3. 3
Prof.& consultant Gastroenterology
&Diabetes
Military Medical Academy
NAFLD; Diabetes
&Heart
1- NAFLD
DV&C2- Its relation to DM
3- TT of NAFLD (diabetes
comorbidity)
A multi-faceted disease
for multi-disciplinary
preventive intervention
4. 4
A variably defined
aggregate of disorders
related to:
Insulin resistance
Diabetes type II
NAFLD
- Dixon JB, et al. Gastroenterology 2002;122-
- Expert panel on Detection Evaluation, and Treatment of High Blood
Cholesterol in Adults. JAMA 2001;285
NAFLD
The consequences
of NAFLD are
not confined to
the liver.
5. 5
Crosstalk of
visceral adipose
tissue and the
liver.
Buechler C, et al: WJG June , 2011 V. 17 (23)
Mitochondrial
dysfunction (respiratory
chain deficiency) ,
modulated by some
genetic polymorphism
T Asselah etal; Gut 2006;55
Systemic inflammation
hepatic IR
gut-liver
axis
TLR
Yasuhiro Miyake & Kazuhide Yamamoto
: Hepatology Research 2013; 43
In NAFLD,
Intestinal permeability
&the prevalence of
SIBO are increased.
6. 6
Vicious circle linking fatty liver to diabetes and diabetes to
progressive liver injury
in predisposed individuals
long-lasting/ decompensated
alone, or in the setting of MS
( May in non-cirrhotic)
NASH ,Pre-
diabetes,
+GGT &
triglycerides
and
insufficient
physical
activity.
Paola Loria, et al : Hepatology Research 2013; 43
T2 DM, 30-60% of NASH pat.
“Red flag”
6
7. 7
There is a very high prevalence of NAFLD (>55%) in
individuals with T2DM.
Chalasani N, et al : HEPATOLOGY, June 2012
Also T2 DM is present in 30%-45% of patients with
non alcoholic steato hepatitis (NASH) .
Harrison SA. : J Clin Gastroenterol 2006; 40
NAFLD is more frequent among obese (76%), and it is
almost universal among diabetic people who are
morbidly obese.
Del Gaudio A, et al : Obes Surg 2002;12
Epidemiology of diabetes & NAFLD
8. 8 Ballestri S et al . World J Gastroenterol 2014 February 21; 20(7)
g-GT= steatosis- IR&OS-
CAD &higher mortality
Atherogenic dyslipidemia and the hepatic secretion of
several pathogenic mediators into the bloodstream
Possible mechanisms leading to cardiac &arrhythmogenic complications in NAFLD
10. 10
Insulin sensitizers
Metformin improves insulin sensitivity and ALT-AST. It has
no significant effect on liver histology.
According to current data, it can be given in patients with both
NAFLD/NASH and type 2 DM.
TZDs improve insulin sensitivity, serum ALT-AST levels and
histology in some cases, but there are some concerns about
the safety of long-term therapy.
These drugs are the best choice for the treatment of NAFLD in
patients with T2 DM who are also candidates for ISA
(Selection of appropriate patients for avoiding side effects)
Zeynel Abidin O. , Abdurrahman Kadayifci :World J Hepatol 2014
April 27; 6(4)
TZDs decrease Risk of HCC development
Lai SW, et al : Am J Gastroenterol. 2012 Jan;107(1)
11. 11
Hypothesized that in NAFLD the DPP-4 enzymatic
activity is increased which might contribute to the
development of type 2 diabetes and metabolic
deterioration.
Incretins in non alcoholic fatty liver disease
Ga´bor Firneisz, et al : PLoS ONE ,August 2010 Vol 5 Issue 8
T Iwasaki, et al. www.hepato-gastroenterology.org 2011; 58(112): Ahead of print
11
DPP-4 inhibitors might offer prevention of metabolic deterioration& control
of diabetes in NAFLD. Also may have impact on liver fibrosis (Effect on
hepatic stellate cells ).
A recent meta-analysis including 4442 patients indicated that
liraglutide decreased aminotransferase levels and that this
effect was dose-dependent.
A pilot study demonstrated that treatment with liraglutide had a good safety
profile and significantly improved liver function and histological features in
NASH patients with GI.
Armstrong MJ, Aliment Pharmacol Ther 2013;37
Eguchi Y, et al. : Hepatol Res. 2014 May 4
12. 12
Niemann-Pick C1-Like1(NPC1L1)Inhibitors. Ezetimibe
Hepatic NPC1L1 may facilitate hepatic cholesterol
accumulation and ezetimibe may be a potential candidate
for NAFLD.
In clinical trials, albeit on a small scale, ezetimibe improved
biochemical parameters , hepatic enzymes and the
histology.
M. Enjoji & M.Nakamuta, World Journal of Gastroenterology, vol. 16,no. 7, 2010.
M. Enjoji, et al., Lipids in Health and Disease, vol. 9, article 29, 2010.
*Statins can be used to treat dyslipidemia in patients with
NAFLD and NASH without increased risk for drug-induced liver
injury . Untill now , statins should not be used to specifically
treat NASH. (Strength – 1, Quality – B)
*Omega-3polyunsaturated fatty acid may be considered as the
first line agent to treat hypertriglyceridemia in NAFLD, but
not as specific treatment for NAFLD. (Strength – 1, Quality –
B)
NAGA CHALASANI, et al :GASTROENTEROLOGY 2012;142
17. 17
17
In addition to its anti-fibrotic effect
, it reduce BP, improve glucose
Tolerance & prevention of new-
onset T2 DM, thus contributing to
further reduce the risk of CVD
events.
18. 18
HOME MESSAGE
*Patients with T2DM should be always assessed for
NAFLD and vise versa to ensure early diagnosis
and medical care to prevent and minimize the
occurrence of NASH , DM & CVD.
*Awareness of NAFLD in general appears to be
disappointingly lacking in the medical community.
NAFLD should be viewed as a complex and
multi-faceted disease often calling for multi-
disciplinary intervention.
19. 19
Topics : including free papers
&case presentation: (speakers
of young doctors 25-35y. of age:
2000 LE as a gift for the best 2
doctor)
1- Diabetes association with
liver disease.
2- Liver in relation to
different specialties ,other
than diabetes
3- Liver VS diabetes & gut
dysmotility; intestinal dysbiosis
4-Obesity
5-Stem cell &
immunotherapy in diabetes
& liver disease
6-Improving
quality of life in chronic
diseases
7-Medical aspects of liver
transplantation
Mob. +2
012221337
50 Fax +2
23939382
E mail: akhalekhamed @gmail.com
