Fat Distribution and its Correlation with Insulin Resistance,
                    Androgen Markers, and Proinflammatory Cytokines in Polycystic Ovary
                    Syndrome

Rebeca Bandeira de Melo Cavalcante; Lenora Maria Camarate Silveira Martins Leão; Ana Beatriz Winter Tavares; Karynne Grutter Lopes; Luiz Guilherme Kraemer-Aguiar

doi:10.1055/a-2386-9281

Hormone and Metabolic Research, Inhaltsverzeichnis

Horm Metab Res 2025; 57(01): 25-32
DOI: 10.1055/a-2386-9281

Original Article: Endocrine Care

Fat Distribution and its Correlation with Insulin Resistance, Androgen Markers, and Proinflammatory Cytokines in Polycystic Ovary Syndrome

Rebeca Bandeira de Melo Cavalcante

¹Postgraduate Program in Clinical and Experimental Pathophysiology, Rio de Janeiro State University Faculty of Medical Sciences, Rio de Janeiro, Brazil (Ringgold ID: RIN468988)

,

Lenora Maria Camarate Silveira Martins Leão

²Endocrinology Department of Internal Medicine, Rio de Janeiro State University Faculty of Medical Sciences, Rio de Janeiro, Brazil (Ringgold ID: RIN468988)

,

Ana Beatriz Winter Tavares

¹Postgraduate Program in Clinical and Experimental Pathophysiology, Rio de Janeiro State University Faculty of Medical Sciences, Rio de Janeiro, Brazil (Ringgold ID: RIN468988)

²Endocrinology Department of Internal Medicine, Rio de Janeiro State University Faculty of Medical Sciences, Rio de Janeiro, Brazil (Ringgold ID: RIN468988)

,

Karynne Grutter Lopes

¹Postgraduate Program in Clinical and Experimental Pathophysiology, Rio de Janeiro State University Faculty of Medical Sciences, Rio de Janeiro, Brazil (Ringgold ID: RIN468988)

³Obesity Unit (SAI-Ob), Multiuser Clinical Research Center (CePeM), Pedro Ernesto University Hospital, Rio de Janeiro State University, Rio de Janeiro, Brazil (Ringgold ID: RIN28130)

,

Luiz Guilherme Kraemer-Aguiar

¹Postgraduate Program in Clinical and Experimental Pathophysiology, Rio de Janeiro State University Faculty of Medical Sciences, Rio de Janeiro, Brazil (Ringgold ID: RIN468988)

²Endocrinology Department of Internal Medicine, Rio de Janeiro State University Faculty of Medical Sciences, Rio de Janeiro, Brazil (Ringgold ID: RIN468988)

³Obesity Unit (SAI-Ob), Multiuser Clinical Research Center (CePeM), Pedro Ernesto University Hospital, Rio de Janeiro State University, Rio de Janeiro, Brazil (Ringgold ID: RIN28130)

› Institutsangaben

Abstract

The high cardiometabolic risk associated with polycystic ovary syndrome (PCOS) may be linked to central fat accumulation. This study compared fat distribution between women with PCOS and controls matched by body mass index. It also sought to determine if insulin resistance (IR), androgens, or inflammatory markers correlate with body composition parameters in PCOS patients. In total, thirty-five women with PCOS and 37 controls, aged 18–40 years, were included. Hormonal/metabolic profiles, inflammatory biomarkers [tumor necrosis factor-alpha (TNF-α and interleukin-6 (IL-6)], anthropometry (waist circumference, waist-to-hip ratio, lipid accumulation product [LAP], visceral adiposity index [VAI]), and body composition assessed through dual-energy X-ray absorptiometry were assessed. The PCOS group exhibited significantly higher androgen levels and markers of IR. However, levels of TNF-α and IL-6 were comparable between the groups. Despite having similar total body fat mass (FM), the PCOS group had excessive central fat, including increased truncal FM and visceral adipose tissue (VAT). In PCOS, androgens were not associated with body fat or its distribution. IL-6 was positively correlated with total and truncal FM, while insulinemia and the homeostatic model assessment for IR were positively associated with VAT, as well as with total and truncal FM. Although anthropometric measurements and indices were positively associated with DXA-derived central FM parameters, our data suggest that LAP is the most effective tool for assessing central fat deposition and metabolic dysfunction in the PCOS patients studied herein. Furthermore, in this population, IR, rather than androgens or proinflammatory cytokines, is more closely associated with abdominal obesity.

