Diabetes Research and Clinical Practice - Volume 120 - Supplement 1

Background:

Data on prevalence and phenotypic distribution

of dyslipidemia in children with type 1 diabetes is scarce.

Studies have shown that lipid abnormality tracks from

childhood to adulthood and contributes to atherosclerotic

process, therefore initial assessment and follow-up is

essential.

Aims:

To study the prevalence and phenotypic distribution of

dyslipidemia in children with type 1 diabetes (T1D) and

compare with type 2 diabetes (T2D).

Methods:

A cross-sectional sample of diabetes patients, age 7

–

18 years on active follow-up between 1st January to 31st

December 2014 were recruited. Fasting blood sample were

analysed for glycated haemoglobin (HbA1C), total cholesterol

(TC), high density lipoprotein (HDL), triglycerides (TG) and low

density lipoprotein (LDL). Baseline demographic data and

biochemical data was analysed using SPSS version 16.

Results:

Total 165 patients were recruited, (T1D: n = 115; 69.7%,

T2D: n = 50; 30.3%). Prevalence of dyslipidemia was 73.3%

(n = 121) and almost similar in T1D & T2D (71.3% vs. 78.0%).

T1D had lower mean age at recruitment (13.61 y ± 2.58 vs.

15.36 y ± 2.00; p < 0.001) and longer mean duration of dia-

betes (5.85 ± 3.69 vs. 2.82 ± 2.12; p < 0.001) compared to T2D.

Phenotypic distribution of dyslipidemia in T1D vs. T2D,

(LDL

≥

2.6 mmol/L:66.1% vs. 70.0%; p = 0.719), (TG

≥

1.7 mmol/

L:11.3% vs.42.0%; p < 0.001), (HDL < 1 mmol/L :4.3% vs. 12.0%;

p = 0.091). T1D & T2D had similar mean LDL (2.92 ± 0.86 vs.

3.01 ± 1.06; p = 0.56). Mean HbA1c was higher in T1D vs T2D

(8.98% ± 1.96 vs. 7.9% ± 2.27; p = 0.095). There were 31 (18.8%)

patients aged

≤

10 yrs, mostly T1D (n = 28; 24.3%), of which

67.7% had LDL

≥

2.6 mmol/L and 87.1% had no family history of

lipid disorder.

Conclusion:

Patients with T1D in the present study showed

higher LDL-C but not triglyceride. Significant proportion of

T1D patients less than 10 years of age have elevated LDL-C

levels without a family history of lipid disorder.

PE-18

GLP-1 action attenuates prostate cancer growth and

progression

Toru SHIGEOKA

, Takashi NOMIYAMA

*, Shinichiro IRIE

Takako KAWANAMI

, Yuriko HAMAGUCHI

Tomoko TANAKA

, Kazuki NABESHIMA

Masatoshi TANAKA

, Toshihiko YANASE

Department of

Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka

University,

Department of Urology, School of Medicine, Fukuoka

University,

Department of Pathology, Faculty of Medicine, Fukuoka

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

that Ex-4 has anti-prostate cancer effect in prostate cancer

cells via reduction of extracellular signal

–

regulated kinase

(ERK)-mitogen-activated protein kinase (MAPK) phosphoryl-

ation (Diabetes 2014). Further, we reported that additive anti-

prostate cancer effect by combined treatment of Ex-4 and

metformin using LNCap cells, prostate cancer cell line (POLS

ONE 2015). In our previous report, Ex-4 did not attenuate cell

proliferation in a prostate cancer cell ALVA-41, which does not

express GLP-1R. In the present study, we examined anti-

prostate cancer effect of Ex-4 in ALVA-41 forced expressed GLP-

1R using lentivirus vector (ALVA-GLP-1R) and association

between GLP-1R expression level and prostate cancer progres-

sion in human prostate cancer tissues. Firstly, we confirmed

abundant GLP-1R expression in ALVA-GLP-1R using immuno-

histochemistry and RT-PCR. Ex-4 significantly decreased

the proliferation of ALVA-GLP-1R in a dose dependent

manner, but not in ALVA-41 transfected with control vector

(ALVA-control). Further, we transplanted ALVA-GLP-1R and

ALVA-control into non diabetic athymicmice and treated them

with vehicle or Ex-4 (300 pM/kg/day) for 4 weeks. As a result,

tumor size of ALVA-GLP-1R was significantly decreased

compared with ALVA-control, with or without Ex-4 treatment.

