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The Journal of Clinical Endocrinology & Metabolism 87(8):3735–3739
Copyright © 2002 by The Endocrine Society
Unlike Type 2 Diabetes, Type 1 Does Not Interact with
the Codon 54 Polymorphism of the Fatty Acid Binding
Protein 2 Gene
ANGELIKI GEORGOPOULOS, OMER ARAS, MARINA NOUTSOU,
AND
MICHAEL Y. TSAI
Minneapolis Veterans Affairs Medical Center (A.G.), Departments of Medicine (A.G.) and Laboratory Medicine and
Pathology (O.A., M.Y.T.), University of Minnesota, Minneapolis, Minnesota 55417; and the Second Department of Medicine
(M.N.), Athens University Medical School, 115 27 Athens, Greece
In type 2 diabetes, the threonine (Thr) for alanine (Ala) codon
54 polymorphism of the fatty acid binding protein 2 gene is
associated with elevated fasting and postprandial triglycerides and dyslipidemia when compared with the wild type (Ala54/Ala-54). To assess whether this is the case in patients with
type 1 diabetes, who usually do not manifest the metabolic
syndrome, we screened 181 patients with similar glycemic
control as the type 2 patients. Thirty percent were heterozygous, and 9% were homozygous for the polymorphism. Mean
(ⴞSEM) fasting plasma triglyceride levels in patients with the
wild type (n ⴝ 84), those heterozygous for Ala-54/Thr-54 (n ⴝ
44), and those homozygous for the Thr-54 (n ⴝ 13) were 1.0 ⴞ
I
N CONTRAST TO PATIENTS with type 2 diabetes, those
with type 1 diabetes are usually normolipidemic as
judged by a fasting lipid profile (1). We have previously
reported that the G to A polymorphism of codon 54 of the
fatty acid binding protein 2 (FABP2) gene is associated with
dyslipidemia and elevated fasting and postprandial triglycerides in type 2 diabetes (2). The mechanism involved is
presumed to be an interaction of the polymorphism with
type 2 diabetes, resulting in the observed lipid abnormalities.
FABP2 is an intracellular protein expressed only in the intestine (3). The polymorphism, which consists of the substitution of Thr for Ala is functional and, as shown in in vitro
experiments, it increases the affinity of the FABP2 for long
chain fatty acids and is associated with increased triglyceride
secretion in a human intestinal cell line (4).
The Thr-54 allele has been associated with increased fat
oxidation and insulin resistance in some but not all studies
(5–12). It was shown to be associated with elevated postprandial triglyceride-rich lipoprotein levels in nondiabetic,
obese middle-aged subjects homozygous for the Thr-54 allele
compared with the wild-type (Ala-54/Ala-54; Ref. 13). However, in a study of young, nonobese, nondiabetic men, there
were no differences in fasting or postprandial triglyceride
levels between those carrying and those lacking the polymorphism (14). Because type 1 diabetes is usually seen in
nonobese, younger, and less insulin-resistant individuals,
compared with type 2 diabetes, we decided to investigate
Abbreviations: Ala, Alanine; apo, apolipoprotein; AUC, area under
the curve; BMI, body mass index; FABP2, fatty acid binding protein 2;
HDL, high-density lipoprotein; LDL, low-density lipoprotein; Thr, threonine; VA, Veterans Affairs; VLDL, very low-density lipoprotein.
0.07, 1.1 ⴞ 0.17, and 1.2 ⴞ 0.23 mmol/liter, respectively. In addition, there were no differences in total, low-density lipoprotein, high-density lipoprotein, and non-high density lipoprotein cholesterol among the three groups. After a fat load, the
postprandial area under the curve of triglyceride in plasma,
chylomicrons, and very low-density lipoprotein were similar
between the wild type (n ⴝ 18) and the Thr-54 homozygotes
(n ⴝ 12). In conclusion, in contrast to type 2, type 1 diabetes
does not interact with the codon 54 polymorphism of the fatty
acid binding protein 2 gene to cause hypertriglyceridemia/
dyslipidemia. Insulin resistance could account possibly for
this difference. (J Clin Endocrinol Metab 87: 3735–3739, 2002)
whether the codon 54 polymorphism of the FABP2 gene is
associated with fasting and postprandial triglyceride elevation or dyslipidemia in type 1 diabetes.
