Diabetes and liver

transcript

Diabetes and Liver

Outline

1. Diabetes and liver -? Vicious cycle

2.Hepatogenous diabetes

3.Elevated transaminases

4.Which agent

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

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

4.Which agent

Hyperinsulinaemia

regulation of

insulin

receptors

• 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

• 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.

• 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.

• 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

4.Which agent

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

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

4.Which agent

• Can metformin and TZDs be used to treat NASH

• Preferred agent for management of diabetes in

NASH and advanced liver disease

NASH Advanced liver disease

Metformin

Sulphonyureas

Metformin

Sulphonyureas

Metformin

Sulphonyureas

Dpp4 inhibitor

Metformin

Sulphonyureas

Dpp4 inhibitor

Metformin

Sulphonyureas

Dpp4 inhibitor

Insulin

4.Which agent

Liver biopsy

Pathophysiology of hepatogenous diabetes

MECHANISMS UNDERLYING THE

EFFECTS OF LIVER DISEASES ON

• Gut microbiota

• Hepatic inflammation and associated insulin

resistance

• Hepatic fat accumulation

• Reactive oxygen species

• Hepatokines

• HCV infection

• 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

• 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

• 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

Diabetes and liver

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