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Elevated fasting free fatty acids in overweight Latino children and adolescents

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Elevated fasting free fatty acids in overweight Latino children and adolescents

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ELEVATED FASTING FREE FATTY ACIDS IN OVERWEIGHT LATINO
CHILDREN AND ADOLESCENTS

by

Kevin Moua

A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(BIOSTATISTICS)

December 2012

Copyright 2012 Kevin Moua
ii

Dedication

I dedicate this to my family, my undying supportive friends, my wonderful
Biostatistics/Epidemiology professors at the University of Southern California, and the
great people at the Childhood Obesity Research Center. Thank you all for your support
and efforts in my education.

iii

Acknowledgements

The DREAM project is supported by NCMHD grant P60MD002254 (M.I. Goran
and M.J. Weigensberg).

iv

Table of Contents

Dedication ii
Acknowledgements iii
List of Tables v
List of Figures vi
Abstract vii
Chapter 1: Introduction 1
Chapter 2: Subjects and Methods 3
Population 3
FFA Assays 4
Variables and Data Collection 5
Statistical Analysis 6
Chapter 3: Results 8
Patient Characteristics 8
Univariate Analysis 10
Repeated Measures Analysis 13
Chapter 4: Conclusion 15
References: 17
Alphabetical References 17
Numerical References 19

v

List of Tables

Table 1: Descriptive Statistics for Latino Children and 9
Adolescents
Table 2: Univariate Analyses Comparing Characteristics 11
Between PD and NGT Children and Adolescents

vi

List of Figures

Figure 1: FFA Curve Between PD and NGT Children and 14
Adolescents

vii

Abstract

Purpose: Over the past decade, there has been a disturbing trend of increasing
incidence of type 2 diabetes in children, with a greater proportion of minority children
being affected. Latino children and adolescents in the United States have a 52% lifetime
risk of type 2 diabetes. Elevated fasting free fatty acids (FFA) is a potential pathway
towards type 2 diabetes among overweight Latino children and adolescents. The
objective of this study is to compare fasting free fatty acid levels in Latino children and
adolescents who are considered to be prediabetic versus those who are considered to have
normal glucose tolerance.
Patients and Methods: Study subjects were healthy overweight Latino children
and adolescents from the University of Southern California’s Diabetes Risk due to
Ectopic Adiposity in Minority Youth (DREAM) project. Free fatty acid levels were
measured through a standard two-hour oral glucose tolerance test. Plasma glucose and
insulin were measured at -5 minutes before and 30, 60, and 120 minutes after ingesting
glucose solution. Those who were considered to be prediabetic met at least one of the
following criteria: fasting glucose 100mg/dL, 2-hour glucose between 140-199mg/dL,
hemoglobin A1C between 6.0-6.4%. The remaining subjects were considered to have
normal glucose tolerance. Univariate analysis used the Student’s t-test to compare mean
differences between pre-diabetic and normal glucose tolerance groups. Repeated
measures analysis of covariance was used to compare the elevated fasting free fatty acid
viii
curves between the prediabetic and normal glucose tolerance groups, adjusting for sex,
Tanner stage, and age.
Results: The normal glucose tolerance and prediabetic groups did not differ on
age, sex, Tanner stage or BMI-Z (p>0.05). By definition of the groups, the prediabetic
group had higher mean hemoglobin A1C, fasting and 2-hour glucose and insulin than the
normal glucose tolerance group (p<0.05). The prediabetic group had a higher overall
FFA curve compared to the normal glucose tolerance group (p<0.01). Looking at each
time measurement individually, at the -5, 30, and 60 minutes, the prediabetic group had
higher fasting free fatty acid levels compared to the normal glucose tolerance group. At
the 120 min there was no difference in fasting free fatty acid levels between the two
groups.
Conclusions: Prediabetic overweight Latino children and adolescents may
experience greater overall exposure to circulating fasting free fatty acids. These results
are consistent with the lipotoxicity theory of diabetes development. These results support
continued investigations of elevated free fatty acids as a potential pathway in the
development of type 2 diabetes in children/adolescents.

