Diabetes Research and Clinical Practice - Volume 120 - Supplement 1

Oral administration of purified PeCSO in type 1 diabetic mice

for 4 weeks reduced blood glucose to an average of 189 mg/dL.

In contrast, diabetic control mice that received saline had their

blood glucose exacerbate to 553 mg/dL, suggesting that PeCSO

was either suppressing the effects of, or ameliorating the

damage caused by STZ. Oral administration of the onion

extract in type 2 diabetic mice tended to decrease the elevated

blood glucose levels and to improve insulin sensitivity. To

determine the possible mode of action, we evaluated in vitro

antioxidant effect of PeCSO by monitoring its 2,2-diphenyl-1-

picrylhydrazyl (DPPH) and H2O2 scavenging abilities. At high

concentration of 50 mg/mL, PeCSO appeared to be an

excellent scavenger of DPPH radical when dissolved in

DMSO, with a DPPH radical formation inhibition ability of

91%, much higher than that of N-Acetyl cysteine (NAC), a

potent antioxidant, which was 51%. The result suggest that

one possible mode of action of the observed antidiabetic effect

is by scavenging reactive oxygen species in the body. However,

PeCSO did not show any significant H2O2 scavenging ability.

From bioavailability assay, the highest concentration of PeCSO

in blood was observed 1 hour post oral administration and was

also detectable 2 and 3 hours after administration. Although

more studies are needed, our results suggest that PeCSO

possess appreciable antidiabetic potential, probably by acting

as an antioxidant and thus promoting insulin sensitivity.

Novel Biomarkers for Diabetes

OL10-2

Pre-beta HDL in type 2 diabetes mellitus

Chi Ho LEE

, Sammy SHIU

, Ying WONG

, Kathryn TAN

University of Hong Kong, Hong Kong

Introduction:

Cellular cholesterol efflux is the first step of

reverse cholesterol transport and the efficiency of this process

is determined partly by the concentration of extracellular

cholesterol acceptors like HDL. Pre-beta HDL mainly com-

poses of apolipoprotein (apo) AI and phospholipids, and

serves as the preferred acceptor of cellular cholesterol efflux

mediated by the ATP-binding cassette transporter A1 (ABCA1).

We have evaluated whether there are changes in pre-beta

HDL concentration in type 2 diabetic patients independent of

the levels of HDL cholesterol (HDL-C) and the effect on

cholesterol efflux.

Methods:

500 type 2 diabetic patients and 360 non diabetic

controls matched for age, gender and serumHDL-C levels were

recruited. Subjects on lipid lowering agents were excluded.

Plasma pre-beta HDL was measured by ELISA. In a random

subgroup of subjects (115 diabetic patients and 70 control

subjects), cholesterol efflux to serum mediated by ABCA1 was

determined by measuring the transfer of [3H]cholesterol from

Fu5AH cells expressing ABCA1 (induced by 22(R)-hydroxycho-

lesterol and 9-cis-retinoic acid) to the medium containing the

tested serum.

Results:

There were no significant differences in the age and in

the proportions of male/female subjects between the 2 groups.

Despite the diabetic subjects having similar HDL-C levels

(1.25 ± 0.35 mmol/L) and apo AI (1.32 ± 0.23 g/L) as controls

(HDL-C: 1.25 ± 0.27 mmol/L, apo AI: 1.35 ± 0.22 g/L), serum pre-

beta HDL was significantly lower in the diabetic patients [190.4

(123.0

–

260.5) ug/mL vs 201.6 (135.7

–

293.6) respectively, median

(interquartile range), p < 0.01]. Cholesterol efflux to serum

mediated by ABCA1 was reduced in diabetic patients com-

pared to control (1.40 ± 0.40% vs 1.72 ± 0.45 respectively, p <

0.05). In the diabetic patients, cholesterol efflux mediated by

ABCA1 correlated with log (pre-beta HDL) (r = 0.30, p < 0.05) but

not with HDL-C.