Experimental subjects and study protocol
All study participants were patients with type 1 diabetes
as defined using criteria of the American Diabetes Association. To assess the prevalence of the polymorphism, 181
diabetic patients who responded to an announcement placed
at the blood drawing room of the Minneapolis Veterans
Affairs (VA) Medical Center or who were patients of the
diabetic or medical clinics at the VA and at the Second Department of Medicine, Athens University Medical School,
were screened. The announcement solicited volunteer patients with diabetes to be screened for our study. All patients
signed consent forms approved by the institutional review
board. Study participants were 98% Caucasians. Patients on
lipid-lowering drugs or steroids and patients with secondary
causes of hyperlipidemia except diabetes were excluded
from the study. Subjects included in the study (n ⫽ 141) were
in good health as determined by review of their history and
physical examination and routine laboratory studies (normal
hematologic, liver, renal, and thyroid studies). Given that the
population of the VA is mostly male, to carry out postprandial studies in equal numbers of men and women homozygous for the polymorphism, 42 female subjects from Athens
were screened for the polymorphism from blood samples
shipped to Minneapolis. After a 12-h fast, blood was drawn
for a fasting lipid profile in all 141 study participants. In a
smaller number of study participants (n ⫽ 30) who were not
homozygous for the apolipoprotein (apo) E2 or apo E4 allele,
postprandial studies were carried out as described below.
3735
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J Clin Endocrinol Metab, August 2002, 87(8):3735–3739
Georgopoulos et al. • Diabetes and FABP2 Gene Polymorphism
Except for four females homozygous for the polymorphism,
who underwent the postprandial studies in Athens, all other
studies were carried out in Minneapolis. The same protocol
was used at both sites. Dr. M. Noutsou, who has done similar
studies in Minneapolis during her research fellowship, carried out the studies in Athens. The postprandial lipid protocol is described below. Subjects ingested a shake containing
egg white, Sweet and Low, fruit flavor, 55 g of corn oil, and
60,000 IU of retinol per square meter of body surface. We
decided not to include sucrose or other carbohydrates in the
meal, because they can increase the production of hepatic
triglycerides. Blood was drawn through an angiocatheter
before and every 2 h for a period of 8 h for measurements of
plasma triglyceride and in two triglyceride-rich lipoprotein
subfractions: Sf ⬎ 400 (chylomicrons), and Sf 20 – 400 [very
low-density lipoprotein (VLDL) and chylomicron remnants].
Subjects were sitting or lying during the duration of the
study. No other meal was consumed until the study was
completed. Subjects were encouraged to drink water after
each blood drawing. To avoid hypoglycemia, 40% of the
morning long-acting insulin dose was administered, and
blood glucose was monitored at each blood sampling time.
If an occasional blood glucose drop of less than 3.3 mmol/
liter occurred, it was treated with a glass of fruit juice.
chloramphenicol, 1.3 mg/ml e-aminocaproic acid, 0.05 mg/ml gentamycin, 0.01 mg/ml benzamidine, and 10 U/ml Trasylol (16). Plasma was
separated by centrifugation at 4 C; the plasma samples from Athens were
shipped on ice after addition of the cocktail; triglyceride-rich lipoprotein
subfractions were separated and analyzed within 5–7 d.
Materials and Methods
Detection of the polymorphism
Retinyl esters were measured in the isolated triglyceride-rich lipoprotein subfractions. Samples were covered with foil to be protected from
light and were kept at ⫺20 C. Retinyl acetate was added to the samples
as internal standard. The samples were extracted with 4 ml ethanol, 5
ml hexane, and 4 ml water. The hexane (upper) phase was collected and
evaporated under nitrogen. The residue was dissolved in 20 ␮l of ethanol
and injected to a Beckman HPLC using a Bondapak C18 column. The
mobile phase was 100% methanol, and the flow rate was 2 ml/min (19).
