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

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PE-45
The role of RBP4 receptor on the pathogenesis of diabetic
kidney
Chao-Hung CHEN 1, Kun-Der LIN2, Tusty-Jiuan HSIEH3,
Yu-Li LEE2, Mei-Yueh LEE2, Pi-Jung HSIAO2, Shyi-Jang SHIN4*.
1 Graduate Institute of Medicine, College of Medicine, Kaohsiung
Medical University, 2Division of Endocrinology and Metabolism,
Kaohsiung Medical University Hospital, Kaohsiung Medical
University, Kaohsiung, 3Department of Medical Genetics, School of
Medicine, College of Medicine, Kaohsiung Medical University
Hospital, Kaohsiung Medical University, 4Department of Internal
Medicine, School of Medicine, College of Medicine, Kaohsiung Medical
University Hospital, Kaohsiung Medical University, Taiwan
Mitochondrial dysfunction and oxidative stress are shown
as an initiating trigger to induce diabetic nephropathy. We
recently reported that the suppression of RBP4 receptor
cascades involves dyslipidemia-induced arterial and renal
damage. We thus investigated whether the suppression of
RBP4 receptor signaling could interact with mitochondrial
dysfunction to cause apoptosis and fibrosis in diabetes. In
the kidneys of streptozotocin(STZ)-induced diabetes and
high glucose(HG)-cultured HEK cells, RBP4 receptor(STRA6),
MnSOD, caspase 3 and collagen 1 protein as well as apoptotic
cells increased, but CRBP1, RAR α, ATP synthase, and cyto-
chrome c expression as well as mitochondrial potential
decreased. By immunoprecipitation method using STRA6
antibody, we found the binding activity of RBP4 on STRA6
in diabetes and HG-cultured cells were markedly reduced.
ROS inhibitor and MnSOD gene transfection reversed above
alterations in HG-cultured cells. MnSOD silencing signi-
ficantly reversed STRA6, CRBP1 and RAR α expression but
didn ’t affect caspase3 and collagen 1 in HG-cultured cells.
Interestingly, CRBP1 gene transfection reversed the suppres-
sion of ATP synthase, cytochrome c, the increase of caspase 3
and collagen 1 protein and mRNA expression, but increased
binding activity of RBP4 with STRA6, and expression of RARα in
HG-cultured cells. This study indicates that interaction
between the suppression of RBP4 Receptor signaling and
mitochondrial dysfunction induces kidney apoptosis and
fibrosis in diabetes.
PE-47
Temporal pattern of plasma glucose levels during oral glucose
tolerance test and the association with cardiovascular risk
Yi Chun LIN 1, Harn Shen CHEN1 *. 1Taipei Veterans General
Hospital, Taiwan
Backgrounds: The pattern of insulin or glucose levels during
an oral glucose tolerance test (OGTT) may provide useful
information on the prediction of subsequent cardiovascular
disease and diabetes mellitus or its related complication.
However, the patient ’s glucose and insulin response pattern
during OGTT are rarely explored. Besides, the clinical implica-
tion of the temporal difference of glucose during OGTT to
major cardiovascular events or risk are unknown. This study
will be carried out to determine whether the glucose response
temporal patterns during OGTT are associated with cardio-
vascular disease risk scores.
Methods: Subjects with impaired glucose tolerance or type 2
diabetes were enrolled in this observational study under
routine clinical care in outpatient setting from Taipei
Veterans General Hospital. Blood samples were obtained at 0,
30, 60, 90 and 120 min during 75 g OGTT after 8 hours fast.
Patients were grouped by the time point when highest glucose
level measured (group 30 min, group 60 min, group 90 min and
group 120 min). The primary outcome is ten-year cardiovas-
cular disease risk which was calculated by Framingham risk
score calculator.
