Study of Plasma Adiponectin and Insulin Resistance in Subjects with Non-Alcoholic Fatty Liver Disease.

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Arch Gen Intern Med 2018 Volume 2 Issue 3
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http://www.alliedacademies.org/archives-of-general-internal-medicine/Research Article
Background: The relation between insulin resistance and the level of plasma adiponectin
hormone in patients with non-alcoholic fatty liver disease (NAFLD) was highly suggested due to
the high prevalence of NAFLD in obese and diabetic patients.
Objectives: This study was conducted to explore the link between the three factors, NAFLD,
insulin resistance and the level of plasma adiponectin.
Methods: The study was run on patients with the diagnosis of NAFLD, depending on the
ultrasound ndings, with exclusion of diabetic, obese, and alcoholic patients. The level of insulin
resistance was evaluated using the homeostasis model assessment (HOMA IR) index, and the
level of plasma adiponectin was measured as well.
Results: There was a signicant degree of insulin resistance in patients with NAFLD, with a
signicantly lower levels of adiponetin hormone compared to the control group.
Conclusion: This study reported lower plasma adiponectin levels in NAFLD patients that were
inversely correlated with insulin resistance, which was markedly documented in the patients of
NAFLD.
Abstract
Introduction
Non-alcoholic fatty liver disease (NAFLD) is a
clinicopathological syndrome characterized by hepatic steatosis
with or without active inammation in patients with a negligible
alcohol intake, NAFLD can progress to brosis and even
cirrhosis and eventually can cause hepatocellular carcinoma.
NAFLD is recognized as one of the leading causes of chronic
liver disorders with a worldwide distribution.
Insulin resistance; a state in which a given concentration of
insulin produces a less than expected biological effect. And it
has been dened as the requirement of 200 or more units of
insulin per day to attain glycemic control and prevent ketosis.
The homeostasis model assessment (HOMA) has been
suggested as a method to assess insulin resistance using fasting
blood glucose and fasting insulin concentrations.
HOMA index = fasting glucose (in mg/dl) / 18 x fasting insulin
(in micro-unit/ml) / 22.5.
It is concluded that HOMA provides a useful model to assess
insulin resistance in epidemiological studies in which only
fasting samples are available [1].
According to the homeostasis model assessment (HOMA),
patient is considered to have insulin resistance if HOMA
index is more than 2.14, it is thought to be the pathognomonic
condition responsible for NAFLD.
Adiponectin is a hormone that is secreted by the adipocytes
and it was reported that it has several anti-atherogenic, anti-
diabetic and anti-inammatory properties. Experimental and
clinical studies have stated that adiponectin concentrations have
a positive correlation with insulin sensitivity.
This study aimed to investigate the relation between NAFLD
and both of insulin resistance and adiponectin hormone and
discover their role in the pathogenesis of the disease.
Methodology
The study included forty patients (twenty four females and
sixteen males) with NAFLD as well as ten age and sex matched
healthy volunteers serving as controls (ve females and
ve males). Patients were selected from those attending the
outpatient clinics of the internal medicine department of Benha
University Hospitals.
Exclusion criteria: alcohol consumption (at any rate), patients
with obesity (BMI = or > 30), evidence of viral or toxic hepatitis,
patients with diabetes mellitus (fasting blood sugar > 126 mg/
dl), patients with hypertention (blood pressure >140/90),
patients with nutritional disorders (e.g. obesity, starvation,
gastrointestinal surgery for obesity, total parentral nutrition),
patients who are consuming some drugs (e.g. glucocorticoid,
synthetic estrogen, amiodarone, calcium channel blockers),
metabolic or genetic causes of fatty liver (e.g. pregnancy, and
lipodystrophy), and patients who are over 70 years.
All patients were subjected to a thorough history taking and
a complete clinical examination, with special stress on the
following:
Abdominal ultrasound to detect patients with NAFLD, fasting
blood glucose, liver function tests [alanine aminotransferase
Study of plasma adiponectin and insulin resistance in subjects with non-alcoholic
fatty liver disease.
Hady Gad*
Department of Internal Medicine, Middle East Medical Center, Kingdom of Bahrain
Accepted on May 14, 2018
Keywords: Non-alcoholic fatty liver disease (NAFLD), Insulin resistance, Adiponectin hormone
ISSN: 2591-7951

24
Citation: Gad H. Study of plasma adiponectin and insulin resistance in subjects with non-alcoholic fatty liver disease. Arch Gen Intern Med. 2018;2(3):23-26.
DOI: 10.4066/ 2591-7951.1000053
Arch Gen Intern Med 2018 Volume 2 Issue 3
(ALT) and aspartate aminotransferase (AST)], fasting serum
insulin, fasting plasma adiponectin hormone, estimation of
insulin resistance according to (HOMA test).
Results
Laboratory ndings
• Patients with NAFLD had a signicantly lower levels of
plasma adiponectin compared to the control group (in the
NAFLD patients the mean was 4.79, while in the control
group it was 11.8 microgram/ml) using the students (t)
test, and signicance was adopted at p<0.05, (Table 1).
