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

This review discusses the genetic factors in the development of arteriosclerosis and coronary heart disease (CHD). In several studies, multivariate analysis of prospective mortality/morbidity data and angiographic findings have indicated that a family history of CHD contributed to CHD risk independently of the established risk factors. In addition, ethnic groups that differ in the prevalence and incidence of CHD also markedly differ in blood groups and protein-enzymatic markers. These or other genetic differences may affect CHD rates. Data from fraternal and identical twins, the source of some early genetic CHD findings, are reviewed. Genetic disorders of lipoprotein metabolism and transport, such as familial hypercholesterolemia, as well as other monogenic disorders are discussed. The role of apoprotein E polymorphism i other monogenic disorders are discussed. The role of apoprotein E polymorphism in determining plasma LDL variability among individuals is considered. Recombinant DNA technology, molecular cloning, and the identification of restriction fragment length polymorphisms are new tools for investigators who assess DNA polymorphism. Recent advances in that domain include: DNA polymorphisms affecting blood levels of apo A-I and A-II, association of a DNA insertion on chromosome 19 with severe premature atherosclerosis, and information concerning linkage of the genes for various apolipoproteins. In addition, the evidence for a major genetic component in diabetes mellitus and research into the genetic aspects of hypertension are reviewed. The male/female ratio in pathologically and epidemiologically assessed atherosclerosis may provide clues to the role of genetics. Early structural changes in the coronary artery intima are compatible with the ethnic and gender predilection. A key question in understanding underlying mechanisms in atherosclerosis is why coronary arteries are occluded in individuals whose other arterial systems are largely unaffected. The review concludes with a discussion of the directions and implications of future genetic research in arteriosclerosis with an emphasis on uncovering genetically determined differences in arterial wall response to blood flow. Subpopulations with different genetic risks may be identified, in which case universal preventive strategies might be replaced with specific ones.
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PMID:Genetic aspects of arteriosclerosis. 352 20

The objective of this paper is to review the extent and mechanisms of lipoprotein alterations in pregnancy, present new data relating to placental lipid transport in normal humans and diabetic animals and consider possible effects on fetal growth and development in normal and diabetic pregnancy. The concentration of all lipoprotein fractions increases during pregnancy. VLDL cholesterol and triglyceride increase 2.5-fold over prepregnancy levels and LDL cholesterol increases 1.6-fold, all with peak levels at term. HDL cholesterol is maximally increased in midgestation by 1.45-fold and subsequently declines to 1.15-fold at term. The mechanisms of these lipoprotein changes have not been studied in humans but the hypertriglyceridemia in animal models is related to enhanced VLDL entry into the circulation. In addition, diminished adipose tissue lipoprotein lipase (LPL) activity in late gestation may cause a rerouting of triglyceride fatty acids to other tissues such as muscle and uterus for oxidation, rather than storage, since triglyceride transport is not reduced in pregnancy. All of these changes appear to be sex hormone mediated. In diabetic pregnancies, the available data indicate that triglyceride concentrations are increased and HDL cholesterol concentrations are decreased with reference to lipoproteins in nondiabetic pregnant women. Previously unpublished data show that a transplacental FFA gradient exists across the umbilical circulation in the direction of the fetus and is proportional to the maternal FFA concentration. No gradient is seen for triglyceride or total plasma cholesterol. However, transport of unmeasured amounts of triglyceride fatty acids may still occur via placental LPL and be exaggerated in diabetes where LPL declines in adipose tissue but not in placenta. The mechanism of transplacental cholesterol transport remains to be defined. Preliminary studies suggest that it depends on HDL as well as LDL since both can provide cholesterol for placental progesterone synthesis. In addition, fetal weight and length are associated with maternal apoproteins A-I and A-II, both major apoproteins of HDL. By lowering HDL in pregnancy, diabetes mellitus could negatively affect these relationships. In conclusion, sex hormone mediated modifications of lipoprotein physiology are described in pregnancy which may enhance triglyceride fatty acid transport to muscle for oxidation and LDL and HDL cholesterol delivery to growing maternal and fetal tissues, a process that diabetes could globally disrupt.
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PMID:Lipoprotein metabolism in pregnancy, fat transport to the fetus, and the effects of diabetes. 354 67

