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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To further characterize the spectrum of potentially atherogenic disturbances in lipoprotein composition in non-insulin-dependent diabetes mellitus (NIDDM), we have studied a subset of women with NIDDM before and after treatment with the lipophilic lipid-lowering drug probucol (1 gm day), which we have shown corrects certain compositional abnormalities these women share with subjects who have hypercholesterolemia. Before treatment, the NIDDM group had a somewhat higher plasma triglyceride level (154 +/- 58.3 mg/dl, vs control, 80.0 +/- 21 mg/dl [mean +/- SD]; p less than 0.025) than controls but their cholesterol and high-density lipoprotein cholesterol (HDL-C) levels did not differ from control levels. A number of significant disturbances, however, were present in the surface and core lipid composition of their lipoproteins. Although the cholesterol content of NIDDM low-density lipoprotein (LDL) was similar to that of controls, its content of sphingomyelin and phosphatidylinositol plus phosphatidylserine and sphingomyelin-to-lecithin ratio all were significantly reduced. Moreover, their very-low-density lipoprotein (VLDL) and HDL2 tended to have reduced amounts of free (unesterified) cholesterol (FC) relative to lecithin, and their HDL2 and HDL3 tended to be triglyceride enriched. Probucol therapy resulted in significant decreases in total plasma cholesterol (-15%), FC (-28%), HDL-C (-22%), and triglyceride (-16%) and in apoproteins A-I, B, and E (apo A-I, B, and E), without changing diabetic control (before probucol: hemoglobin A1, cholesterol, 10.7% +/- 2.7%; after probucol: 10.9% +/- 3.0%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipoprotein composition and HDL particle size distribution in women with non-insulin-dependent diabetes mellitus and the effects of probucol treatment. 185 75

Plasma lipids, lipoproteins and apolipoproteins (apo) were analysed in 30 young Arab IDDM and 50 young insulin-requiring NIDDM women. The mean age of IDDM and NIDDM groups was 20.2 and 34.5 years, and mean duration of diabetes was 5.7 and 4.6 years, respectively. Two groups of 40 and 60 healthy women (matched for age and BMI) provided corresponding control groups. In comparison with control subjects, diabetics showed marked increases in the following parameters: total cholesterol (TC), low density lipoprotein (LDL) cholesterol, total triglycerides (TG), very low density lipoprotein (VLDL) triglycerides, phospholipids, apoB, LDL apoB, glucose and glycosylated hemoglobin (HbA1c) as well as the ratios of total cholesterol/high density lipoprotein (HDL) cholesterol, LDL-cholesterol/HDL-cholesterol, LDL cholesterol/high density lipoprotein (HDL) cholesterol, LDL-cholesterol/HDL-cholesterol, LDL cholesterol/high density lipoprotein 2 (HDL2) cholesterol and apoB/apoAI. Plasma LCAT activity, concentrations of HDL3 apoAI and apoAII in plasma and lipoprotein fractions were normal in both the diabetic groups. Levels of C-peptide, HDL, HDL2 and HDL3 cholesterol, plasma apoAI, HDL apoAI and HDL2 apoAI were markedly decreased in the diabetic groups as compared to their corresponding controls. There was no significant correlation between fasting glucose or HbA1c and any of the above parameters. Despite insulin therapy in both the diabetic groups studied, abnormalities in lipids, apoB and apoAI still persisted. Our data suggest a possible higher risk of atherosclerosis in these patients.
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PMID:Plasma lipoproteins and apolipoproteins in insulin-dependent and young non-insulin-dependent Arab women. 186 93

