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

Patients with insulin dependent diabetes mellitus who develop proteinuria may die prematurely, whereas those who do not develop this complication have a comparatively normal life span. The excess mortality in diabetics with proteinuria is from cardiovascular as well as renal disease, but the reason is unclear. Risk factors for vascular disease were therefore assessed in 22 insulin dependent diabetics with proteinuria, but not renal failure, who were matched for sex, age, duration of diabetes, and glycated haemoglobin (HbA1) values with a similar number who had normal urinary albumin excretion rates. Macrovascular disease (ischaemic heart disease and peripheral vascular disease) was present in 10 patients with proteinuria but in only three with normal albumin excretion rates, and proliferative retinopathy was detected in 11 and four patients in the two groups. There was no significant excess of smokers in the group with proteinuria. Blood pressure was, however, higher in the patients with proteinuria--mean systolic pressure 161 (SD 18) mm Hg compared with 135 (19) mm Hg (95% confidence interval of difference between means 15 to 38 mm Hg); mean diastolic pressure 90 (SD 12) mm Hg compared with 79 (15) mm Hg (confidence interval 3 to 19 mm Hg). The concentration of serum high density lipoprotein (HDL) cholesterol isolated by precipitation was lower in the patients with proteinuria (confidence interval 0.02 to 0.41 mmol/l). Their concentration of HDL2 cholesterol isolated by ultracentrifugation was also decreased (confidence interval 0.02 to 0.40 mmol/l), whereas HDL3 cholesterol tended to be increased (confidence interval -0.01 to 0.23 mmol/l). There was also a trend for serum cholesterol concentrations to be higher in the presence of proteinuria (confidence interval -0.39 to 1.20 mmol/l). The aggregation of risk factors for atherosclerosis in insulin dependent diabetes mellitus complicated by proteinuria helps to explain the increased prevalence of ischaemic heart disease and peripheral vascular disease reported in these patients. Early renal disease in insulin dependent diabetes may have an important role in hypertension and altered lipoprotein metabolism.
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PMID:Influence of proteinuria on vascular disease, blood pressure, and lipoproteins in insulin dependent diabetes mellitus. 311 68

Lipids are transported in the blood in four major classes of lipoproteins. The triacylglycerol-rich lipoproteins are chylomicrons and very-low-density lipoproteins (VLDL) which are produced by the small intestine and liver, respectively. These lipoproteins mainly carry fatty acids to adipose tissue and muscle where the triacylglycerol is hydrolysed by lipoprotein lipase. The resulting particles that remain in the blood are chylomicron remnants and low-density lipoprotein (LDL), respectively. The remnant is taken up by the liver via endocytosis which is mediated by a specific receptor for apolipoprotein E (apoE). LDL, which are rich in cholesterol, can also be taken up by the liver or extrahepatic tissues by a receptor-mediated endocytosis that specifically recognises apoB or apoE. 'Nascent' high-density lipoprotein (HDL) particles are secreted by the liver and intestine and then undergo modification to become HDL3 and then HDL2 as they acquire cholesterol ester. They facilitate the reverse transport of cholesterol back to the liver. Little is known of the hormonal regulation of lipoprotein uptake by the liver. Recently, we have shown that insulin and tri-iodothyronine (T3) increase the specific binding of LDL to cultured hepatocytes whereas dexamethasone (a synthetic glucocorticoid) has the opposite effect. The changes in binding produced by insulin and dexamethasone are paralleled by alterations in the rate of degradation of apoB. These findings may in part explain the hypercholesterolaemia and increased risk of premature atherosclerosis that can be associated with poorly controlled diabetes or hypothyroidism.
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PMID:The biochemistry of lipoproteins. 314 85

