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  • 1
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; HDL cholesterol ; apolipoprotein A-I ; apolipoprotein A-II ; kinetic analyses ; VLDL triglyceride ; lipolytic enzymes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Concentrations of HDL cholesterol and apolipoprotein A-I are commonly increased in Type 1 (insul-independent) diabetes mellitus but the mechanisms whereby diabetes influences HDL metabolism have not been studied. We investigated the metabolism of HDL apoproteins A-I and II in normolipidaemic Type 1 diabetic men (n=17, HbA1 6.4–11.9%) without microalbuminuria but with a wide range of HDL cholesterol (0.85–2.10 mmol/l) and in nondiabetic men (n=18) matched for body mass index and the range of HDL cholesterol. Input rates and fractional catabolic rates for apolipoproteins A-I and II were determined following injection of 125I-apolipoprotein A-I and 131I-apolipoprotein A-II tracers. Additional multicompartmental analysis was performed using a model to describe the kinetics of HDL particles containing only apolipoprotein A-I (Lp A-I) and apolipoprotein A-I and apolipoprotein A-II (Lp A-I/ A-II). No gross differences from normal subjects were observed in the mean levels of lipids, lipoproteins, apoproteins and the lipolytic enzymes in the diabetic men as a result of the selection process. Furthermore, the relationship between apolipoprotein A kinetics and plasma HDL cholesterol levels appeared to be preserved in the diabetic group. However, some normal interrelationships were disrupted in the diabetic men. Firstly, the rate of apolipoprotein A-II synthesis was 22% lower than in control subjects (p〈0.05). Modelling indicated that this was due to decreased input of Lp A-I/A-II particles whereas the input of Lp A-I particles was similar in the two groups. Secondly, there was no correlation between VLDL triglyceride and HDL cholesterol or VLDL triglyceride and the fractional catabolic rate of apolipoproteins A-I and A-II in diabetic men in contrast to that seen in control subjects. We conclude that there is a disruption in the normal association between VLDL and HDL metabolism in Type 1 diabetic men and postulate that the observed differences may be due to the therapeutic use of exogenous insulin.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Non-insulin-dependent diabetes mellitus ; coronary artery disease ; LDL composition ; small dense LDL ; electrophoresis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An increase of low-density lipoprotein triglycerides (LDL-Tg) was found to be an independent coronary artery disease (CAD) risk factor for non-insulin-dependent diabetic (NIDDM) patients in a recent prospective study. We examined the composition and size of LDL particles in 50 NIDDM men with angiographically verified CAD (NIDDM+ CAD+) and in 50 NIDDM men without CAD (NIDDM+ CAD−) as compared to 50 non-diabetic men with CAD (NIDDM− CAD+) and 31 non-diabetic men without CAD (NIDDM− CAD−). The groups had similar ranges of age and BMI LDL particle size was determined by gradient gel electrophoresis, and LDL was isolated by sequential ultracentrifugation for compositional analyses. Serum Tg was increased in NIDDM patients as compared to non-diabetic subjects (p〈0.05), and in patients with CAD as compared to subjects without the disease (p〈0.05). LDL cholesterol was lower in NIDDM patients than in non-diabetic subjects (p〈0.001). Mean diameter of LDL particles was less than 255 å, but closely comparable in all groups. The presence of NIDDM was associated with increases of Tg and protein but lowering of free cholesterol in LDL (p〈0.005 for all). In multivariate regression analyses neither NIDDM nor CAD were associated with LDL particle size, but serum Tg was the major determinant of LDL size in both NIDDM and non-diabetic subjects (p〈0.001). When the patients were divided into quartiles according to fasting serum Tg levels, the LDL particle size and free cholesterol content decreased, but Tg and protein contents of LDL particles increased from the lowest to the highest Tg quartile (analysis of variance p〈0.001 for all). When the subjects were categorized into two groups according to the median of VLDL-Tg (1.10 mmol/l) LDL size was associated with VLDL-Tg in the high but not in the low VLDL-Tg group. We conclude that in NIDDM patients with or without CAD serum Tg is the major determinant of the properties of LDL particles. The clinical implication is that in NIDDM serum Tg should be as low as possible to prevent atherogenic changes in LDL.