Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To understand the relationship between very low-density lipoprotein (VLDL) triglyceride and VLDL apolipoprotein (apo) B, we studied their metabolisms simultaneously in 53 subjects with a range of obesity and glycemia. Obese subjects had increased production of both VLDL apo B and VLDL triglyceride and more VLDL of normal composition. Compared with nondiabetics, diabetic subjects had decreased clearance of both VLDL apo B and VLDL triglyceride, increased production of VLDL triglyceride but not of VLDL apo B, and more VLDL of abnormal composition. Production of both VLDL apo B and VLDL triglyceride were significantly correlated with plasma insulin concentrations, and rates of clearance of both were inversely correlated with plasma glucose. There was no direct correlation between total plasma free fatty acid concentration and production of either VLDL triglyceride or VLDL apo B, but VLDL triglyceride production was found to account for only a very small proportion of the nonoxidative component of free fatty acid turnover. We suggest that in obese subjects hyperinsulinemia induces overproduction of both VLDL apo B and VLDL triglyceride. In diabetes VLDL is increased in part because of decreased clearance; the altered composition is the result of the increase in VLDL-triglyceride production independent of apo B. The increase in VLDL triglyceride production may be mediated through plasma free fatty acids or glucose, although assessment of the relationship between these precursors and VLDL triglyceride is confounded by the fact that only a small portion of free fatty acids or glucose is converted to VLDL triglyceride.
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PMID:Coordination of very low-density lipoprotein triglyceride and apolipoprotein B metabolism in humans: effects of obesity and non-insulin-dependent diabetes mellitus. 354 65

Plasma lipid levels have been proposed as probable risk factors of diabetic retinopathy. To clarify this question, we evaluated the apolipoprotein levels in 68 type I diabetic patients (39 +/- SD 14 years; duration of diabetes 13 +/- SD 8.4 years). By the analysis of fluorescein angiography we have classified diabetic retinopathy as follows: absent retinopathy (AR, n = 23), minimal retinopathy (MR, n = 16), exudative retinopathy (ER, n = 15), proliferative retinopathy (PR, n = 14). For all patients we measured: total, LDL- and HDL-cholesterol (T-CH, LDL-CH, HDL-CH), apolipoproteins A and B (Apo A and B), fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1). The mean age of the patients with ER (47 +/- SD 14 years) was greater than those with MR (36 +/- SD 15 years) or AR (33 +/- SD 13 years) (p less than 0.05). Significant differences within groups were not found for relative body weight, daily insulin dose, FPG, HbA1% (analysis of variance, ANOVA). The groups differed between each other with regard to T-CH, LDL-CH and HDL-CH/LDL-CH ratio (T-cholesterol: AR 186 +/- SD 34, MR 191 +/- SD 32, ER 212 +/- SD 52, PR 215 +/- SD 41 mg/dl; LDL-cholesterol: AR 124 +/- SD 28, MR 122 +/- SD 18, ER 148 +/- SD 38, PR 145 +/- SD 33 mg/dl; HDL/LDL-cholesterol ratio: AR 0.38 +/- SD 0.1, MR 0.35 +/- SD 0.1, ER 0.30 +/- SD 0.1, PR 0.29 +/- SD 0.1). The total-CH levels increased and HDL-CH/LDL-CH ratio decreased along with the severity of the retinopathy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Circulating lipid levels and severity of diabetic retinopathy in type I diabetes mellitus. 360 57

Studies were undertaken to determine whether there is an association between elevated levels of intermediate-density lipoproteins (IDL) (Sf 12-60 lipoproteins) and coronary artery disease. Forty-five to sixty-five-year-old men with objectively documented coronary artery disease (n = 58) who were free of known risk factors (diabetes, hypertension, obesity, hyperuricemia, and hypercholesterolemia) were compared with similar men who were free of coronary artery disease (n = 52). Smokers could not be excluded. The coronary artery disease group had a higher rate of cigarette smoking (NS, due to large variations); higher concentrations of triglycerides in their plasma (p = .003) and higher levels of very low-density lipoproteins (VLDL) (p = .007), IDL (p = .016), and low-density lipoproteins (LDL) (p = .04); as well as somewhat lower levels of high-density lipoprotein (HDL) cholesterol (p = .04). Chi-squared analysis demonstrated a strong association between coronary artery disease and IDL apolipoprotein (apo) B (p = .006), coronary artery disease and IDL triglyceride (p = .032), and coronary artery disease and IDL apo B times IDL triglyceride (p = .006) when the top quintile of the population was compared with the bottom quintile for each of these variables. Stepwise logistic regression analysis resulted in rejection of an association between coronary artery disease and HDL cholesterol, plasma triglyceride, VLDL triglyceride, or LDL triglyceride. However, it did show that coronary artery disease was most strongly associated with smoking and that the second strongest association was with IDL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The association of increased levels of intermediate-density lipoproteins with smoking and with coronary artery disease. 379 98

