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)

The concentration of cholesterol in serum high density lipoproteins (HDL) and their subfractions (HDL2 and HDL3) was determined in men and women with type I diabetes treated with insulin and in non-diabetic men and women matched for age, weight and serum cholesterol, but not for triglyceride-rich lipoproteins which were higher in the diabetic patients. In none of the patients was the diabetes badly controlled as assessed by measurement of the percentage of haemoglobin in the glycosylated state (HbA1). Regardless of their diabetic control, significantly increased serum HDL3 cholesterol concentration was found in male diabetic patients compared to non-diabetic controls, and in both male and female diabetics the ratio of HDL2 to HDL3 cholesterol was significantly reduced. In patients with well-controlled diabetes (HbA1 less than or equal to 9%) serum HDL3 cholesterol was significantly increased in both men and women, whereas in those with less well-controlled diabetes (HbA greater than 9%) it was similar to that of non-diabetic controls. In only one group of patients, the less well controlled men, was there a significant reduction in serum HDL2 cholesterol. On the basis of current theory, the results of this study would support the view that HDL3 does not contribute to the inverse relationship between total serum HDL and the risk of ischaemic heart disease.
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PMID:Serum high density lipoprotein cholesterol subfractions in type I (insulin-dependent) diabetes mellitus. 706 36

Non-insulin-dependent diabetes (NIDD) is a situation at elevated risk for atherosclerosis. The plasma concentration of high-density lipoprotein (HDL) is often lowered. This may be accompanied by an abnormal composition and profile of HDL subfractions. These abnormalities might result in part from a defect in the net cholesterol ester transfer (CET) from HDL to apo B-containing lipoproteins. In the present work, we have studied the net CET and HDL conversion in normolipidemic, hypercholesterolemic, and hypertriglyceridemic NIDD, by comparison with control subjects. HDL conversion was determined by gradient gel electrophoresis after 23 h incubation in plasma with HDL3 labeled with a nontransferable synthetic marker. The net CET in normolipidemic NIDD was similar to that of controls, while it was approximately doubled in hypercholesterolemic or hypertriglyceridemic NIDD. In all groups, HDL conversion was comparable, with the exception of hypertriglyceridemic NIDD. In the latter group, the labeled HDL2/HDL3 ratio was increased, indicating a more complete conversion that was correlated with the triglyceride/cholesterol ester ratio in HDL. In addition, when lecithin:cholesterol acyl transferase was inhibited, a distinct peak of small HDL particles appeared in the density range of HDL2 in contrast with the other groups where only small HDL3 was formed. Recombination experiments showed that these abnormalities were attributable to the plasma in which labeled HDL3 was incubated rather than to the origin (control or hypertriglyceridemic NIDD) of labeled HDL3. These data suggest that in NIDD, hypertriglyceridemia may result in abnormalities of HDL conversion due to alterations in HDL composition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cholesterol ester transfer and high-density lipoprotein conversion in normolipidemic, hypercholesterolemic, and hypertriglyceridemic non-insulin-dependent diabetics. 755 26

The effects of fluvastatin treatment on lipid profile and apolipoproteins were assessed in a group of 31 Chinese patients with hypercholesterolemia, maintained on a constant low-fat diet. Some patients had the additional cardiovascular risk factors of hypertension and non-insulin-dependent diabetes mellitus, and 6 patients had familial hypercholesterolemia. Baseline lipid levels were measured after a 4-week placebo period, and these were repeated after 4 weeks of treatment with fluvastatin 20 mg daily, and after 4 weeks of treatment with fluvastatin 40 mg daily. Total cholesterol, low density lipoprotein cholesterol, and apolipoprotein (apo) B were each reduced to the same extent with the 2 doses of fluvastatin (-20%, -26%, and -20%, respectively). Triglycerides and very low density lipoprotein cholesterol were also reduced by about 12% with the 2 doses of fluvastatin. Apo A-I was increased by 7% and high density lipoprotein cholesterol (HDL-C) was increased by 10% with the 40 mg dose. The increase in HDL-C was due to increases in both HDL2-C (18%) and HDL3-C (7%). Lipoprotein(a) levels did not show any significant change with the 2 doses of fluvastatin in this short-term study. One patient developed reversible asymptomatic elevation of liver enzymes with the higher dose of fluvastatin; otherwise the drug was well tolerated and no patients had to be withdrawn from the study.
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PMID:Effects of fluvastatin on lipid profile and apolipoproteins in Chinese patients with hypercholesterolemia. 760 89

