Are statins diabetogenic?

Uchechukwu K. Sampson, MacRae F. Linton, Sergio Fazio

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

PURPOSE OF REVIEW: Statins are widely utilized for low-density lipoprotein lowering and for prevention of atherosclerotic cardiovascular disease. Although these drugs have a good safety record, increased risk of developing diabetes during extended use has recently garnered attention. Here we review clinical trial evidence related to statin use and incident diabetes, and the potential mechanisms for this association. RECENT FINDINGS: The increased incidence of diabetes with rosuvastatin treatment in Justification for the Use of Statins in Primary Prevention: an intervention Trial Evaluating Rosuvastatin (JUPITER) reignited attention on the link between statin therapy and diabetes. The JUPITER findings are supported by two recent meta-analyses of large-scale placebo-controlled and standard care-controlled trials, which, respectively, observed a 9% [odds ratio 1.09; 95% confidence interval (CI) 1.02-1.17] and 13% (risk ratio 1.13; 95% CI 1.03-1.23) increased risk for incident diabetes associated with statin therapy. However, the underlying mechanisms for this association remain unclear. Experimental evidence supports a paradigm implicating inhibition of β-cell glucose transporters, delayed ATP production, pro-inflammatory and oxidative β-cell effects of plasma-derived cholesterol, inhibition of calcium channel-dependent insulin secretion, and β-cell apoptosis. SUMMARY: The aggregate of large clinical trials supports the notion that statins modestly increase the risk of incident diabetes. Because diabetes is a risk equivalent condition for coronary and peripheral arterial diseases, these findings create a paradox whereby needed statin therapy may be withheld to avoid excess risk of diabetes while representing the strongest cardiovascular risk reduction tool in diabetics. We simply recommend regular glucose monitoring in patients taking statins.

Original languageEnglish (US)
Pages (from-to)342-347
Number of pages6
JournalCurrent Opinion in Cardiology
Volume26
Issue number4
DOIs
StatePublished - Jul 2011
Externally publishedYes

Fingerprint

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Primary Prevention
Odds Ratio
Clinical Trials
Confidence Intervals
Facilitative Glucose Transport Proteins
Peripheral Arterial Disease
Physiologic Monitoring
Risk Reduction Behavior
Calcium Channels
Therapeutics
Plasma Cells
LDL Lipoproteins
Meta-Analysis
Cardiovascular Diseases
Adenosine Triphosphate
Cholesterol
Placebos
Insulin
Apoptosis

Keywords

  • β-cells
  • cardiovascular disease
  • diabetes
  • low-density lipoprotein cholesterol
  • statins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Are statins diabetogenic? / Sampson, Uchechukwu K.; Linton, MacRae F.; Fazio, Sergio.

In: Current Opinion in Cardiology, Vol. 26, No. 4, 07.2011, p. 342-347.

Research output: Contribution to journalArticle

Sampson, Uchechukwu K. ; Linton, MacRae F. ; Fazio, Sergio. / Are statins diabetogenic?. In: Current Opinion in Cardiology. 2011 ; Vol. 26, No. 4. pp. 342-347.
@article{c0de2c476ca6448eb36a42047b9717d9,
title = "Are statins diabetogenic?",
abstract = "PURPOSE OF REVIEW: Statins are widely utilized for low-density lipoprotein lowering and for prevention of atherosclerotic cardiovascular disease. Although these drugs have a good safety record, increased risk of developing diabetes during extended use has recently garnered attention. Here we review clinical trial evidence related to statin use and incident diabetes, and the potential mechanisms for this association. RECENT FINDINGS: The increased incidence of diabetes with rosuvastatin treatment in Justification for the Use of Statins in Primary Prevention: an intervention Trial Evaluating Rosuvastatin (JUPITER) reignited attention on the link between statin therapy and diabetes. The JUPITER findings are supported by two recent meta-analyses of large-scale placebo-controlled and standard care-controlled trials, which, respectively, observed a 9{\%} [odds ratio 1.09; 95{\%} confidence interval (CI) 1.02-1.17] and 13{\%} (risk ratio 1.13; 95{\%} CI 1.03-1.23) increased risk for incident diabetes associated with statin therapy. However, the underlying mechanisms for this association remain unclear. Experimental evidence supports a paradigm implicating inhibition of β-cell glucose transporters, delayed ATP production, pro-inflammatory and oxidative β-cell effects of plasma-derived cholesterol, inhibition of calcium channel-dependent insulin secretion, and β-cell apoptosis. SUMMARY: The aggregate of large clinical trials supports the notion that statins modestly increase the risk of incident diabetes. Because diabetes is a risk equivalent condition for coronary and peripheral arterial diseases, these findings create a paradox whereby needed statin therapy may be withheld to avoid excess risk of diabetes while representing the strongest cardiovascular risk reduction tool in diabetics. We simply recommend regular glucose monitoring in patients taking statins.",
keywords = "β-cells, cardiovascular disease, diabetes, low-density lipoprotein cholesterol, statins",
author = "Sampson, {Uchechukwu K.} and Linton, {MacRae F.} and Sergio Fazio",
year = "2011",
month = "7",
doi = "10.1097/HCO.0b013e3283470359",
language = "English (US)",
volume = "26",
pages = "342--347",
journal = "Current Opinion in Cardiology",
issn = "0268-4705",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Are statins diabetogenic?

