Lipid and Lipoprotein Profiles in Youth With and Without Type 1 Diabetes The SEARCH for Diabetes in Youth Case-Control Study

ArticleinDiabetes care 32(3):416-20 · December 2008with32 Reads
Impact Factor: 8.42 · DOI: 10.2337/dc08-1775 · Source: PubMed
Abstract

The purpose of this study was to compare the lipid profile and the prevalence of lipid abnormalities in youth with and without type 1 diabetes and explore the role of glycemic control on the hypothesized altered lipid profile in youth with type 1 diabetes. We conducted a cross-sectional analysis of 512 youth with type 1 diabetes (mean duration 4.22 years) and 188 healthy control subjects aged 10-22 years in Colorado and South Carolina. SEARCH for Diabetes in Youth (SEARCH) participants with type 1 diabetes and healthy control subjects recruited from primary care offices in the same geographic regions were invited to attend a research visit. Fasting lipid profiles were compared between youth with type 1 diabetes (stratified according to categories of optimal [A1C <7.5%] and suboptimal [A1C >or=7.5%] glycemic control) and healthy nondiabetic youth, using multiple linear and logistic regression. Youth with type 1 diabetes and optimal A1C had lipid concentrations that were similar (total cholesterol, LDL cholesterol, and LDL particle size) or even less atherogenic (HDL cholesterol, non-HDL cholesterol, triglyceride, and triglyceride-to-HDL cholesterol ratio) than those observed in nondiabetic youth, whereas youth with suboptimal glycemic control had elevated standard lipid levels (total cholesterol, LDL cholesterol, and non-HDL cholesterol). Youth with type 1 diabetes also had significantly elevated apolipoprotein B levels and more small, dense LDL particles than nondiabetic youth, regardless of glycemic control. Youth with type 1 diabetes have abnormal lipid levels and atherogenic changes in lipoprotein composition, even after a relatively short disease duration. As in adults, glycemic control is an important mediator of these abnormalities.

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Available from: Dana Dabelea
Lipid and Lipoprotein Profiles in Youth
With and Without Type 1 Diabetes
The SEARCH for Diabetes in Youth Case-Control Study
JOHN GUY,
MPH
1
LORRAINE OGDEN,
PHD
2
R. PAUL WADWA,
MD
3
RICHARD F. HAMMAN,
MD, DRPH
1
ELIZABETH J. MAYER-DAVIS,
PHD
4
ANGELA D. LIESE,
PHD
5
RALPH D’AGOSTINO,JR.,
PHD
6
SANTICA MARCOVINA,
PHD
7
DANA DABELEA,
MD, PHD
1
OBJECTIVE The purpose of this study was to compare the lipid profile and the prevalence
of lipid abnormalities in youth with and without type 1 diabetes and explore the role of glycemic
control on the hypothesized altered lipid profile in youth with type 1 diabetes.
RESEARCH DESIGN AND METHODS We conducted a cross-sectional analysis of
512 youth with type 1 diabetes (mean duration 4.22 years) and 188 healthy control subjects
aged 10–22 years in Colorado and South Carolina. SEARCH for Diabetes in Youth
(SEARCH) participants with type 1 diabetes and healthy control subjects recruited from
primary care offices in the same geographic regions were invited to attend a research visit. Fasting
lipid profiles were compared between youth with type 1 diabetes (stratified according to cate-
gories of optimal [A1C 7.5%] and suboptimal [A1C 7.5%] glycemic control) and healthy
nondiabetic youth, using multiple linear and logistic regression.
RESULTS Youth with type 1 diabetes and optimal A1C had lipid concentrations that were
similar (total cholesterol, LDL cholesterol, and LDL particle size) or even less atherogenic (HDL
cholesterol, non-HDL cholesterol, triglyceride, and triglyceride–to–HDL cholesterol ratio) than
those observed in nondiabetic youth, whereas youth with suboptimal glycemic control had
elevated standard lipid levels (total cholesterol, LDL cholesterol, and non-HDL cholesterol).