The amount of retinyl ester was calculated on the basis of retinyl palmitate standard read at 326 nm with the Gold System software. Apo B
measurement in the lipoprotein subfractions was performed at the laboratory of Dr. P. Alaupovic in the Oklahoma Research Foundation
(Oklahoma City, OK) by using an electroimmunoassay method (20).
DNA isolation was carried out from 10 ml of blood drawn in EDTA
tubes, using a commercially available kit from Puregene (Gentra Systems, Minneapolis, MN).
DNA amplification and digestion by restriction enzyme were done
according to the method described by Baier et al. (5) using digestion by
HhaI to detect the Ala 54 Thr polymorphism, which disrupts a HhaI site.
DNA was amplified by PCR, using primers 5⬘-ACAGGTGTTAATATAGTGAAAAG-3⬘and 5⬘-TACCCTGAGTTCAGTTCCGTC-3⬘ from exon
2. The PCR buffer contained 2.5 mmol/liter MgCl2, 0.2 mmol/liter of
each deoxynucleotide triphosphate (dNTP), and 1.25 U of Amplitaq
DNA polymerase. Temperature was cycled 30 times (60 sec at 95 C, 60
sec at 55 C, and 2 min at 72 C, followed by a 3-min extension at 72 C).
The PCR product was digested by HhaI at 37 C for 3.5 h or overnight,
applied to a 3% agarose gel containing 1 mg/ml of ethidium bromide,
electrophoresed for 40 min at 120 V, and photographed under UV light.
The PCR products that lack the HhaI site migrate as one 180-bp fragment
(those carrying the Thr-54), but PCR products containing the HhaI site
are cleaved to two fragments (a 99 bp and an 81 bp).
Apo E genotyping
DNA samples were genotyped using PCR amplification followed by
restriction enzyme digestion (15). Each amplification reaction contained
PCR buffer with 15 mmol/liter MgCl2, nanogram amounts of genomic
DNA, 20 pmol apo E forward (5N TAA GCT TGG CAC GGC TGT CCA
AGG A 3N) and reverse (5N ATA AAT ATA AAA TAT AAA TAA CAG
AAT TCG CCC CGG CCT GGT ACA C 3N) primers, 1.25 mmol/liter
of each dNTP, 10% dimethyl sulfoxide, and 0.25 ␮l Amplitaq DNA
polymerase. Reaction conditions in a thermocycler included an initial
denaturing period of 3 min at 95 C, 1 min at 60 C, and 2 min at 72 C,
followed by 35 cycles of 1 min at 95 C, 1 min at 60 C, 2 min at 72 C, and
a final extension of 1 min at 95 C, 1 min at 60 C, and 3 min at 72 C. PCR
products were digested with HhaI and separated on a 10% polyacrylamide nondenaturing gel and stained with silver nitrate. Known apo E
isoform standards were included in the analysis.
Handling of blood samples
To avoid lipoprotein degradation, blood samples for lipoprotein analysis were collected in tubes containing 1 mg/ml EDTA, 0.02 mg/ml
Determination of fasting lipoprotein parameters
Plasma triglyceride and total cholesterol were measured enzymatically by commercially available kits (Waco Chemicals, Richmond, VA,
and Boerhinger Mannheim Diagnostics, Indianapolis, IN). The coefficient of variation of these assays is 3.5% for the former and 4% for the
latter. High-density lipoprotein (HDL) cholesterol was measured by
heparin-manganese precipitation according to the Lipid Research Clinics protocol. These measurements are currently performed in the VA
laboratory and are under quality control testing with the Northwest
Lipid Research Laboratory (Seattle, WA).