A polymorphic DNA sequence of the apolipoprotein (apo) A-I gene region was studied in relation to non-insulin-dependent diabetes mellitus (NIDDM). We have examined 100 patients with NIDDM and 100 control subjects as well. The presence of a unique 2.5-kilobase (kb) EcoRI fragment was found in 13 diabetic patients and two control subjects with family history of diabetes. There were six homozygotes and nine heterozygotes among them. The analysis of clinical data did not confirm any linkage between the presence of a 2.5-kb fragment and atherosclerosis. These findings suggest that the observed defect in the apo A-I gene region may confer susceptibility to NIDDM.
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PMID:Apolipoprotein A-I gene polymorphism and susceptibility of non-insulin-dependent diabetes mellitus. 393 51

The hypertriglyceridemia associated with streptozotocin-induced diabetes in rats is largely reflected in the plasma lipoproteins of density less than 1.006 g/ml. Analysis of the plasma apolipoproteins of these rats indicated marked alterations in both the total levels and in the lipoprotein distribution of the major apolipoproteins. In whole plasma, diabetes was associated with significant increases in apolipoprotein (apo)-AIV, apo-AI, and apo-B (mainly in the intestinally derived apo-B240) and a marked decrease in apo-E. In the d less than 1.006 g/ml lipoprotein fraction (very-low-density lipoproteins (VLDL], there were significant increases in apo-B240, apo-AI, and apo-AIV and decreased levels of apo-E and the C apolipoproteins. The decrease in apo-C was primarily due to lower levels of apo-CII, and the ratio of the lipoprotein lipase inhibitor, apo-CIII, to the lipoprotein lipase activator, apo CII, was significantly increased over that in controls. The comparative clearance of triglycerides of VLDL particles from control and diabetic rat plasma was tested in recirculating heart perfusion in vitro. During 45-min perfusions of hearts from control donor rats, lipolysis of triglycerides of VLDL from diabetic rats was only 63-64% of that using plasma VLDL from control rats. Perfusion of hearts from diabetic rats with VLDL from control rats gave lipolysis values of only 53% of that obtained with normal hearts. Where both the VLDL and hearts were obtained from diabetic rats, lipolysis was 23% of that observed when both the lipoprotein and the organ were from control rats. The data suggest that in addition to depressed lipoprotein lipase activity in the tissue from diabetic rats, there are also major compositional changes in circulating lipoproteins which may contribute to defective triglyceride clearance from the circulation.
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PMID:Lipoprotein composition as a component in the lipoprotein clearance defect in experimental diabetes. 396 56

Tri[14C]acylglycerol-labelled chylomicrons, obtained from cannulated mesenteric lymph of streptozotocin-diabetic donor rats, when intravenously injected into non-diabetic recipient rats, disappeared from the circulation at a significantly slower rate than similarly prepared tri[14C]acylglycerol chylomicrons from non-diabetic donor rats (t1/2, 5.6 +/- 0.7 vs. 3.2 +/- 0.5 min-1, P less than 0.02). The appearance of labelled lipolysis products among plasma lipids (free fatty acid, cholesterol ester and phospholipid fractions) was delayed, indicating decreased availability for lipolysis of the chylomicron-borne triacylglycerol of diabetic origin. Tissue distribution of triacylglycerol, 15 min after the injection of chylomicrons to recipient rats, disclosed a 4-5-fold increase in uptake by muscles (heart and diaphragm) in relation to adipose tissues (epididymal and perirenal sites), in the case of chylomicrons of diabetic derivation. Since a large share of the chylomicron triacylglycerol was taken up by the liver, this tissue was perfused with chylomicron 'remnants' prepared by partial in vitro lipolysis with purified lipoprotein lipase. The 'remnants' of diabetic derivation were taken up by the liver at a 2-3-fold slower rate than those of non-diabetic origin. Chylomicrons derived from diabetic rats were found to be similar in size but markedly depleted of E apolipoproteins as determined by SDS-polyacrylamide gel electrophoresis, isoelectric focussing and a specific immunoassay. Decreases were also seen in A-I apolipoproteins by immunoassay and isoelectric focussing. Chylomicron 'remnants' were also markedly apolipoprotein E-deficient. In vitro incubation of the 'diabetic remnants' with high-density lipoproteins raised their apolipoprotein E content approx. 3-fold and considerably increased their hepatic uptake. Injection of intact chylomicrons preincubated with high-density lipoproteins likewise increased their in vivo removal rate toward the range of that of 'non-diabetic' chylomicrons. We conclude that diabetes-induced changes in the apolipoprotein composition of the chylomicrons and chylomicron remnants play an important role in their removal from the circulation. It appears that their recognition pattern is altered, reducing their ability to interact with receptor sites in the peripheral tissues and the liver, respectively.
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PMID:Composition, removal and metabolic fate of chylomicrons derived from diabetic rats. 399 73

