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Risk and effect modifiers for poor glycemic control among the chinese diabetic adults on statin therapy: the kailuan study

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Abstract

Background

Limited studies have investigated the association between statin therapy and poor glycemic control, especially in the Chinese diabetic population.

Methods

Two prospective diabetes cohorts were drawn from the Kailuan Cohort. In Cohort 1, linear regression models were used to evaluate the association between statin therapy and glycated hemoglobin (HbA1c) level change. In Cohort 2, new user design and conditional logistic models were used to assess associations between statin initiation and poor glycemic control which was a composite outcome comprised of hypoglycemic agent escalation and new-onset hyperglycemia.

Results

Among 11,755 diabetic patients with medication information, 1400 statin users and 1767 statin nonusers with repeated HbA1c measurements were included in Cohort 1 (mean age: 64.6 ± 10.0 years). After a median follow-up of 3.02 (1.44, 5.00) years, statin therapy was associated with higher HbA1c levels (β: 0.20%; 95%CI: 0.05% to 0.34%). In Cohort 2, 1319 pairs of matched cases/controls were included (mean age: 61.6 ± 9.75 years). After a median follow-up of 4.87 (2.51, 8.42) years, poor glycemic control occurred in 43.0% of statin new users and 31.8% of statin nonusers (OR: 1.69; 95% CI: 1.32 to 2.17; P < 0.001). The statin-associated poor glycemic control risk was significantly higher among patients with lower body mass index (Pint = 0.089). Furthermore, a nonlinear association was observed between statin therapy duration and poor glycemic control (P = 0.003).

Conclusions

Among Chinese diabetic adults, statin therapy was associated with a higher level of HbA1c, and a higher risk of hypoglycemic agent escalation and new-onset hyperglycemia, especially among those who had lower body mass index levels and longer statin therapy duration.

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Data availability

The data, analytic methods, and study materials will be made available for an onsite audit by third parties for purposes of reproducing the results or replicating the procedure.

References

  1. Magliano DJ, Boyko EJ, committee IDFDAtes (2021) IDF Diabetes Atlas. In: Idf diabetes atlas. International Diabetes Federation © International Diabetes Federation, Brussels

  2. Wang L, Peng W, Zhao Z, Zhang M, Shi Z, Song Z, Zhang X, Li C, Huang Z, Sun X et al (2021) Prevalence and treatment of diabetes in China, 2013–2018. JAMA 326:2498–2506. https://doi.org/10.1001/jama.2021.22208

    Article  PubMed  PubMed Central  Google Scholar 

  3. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE et al (2019) 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 139:e1046–e1081. https://doi.org/10.1161/cir.0000000000000624

    Article  PubMed  Google Scholar 

  4. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA et al (2020) 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 41:111–188. https://doi.org/10.1093/eurheartj/ehz455

    Article  PubMed  Google Scholar 

  5. Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, Shin EK (2010) Atorvastatin causes insulin resistance and increases ambient glycemia in hypercholesterolemic patients. J Am Coll Cardiol 55:1209–1216. https://doi.org/10.1016/j.jacc.2009.10.053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Erlandson KM, Jiang Y, Debanne SM, McComsey GA (2015) Rosuvastatin worsens insulin resistance in HIV-infected adults on antiretroviral therapy. Clin Infect Dis: Off Publ Infect Dis Soc Am 61:1566–1572. https://doi.org/10.1093/cid/civ554

    Article  CAS  Google Scholar 

  7. Cederberg H, Stančáková A, Yaluri N, Modi S, Kuusisto J, Laakso M (2015) Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort. Diabetologia 58:1109–1117. https://doi.org/10.1007/s00125-015-3528-5

    Article  CAS  PubMed  Google Scholar 

  8. Mansi IA, Chansard M, Lingvay I, Zhang S, Halm EA, Alvarez CA (2021) Association of statin therapy initiation with diabetes progression: a retrospective matched-cohort study. JAMA Intern Med 181:1562–1574. https://doi.org/10.1001/jamainternmed.2021.5714

    Article  CAS  PubMed  Google Scholar 

  9. Erqou S, Lee CC, Adler AI (2014) Statins and glycaemic control in individuals with diabetes: a systematic review and meta-analysis. Diabetologia 57:2444–2452. https://doi.org/10.1007/s00125-014-3374-x

    Article  CAS  PubMed  Google Scholar 

  10. Bardini G, Giannini S, Rotella CM, Pala L, Cresci B, Mannucci E (2016) Lower and higher-potency statins on glycemic control in type 2 diabetes: a retrospective cohort study. Diabetes Res Clin Pract 120:104–110. https://doi.org/10.1016/j.diabres.2016.07.015

