Recent adipokines as a markers of diabetic complications

1. Recent adipokines as a markers
of diabetic complications
By
Prof. Moustafa Rizk
Prof. of Clinical Pathology
Faculty of Medicine, University of Alexandria
4/3/2015
10/11/2017 4:30 AM 1

2. Total slides : 51 2 October 11, 2017
Outlines
• Adipose tissue
• Adipose tissue as an endocrine organ
• Diabetic complications

3. Adipose tissue
Adipose tissue or fat is loose connective tissue
composed of adipocytes. Its main role is to
store energy in the form of fat, although it
also cushions and insulates the body.

4. Two types of adipose tissue exist: brown adipose tissue (BAT)
and white adipose tissue (WAT)
WAT
BAT
For letter symbols, see slide 36
A specialised form of adipose tissue in human infants

5. Anatomical features
• In humans, adipose tissue is located beneath the
skin (subcutaneous fat), and is also found around
internal organs (visceral fat). Adipose tissue is
found in specific locations which are referred to as
'adipose depots.
Adipose depots in different
parts of the body have
different biochemical profiles

6. Fat Cell Development
After fat cells have
enlarged and energy
intake continues to
exceed expenditure,
fat cells increase in
number again.
During growth,
fat cells increase
in number.
When energy intake
exceeds
expenditure,
fat cells increase in
size.
With fat loss, the
size of the fat cells
shrinks, but not
the number.

7. Adipose tissue as an endocrine organ
Adipose tissue has come into focus as an endocrine
organ .
Adipose tissue secretes a variety of
bioactive peptides (adipokines).
Adipokines may locally regulate fat mass by
modulating adipocyte size/number or
angiogenesis and inversely increased fat
mass leads to dysregulation of adipocyte
functions.
10/11/2017 4:30 AM 7

8. Adipokines
are proteins secreted from and synthesized by
adipocytes. White adipose tissue (WAT) has been identified as a
metabolically active endocrine organ which affects a plethora of
body functions including energy and feeding regulation, glucose
and lipid metabolism, thermogenesis, neuroendocrine function,
reproduction, immunity and most relevantly, cardiovascular
function.
10/11/2017 4:30 AM 8
Omentin-1

9. In 2013, IDF (International Diabetes Federation)
estimated that there were 34.6 million people with diabetes in
the Middle East and North Africa, 7.5 millions of them were in
Egypt.
10/11/2017 4:30 AM 9

11. Microvascular
Complications of
Diabetes
may be the most
common microvascular complication of
diabetes. It is responsible for ~ 10,000
new cases of blindness every year in
the United States alone.
10/11/2017 4:30 AM 11

12. Microvascular
Complications of
Diabetes
is the leading cause of
renal failure in the United States. It is defined
by proteinuria of > 500 mg in 24 hours in the
setting of diabetes, but this is preceded by
lower degrees of proteinuria, called
“microalbuminuria
10/11/2017 4:30 AM 12

13. Microvascular
Complications of
Diabetes
is recognized by
the American Diabetes Association (ADA) as
“the presence of symptoms and/or signs of
peripheral nerve dysfunction in people
with diabetes after the exclusion of other
causes.
10/11/2017 4:30 AM 13

14. Subjects with type 2 diabetes mellitus show the
characteristic lipid profile of raised LDL cholesterol,
with low HDL cholesterol and mildly elevated
triglyceride concentration.
Insulin resistance could raise blood pressure by loss
of insulin's normal vasodilator activity.
10/11/2017 4:30 AM 14

15. is a peptide that in humans is
encoded by the APLN gene.. It is
widely expressed in various organs
such as the heart, lung, kidney, liver,
adipose tissue, gastrointestinal tract,
brain, adrenal glands, endothelium,
and human plasma.
10/11/2017 4:30 AM 15

16. Vascular
Cardiac
Brain
Bone
Fat cells
10/11/2017 4:30 AM 16

17. Vascular
 Vascular expression of the receptor
participates in the control of blood
pressure and its activation promotes
the formation of new blood vessels
(angiogenesis).
10/11/2017 4:30 AM 17