1

Chapter 1: Introduction

In 2007, 42% of Hispanic children and adolescents, ages 6-19, were considered to
be overweight, having a body mass index (BMI) > 85
th
percentile.
1
Studies suggest that
overweight adolescents are more likely to become overweight adults, which inevitably
makes this an important public health concern,
2-3
as overweight increases the risk of
developing chronic diseases, such as cardiovascular disease, obesity-related cancers, and
type 2 diabetes.
4

Over the past decade, there has been a disturbing trend of increasing incidence of
type 2 diabetes in children, particularly adolescents, with a greater proportion of minority
children affected.
5
Latino children and adolescents have a lifetime risk of 52% of type 2
diabetes.
6
The chances of developing type 2 diabetes increases when one or both parents
are affected.
7
Elevated fasting free fatty acids (FFA) is a potential pathway towards type
2 diabetes among overweight Latino children and adolescents.
8

FFA has long been considered a link between obesity and the development of
type 2 diabetes.
8
Overweight individuals are more likely to have elevated FFA levels,
which have been linked to insulin resistance.
9
Insulin resistance can in turn lead to
impaired glucose tolerance (IGT) and eventually type 2 diabetes.
10
Elevated FFA levels
are also associated with an inability to appropriately increase insulin secretion in response
to insulin resistance, which can indicate -cell deterioration, thus increasing the risk for
2
type 2 diabetes.
10-11
This is consistent with the lipotoxicity theory for diabetes
development.
The purpose of this paper is to investigate the association of FFA levels and
prediabetic status among overweight Latino children and adolescents. We hypothesize
that prediabetic Latino children and adolescents will have higher levels of elevated
fasting FFA compared to Latino children and adolescents who have normal glucose
tolerance (NGT) after a two-hour oral glucose tolerance test (OGTT). To test our
hypothesis, we used data from the project, Diabetes Risk due to Ectopic Adiposity in
Minority Youth (DREAM), conducted at the Childhood Obesity Research Center
(CORC) at the University of Southern California.

3

Chapter 2: Subjects and Methods

2.1 Population:
Study subjects were healthy overweight Latino children and adolescents from the
University of Southern California’s (USC) Diabetes Risk due to Ectopic Adiposity in
Minority Youth (DREAM) project. Project recruitment has been ongoing for the past
two years and the database is repeatedly updated with ongoing data collection and
laboratory results. Recruitment occurred through schools, churches, sports clubs, clinics,
health fairs, and other venues. The children and adolescents were required to meet the
following inclusion criteria: 1) Latino or African American ancestry (i.e. all four
grandparents Latino or African American, self-reported); 2) boys only, for those who are
ages between 8-11 (pre-pubertal); 3) male or female, for those between ages 14-17 (post-
pubertal); 4) Body Mass Index (BMI) ≥ 85
th
percentile for those ages 14-17, and if age 8-
11, BMI <85
th
percentile and at least one parent must have type 2 diabetes or is
considered obese; 5) not been previously diagnosed as diabetic.
This analysis used data from 135 (84 boys/51 girls) overweight Latino
participants. African Americans were not included in this analysis (n=91); Latinos with
a BMI less than the 85
th
percentile (n=14) were also excluded. A total of 42 of the 135
overweight Latino children and adolescents were excluded due to lack of FFA assays.
Subjects without FFA data did not differ in age, height, weight, BMI, or BMI percentile
from those with FFA data. A total of 93 children and adolescents were included in these
4
analysis. Two groups were defined from the remaining 93 subjects, prediabetic (PD,
n=32) and normal glucose tolerance (NGT, n=61). The American Diabetes Association
criteria for PD were used: (1) fasting glucose (IFG) between 100-126 mg/dl, and/or (2)
glucose tolerance (IGT) between 140-200 mg/dl at two hours post-glucose challenge by
oral glucose tolerance test (OGTT)), and/or (3) hemoglobin A1C between 6.0-6.4%.
Subjects not meeting any of these three criteria were classified as NGT. Participants who
met criteria for diabetes (n=5) were excluded from the study and referred to their personal
health care provider. The criterion for diabetes was IFG  126 mg/dl and/or IGT  200
and/or hemoglobin A1C  6.5%.

