Elsevier

The Journal of Pediatrics

Volume 153, Issue 4, October 2008, Pages 458-465.e4
The Journal of Pediatrics

Medical progress
Dyslipidemia in Youth with Diabetes: To Treat or Not to Treat?

https://doi.org/10.1016/j.jpeds.2008.05.062Get rights and content

Section snippets

Data on Atherosclerosis in Youth

Landmark studies, such as the Bogalusa Heart Study,33 the Muscatine Study,34 the Young Finns Study,14 and the Pathobiologic Determinants of Atherosclerosis in Youth (PDAY) study,35 have demonstrated that the atherosclerotic process begins in childhood and that the extent of atherosclerosis (based on postmortem examination or use of surrogate markers of atherosclerosis) is related to the presence and degree of CVD risk factors. Although hyperglycemia was considered an important CVD risk factor

Data on Lipids in Youth with Diabetes

Recent data indicate the existence of dyslipidemia in youth with DM. In an earlier retrospective cross-sectional analysis, we found that 18.6% of children with T1D had an abnormal total cholesterol (TC) (>200 mg/dL) or high-density lipoprotein cholesterol (HDL-c) (<35 mg/dL) level.23 Longitudinal analysis of data from the same clinic population revealed sustained abnormalities in a similar range.26 HbA1c was significantly related to TC and non–HDL-c (calculated as TC minus HDL-c), and body mass

Data on Lipids in Adults with DM

Although lipid levels in patients with T1D have been found to be comparable to or better than those in nondiabetic adults (lower TC, LDL-c, and triglyceride and higher HDL-c levels),45 adults with T1D still commonly have dyslipidemia and are known to be at greater risk for atherosclerotic disease compared with the general population. Dyslipidemia clearly is a major risk factor for atherosclerosis and CVD in adults with both T1D and T2D.7 The NCEP considers the presence of DM to be the risk

Screening and Treatment

The ADA in 2003 and 2005 recommended screening for dyslipidemia in patients with T1D age ≥2 years in the presence of a positive or unknown family history or at age ≥12 years (once glycemic control has been obtained in a newly diagnosed patient) otherwise, and then every 5 years thereafter if normal, and at diagnosis and every 2 years in patients with T2D27, 28 (Table I; available at www.jpeds.com). Ideally, the ADA recommends that screening samples be obtained in the fasting state. But given

Contrasts in Current ADA and AHA Guidelines

The recent AHA guidelines for dyslipidemia screening and treatment in youth with DM include lower LDL-c cutpoints for treatment (<100 mg/dL) than previous AHA and ADA guidelines, as well as a lower age limit of 10 years. Both the AHA and ADA recommend therapeutic lifestyle changes as a first step before pharmacologic treatment. In addition, although the AHA guidelines stress that most patients with T2D will have 2 or more additional CVD risk factors and thus be classified as tier I, or high

Clinical Trials to Treat Dyslipidemia in Youth with Diabetes

Although treatment goals for dyslipidemia in adults with DM have become more aggressive,53 awareness of elevated CVD risk in DM has increased,6, 7, 18 and the first treatment recommendations for dyslipidemia in youth with DM have been published,27, 28, 29, 30 no clinical trials of medications to treat dyslipidemia in youth with DM have been reported to date. The risk exists that these medications may start to be used routinely in youth with DM in the absence of safety or efficacy data from

Surrogate Noninvasive Measures of Subclinical CVD

Multiple noninvasive techniques for assessing cardiovascular risk have been reviewed recently.69, 70 Electron beam computed tomography to evaluate coronary artery calcification has been used in adults,71, 72, 73 but no coronary artery calcification was detected in an adolescent T1D population.74 B-mode ultrasonography to evaluate carotid IMT has demonstrated increased IMT in youth with T1D.75, 76, 77 In youth, the CVD risk from T1D has been compared with that of familial hypercholesterolemia,

Discussion

We must emphasize that because no prospective data exist on safety, cost, or outcomes on dyslipidemia medications in adolescents with DM, how aggressively CVD risk factors should be treated in this population remains uncertain. Because of the lack of clinical trial data, the current controversy surrounding treating dyslipidemia in youth with DM (Table III; available at www.jpeds.com) could be considered analogous to the pre–Diabetes Control and Complications Trial debates on the wisdom of tight

First page preview

First page preview
Click to open first page preview

References (93)

  • M.J. Budoff et al.