18. Cardiac
 Apelin behaves as one of the most potent
stimulator of cardiac contractility.
 Apelin acts as a mediator of the cardiovascular
control. It is one of the most potent
stimulators of cardiac contractility yet
identified.
10/11/2017 4:30 AM 18

19. Brain
 Apelin has a diuretic effect with its
hypotensive effect participates in a global
manner to the homeostatic regulation of body
fluids.
 Apelin is also detected in brain areas, which
control appetite, but its effects on food intake
are very contradictory.
10/11/2017 4:30 AM 19

20. Bone
Receptor expression is also
observed at the surface of
osteoblasts, the cell progenitors
involved in bone formation.
10/11/2017 4:30 AM 20

21. Fat cells
 Adipocytes have recently been demonstrated
to synthesize apelin, and its content was
elevated in adipocytes from different mouse
models of hyperinsulinemia-associated obesity.
 Apelin plasma concentrations were elevated in
obese compared to lean humans as well as in
obese, hyperinsulinemic mice compared to
lean mice.
10/11/2017 4:30 AM 21

22. Comparison between the different studied groups
according to apelin
0
200
400
600
800
1000
Neurpathy
Retinoupathy
Nephropathy
Morethan
onecomplication
Control Diabetic
without
complications
Diabetic with complications
Meanofapelin
Rizk MM,Abd El Aty T,El Saudi W.Study of plasma apelin level in type 2 diabetic patients with and without
microvascular complications and its relation to some anthropometric and metabolic parameters,2014 .10/11/2017 4:30 AM 22

23. Comparison between the different studied groups
according to apelin
Control
(n = 30)
Diabetic
without
complications
(n = 30)
Diabetic with complications
Neuropathy
(n = 7)
Retinopathy
(n = 7)
Nephropathy
(n = 7)
More than
one
complication
(n = 9)
Apelin
Range
320.0 – 2100.0 138.0 – 640.0 475.0 – 875.0 530.0 – 930.0 496.0 – 1175.0 420.0 – 1175.0
Mean ± SD
797.0 ± 436.63 305.43±131.46 664.29±145.67 748.57±171.19 772.57±252.91 833.33±236.84
Median 727.50 271.50 650.0 715.0 830.0 892.0
p1 <0.001* 0.662 0.556 0.560 0.129
p2 <0.001* <0.001* <0.001* <0.001*
10/11/2017 4:30 AM 23

24.  Plasma apelin is reduced in newly diagnosed
and untreated patients with T2DM.
 The serum Apelin level in the patients with the
diabetic type 2 nephropathy was significantly
higher than that of diabetics with no
complications.
Role of apelin in diabetes
mellitus and microangiopathy
10/11/2017 4:30 AM 24

25. Role of apelin in diabetes
mellitus and microangiopathy
 Apelin levels in diabetic patients are higher in
the presence of neuropathy and longer
disease duration.
 The serum Apelin level in the patients with the
diabetic type 2 retinopathy was significantly
higher than that of diabetics with no
complications.
10/11/2017 4:30 AM 25

26. Visfatin, also called pre-B cell
colony-enhancing factor 1
(PBEF1), is a novel adipokine
that is secreted by visceral and
subcutaneous fat, human bone
marrow, liver, and muscle.
10/11/2017 4:30 AM 26

27. Visfatin has been described to exhibit
insulin-like activity by exerting a great
affinity to the insulin receptor.
Besides to its role in atherogenesis,
visfatin has been reported to contribute
to the destabilization process of
atherosclerotic lesions.
10/11/2017 4:30 AM 27

28. Increased plasma visfatin levels
have been reported in patients
with carotid atherosclerosis and
were independently associated
with the maximum carotid intima
media thickness (CIMT).
10/11/2017 4:30 AM 28

29. • Studies in cultures of human
leukocytes (in vitro) showed that
visfatin may increase the expression
of various inflammatory mediators
known to be involved in the
pathogenesis of atherosclerosis.
10/11/2017 4:30 AM 29

30. 0
1
2
3
4
5
6
7
8
9
Cases Control
MeanofHOMA-IR
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31. 0
1
2
3
4
5
6
7
8
Cases Control
MeanofhsCRP(mg/l)
10/11/2017 4:30 AM 31