2.2 FFA Assays:
In the DREAM project, subjects were scheduled for two visits to the USC Clinical
Trials Unit (CTU). FFA levels were measured through a standard two-hour OGTT,
where blood samples were drawn at -5, 30, 60, and 120 minutes after ingesting glucose
solution (1.75 grams/kg to maximum 75 grams). Samples were separated for plasma and
immediately transported on ice to the laboratory where glucose was analyzed on a
Dimension Clinical Chemistry system and an in vitro Hexokinase method (Dade Behring,
Deerfield, IL). Insulin was assayed using an automated random access enzyme
immunoassay system Tosoh AIA 600 II analyser (Gibbco Scientific, Inc. Coon Rapids,
MN) using an immunoenzymemetric assay (IEMA) method.
Insulin sensitivity, acute insulin response, and disposition index were measured
on the second visit to the CTU: intravenous catheters were placed in bilateral antecubital
5
veins, one side for injections and the contralateral side for blood sampling. Within at
least 30 minutes after intravenous placement, glucose was administered at a dose of 300
mg per kg body weight at “Time zero”, followed by 0.02 units of regular insulin per kg
body weight 20 minutes later. A total of 13 blood samples (2.5 ml each) were obtained
from –15 to 180 min after glucose injection and assayed. Insulin sensitivity, acute insulin
response, and disposition index were determined using Bergman’s minimal model
technique (MINMOD MILLENIUM 2002 software (Version 5.15)

2.3 Variables and Data Collection:

From the DREAM database the following variables were extracted: age, Tanner
stage, sex, height, weight, BMI, BMI percentile, pulse rate, insulin sensitivity, acute
insulin response, disposition index, systolic blood pressure, diastolic blood pressure, total
percent fat, total body fat, total lean mass, total mass, and glucose and insulin
measurements at -5 minutes and 120 minutes. The primary comparisons between PD and
NGT subjects used hemoglobin A1C, impaired fasting glucose (IFG), impaired glucose
tolerance (IGT), and FFA levels at -5, 30, 60 and 120 minutes. A priori covariates are
age, sex, and Tanner stage.
Age, height, weight, pulse, blood pressure, and Tanner stage were acquired in a
physical exam performed by licensed pediatric care providers. Height and weight were
measured using a wall-mounted stadiometer and clinical medical balance. BMI was
calculated as weight in kg divided by height in m
2
. Height, pulse, and weight were
measured three times and the average of the three measurements were used. Total body
6
fat, total lean mass, total mass, and total percent fat were measured by dual energy x-ray
absorptiometry (DEXA) using a Hologic QDR 4500 densitometer (Hologic, Inc.,
Bedford, MA) at the Clinical Science Center, Clinical Exercise Research Center, or at the
CTU.

2.4 Statistical Analysis:

Univariate analyses were performed using the Student’s t-test for the following
comparisons between PD and NGT: age, height, weight, BMI, BMI percentile, pulse,
A1C, insulin sensitivity, acute insulin response, disposition index, systolic blood
pressure, diastolic blood pressure, total percent fat, total body fat, total lean mass, total
mass, clinical glucose at five minutes prior, clinical glucose after 120 minutes, insulin at
5 minutes prior, insulin after 120 minutes, and FFA level at -5, 30, 60 and 120 minutes.
These analyses were performed to assess similarity of the two groups on demographic
and other characteristics, while at the same time comparing group differences on body
composition.
As detailed above, subjects with IFG, IGT and/or elevated A1C were classified as
prediabetic (PD), where 1 was considered PD and 0 was considered NGT. FFA levels
were measured at four time points, -5, 30, 60, and 120 minutes from the OGTT. Since
each subject had 4 measurements, to compare PD and NGT levels of FFA, a repeated
measures analysis of covariance (rANCOVA) was used, adjusting for the a priori
covariates: sex, Tanner stage, and age. Sex and Tanner stage were modeled as
categorical variables while age was modeled as a continuous variable.
7
All hypothesis testing was conducted at a two-sided alpha level of 0.05; analyses
used the statistical software SAS 9.2 for Windows.