    Rates of progression of coronary calcium by electron beam tomography

    Am J Cardiol

    (2000)
  • P. Gunczler et al.

    Coronary artery calcification, serum lipids, lipoproteins, and peripheral inflammatory markers in adolescents and young adults with type 1 diabetes

    J Pediatr

    (2006)
  • J.S. Krantz et al.

    Early onset of subclinical atherosclerosis in young persons with type 1 diabetes

    J Pediatr

    (2004)
  • E.M. Urbina et al.

    Impact of multiple coronary risk factors on the intima-media thickness of different segments of carotid artery in healthy young adultsThe Bogalusa Heart Study

    Am J Cardiol

    (2002)
  • T.E. Strandberg et al.

    Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S)

    Lancet

    (2004)
  • C. Arambepola et al.

    Statin treatment for children and adolescents with heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis

    Atherosclerosis

    (2007)
  • A.D. Liese et al.

    The burden of diabetes mellitus among US youth: prevalence estimates from the SEARCH for Diabetes in Youth Study

    Pediatrics

    (2006)
  • Variation and trends in incidence of childhood diabetes in Europe

    Lancet

    (2000)
  • K. Vehik et al.

    Increasing incidence of type 1 diabetes in 0- to 17-year-old Colorado youth

    Diabetes Care

    (2007)
  • M.E. Pavkov et al.

    Effect of youth-onset type 2 diabetes mellitus on incidence of end-stage renal disease and mortality in young and middle-aged Pima Indians

    JAMA

    (2006)
  • P. Libby et al.

    Report of the National Heart, Lung, and Blood Institute–National Institute of Diabetes and Digestive and Kidney Diseases Working Group on Cardiovascular Complications of Type 1 Diabetes Mellitus

    Circulation

    (2005)
  • J.B. Buse et al.

    Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association

    Diabetes Care

    (2007)
  • R.M. Lauer et al.

    Factors affecting the relationship between childhood and adult cholesterol levels: the Muscatine Study

    Pediatrics

    (1988)
  • H.C. McGill et al.

    Effects of serum lipoproteins and smoking on atherosclerosis in young men and womenThe Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group

    Arterioscler Thromb Vasc Biol

    (1997)
  • H.C. McGill et al.

    Relation of glycohemoglobin and adiposity to atherosclerosis in youthThe Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group

    Arterioscler Thromb Vasc Biol

    (1995)
  • W. Bao et al.

    Persistence of multiple cardiovascular risk clustering related to syndrome X from childhood to young adulthood

    Arch Intern Med

    (1994)
  • W. Bao et al.

    Longitudinal changes in cardiovascular risk from childhood to young adulthood in offspring of parents with coronary artery disease: the Bogalusa Heart Study

    JAMA

    (1997)
  • G.S. Berenson et al.

    Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults: the Bogalusa Heart Study

    N Engl J Med

    (1998)
  • O.T. Raitakari et al.

    Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study

    JAMA

    (2003)
  • M. Juonala et al.

    Risk factors identified in childhood and decreased carotid artery elasticity in adulthood: the Cardiovascular Risk in Young Finns Study

    Circulation

    (2005)
  • G. Pambianco et al.

    The 30-year natural history of type 1 diabetes complications: the Pittsburgh Epidemiology of Diabetes Complications Study experience

    Diabetes

    (2006)
  • D.M. Maahs et al.

    Mortality and renal disease in type 1 diabetes mellitus: progress made, more to be done

    J Clin Endocrinol Metab

    (2006)
  • D.M. Nathan et al.

    Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes

    N Engl J Med

    (2005)
  • S.P. Laing et al.

    Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes

    Diabetologia

    (2003)
  • S.S. Soedamah-Muthu et al.