Nonenzymatic glycosylation of plasma proteins may contribute to the excess risk of developing atherosclerosis in patients with diabetes mellitus. Because high-density lipoprotein (HDL) is believed to protect against atherosclerosis and is glycosylated at increased levels in diabetic individuals, the effects of nonenzymatic glycosylation of HDL3 on binding of HDL3 to cultured fibroblasts and to the candidate HDL-receptor protein were examined. HDL3 was glycosylated in vitro with glucose alone or in combination with sodium cyanoborohydride. With this catalyst, up to 40-50% of the lysine residues could be glycosylated, resulting in a progressive drop to nearly 60% in high-affinity binding to cultured fibroblasts at 4 degrees C. Binding to the 110,000-Mr candidate HDL-receptor protein was reduced by almost 75%. At levels of HDL glycosylation equivalent to the 3-5% observed in diabetes, high-affinity binding to fibroblasts at 4 degrees C was diminished by up to 15-20%. Binding kinetic studies paradoxically suggested that glycosylated HDL3 binds with higher affinity to a reduced number of binding sites. The findings in this study suggest that nonenzymatically glycosylated HDL may be functionally abnormal and might contribute to the development of atherosclerosis in patients with diabetes mellitus.
Diabetes 1990 Oct
PMID:Nonenzymatic glycosylation of HDL resulting in inhibition of high-affinity binding to cultured human fibroblasts. 217 Feb 16

To determine whether rigorous insulin therapy, which normalized the routinely measured plasma lipids, also reversed qualitative abnormalities in the composition of lipoproteins in noninsulin-dependent diabetes mellitus (NIDDM), we studied 18 NIDDM patients (eight men and 10 women) before and 2 months after intensive insulin therapy. Glycosylated hemoglobin levels (11.7% vs. 8.7%), plasma triglyceride (TG) (250 +/- 91 vs. 164 +/- 56 mg/dl, p less than 0.001), and cholesterol (214 +/- 43 vs. 198 +/- 31 mg/dl, p less than 0.025) all fell, and both HDL2 cholesterol and HDL3 cholesterol increased (59.1% and 10.9%, respectively, p less than 0.001). However, abnormalities in two indices of lipoprotein surface constituents, which were present before insulin therapy, remained so thereafter. The first of these, the new cardiovascular risk factor, the plasma free cholesterol/lecithin ratio, which was increased before treatment, fell only slightly after therapy (pre-therapy 1.02 +/- 0.29 vs. post-therapy 0.90 +/- 0.17, p less than 0.4; reference group, 0.83 +/- 0.14), and remained elevated in very low density lipoprotein (VLDL) and low density lipoprotein (LDL). Secondly, the sphingomyelin/lecithin ratio, an index of the surface rigidity of lipoproteins, was abnormal before treatment in VLDL, HDL2, and HDL3, and this alteration persisted after insulin therapy in HDL3 (p less than 0.001). Lipoprotein core lipid abnormalities were also present before treatment: the TG/cholesteryl ester ratio was reduced in VLDL and increased in LDL, HDL2, and HDL3. Rigorous insulin therapy improved, but failed to fully correct, this disturbance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Persistent abnormalities in lipoprotein composition in noninsulin-dependent diabetes after intensive insulin therapy. 218 Mar 97

The effect of insulin treatment with 2 different insulin regimens on the plasma concentrations of lipoproteins and apolipoproteins A1 and B was studied in 10 patients with non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to oral hypoglycaemic agents. The investigation was performed as a randomized crossover study with treatment periods of 8 weeks. Insulin was given either as mainly intermediate acting insulin before breakfast and dinner (2-dose insulin) or as regular insulin preprandially with intermediate acting insulin at bedtime (4-dose insulin). A similar improvement in glycaemic control was obtained with both insulin regimens. On treatment with oral agents the patients were found to have higher total plasma triglycerides and lower plasma high density lipoprotein (HDL) cholesterol than a matched non-diabetic control group. Insulin treatment almost completely normalized these lipid disturbances by reducing mean total plasma triglycerides with 36% and increasing plasma HDL cholesterol with 20% on 2-dose and 17% on 4-dose. The triglyceride concentration in the very low density lipoprotein (VLDL) fraction was reduced. Mean plasma low density lipoprotein (LDL)-cholesterol was not affected by any treatment. There was an increase of similar magnitude in both HDL2 and HDL3 concentrations but only the change in the HDL3 subfraction was statistically significant. Mean plasma apolipoprotein A1 concentration increased with 9% (P less than 0.05) while there was no significant change in the plasma apolipoprotein B concentration. The changes in the plasma concentrations of lipoproteins and apolipoproteins A1 and B were almost identical on 2- and 4-dose insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of different insulin regimens on plasma lipoprotein and apolipoprotein concentrations in patients with non-insulin-dependent diabetes mellitus. 218 32