8

Chapter 3: Results

3.1 Patient Characteristics:
A total of 152 Latino children and adolescents were identified from the DREAM
project. Of these, 3 had missing IFG, IGT, and A1C results, and 14 had a BMI less than
the 85
th
percentile. This left 135 Latino children and adolescents available for the study.
Of the 135 subjects, 41 did not have elevated FFA assays completed and 1 had missing
FFA results at the time of this report. Hence 93 total subjects were used for the current
analysis.
Table 1 depicts the demographics of these 93 Latino children and adolescents.
Subjects in the PD and NGT group were similar in age, height, and pulse. The PD group
weighed more than the NGT group, with a concomitantly higher BMI for the PD group
compared to the NGT group. The PD group had a mean BMI that was almost 4 points
higher than that of the NGT group, although, both groups had similar BMI percentile.

9

Table 1: Descriptive Statistics for Latino Children and Adolescents
GROUP
Characteristics ALL PD NGT
Sex (M | F) 63 | 30 24 | 8 39 | 22
Tanner Stage
1
2
3
4
5

16
6
0
16
55

5
3
0
5
19

11
3
0
11
36
Age

(years) 14.75 (2.50)* 15.07 (2.49) 14.57 (2.51)
Height (cm) 161.67 (12.15) 162.96 (12.86) 160.99 (12.80)
Weight (kg) 82.59 (23.07) 90.19 (25.56) 78.60 (20.78)
BMI (kg/m
2
) 31.13 (7.24) 33.62 (7.61) 29.83 (5.38)
BMI % 96.38 (3.56) 97.19 (3.61) 95.95 (3.48)
Pulse (beats/min) 74.40 (13.41) 75.44 (15.97) 73.85 (11.96)
*Mean (St Dev)

10
3.2 Univariate Analysis:
Statistical comparisons of PD and NGT groups on clinical and metabolic
characteristics are presented in Table 2. The groups were similar in age, height, pulse,
and total body fat. The PD group weighed significantly more than the NGT group on the
scale balance measurement (90.19kg vs 78.60kg; p = 0.02) and the DEXA measurement
of total mass (86811.68g vs 77231.95g; p = 0.04). The PD group had a significantly
higher BMI (33.62kg/m
2
vs 29.83kg/m
2
; p<0.01) but did not differ in BMI percentile
(97.19 vs 95.95; p = 0.11). The groups significantly differed on systolic blood pressure
(PD 122mmHg vs 115mmHg; p = 0.02) but not on diastolic blood pressure (66.03mmHg
vs 64.91mmHg; p = 0.37). There was a significant difference at the -5 minutes
measurement for glucose (89.88mg/dL vs 85.93mg/dL; p<0.01) and insulin levels
(20.22µIU/mL vs 14.06; p<0.01). The glucose (131.19mg/dL vs 112.87mg/dL; p<0.01)
and insulin (162.78µIU/mL vs 97.30µIU/mL; p<0.01) levels at 120 minutes also
significantly differed between PD and NGT. The PD group also had a lower mean
insulin sensitivity compared to NGT (1.49mg/dL vs 2.43mg/dL; p<0.01).

