Diabetes is the missing link between cardiometabolic index and gallstones: a large cross-sectional study.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Gallstones*/epidemiology ; Gallstones*/metabolism ; Diabetes Mellitus*/epidemiology ; Diabetes Mellitus*/metabolism; Humans ; Cross-Sectional Studies ; Male ; Female ; Middle Aged ; Adult ; Nutrition Surveys ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/etiology ; Cardiovascular Diseases/metabolism ; Aged ; Prevalence ; Cardiometabolic Risk Factors ; Risk Factors ; Intra-Abdominal Fat/metabolism

Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: The survey protocols were approved by the Ethics Review Board of the NCHS, and all participants provided written informed consent prior to their involvement in the study.
The cardiometabolic index (CMI), which integrates individual lipid and visceral fat parameters, represents a superior new predictive tool for cardiovascular and metabolic disorders, but its predictive value for gallstones (GS) is unclear. Therefore, the present study used this vacancy to explore the relationship between CMI levels and GS in US adults, assess the mediating role of diabetes mellitus in the pathogenesis of both, and provide new clinical ideas for early prevention and screening of GS in patients with diabetes mellitus. This survey extracted information from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 vintage cycle. Cross-sectional analyses and a variety of statistical techniques were used to analyze the correlation between CMI and GS, including logistic regression, propensity score matching, subject work curves, and restricted cubic spline (RCS). Furthermore, mediation analysis was used to investigate whether and to what extent diabetes mediated the effect of CMI on GS. After analysis of 3,395 participants, a significant positive correlation was observed between elevated CMI levels and increased prevalence of GS In the fully corrected model (Model 4), the prevalence of GS exhibited a 23% increase for every incremental unit rise in logarithmically transformed CM. Mediation analysis showed that diabetes largely mediated the association between CMI and GS, with a mediation ratio of 15.1%. Higher CMI levels are closely linked to a greater occurrence of GS, and diabetes plays a key mediating role in the pathogenesis of both. Addressing dyslipidemia while not neglecting blood glucose levels, and co-management of the two may be a proven way to reduce GS risk.
(© 2025. The Author(s).)

