HSPGs in leverbiopten in mensen met of zonder suikerziekte.

Rationale:

Non-alcoholic steato hepatitis (NASH) is one of the most common causes of chronic liver injury in many countries. Currently there is no therapeutic intervention to reduce or cure NASH.

NASH is frequently seen in patients with type 2 diabetes mellitus (DM2) and is associated with insulin resistance. However, patients with familial hypobeta lipoproteinaemia (FHBL) are also characterized by NASH yet were recently characterized NOT to have insulin resistance. Thus, different genetic factors driving different pathophysiological mechanisms are likely to be important for the development of NASH. Animal studies have indicated a role for heparan sulphate proteoglycans (HSPG) in the development of NASH associated dyslipidemia and insulin resistance. We would therefore like to investigate whether changes in expression of HSPG synthesizing and degrading enzymes are associated with presence of dyslipidemia and insulin resistance in NASH.



Primary Objective:

HSPG expression in liver tissue of patients with type 2 diabetes mellitus and NASH compared to liver tissue from subjects without type 2 diabetes mellitus with and without NASH.

Second Objective:

Correlation between HSPG expression in liver tissue with levels of triglyceride rich lipoproteins in non-fasting blood samples.

Third objective:

Correlation between HSPG expression in liver tissue and insulin resistance.



Study design:

Case control study.



Study population:

Caucasian males, aged between 18 and 60 years of age, with type 2 diabetes mellitus, undergoing gastric bypass surgery.

Controls: FHBL patients with NASH and Hepatitis C patients and Heamochromatosis patients undergoing a liverbiopsy for clinical staging of the disease. And patients undergoing hemihepatectomy.



Intervention:

During a clinically scheduled gastric bypass surgery, hemihepatectomy or liver biopsy, liver tissue will be collected and blood will be withdrawn.



Main study parameters/endpoints:

1. HSPGs expression in liver tissue, measured by qPCR and western blot, in insulin resistant NASH versus non-insulin resistance with and without NASH;

2. Association between hepatic HSPGs expression and triglyceride-rich lipoproteins in non fasting lipid samples;

3. Association between hepatic HSPGs expression and HOMA index.

Hepatic HSPG expression is altered in DM2 patients with NASH compared to controls and determines level of insulin resistance.

At the day of liverbiopsy, a fasting and non fasting blood sample will be withdrawn.

1. Liverbiopsy;

2. Bloodwithdrawal.