11
Table 2: Univariate Analyses Comparing Characteristics Between PD and NGT
Children and Adolescents
Characteristic Mean ± St Dev p-value
Age (years)
PD
NGT

15.07 ± 2.49
14.57 ± 2.51

0.35
Height (cm)
PD
NGT

162.96 ± 12.86
160.99 ± 12.80

0.46
Weight (kg)
PD
NGT

90.19 ± 25.56
78.60 ± 20.78

0.02
BMI (cm/kg
2
)
PD
NGT

33.62 ± 7.61
29.83 ± 5.38

<0.01

BMI %
PD
NGT

97.19 ± 3.61
95.95 ± 3.48

0.11
Pulse (beats/minute)
PD
NGT

75.44 ± 15.97
73.85 ± 11.96

0.59
Systolic Blood Pressure (mmHg)
PD
NGT

122.00 ± 12.85
115.77 ± 11.69

0.02
Diastolic Blood Pressure (mmHg)
PD
NGT

66.03 ± 5.83
64.91 ± 5.66

0.37
Total Percent Fat (%)
PD
NGT

35.99 ± 7.46
36.47 ± 7.18

0.76
Total Body Fat (g)
PD**
NGT

31424.21 ± 13006.14
28400.75 ± 9841.55

0.21
Total Lean Mass (g)
PD**
NGT

53059.49 ± 12974.11
46653.65 ± 13084.55

0.03
Total Mass (g)
PD**
NGT

86811.68 ± 23570.86
77231.95 ± 20498.21

0.04

Clinical Glucose -5 minutes (mg/dL)
PD
NGT

89.88 ± 6.69
85.93 ± 5.51

<0.01
*All comparisons done using Student’s t-test
** Missing 1 subject
12
Table 2 (Continued): Univariate Analyses Comparing Characteristics Between PD
and NGT Children and Adolescents
Characteristic Mean ± St Dev p-value
Clinical Glucose 120 minutes (mg/dL)
PD
NGT

131.19 ± 26.98
112.87 ± 16.38

<0.01
Insulin -5 minutes (µIU/mL)
PD
NGT

20.22 ± 13.35
14.06 ± 6.59

<0.01

Insulin 120 minutes (µIU/mL)
PD
NGT

162.78 ± 160.17
97.30 ± 67.58

<0.01
Insulin Sensitivity (mg/dL)
PD**
NGT**

1.49 ± 1.03
2.43 ± 1.39

<0.01

Acute Insulin Response
PD**
NGT**

1499.97 ± 1212.25
1106.16 ± 546.04

0.04
Disposition Index
PD**
NGT**

1779.91 ± 1143.09
2266.78 ± 1170.69

0.06
*All comparisons done using Student’s t-test
** Missing 1 subject

13
3.3 Repeated Measures Analysis:
The FFA curves for PD and NGT children are presented in Figure 1. Comparing
the two curves, PD had higher overall FFA levels compared to that of NGT (p<0.01),
after adjusting for sex, Tanner stage, and age. A feature rANCOVA allowed was
comparing the least squares estimate of FFA level for each time interval. For the
measurement times at -5 (0.75 vs 0.65; p<0.01), 30 (0.55 vs 0.47; p <0.01), and 60
minutes (0.30 vs 0.25; p <0.01), PD had higher FFA levels compared to that of NGT. At
the 120-minute mark, there was no significant difference in FFA level (0.20 vs 0.19; p =
0.42).
While checking normality for each individual time measurement, there existed
non-normality for the 60 and 120-minute mark. Although there can be some precautions
on the interpretation of results with non-normality, rANCOVA is known to be robust to
violations of the normality assumption
17
. As a whole, the multivariate normality
assumption was met under the Shapiro-Wilk test. Since there were only two groups, the
sphericity assumption holds for the analysis. For rANCOVA, the measurements within
each subject are not independent because each subject’s measurements are repeated but
rANCOVA considers each subject as independent.

14

*p<0.05; Repeated measures ANCOVA adjusted for sex and age.
**Least Squares Means for each time measurement are shown

0.75 ± 0.02
0.55 ± 0.02
0.30 ± 0.01
0.20 ± 0.01
0.65 ± 0.01
0.47 ± 0.01
0.25 ± 0.01
0.19 ± 0.01
0.15
0.25
0.35
0.45
0.55
0.65
0.75
-5 30 60 120
Time (minutes)
Figure 1: FFA Curve Between PD and NGT Children and
Adolecents
Prediabetic
Normal Glucose Tolerance
15