To study the effects of rigorous insulin therapy on serum lipoproteins in patients with noninsulin-dependent diabetes not controlled with oral agents only, we measured serum lipoproteins, apoproteins, lipolytic enzymes, and glucose disposal using an insulin clamp technique before and after 4 weeks of insulin therapy. Lipoproteins were isolated by ultracentrifugation and high density lipoprotein (HDL) subfractions, by rate-zonal density gradient ultracentrifugation. The group included 11 women and eight men (age 58 +/- 1 years and RBW 125 +/- 4%). Body weight, glycosylated hemoglobin, mean diurnal glucose, plasma free insulin, and glucose uptake (M-value) were 75 vs. 76 kg; 11.9 vs. 8.9%; 234 vs. 124 mg/dl; 12 vs. 27 microU/ml; and 5.0 +/- 0.4 vs. 7.1 +/- 0.6 mg/kg/min before and after insulin therapy, respectively. After insulin therapy there was a decrease of very low density lipoprotein (VLDL) triglyceride (-60%, p less than 0.001) but an increase of HDL2 cholesterol (+21%, p less than 0.001); HDL2 phospholipids (+38%, p less than 0.001); HDL2 proteins (+23%, p less than 0.01); and HDL2 mass (127 +/- 11 vs. 158 +/- 12 mg/dl, p less than 0.001). There was a decrease of HDL3 cholesterol (-13%, p less than 0.05); HDL3 phospholipids (-16%, p less than 0.05); HDL3 proteins (-18%, p less than 0.001); and HDL3 mass (179 +/- 6 vs. 146 +/- 6, p less than 0.01). Zonal profiles showed a redistribution of particles from HDL3 to HDL2. Serum apo A-I increased (p less than 0.05), apo A-II remained constant, but apo B decreased (-29%, p less than 0.001). The most marked change during insulin therapy was a 2.3-fold increase in adipose tissue lipoprotein lipase (LPL) activity (p less than 0.001). The changes of VLDL and HDL subfractions were not explained by respective changes of the blood glucose, free insulin, or M-value. The data indicate that intensive insulin therapy induces antiatherogenic changes in serum lipids and lipoproteins and suggest that the induction of LPL by insulin is the major factor responsible for redistribution of HDL particles from HDL3 to HDL2.
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PMID:Insulin therapy induces antiatherogenic changes of serum lipoproteins in noninsulin-dependent diabetes. 327 41

A random sample of men (319) aged 20 to 59 was examined in one of the administrative districts in Moscow. A study was made of the blood plasma content of HDL2 and HDL3 cholesterol, triglycerides with relation to insulinemia and glycemia both on an empty stomach and during the GTT. An analysis of the data obtained led to a conclusion that the level of insulinemia was a factor influencing the level of HDL2 and HDL3. Derangements in the metabolism of the above lipoproteins were likely to be associated with a high risk of CHD development especially among patients with diabetes mellitus. Therapeutic measures aimed at insulin secretion reduction were recommended for the normalization of lipid metabolism including the content of HDL2 and HDL3.
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PMID:[Indices of carbohydrate metabolism and levels of HDL2 and HDL3 cholesterol in the blood plasma of males]. 332 Oct 31

The aim of the present study concerning patients with long-term insulin-dependent diabetes mellitus was to determine whether the serum lipid and lipoprotein concentrations differ in subjects with and without residual insulin secretion. We also investigated whether factors such as sex, smoking, physical activity and microvascular lesions were associated with particular lipoprotein profiles. C-peptide excretion (greater than or equal to 0.2 nmol) in 24-hour urine samples was used as an indicator of residual insulin secretion. Twenty-two pairs of patients with and without residual insulin secretion matched for age at onset and disease duration were participating in the investigations of glycaemic control and microvascular lesions. The HbA1c was significantly lower in C-peptide excretors than in the non-excretors (6.9 +/- 0.3 vs. 7.9 +/- 0.3%, p less than 0.025). The lipids and lipoprotein fractions were all within normal limits. The HDL2/3 ratio was significantly higher in C-peptide excretors than in non-excretors (1.72 +/- 0.28 vs. 1.10 +/- 0.09, p less than 0.05). Multiple regression analysis showed that factors, such as physical activity, body mass index and glycaemic control could explain more of the variation in the different lipid and lipoprotein fractions than residual C-peptide excretion alone. The only fraction correlating with C-peptide excretion was HDL3 cholesterol. It is concluded that minute residual insulin secretion per se is of minor importance for the regulation of lipids and lipoproteins. Glucose control and residual insulin secretion together with environmental factors seem to be of great importance for the regulation of the lipid and lipoprotein levels in insulin-dependent diabetes mellitus.
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PMID:Serum lipid and lipoprotein levels in long-term insulin-dependent diabetes mellitus. Relation to residual insulin secretion, microvascular lesions and environmental factors. 332 27

