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

206 / 244

PI-20
Correlation between insulin sensitivity and pathohistological
findings in non-alcoholic fatty liver disease
Eri AMANO 1*, Satoko OHMI1, Masafumi ONO2,
Hiroshi TAKATA 1, Seiki HIRANO1, Shogo FUNAKOSHI1,
Yuichi NISHI1, Kumiko YOSHIMURA1, Yoshio TERADA 1,
Toshiji SAIBARA 2, Shimpei FUJIMOTO1. 1Department of
Endocrinology, Metabolism, and Nephrology, Kochi Medical School,
Kochi University, 2Department of Gastroenterology and Hepatology,
Kochi Medical School, Kochi University, Japan
While the association of the prevalence of non-alcoholic fatty
liver disease (NAFLD) with impaired glucose metabolism has
been reported, the association between the severity of NAFLD
and glucose tolerance remains to be clarified. We previously
reported that the stages of severity in histological findings
(Matteoni ’s classification) independently affect insulin sensi-
tivity/resistance in NAFLD. In this study, correlation between
insulin sensitivity and pathohistological findings of liver
specimens in detail in patients with NAFLD. Glucose tolerance
of 131 Japanese patients [sex: male/female = 73/58; age (y):
46.4 ± 16.5 (mean ± SD); BMI: 29.0 ± 5.2] in our hospital diag-
nosed as NAFLD by histological findings of liver biopsy
specimen was examined by using 75-g OGTT [normal: n = 47;
impaired glucose tolerance: n = 51; diabetes (DM): n = 33]. In
DM, 29 patients did not take any antidiabetic medication and 4
patients took oral hypoglycemic agents (nateglinide: n = 2;
voglibose: n = 2). Based on the OGTT data, QUICKI, which
reflects insulin sensitivity in both liver and skeletal muscle,
Matsuda Index (MI), which mainly reflects insulin sensitivity
in skeletal muscle, and Hepatic insulin resistance index (HRI),
which mainly reflects insulin resistance in liver were calcu-
lated. Pathohistological findings were scored according to
Fibrosis Score by Brunt et al. (F) (0–4) and NAFLD Activity Score
(NAS) (0 –8) composed of scores for steatosis (NAS-S) (0– 3),
lobular inflammation (NAS-I) (0 –3), and ballooning (NAS-B) (0–
2). Stepwise multiple regression analysis was performed to
predict indices of insulin sensitivity/resistance. Analysis using
QUICKI as a dependent variable and sex (female = 0, male = 1),
BMI, age, F, and NAS-T as independent variables shows that
BMI (β = −0.401), F ( β = −0.263), NAS-T (β = −0.193), and sex
( β = −0.158) are predicting factors (R2 = 0.346). Analysis using
QUICKI as a dependent variable and sex, BMI, age, F, NAS-S,
NAS-I, and NAS-B as independent variables shows that BMI
( β = −0.410), F ( β = − 0.296), and NAS-S (β = −0.150) are predicting
factors (R2 = 0.315). Analysis using normally-distributed log-e-
transformed MI (log-e MI) and log-e-transformed HRI (log-e
HRI) as a dependent variable and sex, BMI, age, F, and NAS
(NAS-T or NAS-S, NAS-I, and NAS-B) as independent variables
shows that BMI ( β = −0.456) and F (β = − 0.336) (log-e MI:
R2 = 0.356) and BMI ( β = 0.495) (log-e HRI: R2 = 0.245) are
predicting factors, respectively. These findings indicate that
although adiposity is correlated with insulin sensitivity in
both liver and skeletal muscle, fibrosis in liver histology is an
important factor to predict insulin sensitivity in skeletal
muscle independent of adiposity in NAFLD.