AU - Sampson, Uchechukwu K.

AU - Linton, MacRae F.

AU - Fazio, Sergio

PY - 2011/7

Y1 - 2011/7

N2 - PURPOSE OF REVIEW: Statins are widely utilized for low-density lipoprotein lowering and for prevention of atherosclerotic cardiovascular disease. Although these drugs have a good safety record, increased risk of developing diabetes during extended use has recently garnered attention. Here we review clinical trial evidence related to statin use and incident diabetes, and the potential mechanisms for this association. RECENT FINDINGS: The increased incidence of diabetes with rosuvastatin treatment in Justification for the Use of Statins in Primary Prevention: an intervention Trial Evaluating Rosuvastatin (JUPITER) reignited attention on the link between statin therapy and diabetes. The JUPITER findings are supported by two recent meta-analyses of large-scale placebo-controlled and standard care-controlled trials, which, respectively, observed a 9% [odds ratio 1.09; 95% confidence interval (CI) 1.02-1.17] and 13% (risk ratio 1.13; 95% CI 1.03-1.23) increased risk for incident diabetes associated with statin therapy. However, the underlying mechanisms for this association remain unclear. Experimental evidence supports a paradigm implicating inhibition of β-cell glucose transporters, delayed ATP production, pro-inflammatory and oxidative β-cell effects of plasma-derived cholesterol, inhibition of calcium channel-dependent insulin secretion, and β-cell apoptosis. SUMMARY: The aggregate of large clinical trials supports the notion that statins modestly increase the risk of incident diabetes. Because diabetes is a risk equivalent condition for coronary and peripheral arterial diseases, these findings create a paradox whereby needed statin therapy may be withheld to avoid excess risk of diabetes while representing the strongest cardiovascular risk reduction tool in diabetics. We simply recommend regular glucose monitoring in patients taking statins.

AB - PURPOSE OF REVIEW: Statins are widely utilized for low-density lipoprotein lowering and for prevention of atherosclerotic cardiovascular disease. Although these drugs have a good safety record, increased risk of developing diabetes during extended use has recently garnered attention. Here we review clinical trial evidence related to statin use and incident diabetes, and the potential mechanisms for this association. RECENT FINDINGS: The increased incidence of diabetes with rosuvastatin treatment in Justification for the Use of Statins in Primary Prevention: an intervention Trial Evaluating Rosuvastatin (JUPITER) reignited attention on the link between statin therapy and diabetes. The JUPITER findings are supported by two recent meta-analyses of large-scale placebo-controlled and standard care-controlled trials, which, respectively, observed a 9% [odds ratio 1.09; 95% confidence interval (CI) 1.02-1.17] and 13% (risk ratio 1.13; 95% CI 1.03-1.23) increased risk for incident diabetes associated with statin therapy. However, the underlying mechanisms for this association remain unclear. Experimental evidence supports a paradigm implicating inhibition of β-cell glucose transporters, delayed ATP production, pro-inflammatory and oxidative β-cell effects of plasma-derived cholesterol, inhibition of calcium channel-dependent insulin secretion, and β-cell apoptosis. SUMMARY: The aggregate of large clinical trials supports the notion that statins modestly increase the risk of incident diabetes. Because diabetes is a risk equivalent condition for coronary and peripheral arterial diseases, these findings create a paradox whereby needed statin therapy may be withheld to avoid excess risk of diabetes while representing the strongest cardiovascular risk reduction tool in diabetics. We simply recommend regular glucose monitoring in patients taking statins.

KW - β-cells

KW - cardiovascular disease

KW - diabetes

KW - low-density lipoprotein cholesterol

KW - statins

UR - http://www.scopus.com/inward/record.url?scp=79958861259&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79958861259&partnerID=8YFLogxK

U2 - 10.1097/HCO.0b013e3283470359

DO - 10.1097/HCO.0b013e3283470359

M3 - Article

C2 - 21499090

AN - SCOPUS:79958861259

VL - 26

SP - 342

EP - 347

JO - Current Opinion in Cardiology

JF - Current Opinion in Cardiology

SN - 0268-4705

IS - 4

ER -