Should children with type 1 diabetes and dyslipidemia be treated with lipid-lowering medications?

Issue: November 2017

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Youths with type 1 diabetes should have adequate screening of lipid levels, and when indicated, they should benefit from the use of lipid-lowering medications to improve their vascular health.

Cardiovascular disease remains the leading cause of mortality in people with diabetes. This includes patients diagnosed with type 1 diabetes in childhood. Lipid-lowering medications, including statins, fibrates, bile acid sequestrants and newer medications, offer several effective options to manage dyslipidemia.

Data from studies in youths with familial hypercholesterolemia have demonstrated that use of statins is not only safe, but more effective when started at a younger age. Data from several studies in adults with diabetes have shown improved CVD outcomes in patients on lipid-lowering medications. More recently, a randomized controlled trial from Canas and colleagues demonstrated that the use of a statin effectively improved lipid profiles and was well-tolerated over a 6-month treatment period.

With positive results in short-term studies, there is now a need for longer-term studies starting in adolescence for at-risk patients with type 1 diabetes and dyslipidemia. Such studies will require use of surrogate markers or many years to determine the effects on CVD risk over decades. The need for such extensive studies should not discourage providers from prescribing statins and other lipid-lowering medications that have established safety profiles in youths with familial hypercholesterolemia as well as adults with diabetes. These medications have the potential to lower CVD risk for adolescents with type 1 diabetes.

This information combined with recommendations from the American Diabetes Association, American Heart Association and the International Society for Pediatric and Adolescent Diabetes provides the information and guidance needed for screening of lipids and treatment for those meeting criteria.

References:
Canas JA, et al. Pediatr Diabetes. 2015;doi:10.1111/pedi.12245.
de Jongh S, et al. Circulation. 2002;doi:10.1161/01.CIR.0000035247.42888.82.
Donaghue KC, et al. Pediatr Diabetes. 2014;doi:10.1111/pedi.12180.
Kavey RE, et al. Circulation. 2006;doi:10.1161/CIRCULATIONAHA.106.179568.
Silverstein J, et al. Diabetes Care. 2005;doi:10.2337/diacare.28.1.186.
R. Paul Wadwa, MD, is associate professor of pediatrics at the Barbara Davis Center for Diabetes, University of Colorado School of Medicine in Aurora. Disclosure: Wadwa reports no relevant financial disclosures.

Treating children with type 1 diabetes and dyslipidemia with lipid-lowering medications is of unclear benefit — and emerging harm.

Incidence of type 1 and type 2 diabetes appears to be increasing among youths. Within this cohort, 7% of affected youths were persistently dyslipidemic over 7 years’ follow-up, while 19% became newly dyslipidemic. Considering recent validation of cholesterol as a risk factor for CVD events among type 1 diabetes patients, the high prevalence of dyslipidemia coupled with rising diabetes rates elicits an impulse in compassionate providers to augment management with lipid-lowering medications. Prevailing national guidelines support this impulse by recommending lipid pharmacotherapy for children with type 1 diabetes and even mild dyslipidemia.

This impulse may need to be tempered by the ancient directive “primum non nocere.” In studies of adults using statins, adverse effects of concern have included myalgias or myopathy, transaminitis and alterations in the levels of cholesterol products, such as sex hormones. On balance, double-blind randomized controlled trials imply these effects are not caused by statins.

Nonetheless, these concerns, particularly with respect to subjective myalgias, are pervasive issues for practitioners. In children, data suggest no obvious safety signals with respect to these particular adverse events. However, the data quality in children is woefully inadequate. The pediatric statin literature consists of trial and observational data from less than 2 years’ follow-up. The longest cohort data are limited in generalizability due to a focus on familial hypercholesterolemia.

The focus on genetic dyslipidemia is especially problematic with respect to the most sinister adverse effect caused by statin use: incident diabetes. Occurring in roughly 0.1% of statin users per year, incident diabetes may be related to statin-induced changes in insulin sensitivity. Statins precipitating a change in insulin sensitivity or resistance should give pause to providers of patients with type 1 diabetes lest a combined type 1-type 2 picture emerge with concomitant higher insulin requirements or erratic glycemic swings.

In adults, the trade-off between CVD risk reduction vs. incident diabetes risk induction clearly favors lipid lowering. In youths, the effectiveness of long-term statin use in preventing CVD events is not proven in gold standard trials. Given the paradigm of trials lasting 5 years or less, the time lag until CVD event age means that trials for 15 to 20 years are not forthcoming. The best data on pediatric effectiveness are observational from genetic dyslipidemia patients at apparently lower diabetes risk. To the skeptic who argues that the trial data are not pointing to diabetes risk in statin-treated youths, acquiescence must be awarded. However, new observational data suggest statin-treated youths may be at 96% higher risk for subsequent diabetes. Therefore, the balance in statin-treated youths between proven CVD risk reduction and proven incident type 2 diabetes risk at a minimum deserves more scrutiny. Patients with type 1 diabetes and at higher risk for insulin resistance may be in special jeopardy from statins. Caveat doctor!

References:
Besseling J, et al. JAMA. 2015;doi:10.1001/jama.2015.1206.
Joyce NR, et al. Acad Pediatr. 2017;doi:10.1016/j.acap.2017.02.006.
Shah AS, et al. Diabetes Care. 2017;doi:10.2337/dc16-2193.
Justin P. Zachariah, MD, MPH, is assistant professor in pediatric cardiology at Baylor College of Medicine. Disclosure: Zachariah reports no relevant financial disclosures.