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Hormones

, Volume 16, Issue 4, pp 396–404 | Cite as

Baseline glucose homeostasis predicts the new onset of diabetes during statin therapy: A retrospective study in real life

  • Maria Chantal Ponziani
  • Ioannis Karamouzis
  • Chiara Mele
  • Luisa Chasseur
  • Marco Zavattaro
  • Marina Caputo
  • Maria Teresa Samà
  • Arianna Busti
  • Loredana Pagano
  • Luigi Castello
  • Paolo Marzullo
  • Gianluca Aimaretti
  • Flavia Prodam
Research paper

Abstract

OBJECTIVE

We evaluated the risk of altered glucose levels and new-onset diabetes (NOD) associated with statins according to glucose levels at baseline in a population treated for dyslipidemia on primary prevention for >5 years. DESIGN. The retrospective study included 308 subjects (265 on statins and 43 controls on diet) with a follow-up of 5–15 years. The cohort was classified according to glucose tolerance at both baseline and follow-up.

RESULTS

The cumulative incidence of NOD was 13.6% (9.3% in controls and 13.5% in treated patients). NOD was diagnosed after 3.4±1.8 years. In the group with normal glucose levels at baseline, a family history of diabetes (OR: 3.4, 95% CI 1.3–8.9), BMI >30 kg/m2 (OR: 8.5, 95% CI 2.0–35.8), treatment with thiazide (OR: 21.9, 95% CI 1.2–384.2) and no alcohol consumption (OR: 0.3, 95% CI 0.1–0.8) reduced the risk of developing altered glucose levels or NOD. No effects of statins were seen. In the group with altered glucose levels at baseline, hypertension (OR: 5.0, 95% CI 1.0–25.3) and hypertriglyceridemia (OR: 3.5, 95% CI 1.0–11.8) increased the risk of remaining with altered glucose levels or developing NOD. Treatment with statins (OR: 7.5, 95% CI 1.5–37.4), in particular atorvastatin, was associated with an increased risk. In the whole population, statin therapy (OR: 4.0, 95% CI 1.1–14.1, p<0.020), and in particular simvastatin and atorvastatin, was associated with increased risk of altered glucose levels or NOD. Patients who developed or maintained altered glucose levels or NOD had a poor metabolic phenotype at baseline.

CONCLUSIONS

Statins were associated with an increased risk of NOD or altered glucose levels, mainly in subjects with altered glucose levels before the beginning of therapy. Poor metabolic phenotype and unhealthy behaviors or family history of diabetes contributed to that risk.