Results: A total of 125 patients who underwent OGTT were
included. There are 4, 54, 55 and 9 subjects in the group 30 min,
group 60 min, group 90 min and group 120 min separately. 87%
of themwere in the group 60 min and group 90 min. The group
60 min had younger age (56.15 ± 10.12 years vs 60.58 ± 10.02
years, P = 0.023) and lower HbA1c (6.03 ± 0.44% vs 6.30 ± 0.59%,
P = 0.009) but higher LDL-C (135.40 ± 44.30 mg/dL vs 116.61 ±
35.68 mg/dL, P = 0.051) than the group 90 min. Framingham 10-
year risk score of group 90 min is 1.7 times of that of group
60 min (4.05 ± 4.60% vs 6.98 ± 6.56%, P = 0.023). After multivari-
ate linear regression, group 90 min is still associated with
higher risk score (P = 0.042).
Conclusions: Comparing to the later peak glucose group (group
90 min) during an OGTT, the earlier peak glucose group (group
60 min) had characters of younger age, lower HbA1c level but
higher LDL-C. The later peak glucose group also had higher
Framingham 10-year risk score after adjusting these variables.
PE-48
HbA1C variability is not associated with renal outcomes in
diabetic nephropathy with chronic kidney disease stage 3-5
Mei-Yueh LEE1,2,3, Szu-Chia CHEN2,3,4, Wei-Hao HSU1,2,
Kun-Der LIN1, Pi-Jung HSIAO1, Shyi-Jang SHIN1*. 1Department of
Endocrinology and Metabolism, Kaohsiung Medical University
Hospital, 2Department of Internal Medicine, Kaohsiung Municipal
HsiaoKang Hospital, 3Graduate Institute of Clinical Medicine,
Kaohsiung Medical University, 4Department of Nephrology,
Kaohsiung Medical University Hospital, Taiwan
Background: Higher HbA1C variability had been reported to
be associated with increased risk of progression of nephro-
pathy. However, no previous studies had evaluated the
association between HbA1C variability and renal outcomes in
patients with diabetic nephropathy. Therefore, the aim of this
study was to assess whether HbA1C variability is associated
with rate of renal function decline and progression to renal
replacement therapy (RRT) in diabetic nephropathy with
chronic kidney disease (CKD) stage 3–5 patients.
Methods: This longitudinal study enrolled 352 patients. Intra-
individual HbA1C variability was defined as coefficient of
variation (CV = SD/mean). The renal end point was defined as
commencement of RRT. The change in renal function was
measured by estimated glomerular filtration rate (eGFR) slope.
The study patients were stratified into 3 groups according to
tertiles of coefficient of variation (CV) of HbA1C (<8.4, 8.4–14.1,
≧14.1).
Results: One hundred and nine (31%) patients received RRT
during the follow-up period. the median follow-up period was
3.6 years. Therewas no significant difference of eGFR slope in 3
study groups. The patients with CV tertile 3 (vs. CV tertile 1)
were associated with a higher risk of commencement of
RRT in the unadjusted model (HR, 1.783; 95% CI, 1.129 to 2.814;
p = 0.013) and in the multivariate model after adjusting for
demographic and clinical factors (HR, 1.964; 95% CI, 1.212 to
3.181; p = 0.006). This relationship became non-significant
after further adjusting for biochemical parameters (HR, 1.457;
95% CI, 0.866 to 2.453; p = 0.157).
Conclusions: Our results demonstrated that HbA1C variability
is not associated with rate of renal function decline and
progression to RRT in diabetic nephropathy with CKD stage 3–5
patients. Therefore, HbA1C variability may not be the major
determinant of renal outcomes in diabetic nephropathy with
CKD stage 3–5 patients.
PE-49
Effects of t-PA and PAI-1 on the macro-vascular complications
in type 2 diabetes
Jun ZHANG1*. 1Division of Endocrinology, Department of Medicine,
Shandong Provincial Qianfoshan Hospital, Shandong University, No.
16766 Jingshi Road, Jinan Shandong, China
Objective: To identify the importance of abnormal fibrinolytic
system mainly the content changes of tissue-plasminogen
activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1)
Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65–S211 S145