Isolation of lipoprotein subfractions
All isolations were performed under aseptic conditions within 48 h
from harvesting of plasma. We used salt density gradient ultracentrifugation according to the method of Lindgren (17) as modified by
Redgrave (18) to isolate the triglyceride-rich lipoprotein subfractions as
published previously (2). Two subfractions were isolated: Sf ⬎ 400 at
4.5 ⫻ 106 g ⫻ min and Sf 20 – 400 at 183.2 ⫻ 106 g ⫻ min.
Determination of retinyl ester and apo B in the
isolated subfractions
Statistical analysis
Standard statistical methods (21) were used to display and analyze
the data. The area under the triglyceride curve was calculated by the
trapezoidal rule. The BMDP/Dynamic statistical package (BMDP Statistical Software, Inc., Los Angeles, CA) was used for the analyses.
Comparisons between groups were assessed using the nonparametric
Mann-Whitney rank-sum test. The effect of FABP2 Thr-54 allele was
assessed using an ANOVA (program 2V of BMDP) in which this qualitative factor was entered at three levels (0, absent; 1, heterozygous; 2,
homozygous).
The postprandial studies were analyzed by repeated measure
ANOVA. Finally, the triglyceride/retinyl ester ratios were log-transformed to normalize their distribution and stabilize the variance (21).
Results
One hundred eighty-one patients with type 1 diabetes
were screened for the Thr-54 polymorphism of the FABP2
gene. The population consisted mostly of white men and
women, which is typical of the population served by the two
study sites. One hundred ten individuals (61%) had the wild
type (Ala-54/Ala-54), 54 (30%) were heterozygotes (Ala-54/
Thr-54), and 17 (9%) were homozygous for the Thr-54 allele.
As mentioned above, we excluded patients on lipid-lowering
medications or steroids and those with abnormal liver, kidney, or thyroid function tests. We then assessed in 141 sub-
Georgopoulos et al. • Diabetes and FABP2 Gene Polymorphism
J Clin Endocrinol Metab, August 2002, 87(8):3735–3739 3737
jects whether dyslipidemia or elevated fasting plasma triglyceride levels were associated with the Thr-54 allele by
comparing the lipid profile of the patients who lacked the
Thr-54 allele (wild type) with that of the patients who were
heterozygous or homozygous for it. As shown in Table 1,
fasting plasma triglyceride levels were similar in all groups.
There were no significant differences in mean age, body mass
index (BMI), glycohemoglobin, and total LDL, HDL, and
non-HDL cholesterol levels among the three groups.
To address the question whether postprandial triglyceride
levels were affected by the Thr-54 allele of the FABP2 in men
and women with type 1 diabetes, we gave a fatty meal to 30
patients; group A consisted of 18 patients with the wild type
(12 men and 6 women), and group B consisted of 12 homozygous for the Thr-54 allele (6 men and 6 women). The
apo E allele distributions for the two groups were similar
(data not shown). The patients who underwent the postprandial studies were a representative sample of the groups
they belonged to with regard to confounding factors, because
they were all Caucasians, of similar age, BMI, and glycemic
control to the rest of the subjects in their corresponding group
(data not shown). As expected, because of the lack of both
within-group and between-group differences in age, BMI,
and glycemic control, shown in Table 1, these parameters
were similar between the two groups of representative subjects included in the postprandial studies (data not shown).