32. 0
1
2
3
4
5
6
Cases Control
Meanofvisfatin(ng/ml)
10/11/2017 4:30 AM 32

33. 0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
Cases Control
MeanofIMT(mm)
10/11/2017 4:30 AM 33

34. Visfatin
r p
Age 0.301* 0.020
Duration of DM 0.651* <0.001
BMI 0.595* <0.001
WC 0.633* <0.001
Systolic 0.659* <0.001
Diastolic 0.523* <0.001
FPG 0.257* 0.047
HbA1C 0.657* <0.001
hs CRP 0.813* <0.001
Fasting insulin 0.296* 0.022
HOMAIR 0.687* <0.001
Cholesterol 0.570* <0.001
TG 0.692* <0.001
HDL -0.312* 0.015
LDL 0.379* 0.003
IMT 0.954* <0.001
Degree of stenosis 0.872* <0.001*
10/11/2017 4:30 AM 34

35. Our study revealed elevated circulating serum visfatin
in type 2 diabetics and obese subjects and these results
were supported by a significant association between
visfatin and insulin resistance, which indicates that
visfatin may play a role in the pathophysiology of
insulin resistance, this may represent a new target in
the treatment of type 2 DM in the future.
10/11/2017 4:30 AM 35

36. Plasma visfatin levels are significantly higher in diabetics
with carotid atherosclerosis, and are independently
associated with the carotid intima media thickness (CIMT).
10/11/2017 4:30 AM 36

37. is a newly discovered adipokine , it is a secretory
hydrophilic glycoprotein consisting of 313 amino
acids and 1-linked oligosacharides, secreted
selectively from omental and epicardial adipose
tissue.
10/11/2017 4:30 AM 37

38. It was found that omentin-1 directly induces endothelium-
dependent vasodilatation.
It also promotes activation of the Akt signalling pathway
(critical regulator of cell survival ), modulating the function of
NO synthase in the endothelium.
Recently, several clinical studies show an association
between omentin-1 concentrations and the clinical
manifestations of carotid atherosclerosis and coronary
artery disease (CAD).
10/11/2017 4:30 AM 38

39. Thus omentin appears to be a
‘protective adipokine’ with
respect to CVD, given that it
induces vasodilatation and
inhibits vascular inflammation
and angiogenesis.
10/11/2017 4:30 AM 39

40. 0
500
1000
1500
2000
2500
With macrovascular
complications
Newly diagnosed
without macrovascular
complications
DM Control
Meanofomentin(ng/L)
There was sig. diff. regarding Omentin-1 plasma level.
10/11/2017 4:30 AM 40
OMENTIN-1 AND ITS RELATION TO ARTERIAL STIFFNESS AND CAROTID INTIMA- MEDIA THICKNESS IN TYPE
2 DIABETIC PATIENTS.
Talaat A. Abd El -Atty, MD 1 , Shadya A. Helmy, MD 2 ,Mohamed M. Rezk, MD 3, Kamel H. Rohoma, MD 1 ,Sherihan E.
Hemida, 2015

41. 0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
With macrovascular
complications
Newly diagnosed without
macrovascular
complications
DM Control
MeanofIMT(mm)
There was sig. diff. regarding IMT
10/11/2017 4:30 AM 41

42. 0
1
2
3
4
5
6
7
8
With macrovascular
complications
Newly diagnosed without
macrovascular
complications
DM Control
Meanofhs-CRP(mg/L)
There was sig. diff. regarding hs-CRP
10/11/2017 4:30 AM 42

43. Omentin-1 level is significantly lower in
subjects with diabetes and
macrovascular complications than in
the newly diagnosed diabetic patients.
Omentin-1 level is significantly lower in
newly diagnosed diabetic patients than
in control group.
10/11/2017 4:30 AM 43

44. Only IMT and HbA1C have the most independent negative
correlations with omentin, also they are considered
predictive factors for development of macrovascular
complications in diabetic patients.
10/11/2017 4:30 AM 44

45. 10/11/2017 4:30 AM 45

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