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METABOLIC SYNDROME / RESEARCH PAPER
Association between metabolic syndrome and inflammatory bowel disease: a bidirectional two-sample Mendelian randomized study
1
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University, Guangzhou, China., China
2
Yuebei People’s Hospital of Shantou University Medical College, Shaoguan, China., China
3
Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China., China
4
Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China, China
These authors had equal contribution to this work
Submission date: 2025-01-25
Final revision date: 2025-07-19
Acceptance date: 2025-08-03
Online publication date: 2025-10-05
Corresponding author
Xiaowei Sun
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University, Guangzhou, China., China
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University, Guangzhou, China., China
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Epidemiological studies have revealed parallel increases in the incidences of metabolic syndrome (MetS) and inflammatory bowel disease (IBD). Clinical observational studies have shown a link between MetS and a poor prognosis of IBD. However, the causal relationship between MetS and IBD remains unclear. This study used bidirectional two-sample Mendelian randomisation to investigate potential causal links between MetS and IBD, including ulcerative colitis (UC) and Crohn’s disease (CD).
Material and methods:
Genetic associations of MetS and components, IBD were sourced from public databases of European populations. Inverse variance weighting was conducted, with weighted median, Mendelian randomisation–Egger, and Mendelian randomization (MR) Pleiotropy Residual Sum and Outlier methods used as sensitivity analyses. This process was repeated in the opposite direction.
Results:
The Inverse variance weighted (IVW) method showed that genetic prediction of MetS may be a potential risk factor for CD (OR=1.34, 95% CI: 1.009–1.779; P=0.043). In further estimating the different components of MetS, waist circumference may increase the risk of CD (OR=1.33, 95% CI: 1.05–1.684; P=0.018) and hypertension may increase the risk of UC (OR=1.61, 95% CI: 1.084–2.39; P=0.018). In reverse analysis, IBD may increased triglyceride levels (OR=1.019, 95% CI: 1.000–1.038; P=0.049).
Conclusions:
This MR Analysis showed a causal relationship between genetically predicted MetS and CD, and genetically predicted hypertension and UC. Therefore, these patients need to be closely monitored clinically for the risk of CD/UC comorbidities. In patients with IBD, close monitoring of MetS-associated cardiovascular risk is required.
Epidemiological studies have revealed parallel increases in the incidences of metabolic syndrome (MetS) and inflammatory bowel disease (IBD). Clinical observational studies have shown a link between MetS and a poor prognosis of IBD. However, the causal relationship between MetS and IBD remains unclear. This study used bidirectional two-sample Mendelian randomisation to investigate potential causal links between MetS and IBD, including ulcerative colitis (UC) and Crohn’s disease (CD).
Material and methods:
Genetic associations of MetS and components, IBD were sourced from public databases of European populations. Inverse variance weighting was conducted, with weighted median, Mendelian randomisation–Egger, and Mendelian randomization (MR) Pleiotropy Residual Sum and Outlier methods used as sensitivity analyses. This process was repeated in the opposite direction.
Results:
The Inverse variance weighted (IVW) method showed that genetic prediction of MetS may be a potential risk factor for CD (OR=1.34, 95% CI: 1.009–1.779; P=0.043). In further estimating the different components of MetS, waist circumference may increase the risk of CD (OR=1.33, 95% CI: 1.05–1.684; P=0.018) and hypertension may increase the risk of UC (OR=1.61, 95% CI: 1.084–2.39; P=0.018). In reverse analysis, IBD may increased triglyceride levels (OR=1.019, 95% CI: 1.000–1.038; P=0.049).
Conclusions:
This MR Analysis showed a causal relationship between genetically predicted MetS and CD, and genetically predicted hypertension and UC. Therefore, these patients need to be closely monitored clinically for the risk of CD/UC comorbidities. In patients with IBD, close monitoring of MetS-associated cardiovascular risk is required.
REFERENCES (56)
1.
Buie MJ, Quan J, Windsor JW, Coward S, Hansen TM, King JA, et al. Global Hospitalization Trends for Crohn's Disease and Ulcerative Colitis in the 21st Century: A Systematic Review With Temporal Analyses. Clin Gastroenterol Hepatol. 2023 Aug;21(9):2211-2221.
2.
Noubiap JJ, Nansseu JR, Lontchi-Yimagou E, Nkeck JR, Nyaga UF, Ngouo AT, et al. Geographic distribution of metabolic syndrome and its components in the general adult population: A meta-analysis of global data from 28 million individuals. Diabetes Res Clin Pract. 2022 Jun;188:109924.