Chapter 4: Conclusion

We found that prediabetic overweight Latino children and adolescents had overall
higher levels of FFA compared to overweight Latino children and adolescents who were
classified as normal glucose tolerance; these differences were apparent both before and
during a 2-hour OGTT. At the -5, 30, and 60 minutes time intervals relative to the
standard glucose ingestion, FFA levels significantly differed. In contrast, for the 120
th

minute time interval there was no significant difference between the two groups.
Higher levels of FFA can lead to impaired -cell function, thereby increasing the
chances for a child or an adolescent of developing type 2 diabetes. Elevated FFA also
reflects the current health status of the child or adolescent; even in this overweight
sample of children, higher weight was associated with higher FFA.
Our findings of an association between being overweight and having higher levels
of elevated FFA are consistent with current literature.
12-16
The novelty of this study
includes comparing FFA levels at a prediabetic state to an NGT group, as well as the
study population of overweight children and adolescents. Studies have primarily been
conducted among adults when comparing FFA levels and most comparisons are with a
diabetic group. No prior studies have investigated the direct relationship between FFA
levels and the stages of diabetes in Latino children and adolescents.
The strengths of the study include the Latino population-based design, which
allowed us to recruit obese and overweight Latino children and adolescents. Use of
16
repeated measures ANCOVA allowed us to examine the differences of the two groups
through four different time points relative to a standard glucose ingestion, where the FFA
levels were compared across group at each time point as well as across time points.
Our study has several limitations, including the design of the study, which did not
allow for recruitment of children between 11-14 years old or recruitment of girls, ages 8-
11. An objective of the DREAM project was to ultimately merge data with another
project that included girls of a similar age range to the Latino pre-pubertal cohort, ages 8-
11. Another limitation was the time to complete FFA assays from the labs. Since the
recruitment of the children and adolescents occurred over a three-year period, most FFA
assays at the end of the recruitment were not able to be included in the study or the FFA
assays were not analyzed from the lab in a timely manner. Furthermore, even with all
the recruitment efforts, the small sample size and sources of recruitment may limit
generalizability to a greater population. Although generalizability may be an issue, it
should also be noted that these findings might be specific to our study population of
overweight Latino children/adolescents. These findings should be investigated in other
ethnic groups.
Despite these limitations, the study provides evidence that overweight Latino
youth and adolescents who are considered to be prediabetic have higher levels of FFA
compared to those who are considered NGT. The clinical importance from this study is
that having elevated FFA may be a pathway to future health risks involving these
children and adolescents. Although we feel the study is comparable to others, this
finding warrants further studies involving children and their FFA levels.
17

References

Basu A, Basu R, Shah P, Vella A, Johnson CM, Nair KS, Jensen MD, Schwenk WF,
Rizza RA: Effects of type 2 diabetes on the ability of insulin and glucose to regulate
splanchnic and muscle glucose metabolism: evidence for a defect in hepatic glucokinase
activity. Diabetes 49:272 –283, 2000
Boden G., “Effects of free fatty acids (FFA) on glucose metabolism: significance for
insulin resistance and type 2 diabetes”, Exp Clin Endocrinol Diabetes. 2003 May;
111(3):121-4
Bogardus C, Lillioja S, Howard BV, Reaven G, Mott D: Relationships between insulin
secretion, insulin action, and fasting plasma glucose concentration in nondiabetic and
noninsulin-dependent diabetic subjects. J Clin Invest 74:1238 –1246, 1984
Byrd-Williams CE, Belcher BR, Spruijtz-Metz D, Davis JN, Ventura EE, Kelly LA,
Azen SP & Goran MI “Increased physical activity and Reduced Adiposity in overweight
Hispanic Adolescents” MSSE42: 478-484, 2010
Dabelea D, Pettitt DJ, Jones KL, Arslanian SA. Type 2 diabetes mellitus in minority
children and adolescents: an emerging problem. Endocrinol Metab Clin North Am.
1999;28:709-729
Goran MI, Bergman RN, Avila Q, Watkins M, Ball G, Shaibi GQ, Weigensberg MJ,
Cruz M, “Impaired Glucose Tolerance and Reduced -Cell function in overweight Latino
children with a positive history for Type 2 Diabetes,” 2004, J Clinical Endocrinmology
and Metabolism, 89(1):207-212
Groop LC, Saloranta C, Shank M, Bonadonna RC, Ferrannini E, DeFronzo RA: The role
of free fatty acid metabolism in the pathogenesis of insulin resistance in obesity and
noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 72:96 –107, 1991
Klein BE, Klein R, Moss SE, Cruickshanks KJ: Parental history of diabetes in a
population-based study. Diabetes Care 19:827–830, 1996
Kelly LA, Lane CJ, Weigensberg MJ, Toledo-Corral CM, Goran MI, “Pubertal Changes
of Insulin Sensitivity, Acute Insulin Response, and β-Cell Function in Overweight Latino
Youth”, The Journal of Pediatrics, Volume 158, Issue 3, March 2011, Pages 442-446