Youth with type 1 diabetes also had significantly elevated apolipoprotein B levels and more small,
dense LDL particles than nondiabetic youth, regardless of glycemic control.
CONCLUSIONS Youth with type 1 diabetes have abnormal lipid levels and atherogenic
changes in lipoprotein composition, even after a relatively short disease duration. As in adults,
glycemic control is an important mediator of these abnormalities.
Diabetes Care 32:416–420, 2009
D
iabetes is a major risk factor for car-
diovascular disease (CVD) (1). In
patients with type 1 diabetes, ath-
erosclerosis occurs earlier in life, leading
to increased morbidity and mortality
compared with those in the general pop-
ulation (2). Moreover, studies of the natural
history of atherosclerosis development
point to an origin of the lesions in childhood
and adolescence (3).
Lipid concentrations are strongly re-
lated to the risk of CVD in adults with
diabetes (4), Although lipid levels in
adults with type 1 diabetes have been de-
scribed as comparable to those in nondi-
abetic individuals (5), adults with type 1
diabetes are known to have a higher risk
for atherosclerotic disease compared
with that of the general population (2).
The SEARCH for Diabetes in Youth
(SEARCH) study recently showed that a
substantial proportion of youth aged
10–22 years with type 1 diabetes had
lipid levels outside the recommended tar-
gets (6). However, it is not known
whether the lipid profile (lipid concentra-
tions and lipoprotein composition) in
youth with type 1 diabetes is proathero-
genic compared with that in healthy non-
diabetic youth. Some data suggest that, in
adults with diabetes, lipoprotein compo-
sition is more atherogenic (7) and is sub-
stantially influenced by glycemic control
(8). The goals of this study were to com-
pare the lipid and lipoprotein profile, as
measured by total cholesterol, LDL cho-
lesterol, HDL cholesterol, triglycerides,
non-HDL cholesterol, the triglyceride–
to–HDL cholesterol ratio, apolipoprotein
B (apoB), and LDL particle size and den-
sity in youth with and without type 1 di-
abetes, and to explore the role of glycemic
control, as measured by A1C, on the hy-
pothesized altered lipid profile in type 1
diabetic youth.
RESEARCH DESIGN AND
METHODS Data for this analysis
derive from the SEARCH Case-Control
Study, an ancillary study to SEARCH (9).
SEARCH is a multicenter study that con-
ducts population-based ascertainment of
nongestational cases of physician-
diagnosed diabetes in youth.
SEARCH Case-Control was designed
to assess selected risk factors for child-
hood diabetes in young individuals aged
10–22 years recruited specifically at the
Colorado and South Carolina SEARCH
sites. Diabetes cases were identified at
both sites using a network of health care
providers. All youth aged 10 years who
participated in the SEARCH study visit
between July 2003 and March 2006 in
Colorado and South Carolina and were of
●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●
From the
1
Department of Epidemiology, Colorado School of Public Health, University of Colorado, Denver,
Colorado; the
2
Department of Biostatistics and Informatics, Colorado School of Public Health, University
of Colorado, Denver, Colorado; the
3
Barbara Davis Center, University of Colorado, Denver, Colorado; the
4
Nutrition Department, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; the
5
Department of Epidemiology and Biostatistics and Center for Research in Nutrition and Health Dispar-
ities, University of South Carolina, Columbia, South Carolina; the
6
Department of Public Health Sciences,
Wake Forest University School of Medicine, Winston-Salem, North Carolina; and the
7
Northwest Lipid
Metabolism and Diabetes Research Laboratories, University of Washington, Seattle, Washington.
Corresponding author: Dana Dabelea, dana.dabelea@ucdenver.edu.
Received 26 September 2008 and accepted 9 December 2008.
Published ahead of print at http://care.diabetesjournals.org on 17 December 2008. DOI: 10.2337/dc08-
1775.
