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

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PD-66
Increased body mass index may attenuate the effect of
sitagliptin on glucose control
Junichiro ADACHI 1*, Yuusuke INABA1, Chisato MAKI1,
Toshiyuki HORIUCHI 2. 1Department of Endocrinology and
Metabolism, Ohkubo Hospital, 2Department of Internal Medicine,
Kyoujokai Clinic, Japan
Background: Few studies have been conducted on predictors
of a decrease in glycohemoglobin (HbA1c) level to <7% in
Japanese people with type 2 diabetes undergoing long-term
treatment with dipeptidyl peptidase-4 inhibitors.
Aim: This study aimed to determine predictors of improve-
ment in HbA1c level in Japanese people with type 2 diabetes
treated with sitagliptin.
Methods: We retrospectively evaluated 181 type 2 diabetic
patients (mean age: 65.2 years, male-to-female ratio, 125/56)
who had been taking sitagliptin 50 mg once daily for inad-
equate glycemic control for at least 24 weeks, with or without
other oral hypoglycemic agents. The outcomes assessed
were as follows: (1) changes in Hba1c level from baseline
to 8, 16, and 24 weeks of treatment; (2) proportion of
patients who achieved an HbA1c level <7% with sitagliptin
treatment; (3) differences in predictors (age, sex, body mass
index [BMI], diabetes duration, baseline HbA1c level, hyper-
tension, dyslipidemia, and other oral antidiabetic agents)
between patients with HbA1c levels <7% and those with
HbA1c levels >7%; and (4) independent predictors of achieving
HbA1c levels <7% with sitagliptin treatment on multiple
logistic regression analysis.
Results: HbA1c level significantly reduced from 7.9% at
baseline to 7.4% at 8 weeks, 7.1% at 16 weeks, and 7.1% at 24
weeks. An HbA1c level <7% was achieved in 51.7% of the
patients. The BMI and baseline HbA1c level were significantly
lower in patients with HbA1c level <7% than in those with
HbA1c level >7%. The independent predictors of achieving an
HbA1c level <7% were baseline HbA1c level (odds ratio, 1.96,
p ≤ 0.001) and BMI (odds ratio, 1.11; p = 0.02).
Conclusion: Our findings showed that HbA1c levels at baseline
and BMI are associated with achieving an HbA1c level <7% in
patients taking sitagliptin.
PD-67
The efficacy of DPPIV-inhibitor therapy among adult Chinese
patients with diabetes mellitus in Singapore
Jia Xuan YEO 1 *, Julia ANDRES1, Chin Meng KHOO2–4. 1Yong Loo
Lin School of Medicine, National University of Singapore,
2 Department of Medicine, Yong Loo Lin School of Medicine, National
University of Singapore, 3Division of Endocrinology, Department of
Medicine, National University Health System, 4Duke-NUS Graduate
Medical School, Singapore
Objective: To determine the patient and diabetes-specific
factors that may modify the efficacy of dipeptidyl peptidase-
4 (DPP-IV) inhibitor therapy amongst adult Chinese
Singaporeans with diabetes mellitus (DM).
Research design and methods: This is a retrospective study
from Jan 2014 to May 2015 of 196 Singaporean Chinese with
DM who were prescribed DPP-IV inhibitor as an add-on
therapy. We examined the changes in the glycemic control
(HbA1c) and body weight over a period of 12 months after
initiation of DPPIV-inhibitor using the linear mixed models.
HbA1c and body weight were included as dependent variables.
Patient factors (gender, age, baseline BMI) and diabetes-
specific factors (duration of diabetes, baseline HbA1c [baseline
HbA1c <8% vs 8 –10% vs >10%], insulin therapy, presence of
CKD [defined as presence of kidney damage or eGFR < 60 mL/
min/1.73 m 2 for at least 3 months]) were included as inde-
pendent variables. An interaction term “factor x follow-up
time ” was introduced as independent variable to examine
whether these factors modify the efficacy of DPPIV-inhibitor
therapy.
