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Reviews/Commentaries/Position Statements

C O N S E N S U S S T A T E M E N T

Management of Dyslipidemia in Children


and Adolescents With Diabetes
AMERICAN DIABETES ASSOCIATION Cholesterol Education Program Adult
Treatment Panel (NCEP/ATP III) (5),
childhood obesity is seen as a risk factor
for development of the syndrome in
adulthood (11–13).

M
any studies have demonstrated 4) What is the frequency for monitor-
that the atherosclerotic process ing lipid levels in children with diabetes?
begins in childhood in association 5) How should elevated lipid levels be QUESTION 2: DO LIPID
with high blood cholesterol levels (1–3). treated? LEVELS TRACK FROM
Lipid levels show a strong familial aggre- 6) What additional research needs to CHILDHOOD TO
gation that has both a genetic and envi- be done in this area? ADULTHOOD?
ronmental component (4). Monogenic Children and adolescents with high cho-
disorders including familial hypercholes- lesterol levels are more likely than the
terolemia and familial combined hyper- QUESTION 1: ARE THERE general population to have high levels
lipidemia are expressed in childhood, SPECIFIC LIPID when they become adults (14,15). In the
ABNORMALITIES IN general population, total cholesterol lev-
although adverse diet, polygenic disor-
CHILDREN WITH DIABETES? els are generally 40 mg/dl higher in adults
ders, and environmental causes (includ-
There are insufficient data available to an- than in childhood. While most children
ing obesity) are the most common causes
swer this question. Most reviews specu- with high cholesterol levels will also have
of high cholesterol levels in children.
late that the abnormalities seen in adults high levels as adults, some children with
Adult patients with diabetes are at sig-
with diabetes are also seen in children/ high levels will have normal levels as
nificant risk for cardiovascular disease
adolescents. In children with type 1 dia- young adults. This is in part related to the
(CVD). Because the combination of dia- betes, the pathogenesis of the disease dramatic decrease in total cholesterol seen
betes and dyslipidemia accelerates would not suggest the presence of specific as children progress through puberty
atherogenesis, aggressive lipid manage- lipid abnormalities; however, elevated (16). Data from the Bogalusa Heart Study
ment is suggested for such patients (5). triglycerides would be expected in pa- (1) and the Muscatine study (14), how-
While the American Diabetes Association tients with poorly controlled blood glu- ever, clearly show that cholesterol and
has stated lipid goals for adults with dia- cose levels. The Pittsburgh Diabetes other cardiovascular risk factors often
betes (6), no similar guidelines exist for Clinic found differences between diabetic persist from childhood to adulthood. For
children. To address this issue, a panel of patients and their siblings in an HDL sub- example, the development of obesity in
experts in the areas of pediatric endocri- fraction, but other lipid levels were not childhood predicts a similarly elevated
nology, pediatric cardiology, and pediat- significantly different (7). weight as an adult. The tracking correla-
ric nephrology met on the 28th and 29th In children with type 2 diabetes, the tion coefficients for dyslipidemia suggest
of July 2002 to hear presentations, review patterns seen in adults with type 2 diabe- that most but not all children with lipid
current lipid guidelines for children in tes, i.e., elevated triglycerides, normal to abnormalities will have them as adults
general, and formulate a set of recommen- slightly elevated LDL cholesterol levels (14).
dations regarding the lipid management (with an increase of the small, dense LDL
of children with diabetes. The panel was subfraction), and decreased HDL choles- QUESTION 3: DOES
asked to develop a consensus position on terol levels (8,9) are also seen. Because ATHEROSCLEROSIS BEGIN
the following questions: severe obesity is associated with the pre- IN CHILDHOOD? IS THIS
1) Are there specific lipid abnormali- mature onset of type 2 diabetes in adoles- RELATED TO
ties documented in children with diabe- cence and dyslipidemia is generally found DYSLIPIDEMIA?
tes? in overweight/obese children, the coexist- Autopsy studies demonstrate that aortic
2) Do lipid levels track from child- ence of both risk factors should be ex- and coronary atherosclerosis are com-
hood to adulthood? pected and may contribute to dyslipide- monly seen before age 20 years (1–3).
3) Does atherosclerosis begin in mia (10). Since obesity and dyslipidemia High serum total cholesterol, LDL choles-
childhood? Is this related to dyslipide- are part of the “metabolic syndrome,” as terol, very-low-density lipoprotein (VLDL)
mia? defined by the third report of the National cholesterol levels, and low HDL choles-
terol levels are correlated with the extent
● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● of early atherosclerotic lesions in adoles-
Address correspondence and reprint requests to Nathaniel Clark, MD, MS, RD, American Diabetes Associ- cents and young adults. For example, in
ation, 1701 N. Beauregard St., Alexandria, VA 22311. E-mail: nclark@diabetes.org. the Bogalusa studies, antemortum total
Abbreviations: AHA, American Heart Association; CVD, cardiovascular disease; LFT, liver function test.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion
and LDL cholesterol levels, blood pres-
factors for many substances. sure, BMI, and fasting insulin were all
© 2003 by the American Diabetes Association. positively correlated with aortic and cor-