© 2009 by the American Diabetes Association. Readers may use this article as long as the work is properly
cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.
org/licenses/by-nc-nd/3.0/ for details.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby
marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Epidemiology/Health Services Research
ORIGINAL ARTICLE
416 DIABETES CARE, VOLUME 32, NUMBER 3, MARCH 2009
Page 1
non-Hispanic white, African American,
and Hispanic backgrounds were also in-
vited to participate in SEARCH Case-
Control. Altogether, 64% of eligible type
1 diabetic subjects participated. Control
subjects were recruited from primary care
offices in the same geographic areas and
were confirmed by fasting glucose to be
nondiabetic by American Diabetes Asso-
ciation (ADA) criteria (10). The study was
reviewed and approved by the local insti-
tutional review boards that had jurisdic-
tion over the local study population.
Data collection
The clinical diabetes type assigned by
the health care provider was obtained
from medical records or physician re-
ports and categorized as type 1 diabetes
if the provider assignment was type 1,
type 1a, or type 1b. Race/ethnicity was
collected from self-reports using 2000
U.S. Census–based questions and cate-
gorized as non-Hispanic white, His-
panic, and African American. Pubertal
development was self-assessed using
the method described by Marshall and
Tanner (11) with a standardized series
of drawings with explanatory text. The
Tanner stage ranged from 1 (prepu-
beral) to 5 (adult stage). BMI was calcu-
lated (weight in kilograms divided by
the square of height in meters) and age-
and sex-specific BMI z scores were de-
rived based on the Centers for Disease
Control and Prevention national stan-
dards (12). Physical activity was ob-
tained by self-report using questions
based on the Youth Risk Behavior Sur-
veillance System (13) and was catego-
rized as the average number of 30-min
blocks of moderate-to-vigorous activity
per day.
Laboratory samples were obtained un-
der conditions of metabolic stability, de-
fined as no episode of diabetic ketoacidosis
during the previous month. All specimens
were processed locally and shipped within
24 h to the central laboratory (University of
Washington) for analysis. Measurements of
plasma cholesterol, triglycerides, and HDL
cholesterol were performed enzymatically
on a Hitachi 917 autoanalyzer (Roche Mo-
lecular Biochemicals, Indianapolis, IN).
LDL cholesterol was calculated by the
Friedewald equation for individuals with a
triglyceride concentration 400 mg/dl and
the BetaQuantification procedure for those
with triglycerides of 400 mg/dl (13). A1C
was measured by a dedicated ion-exchange
high-performance liquid chromatography
instrument (TOSOH, San Francisco, CA).
ApoB was measured by a nephelometric
system (BNII; Behring Diagnostics, Deer-
field, IL). Relative flotation number (R
f
) for
LDL was determined by a technique de-
scribed previously (14). Cut points for ele-
vated lipid levels (total cholesterol 200
mg/dl, LDL cholesterol 130 mg/dl, high
non-HDL cholesterol 130 mg/dl, ele-
vated triglycerides 150 mg/dl, and low
HDL cholesterol 35 mg/dl) were taken
from the Third Report of the National
Cholesterol Education Program (Adult
Treatment Panel III) (1) and the ADA (15).
Statistical analysis
Statistical analyses were performed using
SAS for Windows (version 9.2; SAS Insti-
tute, Cary, NC). Demographic character-
istics were described with means and 95%
confidence intervals (CIs) for continuous
variables and frequencies for categorical
variables. The natural logarithmic trans-
formations of total cholesterol, LDL
cholesterol, triglyceride, non-HDL cho-
lesterol, and apoB were used to improve
normality of the residuals. Youth with
type 1 diabetes were categorized accord-
ing to glycemic control as optimal (A1C
7.5%) or suboptimal (A1C 7.5%),
and each category was compared with the
referent control group. Lipid levels were
compared by mixed-effects models using
A1C status (type 1 diabetes optimal A1C
versus control and type 1 diabetes subop-
timal A1C versus control) as the primary
independent variable, with adjustments
for age (as a second-order polynomial),
sex, race/ethnicity, and BMI. Mixed-
effects models were used to allow for un-
equal variances by diabetes status. Mixed-
model analysis results are expressed as
adjusted means (95% CI), adjusted to the
mean age, BMI, and observed race/
ethnicity and sex proportions for the type
1 diabetic group. Adjusted prevalence es-
timates of abnormal lipid concentrations
(95% CIs) were obtained with logistic re-
gression by calculating the predicted
prevalence for type 1 diabetic and control
subjects at the mean age, observed race/
ethnicity, and sex proportions for the type
1 diabetic group.
