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

Longitudinal studies have shown a large excess of cardiovascular mortality in insulin-dependent diabetic patients (IDDM) as compared to non-diabetic controls. Although diabetes appears to be an independent cardiovascular risk factor, increases in total and LDL-cholesterol together with a decrease of HDL-cholesterol are more pronounced in diabetics with cardiovascular disease. The general opinion, however, derived from a large number of cross-sectional studies, is that in well-controlled IDDM lipoprotein abnormalities are modest and only slightly different from matched non-diabetic controls. Most of the studies, however, used absolute criteria based on consensus statements and do not take the internal relations of the lipoproteins into account. When atherogenic indices (such as the relationship between total cholesterol and HDL-cholesterol or the Apo A1/apo B quotient) are used, 20 to 30% of an IDDM population considered to be in clinically acceptable control have to be considered pathological. This observation is even more important since the recent Diabetes Control and Complications Trial has shown that, especially in the younger group of patients, significantly higher total cholesterol and triglycerides and lower HDL-cholesterol were observed. Especially in these patients can diet and drug intervention be the most useful in the prevention of cardiovascular disease. These data are consistent with the fact that more sophisticated techniques have previously shown atherogenic changes in the composition of the VLDL-particles and lipoprotein enrichment in apo B. Since these techniques are not easily available in the clinic one has to refer to more classical techniques and the use of above mentioned atherogenic profiles to decide treatment.
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PMID:Atherogenic profiles in insulin-dependent diabetic patients and their treatment. 150 49

The relation between plasma lipid peroxide and coronary heart disease was investigated at Harapan Hospital in Kita Jakarta. Ninety-eight patients (83 males and 15 females), below 75 years old were included in the study. The samples consisted of 47 cases with angina and 22 cases with myocardial infarction which were proven to suffer from coronary atherosclerosis by the presence of clinical symptoms, ECG abnormalities, angiography and myocardial enzyme measurement. Controls were patients who did not show any abnormalities in the parameters used. Controls and patients were classified into several groups based on the presence or absence of risk factors (smoking, hypertension, diabetes mellitus, hyperlipidemia, obesity, family history). The results of the study showed that plasma lipid peroxide in patients with angina and myocardial infarction which were 3.26 +/- 1.07 mumol and 3.20 +/- 0.82 mumol/l, respectively, were significantly higher (p less than 0.05) than controls 2.50 +/- 0.45 mumol/l. There was no differences in total cholesterol, LDL and triglyceride contents between control and patients with coronary heart disease; whereas HDL cholesterol level was significantly higher in the patients with angina, 38.7 +/- 10.5 mg/dl vs 31.5 +/- 6.76 mg/dl in patients with myocardial infarction. Univariate analysis of various risk factors revealed a strong correlation between plasma lipid peroxide and the chance in developing coronary heart disease. The present study showed that plasma lipid peroxide was increased in coronary heart disease and that it might be used as a determinant in the assessment of the severity of the disease. An investigation on the effects of antioxidants in these patients is planned.
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PMID:Plasma lipid peroxides in coronary heart disease. 150 21

The chemistry, pharmacology, pharmacokinetics, clinical trials, adverse effects, role in lipid-lowering therapy, and dosage and administration of pravastatin are reviewed. Pravastatin sodium is a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor for the treatment of hypercholesterolemia. Its structural formula is similar to those of lovastatin and simvastatin, but it is active in the parent form. It competitively inhibits HMG-CoA reductase, reduces hepatic cellular cholesterol synthesis, increases the expression of hepatic low-density lipoprotein (LDL) receptors, and reduces hepatic very low-density lipoprotein (VLDL) synthesis. Pravastatin has been demonstrated to reduce cholesterol in patients with familial and nonfamilial polygenic hypercholesterolemia and patients with diabetes mellitus. In doses of 10-40 mg/day, pravastatin has been shown to reduce total cholesterol by 15-30% and LDL cholesterol by 15-40%. It also increases high-density lipoprotein cholesterol by 2-20% and reduces triglycerides. It is generally well tolerated, with few adverse effects reported in clinical trials. Pravastatin reduces LDL cholesterol and increases HDL cholesterol comparably to lovastatin but possibly with fewer adverse effects. Further studies and clinical use will be needed to confirm potential differences in adverse effect profiles between the two drugs.
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PMID:Pravastatin: a new drug for the treatment of hypercholesterolemia. 845 77