2194 DIABETES CARE, VOLUME 26, NUMBER 7, JULY 2003


American Diabetes Association

onary artery fatty streaks and plaques Table 1—Management of dyslipidemia in children/adolescents with diabetes
(1,2). The Pathobiological Determinants Screening
of Atherosclerosis in Youth (PDAY) study After glycemic control is achieved
(3) reported that LDL cholesterol, severe Type 1
obesity, and elevated glycohemoglobin Obtain lipid profile at diagnosis and then, if normal, every 5 years
levels were significantly correlated with Begin at age 12 years (or onset of puberty, if earlier)
the postmortem diagnosis of coronary Begin prior to age 12 years (if prepubertal) only if positive family history
atherosclerosis in 15- to 35-year-olds Type 2
(17). In the Muscatine study (18), in- Obtain lipid profile at diagnosis and then every 2 years
creased BMI and blood pressure and de- Goals
creased HDL correlated with the early LDL ⬍100 mg/dl
development of coronary calcification, HDL ⬎35 mg/dl
considered a marker for atherosclerosis. Triglycerides ⬍150 mg/dl
The prevalence of coronary calcium in ad- Treatment strategies
olescents with familial hypercholesterol- Diet
emia is ⬃25%, and the presence of Maximize glycemic control
calcium is more likely in those with the Weight reduction, if indicated
highest BMI (19). Medications
Identified risk factors contributing to Age ⬎10 years
the early onset of CHD in children/ LDL ⱖ160 mg/dl
adolescents include (20): LDL 130–159 mg/dl: consider based on CVD risk profile
Statins ⫾ resins
● Elevated LDL Fibric acid derivatives if triglycerides ⬎1,000 mg/dl
● Family history of premature (aged ⬍55 Manage other CVD risk factors
years) coronary heart disease, CVD, or Blood pressure
peripheral vascular disease Tobacco
● Smoking Obesity
● Hypertension Inactivity
● HDL ⬍35 mg/dl
● Obesity (ⱖ95th percentile weight for
height on National Center For Health achieved and should be repeated every 5 QUESTION 5: HOW
Statistics (NCHS) growth chart) years if the initial screen is normal. SHOULD ELEVATED LIPID
● Physical inactivity In those ⬍12 years of age (generally LEVELS BE TREATED?
● Diabetes prepubertal), in the absence of a parental Treatment recommendations, as noted in
history of dyslipidemia or early coronary Table 1, are similar to established pediat-
heart disease, there is no clear indication ric guidelines (20 –23) with modifications
QUESTION 4: WHAT IS THE
for a screening lipid exam. in response to the higher CVD risk status
FREQUENCY FOR
of patients with diabetes. For children in
MONITORING LIPID LEVELS
Type 2 diabetes general, “borderline” levels of total cho-
IN CHILDREN WITH
Children should be screened at diagnosis lesterol and LDL are defined as 170 –199
DIABETES?
regardless of age but after glycemic con- and 110 –129 mg/dl, respectively. “Elevat-
As noted in Table 1, monitoring should
trol is achieved. If normal lipid values are ed” levels are ⬎200 mg/dl for total cho-
closely follow recommendations cur-
obtained, screening should be repeated lesterol and ⬎130 mg/dl for LDL
rently made for children in general (20 –
every 2 years. cholesterol.
23). That is, lipid levels should be
Optimal lipid levels for children with Whereas previous recommendations
measured initially in children (⬎2 years
diabetes are based on a synthesis of cur- (20,21) suggested a progression from
of age) only in the presence of a positive
rent pediatric recommendations and cur- AHA step 1 to step 2 diet utilization, more
family history (a parental total cholesterol
rent recommendations for adults with recent recommendations suggest the use
level ⱖ240 mg/dl and/or a cardiovascular
diabetes, which recognize that the pres- of the AHA step 2 diet (dietary cholesterol
event in a parent before age 55 years). The
ence of diabetes is now considered a cor- ⬍200 mg/day and saturated fat ⬍7% of
preferred test is the fasting lipid profile. In
onary heart disease equivalent (5,20 –23). total calories) initially upon confirmation
children with diabetes, we recommend
Optimal lipid levels for those with diabe- of hyperlipidemia (23). Drug therapy has
modifications in this protocol based on
tes, as defined here and noted in Table 1, been recommended in children ⬎10
the type of diabetes and the age of the
are in accord with those of the Third years of age if, after an adequate trial of
child.
Adult Treatment Panel (5) and the Amer- dietary therapy, LDL levels remain ⱖ190
ican Heart Association (AHA) (23): mg/dl in those with no CVD risk factors or
Type 1 diabetes ⬎160 mg/dl in those with CVD risk fac-
In those ⬎12 years of age (assumed to be ● LDL ⬍100 mg/dl tors, such as a positive family history, hy-
pubertal), screening should be done at di- ● HDL ⬎35 mg/dl pertension, obesity, and diabetes (20,21).
agnosis but after glycemic control is ● Triglycerides ⬍150 mg/dl The goal LDL is ⬍130 mg/dl for children