Table 1—Demographic, metabolic, and clinical characteristics of participants, according to study group
Variable Type 1, A1C 7.5% P value* Control P value† Type 1, A1C 7.5%
n 164 188 348
Age at visit 13.9 (13.4–14.4) 0.1 14.4 (14.0–14.8) 0.02 15.0 (14.7–15.4)
Sex (% male) 57.3 0.001 39.9 0.1 46.6
Race/ethnicity (%) 0.0001 0.0001
Non-Hispanic white 82.9 54.3 79.9
Hispanic 8.5 17.6 9.8
African American 8.5 28.2 10.3
A1C (%) 6.5 (6.4–6.6) 0.001 5.1 (5.1–5.2) 0.001 9.2 (9.0–9.4)
BMI (kg/m
2
)
22.7 (22.0–23.4) 0.07 23.7 (22.8–24.7) 0.001 22.0 (21.6–22.5)
BMI z score 0.6 (0.4–0.8) 0.5 0.7 (0.5–0.8) 0.03 0.5 (0.4–0.6)
Waist (cm) 79.5 (77.7–81.4) 0.7 80.1 (77.9–82.3) 0.1 78.2 (77.0–79.5)
Systolic blood pressure (mmHg) 106.5 (104.8–108.2) 0.3 107.6 (106.0–109.2) 0.2 106.3 (105.0–107.6)
Diastolic blood pressure (mmHg) 69.0 (67.5–70.5) 0.3 69.9 (68.6–71.3) 0.2 68.8 (67.8–69.9)
Physical activity 4.21 (3.47–4.94) 0.01 5.41 (4.66–6.17) 0.7 5.21 (4.57–5.86)
Insulin dose (units kg
1
day
1
)
0.54 (0.50–0.59) N/A 0.82 (0.78–0.86)
Duration (years) 2.2 (1.7–2.8) N/A 5.1 (4.6–5.6)
Characteristics are expressed as means (95% CI) or %. *Type 1 diabetes and A1C 7.5 versus control. †Type 1 diabetes and A1C 7.5 versus control. N/A, not
applicable.
Guy and Associates
DIABETES CARE, VOLUME 32, NUMBER 3, MARCH 2009 417
Page 2
RESULTS Table 1 summarizes the
demographic, metabolic, and clinical
characteristics of participants, according
to study category. There were 164 youth
with type 1 diabetes and optimal A1C val-
ues, 348 youth with suboptimal A1C val-
ues, and 188 healthy control subjects
with complete data on the main variables
of interest. Compared with control youth,
patients with type 1 diabetes and optimal
A1C values were more likely to be male
and non-Hispanic white and tended to be
slightly younger and less physically ac-
tive. Compared with control youth, pa-
tients with type 1 diabetes and suboptimal
A1C values were older and subwere more
likely to be non-Hispanic white and to
have lower BMI. Waist circumference,
blood pressure levels, and Tanner stage
were not different among the three
groups. As expected, mean A1C levels
were higher in both subgroups with type
1 diabetes than in control youth. Given
these differences, lipid levels explored in
Table 2 were adjusted for age, sex, race/
ethnicity, and BMI. There were significant
differences between the two type 1 dia-
betic subgroups in terms of disease dura-
tion, physical activity, and daily insulin
dose. Separate analyses to assess the po-
tential influence of these differences be-
tween the two diabetic subgroups on
various lipid parameters were also
conducted.
