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

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PJ-59
RBP2R expression and retinol homeostasis in the liver of
diabetes
Wen-Chen KUO 1, Chao-Hung CHEN2, Kun-Der LIN1,
Mei-Yueh LEE 2, Yu-Li LEE1, Pi-Jung HSIAO2, Shyi-Jang SHIN2*.
1 Department of Internal Medicine, Kaohsiung Medical University
Hospital, 2College of Medicine, Kaohsiung Medical University,
Taiwan
Vitamin A (retinol) absorbed from small intestine and
circulation, stored in liver, and secreted into circulation
bound to serum retinol-binding protein (RBP4). A novel
retinol transporter, RBPR2, expressed primarily in liver of
mice, was found to potentially regulate retinol homeostasis in
liver. We hypothesize that diabetes and obesity might affect
RBPR2 and its signaling (CRBP1, RARs), and circulating RBP4
concentration. Here, we showed our results; (1) In the liver of
high fat diet (HFD)-fed mice, RBPR2 mRNA, CRBP1 and RARα
protein level markedly decreased while blood RBP4 concen-
tration increased. (2) In the liver of db/db mice, CRBP1
and RARα protein level significantly decreased, but RBPR2
mRNA and protein markedly increased. (3) By using RBPR2
immunoprecipationmethod, RBP4 binding activity with RBP2R
remarkably declined in high glucose-cultured clone 9 hepatic
and HepG2 cells. (4) In RBPR2 immunoprecipation method,
O-GlcNAc modification of RBP2R was found in HG-cultured
HepG2 cells. (5) HG- induced RBP4 overproduction was
attenuated by O-GlcNAc transferase siRNA in HepG2 cells.
Thus, high fat feeding causes down-regulation of RBPR2 while
diabetes enhances O-GlcNAc modification of RBP2R, and both
reduce retinol homeostasis in liver and possibly affect
circulating RBP4 concentration.
PJ-60
Long-term effectiveness of sulfonylureas in type 2 diabetes
Akihiro HAMASAKI 1,2*, Yuichi SUGIYAMA3,
Kazuya OKAMOTO4, Purnomo H. KHOTIMAH3,
Ryosuke SAWANO 3, Masatoshi YOSHIKAWA3,
Tomohiro KURODA4, Nobuya INAGAKI2. 1Center for Diabetes and
Endocrinology, Tazuke Kofukai Medical Research Insutitute Kitano
Hospital, Osaka, 2Department of Diabetes, Endocrinology and
Nutrition, Graduate school of Medicine, Kyoto University,
3 Department of Social Informatics, Graduate school of Informatics,
Kyoto University, 4Division of Medical Information Technology and
Administration Planning, Kyoto University Hospital, Kyoto
University, Kyoto, Japan
Background: Very long-term drug therapy is commonly
needed for proper management of the type 2 diabetes
(T2DM). Sulfonylureas (SU) have been widely and long used
for T2DM treatment in Japan since insulin secretagougues are
suitable for pathophysiology of Asian T2DMwith predominant
insulin secretory defect. There is, however, few clinical finding
about the T2DM under very long-term treatment of SU. In this
study, T2DM patients with decade SU treatment period are
extracted by analyses of the dataset of prescriptions aiming to
reveal the clinical features of very long-term SU using.
Method: The dataset which consists of 220,000 medical
prescriptions for 15 years was reconstructed and analyzed.
Patients whowere continuously prescribed SU at least 10 years
were extracted and investigated their clinical features.
Result: Fifty T2DM patients (72.9 ± 9.3 y.o.) were extracted.
Dosages of SU were 47.6, 1.4 (gliclazide, glimepiride respect-
ively) (mg/day). 1.4 ± 0.9 oral hypoglycemic agents other than
insulin secretagogues were used as combination therapy.
Recent HbA1c of extracted patients was 7.2 ± 0.9%.
Conclusion: Our results revealed that sulfonylureas have very
long-term effectiveness for treatment of T2DM in relatively
low-dose use. Analysis of reconstructed medical prescription
records was very useful method for obtaining long-term
clinical findings.
Endocrinology
PK-01
Dynamic risk estimates of outcome in patients with well-
differentiated thyroid cancer after initial treatment
Feng-Chih SHEN1, Ching-Jung HSIEH1, Pei-Wen WANG1*.
1Division of Endocrinology and Metabolism, Department of Internal
Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung,
Taiwan
Introduction: This study was conducted to evaluate the
American Joint Cancer Committee (AJCC), American Thyroid
Association (ATA) staging systems and response to initial
therapy reclassification system for the prediction of long term
disease status in patients with well-differentiated thyroid
carcinoma (WDTC).
Patients and methods: Patients with WDTC (n = 356) treated
with total or near-total thyroidectomy followed by 131I
remnant ablation at Kaohsiung Chang Gung Memorial
Hospital were retrospectively studied. A minimum of 5 years
of follow-upwas required and patients with anti-thyroglobulin
(Tg) autoantibodies were excluded. Each patient was risk-
stratified using the AJCC (stage I–IV) and 2009 ATA staging
systems (low, intermediate, high risk) immediately after
operation and first 131I remnant ablation, and response to
initial therapy reclassification system (excellent response,
biochemical incomplete, indeterminate, structural persistent)
at 6–24 months after the first 131I remnant ablation. The
clinical outcome at last follow-up is defined as no evidence of
disease (NED) (suppressedTg < 0.5 ng/mL, stimulatedTg < 1 ng/
mL and no structural detectable disease), biochemical persist-
ent disease (BPD) (suppressed Tg > 0.5 ng/mL or stimulated
Tg > 1 ng/mL in the absence of structural disease), structural
persistent disease (SPD) (locoregional or distant metastases
with any Tg level), or recurrence disease (RD) (biochemical or
structural disease identified after a period of NED).
Results: The mean age of the 356 patients was 41.5 ± 12.7 years
and duration of follow-up was 12.3 ± 5.0 years. At the time of
last follow-up, 78% (n = 279) of the patients were NED, 9.3%
(n = 33) had BPD, 10.1% (n = 36) had SPD and 2.2% (n = 8)
developed RD. SPD was identified in 6.7%, 9.5%, 16.7%, and
29.3% of stage I, II, III and IV patients, respectively (p < 0.001)
according to AJCC classification. SPD was identified in 0.5%,
4.9%, and 28.3% of the low-, intermediate-, and high-risk
patients, respectively (p < 0.001) according to ATA staging
system. As using response to initial therapy re-classification
system, the likelihood of finding SPDwas 0.5%, 6.2%, 27.7% and
80% in patients with excellent, indeterminate, biochemical
incomplete and structural incomplete response, respectively
(p < 0.001).
Conclusions: Our results are consistent with ATA guideline
that recommends a dynamic risk assessment to incorporate
the response to therapy during follow-up in an ongoing
process for individual patient.
PK-02
Consumptive hypothyroidism associated with hepatic
hemangiomas
Chia-Luen HUANG1, Wen-Yu TSAI2, Chien-Ming LIN 3*.
1Division of Metabolism and Endocrinology, Department of Internal
Medicine, Tri-Service General Hospital, National Defense Medical
Center, 2Department of Pediatrics, National Taiwan University
Hospital and College of Medicine, National Taiwan University,
3Graduate Institute of Medical Sciences, National Defense Medical
Center, Taipei, Taiwan
The vast majority of hemangiomas never cause symptoms,
however, huge and diffuse hepatic hemangiomas can cause
consumptive hypothyroidism through the overproduction
of type 3 iodothyronine deiodinase. Here, we reported a
Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65–S211 S210