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

156 / 244

Conclusions: The prevalence of impaired thermal thresholds
was extremely high in the type 2 diabetic patients. Age, male
sex, and a low TBI are major determinants of peripheral small
fiber dysfunction, identified as impaired thermal thresholds of
the lower extremities in patients with type 2 diabetes without
apparent cardiovascular disease. Early detection of high-risk
groups is warranted to reduce complications associated with
diabetic foot ulcerations.
PE-23
Overexpression of GLP-1 receptor in hepatocellular carcinoma
causes anti-cancer effect of Exendin-4
Tomohiro NODA 1, Takashi NOMIYAMA1*,
Takako KAWANAMI 1, Yuriko HAMAGUCHI1,
Tomoko TANAKA 1, Toshihiko YANASE1. 1Fukuoka University,
Japan
Incretin therapy has emerged as one of the most popular
treatment for type 2 diabetes. GLP-1R agonist, Exendin-4(Ex-4),
has received much attention, because of its tissue protective
effects beyond glycemic control. We have previously reported
vascular protective effect (Diabetes 2010, BBRC 2011) and anti-
prostate cancer effect (Diabetes 2014, PLOS ONE 2015) of Ex-4.
On the other hand, liver cancer is one of the most popular and
critical cancers in patients with type 2 diabetes and fatty liver.
Then, we next examinedwhether GLP-1 action could attenuate
liver cancer in the present study.
First of all, we treated HepG2 cells, human hepatocellular
carcinoma cell line, with Ex-4. Unfortunately, Ex-4 did not
attenuate HepG2 cell proliferation in vivo and in vitro, because
GLP-1 receptor expression was almost negligible amount in
HepG2 cells. Then, we next demonstrated overexpression of
human GLP-1 receptor in HepG2 cells using lentivirus vector.
Abundant GLP-1 receptor expressionwas observed HepG2 cells
transfected GLP-1R (HepG2-GLP1R), compared with HepG2
cells transfected with control vector (HepG2-control). Ex-4
increased intracellular cAMP concentration in HepG2-GLP1R
significantly, suggesting that overexpressed GLP-1 receptor
should be intact. Ex-4 attenuated cell number of HepG2-GLP-
1R in a growth curve significantly and dose dependently. As a
mechanism by which Ex-4 attenuates HepG2-GLP1R, we
investigated reduction of epidermal growth factor receptor in
HepG2 cells. We next transplanted HepG2-GLP1R or HepG2-
control into athymic nude mice. Surprisingly, tumor size of
HepG2-GLP-1R was larger than HepG2-control, however Ex-4
treatment decreased tumor size and Ki67 positive cells of
HepG2-GLP-1R compared with non-treated HepG2-GLP1R.
These data suggest that overexpressed GLP-1 receptor causes
anti-cancer effect of Ex-4 in hepatocellular carcinoma.
PE-24
Diabetic retinopathy predicts all-cause mortality in type 2
diabetic patients with chronic kidney disease without overt
albuminuria
Yu Hsuan LI 1, Wayne H.-H. SHEU1,3,4, Shih-Yi LIN1,3,5,
Jun-Sing WANG 1,2, I-Te LEE 1,3*. 1Division of Endocrinology and
Metabolism, Department of Internal Medicine, Taichung Veterans
General Hospital, Taichung, 2Institute of Clinical Medicine, School of
Medicine, National Yang-Ming University, 3School of Medicine,
National Yang Ming University, 4College of Medicine, National
Defense Medical Center, Taipei, 5Center for Geriatrics and
Gerontology, Taichung Veterans General Hospital, Taichung, Taiwan
Diabetic nephropathy (DN) is a complex disease with hetero-
geneous clinical courses. Chronic kidney disease (CKD)
without overt albuminuria represents a distinct phenotype of
DN. In this study, we aimed to investigate whether diabetic
retinopathy (DR), another chronicmicrovascular complication,
can predict all-cause mortality in these patients.