Table 2 compares the mean lipid lev-
els among control subjects, youth with
type 1 diabetes with optimal A1C levels
(7.5%), and youth with suboptimal val-
ues for A1C (7.5%) after adjustment for
age, sex, race/ethnicity, and BMI. Com-
pared with control subjects, youth with
optimal A1C levels had similar mean lev-
els of total cholesterol, LDL cholesterol,
non-HDL cholesterol, and LDL particle
size (LDL R
f
); lower levels of triglyceride;
higher HDL cholesterol levels; and a
lower triglyceride–to–HDL cholesterol
ratio. However, mean apoB concentra-
tions were higher, despite no differences
in LDL cholesterol levels. Type 1 diabetic
youth with suboptimal levels of A1C had
a more atherogenic lipid and lipoprotein
pattern, such that mean values were sig-
nificantly higher than those in control
subjects for total cholesterol, LDL choles-
terol, non-HDL cholesterol, and apoB and
significantly lower for LDL particle size.
Nevertheless, even youth with subopti-
mal A1C had higher HDL cholesterol lev-
els than control subjects. These patterns
were virtually unchanged with additional
adjustment for differences in duration of
diabetes between the two groups of youth
with type 1 diabetes (2.2 vs. 5.1 years in
youth with type 1 diabetes with optimal
and suboptimal A1C, respectively). Addi-
tional adjustment for minor differences in
physical activity patterns did not influ-
ence the observed differences in HDL
cholesterol. Adjustment for different daily
insulin doses only slightly attenuated the
difference in triglyceride levels between
the two diabetes subgroups (62.7 vs. 71.5
mg/dl in type 1 diabetes with optimal and
suboptimal A1C, respectively).
Figure 1 shows the age-, sex- and
race/ethnicity-adjusted prevalence esti-
mates of abnormal lipid concentrations in
each study group, with P values compar-
ing each type 1 diabetic group with the
healthy control group. Similar to the find-
ings regarding mean lipid levels, the
prevalence of abnormal standard lipid
Figure 1—Prevalence of abnormal lipid concentrations, adjusted for age, sex, and race/ethnicity
in nondiabetic youth, youth with type 1 diabetes in optimal (A1C 7.5%), and suboptimal (A1C
7.5%) glycemic control. *P 0.05, type 1 diabetes with optimal or suboptimal A1C versus
healthy youth.
P 0.01, type 1 diabetes with optimal or suboptimal A1C versus healthy youth.
Table 2—Lipid levels in nondiabetic control youth and youth with type 1 diabetes with optimal (A1C <7.5%) and suboptimal (A1C >7.5%)
glycemic control
Variable Type 1, A1C 7.5% P value* Control P value† Type 1, A1C 7.5%
164 188 348
Cholesterol (mg/dl) 155.6 (151.0–160.3) 0.8 156.2 (152.0–160.5) 0.0001 169.8 (165.8–174.0)
LDL cholesterol (mg/dl) 91.2 (87.3–95.3) 0.7 91.9 (88.3–95.6) 0.0003 100.1 (96.9–103.5)
Triglyceride (mg/dl) 62.8 (58.5–67.3) 0.0001 81.2 (75.5–87.4 0.2 76.6 (71.8–81.7)
HDL cholesterol (mg/dl) 50.6 (48.7–52.5) 0.0001 46.1 (44.4–47.7) 0.0001 52.3 (50.8–53.8)
Non–HDL cholesterol (mg/dl) 104.5 (100.4–108.8) 0.07 109.4 (105.4–113.5) 0.006 116.5 (112.7–120.4)
Triglyceride-to–HDL cholesterol ratio 1.45 (1.29–1.60) 0.0001 2.10 (1.89–2.31) 0.9 2.14 (1.73–2.55)
ApoB (mg/dl) 69.1 (65.9–72.5) 0.0001 54.3 (52.0–56.7) 0.0001 76.9 (74.1–79.9)
LDL (R
f
)
0.283 (0.280–0.286) 0.4 0.282 (0.279–0.285) 0.001 0.275 (0.272–0.278)
Data are adjusted means (95% CI). *Type 1 diabetes and A1C 7.5 versus control. †Type 1 diabetes and A1C 7.5 versus control.