    Article  CAS  PubMed  Google Scholar 

  11. Li H, Zuo Y, Qian F, Chen S, Tian X, Wang P, Li X, Guo X, Wu S, Wang A (2022) Triglyceride-glucose index variability and incident cardiovascular disease: a prospective cohort study. Cardiovasc Diabetol 21:105. https://doi.org/10.1186/s12933-022-01541-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cui H, Liu Q, Wu Y, Cao L (2022) Cumulative triglyceride-glucose index is a risk for CVD: a prospective cohort study. Cardiovasc Diabetol 21:22. https://doi.org/10.1186/s12933-022-01456-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zhou YF, Wang Y, Wang G, Zhou Z, Chen S, Geng T, Zhang YB, Wang Y, Chen JX, Pan A et al (2022) Association between statin use and progression of arterial stiffness among adults with high atherosclerotic risk. JAMA Netw Open 5:e2218323. https://doi.org/10.1001/jamanetworkopen.2022.18323

    Article  PubMed  PubMed Central  Google Scholar 

  14. Shipman KE, Jawad M, Sullivan KM, Ford C, Gama R (2014) HbA1c is a reliable test for type 2 diabetes in primary care irrespective of chronic kidney disease. BMJ (Clinical research ed) 348:g3780. https://doi.org/10.1136/bmj.g3780

    Article  CAS  PubMed  Google Scholar 

  15. Yoshida K, Solomon DH, Kim SC (2015) Active-comparator design and new-user design in observational studies. Nat Rev Rheumatol 11:437–441. https://doi.org/10.1038/nrrheum.2015.30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lund JL, Richardson DB, Stürmer T (2015) The active comparator, new user study design in pharmacoepidemiology: historical foundations and contemporary application. Curr Epidemiol Rep 2:221–228. https://doi.org/10.1007/s40471-015-0053-5

    Article  PubMed  PubMed Central  Google Scholar 

  17. Brouilette SW, Moore JS, McMahon AD, Thompson JR, Ford I, Shepherd J, Packard CJ, Samani NJ (2007) Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study. Lancet (London, England) 369:107–114. https://doi.org/10.1016/s0140-6736(07)60071-3

    Article  CAS  PubMed  Google Scholar 

  18. Jin C, Chen S, Vaidya A, Wu Y, Wu Z, Hu FB, Kris-Etherton P, Wu S, Gao X (2017) Longitudinal change in fasting blood glucose and myocardial infarction risk in a population without diabetes. Diabetes Care 40:1565–1572. https://doi.org/10.2337/dc17-0610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. (2022) 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022. Diabetes Care 45:S17–s38. https://doi.org/10.2337/dc22-S002

  20. Li Y, Huang Z, Jin C, Xing A, Liu Y, Huangfu C, Lichtenstein AH, Tucker KL, Wu S, Gao X (2018) Longitudinal change of perceived salt intake and stroke risk in a Chinese population. Stroke 49:1332–1339. https://doi.org/10.1161/strokeaha.117.020277

    Article  PubMed  PubMed Central  Google Scholar 

  21. Wu S, Huang Z, Yang X, Zhou Y, Wang A, Chen L, Zhao H, Ruan C, Wu Y, Xin A et al (2012) Prevalence of ideal cardiovascular health and its relationship with the 4-year cardiovascular events in a northern Chinese industrial city. Circ Cardiovasc Qual Outcomes 5:487–493. https://doi.org/10.1161/circoutcomes.111.963694

    Article  PubMed  Google Scholar 

  22. Wu Z, Huang Z, Jin W, Rimm EB, Lichtenstein AH, Kris-Etherton PM, Wu S, Gao X (2017) Peripheral inflammatory biomarkers for myocardial infarction risk: a prospective community-based study. Clin Chem 63:663–672. https://doi.org/10.1373/clinchem.2016.260828

    Article  CAS  PubMed  Google Scholar 

  23. Bartlett JW, Seaman SR, White IR, Carpenter JR (2015) Multiple imputation of covariates by fully conditional specification: accommodating the substantive model. Stat Methods Med Res 24:462–487. https://doi.org/10.1177/0962280214521348

    Article  PubMed  PubMed Central  Google Scholar 

  24. Liu H, Chen S, Li Z, Xing A, Liu Y, Yu J, Li D, Li Y, Zhou X, Yang Q et al (2022) Long-term risks for cardiovascular disease and mortality across the glycaemic spectrum in a male-predominant Chinese cohort aged 75 years or older: the Kailuan study. Age Ageing 51. https://doi.org/10.1093/ageing/afac109

  25. Niiranen TJ, Kalesan B, Mitchell GF, Vasan RS (2019) Relative contributions of pulse pressure and arterial stiffness to cardiovascular disease. Hypertension (Dallas, Tex : 1979) 73:712–717. https://doi.org/10.1161/hypertensionaha.118.12289

