MedWire News: Treating diabetic patients with the
thiazolidinedione pioglitazone significantly decreases triglyceride
content in the liver and reduces cholesteryl ester transfer protein
(CETP) mass, research shows.
In addition, treatment with pioglitazone was also associated
with an accompanying increase in high-density lipoprotein (HDL)
cholesterol levels.
The findings, report Jacqueline Jonker (Leiden University
Medical Center, The Netherlands) and colleagues in the journal
Diabetes Care, are "in full agreement with our recent
findings in apolipoprotein (APO)E*3-Leiden CETP mice and support
the validity of these mice as a model for human-like lipoprotein
metabolism."
Patients with diabetes are often characterized by marked
dyslipidemia, with high levels of apoB-lipoproteins and
triglycerides, and low HDL cholesterol levels.
Previous research has suggested that hepatic steatosis, a common
condition in patients with Type 2 diabetes, is associated with more
severe dyslipidemia.
The purpose of this study was to confirm the previous findings
from the mouse model showing that pioglitazone favorably reduces
triglycerides in the liver.
In total, 78 men with Type 2 diabetes mellitus were randomly
assigned to receive pioglitazone 30 mg/day, metformin 2000 mg/day,
or matching placebo, all in addition to treatment with
glimepiride.
After 24 weeks, hepatic triglyceride content decreased from 5.9%
to 4.1% in patients taking pioglitazone. Accompanying the change,
CETP mass declined from 2.33 µg/ml to 2.06 µg/ml, while
HDL cholesterol levels increased from 1.22 mmol/l to 1.34
mmol/l.
Treatment with metformin had no significant effect on hepatic
triglyceride content, CETP mass, or HDL cholesterol levels.
In an analysis stratified according to statin use at baseline,
the researchers note that pioglitazone had an additional effect on
liver triglyceride content, reducing it from 8.0% to 3.7% at 24
weeks in 19 patients taking both drugs, compared with a decrease
from 6.4% to 4.9% in non-statin users.
However, pioglitazone did not further decrease CETP mass or HDL
cholesterol in patients taking statins at baseline.
"We hypothesize that statins specifically decrease hepatic
cholesterol content and downregulate CETP mRNA expression," explain
Jonker and colleagues. "Therefore, additional lowering of hepatic
triglyceride content will not result in an additional decrease in
CETP expression."
They conclude: "These results in patients with Type 2 diabetes
fully confirm recent findings in mice."
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Springer Healthcare Limited. © Springer Healthcare Ltd;
2010
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