Lipid and lipoprotein profiles
418 DIABETES CARE, VOLUME 32, NUMBER 3, MARCH 2009
Page 3
concentrations (total cholesterol, LDL
cholesterol, and HDL cholesterol) was
similar in youth with type 1 diabetes and
optimal A1C levels versus nondiabetic
youth. Youth with type 1 diabetes with
optimal glycemic control also had the
lowest prevalence of elevated triglyceride
of all three groups. The type 1 diabetic
youth with suboptimal glycemic control
had a higher prevalence of abnormal stan-
dard lipid factors than control subjects,
reaching statistical significance for ele-
vated total cholesterol. The proportion of
youth with elevated nontraditional lipid
factors, high apoB, and small, dense LDL
particles was significantly higher in type 1
diabetic patients with both optimal and
suboptimal A1C levels compared with
healthy control subjects. There was a gra-
dient of increasing prevalence of elevated
apoB levels with increasing A1C.
CONCLUSIONS We found that in
youth with type 1 diabetes and relatively
short disease duration (mean 4.2 years)
mean lipid levels and prevalence of lipid
abnormalities are substantially influenced
by glycemic control. Youth with type 1
diabetes and optimal A1C levels have
lipid profiles that are similar (total and
LDL cholesterol) or even less atherogenic
(HDL cholesterol, triglyceride, and tri-
glyceride-to-HDL ratio) than those ob-
served in nondiabetic youth. In contrast,
youth with type 1 diabetes and subopti-
mal glycemic control have higher stan-
dard lipid levels and prevalence of lipid
abnormalities (total cholesterol, LDL cho-
lesterol, and non-HDL cholesterol) than
nondiabetic youth. Moreover, youth
with type 1 diabetes have significantly
elevated apoB levels and more small,
dense LDL particles than nondiabetic
youth, regardless of glycemic control.
We also found that the most frequent
lipid abnormalities in youth with type 1
diabetes compared with nondiabetic
control subjects are elevated apoB levels
and an increased proportion with small,
dense LDL particles.
Data on lipid and lipoprotein factors
in youth with type 1 diabetes are scarce;
studies are relatively small and often do
not include a control group. Most data are
based on adults with childhood-onset di-
abetes. Our observation that youth with
type 1 diabetes and optimal glycemic con-
trol have a less atherogenic standard lipid
profile, especially with respect to triglyc-
eride and HDL cholesterol levels, agrees
with previous data in adults (16). In gen-
eral, lipid concentrations were shown to
be antiatherogenic in adults with type 1
diabetes who had optimal glycemic con-
trol or intensive insulin treatment (16).
However, the lack of abnormal lipid levels
does not exclude the possibility of com-
positional changes that may be athero-
genic, especially among those with poor
glycemic control. James and Pometta (17)
found that in adults with poorly con-
trolled type 1 diabetes, triglyceride-rich
lipoprotein particles are increased; LDL
subclass distribution shifts to relative ex-
cess of small, dense LDL; and LDL parti-
cles are more triglyceride rich compared
with those of normal subjects. Under nor-
mal circumstances, triglyceride-rich parti-
cles are rapidly hydrolyzed by lipoprotein
lipase. The enzyme is induced in adipose
tissue by insulin, and thus, intensive insulin
therapy is typically associated with a
marked fall of triglyceride-rich particles
(17). This may be one explanation for lower
triglyceride and higher HDL cholesterol
concentrations in youth with type 1 diabe-
tes versus healthy control subjects.
Our findings that youth with subop-
timal glycemic control have increased
concentrations and a higher prevalence of
abnormal standard lipid levels, as well as
more small, dense LDL particles and
higher apoB levels, also agree with the
previous literature in adults (18). Simi-
larly, among SEARCH youth with type 1
diabetes, total and LDL cholesterol, tri-
glyceride, and non-HDL cholesterol lev-
els (19) and also dense LDL and apoB
concentrations (14) increased with in-
creasing A1C.