3.
Dobrowolski P, Prejbisz A, Kuryłowicz A, Baska A, Burchardt P, Chlebus K, et al. Metabolic syndrome - a new definition and management guidelines: A joint position paper by the Polish Society of Hypertension, Polish Society for the Treatment of Obesity, Polish Lipid Association, Polish Association for Study of Liver, Polish Society of Family Medicine, Polish Society of Lifestyle Medicine, Division of Prevention and Epidemiology Polish Cardiac Society, "Club 30" Polish Cardiac Society, and Division of Metabolic and Bariatric Surgery Society of Polish Surgeons. Arch Med Sci. 2022;18(5):1133-1156.
4.
Huang PL. A comprehensive definition for metabolic syndrome. Dis Model Mech. 2009 May-Jun;2(5-6):231-7.
5.
Tune JD, Goodwill AG, Sassoon DJ, Mather KJ. Cardiovascular consequences of metabolic syndrome. Transl Res. 2017 May;183:57-70.
6.
Cheng K, Faye AS. Venous thromboembolism in inflammatory bowel disease. World J Gastroenterol. 2020 Mar 28;26(12):1231-1241.
7.
Principi M, Iannone A, Losurdo G, Mangia M, Shahini E, Albano F, et al. Nonalcoholic Fatty Liver Disease in Inflammatory Bowel Disease: Prevalence and Risk Factors. Inflamm Bowel Dis. 2018 Jun 8;24(7):1589-1596.
8.
Yki-Järvinen H. Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome. Lancet Diabetes Endocrinol. 2014 Nov;2(11):901-10.
9.
Chan SSM, Chen Y, Casey K, Olen O, Ludvigsson JF, Carbonnel F, et al. Obesity is Associated With Increased Risk of Crohn's disease, but not Ulcerative Colitis: A Pooled Analysis of Five Prospective Cohort Studies. Clin Gastroenterol Hepatol. 2022 May;20(5):1048-1058.
10.
Bacha RA, Bouhnik Y, Serrero M, Filippi J, Roblin X, Bourrier A, et al. Obesity in adult patients with inflammatory bowel disease: Clinical features and impact on disability. A cross-sectional survey from the GETAID. Dig Liver Dis. 2023 Dec;55(12):1632-1639.
11.
Michalak A, Mosińska P, Fichna J. Common links between metabolic syndrome and inflammatory bowel disease: Current overview and future perspectives. Pharmacol Rep. 2016 Aug;68(4):837-46.
12.
Khakoo NS, Ioannou S, Khakoo NS, Vedantam S, Pearlman M. Impact of Obesity on Inflammatory Bowel Disease. Curr Gastroenterol Rep. 2022 Jan;24(1):26-36.
13.
Argollo M, Gilardi D, Peyrin-Biroulet C, Chabot JF, Peyrin-Biroulet L, Danese S. Comorbidities in inflammatory bowel disease: a call for action. Lancet Gastroenterol Hepatol. 2019 Aug;4(8):643-654.
14.
Adolph TE, Meyer M, Jukic A, Tilg H. Heavy arch: from inflammatory bowel diseases to metabolic disorders. Gut. 2024 Jul 11;73(8):1376-1387.
15.
Doyle SL, Donohoe CL, Lysaght J, Reynolds JV. Visceral obesity, metabolic syndrome, insulin resistance and cancer. Proc Nutr Soc. 2012 Feb;71(1):181-9.
16.
Burgess S, Davey Smith G, Davies NM, Dudbridge F, Gill D, Glymour MM, et al. Guidelines for performing Mendelian randomization investigations: update for summer 2023. Wellcome Open Res. 2023 Aug 4;4:186.
17.
Skrivankova VW, Richmond RC, Woolf BAR, Davies NM, Swanson SA, VanderWeele TJ, et al. Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR): explanation and elaboration. BMJ. 2021 Oct 26;375:n2233.
18.
van Walree ES, Jansen IE, Bell NY, Savage JE, de Leeuw C, Nieuwdorp M, van der Sluis S, Posthuma D. Disentangling Genetic Risks for Metabolic Syndrome. Diabetes. 2022 Nov 1;71(11):2447-2457.
19.
Kurki MI, Karjalainen J, Palta P, Sipilä TP, Kristiansson K, Donner KM, et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 2023 Jan;613(7944):508-518.
20.
Hemani G, Tilling K, Davey Smith G. Orienting the causal relationship between imprecisely measured traits using GWAS summary data. PLoS Genet. 2017 Nov 17;13(11):e1007081.