Out of a total of 170 patients with a first myocardial infarction, aged below 65 years, consecutively admitted to the Coronary Care Unit of a large urban hospital, only 14 did not present with any risk factor(s) for atherosclerosis (smoking, hypertension, diabetes and obesity). None of these 14 patients showed significant hyperlipidemia. Compared to a control series of normal individuals of the same age (50.0 +/- 5.8 years for males and 61.6 +/- 3.0 years for females), they showed a significant reduction of high-density lipoprotein (HDL)-cholesterol and of apolipoprotein A-I (respectively -18.2 and -9.5%). However, the most striking abnormality was a 30% decrease of the HDL2 mass and of HDL2 cholesterol; both HDL2 and HDL3 had a reduced cholesteryl ester content in the patients. Reduced HDL2 mass and cholesterol levels in plasma, accompanied by significant alterations in HDL subfraction composition, are consistent with a defective cholesterol esterification in HDL. HDL2 deficiency may be a primary alteration in myocardial infarction patients without other significant risk factors.
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PMID:Reduced HDL2 levels in myocardial infarction patients without risk factors for atherosclerosis. 342 54

There is much evidence that altered lipid metabolism contributes to the development of coronary artery disease (CAD). It is generally accepted that there is a direct association between the extent of CAD and total plasma cholesterol, as well as an inverse association between the extent of CAD and plasma HDL-cholesterol. No general agreement exists about the atherogenetic potential of plasma triglycerides and of triglyceride-rich lipoproteins. Since lipoprotein lipase (LPL) is the key-enzyme in the catabolism of triglyceride-rich lipoproteins (chylomicrons and very low-density lipoproteins), we examine the relationship between triglyceride-rich lipoproteins and LPL in vitro and in vivo. The concentrations of the main lipoprotein density classes, namely very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), high-density lipoproteins2 (HDL2) and HDL3, are measured by rate zonal ultracentrifugation. The preparation of VLDL, IDL, LDL, HDL2, and HDL3 is performed by sequential ultracentrifugation. The activity of LPL is measured radioenzymatically in a glycerol-based triolein emulsion. It can be demonstrated in vitro that VLDL, IDL, and HDL2 from normal plasma are able to increase LPL-activity in contrast to VLDL, IDL, and HDL2 from hyperlipemic plasma. This difference seems to be caused by an altered composition of apolipoproteins in hyperlipemic lipoproteins. An artificial acidosis in three healthy subjects shows in contrast to alkalotic and neutral blood-pH a significant decrease of LPL-activity. This result seems to be of some interest, since diseases associated with acidotic blood-pH, such as chronic renal disease, diabetes mellitus or chronic alcoholism, show secondary hyperlipemias caused by a deficit of LPL-activity. It can be shown in 15 male patients who produce a secondary type-V hyperlipemia during severe abuse of alcohol, that LPL-activity is decreased significantly as compared to 15 healthy controls. During sober phases, this alcohol-induced hyperlipemia and the impairment of LPL-activity disappears completely. In an other group of 8 male patients, who are not producing severe secondary hyperlipemia during approximately the identical alcohol intake, LPL-activity is also significantly decreased, but the activity of hepatic lipase is significantly increased. This increase of the activity of hepatic lipase seems to protect these patients from the development of secondary type-V hyperlipemia. In 89 male patients with angiographically assessed CAD a very strong inverse association between the activity of LPL and the extent of CAD is found.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Pathologic decrease in lipoprotein lipase activity in relation to the development of hyperlipemias and their significance for coronary heart disease]. 345 43