Lammert, F. et al. Gallstones. Nat. Rev. Dis. Primers 2, 16024 (2016). (PMID: 2712141610.1038/nrdp.2016.24)
de Sousa, S. et al. Management of suspected common bile duct stones on cholangiogram during same-stay cholecystectomy for acute gallstone-related disease. BMC Surg. 17(1), 39 (2017). (PMID: 28412956539299710.1186/s12893-017-0232-z)
Stinton, L. M. & Shaffer, E. A. Epidemiology of gallbladder disease: Cholelithiasis and cancer. Gut Liver 6(2), 172–187 (2012). (PMID: 22570746334315510.5009/gnl.2012.6.2.172)
Everhart, J. E. & Ruhl, C. E. Burden of digestive diseases in the united States part III: Liver, biliary tract, and pancreas. Gastroenterology 136(4), 1134–1144 (2009). (PMID: 1924586810.1053/j.gastro.2009.02.038)
Festi, D. et al. Natural history of gallstone disease: Expectant management or active treatment? Results from a population-based cohort study. J. Gastroenterol. Hepatol. 25(4), 719–724 (2010). (PMID: 2049232810.1111/j.1440-1746.2009.06146.x)
Shaffer, E. A. Epidemiology and risk factors for gallstone disease: Has the paradigm changed in the 21st century? Curr. Gastroenterol. Rep. 7(2), 132–140 (2005). (PMID: 1580210210.1007/s11894-005-0051-8)
Granel-Villach, L. et al. Factors that influence bile fluid microbiology in cholecystectomized patients. Rev. Gastroenterol. Mex (Engl Ed) 85(3), 257–263 (2020). (PMID: 32019715)
Rai, R., Tewari, M., Kumar, M., Singh, T. B. & Shukla, H. S. Expression profile of cholecystokinin type-A receptor in gallbladder cancer and gallstone disease. Hepatobiliary Pancreat. Dis. Int. 10(4), 408–414 (2011). (PMID: 2181339110.1016/S1499-3872(11)60069-6)
Shabanzadeh, D. M. et al. Are incident gallstones associated to sex-dependent changes with age? A cohort study. Andrology 5(5), 931–938 (2017). (PMID: 2870459710.1111/andr.12391)
Jain, K. & Garg, P. K. Could type and size of gallstones influence gallbladder carcinogenesis?? Ann. Surg. 263(3), e57 (2016). (PMID: 2557526110.1097/SLA.0000000000001083)
Wirth, J. et al. Presence of gallstones and the risk of cardiovascular diseases: The EPIC-Germany cohort study. Eur. J. Prev. Cardiol. 22(3), 326–334 (2015). (PMID: 2417726710.1177/2047487313512218)
Chen, H. et al. Dissolved oxygen from microalgae-gel patch promotes chronic wound healing in diabetes. Sci. Adv. 6(20), eaba4311 (2020). (PMID: 32440554722876110.1126/sciadv.aba4311)
Li, X. et al. Targeting long noncoding RNA-AQP4-AS1 for the treatment of retinal neurovascular dysfunction in diabetes mellitus. EBioMedicine 77, 103857 (2022). (PMID: 35172268885068210.1016/j.ebiom.2022.103857)
Araneta, M. R. et al. Optimum BMI cut points to screen Asian Americans for type 2 diabetes. Diabetes Care. 38(5), 814–820 (2015). (PMID: 25665815440775310.2337/dc14-2071)
Wiwanitkit, V. BMI, waist circumference and waist-to-hip ratio: Diabetes mellitus type 2. Eur. J. Clin. Nutr. 64(11), 1377 (2010). (PMID: 2064804210.1038/ejcn.2010.119)
Alzeidan, R., Fayed, A., Rabiee, F., Hersi, A. & Elmorshedy, H. Diagnostic performance of waist-to-height ratio in identifying cardiovascular risk factors and metabolic syndrome among adult Saudis. A cross-sectional study. Saudi Med. J. 41(3), 253–260 (2020). (PMID: 32114597784155710.15537/smj.2020.3.24915)
Corrêa, M. M., Thumé, E., De Oliveira, E. R. & Tomasi, E. Performance of the waist-to-height ratio in identifying obesity and predicting non-communicable diseases in the elderly population: A systematic literature review. Arch. Gerontol. Geriatr. 65, 174–182 (2016). (PMID: 2706166510.1016/j.archger.2016.03.021)
Hou, X. et al. Stronger associations of waist circumference and waist-to-height ratio with diabetes than BMI in Chinese adults. Diabetes Res. Clin. Pract. 147, 9–18 (2019). (PMID: 3014447810.1016/j.diabres.2018.07.029)
Zhang, S. et al. Is waist-to-height ratio the best predictive indicator of cardiovascular disease incidence in hypertensive adults? A cohort study. BMC Cardiovasc. Disord. 22(1), 214 (2022). (PMID: 35545759909268310.1186/s12872-022-02646-1)
