Lower HOMA %B Correlated with Higher Increment of GLP1 a er
OGTT in Subject with Diabetes Risk Allele of TCF7L2 Gene
Poster number: 0252-P
1) 1) 1) 2) 2)
Made Ratna Saraswa , Ketut Suas ka , AAG Budhiarta , Herawa Sudoyo , Safarina G. Malik
1)Endocrinology and Metabolism Division, Department of Internal Medicine Faculty of Medicine Udayana University/Sanglah Hospital
2)Eijkman Ins tute for Molecular Biology, Jl. Diponegoro 69 Jakarta 10430
Transcrip on factor 7 like 2 (TCF7L2) polymorphisms have been consistently reported to be associated with type 2 diabetes. We inves gate whether this diabetes
suscep bility gene related to insulin deficient or insulin resistance and its associa on with GLP1 level a er oral glucose tolerance test in Balinese popula on.
The protocol was approved by Udayana University ethics commi ee and wri en informed consent was obtained from all par cipants. A total of 56 subjects from
popula on in Legian Kuta Bali were par cipated. Genotyping has conducted in the previous study (Saraswa et al., 2011) by PCR-RFLP method. Subject with
heterozygote or mutant of rs12255372 SNP (GT or TT), rs7903146 (CT or TT), and rs10885406 (AG or GG), were grouped into subject carrying diabetes risk allele of
TCF7L2 gene. The second group were wild type of rs12255372 (GG), rs7903146 (CC), and rs10885406 (AA). There were 28 subjects in each group, age and sex matched,
age between 30-74 years, male : female 36 : 20. Par cipants were subjected to oral glucose tolerance test (OGTT), insulin and GLP1 were measured on 0 and 60 minute.
Insulin was measured by solid phase, enzyme-labeled chemiluminescent immunometric assay (Immulite® 2000 Insulin, Cat. No. L2KIN2, Siemens). Determina on of
GLP1 in plasma was based on a compe ve enzyme immunoassay detec ng GLP1 (7-36) amide and GLP1 (9-36) amide in the range of 0,206-50ng/ml (Human GLP1
Elisa, mul species specificity, Cat. No.: RSCYK160R, Biovendor®).
Among 56 subject, 7 (12.50%) were diabetes, prevalence of diabetes was 5/28
(17.85%) in the diabetes risk allele group; 2/28 (7.14%) in the non risk allele group
(Table 1). HOMA %B was lower among subjects carrying diabetes risk allele
compare with subjects without diabetes risk allele, 71.64±24.72 and 103.23±68.00
respec vely (mean difference [-31.59], 95%CI [-60.24]–[-2.93], p=.011). Diabetes
risk allele of SNP in the TCF7L2 gene was associated with low HOMA %B (OR=7.20,
95% CI=1.36–37.96, p=0.011), probability of low HOMA %B among diabetes risk
allele was 87.80%. HOMA %B correlated nega vely with GLP1 level a er 1 hour oral
glucose (Spearman’s rho r= -.281, p= .048) and delta increment of GLP1 (r=-.353,
p=.012), Figure 1.
The result of this study showed the associa on of SNPs TCF7L2 gene with response
of GLP1 increment a er oral glucose load and beta cell func on in insulin secre on
(HOMA %B) in Balinese popula on. Higher response of GLP1 increment and lower
pancrea c beta cell func on (lower HOMA %B) was found in subject with diabetes
risk allele compare with subject without diabetes risk allele of SNPS in the TCF7L2
gene. The reason of this finding is that subject with diabetes risk allele may need
higher increment of GLP1 to increase the insulin secre on in order to maintain
blood glucose in the normal range, which bring up a new concept of GLP1 resistance
of the pancrea c beta cell.
Our previous study in diabetes and normal subjects found lower GLP1 level both
fas ng and 1 hour a er oral glucose loading in diabetes compare with normal
subjects (Lastya et al., 2014). In this recent study, fas ng GLP1 in diabetes was lower
than normal subjects, however 1 hour a er oral glucose load GLP1 level was higher.