Concentrations of HDL cholesterol and apolipoprotein A-I are commonly increased in Type 1 (insulin-dependent) 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 less than 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.
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PMID:Metabolism of HDL apolipoprotein A-I and A-II in type 1 (insulin-dependent) diabetes mellitus. 151 63

Normolipidemic patients of both sexes with insulin-dependent diabetes mellitus have the same pervasive changes in lipoprotein surface and core lipid composition. The disproportionate increase observed in their lipoprotein free (unesterified) cholesterol relative to the predominant surface phospholipid lecithin (phosphatidylcholine) is reflected by elevation of the FC-L ratio in their whole plasma, VLDL, HDL2, and HDL3. As a possible consequence of this qualitative disturbance, cholesteryl ester transfer is pathologically increased and the mass of cholesteryl ester transferred from HDL to VLDL + LDL is significantly greater in IDDM patients than in control subjects at 1, 2, and 4 hr (P less than 0.001). Consistent with accelerated CET in vivo, the TG-CE core lipid ratio was decreased in VLDL from six subjects (IDDM 9.5 +/- 0.8 vs. control 12.9 +/- 3.4; P less than 0.01) and increased in their HDL (diabetic 0.55 +/- 0.11 vs. control 0.42 +/- 0.04: P less than 0.025). These abnormalities in lipoprotein composition and CET do not correlate with glycemic control and persist after intensive management with s.c. insulin. They may be related to the peripheral hyperinsulinemia that is an unavoidable consequence of conventional s.c. insulin administration because preliminary studies indicate that these disturbances in lipoprotein composition and function are reversed when systemic insulin levels are lowered and insulin is delivered into the portal circulation from an i.p. catheter connected to an implanted programmable s.c. insulin pump.
Diabetes 1992 Oct
PMID:Effects of insulin treatment on lipoprotein composition and function in patients with IDDM. 152 28

In people with diabetes, glycation of apolipoproteins correlates with other indices of recent glycemic control, including HbA1. For several reasons, increased glycation of apolipoproteins may play a role in the accelerated development of atherosclerosis in diabetic patients. Recognition of glycated LDL by the classical LDL receptor is impaired, whereas its uptake by human monocyte-macrophages is enhanced. These alterations may contribute to hyperlipidemia and accelerated foam-cell formation, respectively. Glycation of LDL also enhances its capacity to stimulate platelet aggregation. The uptake of VLDL from diabetic patients by human monocyte-macrophages is enhanced. This enhancement may be due, at least in part, to increased glycation of its lipoproteins. Glycation of HDL impairs its recognition by cells and reduces its effectiveness in reverse cholesterol transport. Glycation of apolipoproteins may also generate free radicals, increasing oxidative damage to the apolipoproteins themselves, the lipids in the particle core, and any neighboring macromolecules. This effect may be most significant in extravasated lipoproteins. In these, increased glycation promotes covalent binding to vascular structural proteins, and oxidative reactions may cause direct damage to the vessel wall. Glycoxidation, or browning, of sequestered lipoproteins may further enhance their atherogenicity. Finally, glycated or glycoxidized lipoproteins may be immunogenic, and lipoprotein-immune complexes are potent stimulators of foam-cell formation.
Diabetes 1992 Oct
PMID:Lipoprotein glycation and its metabolic consequences. 152 39

Lipoprotein particles containing apoA-I but not apoA-II are, among high-density lipoproteins, effective protectors against atherosclerosis that act by promoting the efflux of cellular cholesterol and the reverse cholesterol transport process. Because previous studies showed that in vitro nonenzymatic glycosylation of HDL impairs HDL receptor-mediated cholesterol efflux, we isolated Lp A-I from two poorly controlled insulin-dependent diabetic patients and compared the chemical composition and ability to promote cholesterol efflux with the same particles purified from two matched nondiabetic control subjects. No differences in lipid composition or in the ability to promote cholesterol efflux from cultured adipose cells were noted between the two types of Lp A-I preparations. However, when we separated Lp A-I from diabetic subjects by degree of glycosylation, the specifically glycosylated subfractions were about 50% less effective in producing cholesterol efflux than the nonglycosylated particles.
Diabetes 1992 Oct
PMID:Apolipoprotein A-I-containing particles and reverse cholesterol transport in IDDM. 152 42

