Skip to main content
SpringerLink
Log in

The association between gallstone disease and metabolic syndrome related abnormalities: a systematic review and meta-analysis

  • Review Article
  • Published:
International Journal of Diabetes in Developing Countries Aims and scope Submit manuscript

Abstract

Background

Bile excretion is one of the important metabolite excretion pathways of the human body. In recent years, it has been reported that metabolic diseases are associated with the occurrence of gallstone disease. The main purpose of this systematic review is to examine the relationship between metabolic syndrome and cholelithiasis, including components of the metabolic syndrome such as abnormal blood glucose regulation, hyperlipidemia, and obesity.

Methods

PubMed, Cochrane Library, and Embase were searched for all English language articles for the following relevant keywords: Metabolic Syndrome, Reaven Syndrome X, Biliary Calculi, Cholelithiasis Gallstones. Case-control study, cross-sectional study, and cohort study were included. Pooled relative risks (RRs) or odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated. The pooled mean differences of the outcome measures were compared between patients with and without metabolic syndrome.

Results

After screening, a total of 5 cross-sectional studies and 1 cohort study were included in the meta-analysis. The 6 studies evaluated a total of 49,101 people, of whom 9055 had metabolic syndrome and 2308 had gallstone disease. There is a significant correlation between metabolic syndrome and gallstone disease (z = 6.65, p = 0.000), and it’s more significant in female. All studies displayed increasing odds of gallstone disease with increasing number of metabolic syndrome traits, where patients with three or more metabolic syndrome traits tended to have a higher prevalence of nephrolithiasis.

Conclusions

Our review shows a definite association of metabolic syndrome with gallstone disease, and the more the components of metabolic syndrome, the higher the prevalence of gallstone disease. Although not as obvious as women, men also support this conclusion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

Not applicable

References

  1. Portincasa P, Moschetta A, Palasciano G. Cholesterol gallstone disease. Lancet. 2006;368(9531):230.

    Article  CAS  Google Scholar 

  2. Everhart JE, Khare M, Hill M, Maurer KR. Prevalence and ethnic differences in gallbladder disease in the United States. Gastroenterology. 1999;117(3):632–9.

    Article  CAS  Google Scholar 

  3. Sandler RS, Everhart JE, Donowitz M, Adams E, Cronin K, Goodman C, et al. The burden of selected digestive diseases in the United States ☆ ☆☆. Gastroenterology. 2002;122(5):1500–11.

    Article  Google Scholar 

  4. Shaffer EA. Epidemiology of gallbladder stone disease. Best Pract Res Clin Gastroenterol. 2006;20(6):981–96.

    Article  Google Scholar 

  5. Stinton LM, Shaffer EA. Epidemiology of gallbladder disease: cholelithiasis and cancer. Gut Liver. 2012;6(2):172–87.

    Article  Google Scholar 

  6. Lin IC, Yang YW, Wu MF, Yeh YH, Liou JC, Lin YL, et al. The association of metabolic syndrome and its factors with gallstone disease. BMC Fam Pract. 2014;15(1):138.

    Article  Google Scholar 

  7. Aguilar M, Bhuket T, Torres S, Liu B, Wong RJ. Prevalence of the metabolic syndrome in the United States, 2003-2012. Jama. 2015;313(19):1973–4. https://doi.org/10.1001/jama.2015.4260.

    Article  CAS  PubMed  Google Scholar 

  8. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640–5. https://doi.org/10.1161/circulationaha.109.192644.

    Article  CAS  PubMed  Google Scholar 

  9. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement: Executive Summary. Crit Pathw Cardiol. 2005;4(4):198–203. https://doi.org/10.1097/00132577-200512000-00018.

    Article  PubMed  Google Scholar 

  10. Kim HJ, Kim Y, Cho Y, Jun B, Kyung Won O. Trends in the prevalence of major cardiovascular disease risk factors among Korean adults: results from the Korea National Health and Nutrition Examination Survey, 1998-2012. Int J Cardiol. 2014;174(1):64–72. https://doi.org/10.1016/j.ijcard.2014.03.163.

    Article  PubMed  Google Scholar 

  11. Li Y, Zhao L, Yu D, Wang Z, Ding G. Metabolic syndrome prevalence and its risk factors among adults in China: a nationally representative cross-sectional study. PLoS One. 2018;13(6):e0199293.

    Article  Google Scholar 

  12. Méndez-sánchez N, Chaveztapia NC, Motolakuba D, Sanchezlara K, Poncianorodríguez G, Baptista H, et al. Metabolic syndrome as a risk factor for gallstone disease. World J Gastroenterol. 2005;11(11):1653–7.

    Article  Google Scholar 

  13. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. Jama. 2000;283(15):2008–12.