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

It has been hypothesized that plasma triglyceride fatty acids may traverse the placenta and contribute to infant adiposity particularly in GDM pregnancy. It has also been hypothesized that high-density lipoproteins (HDL) can both deliver cholesterol to and remove cholesterol from the placenta. To determine if these maternal parameters are related to fetal growth in normal pregnancy, we have examined relationships of lipoprotein lipids, apoproteins, hormones, fuels, clinical chemistries, and maternal weight at 36 wk gestation to infant birth weight, birth weight ratio (birth weight corrected for gestational age), birth length, and head circumference in a cohort of pregnant women attending a prepaid health plan, Group Health Cooperative of Puget Sound. Associations were examined using a multivariate regression analysis of several groups of related variables. Results show that the birth weight and/or birth weight ratio are weakly positively associated with maternal very-low-density lipoprotein (VLDL) triglyceride and statistically significantly positively associated with apoprotein A-I, placental lactogen, estradiol, bilirubin, and maternal prepregnancy weight and pregnancy weight gain. Glucose and insulin predict birth weight only in pairwise analysis. Significant negative predictors of birth weight or birth weight ratio include VLDL cholesterol, apoprotein A-II, SGOT, and creatinine. Significant positive predictors of birth length include apoproteins A-I, placental lactogen, and maternal weight. Apoprotein A-II negatively predicts birth length. Only maternal prepregnancy weight predicts head circumference.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Jun
PMID:Relationships of infant birth size to maternal lipoproteins, apoproteins, fuels, hormones, clinical chemistries, and body weight at 36 weeks gestation. 392 27

Serum levels of cholesterol (C), triglycerides (TG), lipoprotein-C and apolipoproteins (apo) A-I, A-II and B were measured in 30 children with type I diabetes mellitus (16 boys, 14 girls, aged 11-14 years) and in 26 healthy controls (15 boys, 11 girls, aged 10-13 years). For 19 diabetics controls matched for age, sex and relative body weight were selected. The diabetic patients were considered to be in fair metabolic control according to HbA1 levels and glycosylated serum protein concentrations. Mean serum apo A-I, A-II and B, C, TG, low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) did not differ significantly between diabetic nondiabetic children. Very low density lipoprotein cholesterol (VLDL-C) was significantly higher in diabetic children than in controls. Serum C and LDL-C levels showed close univariate linear correlations with glycosylated serum protein (LDL-C: r = 0.53, p less than 0.01, C: r = 0.58, p less than 0.01) in diabetics. The ratio LDL/HDL-C was significantly correlated to HbA1 levels (r = 0.47, p less than 0.01). By canonical and multiple linear correlation analysis significant relations of a selected set of variables concerning the control and therapy of diabetes (serum glucose, HbA1, glycosylated serum protein, insulin dose) with a set of lipoprotein variables (C, TG, VLDL-C, HDL-C, LDL-C, apo A-I, A-II, B) could be demonstrated. From these data we conclude that significant relations between atherogenic serum lipids and lipoproteins (C, LDL-C) and the degree of metabolic control exist in diabetic children, even in the absence of marked dyslipoproteinemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Apolipoproteins and lipoproteins in children with type I diabetes: relation to glycosylated serum protein and HbA1. 409 Sep 71

