7. The putative mechanisms underlying the contribution of
NAFLD to the increased risk of developing CVD and T2DM
Anstee, Q. M. et al. (2013) Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis
Nat. Rev. Gastroenterol. Hepatol. doi:10.1038/nrgastro.2013.41
8. Anstee, Q. M. et al. (2013) Progression of NAFLD to diabetes mellitus, cardiovascular disease or
irrhosis Nat. Rev. Gastroenterol. Hepatol. doi:10.1038/nrgastro.2013.41
13. • Hepatogenous diabetes differs from type 2 diabetes
in that there is less often a positive family history
and that the cardiovascular and retinopathic risk is
low.
• The prognosis of cirrhotic patients with diabetes is
more likely to be negatively affected by the
underlying hepatic disease and its complications
than by the diabetes.
14. • Liver transplantation did not correct the diabetes
in one-third of patients with hepatogenous
diabetes undergoing transplantation.
• HbA 1c is an unreliable
- undetected bleeding episodes
- hemolysis due to hypersplenism are
frequent in
• Using a fructosamine test in addition to blood
glucose self-monitoring may provide a more
suitable assessment of metabolic control.
15. • no dietary restrictions should be prescribed for
patients with hepatogenous diabetes.
The survival of patients with liver cirrhosis
depends on an adequate calorie intake; a
hypocaloric diet even leads to increased mortality.
Patients with liver cirrhosis, may suffer from
protein malnutrition, should eat a balanced diet with
sufficient calories;
a late snack prevents nocturnal hypoglycemia
and improves nutritional status
20. 1.Are elevations in serum aminotransferase levels
associated with 3-hydroxy-3-methylglutaryl
coenzyme A (HMG-CoA) reductase inhibitor, or
statin, therapy?. YES
2. Are statin-associated elevations in
aminotransferase levels indicative of liver
damage or dysfunction? NO
3. Should liver enzymes and liver function tests be
monitored in patients receiving long-term statin
therapy? NO
21. 4.Are any of the following conditions a
contraindication for statin therapy?
- Chronic liver disease: No
- Compensated cirrhosis :No
- Decompensated cirrhosis or acute liver failure:Yes
5. Can statins be used in patients with NAFLD or
nonalcoholic steatohepatitis (NASH)? Yes
46. MECHANISMS UNDERLYING THE
EFFECTS OF LIVER DISEASES ON
T2DM
• Gut microbiota
• Hepatic inflammation and associated insulin
resistance
• Hepatic fat accumulation
• Reactive oxygen species
• Hepatokines
• HCV infection
47. • Insulin resistance of the peripheral tissues and the
liver caused by liver damage is regarded as the
central disturbance of glucose metabolism.
• Reduced insulin extraction by the liver as a result of
the functional disturbance or portosystemic shunts
results in hyperinsulinemia,
• This hyperinsulinaemia is potentiated by raised
levels of contrainsulin hormones (e.g. glucagon,
growth hormone, insulin-like growth factor), free fatty
acids and cytokines
48.
49. • The “two-hit” hypothesis proposed by Day and
James in 1998[15] postulates that the steatotic liver
is susceptible to secondary insults including a
vulnerability to reactive oxygen species, gut-derived
endotoxins, and adipocytokines such as tumor
necrosis factor-α (TNF-α) and other cytokines. The
first “hit” is thought to be an accumulation of fatty
acids and triglycerides within the liver, possibly due
to insulin resistance. Chronic stress such as portal
endotoxemia (the second “hit”) leads to
mitochondrial dysfunction and Kupffer cell adaptive
changes[16,17], which in turn result in hepatocyte
survival adaptation[18] and subsequent necrosis
50. • The excess in free fatty acids found in the insulin-resistant
state is directly toxic to hepatocytes.
mechanisms include
- cell membrane disruption at high concentration,
- mitochondrial dysfunction
- oxidant stress from reactive lipid peroxidation,
peroxisomal beta-oxidation
- increase in proinflammatory cytokines TNF-a
contribute to hepatocellular injury