    Article  CAS  Google Scholar 

  14. Tarsilla M. Cochrane handbook for systematic reviews of interventions. J Multidiscip Eval. 2008;6:142–8.

    Google Scholar 

  15. Wells G, Shea B, O'Connell J (2014) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Health Research Institute. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.

  16. Zeng X, Zhang Y, Kwong JS, Zhang C, Li S, Sun F, et al. The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review. J Evid Based Med. 2015;8(1):2–10. https://doi.org/10.1111/jebm.12141.

    Article  PubMed  Google Scholar 

  17. Sanderson S, Tatt ID, Higgins JP. Tools for assessing quality and susceptibility to bias in observational studies in epidemiology: a systematic review and annotated bibliography. Int J Epidemiol. 2007;36(3):666.

    Article  Google Scholar 

  18. Sterne JA, Egger M. Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. J Clin Epidemiol. 2001;54(10):1046–55. https://doi.org/10.1016/s0895-4356(01)00377-8.

    Article  CAS  PubMed  Google Scholar 

  19. Shabanzadeh DM, Skaaby T, Sørensen LT, Eugen-Olsen J, Jørgensen T. Metabolic biomarkers and gallstone disease – a population-based study. Scand J Gastroenterol. 2017:52(11):1270–7. https://doi.org/10.1080/00365521.2017.1365166.

  20. Li-Ying C, Qiao-Hua Q, Shan-Chun Z, Yu-Hao C, Chao G-Q. Metabolic syndrome and gallstone disease. World J Gastroenterol: WJG. 2012;18(31):4215.

    Article  Google Scholar 

  21. Zhu Q, Sun X, Ji X, Zhu L, Xu J, Wang C, et al. The association between gallstones and metabolic syndrome in urban Han Chinese: a longitudinal cohort study. Sci Rep. 2016;6:29937.

    Article  CAS  Google Scholar 

  22. Chung-Hung T, Wu J-S, Chang Y-F, Lu F-H, Yang Y-C, Chang C-J. The number of metabolic abnormalities associated with the risk of gallstones in a non-diabetic population. PLoS One. 2014;9(3):e90310.

    Article  Google Scholar 

  23. Chaimani A, Higgins JPT, Mavridis D, Spyridonos P, Salanti G. Graphical tools for network meta-analysis in STATA. PLoS One. 2013;8(10):e76654. https://doi.org/10.1371/journal.pone.0076654.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. In Sook K, Myung S-J, Lee S-S, Lee S-K, Kim M-H. Classification and nomenclature of gallstones revisited. Yonsei Med J. 2003;44(4):561.

    Article  Google Scholar 

  25. Fridhandler TM, Davison JS, Shaffer EA. Defective gallbladder contractility in the ground squirrel and prairie dog during the early stages of cholesterol gallstone formation. Gastroenterology. 1983;85(4):830–6.

    Article  CAS  Google Scholar 

  26. Portincasa P, Di Ciaula A, Vanberge-Henegouwen GP. Smooth muscle function and dysfunction in gallbladder disease. Curr Gastroenterol Rep. 2004;6(2):151–62.

    Article  Google Scholar 

  27. Kishk SM, Darweesh RM, Dodds WJ, Lawson TL, Stewart ET, Kern MK, et al. Sonographic evaluation of resting gallbladder volume and postprandial emptying in patients with gallstones. AJR Am J Roentgenol. 1987;148(5):875.

    Article  CAS  Google Scholar 

  28. Yongsheng C, Jing K, Shuodong W. Cholesterol gallstone disease: focusing on the role of gallbladder. Lab Investig. 2015;95(2):124–31.

    Article  Google Scholar 

  29. Yoosoo C, Sung E, Ryu S, Park Y-W, Jang YM, Park M. Insulin resistance is associated with gallstones even in non-obese, non-diabetic Korean men. J Korean Med Sci. 2008;23(4):644–50.

    Article  Google Scholar 

  30. Shaffer EA. Epidemiology and risk factors for gallstone disease: has the paradigm changed in the 21st century? Curr Gastroenterol Rep. 2005;7(2):132–40.

    Article  Google Scholar 

  31. Reaven GM. Role of insulin resistance in human disease (syndrome X): an expanded definition. Annu Rev Med. 1993;44(1):121.

    Article  CAS  Google Scholar 

  32. Samson SL, Garber AJ. Metabolic syndrome. Endocrinol Metab Clin N Am. 2014;43(1):1–23. https://doi.org/10.1016/j.ecl.2013.09.009.

    Article  Google Scholar 

  33. Balkau B, Charles MA. Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med. 1999;16(5):442–3. https://doi.org/10.1046/j.1464-5491.1999.00059.x.

    Article  CAS  PubMed  Google Scholar 

  34. Executive Summary of the third report of The National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). Jama. 2001;285(19):2486–97. https://doi.org/10.1001/jama.285.19.2486.