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

Plasma triglycerides, cholesterol, high-density lipoprotein (HDL) cholesterol, and apolipoproteins (apo) A-I, A-II, C-II, and C-III were determined and analyzed in 170 diabetic patients and 46 age-matched healthy normal subjects. The diabetics were separated into two groups: insulin-dependent diabetes mellitus (IDDM, n = 78) and noninsulin-dependent diabetes mellitus (NIDDM, n = 92). Significantly increased triglycerides, low HDL cholesterol, and normal cholesterol levels were found in the diabetics. The lipid profiles were similar in the IDDM and NIDDM groups. Plasma apo A-I, but not apo A-II, was low in both groups of diabetics. However, only in the IDDM subjects was there a statistically significant decrease in apo A-I when compared to normal subjects. The decreased apo A-I level negatively correlated with plasma triglycerides. Apo C-II and apo C-III were slightly increased in the diabetics compared to normal subjects. Apo C-II and apo C-III levels significantly correlated with plasma triglycerides (apo C-II, r = 0.70, P less than 0.0001; apo C-III, r = 0.71, P less than 0.0001). Only apo C-II correlated with total cholesterol. Thirty-eight to forty-two percent of the IDDM and NIDDM subjects had a clinical diagnosis of coronary artery disease (CAD) and/or peripheral arteriovascular disease (PAD). In the IDDM subjects, but not in the NIDDM subjects the incidence of CAD and/or PAD was associated with the decreased apo A-I levels as evaluated by a univariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of plasma lipids and apolipoproteins in insulin-dependent and noninsulin-dependent diabetics. 641 12

Changes in plasma levels of apolipoproteins A-I, A-II, C-II, and C-III, cholesterol, triglycerides, glucose, and insulin were studied after administration of a glucose load in six normal subjects and five patients with non-insulin-dependent diabetes mellitus. The main finding of our study was the significantly increased responses of total triglycerides and apolipoproteins C-II and C-III from the baseline values in the normal subjects but not in the diabetic group. High-density lipoprotein cholesterol levels at baseline and after glucose loading were significantly lower in diabetic than in normal subjects. As expected, abnormal glucose tolerance and hyperinsulinemia were observed in the diabetic subjects after the glucose loading. The peak glucose and insulin levels and their decline after the glucose loading were delayed in the diabetic patients. The glucose load did not significantly alter total plasma cholesterol, high-density lipoprotein cholesterol, and apolipoprotein A-I and A-II concentrations in normal and diabetic subjects. The apparent blunted response of total triglycerides and apolipoproteins C-II and C-III in the diabetic subjects may be related to maximal stimulation of synthesis of triglycerides and apolipoproteins C-II and C-III by the hyperglycemia and hyperinsulinemia (or both) present in these patients.
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PMID:Acute effects of a glucose load on plasma apolipoproteins A-I, A-II, C-II, and C-III in normal and non-insulin-dependent diabetic men. 642 34

Total plasma cholesterol, triglycerides, VLDL-C, VLDL-TG, HDL-C and the apoproteins A-I, A-II, B and D were measured in 111 male non-obese diabetic patients and in 90 male control subjects of similar age and body weight distribution. Forty-eight patients had Type 1 (insulin-dependent diabetes) and 63 had Type 2 (non-insulin-dependent diabetes); all were in stable metabolic control while following an appropriate diet and therapy with insulin or oral hypoglycemic agents. HDL-C, apoA-I, apoB and the apoA-I/apoA-II ratio were significantly increased in the Type 1 patients, whereas the VLDL-C/VLDL-TG and LDL-C/apoB ratios were decreased significantly. Type 2 diabetics showed low HDL-C and low apoA-I/apoA-II ratio, while the values of apoA-I, A-II, D and the VLDL-C/VLDL-TG ratio were significantly higher than in controls. Type 1 diabetics in 'fair' metabolic control presented higher values of TG, VLDL-C, VLDL-TG and apoB than patients in 'good' control: lower values of apoA-I and of the ratios apoA-I/apoA-II, apoA-I/apoB and LDL-C/apoB were recorded in the same subgroup. In Type 2 diabetics no significant differences were observed according to metabolic control, with the exception of a higher apo-D value in subjects in 'fair' control. The data obtained support the view that good metabolic control may be important for the prevention of a relevant derangement of lipoprotein components, particularly in Type 1 patients.
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PMID:Lipids, lipoproteins and apolipoproteins in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus. 652 91


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