Effects of NIDDM on very-low-density lipoprotein triglyceride and apolipoprotein B metabolism. Studies before and after sulfonylurea therapy

Taskinen, Marja‐Riitta; Beltz, William F.; Harper, Ingeborg T.; Fields, Rose M.; Schonfeld, G.; Grundy, Scott M.; Howard, Barbara V.

doi:10.2337/diabetes.35.11.1268

Cited by 106 publications

(95 citation statements)

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“…In addition, plasma triglyceride and VLDL-triglyceride concentrations decreased in association with glipizide treatment. This finding is similar to results of earlier studies of sulphonylurea treatment of patients with NIDDM [29][30][31], and seems to be related to both a decrease in hepatic VLDL-triglyceride secretion and an increase in rate of removal of VLDL-triglyceride from plasma. It is tempting to speculate that the former is related to the observed fall in ambient NEFA concentrations, and the latter to the increase in lipase activity.…”

Section: Discussionsupporting

confidence: 81%

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: Discussionsupporting

confidence: 81%

Effect of glipizide treatment on postprandial lipaemia in patients with NIDDM

et al. 1994

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“…Interestingly the improvement of glycemic control by sulfonylureas was also associated with a lowering of plasma FFA and VLDL levels, but the changes were less than those induced by insulin. 39 The lack of any correlation between the changes of VLDL and those of plasma FFA in the fasting state during insulin or sulfonylurea therapy or both 39 does not exclude a causal relation. Pertinent is the fact that resistance to the antilipolytic effect of insulin in the postprandial state could be an important factor leading to the elevation of VLDL levels (Yki-Jarvinen and Taskinen, unpublished data).…”

Section: Insulin Therapy and Very Low Density Lipoprotein Metabolismmentioning

confidence: 99%

Insulin therapy induces antiatherogenic changes of serum lipoproteins in noninsulin-dependent diabetes.

et al. 1988

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To study the effects of rigorous insulin therapy on serum lipoproteins in patients with noninsulin-dependent diabetes not controlled with oral agents only, we measured serum lipoproteins, apoproteins, lipolytic enzymes, and glucose disposal using an insulin clamp technique before and after 4 weeks of insulin therapy. Lipoproteins were isolated by ultracentrifugation and high density lipoprotein (HDL) subfractions, by rate-zonal density gradient ultracentrifugation. The group included 11 women and eight men (age 58 +/- 1 years and RBW 125 +/- 4%). Body weight, glycosylated hemoglobin, mean diurnal glucose, plasma free insulin, and glucose uptake (M-value) were 75 vs. 76 kg; 11.9 vs. 8.9%; 234 vs. 124 mg/dl; 12 vs. 27 microU/ml; and 5.0 +/- 0.4 vs. 7.1 +/- 0.6 mg/kg/min before and after insulin therapy, respectively. After insulin therapy there was a decrease of very low density lipoprotein (VLDL) triglyceride (-60%, p less than 0.001) but an increase of HDL2 cholesterol (+21%, p less than 0.001); HDL2 phospholipids (+38%, p less than 0.001); HDL2 proteins (+23%, p less than 0.01); and HDL2 mass (127 +/- 11 vs. 158 +/- 12 mg/dl, p less than 0.001). There was a decrease of HDL3 cholesterol (-13%, p less than 0.05); HDL3 phospholipids (-16%, p less than 0.05); HDL3 proteins (-18%, p less than 0.001); and HDL3 mass (179 +/- 6 vs. 146 +/- 6, p less than 0.01). Zonal profiles showed a redistribution of particles from HDL3 to HDL2. Serum apo A-I increased (p less than 0.05), apo A-II remained constant, but apo B decreased (-29%, p less than 0.001). The most marked change during insulin therapy was a 2.3-fold increase in adipose tissue lipoprotein lipase (LPL) activity (p less than 0.001). The changes of VLDL and HDL subfractions were not explained by respective changes of the blood glucose, free insulin, or M-value. The data indicate that intensive insulin therapy induces antiatherogenic changes in serum lipids and lipoproteins and suggest that the induction of LPL by insulin is the major factor responsible for redistribution of HDL particles from HDL3 to HDL2.