21.
Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ. 2018 Jul 12;362:k601.
22.
Bowden J, Davey Smith G, Haycock PC, Burgess S. Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol. 2016 May;40(4):304-14.
23.
Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015 Apr;44(2):512-25.
24.
Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018 May;50(5):693-698.
25.
Shen Z, Zhang M, Liu Y, Ge C, Lu Y, Shen H, et al. Prevalence of metabolic syndrome in patients with inflammatory bowel disease: a systematic review and meta-analysis. BMJ Open. 2024 Mar 7;14(3):e074659.
26.
Méndez-Sánchez N, Bugianesi E, Gish RG, Lammert F, Tilg H, Nguyen MH, et al. Global multi-stakeholder endorsement of the MAFLD definition. Lancet Gastroenterol Hepatol. 2022 May;7(5):388-390.
27.
Jiang K, Chen B, Lou D, Zhang M, Shi Y, Dai W, et al. Systematic review and meta-analysis: association between obesity/overweight and surgical complications in IBD. Int J Colorectal Dis. 2022 Jul;37(7):1485-1496.
28.
Sehgal P, Su S, Zech J, Nobel Y, Luk L, Economou I, et al. Visceral Adiposity Independently Predicts Time to Flare in Inflammatory Bowel Disease but Body Mass Index Does Not. Inflamm Bowel Dis. 2024 Apr 3;30(4):594-601.
29.
Yarur AJ, Bruss A, Moosreiner A, Beniwal-Patel P, Nunez L, Berens B, et al. Higher Intra-Abdominal Visceral Adipose Tissue Mass Is Associated With Lower Rates of Clinical and Endoscopic Remission in Patients With Inflammatory Bowel Diseases Initiating Biologic Therapy: Results of the Constellation Study. Gastroenterology. 2023 Oct;165(4):963-975.e5.
30.
Wunderlich CM, Ackermann PJ, Ostermann AL, Adams-Quack P, Vogt MC, Tran ML, et al. Obesity exacerbates colitis-associated cancer via IL-6-regulated macrophage polarisation and CCL-20/CCR-6-mediated lymphocyte recruitment. Nat Commun. 2018 Apr 25;9(1):1646.
31.
Nagahori M, Hyun SB, Totsuka T, Okamoto R, Kuwahara E, Takebayashi T, et al. Prevalence of metabolic syndrome is comparable between inflammatory bowel disease patients and the general population. J Gastroenterol. 2010 Oct;45(10):1008-13.
32.
Jovanovic M, Simovic Markovic B, Gajovic N, Jurisevic M, Djukic A, Jovanovic I, et al. Metabolic syndrome attenuates ulcerative colitis: Correlation with interleukin-10 and galectin-3 expression. World J Gastroenterol. 2019 Nov 21;25(43):6465-6482.
33.
Milajerdi A, Abbasi F, Esmaillzadeh A. A systematic review and meta-analysis of prospective studies on obesity and risk of inflammatory bowel disease. Nutr Rev. 2022 Feb 10;80(3):479-487.
34.
Je Y, Han K, Chun J, Kim Y, Kim JH, Hoon Youn Y, et al. Association of Waist Circumference with the Risk of Inflammatory Bowel Disease: a Nationwide Cohort Study of 10 Million Individuals in Korea. J Crohns Colitis. 2023 May 3;17(5):681-692.
35.
Harpsøe MC, Basit S, Andersson M, Nielsen NM, Frisch M, Wohlfahrt J, et al. Body mass index and risk of autoimmune diseases: a study within the Danish National Birth Cohort. Int J Epidemiol. 2014 Jun;43(3):843-55.
36.
Rahmani J, Kord-Varkaneh H, Hekmatdoost A, Thompson J, Clark C, Salehisahlabadi A, et al. Body mass index and risk of inflammatory bowel disease: A systematic review and dose-response meta-analysis of cohort studies of over a million participants. Obes Rev. 2019 Sep;20(9):1312-1320.
37.
Chan SS, Luben R, Olsen A, Tjonneland A, Kaaks R, Teucher B, et al. Body mass index and the risk for Crohn's disease and ulcerative colitis: data from a European Prospective Cohort Study (The IBD in EPIC Study). Am J Gastroenterol. 2013 Apr;108(4):575-82.
38.
Jensen CB, Ängquist LH, Mendall MA, Sørensen TIA, Baker JL, Jess T. Childhood body mass index and risk of inflammatory bowel disease in adulthood: a population-based cohort study. Am J Gastroenterol. 2018 May;113(5):694-701.