18
McMillan DC, Sattar N, Lean M, McArdle CS. Obesity and cancer. BMJ.
2006;333:1109-11

Narayan KM, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF “Lifetime risk for
diabetes mellitus in the United States.” JAMA 290:1884–1890, 2003

Nestel PJ, Whyte HM: Plasma free fatty acid and triglyceride turnover in obesity.
Metabolism 17:1122 –1128, 1968

Ogden CL, Carroll MD, Curtin LR, Lamb MM, Flegal KM. “Prevalence of High Body
Mass Index in US Children and Adolescents, 2007–2008.” Journal of the American
Medical Association, 303(3): 242–249, 2010.

Olejnik SF, Algina J: Parametric ANCOVA vs. Rank Transform ANCOVA when
Assumptions of Conditional Normality and Homoscedasticity Are Violated. Journal of
Educational Statistics. 9(2) 129-149, January 1984

Paolisso G., Tataranni P.A., Foley J.E., Bogardus C., Howard B.V., Ravussin E., “A high
concentration of fasting plasma non-esterified fatty acids is a risk factor for the
development of niddm”, Diabetologia 38 (1995) 1213–1217.

Serdula MK, Ivery D, Coates RJ, Freedman DS, Williamson DF, Byers T. “Do obese
children become obese adults? A review of the literature.” Prev Med. 1993;22:167-77

Shah P, Vella A, Basu A, Basu R, Adkins A, Schwenk WF, Johnson CM, Nair KS,
Jensen MD, Rizza RA: Elevated Free Fatty Acids Impair Glucose Metabolism in
Women. Diabetes. 52(1): 38-42, January 2003.

19

References

Numerical:

1) Ogden CL, Carroll MD, Curtin LR, Lamb MM, Flegal KM. “Prevalence of High
Body Mass Index in US Children and Adolescents, 2007–2008.” Journal of the
American Medical Association, 303(3): 242–249, 2010.

2) Serdula MK, Ivery D, Coates RJ, Freedman DS, Williamson DF, Byers T. “Do
obese children become obese adults? A review of the literature.” Prev Med.
1993;22:167-77

3) Byrd-Williams CE, Belcher BR, Spruijtz-Metz D, Davis JN, Ventura EE, Kelly
LA, Azen SP & Goran MI “Increased physical activity and Reduced Adiposity in
overweight Hispanic Adolescents” MSSE42: 478-484, 2010

4) McMillan DC, Sattar N, Lean M, McArdle CS. Obesity and cancer. BMJ.
2006;333:1109-11

5) Dabelea D, Pettitt DJ, Jones KL, Arslanian SA. Type 2 diabetes mellitus in
minority children and adolescents: an emerging problem. Endocrinol Metab Clin
North Am. 1999;28:709-729

6) Narayan KM, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF “Lifetime
risk for diabetes mellitus in the United States.” JAMA 290:1884–1890, 2003

7) Klein BE, Klein R, Moss SE, Cruickshanks KJ: Parental history of diabetes in a
population-based study. Diabetes Care 19:827–830, 1996

8) Paolisso G., Tataranni P.A., Foley J.E., Bogardus C., Howard B.V., Ravussin E.,
“A high concentration of fasting plasma non-esterified fatty acids is a risk factor
for the development of niddm”, Diabetologia 38 (1995) 1213–1217.