• Patients with NAFLD had higher levels of fasting blood
glucose, fasting serum insulin and insulin resistance
(HOMA test) compared to the control group, using the
students (t) test, and signicance was adopted at p<0.05,
(Table 2).
• This study demonstrated that plasma adiponectin levels
were higher in females than in males (in females the
mean was 3.14, while in males it was 2.26 microgram/
ml) using the students (t) test, and signicance was
adopted at p<0.05, (Table 3).
• Plasma Adiponectin level was negatively correlated with:
fasting blood glucose, fasting serum insulin level, and
insulin resistance (HOMA test), with Spearman's rank
correlation (r) - 0.671, - 0.426, and – 0.66 respectively,
(Table 4).
Discussion
Non-alcoholic fatty liver disease (NAFLD) is emerging as one
of the most common liver disorders claiming the urgent attention
of both medical professionals and the public sphere, as it is
revealed that simple triglyceride accumulation in hepatocytes
(steatosis) frequently becoming complicated by inammation
(non-alcoholic steatohepatitis or NASH) that may progress
into more advanced stages of the disease including cirrhosis
or, eventually, hepatocellular carcinoma. NAFLD is intimately
associated with progressive manifestation of insulin resistance
in the liver, and it was approved that insulin resistance in liver
and adipose tissue precedes the impairment of insulin sensitivity
in skeletal muscle [2].
Adiponectin is a fat derived hormone, that is produced by
the adipocytes [3]. It is an anti-diabetic and anti-atherogenic
hormone that correlates with insulin sensitivity. Adiponectin
directly counteracts the effect of tumor necrosis factor alpha
(TNF-α) on insulin signaling and lipid metabolism [4].
The discovery of adiponectin has added an additional potential
mechanism to explain the pathogenesis of liver steatosis [5].
Adiponectin is a relatively abundant serum hormone which
was reported to inuence both lipid and glucose metabolism
in the liver and in muscle tissue. In the liver, it increases the
sensitivity to insulin so it inhibits gluconeogenesis and regulates
hepatic non-estried fatty acid metabolism, via suppression of
lipogenesis and activation of non-estried fatty acid oxidation.
It is proposed that adiponectin enhances expression of the
peroxisome-proliferator activated receptor alpha (PPAR-α)
gene, leading to increased fat oxidation [6]. In healthy adults,
a relationship was observed between adiponectin deciency
and increased liver fat [7]. It is found that in mild obesity,
hypoadiponectinemia predicted the presence of hepatic
steatosis at abdominal ultrasound [8]. Adiponectin has anti-
inammatory properties in the liver, and its deciency might
account for high aminotransferase and liver disease progression
[6], it may be able to preserve liver function by preventing lipid
accumulation in hepatocytes [9]. Moreover a direct antibrotic
effect of adiponectin has been suggested on the basis of
adiponectin receptor gene expression in hepatic stellate cells
and the inhibition of stellate cells proliferation and migration
after adiponectin treatment [10], it also inhibits tumor necrosis
Patients group
(NAFLD)
"n=40"
Control group
"n=10"
t p
Plasma Adiponectin
(microgram/ml)
Range
Mean
±S.D.
3-13
4.79
1.41
10.5-13
11.8
0.82 7.56 <0.05 (S)
Table 1. Range and mean ± SD (standard deviation) of plasma
adiponectin in the studied groups and their statistical difference.
Patients group
(NAFLD)
"n=40"
Control group
"n=10"
t p
Fasting blood
glucose (mg/dl)
Range
Mean
±S.D.
70-120
83.70
10.28
65-100
78.4
11.56 1.65 >0.05 (N.S.)
Fasting
serum insulin
(microunit/ml)
Range
Mean
±S.D.
3.599-34.557
11.21
6.81
4.67-15.73
7.79
3.21 2.98 <0.05 (S)
Insulin
resistance
(HOMA test)
Range
Mean
±S.D.
0.37-10.58
2.73
2.06
0.816-1.23
1.01
0.79
5.11 <0.05 (S)
Table 2. Range and mean ± SD (standard deviation) of fasting blood
glucose, fasting serum insulin and insulin resistance in the studied
groups and their statistical difference. Females
“n=29”
Males
“n=21” t p
Plasma adiponectin
(microgram/ml)
Mean
±S.D.
3.14
1.81
2.26
1.07 1.85 <0.05 (S)
Table 3. Mean ± SD (standard deviation) of plasma adiponectin in
females and males in both groups (NAFLD group and control group)
and their statistical difference.
Adiponectin
r p
FBG (mg/dl) -0.671 <0.05 (S)
Fasting serum insulin (microunit/ml) -0.426 <0.05 (S)
insulin resistance (HOMA test) -0.66 <0.05 (S)
Table 4. Correlation between plasma adiponectin levels (microgram/
ml) and fasting blood glucose (mg/dl), fasting insulin (microunit/ml),
and insulin resistance.

Gad
25 Arch Gen Intern Med 2018 Volume 2 Issue 3
factor alpha (TNF-α) expression and prevents the expression
of cytokines in hepatic stellate cells and it may protect against
steatohepatitis through its anti-inammatory action, as it is well
known that inammation is a key mechanism in the progression
of fatty liver to steatohepatitis and cirrhosis [5].
