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PD-18

An observational study of diabetes outpatients switching from

glargine or detemir to degludec

Miki SATO

1

*, Seiya SHIMODA

1

, Taiji SEKIGAMI

2,3

,

Hiroyuki MOTOSHIMA

1

, Ryohei YOSHIMURA

4

,

Kazuki FUKUDA

1,5

, Yasuto MATSUO

6

, Mina OKUBO

7

,

Shinji ICHIMORI

8

, Kazuo FUJISAWA

9

, Eiichi ARAKI

1

.

1

Department of Metabolic Medicine, Faculty of Life Sciences,

Kumamoto University,

2

Kumamoto General Hospital Japan

Community Healthcare Organization,

3

Sekigami Clinic,

4

Yoshimura

Clinic,

5

Amakusa Central General Hospital Japan Community

Healthcare Organization,

6

Saiseikai Kumamoto Hospital,

7

Kumamoto Chuo Hospital,

8

Kumamoto Municipal Ueki Hospital,

9

Minamata City Hospital and Medical Center, Kumamoto, Japan

Objectives:

The aim of the present prospective observational

study is to assess long-term efficacy and safety of insulin

degludec (IDeg) as a part of basal supported oral therapy (BOT)

or basal-bolus therapy (BBT) for Japanese subjects with type 1

(T1D) or type 2 diabetes (T2D) in routine clinical practice.

Materials andmethods:

In this study, 93 T1D-BBT subjects and

158 T2D subjects (T2D-BOT; n = 23, T2D-BBT; n = 135) treated

insulin glargine (IGlar) or detemir (IDet) were switched from

their basal insulin to IDeg. The primary endpoints were the

changes in HbA1c from baseline at 3, 6 and 12 months. The

secondary endpoints were changes in body mass index (BMI),

insulin dose and frequency of hypoglycemia.

Results:

During the 1-year observation period, HbA1c levels

improved significantly from 8.7 ± 1.4% at baseline to 8.4 ± 1.4%

at end of study in T1D-BBT subjects (p < 0.01), and from 8.1

1.4% to 7.8 ± 1.3% in T2D-BBT subjects (p < 0.001). In T2D-BOT

subjects, HbA1c level at 3 months were significantly lower

than that at baseline (7.5% ± 0.8% vs 8.0% ± 1.0%, p < 0.01).

However, there was no significant difference between HbA1c

level at baseline and that at month 12. The change in HbA1c

levels from baseline to 3, 6 and 12 months were

0.4%,

0.4%,

and

0.3% in T1D-BBT subjects, respectively, and

0.5%,

0.1%,

and

0.1% in T2D-BOT subjects, respectively, and

0.5%,

0.5%, and

0.3% in T2D-BBT subjects, respectively. BMI in

T1D-BBT subjects increased significantly (p < 0.05), whereas

that in both T2D-BOT and T2D-BBT subjects did not change.

Basal insulin dose decreased significantly at 3 months after

switching (p < 0.05), and returned to baseline dose at 12

months in T1D-BBT and T2D-BBT subjects. On the other

hand, that in T2D-BOT subjects did not change during the

study period. The frequency of both total and nocturnal

hypoglycemia decreased significantly in both T1D-BBT and

T2D-BBT subjects (p < 0.05). No hypoglycemia was observed

before and after switching in T2D-BOT subjects.

Conclusion:

In both T1D-BBT and T2-BBT subjects, switching

from IGlar or IDet to IDeg led to an improvement of glycemic

control with a significant reduction of hypoglycemia. As a

novel basal insulin analog, IDeg might provide benefit for

diabetic subjects in clinical practice.

PD-19

Different effect of testosterone and estrogen on urinary

excretion of metformin via regulating OCTs and MATEs

expression in the kidney

Rui HE

1

, Ligen AI

1

, Dandan ZHANG

1

, Taishan ZHENG

1

,

Jun YIN

1

, Fang LIU

1

*, Weiping JIA

1

.

1

Shanghai Jiao-Tong

University Affiliated Sixth People

s Hospital, China

Objective:

Metformin, a commonly prescribed first-line anti-

diabetic drug, is eliminated into the urine in an unchanged

form, primarily secreting by the renal tubule. Membrane

transporters, manly including the organic cation transporters

(Octs) and multidrug and toxin extrusion proteins (Mates),

have influence on the efficiency of metformin and there are

gender differences in renal basolateral membrane organic

cation transporter activity. The aim of this study is to

investigate the effect of testosterone and estrogen on

regulating Octs and Mates expression in the kidney of mice

and urinary excretion of metformin.