The inverse finding of these two studies may relate to different diabetes dura on. In
the previous study, diabetes subjects were inpa ent with diabetes complica on
and diabetes subjects in this recent study was in early stage.
Further study need to elaborate whether disease dura on affect the GLP1 level as
well GLP1 increment during oral glucose load.
Conclusions:
The lower HOMA %B in the TCF7L2 diabetes allele risk group
confirmed that TCF7L2 diabetes suscep bility is associated with impaired beta cell
func on which may cause a respond of increasing GLP1 a er oral glucose load.
Keywords:
TCF7L2, GLP1, HOMA %B
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Copyright © 2015 Made Ratna Saraswati, [email protected]
Conflict of Interest Disclosure: None.
[image:1.2324.1148.2262.1238.1876.2]This poster does not contain any trade names. This poster does not cover any unapproved uses of specific drugs, other products or devices.
Table 1. Characteris c of the Subjects
Subject carrying
diabetes risk allele
of TCF7L2 gene
1)Subject without
diabetes risk
allele
2)Total
n= 28
n=28
n=56
Diabetes prevalence
5/28 (17.85%)
2/28 (7.14%)
7/56 (12.50)
Body weight (kg)
71.52 ± 11.25
70.24 ± 17.40
70.88 ±14.53
Body height (cm)
162.55 ± 9.21
161.17 ± 9.71
161.86 ± 9.40
BMI (kg/m
2)
27.02 ± 3.44
26.73 ± 4.70
26.88 ± 4.08
WC
89.71 ± 9.67
90.60 ± 12.08
90.16 ± 10.85
FPG
111.57 ± 53.48
92.89 ± 7.78
102.23 ± 38.89
1h PG (mg/dL)
191.64 ± 104.53
156.28 ± 41.17
173.96 ± 80.71
2h PG (mg/dL)
155.39 ± 108.75
124.57 ± 41.49
138.98 ± 83.02
Fasting insulin (µIU/mL)
7.14 ± 4.03
7.30 ± 3.76
7.22 ± 3.86
Fasting GLP1 (ng/ml)
3.29 ± 1.19
3.28 ± 0.85
3.28 ±1.02
1h GLP1(ng/ml)
3.63 ± 1.22
3.23 ± 0.84
3.43 ± 1.06
Delta GLP1(ng/ml)
0.34 ± 0.80
– 0.04 ± 0.57
0.148 ± 0.718
HOMA %B
71.64 ± 24.72
103.23 ± 68.00
86.81 ± 52.31
HOMA IR
1.07 ± 0.73
1.32 ± 1.22
1.19 ± 1,00
Note:
1) Heterozygote or mutant of rs12255372 SNP (GT or TT), rs7903146 (CT or TT), and rs10885406 (AG or GG)
2) Wild type of rs12255372 (GG), rs7903146 (CC), and rs10885406 (AA)
BMI=body mass index, WC=waist circumference, FBS=fas ng plasma glucose, 1h PG=1 hour a er 75g glucose
load plasma glucose, 2h PG=2 hour a er 75g glucose load plasma glucose, GLP1=glucagon like pep de 1, 1h
GLP1=1 hour a er 75g glucose load GLP1, Delta GLP1=(1h GLP1 – fas ng GLP1), HOMA %B=homeostasis model
of beta cell func on, HOMA IR= homeostasis model of insulin resistance.
1h
G
LP
1
Delta
G
LP
1
HOMA %B
Spearman's rho: r= -.281, p=.048 Spearman's rho: r=-.353, p=.012HOMA %B
Figure 1. Correla on of HOMA %B with 1h GLP1 and delta GLP1
Note:
HOMA %B=homeostasis model of beta cell func on, 1h GLP1=1 hour a er 75g glucose load GLP1
Delta GLP1=delta of fas ng and 1 hour a er 75g glucose load GLP1 (1h GLP1 – fas ng GLP1).
Results
Discussion
References
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