Key words

Altered glucose levels Dyslipidemia New-onset diabetes Statin 

References

  1. 1.
    WHO Statistical Information System (WHOSIS). World Health Organization. https://doi.org/who.int/whosis/en/ Accessed 20 September 2015.
  2. 2.
    Cholesterol Treatment Trialists’ (CTT) Collaborators, Kearney PM, Blackwell L, Collins R, et al, 2008 Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a metaanalysis. Lancet 371: 117–125.CrossRefGoogle Scholar
  3. 3.
    Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, et al, 2010 Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376: 1670–1681.CrossRefGoogle Scholar
  4. 4.
    Sattar N, Preiss D, Murray HM, et al, 2010 Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 375: 735–742.CrossRefGoogle Scholar
  5. 5.
    Preiss D, Seshasai SR, Welsh P, et al, 2011 Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 305: 2556–64.CrossRefGoogle Scholar
  6. 6.
    Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ, 2012 Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet 380: 565–571.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Waters DD, Ho JE, Boekholdt SM, et al, 2013 Cardiovascular event reduction versus new-onset diabetes during atorvastatin therapy: effect of baseline risk factors for diabetes. J Am Coll Cardiol 61: 148–152.CrossRefGoogle Scholar
  8. 8.
    Carter AA, Gomes T, Camacho X, Juurlink DN, Shah BR, Mamdani MM, 2013 Risk of incident diabetes among patients treated with statins: population based study. BMJ 346: f2610.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Emerging Risk Factors Collaboration, Sarwar N, Gao P, Seshasai SR, et al, 2010 Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375: 2215–2222.CrossRefGoogle Scholar
  10. 10.
    US Food and Drug Administration. FDA drug safety communication: important safety label changes to cholesterol lowering statin drugs. https://doi.org/www.fda.gov/Drugs/DrugSafety/ucm293101.html. Accessed 14 May 2016.
  11. 11.
    Waters DD, Guyton JR, Herrington DM, et al, 2004 Treating to New Targets (TNT) Study: does lowering low-density lipoprotein cholesterol levels below currently recommended guidelines yield incremental clinical benefit? Am J Cardiol 93: 154–158.CrossRefGoogle Scholar
  12. 12.
    La Rosa JC, Grundy SM, Waters DD, et al, 2005 Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 352: 1425–1435.CrossRefGoogle Scholar
  13. 13.
    Pedersen TR, Faergeman O, Kastelein JJ, et al, 2005 High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA 294: 2437–2445.CrossRefGoogle Scholar
  14. 14.
    Waters DD, Ho JE, De Micco DA, et al, 2011 Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials. J Am Coll Cardiol 57: 1535–1545.CrossRefGoogle Scholar
  15. 15.
  16. 16.
    American Diabetes Association 2015 Classification and diagnosis of diabetes. Diabetes Care 38 Suppl: S8–S16.CrossRefGoogle Scholar
  17. 17.
    Harding AH, Wareham NJ, Bingham SA, et al 2008 Plasma vitamin C level, fruit and vegetable consumption, and the risk of new-onset type 2 diabetes mellitus: the European prospective investigation of cancer—Norfolk prospective study. Arch Intern Med 168: 1493–1499.CrossRefGoogle Scholar
  18. 18.
    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.CrossRefGoogle Scholar
  19. 19.
    Mizuno K, Tajima N, Ohashi Y, Nakamura H, 2013 Is the risk of new-onset diabetes by statins associated with diet adherence? Int J Cardiol 166: 277.CrossRefGoogle Scholar
  20. 20.
    Kohli P, Waters DD, Nemr R, et al, 2015 Risk of new-onset diabetes and cardiovascular risk reduction from high-dose statin therapy in pre-diabetics and non-prediabetics: an analysis from TNT and IDEAL. J Am Coll Cardiol 65: 402–404.CrossRefGoogle Scholar
  21. 21.
    Alberti KG, Eckel RH, Grundy SM, et al, 2009 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 120: 1640–1645.CrossRefGoogle Scholar
  22. 22.
    O’Neill S, O’Driscoll L, 2015 Metabolic syndrome: a closer look at the growing epidemic and its associated pathologies. Obes Rev 16: 1–12.CrossRefGoogle Scholar
  23. 23.
    Meigs JB, Cupples LA, Wilson PW, 2000 Parental transmission of type 2 diabetes: the Framingham Offspring Study. Diabetes 49: 2201–2207.CrossRefGoogle Scholar
  24. 24.
    Valdez R, Yoon PW, Liu T, Khoury MJ, 2007 Family history and prevalence of diabetes in the U.S. population: the 6-year results from the National Health and Nutrition Examination Survey (1999–2004). Diabetes Care 30: 2517–2522.CrossRefGoogle Scholar
  25. 25.
    Nakanishi N, Suzuki K, Tatara K, 2003 Alcohol consumption and risk for development of impaired fasting glucose or type 2 diabetes in middle-aged Japanese men. Diabetes Care 26: 48–54.CrossRefGoogle Scholar
  26. 26.
    Knott C, Bell S, Britton A, 2015 Alcohol Consumption and the Risk of Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis of More Than 1.9 Million Individuals From 38 Observational Studies. Diabetes Care 38: 1804–1812.CrossRefGoogle Scholar
  27. 27.
    Mita T, Watada H, Nakayama S, et al, 2007 Preferable effect of pravastatin compared to atorvastatin on beta cell function in Japanese early-state type 2 diabetes with hypercholesterolemia. Endocr J 54: 441–447.CrossRefGoogle Scholar
  28. 28.
    Ray K, 2013 Statin diabetogenicity: guidance for clinicians. Cardiovasc Diabetol 12 Suppl 1: S3.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Vallejo-Vaz AJ, Kondapally Seshasai SR, Kurogi K, et al, 2015 Effect of pitavastatin on glucose, HbA1c and incident diabetes: A meta-analysis of randomized controlled clinical trials in individuals without diabetes. Atherosclerosis 241: 409–418.CrossRefGoogle Scholar
  30. 30.
    Yu Q, Chen Y, Xu CB, 2017 Statins and New-Onset Diabetes Mellitus: LDL Receptor May Provide a Key Link. Front Pharmacol 8: 372.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Fuentes F, Alcala-Diaz JF, Watts GF, et al, 2015 Statins do not increase the risk of developing type 2 diabetes in familial hypercholesterolemia: The SAFEHEART study. Int J Cardiol 201: 79–84.CrossRefGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2017

Authors and Affiliations

  • Maria Chantal Ponziani
    • 1
  • Ioannis Karamouzis
    • 1
  • Chiara Mele
    • 1
    • 2
  • Luisa Chasseur
    • 1
  • Marco Zavattaro
    • 1
  • Marina Caputo
    • 1
  • Maria Teresa Samà
    • 1
  • Arianna Busti
    • 1
  • Loredana Pagano
    • 1
  • Luigi Castello
    • 1
  • Paolo Marzullo
    • 1
    • 2
  • Gianluca Aimaretti
    • 1
  • Flavia Prodam
    • 3
  1. 1.Department of Translational MedicineUniversity of Piemonte OrientaleNovaraItaly
  2. 2.Division of General Medicine, Istituto Auxologico ItalianoOspedale S. GiuseppePiancavalloItaly
  3. 3.Department of Health SciencesUniversity of Piemonte OrientaleNovaraItaly

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