Methods:

In this study, 8 week-old male db/db mice were

treated with estradiol, testosterone or olive oil with same

volume. Metformin is injected to observe the difference of

serum concentration and urinary excretion. Plasma, urine and

tissue concentrations of metformin were determined by HPLC

assay, whileWestern blotting and Real-time PCR analysis were

used to evaluate the renal expression of Octs and Mates.

Results:

After 7 days treatment, the expression of Mate1 and

Oct2 in testosterone group was significantly increased than

those in control group and the expression of Mate1 and Oct2 in

estradiol group was significantly reduced by 29.4% and 43.3%

respectively compared to those in control group, showing a

good agreement with the change inmRNA level (all p < 0.05). In

addition, the plasma metformin concentration (ng/mL) in

mice treated with estradiol was significantly higher than

control and testosterone group (677.56 ± 72.49 vs 293.92 ± 83.27

and 261.46 ± 79.45; p < 0.01). Moreover, testosterone increased

the metformin urine excretion of mice while estradiol

decreasing (both p < 0.01). Spearman correlation analysis

showed that gonadal hormone was closely associated with

MATE1 and Oct2 expression and metformin urine excretion in

db/db mice (all p < 0.05).

Conclusions:

Testosterone and estrogen exert reverse effect

on metformin urinary excretion via regulating Octs and Mates

expression in the kidney of mice.

PD-20

Comparison of acarbose versus voglibose monotherapy on

GLP-1 secretion and postprandial dyslipidemia in patients

with type 2 diabetes

Kosuke SHIMA

1

*, Rika USUDA

2

, Yinhua NI

1

, Shuichi KANEKO

1

,

Toshinari TAKAMURA

1

, Tsuguhito OTA

1

.

1

Department of Disease

Control and Homeostasis, Kanazawa University Graduate School of

Medical Science,

2

Toyama Prefectural Central Hospital, Japan

An

α

-glucosidase inhibitor (

α

GIs), such as acarbose, reduces

the risk of impaired glucose tolerance (IGT) progressing to type

2 diabetes mellitus (T2DM), and it prevented the development

of cardiovascular disease in the STOP-NIDDM trial. However,

the effect of

α

GIs on incretin secretion and postprandial

dyslipidemia remains largely unknown. In this study, we

compared the effects of acarbose and voglibose monotherapy

on GLP-1 secretion and postprandial dyslipidemia in patients

with T2DM. The study enrolled Japanese patients who had

T2DM with HbA1c levels

7.4% who were not taking any

antihyperglycemic agents. The 30 patients (51.2 ± 11.5 years,

HbA1c 6.3 ± 0.6%) were randomized to 300 mg acarbose (n = 15)

or 0.3 mg voglibose (n = 15). All patients had a meal tolerance

test (MTT) performed before and after 12 weeks of treatment.

Twelve weeks after treatment, HbA1c decreased by

0.09 ± 0.26% with acarbose and 0.05 ± 0.61% with voglibose,

and the difference was not significant. Triglyceride (TG)

decreased by 17.7% with acarbose (P < 0.02) and increased by

5.5%with voglibose (NS). The delta active GLP-1, defined as the

difference between the peak and baseline, was +6.6% (NS) with

acarbose and +116.5% with voglibose (P < 0.05). Comparing the

change in the incremental area under the MTT curves (AUC)

for GLP-1 and lipids from baseline to 12 weeks of treatment,

the AUC for active GLP-1 decreased by 6.1% with acrabose

whereas it increased by 19.6% with voglibose, and the

difference was significant (P < 0.05). In comparison, the AUC

for triglyceride (TG) and remnant like particles cholesterol

(RLP-C) decreased by 13% and 6.5% respectively, with acarbose,

whereas they increased by 3.5% and 8.3% respectively, with

voglibose, and the difference was significant (P < 0.05, respect-

ively). In conclusion, the treatment of T2DM with voglibose

resulted in a greater increase in active GLP-1 levels during the

MMT than with acarbose, while acarbose significantly reduced

the postprandial TG and RLP-C levels. Therefore, voglibose

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

S211

S97