Conclusion:

Low HDL-C level is common in patients with type

2 diabetes. However, even when type 2 diabetic patients were

compared with a group of non-diabetic control subjects with

similar HDL-C levels in our study, plasma pre-beta HDL level

was significantly decreased in diabetic subjects and was

associated with a reduction in cholesterol efflux to serum

mediated by ABCA1 ex vivo. Our data therefore suggest that

low pre-beta HDL level in type 2 diabetes might cause

impairment in reverse cholesterol transport.

OL10-3

The association among cardiotrophin-1, insulin resistance

and nonalcoholic fatty liver disease

Kai-Chou CHUANG

, Hao-Chang HUNG

, Hung-Tsung WU

Horng-Yih OU

, Ching-Han LIN

, Chih-Jen CHANG

Department of Internal Medicine, National Cheng Kung University

Hospital,

Research Center of Clinical Medicine, National Cheng Kung

University Hospital,

Department of Family Medicine, National

Cheng Kung University Hospital, Taiwan

Nonalcololic fatty liver disease (NAFLD) is the most common

cause of chronic liver disease worldwide. The disease is

characterized by awide spectrumof histological abnormalities

ranging from simple hepatic steatosis, to nonalcoholic steato-

hepatitis, to liver fibrosis, and to cirrhosis. Although the

precise mechanism of NAFLD remains incompletely under-

stood, the most accepted pathophysiologic model for NAFLD is

the

“

two-hit hypothesis

”

Cardiotrophin-1 is one member of the interleukin-6 family

cytokines. In the liver, previous studies demonstrated the

hepato-protective effects of cardiotrophin-1 in different

models of acute liver injury. Moreover, cardiotrophin-1 was

found to be upregulated in human and murine steatotic livers,

and chronic administration of recombinant cardiotrophin-1

eliminated hepatic steatosis in obese mice.

Recently, one animal study suggested that cardiotrophin-1

may be a promising therapy for insulin resistance and linked

metabolic disorders. Although cardiotrophin-1 protects liver

against acute injury, it is unclear whether cardiotrophin-1 is

involved in the pathogenesis of NAFLD. Therefore, the aim of

this study is to clarify the association between cardiotrophin-1

and NAFLD.

We recruited 287 subjects with (n = 148) or without (n = 139)

NAFLD. All subjects received a health checkup and completed a

structuredquestionnaire, and thosewho did not have amedical

history of diabetes received a standard 75-g oral glucose

tolerance test. Subjects with the following conditions or

diseases were excluded: (1) alcohol consumption

≧

20 g/day in

the last year; (2) a positive test for hepatitis B surface antigen or

hepatitis C antibody or other causes of liver disease; (3) serum

creatinine >1.5 mg/dL; (4) any acute or chronic inflammatory

disease as determined by a leukocyte count >10000/mm

clinical sighs of infections; (5) any other major including

generalized inflammation or advanced malignant disease.

Individuals with NAFLD had significant higher body mass

index (BMI), systolic and diastolic blood pressure, fasting

plasmaglucose, homeostaticmodel assessment-insulin resist-

ance (HOMA-IR) index, triglyceride, and high density lipopro-

tein (HDL) levels than those without it. Furthermore, subjects

with NAFLD had significant higher cardiotrophin-1 concentra-

tions than those without it. The results of multivariate linear

regression analysis showed that NAFLD was positively asso-

ciated with cardiotrophiin-1 after adjusting for age, gender,

BMI, HOMA-IR, systolic blood pressure (SBP), creatinine,

triglyceride, HDL, hsCRP, smoking, and habitual exercise.

Subjects with NAFLD had significant higher cardiotrophin-1

concentrations than those without it. Furthermore, NAFLD an

independent predictor of cardiotrophin-1 levels after adjusting

for age, gender, BMI, HOMA-IR, SBP, creatinine, triglyceride,

HDL, hsCRP, smoking, and habitual exercise. Cardiotrophin-1

may be a surrogate biomarker of NAFLD.

Oral Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S40

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