Immunohistochemistry of Ki67 revealed that ALVA-GLP-1R

had a reduction of cell proliferation compared with ALVA-

control. Although severe necrotic lesion was observed in all

tumors, apoptotic cells were not detected by TUNNEL assay.

Prostatic acid phosphatase, a marker of prostate cancer, was

decreased in serum of mice transplanted with ALVA-GLP-1R

compared with ALVA-control. In addition, we next performed

immunohistochemistry of GLP1-R and Ki67 of 40 nondiabetic

prostate cancer patients. Interestingly, GLP-1R expression

level was inversely associated with percentage of Ki67 positive

cells and Gleason grading system of prostate cancers, signi-

ficantly. Gleason score 6, highly differentiated carcinoma,

has significantly higher expression of GLP1-R compared with

Gleason score 8 over, lower differentiated carcinoma.

These data suggest that GLP-1R expression and GLP-1 action

attenuates prostate cancer growth and progression in model

mice and patients.

PE-19

Effects of arecoline on insulin signaling in human endothelial

cells

Chien-Hsing LEE

*, Yi-Shing SHIEH

2,3

, Yi-Jen HUNG

Division

of Endocrinology and Metabolism, Department of Internal Medicine,

Tri-Service General Hospital, National Defense Medical Center,

School of Dentistry, National Defense Medical Center,

Department

of Oral Diagnosis and Pathology, Tri-Service General Hospital,

Taipei, Taiwan

Background:

Betel nut is the most widely used addictive

substance in the world, and betel quid chewing is a common

oral habit in South Asia and Taiwan. Being a major alkaloid in

betel nut, arecoline has long been considered a potential

carcinogen. Several reports showed that arecoline can increase

reactive oxygen species (ROS) to produce cytotoxicity and

genotoxicity. Recent reports indicate that betel quid chewing

also increase the risk of atherosclerosis and diabetes. However,

the detail mechanism remains unknown. Most recently,

arecoline have diabetogenic potential on adipocytes that

may result in insulin resistance and diabetes at least in part

via the obstruction of insulin signaling and the blockage of

lipid storage. In this study, we try to investigate the possible

mechanisms of arecoline induced insulin resistance and

endothelial dysfunction.

Methods:

Human dermal microvascular endothelial cell

(HMEC-1) were treated in different arecoline concentrations

and tested the ROS levels and the expression of adhesion

molecules, insulin signaling pathways and cell adhesion

function. Then N-acetylcysteine (NAC) and Rosiglitazone

were added to exam the effect on arecoline-induced endothe-

lial dysfunction.

Results:

Our data showed that the ROS levels and adhesion

molecules (ICAM-1, VCAM-1) significantly increased after

arecoline treatment and along with increased adhesion

ability between HMEC-1 and monocyte. The results also

revealed that increased phosphorylation of JNK then down-

regulated insulin signaling pathways through IRS-1 and AKT

after arecoline treatment. With the use of reducing agent NAC

and Rosiglitazone in the arecoline-induced endothelial cell

dysfunction, these cell dysfunctions and downstream signal-

ing were found to be diminished and recovered.

Conclusions:

Our present study explore the influence of betel

nut extract

–

arecoline on insulin signaling and endothelial

dysfunction and partially explain the increased risk of insulin

resistance and cardiovascular disease from betel nut chewing .

In addition, our data showed Rosiglitazone reduced arecoline-

induced endothelial dysfunction and insulin resistance

including of reducing ICAM-1 and VCAM-1 expression and

monocyte adhesion by modulating the JNK-IRS-1-PI3K/AKT

signaling pathway in endothelial cells.

Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65

–

S211

S136