    Risk factors for coronary heart disease in type 1 diabetic patients in Europe: the EURODIAB Prospective Complications Study

    Diabetes Care

    (2004)
  • R. Collins et al.

    The MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial

    Lancet

    (2003)
  • K.O. Schwab et al.

    Spectrum and prevalence of atherogenic risk factors in 27 358 children, adolescents, and young adults with type 1 diabetes: cross-sectional data from the German diabetes documentation and quality management system (DPV)

    Diabetes Care

    (2006)
  • D.M. Maahs et al.

    Longitudinal lipid screening and use of lipid-lowering medications in pediatric type 1 diabetes

    J Pediatr

    (2007)
  • F.R. Kaufman et al.

    Management of dyslipidemia in children and adolescents with diabetes

    Diabetes Care

    (2003)
  • J. Silverstein et al.

    Care of children and adolescents with type 1 diabetes: a statement from the American Diabetes Association

    Diabetes Care

    (2005)
  • R.E. Kavey et al.

    Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research, endorsed by the American Academy of Pediatrics

    Circulation

    (2006)
  • B.W. McCrindle et al.

    Drug therapy for high-risk lipid abnormalities in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, with the Council on Cardiovascular Nursing

    Circulation

    (2007)
  • K. Dahl-Jorgensen et al.

    Atherosclerosis in childhood and adolescent type 1 diabetes: early disease, early treatment?

    Diabetologia

    (2005)
  • W.P. Newman et al.

    Relation of serum lipoprotein levels and systolic blood pressure to early atherosclerosis: the Bogalusa Heart Study

    N Engl J Med

    (1986)
  • P.H. Davis et al.

    Carotid intimal-medial thickness is related to cardiovascular risk factors measured from childhood through middle age: the Muscatine Study

    Circulation

    (2001)
  • Relationship of atherosclerosis in young men to serum lipoprotein cholesterol concentrations and smoking: a preliminary report from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group

    JAMA

    (1990)
  • Cited by (39)

    • Piperine mitigates aortic vasculopathy in streptozotocin-diabetic rats via targeting TXNIP-NLRP3 signaling

      2023, Life Sciences
      Citation Excerpt :

      PIP significantly lowered serum AGEs levels in diabetic rats, an effect that might be attributed to its hypoglycemic effect. Dyslipidemia is a common metabolic abnormality in patients with type 1 diabetes, which markedly increases the risk of cardiovascular disease [38]. In this research, STZ rats developed dyslipidemia, which was demonstrated by elevated serum levels of TGs, TCs, and LDL-C. Daily treatment with PIP attenuated the elevated TGs, TCs, and LDL-C levels in diabetic rats.

    • Higher hemoglobin A1C and atherogenic lipoprotein profiles in children and adolescents with type 2 diabetes mellitus

      2019, Journal of Clinical and Translational Endocrinology
      Citation Excerpt :

      ApoB has been shown in epidemiological studies to be significantly elevated in children with T2DM despite normal concentrations of LDL-C [13]. The number and size of LDL particles play a role in atherogenicity [8,14–16]. To our knowledge, few studies have reported on the lipoprotein profiles of children with T2DM [7,12,13].

    • Update on Care of Children with Type 1 Diabetes

      2012, Advances in Pediatrics
      Citation Excerpt :

      If treatment is recommended, currently approved lipid-lowering medications include bile acid sequestrants and statins. Despite these recommendations, only a small percentage of those with dyslipidemia are started on lipid-lowering therapy [75], with 0.4% of patients in the DPV study on lipid-lowering medication [78]. Cardiovascular disease continues to be a major cause of death, with a diagnosis of T1D increasing one’s risk of cardiovascular disease significantly.

    View all citing articles on Scopus

    Drs Maahs, Wadwa, Klingensmith, and Rewers have received a grant (but no salary support) from Merck/Schering Plough Investigator Initiated Study Program Grant for a clinical trial evaluating the safety and efficacy of lipid-lowering medications in youth with type 1 diabetes and elevated LDL-c. Dr Maahs is supported by National Institute of Diabetes and Digestive and Kidney Diseases grant K23 DK075360.

    View full text