9) Boden G., “Effects of free fatty acids (FFA) on glucose metabolism: significance
for insulin resistance and type 2 diabetes”, Exp Clin Endocrinol Diabetes. 2003
May; 111(3):121-4

20
10) Goran MI, Bergman RN, Avila Q, Watkins M, Ball G, Shaibi GQ, Weigensberg
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Abstract (if available)

Abstract Purpose: Over the past decade, there has been a disturbing trend of increasing incidence of type 2 diabetes in children, with a greater proportion of minority children being affected. Latino children and adolescents in the United States have a 52% lifetime risk of type 2 diabetes. Elevated fasting free fatty acids (FFA) is a potential pathway towards type 2 diabetes among overweight Latino children and adolescents. The objective of this study is to compare fasting free fatty acid levels in Latino children and adolescents who are considered to be prediabetic versus those who are considered to have normal glucose tolerance. ❧ Patients and Methods: Study subjects were healthy overweight Latino children and adolescents from the University of Southern California’s Diabetes Risk due to Ectopic Adiposity in Minority Youth (DREAM) project. Free fatty acid levels were measured through a standard two-hour oral glucose tolerance test. Plasma glucose and insulin were measured at -5 minutes before and 30, 60, and 120 minutes after ingesting glucose solution. Those who were considered to be prediabetic met at least one of the following criteria: fasting glucose ≥100mg/dL, 2-hour glucose between 140-199mg/dL, hemoglobin A1C between 6.0-6.4%. The remaining subjects were considered to have normal glucose tolerance. Univariate analysis used the Student’s t-test to compare mean differences between pre-diabetic and normal glucose tolerance groups. Repeated measures analysis of covariance was used to compare the elevated fasting free fatty acid curves between the prediabetic and normal glucose tolerance groups, adjusting for sex, Tanner stage, and age. ❧ Results: The normal glucose tolerance and prediabetic groups did not differ on age, sex, Tanner stage or BMI-Z (p>0.05). By definition of the groups, the prediabetic group had higher mean hemoglobin A1C, fasting and 2-hour glucose and insulin than the normal glucose tolerance group (p<0.05). The prediabetic group had a higher overall FFA curve compared to the normal glucose tolerance group (p<0.01). Looking at each time measurement individually, at the -5, 30, and 60 minutes, the prediabetic group had higher fasting free fatty acid levels compared to the normal glucose tolerance group. At the 120 min there was no difference in fasting free fatty acid levels between the two groups. ❧ Conclusions: Prediabetic overweight Latino children and adolescents may experience greater overall exposure to circulating fasting free fatty acids. These results are consistent with the lipotoxicity theory of diabetes development. These results support continued investigations of elevated free fatty acids as a potential pathway in the development of type 2 diabetes in children/adolescents.

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Asset Metadata

Creator Moua, Kevin (author)

Core Title Elevated fasting free fatty acids in overweight Latino children and adolescents

School Keck School of Medicine

Degree Master of Science

Degree Program Biostatistics

Publication Date 11/21/2012

Defense Date 11/21/2012

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag Adolescents,Children,fatty acid,Latino,OAI-PMH Harvest,overweight

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Mack, Wendy Jean (committee chair), Azen, Stanley P. (committee member), Eckel, Sandrah (committee member), Weigensberg, Marc (committee member)

Creator Email kmoua@usc.edu

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c3-112648

Unique identifier UC11289052

Identifier usctheses-c3-112648 (legacy record id)

Legacy Identifier etd-MouaKevin-1325.pdf

Dmrecord 112648

Document Type Thesis

Rights Moua, Kevin

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Source University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

Access Conditions The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the a...

Repository Name University of Southern California Digital Library

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