Appearance of multidisperse low density lipoprotein and altered lipoprotein composition in non-insulin-dependent diabetes with type IIa hyperlipoproteinemia

Suzuki, Norihiro; Oikawa, Shinichi; Hori, Shuichiro; Fujii, Yutaka; Sakuma, Eriko; Kotake, Hidetoshi; Namai, Kazuyuki; Yoshie, Kazuko; Gotō, Yoshio

doi:10.1016/0026-0495(89)90079-6

Cited by 20 publications

(6 citation statements)

References 27 publications

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“…However, the link between a high plasma triglyceride concentration and CHD is far from obvious. For example, patients with NIDDM and/or hypertriglyceridaemia have been shown to have increases in plasminogen activator inhibitor-1 [35,36], smaller, denser LDL particles [37,38], and increased postprandial lipaemia [2,39]; changes which have been proposed as increasing the risk of CHD in non-diabetic subjects [3][4][5][6][7][8][9]. It seems reasonable to speculate that a similar relationship between these changes and CHD would also exist in patients with NIDDM.…”

Section: Discussionmentioning

confidence: 99%

Effect of glipizide treatment on postprandial lipaemia in patients with NIDDM

et al. 1994

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SummaryThe primary goal of the present study was to examine the effects of improved glycaemic control associated with glipizide treatment on postprandial lipaemia in non-insulin-dependent diabetic patients. The metabolism of triglyceride-rich lipoproteins of intestinal origin was assessed by measuring the retinyl palmitate content in plasma and the Svedberg flotation index (Sf) > 400 and Sf 20-400 lipoprotein fractions. Fasting plasma glucose concentrations (14.5 + 0.5 vs 9.0 + 0.5 mmol/1), glycated haemoglobin levels (13.1 + 0.6 vs 9.7 _+ 0.6 %), and daylong plasma glucose concentrations were all significantly lower after glipizide treatment (p < 0.001). The improvement in glycaemic control was associated with increases in insulin-mediated glucose uptake (p < 0.001) and plasma post-heparin lipoprotein and hepatic lipolytic activities Go < 0.02). Both fasting plasma triglyceride (3.09 + 0.51 vs 2.37 + 0.34 mmol/1), and postprandial triglyceride concentrations (p < 0.05-0.001) were lower following glipizide treatment, associated with a significant fall in retinyl palmitate content in all three lipoprotein fractions (p < 0.02-0.001), with the most substantial decrease seen in the Sf 20-400 fraction. These data indicate that glipizide-induced improvement in glycaemic control was associated with changes in the metabolism of triglyceride-rich lipoproteins of intestinal origin that would be anticipated to reduce risk of coronary heart disease in non-insulin-dependent diabetic patients. [Diabetologia (1994) proteins of intestinal origin were higher in patients with NIDDM [2]. In 1979 Zilversmit [3] suggested that triglyceride-rich lipoproteins of intestinal origin, especially the cholesteryl ester-rich chylomicron remnants, could play a very important role in atherogenesis, and since then, several reports have been published supporting this hypothesis [4][5][6][7][8][9][10]. Thus, our observation that postprandial lipaemia was increased in NIDDM raised the possibility that abnormalities in the metabolism of intestinally-derived lipoproteins may contribute to the increased risk of CHD in these patients. Although we could not detect any correlation in our earlier paper between the magnitude of postprandial lipaemia and the level of glycaemic control, the crosssectional nature of the study protocol was not designed to carefully explore such a relationship. Consequently, we initiated the current study to see if improved glycaemic control associated with glipizide

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Section: Discussionmentioning

confidence: 99%

Effect of glipizide treatment on postprandial lipaemia in patients with NIDDM

et al. 1994

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“…2C). Polydisperse LDL has been reported in subjects with hypertriglyceridaemia [ 19-2 I] and diabetes mellitus [21,22], but the LDL observed in patients with CETP deficiency consisted of lipoproteins ranging more widely in size. Our data suggest that CETP plays an important role in converting LDL particles to more homogeneous particles which are large and rich in CE.…”