Results: There were 111 (56.6%) males. The mean ± SD age was
59.1 ± 14.7 years and the mean duration of diabetes was
14.0 ± 9.28 years. 83 (42.6%) patients were on insulin therapy.
The mean change for HbA1c over the 12 months period was
−0.37 ± 1.61% (p = 0.006) with the greatest decline seen in the
first 3months (ΔHbA1c = −0.61 ± 1.42%, p < 0.001). Therewas no
significant change in the body weight over 12 months ( Δbody
weight = −0.82 ± 6.21 kg, p = 0.110). Using the linear mixed
model, the interaction term for “factor x follow-up time” was
significant for baseline HbA1c, basal-bolus insulin regimen,
and presence of CKD. Those with baseline HbA1c > 10% had a
more significant decrease in HbA1c levels as compared to
those with baseline HbA1c 8–10% and HbA1c < 8% (P inter-
action <0.001). Patients on basal-bolus insulin therapy had
significantly greater reduction in body weight (P interaction =
0.034) as compared to those who were either on other insulin
regimes or were not on insulin therapy. Patients without CKD
had a significantly greater reduction in body weight (P
interaction = 0.039) but similar reduction in HbA1c as com-
pared to those with CKD. Age, gender, baseline BMI and
duration of diabetes did not modify the efficacy of DPP-IV
inhibitors in this population.
Conclusions: As an add-on therapy, DPP-IV inhibitors are
effective in improving glycemia and body weight in the adult
Chinese population in Singapore, particularly in patients with
baseline HbA1c>10%, those who are on basal-bolus insulin
therapy and patients without CKD.
PD-68
Fenretinide decreases insulin resistance and blood pressure,
and inhibits macrophage inflammatory mediators via the
peroxisome proliferator activated receptor pathway
Yu-Pin HUANG1, Horng-Yih OU1*, Hung-Tsung WU2,3,
Ching-Han LIN1, Hao-Chang HUNG1, Chih-Jen CHANG3.
1Division of Endocrinology and Metabolism, Department of Internal
Medicine, National Cheng Kung University Hospital, 2Clinical
Medicine Research Center, National Cheng Kung University Hospital,
College of Medicine, National Cheng Kung University, 3Department of
Family Medicine, College of Medicine, National Cheng Kung
University, Taiwan
Fenretinide [N-(4-hydroxyphenyl) retinamide] is a synthetic
retinoid derivative that has been widely used as a chemopre-
ventive and chemotherapeutic agent in cancer treatment.
Recent research also demonstrated that fenretinide prevents
obesity and fatty liver in high fat diet-induced obese mice.
Furthermore, fenretinide ameliorates insulin resistance
through the reduction of retinol binding protein 4 (RBP4) in
spontaneously hypertensive rats.
Peroxisome proliferator-activated receptor γ (PPARγ ) is a
ligand-activated transcription factor belonging to the nuclear
receptor superfamily that undergoing transactivation or
transrepression by distinct mechanisms, and thus leading to
induction or repression of target genes expression. PPARγ plays
an important role in many physiological functions, especially
those involved in the regulation of vascular tone, inflamma-
tion, and energy homeostasis. Therefore, PPARγ may represent
an important target for treatment of hypertension, obesity,
obesity-induced inflammation, and metabolic syndrome.
PPARγ may influence the inflammatory response by direct
transcriptional downregulation of pro-inflammatory genes.
Although it is known that fenretinide is a ligand for PPARγ, the
role of PPARγ in fenretinide-induced anti-inflammatory activ-
ity remains unknown. Despite the role of fenretinide in the
improvement of insulin resistance has been known, however,
the effects of fenretinide on blood pressure are still obscure.
In this study, we show that treatment with lipopolysaccharide
(LPS) decreased the expression of PPARγ in raw264.7 macro-
phages, and pretreatment with fenretinide reversed the
effect of LPS on PPARγ expression. In addition, LPS-induced
proinflammatory cytokine productions, including tumor
Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65–S211 S112