Ye, R. et al. Association of cardiometabolic and triglyceride-glucose index with left ventricular diastolic function in asymptomatic individuals. Nutr. Metab. Cardiovasc. Dis. 34(7), 1590–1600 (2024). (PMID: 38499451)
Tohidi, M. et al. Association of triglycerides to high-density lipoprotein cholesterol ratio to identify future prediabetes and type 2 diabetes mellitus: Over one-decade follow-up in the Iranian population. Diabetol. Metab. Syndr. 15(1), 13 (2023). (PMID: 36732786989369110.1186/s13098-023-00988-0)
Acosta-García, E. & Concepción-Páez, M. [Cardiometabolic index as a predictor of cardiovascular risk factors in adolescents]. Rev. Salud Publica (Bogota) 20(3), 340–345 (2018). (PMID: 3084400710.15446/rsap.v20n3.61259)
Shi, W. R. et al. Estimate of prevalent diabetes from cardiometabolic index in general Chinese population: a community-based study. Lipids Health Dis. 17(1), 236 (2018). (PMID: 30314516618604610.1186/s12944-018-0886-2)
Wang, H. et al. Validity of cardiometabolic index, lipid accumulation product, and body adiposity index in predicting the risk of hypertension in Chinese population. Postgrad. Med. 130(3), 325–333 (2018). (PMID: 2947836510.1080/00325481.2018.1444901)
Zou, J. et al. Association between the cardiometabolic index and non-alcoholic fatty liver disease: Insights from a general population. BMC Gastroenterol. 22(1), 20 (2022). (PMID: 35021995875666310.1186/s12876-022-02099-y)
Zuo, Y. Q., Gao, Z. H., Yin, Y. L., Yang, X. & Feng, P. Y. Association between the cardiometabolic index and hyperuricemia in an asymptomatic population with normal body mass index. Int. J. Gen. Med. 14, 8603–8610 (2021). (PMID: 34849005862728210.2147/IJGM.S340595)
Cheng, J. et al. Association of pro-inflammatory diet with increased risk of gallstone disease: A cross-sectional study of NHANES January 2017-March 2020. Front. Nutr. 11, 1344699 (2024). (PMID: 385497481097290510.3389/fnut.2024.1344699)
Wen, S. H., Tang, X., Tang, T. & Ye, Z. R. Association between weight-adjusted-waist index and gallstones: An analysis of the National health and nutrition examination survey. BMC Gastroenterol. 24(1), 40 (2024). (PMID: 382387001079785210.1186/s12876-024-03127-9)
Global guideline for. Type 2 diabetes. Diabetes Res. Clin. Pract. 104(1), 1–52 (2014). (PMID: 10.1016/j.diabres.2012.10.001)
Nayak, S. S. et al. Diagnostic and prognostic value of triglyceride glucose index: A comprehensive evaluation of meta-analysis. Cardiovasc. Diabetol. 23(1), 310 (2024). (PMID: 391800241134439110.1186/s12933-024-02392-y)
Wakabayashi, I. & Daimon, T. The cardiometabolic index as a new marker determined by adiposity and blood lipids for discrimination of diabetes mellitus. Clin. Chim. Acta. 438, 274–278 (2015). (PMID: 2519985210.1016/j.cca.2014.08.042)
Gong, R. et al. Associations between TG/HDL ratio and insulin resistance in the US population: A cross-sectional study. Endocr. Connect. 10(11), 1502–1512 (2021). (PMID: 34678755863076910.1530/EC-21-0414)
Liu, M. et al. Predicted fat mass and lean mass in relation to all-cause and cause-specific mortality. J. Cachexia Sarcopenia Muscle 13(2), 1064–1075 (2022). (PMID: 35068076897801510.1002/jcsm.12921)
Liu, X. et al. Cardiometabolic index: A new tool for screening the metabolically obese normal weight phenotype. J. Endocrinol. Invest. 44(6), 1253–1261 (2021). (PMID: 3290917510.1007/s40618-020-01417-z)
Zheng, Y. et al. Gallstones and risk of coronary heart disease: Prospective analysis of 270 000 men and women from 3 US cohorts and Meta-Analysis. Arterioscler. Thromb. Vasc Biol. 36(9), 1997–2003 (2016). (PMID: 27540264500191410.1161/ATVBAHA.116.307507)
Ratheesh, R., Ulrich, M. T., Ghozy, S., Al-Jaboori, M. & Nayak, S. S. The association between diabetes and gallstones: A nationwide population-based cohort study. Prz Gastroenterol. 18(3), 292–299 (2023). (PMID: 3793711510626383)