To assess the effects of sulfonylurea therapy on plasma lipids and high-density lipoprotein composition, 11 obese diabetic Pima Indians with type II, or non-insulin-dependent, diabetes mellitus were studied before and after tolazamide therapy for one month. Diet composition and weight were kept constant, and the data were compared with a control group of 18 age-, sex-, and weight-matched non-diabetic subjects. Improvement of glycemic control was accompanied by significant decreases in total and very-low-density lipoprotein triglycerides. Total and low-density lipoprotein cholesterol also declined significantly, and there was an increase in the ratio of high-density lipoprotein to low-density lipoprotein cholesterol. Concentrations of total high-density lipoprotein cholesterol, phospholipid, and apolipoprotein AI were unchanged. An increase in the proportion of the high-density lipoprotein 2 subfraction, however, was suggested by significant increases in the ratios of high-density lipoprotein 2 to high-density lipoprotein 3 cholesterol and apolipoprotein AI. There was also a change in the composition of the high-density lipoprotein 2 particle, as indicated by changes in the molar ratio of cholesterol to apolipoprotein AI. The data suggest that improvement of glycemic control after sulfonylurea therapy, when weight and diet composition remain constant, reverses several of the lipoprotein abnormalities observed in type II diabetic patients. There was no evidence of changes in lipoproteins in directions associated with an increased risk for atherosclerosis.
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PMID:Effect of sulfonylurea therapy on plasma lipids and high-density lipoprotein composition in non-insulin-dependent diabetes mellitus. 405 Aug 25

Concentrations of HDL cholesterol, apolipoprotein (apo) A-I and apo A-II were found to be significantly decreased in patients with insulin-dependent diabetes (IDD) and non-insulin-dependent diabetes (NIDD) compared with carefully selected controls matched for sex, age and body weight. LDL cholesterol and apo B levels did not differ significantly between diabetics and controls. Concentrations of lipoprotein Lp(a), an independent risk factor for coronary artery disease in non-diabetics, were above 20 mg/dl in only 14% of diabetics and in 5% of controls. LCAT activity was normal in diabetics, irrespective of type of diabetes, sex and age of patients. No correlation between HbA1 and either HDL cholesterol or A-I and A-II was found in IDD and NIDD. A positive correlation between HbA1 and either triglyceride or VLDL triglyceride was noted in IDD and NIDD. There was also a positive correlation between insulin dosage in IDD and HDL cholesterol, apolipoprotein A-I and A-II.
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PMID:Apolipoproteins (A-I, A-II, B), Lp(a) lipoprotein and lecithin: cholesterol acyltransferase activity in diabetes mellitus. 622 55

To evaluate the optimal discriminators for peripheral atherosclerosis, we studied retrospectively 49 male patients and 39 male controls between 40 and 60 years of age. In addition to hypertension, cigarette smoking, diabetes mellitus, and hyperuricemia, we determined the most common lipids, lipoproteins, and apolipoproteins. Highly significant differences of median values between patients and controls in decreasing order of magnitude were recorded for apo A-II/apo B, apo A-I/apo B, apo B, total cholesterol, and LDL-cholesterol. A retrospective classification of patients and controls under optimal conditions with one variable (apo A-I/apo B) yielded an error rate of 25%. We found that apolipoproteins were better discriminators for peripheral atherosclerosis than than were lipids or lipoprotein lipids. The application of a linear regression discriminant analysis including 29 variables greatly decreased the rate of error and increased the sensitivity and specificity of the classification. From 229 possible models, we used an economic selection strategy to sort out those which either gave the best segregation or were considered the most practicable. The optimal model with 14 variables gave an error rate of less than 5% for the group studied. Suboptimal models yielded error rates between 13% and 18%. We conclude that a mathematical treatment of laboratory data which includes lipid parameters in addition to apolipoprotein values can improve the classification of peripheral vascular atherosclerosis.
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PMID:Risk factors for peripheral atherosclerosis. Retrospective evaluation by stepwise discriminant analysis. 640 92

Two gene specific probes have been used to identify polymorphic DNA loci on chromosome 11 close to the insulin and apoprotein A-1 genes in a genetic analysis of hypertriglyceridaemic patients with and without co-existing diabetes. Of the 45 patients studied with both probes, 15 were diabetic of whom nine possessed class 3/3 insulin polymorphism genotypes, compared with none in the non-diabetic group (p less than 0.001; chi 2 test). In contrast, an uncommon apolipoprotein A-1 polymorphism was found to be equally distributed in the diabetic and the non-diabetic patients. No co-segregation of these two particular genetic polymorphisms was found in either patient group. The differing associations of the two disease-related polymorphism genotypes in patients with hypertriglyceridaemia with or without co-existing diabetes may possibly reflect differing aetiologies of the hyperlipidaemia.
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PMID:Insulin and apolipoprotein A-1/C-III gene polymorphisms relating to hypertriglyceridaemia and diabetes mellitus. 643 27


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