There was no effect of gender or gender by polymorphism
interaction on plasma triglyceride. Therefore, the plasma
triglyceride levels of both genders were pooled. In addition,
the levels of postprandial triglyceride in plasma over time
were similar in the Thr-54 homozygotes compared with the
wild type (Fig. 1, top panel). The area under the curve (AUC)
of the plasma triglyceride levels before or after subtracting
the baseline was not different between the two groups. To
assess whether the distribution of triglyceride in the two
isolated postprandial triglyceride-rich lipoprotein subfractions differed between the two groups, we compared the
AUC of the triglyceride levels in the chylomicron subfraction
(Sf ⬎400) and the VLDL/chylomicron remnant subfraction
(Sf 20 – 400). As shown in Fig. 1, bottom panel, there were again
no differences between the two groups. However, the
triglyceride/retinyl ester ratio in the chylomicron subfraction (Sf ⬎400), measured at 4, 6, and 8 h after fat ingestion,
was significantly higher in those who were homozygous for
the polymorphism compared with the wild type (P ⫽ 0.007;
F test, ANOVA; Fig. 2). This is consistent with a higher
triglyceride content of the chylomicron particles in those
carrying the polymorphism. A smaller nonsignificant difference (ANOVA) in the triglyceride to retinyl ester ratio was
seen in the VLDL/chylomicron remnant subfraction (Sf 20 –
400) between the two groups. The mean values for the wild
type vs. the Thr-54 homozygotes were as follows: at 4 h, 8.7
vs. 9.5; at 6 h, 8.4 vs. 8.9; and at 8 h, 8.2 vs. 8.6. Lastly, to assess
whether the number of particles in the VLDL/chylomicron
remnant subfraction (Sf 20 – 400) differed between the two
groups, we measured apo B levels in this subfraction. The
AUC of apo B was not significantly different between the two
groups (t test); the mean ⫾ sem was 121.7 ⫾ 41.7 in the wild
type vs. 105.4 ⫾ 66.7 mg*h/liter in the Thr-54 homozygotes.
Discussion
Our study shows that in patients with type 1 diabetes the
frequency of the Thr-54 homozygotes for the Thr-54 polymorphism was similar to that of type 2 diabetes i.e. 9% vs.
FIG. 1. Effect of the Thr-54 allele of the FABP2 gene on mean (⫾SEM)
triglycerides after a fat load. Top, Plasma triglycerides time course.
Bottom, Mean AUC of postprandial triglycerides in chylomicrons (Sf
⬎400) and VLDL/chylomicron remnants (Sf 20 – 400). Hatched bars,
Patients with the wild type (Ala-54/Ala-54); solid bars, patients homozygous for the Thr-54 allele.
TABLE 1. Characteristics of study patients with type 1 diabetes grouped by codon 54 FABP2 genotype
Genotype
Wild type
n ⫽ 84
Heterozygous
n ⫽ 44
Homozygous
n ⫽ 13
Codon 54 allele
Age (yr)
BMI (kg/m2)
Glyco-hemoglobin (%)
Total cholesterol (mmol/liter)
Triglycerides (mmol/liter)
HDL cholesterol (mmol/liter)
Non-HDL cholesterol (mmol/liter)
LDL cholesterol (mmol/liter)
Ala/Ala
39 ⫾ 1.3
24.9 ⫾ 0.4
9.7 ⫾ 0.3
4.7 ⫾ 0.13
1.0 ⫾ 0.07
1.3 ⫾ 0.04
3.4 ⫾ 0.13
2.9 ⫾ 0.10
Ala/Thr
40 ⫾ 1.9
25.7 ⫾ 0.6
10.0 ⫾ 0.5
4.8 ⫾ 0.28
1.1 ⫾ 0.17
1.2 ⫾ 0.04
3.8 ⫾ 0.18
3.3 ⫾ 0.16
Thr/Thr
44 ⫾ 2.6
24.0 ⫾ 0.3
10.3 ⫾ 0.8
4.6 ⫾ 0.39
1.2 ⫾ 0.23
1.3 ⫾ 0.12
3.5 ⫾ 0.34
3.0 ⫾ 0.23
Data are expressed as mean ⫾
SEM.
3738
J Clin Endocrinol Metab, August 2002, 87(8):3735–3739
Georgopoulos et al. • Diabetes and FABP2 Gene Polymorphism
11%, respectively (2). These values are similar to those reported by others in both control and diabetic subjects (6 –12).