Keywords

body composition - trunk fat mass - visceral fat mass - hyperandrogenism - tumor necrosis factor-alpha - interleukin-6

Volltext

Referenzen

References
1 Deswal R, Narwal V, Dang A. et al. The prevalence of olycystic ovary syndrome: a brief systematic review. J Hum Reprod Sci 2020; 13: 261-271
2 Daniilidis A, Dinas K. Long term health consequences of polycystic ovarian syndrome: a review analysis. Hippokratia 2009; 13: 90-92
3 Cibula D, Cífková R, Fanta M, Poledne R, Zivny J, Skibová J. Increased risk of non-insulin dependent diabetes mellitus, arterial hypertension and coronary artery disease in perimenopausal women with a history of the polycystic ovary syndrome. Hum Reprod 2000; 15: 785-789
4 Lord J, Thomas R, Fox B. et al. The central issue? Visceral fat mass is a good marker of insulin resistance and metabolic disturbance in women with polycystic ovary syndrome. BJOG. 2006; 113: 1203-1209
5 Pasquali R, Oriolo C. Obesity and androgens in women. Front Horm Res 2019; 53: 120-134
6 Sekizkardes H, Chung ST, Chacko S. et al. Free fatty acid processing diverges in human pathologic insulin resistance conditions. J Clin Invest 2020; 130: 3592-3602
7 Linscheid P, Seboek D, Nylen ES. et al. In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue. Endocrinology 2003; 144: 5578-5584
8 Kelly CC, Lyall H, Petrie JR. et al. Low grade chronic inflammation in women with polycystic ovarian syndrome. J Clin Endocrinol Metab 2001; 86: 245-2455
9 Ali DE, Shah M, Ali A. et al. Treatment with metformin and combination of metformin plus pioglitazone on serum levels of IL-6 and IL-8 in polycystic ovary syndrome: a randomized clinical trial. Horm Metab Res 2019; 51: 714-722
10 Pekcan MK, Tokmak A, Akkaya H. et al. Assessment of the relationship between serum high molecular weight adiponectin hormone levels and insulin resistance in patients with polycystic ovary syndrome. Horm Metab Res 2019; 51: 261-266
11 Jin CH, Yuk JS, Choi KM. et al. Body fat distribution and its associated factors in Korean women with polycystic ovary syndrome. J Obstet Gynaecol Res 2015; 41: 1577-1583
12 Patel P, Abate N. Body fat distribution and insulin resistance. Nutrients 2013; 5: 2019-2027
13 Zheng SH, Li XL. Visceral adiposity index as a predictor of clinical severity and therapeutic outcome of PCOS. Gynecol Endocrinol 2016; 32: 177-183
14 Neeland IJ, Grundy SM, Li X. et al. Comparison of visceral fat mass measurement by dual-X-ray absorptiometry and magnetic resonance imaging in a multiethnic cohort: the Dallas Heart Study. Nutr Diabetes 2016; 6: e221
15 Zhu S, Li Z, Hu C. et al. Li. Imaging-based body fat distribution in polycystic ovary syndrome: a systematic review and meta-analysis. Front Endocrinol 2021; 12: 697223
16 Macruz CF, Lima SMRR, Salles JEN. et al. Assessment of the body composition of patients with polycystic ovary syndrome using dual-energy X-ray absorptiometry. Int J Gynecol Obstet 2017; 136: 285-289
17 Teede HJ, Tay CT, Laven JJE. et al. Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Eur J Endocrinol 2023; 189: G43-G64
18 Glintborg D, Petersen MH, Ravn P. et al. Comparison of regional fat mass measurement by whole body DXA scans and anthropometric measures to predict insulin resistance in women with polycystic ovary syndrome and controls. Acta Obstet Gynecol Scand 2016; 95: 1235-1243
19 Kirchengast S, Gruber D, Sator M. et al. The fat distribution index – a new possibility to quantify sex specific fat patterning in females. Homo 1997; 48: 285-295
20 Ezeh U, Pall M, Mathur R. et al. Association of fat to lean mass ratio with metabolic dysfunction in women with polycystic ovary syndrome. Hum Reprod 2014; 29: 1508-1517
21 Jones H, Sprung VS, Pugh CJ. et al. Polycystic ovary syndrome with hyperandrogenism is characterized by an increased risk of hepatic steatosis compared to nonhyperandrogenic PCOS phenotypes and healthy controls, independent of obesity and insulin resistance. J Clin Endocrinol Metab 2012; 97: 3709-3716
22 Kahn HS. The “lipid accumulation product” performs better than the body mass index for recognizing cardiovascular risk: a population-based comparison. BMC Cardiovasc Disord 2005; 5: 26
23 Amato MC, Giordano C, Galia M. et al. Visceral adiposity index: a reliable indicator of visceral fat function associated with cardiometabolic risk. Diabetes Care 2010; 33: 920-922
24 Jena D, Choudhury AK, Mangaraj S. et al. Study of visceral and subcutaneous abdominal fat thickness and its correlation with cardiometabolic risk factors and hormonal parameters in polycystic ovary syndrome. Indian J Endocrinol Metab 2018; 22: 321-327
25 Elffers TW, de Mutsert R, Lamb HJ. et al. Body fat distribution, in particular visceral fat, is associated with cardiometabolic risk factors in obese women. PLoS ONE 2017; 12: e0185403