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“…We have recently shown that in healthy subjects acute hyperinsulinaemia suppresses VLDL1 apo B production but has no effect on direct VLDL2 apo B synthesis [8]. In NIDDM the VLDL spectrum is characterised by an abundance of VLDL1 particles [3] indicating a specific defect in the metabolic behaviour of this subclass rather than a general defect in VLDL metabolism. There is, however at present no information on the effect of acute hyperinsulinaemia on VLDL subclasses in NIDDM.…”

mentioning

confidence: 99%

“…The mechanism underlying hypertriglyceridaemia in NIDDM is still unclear. A majority of studies indicate that the elevation of plasma triglycerides in NIDDM result from an overproduction of VLDL triglyceride [2,3] and apo B [4,5] but it is unclear and a matter of controversy whether the increased production of VLDL particles is driven by a direct effect of hyperinsulinaemia or is a consequence of defective suppression of VLDL production by insulin [1]. In healthy subjects acute insulin administration suppresses VLDL apo B production [6][7][8].…”

mentioning

confidence: 99%

Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM

et al. 1997

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Features of diabetic dyslipidaemia in non-insulin-dependent diabetes mellitus (NIDDM), such as a low HDL cholesterol concentration, the preponderance of small dense LDL and postprandial fat intolerance are considered to be metabolic consequences of elevated plasma triglycerides [1]. The mechanism underlying hypertriglyceridaemia in NIDDM is still unclear. A majority of studies indicate that the elevation of plasma triglycerides in NIDDM result from an overproduction of VLDL triglyceride [2,3] and apo B [4,5] but it is unclear and a matter of controversy whether the increased production of VLDL particles is driven by a direct effect of hyperinsulinaemia or is a consequence of defective suppression of VLDL production by insulin [1]. In healthy subjects acute insulin administration suppresses VLDL apo B production [6][7][8]. Data on the suppression of VLDL production by insulin in insulin resistant states are controversial. Lewis et al. [6] showed an impaired suppression of VLDL apo B production in obese subjects while Cummings et al. [9] did not find any defect in the ability of insulin to suppress VLDL apo B production in patients with NIDDM.Two major subclasses of VLDL particles are recognised, large triglyceride-rich VLDL1 particles Diabetologia (1997) 40: 454-462 Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM Summary Insulin administration to healthy subjects inhibits the production of very low density lipoprotein (VLDL)1 (Svedbergs flotation (Sf) rate 60-400) without affecting that of VLDL2 (Sf 20-60) subclass. This study was designed to test whether this hormonal action is impaired in non-insulin-dependent diabetes mellitus (NIDDM). We studied six men with NIDDM (age 53 ± 3 years, body mass index 27.0 ± 1.0 kg/m 2 , plasma triglycerides 1.89 ± 0.22 mmol/l) during an 8.5 h infusion of saline (control) and then in hyperinsulinaemic (serum insulin ∼ 540 pmol/l) conditions during 8.5 h infusions of glucose and insulin to give either hyper-and normoglycaemic conditions. [3-2 H]-leucine was used as tracer and kinetic constants derived using a non-steadystate multicompartmental model. Compared to the control study, patients with NIDDM reduced VLDL1 apo B production by only 3 ± 8 % after 8.5 h of hyperinsulinaemia (701 ± 102 vs 672 ± 94 mg/day respectively, NS) in hyperglycaemic conditions and by 9 ± 21 % under normoglycaemic conditions (603 ± 145 mg/day). In contrast, in normal subjects insulin induced a 50 ± 15 % decrement in VLDL1 apo B production (p < 0.05). Direct synthesis of VLDL2 apo B in patients with NIDDM was not markedly affected by insulin. We conclude that a contributory factor to hypertriglyceridaemia in NIDDM is the inability of insulin to inhibit acutely the release of VLDL1 from the liver, despite efficient suppression of serum nonesterfied fatty acids. [Diabetologia (1997) 40: 454-462]

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Effects of NIDDM on very-low-density lipoprotein triglyceride and apolipoprotein B metabolism. Studies before and after sulfonylurea therapy

Cited by 106 publications

References 0 publications

Effect of glipizide treatment on postprandial lipaemia in patients with NIDDM

Effect of glipizide treatment on postprandial lipaemia in patients with NIDDM

Insulin therapy induces antiatherogenic changes of serum lipoproteins in noninsulin-dependent diabetes.

Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM

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