Medical progressDyslipidemia in Youth with Diabetes: To Treat or Not to Treat?
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
References (93)
- et al.
The global spread of type 2 diabetes mellitus in children and adolescents
J Pediatr
(2005) - et al.
Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS), a multicentre randomised placebo-controlled trial
Lancet
(2004) - et al.
Total cholesterol and high-density lipoprotein levels in pediatric subjects with type 1 diabetes mellitus
J Pediatr
(2005) - et al.
Lipid abnormalities are prevalent in youth with type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth study
J Pediatr
(2006) - et al.
American Heart Association guidelines for primary prevention of atherosclerotic cardiovascular disease beginning in childhood
J Pediatr
(2003) - et al.
PDAY risk score predicts advanced coronary artery atherosclerosis in middle-aged persons as well as youth
Atherosclerosis
(2007) - et al.
Acute and chronic complications of type 2 diabetes mellitus in children and adolescents
Lancet
(2007) The prevention of diabetic microvascular complications of diabetes: is there a role for lipid lowering?
Diabetes Res Clin Pract
(2005)- et al.
Dietary intake among youth with diabetes: the SEARCH for Diabetes in Youth Study
J Am Diet Assoc
(2006) - et al.
Ezetimibe co-administered with simvastatin in patients with primary hypercholesterolemia
J Am Coll Cardiol
(2002)
Rates of progression of coronary calcium by electron beam tomography
Am J Cardiol
Coronary artery calcification, serum lipids, lipoproteins, and peripheral inflammatory markers in adolescents and young adults with type 1 diabetes
J Pediatr
Early onset of subclinical atherosclerosis in young persons with type 1 diabetes
J Pediatr
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
Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S)
Lancet
Statin treatment for children and adolescents with heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis
Atherosclerosis
The burden of diabetes mellitus among US youth: prevalence estimates from the SEARCH for Diabetes in Youth Study
Pediatrics
Variation and trends in incidence of childhood diabetes in Europe
Lancet
Increasing incidence of type 1 diabetes in 0- to 17-year-old Colorado youth
Diabetes Care
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
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
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
Factors affecting the relationship between childhood and adult cholesterol levels: the Muscatine Study
Pediatrics
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
Relation of glycohemoglobin and adiposity to atherosclerosis in youthThe Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group
Arterioscler Thromb Vasc Biol
Persistence of multiple cardiovascular risk clustering related to syndrome X from childhood to young adulthood
Arch Intern Med
Longitudinal changes in cardiovascular risk from childhood to young adulthood in offspring of parents with coronary artery disease: the Bogalusa Heart Study
JAMA
Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults: the Bogalusa Heart Study
N Engl J Med
Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study
JAMA
Risk factors identified in childhood and decreased carotid artery elasticity in adulthood: the Cardiovascular Risk in Young Finns Study
Circulation
The 30-year natural history of type 1 diabetes complications: the Pittsburgh Epidemiology of Diabetes Complications Study experience
Diabetes
Mortality and renal disease in type 1 diabetes mellitus: progress made, more to be done
J Clin Endocrinol Metab
Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes
N Engl J Med
Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes
Diabetologia
Risk factors for coronary heart disease in type 1 diabetic patients in Europe: the EURODIAB Prospective Complications Study
Diabetes Care
The MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial
Lancet
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
Longitudinal lipid screening and use of lipid-lowering medications in pediatric type 1 diabetes
J Pediatr
Management of dyslipidemia in children and adolescents with diabetes
Diabetes Care
Care of children and adolescents with type 1 diabetes: a statement from the American Diabetes Association
Diabetes Care
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
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
Atherosclerosis in childhood and adolescent type 1 diabetes: early disease, early treatment?
Diabetologia
Relation of serum lipoprotein levels and systolic blood pressure to early atherosclerosis: the Bogalusa Heart Study
N Engl J Med
Carotid intimal-medial thickness is related to cardiovascular risk factors measured from childhood through middle age: the Muscatine Study
Circulation
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
Cited by (39)
Piperine mitigates aortic vasculopathy in streptozotocin-diabetic rats via targeting TXNIP-NLRP3 signaling
2023, Life SciencesCitation 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 EndocrinologyCitation 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].
Glucose control predicts 2-year change in lipid profile in youth with type 1 diabetes
2013, Journal of PediatricsUpdate on Care of Children with Type 1 Diabetes
2012, Advances in PediatricsCitation 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.
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.