    Article  CAS  PubMed  Google Scholar 

  26. Ganatra RB, Bhatnagar A, Herzig SJ (2022) Strengthening a study of diabetes progression after statin use. JAMA Intern Med 182:459–460. https://doi.org/10.1001/jamainternmed.2021.8353

    Article  PubMed  Google Scholar 

  27. Liew SM, Lee PY, Hanafi NS, Ng CJ, Wong SS, Chia YC, Lai PS, Zaidi NF, Khoo EM (2014) Statins use is associated with poorer glycaemic control in a cohort of hypertensive patients with diabetes and without diabetes. Diabetol Metab Syndr 6:53. https://doi.org/10.1186/1758-5996-6-53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sukhija R, Prayaga S, Marashdeh M, Bursac Z, Kakar P, Bansal D, Sachdeva R, Kesan SH, Mehta JL (2009) Effect of statins on fasting plasma glucose in diabetic and nondiabetic patients. J Invest Med: Off Publ Am Fed Clin Res 57:495–499. https://doi.org/10.2310/JIM.0b013e318197ec8b

    Article  CAS  Google Scholar 

  29. Swerdlow DI, Preiss D, Kuchenbaecker KB, Holmes MV, Engmann JE, Shah T, Sofat R, Stender S, Johnson PC, Scott RA et al (2015) HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet (London, England) 385:351–361. https://doi.org/10.1016/s0140-6736(14)61183-1

    Article  CAS  PubMed  Google Scholar 

  30. Henriksbo BD, Lau TC, Cavallari JF, Denou E, Chi W, Lally JS, Crane JD, Duggan BM, Foley KP, Fullerton MD et al (2014) Fluvastatin causes NLRP3 inflammasome-mediated adipose insulin resistance. Diabetes 63:3742–3747. https://doi.org/10.2337/db13-1398

    Article  CAS  PubMed  Google Scholar 

  31. Mitchell P, Marette A (2014) Statin-induced insulin resistance through inflammasome activation: sailing between Scylla and Charybdis. Diabetes 63:3569–3571. https://doi.org/10.2337/db14-1059

    Article  CAS  PubMed  Google Scholar 

  32. Nakata M, Nagasaka S, Kusaka I, Matsuoka H, Ishibashi S, Yada T (2006) Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycaemic control. Diabetologia 49:1881–1892. https://doi.org/10.1007/s00125-006-0269-5

    Article  CAS  PubMed  Google Scholar 

  33. Mansi I, Mortensen E (2013) The controversy of a wider statin utilization: why? Expert Opin Drug Saf 12:327–337. https://doi.org/10.1517/14740338.2013.779667

    Article  CAS  PubMed  Google Scholar 

  34. Brault M, Ray J, Gomez YH, Mantzoros CS, Daskalopoulou SS (2014) Statin treatment and new-onset diabetes: a review of proposed mechanisms. Metabolism: Clin Exp 63:735–745. https://doi.org/10.1016/j.metabol.2014.02.014

    Article  CAS  Google Scholar 

  35. Goldstein MR, Mascitelli L (2013) Do statins cause diabetes? Curr DiabRep 13:381–390. https://doi.org/10.1007/s11892-013-0368-x

    Article  CAS  Google Scholar 

  36. Salunkhe VA, Mollet IG, Ofori JK, Malm HA, Esguerra JL, Reinbothe TM, Stenkula KG, Wendt A, Eliasson L, Vikman J (2016) Dual effect of rosuvastatin on glucose homeostasis through improved insulin sensitivity and reduced insulin secretion. EBioMedicine 10:185–194. https://doi.org/10.1016/j.ebiom.2016.07.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Qian L, Zhu K, Lin Y, An L, Huang F, Yao Y, Ren L (2019) Insulin secretion impairment induced by rosuvastatin partly though autophagy in INS-1E cells. Cell Biol Int. https://doi.org/10.1002/cbin.11208

    Article  PubMed  Google Scholar 

  38. Kim J, Lee HS, Lee KY (2018) Effect of statins on fasting glucose in non-diabetic individuals: nationwide population-based health examination in Korea. Cardiovasc Diabetol 17:155. https://doi.org/10.1186/s12933-018-0799-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, Seshasai SR, McMurray JJ, Freeman DJ, Jukema JW et al (2010) Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet (London, England) 375:735–742. https://doi.org/10.1016/s0140-6736(09)61965-6

    Article  CAS  PubMed  Google Scholar 

  40. Park HJ, Cho JH, Kim HJ, Park JY, Lee HS, Byun MK (2019) The effect of low body mass index on the development of chronic obstructive pulmonary disease and mortality. J Intern Med 286:573–582. https://doi.org/10.1111/joim.12949