Tang, C. et al. Correlation between the cardiometabolic index and arteriosclerosis in patients with type 2 diabetes mellitus. BMC Cardiovasc. Disord 24(1), 186 (2024). (PMID: 385391021097682210.1186/s12872-024-03853-8)
Zhou, X. et al. Association between cardiometabolic index and depression: National health and nutrition examination survey (NHANES) 2011–2014. J. Affect. Disord 351, 939–947 (2024). (PMID: 3834115710.1016/j.jad.2024.02.024)
Zha, F. et al. The nonlinear correlation between the cardiometabolic index and the risk of diabetes: A retrospective Japanese cohort study. Front. Endocrinol. (Lausanne) 14, 1120277 (2023). (PMID: 3687546010.3389/fendo.2023.1120277)
Chen, X., Zhao, Y., Sun, J., Jiang, Y. & Tang, Y. Identification of metabolic syndrome using lipid accumulation product and cardiometabolic index based on NHANES data from 2005 to 2018. Nutr. Metab. (Lond) 21 (1), 96 (2024). (PMID: 3956806710.1186/s12986-024-00864-2)
Carmichael, L. et al. Is vascular insulin resistance an early step in diet-induced whole-body insulin resistance? Nutr. Diabetes 12(1), 31 (2022). (PMID: 35676248917775410.1038/s41387-022-00209-z)
Boden, G. Obesity, insulin resistance, type 2 diabetes and free fatty acids. Expert Rev. Endocrinol. Metab. 1(4), 499–505 (2006). (PMID: 3029045610.1586/17446651.1.4.499)
Kahn, S. E., Hull, R. L. & Utzschneider, K. M. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444(7121), 840–846 (2006). (PMID: 1716747110.1038/nature05482)
Barazzoni, R., Gortan Cappellari, G., Ragni, M. & Nisoli, E. Insulin resistance in obesity: An overview of fundamental alterations. Eat. Weight Disord 23(2), 149–157 (2018). (PMID: 2939756310.1007/s40519-018-0481-6)
Ruze, R. et al. Obesity and type 2 diabetes mellitus: Connections in epidemiology, pathogenesis, and treatments. Front. Endocrinol. (Lausanne) 14, 1161521 (2023). (PMID: 3715294210.3389/fendo.2023.1161521)
Poitout, V. & Robertson, R. P. Glucolipotoxicity: Fuel excess and beta-cell dysfunction. Endocr. Rev. 29(3), 351–366 (2008). (PMID: 1804876310.1210/er.2007-0023)
Tang, X. et al. Associations of insulin resistance and beta-cell function with abnormal lipid profile in newly diagnosed diabetes. Chin. Med. J. (Engl) 135(21), 2554–2562 (2022). (PMID: 3524592410.1097/CM9.0000000000002075)
Taskinen, M. R. & Borén, J. New insights into the pathophysiology of dyslipidemia in type 2 diabetes. Atherosclerosis 239(2), 483–495 (2015). (PMID: 2570606610.1016/j.atherosclerosis.2015.01.039)
Arshad, F., Laway, B. A., Rather, T. A., Kuchay, M. S. & Khan, S. H. Impaired gallbladder motility in adults with newly detected type 2 diabetes and lack of reversibility after achieving euglycemia. Can. J. Diabetes. 39(2), 101–104 (2015). (PMID: 2544468010.1016/j.jcjd.2014.07.223)
Škrha, J. Jr. Diabetes, lipids, and CV risk. Curr. Atheroscler Rep. 23(3), 8 (2021). (PMID: 3346440210.1007/s11883-021-00905-8)
Vergès, B. Pathophysiology of diabetic dyslipidaemia: Where are we? Diabetologia 58(5), 886–899 (2015). (PMID: 25725623439216410.1007/s00125-015-3525-8)
Pendleton, H., Ekman, R., Olsson, R., Ekberg, O. & Ohlsson, B. Motilin concentrations in relation to gastro intestinal dysmotility in diabetes mellitus. Eur. J. Intern. Med. 20(6), 654–659 (2009). (PMID: 1978293210.1016/j.ejim.2009.05.015)
Rehfeld, J. F. et al. Cholecystokinin secretion is suppressed by glucagon-like peptide-1: Clue to the mechanism of the adverse gallbladder events of GLP-1-derived drugs. Scand. J. Gastroenterol. 53(12), 1429–1432 (2018). (PMID: 3044920710.1080/00365521.2018.1530297)

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Keywords: Cardiometabolic index; Cross-sectional study; Gallstones

Date Created: 20250323 Date Completed: 20250323 Latest Revision: 20250326

20250327

PMC11929793

10.1038/s41598-025-93908-3

40121318