  35. Sirdah MM, Abu Ghali AS, Al Laham NA. The reliability of the National Cholesterol Education Program’s Adult Treatment Panel III (NCEP/ATP III) and the International Diabetes Federation (IDF) definitions in diagnosing metabolic syndrome (MetS) among Gaza Strip Palestinians. Diabetes Metab Syndr Clin Res Rev. 2012;6(1):4–8.

    Article  Google Scholar 

  36. Zimmet P, DMatsuzawa Y, Magliano GA, Shaw J. The metabolic syndrome: a global public health problem and a new definition. J Atheroscler Thromb. 2005;12(6):295–300.

    Article  CAS  Google Scholar 

  37. Alberti KG, Zimmet P, Shaw J. The metabolic syndrome--a new worldwide definition. Lancet. 2005;366(9491):1059–62. https://doi.org/10.1016/s0140-6736(05)67402-8.

    Article  PubMed  Google Scholar 

  38. Sang JH, Ki NK, Cho JH, Ahn JO, Sunwoo JG. Correlations between metabolic syndrome, serologic factors, and gallstones. J Phys Ther Sci. 2016;28(8):2337–41.

    Article  Google Scholar 

  39. Nervi F, Miquel JF, Alvarez M, Ferreccio C, García-Zattera MJ, González R, et al. Gallbladder disease is associated with insulin resistance in a high risk Hispanic population. J Hepatol. 2006;45(2):299–305.

    Article  CAS  Google Scholar 

  40. Nakeeb A, Comuzzie AG, Al-Azzawi H, Sonnenberg GE, Kissebah AH, Pitt HA. Insulin resistance causes human gallbladder dysmotility. J Gastrointest Surg. 2006;10(7):940–9.

    Article  Google Scholar 

  41. Twisk J, Hoekman MF, Lehmann EM, Meijer P, Mager WH, Princen HM. Insulin suppresses bile acid synthesis in cultured rat hepatocytes by down-regulation of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase gene transcription. Hepatology. 1995;21(2):501–10.

    CAS  PubMed  Google Scholar 

  42. Holland WL, Xia JY, Johnson JA, Sun K, Pearson MJ, Sharma AX, et al. Inducible overexpression of adiponectin receptors highlight the roles of adiponectin-induced ceramidase signaling in lipid and glucose homeostasis. Mol Metab. 2017;6(3):267–75. https://doi.org/10.1016/j.molmet.2017.01.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Grundy SM. Cholesterol gallstones: a fellow traveler with metabolic syndrome? Am J Clin Nutr. 2004;80(1):1–2.

    Article  CAS  Google Scholar 

  44. Pitt HA. Hepato-pancreato-biliary fat: the good, the bad and the ugly. HPB. 2007;9(2):92–7.

    Article  Google Scholar 

  45. Cecilia G, Francisco MJ, Maria PR, Curt E, Lars S, Guillermo M, et al. Bile acid synthesis is increased in Chilean Hispanics with gallstones and in gallstone high-risk Mapuche Indians. Gastroenterology. 2004;126(3):741–8.

    Article  Google Scholar 

  46. Cojocaru D-C, Mitu F, Dascălu CG, Manole A, Dima-Cozma C. The predictors of cholelithiasis in female patients with metabolic syndrome. Cent Eur J Med. 2014;2014(9):108–14. https://doi.org/10.2478/s11536-013-0255-5.

    Article  CAS  Google Scholar 

Download references

Funding

This study was funded by the Zhejiang Medical and Health Science and Technology (grant number 2021KY927) and Zhejiang Traditional Chinese Medicine Administration (CN) (grant number 2021ZB208).

Author information

Authors and Affiliations

  1. Department of General Surgery, Hangzhou Dingqiao Hospital, Hangzhou, Zhejiang, People’s Republic of China

    Peiwu Jiang, Shifei Huang & Hai Huang

  2. Department of General Surgery, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, People’s Republic of China

    Zhongkai Ni, Xiaowen Li, Ye Li & Hai Huang

Authors
  1. Peiwu Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhongkai Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shifei Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaowen Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ye Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hai Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

PJ and HH conceived and designed the study. ZN and XL performed the experiments. PJ and SH wrote the paper. PJ, ZN, XL, YL, and HH reviewed and edited the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Hai Huang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Code availability

Not applicable

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

A pre-print version have been posted at Research Square on 19 Feb, 2020. (https://www.researchsquare.com/article/rs-14528/v1) https://doi.org/10.21203/rs.2.23967/v1

A pre-print version have been posted at Research Square on 19 Feb, 2020.

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, P., Ni, Z., Huang, S. et al. The association between gallstone disease and metabolic syndrome related abnormalities: a systematic review and meta-analysis. Int J Diabetes Dev Ctries 41, 196–204 (2021). https://doi.org/10.1007/s13410-020-00890-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13410-020-00890-9

Keywords

Search

Navigation