    Article  CAS  PubMed  Google Scholar 

  41. Mansi IA, Chansard M, Lingvay I, Zhang S, Halm EA, Alvarez CA (2022) Statins and renal disease progression, ophthalmic manifestations, and neurological manifestations in veterans with diabetes: a retrospective cohort study. PLoS ONE 17:e0269982. https://doi.org/10.1371/journal.pone.0269982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Peto R, Armitage J, Baigent C (2008) Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet (London, England) 371:117–125. https://doi.org/10.1016/s0140-6736(08)60104-x

    Article  CAS  PubMed  Google Scholar 

  43. de Vries FM, Denig P, Pouwels KB, Postma MJ, Hak E (2012) Primary prevention of major cardiovascular and cerebrovascular events with statins in diabetic patients: a meta-analysis. Drugs 72:2365–2373. https://doi.org/10.2165/11638240-000000000-00000

    Article  PubMed  Google Scholar 

  44. Yang XH, Zhang BL, Cheng Y, Fu SK, Jin HM (2022) Statin use and the risk of CVD events, stroke, and all-cause mortality in patients with diabetes: A systematic review and meta-analysis. Nutr Metab Cardiovasc Dis 32:2470–2482. https://doi.org/10.1016/j.numecd.2022.07.018

    Article  CAS  PubMed  Google Scholar 

  45. Brinton EA (2021) Statin-related new-onset diabetes appears driven by increased insulin resistance: are there clinical implications? Arterioscler Thromb Vasc Biol 41:2798–2801. https://doi.org/10.1161/atvbaha.121.316893

    Article  CAS  PubMed  Google Scholar 

  46. Danaei G, Tavakkoli M, Hernán MA (2012) Bias in observational studies of prevalent users: lessons for comparative effectiveness research from a meta-analysis of statins. Am J Epidemiol 175:250–262. https://doi.org/10.1093/aje/kwr301

    Article  PubMed  PubMed Central  Google Scholar 

  47. Mach F, Ray KK, Wiklund O, Corsini A, Catapano AL, Bruckert E, De Backer G, Hegele RA, Hovingh GK, Jacobson TA et al (2018) Adverse effects of statin therapy: perception vs. the evidence - focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract. Eur Heart J 39:2526–2539. https://doi.org/10.1093/eurheartj/ehy182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank all the members of the Kailuan Study Team for their contributions and the participants who contributed their data.

Funding

This work was supported by the National Natural Science Foundation of China (72274133 and 82270349), Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-069C), Tianjin Municipal Science and Technology Commission (19JCQNJC11500) and double First-Class Project of Tianjin Medical University (SYL001-303078100820 and SYL002-303078100821).

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Author notes

  1. Zhaogui Wu and Shuohua Chen contributed equally to this study.

Authors and Affiliations

  1. Department of Cardiology, Tianjin Medical University General Hospital, 154, Anshan Road, Heping District, Tianjin, 300052, China

    Zhaogui Wu, Xixi Tao, Hangkuan Liu, Pengfei Sun, Qing Yang & Xin Zhou

  2. Department of Cardiology, Kailuan General Hospital, 57 Xinhuadong Street, Lubei District, TangshanHebei, 063001, China

    Shuohua Chen & Shouling Wu

  3. Cardiovascular Research Institute, National University Health System, 14 Medical Drive, Singapore, 117599, Singapore

    Arthur Mark Richards

  4. Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive (MD6), Singapore, 117597, Singapore

    Arthur Mark Richards & Huay Cheem Tan

  5. Department of Cardiology, National University Heart Centre, 5 Lower Kent Ridge Rd, Singapore, 119074, Singapore

    Huay Cheem Tan

  6. Department of Pharmacology and Tianjin Key Laboratory of Inflammatory Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China

    Ying Yu

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  1. Zhaogui Wu
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Contributions

ZW and SC contributed to the study concept and design, analysis and interpretation of data, drafting of the manuscript, and served as the equally contributing first authors of the manuscript. XM, HL, PS, AR, HT, and YY contributed to the interpretation of data and revisions of the manuscript. XZ, SW, and QY contributed to the study concept and design, study supervision or coordination, revisions of the manuscript, and served as the corresponding authors of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Qing Yang, Shouling Wu or Xin Zhou.

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This study was approved by the Ethics Committee of the Kailuan General Hospital. Written informed consent was obtained from all participants.

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Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Wu, Z., Chen, S., Tao, X. et al. Risk and effect modifiers for poor glycemic control among the chinese diabetic adults on statin therapy: the kailuan study. Clin Res Cardiol (2024). https://doi.org/10.1007/s00392-024-02381-x

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