PI-21
Circulating soluble IL-6 receptor levels and visceral adipocyte
size are associated with insulin resistance in morbidly obese
subjects
Feng-Chih KUO 1*, Ya-Hsien HUANG2,3, Fu-Huang LIN3,
Yi-Jen HUNG 1, Chang-Hsun HSIEH1, Nain-Feng CHU3,4,
Chien-Hsing LEE 1. 1 Division of Endocrinology and Metabolism,
Department of Internal Medicine, Tri-Service General Hospital,
National Defense Medical Center, Taipei, 2Clinical Laboratory Section,
Cardinal Tien Hospital, New Taipei City, 3School of Public Health,
National Defense Medical Center, Taipei, 4Taitung Hospital, Ministry
of Health and Welfare, Taitung, Taiwan, Taiwan
Background: Morbid obesity is related to chronic inflammation
and many related metabolic complications. Interleukin (IL)-6
plays a pivotal pathophysiological role in obesity, and IL-6
trans-signaling via the soluble IL-6 receptor (sIL-6R) has a
major pro-inflammatory effect. The aim of this study was to
investigate the associations between sIL-6R, adipocyte size
and insulin resistance in morbidly obese individuals.
Methods: We measured levels of sIL-6R, high-sensitivity C-
reactive protein (hs-CRP), and lipid parameters and estimated
insulin resistance using homeostasis model assessment
(HOMA-IR) before the patients underwent bariatric surgery.
Mesenteric adipose tissue was collected during surgery,
adipocyte size and levels of membrane bound IL-6 receptor
(mIL-6R) were evaluated. In total, 35 adults (20 men and 15
women) were recruited.
Results: The subjects with high HOMA-IR (≥ 2.4) had higher
fasting glucose/insulin, triglycerides, sIL-6R, adipocyte size
and lower high-density lipoprotein (HDL) cholesterol and mIL-
6R than those with low HOMA-IR (<2.4). Adipocyte size
positively correlated with sIL-6R (r = 0.559, P = 0.001) and
HOMA-IR (r = 0.773, P = <0.001) independent of age, sex, body
mass index (BMI), waist and use of diabetic drugs. In addition,
every 1 ng/mL increase in sIL-6R concentration corresponded
to a 10.9% decrease in the likelihood of maintaining lower
insulin resistance. Furthermore, a sIL-6R level of 77.45 ng/mL
was a reasonable cutoff level to predict lower insulin
resistance in morbidly obese subjects.
Conclusion: Circulating sIL-6R and adipocyte size are more
closely associated with insulin status than waist circumfer-
ence or BMI in morbidly obese adults. sIL-6R may be a useful
biomarker to predict insulin status among morbid obese
subjects.
PI-22
Inhibition of local macrophage growth ameliorates obesity-
associated adipose tissue inflammation, insulin resistance
and hepatic steatosis in HFD-fed mice
Yutaro MORITA1, Takafumi SENOKUCHI 1*, Sarie YAMADA1,
Takeshi MATSUMURA1, Eiichi ARAKI1. 1Department of Metabolic
Medicine, Faculty of Life Sciences, Kumamoto University, Japan
Objective: Chronically increased activity of the innate
immune system has been implicated in the pathogenesis of
the insulin resistance associated with obesity and type 2
diabetes. Although the tissue macrophage has been demon-
strated proliferating in the adipose tissue and the liver,
the roles of the macrophage proliferation in the development
of insulin resistance and hepatic steatosis are largely
unknown.
Research design and methods: To verify the direct evidence of
involvement of tissue macrophage proliferation for adipose
tissue inflammation and hepatic steatosis, we generated a
transgenic mouse whose macrophage proliferation is specif-
ically suppressed by inducing the expression of cyclin
dependent kinase inhibitor, p27kip under the regulation of
the scavenger receptor promoter/enhancer (mac-p27Tg). The
mac-p27Tg mice were fed High-Fat Diet (HFD) to assess the
impact on adipose tissue inflammation, insulin resistance and
hepatic steatosis.
Results: Glucose and insulin tolerance tests in HFD-fed mac-
p27Tg indicate significantly enhanced glucose clearance and
insulin sensitivity compared with the control littermates.
Macrophages were less accumulated in mac-p27Tg adipose
tissue. The crown-like structure formation was significantly
reduced in mac-p27Tg along with decreased inflammatory
cytokine mRNA expression in adipose tissue. The triglyceride
content in the liver was significantly decreased in HFD-fed
mac-p27Tg mice compared with the controls. Azan staining
showed significant reduction of liver fibrosis in mac-p27Tg
liver. The mRNA expression of fibrosis markers (collagen1a1,
alpha-SMA) and the NADPH oxidase (p22phox) were signifi-
cantly decreased in mac-p27Tg liver.
Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65–S211 S188