Since insulin modulates key enzymes of lipid metabolism, different biological activities of biosynthetic human insulin (BHI) and conventional insulins might induce different plasma lipid and apolipoprotein patterns in diabetic patients chronically treated with the former or the latter insulin preparation. In this study we have evaluated the effects of 3 months of therapy with BHI on plasma lipid and apolipoprotein concentrations in a group of type I diabetics previously treated with insulin of animal origin and the results have been compared with those from diabetics maintained on conventional insulin therapy. In the latter, no change occurred in the clinical and metabolic parameters. Patients transferred to BHI showed lower HDL-cholesterol and HDL3-cholesterol levels at 30 days from the beginning of BHI treatment, and both parameters returned to, and were maintained the basal values at subsequent controls. Total cholesterol, HDL2-cholesterol, triglycerides, apolipoproteins AI, AII and B remained substantially constant throughout the study. Glycometabolic control, which was evaluated by fasting plasma glucose and glycosylated hemoglobin, exhibited a transient, moderate deterioration at the 30-day control, and returned to basal level in the following weeks. No major change was noted as far as daily insulin dosage and relative body weight were concerned. Thus, long-term BHI treatment of type I diabetics does not cause any major change in plasma lipid and apolipoprotein patterns in comparison with animal insulin therapy, so that the validity of using BHI in the treatment of type I diabetes is confirmed.
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PMID:Biosynthetic human insulin does not modify circulating lipid and apolipoprotein concentrations in type I diabetic patients. 352 Nov 80

The effects of glipizide on HDL subclass levels were prospectively evaluated in 7 women and 2 men with non-insulin dependent (Type 2) diabetes. Total HDL, HDL2 and HDL3 levels were unchanged during the treatment period. Baseline HDL levels were lower when compared to a control population which may have been due to the elevated body weight present in most subjects. Mean blood glucose and HbA1 levels were unchanged for the entire group although significant improvement was noted in 5 individuals. Triglyceride and cholesterol levels were not affected by treatment with glipizide. In conclusion, glipizide does not have an adverse affect on HDL lipoprotein levels when patients are followed prospectively.
Diabetes Res 1986 Jun
PMID:The effect of glipizide on HDL and HDL subclasses. 374 45

Different types of diabetes mellitus have different effects on high density lipoprotein (HDL) metabolism. Impaired glucose tolerance may be associated with no change or a slight decrease in HDL cholesterol. Type I diabetes may have normal or elevated HDL cholesterol levels. This HDL elevation may be due to an increase in HDL2 or HDL3. Apo A-I/Apo A-II ratio is also higher in these diabetics. Type II diabetics may have normal or low HDL cholesterol levels as well as normal or decreased Apo A-I levels. In gestational diabetics, the mean HDL cholesterol is lower than controls. Dietary therapy resulting in greater than 10% weight loss in obese diabetics leads to an increase in their HDL-cholesterol levels, although the effect on the latter is controversial. Intensive insulin therapy (for 2-3 weeks) increases serum apo A-I and HDL-cholesterol levels. End-stage renal disease also affects HDL metabolism. In general, patients with this disorder have a decrease of cholesterol and an increase in triglyceride in their HDL. There is an increase in apo E and a decrease in apo CII in their HDL. Apo A-I levels are unaffected whereas apo A-II levels are decreased. Renal transplant patients may have low, normal or high HDL cholesterol and normal or high apo-I levels. In non-diabetic, normotriglyceridemic patients peritoneal dialysis increases their HDL-cholesterol. In non-diabetic hypertriglyceridemic and diabetic patients, peritoneal dialysis causes no change in their HDL-cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of diabetes mellitus and end-stage renal disease on HDL metabolism. 379 61


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