Probucol normalizes cholesteryl ester transfer in type 2 diabetes.
OBJECTIVE
Accelerated cholesteryl ester transfer (CET) protein (CETP) activity is believed to promote macrovascular disease in patients with type 2 diabetes (T2D) by increasing the cholesterol burden of the apoB - containing triglyceride-rich lipoprotein (TGRLP) CE acceptors and promoting small dense LDL formation. While previous studies have shown that this same abnormality is present in patients with type 1 diabetes (T1D) and was normalized by the anti-oxidant drug probucol, its effects on CET in T2D are unknown.


METHODS
The net mass transfer of CE from HDL to the apoB lipoproteins (VLDL+LDL) was studied in intact plasma from seven T2D patients before and two months after treatment with probucol (1g/day).


RESULTS
Before treatment, CET was significantly greater than controls at 1 and 2h (p<.005). Recombination studies showed that this disturbance was attributable to dysfunction of VLDL and not due to altered behavior of HDL or CETP. Probucol treatment normalized CET in all subjects and significantly lowered plasma cholesterol (pre-Rx: 197±4.5 vs post-Rx: 162±27.1mg/dL; mean±S.D.; p<.025) and HDL-C (pre-Rx: 46.4±7.5 vs post-Rx: 39.1±4.0; p<.025) without changing glycemic control.


CONCLUSIONS
By normalizing CET in T2D, probucol likely reduces the formation of atherogenic lipoproteins. This effect on CET is achieved through qualitative alterations in CETP's lipoprotein substrates and not through changes in CETP or HDL. Since probucol also has potent anti-oxidative and anti-inflammatory properties, it may have a new role to play in lipoprotein remodeling that reduce cardiovascular risk in T2D.
Rush University Medical Center, 1725 West Harrison, Chicago, IL 60612, United States. Electronic address: jbagdademd@gmail.com.
John D
JD
Bagdade
Oklahoma University Health Sciences Center, Oklahoma City, OK, United States.
James T
JT
Lane
Department of Medicine, University of Illinois at Chicago College of Medicine, 909 S. Wolcott, Chicago, IL 60612, United States; Department of Biochemistry, University of Illinois at Chicago College of Medicine, 909 S. Wolcott, Chicago, IL 60612, United States.
P V
PV
Subbaiah
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000378:metabolism; D016022:Case-Control Studies; D002788:Cholesterol Esters / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000378:metabolism; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008075:Lipoproteins, HDL / Q000187:drug effects* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000187:drug effects* / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011341:Probucol / Q000494:pharmacology*; D012307:Risk Factors
D000924:Anticholesteremic Agents; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011341:Probucol
CETP; Cholesteryl ester transfer; Probucol; Type 2 diabetes