39.
Khalili H, Ananthakrishnan AN, Konijeti GG, Higuchi LM, Fuchs CS, Richter JM, et al. Measures of obesity and risk of Crohn's disease and ulcerative colitis. Inflamm Bowel Dis. 2015 Feb;21(2):361-8.
40.
He Z, Fu T, Lu S, Sun Y, Zhang Y, Shi W, et al. Adiposity as a risk factor for inflammatory bowel disease and the mediating effect of metabolic and inflammatory status: A population-based cohort study. United European Gastroenterol J. 2023 Dec;11(10):973-984.
41.
Zafar U, Khaliq S, Ahmad HU, Manzoor S, Lone KP. Metabolic syndrome: an update on diagnostic criteria, pathogenesis, and genetic links. Hormones (Athens). 2018 Sep;17(3):299-313.
42.
Choe SS, Huh JY, Hwang IJ, Kim JI, Kim JB. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders. Front Endocrinol (Lausanne). 2016 Apr 13;7:30.
43.
Leal Vde O, Mafra D. Adipokines in obesity. Clin Chim Acta. 2013 Apr 18;419:87-94.
44.
Kahn CR, Wang G, Lee KY. Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome. J Clin Invest. 2019 Oct 1;129(10):3990-4000.
45.
Chung S, Cuffe H, Marshall SM, McDaniel AL, Ha JH, Kavanagh K, et al. Dietary cholesterol promotes adipocyte hypertrophy and adipose tissue inflammation in visceral, but not in subcutaneous, fat in monkeys. Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):1880-7.
46.
Tchernof A, Després JP. Pathophysiology of human visceral obesity: an update. Physiol Rev. 2013 Jan;93(1):359-404.
47.
Hamdy O, Porramatikul S, Al-Ozairi E. Metabolic obesity: the paradox between visceral and subcutaneous fat. Curr Diabetes Rev. 2006 Nov;2(4):367-73.
48.
Gonçalves P, Magro F, Martel F. Metabolic inflammation in inflammatory bowel disease: crosstalk between adipose tissue and bowel. Inflamm Bowel Dis. 2015 Feb;21(2):453-67.
49.
Xiong Z, Wu P, Zhang Y, Chen J, Shen Y, Kamel I, et al. Radiological biomarkers reflecting visceral fat distribution help distinguish inflammatory bowel disease subtypes: a multicenter cross-sectional study. Insights Imaging. 2024 Mar 13;15(1):70.
50.
Zulian A, Cancello R, Ruocco C, Gentilini D, Di Blasio AM, Danelli P, et al. Differences in visceral fat and fat bacterial colonization between ulcerative colitis and Crohn's disease. An in vivo and in vitro study. PLoS One. 2013 Oct 24;8(10):e78495.
51.
Sinha T, Zain Z, Bokhari SFH, Waheed S, Reza T, Eze-Odurukwe A, et al. Navigating the Gut-Cardiac Axis: Understanding Cardiovascular Complications in Inflammatory Bowel Disease. Cureus. 2024 Feb 29;16(2):e55268.
52.
He J, Zhang S, Qiu Y, Liu F, Liu Z, Tan J, et al. Ulcerative colitis increases risk of hypertension in a UK biobank cohort study. United European Gastroenterol J. 2023 Feb;11(1):19-30.
53.
Jaiswal V, Batra N, Dagar M, Butey S, Huang H, Chia JE, et al. Inflammatory bowel disease and associated cardiovascular disease outcomes: A systematic review. Medicine (Baltimore). 2023 Feb 10;102(6):e32775.
54.
Koutroumpakis E, Ramos-Rivers C, Regueiro M, Hashash JG, Barrie A, Swoger J, et al. Association Between Long-Term Lipid Profiles and Disease Severity in a Large Cohort of Patients with Inflammatory Bowel Disease. Dig Dis Sci. 2016 Mar;61(3):865-71.
55.
Chen H, Li W, Hu J, Xu F, Lu Y, Zhu L, et al. Association of serum lipids with inflammatory bowel disease: a systematic review and meta-analysis. Front Med (Lausanne). 2023 Aug 24;10:1198988.
56.
Toth PP. Triglycerides and Cardiovascular Risk: Getting to the Heart of the Matter. J Am Coll Cardiol. 2024 Sep 10;84(11):1007-1009.
| eISSN: | 1896-9151 |
| ISSN: | 1734-1922 |
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