Platelets from diabetic patients are hypersensitive to agonists in vitro. Membrane fluidity modulates cell function, and reduced membrane fluidity in cholesterol-enriched platelets is associated with platelet hypersensitivity to agonists, including thrombin. Decreased membrane fluidity of these platelets is attributed to an increased cholesterol-phospholipid molar ratio in platelet membranes. We examined the response of platelets from diabetic subjects to thrombin, platelet membrane fluidity, and platelet cholesterol-phospholipid molar ratio. Twelve poorly controlled diabetic subjects were compared with 12 age- and sex-matched control subjects. In response to a low concentration of thrombin, mean values for release of [14C]serotonin from washed prelabeled platelets were not significantly different between diabetic and control subjects, but in 8 of 12 diabetic subjects, the release response was greater than in their paired control subjects. Mean steady-state fluorescence polarization values in 1,6-diphenyl-1,3,5-hexatriene-labeled platelets prepared from diabetic subjects were significantly greater than in control subjects; this indicates a decreased membrane fluidity in platelets from diabetic subjects. Total or very-low-density (VLDL), low-density (LDL), or high-density (HDL2, HDL3) lipoprotein cholesterol concentrations in plasma were not significantly different between groups; however, the ratio of VLDL + LDL to HDL2 + HDL3 was significantly greater in diabetic than in control subjects. There was no difference in the total platelet cholesterol-phospholipid molar ratio between groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Feb
PMID:Reduced membrane fluidity in platelets from diabetic patients. 222 32

We studied the association of obesity with lipid and lipoprotein concentrations in 92 patients (49 men, 43 women) with insulin-dependent diabetes (IDDM), in 305 patients (152 men, 153 women) with non-insulin-dependent diabetes (NIDDM), and in 122 nondiabetic control subjects (65 men, 57 women). Obesity (body mass index, BMI) was associated with abnormal lipid and lipoprotein levels only in the presence of diabetes, and lipid and lipoprotein changes were substantially more abnormal in patients with NIDDM than in patients with IDDM. In men and women with NIDDM, obesity was associated with low high-density lipoprotein (HDL) and HDL2 cholesterol and high total, low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) triglyceride concentrations. In men with IDDM, obesity was related only to low HDL and HDL2 cholesterol and in women with IDDM to low HDL3 cholesterol. BMI and diabetes status had a statistically significant interaction (analysis of variance) with respect to HDL and HDL2 cholesterol and total and VLDL triglycerides, indicating that the effects of obesity on lipids and lipoproteins were more severe in patients with diabetes than in nondiabetic subjects. In conclusion, obesity and diabetes status have an unfavorable interaction that results in multiple pathologic lipid and lipoprotein changes, particularly in NIDDM.
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PMID:Adverse effects of obesity on lipid and lipoprotein levels in insulin-dependent and non-insulin-dependent diabetes. 229 84

Because the apparent reduction in cardiovascular risk noted in nondiabetic populations that ingest diets rich in marine lipids containing omega-3 fatty acids is believed to result in part from their capacity to modify the composition and physicochemical behavior of lipoproteins, we sought to determine whether dietary supplementation with marine lipids might favorably affect lipoprotein composition in insulin-dependent diabetes mellitus (IDDM). Eight normolipidemic IDDM women (mean +/- SD age 29.8 +/- 4.7 yr) were studied before and 3 mo after receiving a marine-lipid concentrate (Super-EPA) containing 6 g omega-3 fatty acids and a total of 12 mg of cholesterol daily. Weight, insulin requirements, and glycosylated hemoglobin remained stable. After treatment, mean +/- SD plasma triglyceride (TG) levels fell (before, 81.7 +/- 22 mg/dl; after, 69.19 +/- 17; P less than 0.025). High-density lipoprotein2 (HDL2) cholesterol (before, 10.98 +/- 5.45 mg/dl; after, 18.43 +/- 7.93; P less than 0.01), its major apolipoprotein A-I (apoAI), and the major phospholipids (sphingomyelin and lecithin) all rose significantly. ApoB and plasma and low-density lipoprotein cholesterol levels and HDL3 composition were unchanged. Postheparin hepatic and lipoprotein lipase activities were unaffected by marine lipids. These data indicate that women with IDDM experience apparently beneficial effects on TG and HDL2 from dietary supplementation with omega-3 fatty acids administered in a low-cholesterol-containing oil without adversely affecting overall diabetes management. If these changes in lipoprotein concentration and composition prove to have antiatherogenic consequences and are free of long-term toxicity, these agents may have a role in the therapy of IDDM patients.
Diabetes 1990 Apr
PMID:Effects of omega-3 fish oils on plasma lipids, lipoprotein composition, and postheparin lipoprotein lipase in women with IDDM. 231 45

