Assessment of hepatic HSPG*s in NASH associated dyslipidemia in 8 subjects with DM2 associated NASH (insulin resistant, n=8) vs NASH in FHBL (non insulin resistant, n=8) and control subjects (hemochromatosis, n=8)
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Diabetic complications
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
HSPG expression will be altered (HS synthesizing enzymes: EXT/NDST/OST
decreased and HS degrading enzymes: SULF2 and heparinase increased) in DM2
Secondary outcome
Second Objective: HSPG expression is linearly correlated with increased levels
of triglyceride rich lipoproteins in non-fasting blood samples
Third objective: HSPG expression is inversely correlated with insulin
resistance
Background summary
Nonalcoholic steatosis 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 associated dyslipidemia. NASH is frequently
seen in patients with type 2 diabetes mellitus (DM2) and tends to be 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
heparansulphate 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
Study objective
Assessment of hepatic HSPG*s in NASH associated dyslipidemia in 8 subjects with
DM2 associated NASH (insulin resistant, n=8) vs NASH in FHBL (non insulin
resistant, n=8) and control subjects (hemochromatosis, n=8)
Study design
Case control study
Study burden and risks
Liverbiopsy and fibroscan performed by experienced hepatologist, venapuncture
for lipidprofile and determination in insulinresistance (HOMAr) will be
performed. A liverbiopsy is routine test performed at dept of Hepatology for
patientcare and is associated with a very low complication risk. As we only aim
to include patient who will need liverbiopsy for clinical staging of
liverdisease, the benefit for the patient will be accurate information on stage
of liverdisease as well as prognosis. Moreover, from a scientific point of view
this observational study will help us identify the role of heparansulfates in
development of DM2 associated NASH vs non insulin resistant stages (FHBL). We
believe that the information gathered from this study as well as potential
therapeutic insights for NASH outweigh the burden of the interventions.
meibergdreef 9
1105 AZ Amsterdam
NL
meibergdreef 9
1105 AZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
Caucasian males aged between 18 and 60 years of age with either type 2 diabetes mellitus or FHBL AND presence of ultrasound confirmed NASH in conjunction with elevated liverfunction tests. Subjects with stable hereditary hemochromatosis (treated with venesection therapy) who need a liverbiopsy for staging of disease will be used as controls
Exclusion criteria
Use of medication which is known to influence cholesterol metabolism, an active malignancy or presence of a contraindication for liver biopsy
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL29252.018.09 |