However, our data show that in type 1 diabetes the FABP2
polymorphism is not associated with the hypertriglyceridemia/dyslipidemia phenotype, because the triglyceride, LDL,
HDL, and non-HDL cholesterol levels were similar in all
study groups (Table 1). This is clearly different from the
interaction of the polymorphism with type 2 diabetes, which
we reported previously to result in the phenotype of hypertriglyceridemia/dyslipidemia (2). Our results show that the
lack of an effect of the FABP2 polymorphism in type 1 diabetes is not due to differences in any confounding factors
like BMI, age, or glycemic control, because these parameters
were similar among the three genotypic groups with type 1
diabetes (Table 1).
In addition, in type 1 diabetes there were no differences in
postprandial plasma and chylomicron triglyceride levels between the Thr-54 homozygotes and the wild type (Fig. 1).
This again is in contrast to the results observed in type 2
diabetes where both fasting and postprandial plasma triglyceride and postprandial chylomicron triglyceride were
elevated in those homozygous for the polymorphism vs. the
wild type (2). The only difference between the two groups in
patients with type 1 diabetes was in the particle composition
of the chylomicrons (Sf ⬎400). We used the measurement of
retinyl esters as a marker of the intestinal origin of the particles, because retinyl esters are formed in the intestine after
ingestion of retinol and are not resecreted in the circulation
as VLDL after their uptake by the liver (22). We calculated
the triglyceride to retinyl ester ratio of the chylomicrons to
assess intestinal particle core composition and found it to be
FIG. 2. Effect of the Thr-54 allele of the FABP2 gene on mean (⫾SEM)
postprandial triglyceride (TG) to retinyl ester (RE) ratio in the chylomicron (Sf ⬎400) subfraction at 4, 6, and 8 h after a fat load (P ⫽
0.007; F test ANOVA). A logarithmic transformation of the data was
performed (see Materials and Methods).
enriched in triglyceride in the Thr-54 homozygotes vs. the
wild type (Fig. 2). This goes along with the functional alteration of the FABP2, in the presence of the codon 54 polymorphism of the gene described in in vitro studies. Those
studies reported that the Thr-54 FABP2 polymorphism was
associated with increased affinity for long chain fatty acids,
which lead to increased intestinal fatty acid transport and
increased intestinal triglyceride secretion when compared
with the wild type (4).
What are the differences between the study patients with
type 1 and type 2 diabetes that could account for the lack of
an interaction of the Thr-54 polymorphism in type 1 diabetes? Glycemic control was similar between the two types, but
age and BMI were higher in the study patients with type 2
vs. those with type 1 diabetes. Specifically, the ages of type
1 vs. type 2 diabetes in the three genotypes were as follows:
for the wild type, 39 vs. 57 yr; for the Thr-54 heterozygotes,
40 vs. 58 yr; and for the Thr-54 homozygotes, 44 vs. 56 yr. To
assess the effects of age, we performed data analysis comparing patients with type 1 diabetes and age below 40 yr
(young) vs. those above 50 yr (older). Both Thr-54 homozygotes and heterozygotes were included in this analysis. There
were no differences in plasma triglycerides between those
carrying the Thr-54 polymorphism and the wild type in
either age group. The mean ⫾ sem plasma triglyceride values
were as follows: young wild type, 0.898 ⫾ 0.08, vs. young
Thr-54 carriers, 0.964 ⫾ 0.11; older wild type, 1.3 ⫾ 0.132, vs.
older Thr-54 carriers, 1.30 ⫾ 0.154 mmol/liter. The mean ages
of the young and older type 1 groups were 31 and 56 yr,
respectively. It is of note, that the average age of the older
type 1 group (56 yr) was very similar to the average ages of
all genotype groups with type 2 diabetes (56 –58 yr). Therefore, it is unlikely that differences in age can explain the lack
of interaction of the Thr-54 polymorphism of the FABP2 gene
with type 1 diabetes.
A similar data analysis was performed using data from
both type 1 and type 2 diabetes (reported by us previously;
Ref. 2) to assess the effect of BMI on the differences between
the two types of diabetes in the manifestation of hypertriglyceridemia in the carriers of the Thr-54 polymorphism.