To determine whether nonhuman primates demonstrate the same alterations in transport of cholesteryl ester (CE) in plasma observed in diabetic humans, cholesteryl ester transfer (CET) was measured in cynomolgus monkeys with chronic spontaneous diabetes mellitus (glycated hemoglobin: diabetics 10.7 +/- 4.1%; controls 3.8 +/- 0.8%, P < 0.005). Among the plasma lipids, only triglycerides were significantly increased in diabetic monkeys (diabetics 303 +/- 294 mg/dl; controls 85 +/- 34 mg/dl; P < 0.05); total plasma, LDL, HDL2, and HDL3 cholesterol concentrations did not differ significantly from those of control animals. Similar to human beings with insulin-dependent and non-insulin-dependent diabetes mellitus, CET estimated both as the mass of cholesteryl ester transferred from HDL to the apoB-containing lipoproteins (VLDL + LDL) and as the loss of radiolabeled cholesteryl ester from HDL was significantly greater (P < 0.001) in diabetic compared to control monkeys. Glycated hemoglobin levels in the combined control and diabetic groups correlated directly with both the mass of cholesteryl ester transferred at 2 h (r = 0.75; P < 0.001) and the isotopic transfer (k) (r = 0.64; P < 0.005). The mass of cholesteryl ester transfer protein (CETP) tended to be higher in the diabetic animals (diabetic 4.06 +/- 0.73 microgram/ml versus control 3.05 +/- 0.93; P < 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Accelerated cholesteryl ester transfer and altered lipoprotein composition in diabetic cynomolgus monkeys. 761 22

In postmenopausal women, partly in relation to advancing age and partly due to oestrogen deficiency, there is a frequent increase in body weight, and more specifically, in android fat distribution. In addition, loss of ovarian function is associated with the development of a more atherogenic profile with increased triglycerides, LDL-cholesterol and its smaller dense subfractions, decreased HDL- and HDL2-cholesterol and, potentially, an irregular increase in Lp(a). Not only does oestrogen therapy counteract all these changes towards a definitely less atherogenic profile but oestrogens seem also implicated in reducing LDL oxidative products, in favouring a higher ratio of prostacyclin to thromboxane and, potentially, of endothelium derived relaxing factor to endothelin, and also in acting as a calcium antagonist in the vessel wall. All of these favourable vascular effects are not solely attributable to lipid-related oestrogen effects. Excess weight and central obesity, diet changes and lack of exercise, more frequent with advancing age, all concur to alter glucose tolerance and increase insulin resistance during the postmenopause. Impaired glucose tolerance and diabetes mellitus may be found in nearly 20% of women aged 55 to 65 years. In addition, oestrogen deficiency may be further responsible for decreased pancreatic insulin secretion and alteration of its metabolic clearance rate-changes that can be reversed toward improved insulin secretion and sensitivity by oestrogen treatment in small dosages. By contrast, synthetic androgenic progestins can counteract these effects of oestrogens more than progesterone derivatives do, and they may partly help to promote insulin resistance and hyperinsulinism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Postmenopausal changes of lipid and glucose metabolism: a review of their main aspects. 761 65

