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Question: How should the risk of cardiovascular disease be reduced in children with diabetes?
Answer: Parents of children with diabetes often realize their kids will enter adulthood already bearing a long history of diabetes disease burden.
Understanding the fact that cardiovascular disease (CVD) is the leading cause of morbidity and mortality in adults with diabetes, it is increasingly common for parents to ask about cholesterol screening and risk-reduction strategies.
Dyslipidemia in childhood has been found to track into adulthood,1 so it is not unreasonable to assume that failure to address lipid disorders in youth with diabetes adds to CVD risk later in life.
For youth with type 1 diabetes, elevated triglyceride values have been reported in those with poorly controlled blood glucose levels, as have lower HDL levels compared to siblings.2 Children with type 2 diabetes have a similar pattern to adults, with the disease-elevated triglycerides, decreased HDL cholesterol, and normal-to-slightly elevated LDL with increased small, dense particles.
There is sufficient data supporting the role of dyslipidemia in the pathogenesis of atherosclerosis in youth.3–6 The American Diabetes Association (ADA) has published Care of Children and Adolescents with Type 1 Diabetes Mellitus7 and Management of Dyslipidemia in Children and Adolescents with Diabetes,2 which give specific recommendations to help pediatric providers reduce CVD risk.
LIPID SCREENING
For children older than age 2 with type 1 diabetes, there is no clear indication that a lipid screening examination is warranted. However, if there is a family history of hypercholesterolemia (total cholesterol >240 mg/dl) or a family history of a cardiovascular event before age 55—or if the family history is unknown—a fasting lipid profile should be performed at the time of diagnosis. (All lipid screens at diagnosis should be performed after glucose control has been established, and borderline or abnormal values should be repeated for confirmation.)
If values fall within the accepted risk levels, a lipid profile should be repeated every 5 years. For those with diabetes, optimal lipid levels are LDL <100 mg/dl, HDL >35 mg/dl, and triglycerides <150 mg/dl.
For pubertal children over age 12 with type 1 diabetes, a fasting lipid profile should be performed at diagnosis. If the initial screen is normal, the measurement should be repeated every 5 years.
All children with type 2 diabetes should have a lipid screen at diagnosis. If values are in the acceptable range, this screening should be repeated every 2 years.
THERAPY
Initial therapy should consist of optimization of glucose control and medical nutrition therapy aimed at a decrease in the amount of total and saturated fat in the diet, as well as encouragement of lifestyle changes to control weight, increase exercise, and, if applicable, discontinue tobacco use. In the face of elevated glucose levels that cannot be adequately controlled, treatment should be considered depending on lipid values and other risk factors.
The addition of lipid-lowering drugs is strongly recommended for LDL >160 mg/dl. It is also recommended in patients who have LDL cholesterol values of 130–159 mg/dl after failure of medical nutrition therapy and lifestyle changes. While there is no evidence that children with LDL values between 100 and 130 mg/dl should receive pharmacotherapy, I do consider this for my adolescent patients, depending on other risk factors.
The goal of pharmacologic therapy in adults is an LDL <100 mg/dl, and that likely should be the same for children placed on pharmacotherapy.8 It is not known what the duration of treatment should be in youth, but I consider weaning medication if LDL levels are <100 mg/dl for longer than 6 months and other risk factors have been modified.
In the past, the mainstay of drug therapy for dyslipidemia in children has been the bile acid sequestrants, including cholestyramine and colestipol. However, these agents have modest effects on cholesterol, lowering it just 10% to 25%, and they are not tolerated well. Aspirin therapy is not recommended in youth under age 21 due to the risk of Reyes syndrome. Short-term trials of HMG-CoA reductase inhibitors in children with familial hypercholesterolemia have shown they are safe and effective.9 Rigorous prospective studies of the effectiveness of HMG-CoA reductase inhibitors, ezetimibe, and fibric acid derivatives are needed in the pediatric diabetes population.
Pending clinical trials, physicians should consider adding lipid-lowering
drug therapy to the regimen of pubertal patients who have LDL cholesterol
values >100–130 mg/dl after step 2 diet intervention. This would be
of potential value as a primary preventive of CVD in the future. 
Footnotes
Do you have a clinical question? Send it to docnews{at}diabetes.org.
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References
2. American Diabetes Association: Management of dyslipidemia in
children and adolescents with diabetes. Diabetes Care 26: 2194–2197, 2003.
3. Berenson GS, Srinivasan SR, Bao W, et al., for the Bogalusa Heart
Study: Association between multiple cardiovascular risk factors and
atherosclerosis in children and young adults. N Engl J
Med 338:1650–1656, 1998.
4. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group: Relationship of atherosclerosis in young men to serum lipoprotein cholesterol concentrations. JAMA 264: 3018–3024, 1990.[Abstract]
5. Krantz JS, Mack WJ, Hodis HN, et al.: Early onset of subclinical atherosclerosis in young persons with type 1 diabetes. J Pediatr 145:452–457, 2004.[Medline]
6. NCEP Expert Panel on Blood Cholesterol: Levels in children and
adolescents: National Cholesterol Education Program (NCEP): highlights of the
Report of the Expert Panel on Blood Cholesterol Levels in Children and
Adolescents. Pediatrics 89:495–501, 1992.
7. Silverstein J, Klingensmith G, Copeland K, et al.: Care of children
and adolescents with type 1 diabetes. Diabetes Care 28: 186–212, 2005.
8. Orchard TJ, Forrest KY, Kuller LH, et al.: Lipid and blood pressure
treatment goals for type 1 diabetes. Diabetes Care 24: 1053–1059, 2001.
9. Stein EA, Illingworth DR, Kwiterovich PO, et al.: Efficacy and
safety of lovastatin in adolescent males with heterozygous familial
hypercholesterolemia: A randomized controlled trial.
JAMA 281:137–144, 1999.
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