Diabetes Research and Clinical Practice - Volume 120 - Supplement 1 - October 2016

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594 individuals with diabetes were recruited, including 201
with diabetic retinopathy and 393 with diabetes of ≥5 years
duration but without retinopathy. GCKR rs780094 genotyping
was conducted with Sequenom. The diagnose and grading of
diabetic retinopathy were according to fundus examination.
24-hour urinary albumin excretion rate and estimated
glomerular filtration rate were used to evaluate diabetic
nephropathy.
Results: In the first stage, rs10010131 was significantly
associated with diabetic retinopathy (OR = 1.629, 95% CI
1.019–2.606, P = 0.0416) after adjusting for duration of diabetes,
HbA1c, blood pressure and body mass index. However,
rs10010131 did not show association with Diabetic nephro-
pathy (OR = 0.991, 95% CI 0.619 –1.586, P = 0.970). In the second
stage, no significant association of rs10010131 and DR was
observed (OR = 0.837, 95% CI 0.408 –1.716, P = 0.627). The meta-
analysis showed that rs10010131 was not significantly asso-
ciated with DR (OR = 1.334, 95% CI 0.901–1.977, P = 0.150).
Conclusion: WFS1 rs10010131 was not associated with diabetic
nephropathy and diabetic retinopathy in the Chinese indivi-
duals with type 2 diabetes.
PB-11
In type 2 diabetes, smoking cessation is associated with
deterioration in glycemic control and this is unrelated to
weight gain
Takako KIKUCHI 1*, Kenichiro ENOOKU2,
Akifumi KUSHIYAMA 1, Yoko YOSHIDA1,
Sayaka WAKABAYASHI 1, Yasuhiko IWAMOTO1. 1The Institute
for Adult Diseases, Asahi Life Foundation, 2University of
Tokyo, Japan
Background/aims: Diabetes mellitus (DM) are closely
associated with the development of cardiovascular diseases.
Smoking represents one of the most important preventable
risk factors for the development of atherosclerosis. In patients
with DM, smoking works synergistically in increasing the risk
of cardiovascular events and death.
There are some studies suggesting that diabetes control
deteriorates temporarily during the first year after smoking
quitting. The aims of this study were to examine whether or
not quitting smoking was associated with altered diabetes
control, and whether or not this association was mediated by
weight change.
Patients and methods: From May 2010 to October 2014, we
recruited 131 patients onmedication for DM and in hope to use
Varenicline for smoking cessation at the Institute for Adult
Diseases, Asahi Life Foundation. Physical examinations and
blood samples were taken on the day of starting admini-
stration, and every two weeks thereafter. Varenicline were
administered for three months. All patients gave informed
written consent. We investigated the association between a
quit event, smoking abstinence duration, change in HbA1c,
and the mediating effect of weight change.
Results: 97 (74.0%) quit smoking and remained abstinent for at
least 1 year. The majority (89.7%) was male and the median
body mass index (BMI) was 24.2 kg/m 2 (IQR 21.8–26.9).
BMI and HbA1c level showed a significant increase during
smoking cessation. But this increase in HbA1c was not
mediated by weight change. The changes in HbA1c during
smoking cessation were not correlated with the changes in
BMI, and HbA1c level increased in 75.0% of patients who
decreased BMI during smoking cessation. In patients whowere
treated with insulin, HbA1c level increased higher than in
those who were treated with oral drugs only. Patients who
increased BMI during smoking cessation gained significantly
more weight within the first year after quitting than thosewho
decreased BMI during smoking cessation.
Spearman’s rank correlation revealed that the white blood cell
count and neutrophil to lymphocyte ratio (NLR) significantly
improved immediately after smoking cessation. High-density
lipoprotein cholesterol levels increased after smoking cessa-
tion, although BMI also significantly increased.
Conclusions: In type 2 diabetes, smoking cessation is asso-
ciated with deterioration in glycemic control and this is
unrelated to weight gain, although smoking cessation signifi-
cantly and immediately decreased systemic inflammation and
increased serum HDL cholesterol level in diabetic patients.
PB-12
New findings of genetic determinants of sulfonylurea efficacy
from next-generation sequencing in sulfonylurea sensitive
patients
Qian REN1, Xueyao HAN 1, Siqian GONG1 , Yumin MA1,
Linong JI1*. 1Peking University People’s Hospital, China
Background: The genetic determinants for sulfonylureas
efficacy has not been well understood until now.
Methods: This pharmacogenetic study was divided into three
stages. In the First stage, we screened a total of 747 patients
with type 2 diabetes enrolled from the Xiaoke Pills Clinical
Trial to select patients with extreme phenotype. We regarded
“very sensitive to sulfonylurea ” as an extreme phenotype,
including two conditions (1) sulfonylurea treatment best
responders: HbA1c level was decreased by more than 1%, and
body weight increased by more than 5% during the first three
months of follow up. (2) hypoglycemia occurred so frequently
that the dose of glybeclamide was 1.25 mg/d during the whole
follow up period as initial dose or the patient lost follow up
because of hypoglycemia. In the second stage, next-generation
sequencing was performed in patients with extreme pheno-
type. Variants with prediction of harmful were selected and
validated by first-generation sequencing and re-sequenced
them in subjects with normal glucose metabolism. In the third
stage, we did case-control study in 340 patients treated with
glybenclamide to investigate if the selected variants could
really influence sulfonylurea efficacy.
Results: We selected 32 “sulfonylurea very sensitive patients’.
After next-generation sequencing, we selected 48 variants (39
genes), which seem to be harmful in prediction. Then 26
variants were successfully validated by first-generation
sequencing and were re-sequenced in 20 normal glucose
metabolism subjects to compare genotype between patients
and controls. The genotypes were similar between patients
and normal glucose metabolism subjects, except rs56743379.
Rs56743379 was an insert/delete mutation in exon 5 of
DMKN gene. So we did case-control study in 340 patients
treated with glybenclamide to investigate the association
between rs56743379 and sulfonylurea efficacy. There were 35
(10.3%) homozygous with insert mutation (Ins group), 50
(14.7%) homozygous with delete mutation (Del group). And
because there were 58 SNPs downstream to the rs56743379,
including 3 SNPs hit on the same contig position of rs56743379.
So we regarded 255 (75%) subjects as heterozygous with
varying degrees of insert/delete mutation (Hetero group).
There were no significant difference between genotypes and
treatment failure of glybenclamide (OR = 1.488, 95%CI 0.937–
2.361, P = 0.092). However, Logistic regression analysis showed
that rs56743379 were significantly associated with proportion
of patients with FPG < 7 mmol/L after adjustment of age and
sex (OR = 0.630, 95% CI 0.405–0.979, P = 0.040).
Conclusions: Rs56743379 in DMKN gene may be associated
with sulfonylurea efficacy. Further pharmacogenetic and
functional studies are needed to confirm this observation.
PB-14
Impact of diabetes and Intercellular adhesion molecule-1
genetic polymorphism on coronary artery disease
susceptibility in Taiwan
Chihung CHOU1,2*, Kwo-Chang UENG3,4, Shun-Fa YANG1,5,
Po-Hui WANG1,4,6. 1Institute of Medicine, Chung Shan Medical
University, Taichung, 2Division of Cardiology, Department of Internal
Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65–S211 S79