26 Dumesic DA, Akopians AL, Madrigal VK. et al. Hyperandrogenism accompanies increased intra-abdominal fat storage in normal weight polycystic ovary syndrome women. J Clin Endocrinol Metab 2016; 101: 4178-4188
27 Kajaia N, Binder H. Dittrich Rm et al. Low sex hormone-binding globulin as a predictive marker for insulin resistance in women with hyperandrogenic syndrome. Eur J Endocrinol 2007; 157: 499-507
28 Kałużna M, Czlapka-Matyasik M, Bykowska-Derda A. et al. Indirect predictors of visceral adipose tissue in women with polycystic ovary syndrome: a comparison of methods. Nutrients 2021; 13: 2494
29 Abruzzese GA, Cerrrone GE, Gamez JM. et al. Lipid accumulation product (LAP) and visceral adiposity index (VAI) as markers of insulin resistance and metabolic associated disturbances in young Argentine women with polycystic ovary syndrome. Horm Metab Res 2017; 49: 23-29
30 Oh JY, Sung YA, Lee HJ. The visceral adiposity index as a predictor of insulin resistance in young women with polycystic ovary syndrome. Obesity (Silver Spring) 2013; 21: 1690-1694
31 Durmus U, Duran C, Ecirli S. Visceral adiposity index levels in overweight and/or obese, and non-obese patients with polycystic ovary syndrome and its relationship with metabolic and inflammatory parameters. J Endocrinol Invest 2017; 40: 487-497
32 Ilhan GA, Yildizhan B, Pekin T. The impact of lipid accumulation product (LAP) and visceral adiposity index (VAI) on clinical, hormonal and metabolic parameters in lean women with polycystic ovary syndrome. Gynecol Endocrinol 2019; 35: 233-236
33 Androulakis II, Kandaraki E, Christakou C. et al. Visceral adiposity index (VAI) is related to the severity of anovulation and other clinical features in women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 2014; 81: 426-431
34 Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Ver 2012; 33: 981-1030
35 Sam S. Adiposity and metabolic dysfunction in polycystic ovary syndrome. Horm Mol Biol Clin Investig 2015; 21: 107-116
36 Mannerås-Holm L, Leonhardt H, Kullberg J. et al. Adipose tissue has aberrant morphology and function in PCOS: enlarged adipocytes and low serum adiponectin, but not circulating sex steroids, are strongly associated with insulin resistance. J Clin Endocrinol Metab 2011; 96: 304-311
37 Echiburú B, Pérez-Bravo F, Galgani JE. et al. Enlarged adipocytes in subcutaneous adipose tissue associated to hyperandrogenism and visceral adipose tissue volume in women with polycystic ovary syndrome. Steroids 2018; 130: 15-21
38 Puder JJ, Varga S, Kraenzlin M. et al. Central fat excess in polycystic ovary syndrome: relation to low-grade inflammation and insulin resistance. J Clin Endocrinol Metab 2005; 90: 6014-6021
39 Barber TM, Golding SJ, Alvey C. et al. Global adiposity rather than abnormal regional fat distribution characterizes women with polycystic ovary syndrome. J Clin Endocrinol Metab 2008; 93: 999-1004
40 Penaforte FR, Japur CC, Diez-Garcia RW. et al. Upper trunk fat assessment and its relationship with metabolic and biochemical variables and body fat in polycystic ovary syndrome. J Hum Nutr Diet 2011; 24: 39-46
41 Lim SS, Norman RJ, Davies MJ. et al. The effect of obesity on polycystic ovary syndrome: a systematic review and meta-analysis. Obes Ver 2013; 14: 95-109
42 Tosi F, Di Sarra D, Kaufman JM. et al. Total body fat and central fat mass independently predict insulin resistance but not hyperandrogenemia in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2015; 100: 661-669
43 Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm. 2013: 139239
44 Fernández-Real JM, Ricart W. Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 2003; 24: 278-301
45 Hotamisligil GS, Arner P, Caro JF. et al. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 1995; 95: 2409-2415
46 Yudkin JS, Kumari M, Humphries SE. et al. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link?. Atherosclerosis 2000; 148: 209-214
47 Escobar Morreale HF, Laque-Ramirez M, Gonzalez F. Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and meta-analysis. Fertil Steril 2011; 95: 1048-1058
48 Shroff R, Kerchner A, Maifeld M. et al. Young obese women with polycystic ovary syndrome have evidence of early coronary atherosclerosis. J Clin Endocrinol Metab 2007; 92: 4609-4614
49 Cardoso NS, Ribeiro VB, Dutra SGV. et al. Polycystic ovary syndrome associated with increased adiposity interferes with serum levels of TNF-alpha and IL-6 differently from leptin and adiponectin. Arch Endocrinol Metab 2020; 64: 4-10
50 González F, Rote NS, Minium J. et al. Evidence of proatherogenic inflammation in polycystic ovary syndrome. Metabolism 2009; 58: 954-962

Zusatzmaterial

Supplementary Material