Remnant-like lipoprotein particles in type 2 diabetic patients with apolipoprotein E3/3 and apolipoprotein E2 genotypes.

Abstract

Apolipoprotein (apo) E2 and diabetes mellitus are known to be associated with an accumulation of remnant lipoproteins in plasma. In this study, effects of type 2 diabetes mellitus and/or apo E2 genotypes on remnant-like lipoprotein particles (RLP) were assessed. Thirty-three subjects were divided into 6 groups: 7 apo E3/3 nondiabetic subjects, 6 apo E3/3 diabetic patients, 5 apo E3/2 nondiabetic subjects, 6 apo E3/2 diabetic patients, 5 apo E2/2 nondiabetic subjects, and 4 apo E2/2 diabetic patients. First, the effect of diabetes mellitus on RLP were estimated by comparing the apo E3/3 nondiabetic group with the apo E3/3 diabetic group. Plasma levels of RLP-cholesterol (chol) in the apo E3/3 diabetic group and the uptake of RLP from the apo E3/3 diabetic group by macrophages were significantly greater compared with the apo E3/3 nondiabetic group. Second, the effect of apo E2 on RLP was estimated in nondiabetic subjects. Apo E2/2 nondiabetic subjects had type III hyperlipoproteinemia (HLP). Plasma levels of RLP-chol in the apo E2/2 nondiabetic group and the uptake of RLP from the apo E2/2 nondiabetic group by macrophages were significantly greater compared with the apo E3/3 and apo E3/2 nondiabetic groups. Third, the effects of both apo E2 and diabetes on RLP were estimated. Plasma levels of RLP-chol in the apo E2 (E3/2 and E2/2) diabetic groups and the uptake of RLP from apo E2 (E3/2 and E2/2) diabetic groups by macrophages were significantly greater compared with apo E3/3 nondiabetic and diabetic groups or the apo E3/2 nondiabetic group. In diabetes, a gene dose effect of apo E2 on plasma levels of RLP-chol and uptake of RLP by macrophages was present (apo E3/3 < apo E3/2 < apo E2/2). The apo E2/2 diabetic group had type III HLP. Furthermore, uptake of RLP from the apo E2/2 diabetic group with type III HLP was significantly greater compared with the apo E2/2 nondiabetic group with type III HLP. In conclusion, type 2 diabetes was associated with increased RLP-chol in plasma and atherogenic RLP. In nondiabetes, apo E2/2 contributes to increased plasma RLP-chol and atherogenic RLP. In diabetes, additional effects of apo E2 to increase RLP-chol in plasma and to enhance the uptake of RLP by macrophages are present. RLP from apo E2/2 diabetes with type III HLP are more atherogenic than those from apo E2/2 nondiabetes with type III HLP.

• Authors: Mieko Saito, Masaaki Eto, Kohei Kaku
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 51 Issue 8 Pg. 964-9 (Aug 2002) ISSN: 0026-0495 [Print] United States
• PMID: 12145767 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002, Elsevier Science (USA). All rights reserved.

Chemical References

• Apolipoprotein E2
• Apolipoprotein E3
• Apolipoproteins E
• Cholesterol Esters
• Lipoproteins
• Triglycerides
• remnant-like particle cholesterol
• Cholesterol

Topics

• Adult
• Aged
• Apolipoprotein E2
• Apolipoprotein E3
• Apolipoproteins E (genetics)
• Arteriosclerosis (etiology)
• Cholesterol (blood, physiology)
• Cholesterol Esters (biosynthesis)
• Diabetes Mellitus, Type 2 (blood, complications)
• Female
• Genotype
• Humans
• Lipoproteins (blood, physiology)
• Macrophages (metabolism)
• Male
• Middle Aged
• Triglycerides (blood, physiology)