The measurement of apoB and dense
LDL in individuals with diabetes has been
sparse, particularly in children and ado-
lescents. The higher proportion of youth
with type 1 diabetes with elevated apoB
versus healthy control subjects can be ex-
plained by the increased concentration of
triglyceride-rich apoB-containing li-
poproteins and by the presence of dense
LDL that is enriched in apoB relative to its
cholesterol content. In our study, even
youth with optimal A1C levels had ele-
vated apoB and an increased proportion
of small, dense LDL particles relative to
those in nondiabetic control subjects,
suggesting that even mild hyperglycemia
may be associated with atherogenic
compositional lipoprotein changes even if
concentrations of standard lipid are
unaffected.
Both apoB and small, dense LDL par-
ticles have been shown to be strong and
independent predictors of CVD. ApoB
has been shown to be a better predictor of
incident CVD than LDL cholesterol and
non-HDL cholesterol (20). The dense
LDL particle subclass is associated with
increased risk of ischemic heart disease
events (21) and narrowing of an existing
cardiac stenosis in adults (22). Thus, ele-
vated apoB and/or dense LDL particles in
youth with type 1 diabetes may contrib-
ute substantially to increased cardiovascu-
lar morbidity and mortality in adulthood.
Currently, the ADA guidelines for manag-
ing dyslipidemia in children and adoles-
cents with diabetes advise optimizing
glycemic control, improving diet, and keep-
ing LDL cholesterol, HDL cholesterol, and
triglycerides within specific targets (15).
Our data suggest that apoB and small, dense
LDL particles may also represent important
targets because they appear to be elevated
even among patients with well-controlled
type 1 diabetes and because CVD risk re-
lates more closely to the level of apoB than
to cholesterol indexes.
This study has several potential limi-
tations. First, it is cross-sectional and thus
is limited to describing observed associa-
tions. Half of the patients with type 1 di-
abetes in this study had a disease duration
of 2 years, thus limiting the generaliz-
ability of our findings to the larger popu-
lation of youth with type 1 diabetes. We
had limited power to conduct race/
ethnicity-specific analyses; however, sim-
ilar patterns were noted across all racial/
ethnic groups. Major strengths of our
study include a relatively large sample of
youth with type 1 diabetes, with a range of
A1C levels, a detailed examination of lipid
and lipoprotein profiles, and, impor-
tantly, a nondiabetic control group.
In summary, our study presents novel
information on characteristics of dyslipi-
demia in youth with type 1 diabetes com-
pared with nondiabetic control subjects.
Youth with type 1 diabetes present with
abnormal lipid levels and atherogenic
changes in lipoprotein composition, even
after a relatively short disease duration. As
in adults, glycemic control seems to be an
important mediator of these abnormali-
ties. Further research is needed to fully
understand the mechanisms by which
type 1 diabetes contributes to altered lipid
profiles and increased cardiovascular
risk.
Acknowledgements No potential conflicts
of interest relevant to this article were
reported.
Guy and Associates
DIABETES CARE, VOLUME 32, NUMBER 3, MARCH 2009 419
Page 4
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Lipid and lipoprotein profiles
420 DIABETES CARE, VOLUME 32, NUMBER 3, MARCH 2009
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    • "Deranged lipids have been reported amongst adolescents and youth in the SEARCH for Diabetes in Youth study[1]. Although data on the influence of blood glucose control on development of atherosclerosis is conflicting, there is increasing evidence of an association between the two2345. This study was conducted to i) compare lipid parameters between diabetic children and controls; ii) determine factors influencing lipid parameters in diabetic children; and iii) examine effect of lowering of glycosylated hemoglobin on lipids in diabetic children at one year. "
    [Show abstract] [Hide abstract] ABSTRACT: Objectives To compare lipid parameters between diabetics and controls and to study association between metabolic control and lipid profile. Methods Lipid profile and HbA1c were measured (n=80, 39 boys) in diabetic children [age 10.7(3.4) y] and 54 controls, tests repeated after 1 year (in 45 diabetics). Results Diabetic children had higher mean (SD) LDL-C [95.3(27.7) vs 84.5(26.4) mg/dL], lower HDL-C [48.2 (13.1) vs 53.1(11.9) mg/dl]. Moderate physical activity (P=0.014) protected against high LDL-C levels. HbA1c (P=0.00) predicted total and LDL-C levels. At 1year, 63% showed reduced LDL-C with improving HbA1c; 72% showed increased LDL-C with deteriorated HbA1c. Conclusion Improving metabolic control is cardinal to reduce cardiometabolic risk; physical activity is beneficial.
