Link

Cite this Article

Cite this Article: export Copy Download Format; Close

Download Citation

Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

Format:

RIS — For EndNote, ProCite, RefWorks, and most other reference management software
BibTeX — For JabRef, BibDesk, and other BibTeX-specific software

Include:

Citation for the content below
Citation and abstract for the content below

Implication of Sex Differences in Visceral Fat for the Assessment of Incidence Risk of Type 2 Diabetes Mellitus

Diabetes Metab J. 2022;46(3):414-416. Published online May 25, 2022

DOI: https://doi.org/10.4093/dmj.2022.0089

XML Download

Related articles

Implication of Sex Differences in Visceral Fat for the Assessment of Incidence Risk of Type 2 Diabetes Mellitus

About this article

Ju SH, Yi HS. Implication of Sex Differences in Visceral Fat for the Assessment of Incidence Risk of Type 2 Diabetes Mellitus. Diabetes Metab J. 2022;46(3):414-416.

DOI: https://doi.org/10.4093/dmj.2022.0089.

Download citation ↓