Methods: In this retrospective cohort, type 2 diabetic patients
who had hospitalized with the main diagnosis of poorly
glucose control to one medical center in central Taiwan,
between August 1996 and August 2007, were consecutively
enrolled. We collected data from medical records, including
estimated glomerular filtration rate (eGFR), albuminuria,
medication history, and linked to mortality information
provided from the national registry dataset. Chronic kidney
disease (CKD) was defined as eGFR <60 mL/min/1.73 m2
calculated by using the Modification of Diet in Renal Disease
(MDRD) equation. Overt albuminuria was defined as urine
albumin creatinine ratio (ACR)≥ 300 mg/g
Results: A total of 749 type 2 diabetic patients with were
included with median follow-up time of 6.7 years (inter-
quartile range 4.1–9.6 years). Among 332 patients with CKD,
60.8% (N = 202) of them without overt albuminuria. DR was
detected in 37.1% of patients of CKD without overt albumin-
uria. In multivariable cox regression, HR of DR for all-cause
mortality was 1.96 (95% CI, 1.19– 3.26, P = 0.008) compared with
those without DR among CKD without overt albuminuria. DR
did not significantly predict all-cause mortality in CKD with
albuminuria.
Conclusions: DR is a robust predictor for all-cause mortality
in the type 2 diabetic patients with CKD but no overt
albuminuria.
PE-25
Serum osteocalcin levels are inversely associated with the
presence of nonalcoholic fatty liver disease in patients with
coronary artery disease
Jing DU1, Xiaoping PAN 1, Zhigang LU2, Meifang GAO2,
Xiang HU1, Xueli ZHANG1, Yuqian BAO1 *, Weiping JIA1.
1Department of Endocrinology and Metabolism, Shanghai Jiao Tong
University Affiliated Sixth People’s Hospital; Shanghai Clinical Center
for Diabetes; Shanghai Diabetes Institute, 2 Department of
Cardiology, Shanghai Jiao Tong University Affiliated Sixth People’s
Hospital, China
Objective: Osteocalcin plays roles in energy, glucose, and lipid
metabolism. Consequently, the relationship between osteo-
calcin and nonalcoholic fatty liver disease (NAFLD) is of
interest. The present study explored the possible correlation
between serum osteocalcin levels and NAFLD in patients with
coronary artery disease (CAD).
Methods: The study enrolled 174 inpatients diagnosed with
CAD by coronary angiography. The presence of fatty liver
disease was confirmed by abdominal ultrasonography. NAFLD
was diagnosed using the working definition of the revised
guidelines for the management of NAFLD published by the
Chinese Liver Disease Association (2010). Serum osteocalcin
levels were determined using electrochemiluminescent
immunoassays.
Results: Compared with non-NAFLD subjects, those with
NAFLD had significantly higher body mass index (BMI), waist
circumference, blood pressure, fasting plasma glucose (FPG), 2
hour plasma glucose, glycated hemoglobin A1c (HbA1c),
homeostasis model assessment-insulin resistance, totoal
cholesterol, triglyceride (TG), c-reactive protein, alanine ami-
notransferase, and glutamyl endopeptidase levels (P < 0.05).
These patients also used more anti-hypertensive drugs, but
had significantly lower high density lipoprotein- cholesterol
levels (P < 0.05). Especially the patients with NAFLD had lower
serum osteocalcin levels than those without NAFLD [16.2
(14.2–23.8) vs. 20.7 (15.6–26.2) ng/mL, P < 0.05]. After adjust-
ment for gender and age, serum osteocalcin levels correlated
with the presence of NAFLD (r = –0.260, P = 0.010), FPG level
(r =–0.230, P = 0.023) and HbA1c level (r = –0.229, P = 0.023).
Osteocalcin (β = –0.097, P = 0.025), BMI (β = 0.345, P < 0.001),
HbA1c (β = 0.641, P = 0.004) and TG (β = 1.002, P < 0.001) were
the independent factor for the presence of NAFLD.
Conclusions: Serum osteocalcin levels were negatively asso-
ciated with the presence of NAFLD in patients with CAD.
Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65–S211 S138