    No preview · Article · Feb 2016 · Indian pediatrics
    • "However, this finding is controversial, as it may depend on the method used and the clinical characteristics of the population under study. As noticed, Guy and colleagues [35] identified that young T1D patients presented higher levels of small LDL particles than subjects without diabetes, independent of their glycemic control. Different findings were described by Alberts and cols., in which poor glycemic control was related to more dense LDL particles [36]. "
    [Show abstract] [Hide abstract] ABSTRACT: Patients with type 1 diabetes (T1D) present increased risk of cardiovascular disease (CVD). The aim of this study is to improve the assessment of lipoprotein profile in patients with T1D by using a robust developed method 1H nuclear magnetic resonance spectroscopy (1H NMR), for further correlation with clinical factors associated to CVD. Thirty patients with T1D and 30 non-diabetes control (CT) subjects, matched for gender, age, body composition (DXA, BMI, waist/hip ratio), regular physical activity levels and cardiorespiratory capacity (VO2peak), were analyzed. Dietary records and routine lipids were assessed. Serum lipoprotein particle subfractions, particle sizes, and cholesterol and triglycerides subfractions were analyzed by 1H NMR. It was evidenced that subjects with T1D presented lower concentrations of small LDL cholesterol, medium VLDL particles, large VLDL triglycerides, and total triglycerides as compared to CT subjects. Women with T1D presented a positive association with HDL size (p<0.005; R = 0.601) and large HDL triglycerides (p<0.005; R = 0.534) and negative (p<0.005; R = -0.586) to small HDL triglycerides. Body fat composition represented an important factor independently of normal BMI, with large LDL particles presenting a positive correlation to total body fat (p<0.005; R = 0.505), and total LDL cholesterol and small LDL cholesterol a positive correlation (p<0.005; R = 0.502 and R = 0.552, respectively) to abdominal fat in T1D subjects; meanwhile, in CT subjects, body fat composition was mainly associated to HDL subclasses. VO2peak was negatively associated (p<0.005; R = -0.520) to large LDL-particles only in the group of patients with T1D. In conclusion, patients with T1D with adequate glycemic control and BMI and without chronic complications presented a more favourable lipoprotein profile as compared to control counterparts. In addition, slight alterations in BMI and/or body fat composition showed to be relevant to provoking alterations in lipoproteins profiles. Finally, body fat composition appears to be a determinant for cardioprotector lipoprotein profile.
    Full-text · Article · Aug 2015 · PLoS ONE
    • "11,15 In the present work, mean duration of diabetes showed no significant difference between the dyslipidemic group and the normolipidemic group (4.1 ± 2.7 and 4.6 ± 2.6 years respectively ); there were patients with less than 2 years diabetes duration and having dyslipidemia. This finding is in agreement with Kanagalakshmi and Sultana (2012) and Guy et al. (2009) who found that the dyslipidemia in children and adolescents with T1DM is present despite short duration of diabetes. 18,19 This is in contrast to the results reported by Moayeri and Oloomi (2006) who found that lipid concentrations correlate positively with the duration of diabetes. "
    [Show abstract] [Hide abstract] ABSTRACT: Diabetes is associated with a high risk of cardiovascular disease (CVD). The classic “diabetic dyslipidemia” is mostly described as hypertriglyceridemia and low levels of HDL-C. Elevated LDL-C is an established risk factor for CVD.
    Full-text · Article · Apr 2015 · The Gazette of the Egyptian Paediatric Association
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