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Insulin resistance ; lipase activities ; lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activities of hepatic and lipoprotein lipase and the levels of lipo- and apoproteins were compared in two groups of normoglycaemic men representing the highest (n=18) and lowest (n=15) fasting insulin quintiles of first degree male relatives of non-insulin-dependent diabetic patients. The high insulin group representing insulin-resistant individuals had significantly lower post-heparin plasma lipoprotein lipase activity than the low insulin group (14.2±4.0 vs 20±5.8 Μmol NEFA·ml−1·h−1, p〈0.001); hepatic lipase activity did not differ between the two groups (24.2±11 vs 18.0±5.3 Μmol NEFA·ml−1·h−1, NS). The lipoprotein lipase/hepatic lipase ratio in the high insulin group was decreased by 66% as compared to the low insulin group (0.75±0.57 vs 1.25±0.65, p〈0.01). In the high insulin group both total and VLDL triglycerides were higher than in the low insulin group (1.61±0.57 vs 0.86±0.26 mmol/l, p〈 0.001 and 1.00±0.47 vs 0.36±0.16 mmol/l, p〈0.001, respectively) whereas HDL cholesterol and HDL2 cholesterol were lower (1.20±0.30 vs 1.43±0.22 mmol/l, p〈0.05 and 0.49±0.21 vs 0.71±0.17 mmol/l, p〈0.05, respectively). Total cholesterol, LDL cholesterol or HDL3 cholesterol did not differ between the two groups. The mean particle size of LDL was smaller in the high insulin group than in the low insulin group (258±7 vs 265±6 å, p〈0.05). We propose that the changes of lipoprotein lipase and lipoprotein lipase/hepatic lipase ratio cluster with insulin resistance and provide a possible mechanism to explain the lowering of HDL cholesterol and elevation of triglyceride concentrations observed in insulin-resistant subjects.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Keywords Non-insulin-dependent diabetes mellitus ; coronary artery disease ; LDL composition ; small dense LDL ; electrophoresis.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An increase of low-density lipoprotein triglycerides (LDL-Tg) was found to be an independent coronary artery disease (CAD) risk factor for non-insulin-dependent diabetic (NIDDM) patients in a recent prospective study. We examined the composition and size of LDL particles in 50 NIDDM men with angiographically verified CAD (NIDDM + CAD +) and in 50 NIDDM men without CAD (NIDDM + CAD −) as compared to 50 non-diabetic men with CAD (NIDDM − CAD +) and 31 non-diabetic men without CAD (NIDDM − CAD −). The groups had similar ranges of age and BMI. LDL particle size was determined by gradient gel electrophoresis, and LDL was isolated by sequential ultracentrifugation for compositional analyses. Serum Tg was increased in NIDDM patients as compared to non-diabetic subjects (p 〈 0.05), and in patients with CAD as compared to subjects without the disease (p 〈 0.05). LDL cholesterol was lower in NIDDM patients than in non-diabetic subjects (p 〈 0.001). Mean diameter of LDL particles was less than 255 Å, but closely comparable in all groups. The presence of NIDDM was associated with increases of Tg and protein but lowering of free cholesterol in LDL (p 〈 0.005 for all). In multivariate regression analyses neither NIDDM nor CAD were associated with LDL particle size, but serum Tg was the major determinant of LDL size in both NIDDM and non-diabetic subjects (p 〈 0.001). When the patients were divided into quartiles according to fasting serum Tg levels, the LDL particle size and free cholesterol content decreased, but Tg and protein contents of LDL particles increased from the lowest to the highest Tg quartile (analysis of variance p 〈 0.001 for all). When the subjects were categorized into two groups according to the median of VLDL-Tg (1.10 mmol/l) LDL size was associated with VLDL-Tg in the high but not in the low VLDL-Tg group. We conclude that in NIDDM patients with or without CAD serum Tg is the major determinant of the properties of LDL particles. The clinical implication is that in NIDDM serum Tg should be as low as possible to prevent atherogenic changes in LDL. [Diabetologia (1996) 39: 453–461]
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Key words Insulin resistance ; lipase activities ; lipoproteins.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activities of hepatic and lipoprotein lipase and the levels of lipo- and apoproteins were compared in two groups of normoglycaemic men representing the highest (n = 18) and lowest (n = 15) fasting insulin quintiles of first degree male relatives of non-insulin-dependent diabetic patients. The high insulin group representing insulin-resistant individuals had significantly lower post-heparin plasma lipoprotein lipase activity than the low insulin group (14.2 ± 4.0 vs 20 ± 5.8 μmol NEFA · ml−1· h−1, p 〈 0.001); hepatic lipase activity did not differ between the two groups (24.2 ± 11 vs 18.0 ± 5.3 μmol NEFA · ml−1· h−1, NS). The lipoprotein lipase/hepatic lipase ratio in the high insulin group was decreased by 66 % as compared to the low insulin group (0.75 ± 0.57 vs 1.25 ± 0.65, p 〈 0.01). In the high insulin group both total and VLDL triglycerides were higher than in the low insulin group (1.61 ± 0.57 vs 0.86 ± 0.26 mmol/l, p 〈 0.001 and 1.00 ± 0.47 vs 0.36 ± 0.16 mmol/l, p 〈 0.001, respectively) whereas HDL cholesterol and HDL2 cholesterol were lower (1.20 ± 0.30 vs 1.43 ± 0.22 mmol/l, p 〈 0.05 and 0.49 ± 0.21 vs 0.71 ± 0.17 mmol/l, p 〈 0.05, respectively). Total cholesterol, LDL cholesterol or HDL3 cholesterol did not differ between the two groups. The mean particle size of LDL was smaller in the high insulin group than in the low insulin group (258 ± 7 vs 265 ± 6 Å, p 〈 0.05). We propose that the changes of lipoprotein lipase and lipoprotein lipase/hepatic lipase ratio cluster with insulin resistance and provide a possible mechanism to explain the lowering of HDL cholesterol and elevation of triglyceride concentrations observed in insulin-resistant subjects. [Diabetologia (1995) 38: 344–350]
    Type of Medium: Electronic Resource
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