Plasma triglycerides were compared in lean (BMI ⱕ 26 kg/
m2) vs. obese (BMI ⱖ 28 kg/m2) study subjects. Both homozygotes and heterozygotes for the Thr-54 polymorphism
were included in this analysis. As shown in Table 2, the
hypertiglyceridemia phenotype was present in both lean and
obese subjects with type 2 diabetes carrying the polymorphism. There was no such effect in the patients with type 1
diabetes. It seems therefore unlikely that BMI could account
for the observed differences between type 1 and type 2 di-
TABLE 2. Effect of BMI on plasma triglycerides (mmol/liter) in type 1 and 2 diabetic study patients grouped by the codon 54
FABP2 genotype
Genotype
Type 1 Diabetes
Lean (BMI ⱕ 26 kg/m2)
Obese (BMI ⱖ 28 kg/m2)
Type 2 Diabetes
Lean (BMI ⱕ 26 kg/m2)
Obese (BMI ⱖ 28 kg/m2)
Data are expressed as mean ⫾
SEM.
Wild type (Ala/Ala)
Carrier (Thr/Thr or Ala/Thr)
1.02 ⫾ 0.086 (n ⫽ 52)
1.24 ⫾ 0.161 (n ⫽ 36)
1.03 ⫾ 0.103 (n ⫽ 15)
1.27 ⫾ 0.196 (n ⫽ 10)
1.53 ⫾ 0.157 (n ⫽ 14)
2.09 ⫾ 0.108 (n ⫽ 59)
2.33 ⫾ 0.371 (n ⫽ 8)
3.09 ⫾ 0.228 (n ⫽ 58)
Georgopoulos et al. • Diabetes and FABP2 Gene Polymorphism
abetes, regarding the manifestation of hypertriglyceridemia
in the patients carrying the Thr-54 FABP2 polymorphism.
Another characteristic difference between the two types of
diabetes that needs to be considered is the presence of significantly more insulin resistance in type 2 vs. type 1 diabetes.
We have no data on insulin resistance at this point. It is of
interest that studies performed in nondiabetic individuals
carrying the polymorphism show different results in young
(in their 20s) nonobese men (14) than in older (in their 50s)
obese men (13). There were no differences in fasting and
postprandial triglycerides in the young men (14), whereas
the postprandial, but not the fasting plasma triglyceride levels were elevated in the older men who were homozygous for
the Thr-54 polymorphism (13). These data are consistent with
the hypothesis that insulin resistance associated with increasing age and obesity could be mediating the interaction
of the polymorphism with type 2 diabetes. However, other
unknown factors, like an interaction of the Thr-54 FABP2
polymorphism with other genetic polymorphisms affecting
the triglyceride levels, such as those in hepatic or lipoprotein
lipase genes, cannot be ruled out. Further studies are needed
to elucidate the mechanisms involved.
In conclusion, our results show that in contrast to type 2,
type 1 diabetes does not interact with the codon 54 polymorphism of the FABP2 gene to cause hypertriglyceridemia/
dyslipidemia. Because glycemic control between the two
types of diabetes was similar, other factors, like insulin resistance or unknown genetic interactions, may be involved in
the development of the diabetic dyslipidemia phenotype.
Acknowledgments
J Clin Endocrinol Metab, August 2002, 87(8):3735–3739 3739
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
We acknowledge the expert technical help of Laura Salvati of the staff
of the Special Diagnostic Treatment Unit and the staff of the blood
drawing room at the Minneapolis Veterans Affairs Medical Center.
16.
Received December 5, 2001. Accepted April 26, 2002.
Address all correspondence and requests for reprints to: Angeliki
Georgopoulos, M.D., Medicine Service 111M, VAMC, One Veterans
Drive, Minneapolis, Minnesota 55417. E-mail: [email protected].
This research was supported by Department of Veterans Affairs
funds.
18.
17.
19.
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