Apolipoprotein A-IV is considered to play a role in triglyceride-rich lipoprotein metabolism, in reverse cholesterol transport, and in facilitation of CETP (Cholesterolyl Ester Transfer Protein) activity. Moreover, apoA-IV is genetically polymorphic in humans, in whom two major isoproteins (apoA-IV 1 and apoA-IV 2) are present and have differences that influence the apoA-IV phenotype in lipid metabolism. In non-insulin-dependent-diabetes, increased apoA-IV levels are found, mainly related to hypertriglyceridemia and to a lesser extent to HDL cholesterol level; apoA-IV phenotype distribution is not different from controls; in the control population, the potential protective lipid profile (characterized by increased HDL and HDL2 cholesterol levels) related to the apoA-IV 1-2 phenotype, is no longer found in NIDDM patients (the metabolic state of NIDDM appears to have effected the potential protective lipid profile related to the apoA-IV 1-2 phenotype); and plasma apoA-IV levels is associated with increased prevalence for macrovascular disease. In non-insulin-dependent diabetes treated with insulin, apoA-IV levels are increased. Unlike results for NIDDM patients undergoing oral treatment, the increase in apoA-IV level is not related to hypetriglyceridemia, so that the effect on lipid metabolism may be different.
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PMID:Apolipoprotein A-IV in diabetes mellitus. 762 79

High density lipoprotein (HDL) subfractions (2b, 2a, 3a, 3b, and 3c) separated by gradient gel electrophoresis (GGE) and defined by Gaussian summation analysis, and the compositions of HDL2 and HDL3, separated by preparative ultracentrifugation, were studied in four groups of men with or without non-insulin-dependent diabetes mellitus (NIDDM) and coronary artery disease (CAD): group 1 (DM+CAD+, n = 50); group 2 (DM-CAD+, n = 50); group 3 (DM+CAD-, n = 50); and group 4 (DM-CAD-, n = 31). HDL GGE subfraction distributions, available in 125 subjects, were not significantly different among the groups. In contrast, dividing the whole study population into quartiles of serum triglyceride (TG) concentration showed that high TG levels were significantly associated with low HDL2b and high HDL3b concentrations. In a multivariate linear regression model, postheparin plasma hepatic lipase (HL) activity, and fasting serum insulin and TG concentrations were all associated independently and inversely with low HDL2b, but lipoprotein lipase or cholesteryl ester transfer protein activities were not correlated with HDL2b concentrations. Group 1 tended to have the smallest mean particle sizes in the HDL subfractions, significantly (P < 0.03, CAD vs. non-CAD) for HDL2b and for HDL2a. These differences were independent of TG, insulin and HL, but lost their significance when adjusted for beta-blocker therapy. Both HDL2 and HDL3 particles in group 1 were significantly depleted of unesterified cholesterol, and their HDL2 was TG-enriched (P = 0.053). A high HL activity, hyperinsulinemia and hypertriglyceridemia are independently associated with low levels of HDL2b and generally small HDL particle size. HDL particles in subjects with NIDDM and CAD are small-sized and have a low free cholesterol content. Both these characteristics may be markers of impaired reverse cholesterol transport.
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PMID:High density lipoprotein subfractions in non-insulin-dependent diabetes mellitus and coronary artery disease. 777 69

These are the preliminary data of an open multicenter trial of antihypertensive treatment with isradipine as monotherapy (dose, 4.55 +/- 0.56 mg twice daily; n = 11) or isradipine (7.5 +/- 0.63 mg twice daily) in combination with bopindolol (1.16 +/- 0.12 mg once daily; n = 30) administered for 3 years to patients with essential hypertension (WHO classification I or II). Blood pressure was significantly decreased in both treatment groups and there was no indication of resistance to therapy. Plasma levels of total cholesterol and triglycerides were decreased by the end of the second year of treatment, and there was a tendency toward increase in plasma levels of high-density lipoprotein cholesterol (HDL2 or HDL3). The atherogenic index (ratio between total cholesterol and HDL2 plus HDL3) was also decreased. Blood glucose levels remained unchanged in both normoglycemic patients and those with non-insulin-dependent diabetes mellitus (NIDDM) during 3 years of therapy. It is concluded that isradipine is safe and effective when administered long-term in the treatment of hypertensive patients with either hyperlipidemia or NIDDM.
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PMID:Hungarian Isradipine Study (HIS): long-term (3-year) effects on blood pressure and plasma lipids. 794 81