In this study the plasma adiponectin levels were signicantly
lower in the NAFLD patients group, this result agrees with
other studies; Bugianesi et al. [6], Pagano et al. [5], Sargin et
al. [9] and Yoon et al. [11]. And this reduction was associated
with insulin resistance. The strong association between insulin
resistance and NAFLD has been extensively demonstrated [5].
In this study the levels of plasma adiponectin were signicantly
higher in females than in males, this observation was
supported by Yamamoto et al. [12] who stated that adiponectin
concentrations seem to be gender-dependent, being higher in
women than in men. This fact was also documented in many
other studies; Bugianesi et al. [6], Sargin et al. [9] and Yoon et
al. [11] who stated higher adiponectin expression in women, as
compared to men.
The study showed that patients with NAFLD had signicantly
increased values of fasting serum insulin and insulin resistance
(HOMA test) compared to the control group, while there was a
non signicant change in the fasting glucose levels in both groups.
This result is advocated for the statement that, insulin resistance
is the pathognomonic condition responsible for NAFLD [11].
And this notion was supported by Bloomgarden [13] who stated
that individuals with NAFLD have the same degree of insulin
resistance as those with type 2 diabetes mellitus.
In agreement with this study Pagano et al. [5] demonstrated
the strong association between insulin resistance and NAFLD,
it was shown that fasting serum insulin and insulin resistance
(HOMA test) levels were signicantly higher in NAFLD
patients than in control subjects.
Bugianesi et al. [6] enforced this result as it was found that
patients with NAFLD had higher serum insulin levels and
insulin resistance (HOMA test) than the control group despite
of the similar glucose tolerance in the two groups.
In a population-based study of >2,000 individuals having
magnetic resonance spectroscopy, more than one-third of the
population had evidence of elevated hepatic triglycerides, with
30% of these individuals having insulin resistance syndrome,
suggesting insulin resistance to be the primary factor in inducing
fatty liver [14].
This result was also supported by the study of Sargin et al.
[9], which revealed that levels of fasting insulin and insulin
resistance were statistically and signicantly higher in NAFLD
patients than in the control group.
Insulin resistance is the most reproducible factor in the
development of NAFLD [15] and it is a virtually universal
feature of NASH that occurs independently of obesity, as
insulin resistance leads to chronic hyperinsulinemia due to an
impaired response of adipose, muscle, and liver tissue to the
glucoregulatory effects of insulin. Insulin resistance at the
level of the adipocyte further exacerbates excess fatty acids
delivery through ongoing lipolysis in the fed state, where under
normal circumstances lipolysis would be inhibited. In addition,
hyperinsulinemia stimulates de novo lipogenesis and can impair
fatty acids oxidation and very low density lipoprotein (VLDL)
secretion. This excessive intrahepatic lipid accumulation impairs
insulin signaling (hepatic insulin resistance). In the setting of
hepatic insulin resistance, gluconeogenesis is stimulated despite
high insulin levels, thus contributing to the already distorted
glucose metabolism [4].
This study found that there was a signicant negative correlation
between plasma adiponectin levels and fasting blood glucose,
fasting serum insulin levels and insulin resistanc (HOMA test).
This is agreed with Yamamoto et al. [12], Bugianesi et al. [6],
Pagano et al. [5] and Yoon et al. [11].
Conclusion
In conclusion, this study reported lower adiponectin levels in
NAFLD patients that were inversely correlated with insulin
resistance, which was markedly documented in the patients of
NAFLD. These data support that insulin resistance is a primary
pathognomonic factor in NAFLD and also support a role for
adiponectin hormone in the protection against liver injury, in
the context of the hypothesis that an imbalance between the
pro-inammatory and the anti-inammatory cytokines may
have a pathogenic role in the development of the liver damage
in NAFLD. Moreover the relation between the adipose tissue
and the liver may act as a major player in the link between the
metabolic syndrome and the NAFLD.
Adiponectin may be applicable in human diseases as a novel
agent for diagnosis and treating insulin resistance and NAFLD,
as increased levels of the hormone have been correlated to
improving histopathology of the liver, suggesting that it may
play an important role in the progression from NAFLD to
NASH, in NASH patients with a positive histological response
to treatment, increased levels of adiponectin could be seen
in as early as 1 to 3 months post-treatment. Levels continued
to rise throughout the course of therapy. On the contrary, as
demonstrated by another study, patients receiving a placebo
experienced minimal changes, while non-responders showed
decreased adiponectin levels [16,17].
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Citation: Gad H. Study of plasma adiponectin and insulin resistance in subjects with non-alcoholic fatty liver disease. Arch Gen Intern Med. 2018;2(3):23-26.
DOI: 10.4066/ 2591-7951.1000053
Arch Gen Intern Med 2018 Volume 2 Issue 3
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*Correspondence to:
Hady Gad
Department of Internal Medicine
Middle East Medical Center
Kingdom of Bahrain
E-mail: hady_gad@yahoo.com