The prevalence of hypercholesterolaemia and the frequency of a reduced HDL-cholesterol (at different cholesterol concentrations) were evaluated in a group of 400 diabetic patients attending a single diabetic clinic. Despite regularly supervised diabetes, including dietary advice, over one quarter of the patients had a serum total cholesterol concentration greater than 6.5 mmol/l, while over a quarter of the non-insulin treated and one eighth of the insulin treated diabetic subjects had an HDL-cholesterol less than 0.9 mmol/l, with a greater prevalence in the males compared with the females. More than 60% of all the diabetic patients who had a reduced HDL-cholesterol less than 0.9 mmol/l also had a total cholesterol concentration less than 6.5 mmol/l. When the total/HDL-cholesterol ratio was calculated more non-insulin treated subjects had a value greater than 4.5 as compared with insulin treated diabetic patients. When comparisons were made between an age matched group of diabetic patients (n = 185) and a group of non-diabetic subjects attending for a health screen (n = 155), the frequencies of serum cholesterol concentrations greater than 5.2, 6.5, and 7.8 mmol/l were similar for both groups. Significantly greater numbers of diabetic patients had a reduced HDL-cholesterol less than 0.9 mmol/l (at any level of serum cholesterol) and a total/HDL cholesterol ratio greater than 4.5. This study has shown that the measurement of serum total cholesterol concentration alone will not characterize many subjects who are at risk of macrovascular complications due to a reduced HDL-cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Importance of routine measurement of HDL with total cholesterol in diabetic patients. 843 5

Patients with diabetes commonly manifest hypertriglyceridemia along with decreased adipose tissue lipoprotein lipase (LPL) activity, and improved diabetes control tends to reverse these abnormalities. To better understand the mechanism of regulation of LPL in diabetes, 11 diabetic patients (3 type I, 8 type II) were brought under improved glycemic control, and adipose tissue LPL gene expression was assessed by performing paired fat biopsies. Six of the 11 patients attained improved control with insulin, with a decrease in glycohemoglobin (glyc Hgb) from 13.8 +/- 0.9 to 10.4 +/- 0.6%; 5 patients attained improved control with glyburide (glyc Hgb fell from 14.2 +/- 2.4 to 8.8 +/- 0.6%), and together they demonstrated a lowering of serum triglycerides and total cholesterol. No changes were observed in HDL cholesterol. Improved diabetes control resulted in a significant increase in LPL activity in both the heparin-releasable (HR) and extractable (EXT) fractions of adipose tissue, as well as in LPL immunoreactive mass. The change in LPL activity with improved control was variable, and showed a positive correlation with the HDL levels prior to treatment (r = 0.74, P less than 0.02). When adipose tissue was pulse-labeled with [35S]methionine, there was an increase in isotope incorporation into LPL after treatment, indicating an increase in LPL synthetic rate. However, improved diabetes control resulted in no significant change in LPL mRNA levels. Thus, improved glycemic control resulted in an increase in LPL activity which correlated with each patient's basal high density lipoprotein. This increase in LPL activity was accompanied by an increase in LPL immunoreactive mass, and an increase in LPL synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of improved diabetes control on the expression of lipoprotein lipase in human adipose tissue. 155 36

The predictors of premature coronary atherosclerosis were examined in 203 patients (99 men aged less than or equal to 50 years, and 104 women aged less than or equal to 60 years) undergoing elective diagnostic coronary arteriography. Age, cigarette smoking, hypertension, obesity, diabetes, positive family history of premature coronary artery disease (CAD), and plasma levels of total cholesterol, triglyceride, lipoproteins (i.e., very low, intermediate-, low-, and high-density [HDL] lipoproteins and their subfractions [HDL2 and HDL3], and lipoprotein [a]) and apolipoproteins (apoA-1, apoA-2 and apoB, respectively) were examined using univariate analyses and multivariate logistic regression. In men, age (p less than 0.05), smoking (p less than 0.05), and plasma triglyceride (p less than 0.02) and apoA-1 (p less than 0.05) levels were independently associated with CAD. In women, smoking (p less than 0.001) and plasma apoB levels (p less than 0.04) were the strongest variables independently associated with CAD. It is concluded that the "nontraditional" risk factors (plasma apoA-1 and apoB levels) are better predictors of premature CAD than are plasma lipoproteins and that smoking is the strongest of the traditional nonlipid risk factors.
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PMID:Comparison of the plasma levels of apolipoproteins B and A-1, and other risk factors in men and women with premature coronary artery disease. 156 71


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