To determine whether compositional abnormalities are present in high-density lipoprotein (HDL) in patients with insulin-dependent diabetes mellitus (IDDM) that might negate its putatively protective cardiovascular effects, we studied the plasma lipoproteins of 12 men with varying degrees of clinical control (mean fasting glucose 193 +/- 10 mg/dl, mean glycoalbumin greater than 73% above control mean). The diabetic patients' basal plasma triglyceride, total- and free- (unesterified) cholesterol, HDL cholesterol (HDL-chol), and apolipoprotein AI, AII, and B concentrations were similar to those of control subjects, but the free-cholesterol-to-lecithin ratio, a new index of cardiovascular disease risk, was significantly increased in their plasma (0.97 +/- 0.14 vs. 0.88 +/- 0.07, P less than .02) and their very-low-density lipoprotein (VLDL)-low-density lipoprotein (LDL) subfraction (1.50 +/- 0.51 vs. 1.08 +/- 0.15, P less than .005). Although HDL2-chol was similar in diabetic and control groups, the HDL2-chol-to-free-cholesterol ratio (diabetic vs. control, 4.64 +/- 1.7 vs. 1.96 +/- 1.0 mumol/ml, P less than .025) and the sphingomyelin-to-lecithin ratio (0.23 +/- 0.08 vs. 0.20 +/- 0.09, P less than .025) were both significantly increased in the IDDM group. HDL3-chol was higher in the IDDM than in the control subjects (diabetic vs. control, 38.6 +/- 5.2 vs. 32.7 +/- 2.7 mg/dl, P less than .005). In contrast to whole plasma and the VLDL + LDL subfraction, the free-cholesterol-to-lecithin ratio of IDDM and control HDL subfractions were similar.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1989 Oct
PMID:Whole-plasma and high-density lipoprotein subfraction surface lipid composition in IDDM men. 250 76

High-density lipoprotein (HDL3) particles bind to a cell surface receptor, thereby promoting the efflux of cholesterol from extrahepatic nonsteroidogenic cells. This receptor appears to be upregulated by increased cell cholesterol content and also may be responsive to the growth state of cells. Because insulin can be mitogenic, the effect of insulin on HDL-receptor function was tested. HDL-receptor activity of cholesterol-loaded fibroblasts was inhibited by insulin treatment. Insulin decreased HDL binding in a log-dose fashion (-25% at 67 nM insulin) in association with increases in [3H]thymidine incorporation into DNA. HDL-mediated cholesterol efflux from cholesterol-loaded cells was diminished by insulin treatment of cells in parallel with decreased HDL binding. Insulin induced reciprocal changes in HDL- and low-density lipoprotein (LDL)-receptor activity. In cells in which these receptors were upregulated by varying cell cholesterol content, insulin increased LDL binding (+88%) and decreased HDL binding (-24%). Insulin-like growth factor I (IGF-I, 100 ng/ml) also significantly decreased HDL binding and HDL-mediated cholesterol efflux to a comparable degree. Pooled human serum similarly induced a reduction in HDL binding to its receptor. These results are consistent with the hypothesis that growth factors in general, and insulin and IGF-I in particular, decrease HDL-receptor activity, possibly to promote retention of cholesterol needed for new membrane synthesis during cell proliferation. Such a mechanism could be partly responsible for accumulation of cholesteryl esters in arterial wall cells during atherogenesis in diabetes mellitus.
Diabetes 1989 Jan
PMID:Downregulation of high-density lipoprotein receptor in human fibroblasts by insulin and IGF-I. 253 24


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