Curriculum in CardiologyCardiovascular drugs that increase the risk of new-onset diabetes
Section snippets
Predictors of NOD
Studies in different populations have consistently identified the same cluster of risk factors for NOD. Impaired fasting glucose (IFG; defined as a fasting blood sugar from 100 to 125 mg/dL), a family history of diabetes, and features of the metabolic syndrome are associated with an increased risk of NOD.4 Lifestyle factors, low body mass index (BMI), diet, nonsmoking, moderate alcohol consumption, and regular physical activity were all associated with a reduced risk of NOD in a large cohort
Statins and NOD
In a meta-analysis of 13 large randomized placebo-controlled statin trials with 91,140 participants, of whom 4,278 developed diabetes during a mean follow-up of 4 years,8 statin treatment was associated with a 9% increased risk of diabetes (odds ratio [OR] 1.09, 95% CI 1.02-1.17). It was concluded from this meta-analysis that treatment for 225 patients with a statin for 4 years would result in one extra case of diabetes. The risk appeared to be similar for lipophilic and hydrophilic statins.
Niacin and NOD
The Coronary Drug Project was completed in 1975, but the results with respect to NOD were not published until 2013.26 During a mean follow-up of 6.2 years, the incidence of NOD was 11.4% in niacin-treated patients and 8.62% in the placebo group (HR 1.37, 95% CI 1.12-1.68, P = .012). Randomization to niacin treatment was associated with an increase in NOD both in those with a normal FBG at baseline (6.8% vs 4.9%, HR 1.41, 95% CI 0.97-2.05, P = .07) and in those with IFG (19.8% vs 15.2%, HR 1.34,
Thiazide diuretics and NOD
Shortly after the introduction of thiazide diuretics in the 1950s, it became apparent that they could worsen the control of established type 2 diabetes29 and increase the incidence of NOD.30 Despite this, thiazide diuretics continue to be recommended as first-line therapy for hypertension,31 although at lower doses than those used in the early trials. Calibrating the risk of NOD from clinical trials of antihypertensive drugs is complicated because the comparator drug is rarely placebo and may
ß-Blockers and NOD
ß-Blockers were recommended as first-line therapy for hypertensive patients with ischemic heart disease, according to the seventh Joint National Committee guidelines published in 2003.31 However, in the United Kingdom, ß-blockers have not been first- or second-line treatment since 2006.48 Recent meta-analyses suggest that for uncomplicated hypertension, compared with other antihypertensive drugs, ß-blockers are associated with an increased risk of stroke, especially in the elderly, with no
Prevention of drug-related NOD
Irrespective of whether or not drug-related NOD affects long-term CV risk, its prevention is important. New-onset diabetes increases the health care burden at both a population level and an individual level. The patient with NOD will likely require more medications, more medical visits, more laboratory tests, and glucose monitoring. In some health care systems, such a patient may have to pay more for health insurance. The cumulative effect of these changes is likely to worsen quality of life,
Acknowledgements
No extramural funding was used to support this work. The authors are solely responsible for the design and conduct of this work, the drafting and editing of the manuscript, and its final contents.
References (67)
Pre-diabetes, metabolic syndrome, and cardiovascular risk
J Am Coll Cardiol
(2012)- et al.
Risk scores based on self-reported or available clinical data to detect undiagnosed type 2 diabetes: a systematic review
Diabetes Res Clin Pract
(2012) - et al.
Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials
Lancet
(2010) - et al.
Predictors of new-onset diabetes in patients treated with atorvastatin. Results from 3 large randomized clinical trials
J Am Coll Cardiol
(2011) - et al.
Cardiovascular event reduction versus new-onset diabetes during atorvastatin therapy: effect of baseline risk factors for diabetes
J Am Coll Cardiol
(2013) - et al.
Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial
Lancet
(2012) - et al.
Atorvastatin causes insulin resistance and increased ambient glycemia in hyperglycemic patients
J Am Coll Cardiol
(2010) - et al.
Statin use and the risk of incident diabetes mellitus: a review of the literature
Can J Cardiol
(2012) - et al.
Cardiovascular therapies and associated glucose homeostasis: implications across the dysglycemia continuum
J Am Coll Cardiol
(2009) - et al.
Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis
Lancet
(2007)
Long-term effect of diuretic-based therapy on fatal outcomes in subjects with isolated systolic hypertension with and without diabetes
Am J Cardiol
A meta-analysis of 94,492 patients with hypertension treated with beta blockers to determine the risk of new-onset diabetes mellitus
Am J Cardiol
Opposing effects of β blockers and angiotensin-converting enzyme inhibitors on development of new-onset diabetes mellitus in patients with stable coronary artery disease
Am J Cardiol
Antihypertensive therapy and insulin sensitivity: do we have to redefine the role of beta-blocking agents?
Am J Hypertens
Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study
Lancet
Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the Treating to New Targets study
Lancet
IDF diabetes atlas update
Achievement of goals in U.S. diabetes care, 1999-2010
N Engl J Med
Trends in C-reactive protein levels in US adults from 1999 to 2010
Am J Epidemiol
Lifestyle factors and risk for new-onset diabetes: a population-based cohort study
Ann Intern Med
Prediction of incident diabetes mellitus in middle-aged adults: the Framingham Offspring Study
Arch Intern Med
Risk of incident diabetes with intensive-dose compared to moderate-dose statin therapy: a meta-analysis
JAMA
Atorvastatin in Factorial with Omega-3 EE90 Risk Reduction in Diabetes (AFORRD): a randomized controlled trial
Diabetalogia
The safety and tolerability of atorvastatin 10 mg in the Collaborative Atorvastatin Diabetes Study (CARDS)
Diab Vasc Dis Res
Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes
Diabetes Care
MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial
Lancet
Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial
Lancet
Efficacy of cholesterol-lowering therapy in 18 686 people with diabetes in 14 randomised trials of statins: a meta-analysis
Lancet
Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes
Diabetes Care
Distinct effects of pravastatin, atorvastatin, and simvastatin on insulin secretion from a beta-cell line, MIN6 cells
J Atheroscler Thromb
Effects of atorvastatin and pravastatin on glucose tolerance in diabetic rats mildly induced by streptozotocin
Biol Pharm Bull
Atorvastatin administration is associated with dose-related changes in IGF bioavailability
Eur J Endocrinol
Blunted Akt/FOXO signalling and activation of genes controlling atrophy and fuel use in statin myopathy
J Physiol
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Drug-induced hyperglycemia and diabetes
2024, TherapiesLiver fat accumulation assessed by computed tomography is an independent risk factor for diabetes mellitus in a population-based study: SESSA (Shiga Epidemiological Study of Subclinical Atherosclerosis)
2020, Diabetes Research and Clinical PracticeCitation Excerpt :And the effect of self-selection bias might remain. Finally, we did not consider the medication class effect which relate to insulin secretion or sensitivity although some of the antihypertensive and lipid-lowering agents were reported to be related with the new onset of diabetes [42] or reduce the risk of it [43–45]. In conclusion, the L/S ratio, indicating liver fat accumulation as assessed by CT, was associated with a higher risk for diabetes mellitus during a 5-year follow-up in a Japanese community-based study.
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2019, Archives des Maladies du Coeur et des Vaisseaux - PratiqueThe Evolution of Myocardial Infarction: When the Truths We Hold To Be Self-Evident No Longer Have Evidence
2017, Canadian Journal of CardiologyAgeing and fasting glucose values - The role of cardiovascular events
2015, European Geriatric MedicineCitation Excerpt :Our evaluation reveals some limitations, because the study participants were patients attending a medical outdoor center. A further critical aspect is the influence of cardiovascular medication with an influence on the risk of new-onset diabetes [38], especially regarding the effects of statin therapy with a possible association between statin use and incident diabetes in patients with underlying risk factors [39]. However, fasting glucose levels were already higher at entry to the evaluation – and thus years before the cardiovascular complication – in patients with a future CVE.
New-onset diabetes and statins: Throw the bath water out, but, please, keep the baby!
2015, Metabolism: Clinical and Experimental
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K.L.O. was supported by the program grant (1037903) from the National Health and Medical Research Council of Australia and a Grant-in-Aid (G 12S 6681) from the National Heart Foundation of Australia.