The present study was designed to evaluate the potential role of plasma cholesteryl ester transfer protein (CETP) activity in the regulation of high-density lipoprotein (HDL) subclasses in non-insulin-dependent diabetes mellitus (NIDDM). We studied 45 men with NIDDM and angiographically defined coronary artery disease ([CAD] DM+CAD+, aged 54.4 +/- 6.1 years, mean +/- SD); 47 nondiabetic men with similarly proven CAD (DM-CAD+, aged 54.9 +/- 6.6 years; 43 men with NIDDM but no CAD (DM+CAD-, aged 55.2 +/- 7.3 years); and 29 nondiabetic men without CAD (DM-CAD-, aged 53.2 +/- 5.3 years). The groups were matched for age and body mass index (BMI). Plasma CETP activity was determined by measuring the ability of the plasma sample to transfer esterified cholesterol from exogenous 14C-cholesteryl ester-labeled low-density lipoprotein (LDL) to exogenous HDL. Plasma lipoproteins were separated by ultracentrifugation. The concentration of HDL cholesterol was reduced in the DM+CAD+ group as compared with the DM-CAD- group (P < .01). This change was due to a decrease of both HDL2 cholesterol (P < .05) and HDL3 cholesterol (P < .001). There was a clear-cut decrease in HDL3 cholesterol in the DM-CAD+ (P < .01) and DM+CAD- (P < .05) groups as compared with the DM-CAD- group. Plasma CETP activity was lower in the DM+CAD- group (1.06 +/- 0.24 arbitrary units [AU]) than in the DM-CAD- group (1.19 +/- 0.26 AU, P < .05). In the DM+CAD+ group, the mean of CETP activities was 1.09 AU.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma cholesteryl ester transfer protein activity in non-insulin-dependent diabetic patients with and without coronary artery disease. 799 Jul 2

On initial diagnosis or when metabolic control is poor, subjects with type 1 (insulin-dependent) diabetes mellitus often exhibit decreased high density lipoprotein (HDL) cholesterol levels, which have been associated in numerous studies in non-diabetic subjects with atherosclerosis and coronary artery disease. We measured the activities of plasma lecithin:cholesterol acyltransferase (LCAT), post-heparin lipoprotein lipase, and the composition of the HDL subfractions HDL2 and HDL3, in ten poorly controlled type 1 diabetic patients admitted to a metabolic ward (six women and four men, aged 18-37 years). The measurements were repeated after metabolic control had been optimised and again a week after discharge. The results were compared with those of ten healthy normolipidaemic subjects matched for age, sex and body mass. LCAT activity increased significantly (P < 0.05) with improved metabolic control in the diabetic patients, and showed positive within-person correlation with HDL2 cholesterol ester (r = 0.67; P < 0.01), HDL2 free cholesterol (r = 0.67; P < 0.01), phosphatidylcholine (r = 0.49; P < 0.05), total phospholipids (r = 0.50; P < 0.01) and apolipoprotein A-I (apo A-I: r = 0.72; P < 0.01). With improving metabolic control HDL2 lipid levels increased more than twofold and the compositional changes in HDL2 were reflected by an increased apo A-I:apo A-II ratio (P < 0.05) and a decreased triglyceride:apo A-I ratio (P < 0.05). Changes in HDL3 levels and composition were minor. The results of this study indicate that an increase in LCAT activity increases the concentration and changes the composition of HDL2 in type 1 diabetic patients with improved metabolic control.
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PMID:Lecithin:cholesterol acyltransferase activity and high-density lipoprotein subfraction composition in type 1 diabetic patients with improving metabolic control. 811 Oct 77


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