Section: Discussionmentioning

confidence: 99%

Decreased affinity of low density lipoprotein (LDL) particles for LDL receptors in patients with cholesteryl ester transfer protein deficiency

Sakai

Yamashita

Hirano

et al. 1995

Eur J Clin Investigation

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We have reported that the disorder of lipoprotein metabolism in hyperalphalipoproteinaemic patients with a deficiency of cholesteryl ester transfer protein (CETP) is characterized by the polydisperse low density lipoprotein (LDL) particles and the accumulation of cholesteryl ester (CE) in high density lipoprotein (HDL) particles, forming cholesterol-induced HDL (HDLc)-like particles. In the present study we have investigated the interaction of these abnormal LDL with LDL receptors of normal human fibroblasts. Since the ultracentrifugally separated LDL fraction (1.019 < d < 1.063 g mL-1) from the CETP-deficient patients contained HDLc-like particles, these particles were removed by anti-apolipoprotein (apo) A-I immunoaffinity column chromatography. The lipoproteins eluted in the unbound fraction of this column did not contain apo A-I, so this fraction was considered to be authentic LDL. The authentic LDL of the patients were deficient in CE and rich in triglycerides and apo B. The authentic LDL itself showed polydispersity, ranging in size from 23 nm to 30 nm. The affinity of these abnormal LDL particles for LDL receptors was analysed by a competitive assay in which cold LDL from the patients or control compete with 125I-labelled LDL for fibroblast LDL receptors. The concentration of LDL particles at which 50% of 125I-labelled normal LDL was replaced was two to three times higher for the patients than for the normal control. Therefore, the affinity of patient LDL was thought to be reduced compared to that of control LDL. These results demonstrate that CETP may play an important role in making LDL particles homogeneous and rich in CE.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

Effect of glipizide treatment on postprandial lipaemia in patients with NIDDM

et al. 1994

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The primary goal of the present study was to examine the effects of improved glycaemic control associated with glipizide treatment on postprandial lipaemia in non-insulin-dependent diabetic patients. The metabolism of triglyceride-rich lipoproteins of intestinal origin was assessed by measuring the retinyl palmitate content in plasma and the Svedberg flotation index (Sf) > 400 and Sf 20-400 lipoprotein fractions. Fasting plasma glucose concentrations (14.5 +/- 0.5 vs 9.0 +/- 0.5 mmol/l), glycated haemoglobin levels (13.1 +/- 0.6 vs. 9.7 +/- 0.6%), and daylong plasma glucose concentrations were all significantly lower after glipizide treatment (p < 0.001). The improvement in glycaemic control was associated with increases in insulin-mediated glucose uptake (p < 0.001) and plasma post-heparin lipoprotein and hepatic lipolytic activities (p < 0.02). Both fasting plasma triglyceride (3.09 +/- 0.51 vs 2.37 +/- 0.34 mmol/l), and postprandial triglyceride concentrations (p < 0.05-0.001) were lower following glipizide treatment, associated with a significant fall in retinyl palmitate content in all three lipoprotein fractions (p < 0.02-0.001), with the most substantial decrease seen in the Sf20-400 fraction. These data indicate that glipizide-induced improvement in glycaemic control was associated with changes in the metabolism of triglyceride-rich lipoproteins of intestinal origin that would be anticipated to reduce risk of coronary heart disease in non-insulin-dependent diabetic patients.

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Appearance of multidisperse low density lipoprotein and altered lipoprotein composition in non-insulin-dependent diabetes with type IIa hyperlipoproteinemia

Cited by 20 publications

References 27 publications

Effect of glipizide treatment on postprandial lipaemia in patients with NIDDM

Effect of glipizide treatment on postprandial lipaemia in patients with NIDDM

Decreased affinity of low density lipoprotein (LDL) particles for LDL receptors in patients with cholesteryl ester transfer protein deficiency

Effect of glipizide treatment on postprandial lipaemia in patients with NIDDM

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