DIABETES CARE, VOLUME 26, NUMBER 7, JULY 2003 2195


Management of dyslipidemia

in general and ⬍100 mg/dl in those with toring of creatine phosphokinase levels is ● The influence of diet on hyperlipidemia
diabetes (23). not felt to be helpful. In addition, the use and the treatment of obesity (specifical-
Based on the above considerations, of statins in sexually active adolescent fe- ly high- versus low-carbohydrate diets)
the panel recommends the following for males must be very carefully considered needs clarification.
children and adolescents with lipid values and the risks explicitly discussed, as these
greater than the optimal levels, as noted drugs are not approved in pregnancy. ● The influence of demographic charac-
above. teristics (e.g., race, gender) on the prog-
3) Elevated triglyceride levels are not di- nosis of abnormal lipid levels should be
1) Blood glucose control should be max- rectly managed with medication. If the studied.
imized and dietary counseling should be tryglyceride level is ⱖ150 mg/dl, one
provided. Dietary change has been docu- should enhance efforts to maximize blood
APPENDIX
mented to reduce LDL levels (24). The glucose control and achieve desirable
use of products such as Benachol marga- weight. If triglycerides are ⱖ1,000 mg/dl,
Consensus panel members
rine and increasing amounts of soluble fi- significantly increased risk of pancreatitis
Francine R. Kaufman, MD (Chair); Silva
ber should be considered as part of the is present, and treatment with a fibric acid
Arslanian, MD; Gerald Berenson, MD;
dietary approach. Follow-up fasting lipid medication should be considered.
Nathaniel G. Clark, MD, MS, RD; Samuel
profiles should be performed at 3 months Gidding, MD; Kenneth Lee Jones, MD;
and then at 6 months to determine the 4) The cardiovascular risk approach to
Ronald Lauer, MD; Richard Schieken,
effects of blood glucose management and children with diabetes should be compre-
MD; and Alan R. Sinaiko, MD.
dietary change. If treatment goals are hensive. Thus, blood pressure should be
achieved, the lipid profile should be re- regularly measured, anti-tobacco coun-
peated yearly. If after 6 months of opti- seling provided, physical activity encour-
aged, and obesity managed (8,9,22,23). References
mized blood glucose control and dietary 1. Berenson G, Srinivasan S, Bao W, New-
intervention there is no significant im- man W, Tracy R, Wattigney W, for the
provement in lipid parameters, further in- Bogalusa Heart Study: Association be-
QUESTION 6: WHAT
tervention is warranted based on LDL tween multiple cardiovascular risk factors
ADDITIONAL RESEARCH
levels shown below: and atherosclerosis in children and young
NEEDS TO BE DONE IN THIS
adults. N Engl J Med 338:1650 –1656,
AREA? 1998
● LDL 100 –129 mg/dl: maximize non- 2. Newman W, Freedman D, Voors A, Gard
pharmacologic treatment. Important research questions P, Srinivasan S, Cresanta J, Williamson
● LDL 130 –159 mg/dl: “consider” medi- The panel identified a number of critical GD, Webber L, Berenson G: Relation of
cation, basing the treatment decision areas of research: serum lipoprotein levels and systolic
on the child’s complete CVD risk pro- blood pressure to early atherosclerosis.
file, including assessment of blood ● Longitudinal tracking of lipid levels in
N Engl JMed 314:138 –144, 1986
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children with type 1 and type 2 diabetes R, Newman W, Herderick E, Cornhill JF,
status. are needed, as well as studies regarding
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the relationship of glycemic control and Atherosclerosis in Youth Research Group
exercise to lipid levels. (PDAY): Prevalence and extent of athero-
2) Resins (bile acid sequestrants) continue sclerosis in adolescents and young adults:
to be generally recommended as first- ● Studies are needed on the transition implications for prevention from the
choice treatments in this age group; how- from obesity or insulin resistance to the Pathobiological Determinants of Athero-
ever, compliance rates with this class of onset of type 2 diabetes to determine at sclerosis in Youth Study. JAMA 281:727–
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4. Kwiterovich PO Jr: Biochemical, clinical,
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should also be considered. Despite con- whether dyslipidemia precedes or is co- data in the pediatric age group relevant to
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the lowest available dose and dose in- (carotid intimal medial thickening, in Adults: Executive Summary of the
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side effects. Liver function tests (LFTs) vascular resistance, and vascular com- Education Program (NCEP) Expert Panel
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2196 DIABETES CARE, VOLUME 26, NUMBER 7, JULY 2003


American Diabetes Association

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