Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0242339 (dyslipidemia)
13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is clearly recognized that patients with NIDDM have an increased risk for CHD. Recent data indicate that persons with glucose concentrations in the nondiabetic range also may be at higher risk for CHD. These associations may not represent cause and effect, however. Emerging data suggest that hyperglycemia and CHD may both arise from hyperinsulinemia/insulin resistance. In support of this hypothesis are studies showing that NIDDM and CHD have many risk factors in common, including age, elevated blood pressure, dyslipidemia, adiposity, and a central pattern of fat distribution. Moreover, these risk factors are frequent concomitants of hyperinsulinemia, itself a risk factor for CHD and perhaps for NIDDM. Although the duration of NIDDM has been infrequently related to risk of CHD, the authors hypothesize that duration of hyperinsulinemia/insulin resistance would be a more sensitive marker for risk of CHD. The relation of IDDM to CHD is a different situation. The etiological process leading to IDDM, namely the destruction of beta-cells in genetically predisposed persons, is not related to cardiovascular risk. However, IDDM patients still have an excess of CVD, the risk factors for which may vary according to the location of the diseases (e.g., LEAD vs. CHD). There is a strong relationship between proteinuria and CVD, which has led to a general theory of vascular complications in IDDM based on defective heparan sulfate metabolism (Steno hypothesis). Recent evidence challenges parts of this hypothesis, and the possibility is raised that a higher case-fatality rate in a subgroup of patients with both renal and CVD explains part of the renal connection, as does the general worsening of CVD risk factors.
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PMID:Diabetes mellitus and macrovascular complications. An epidemiological perspective. 139 12

Low-density lipoprotein apheresis (LDL-apheresis) was done with either cascade filtration (DF) or dextran sulfate cellulose adsorption (DSC) in a patient with primary biliary cirrhosis who developed severe dyslipidemia associated with cholestasis and accumulation of lipoprotein-X (LP-X). The extracorporeal treatment was initially performed weekly, and resulted in a sharp drop in total cholesterol from 1038 to 430 mg/dl. During the next four months the patient was treated every 10-15 days, and pre-apheresis cholesterol levels were maintained between 438 and 505 mg/dl, until an orthotopic liver transplantation was successfully performed. With semi-selective DF a mean 47.1% of total cholesterol was removed per procedure compared to 30.0% with DSC, although the volume of treated plasma was 38.0 vs 49.9 ml/kg body weight. The changes in plasma cholesterol levels during DSC and DF showed that the kinetics of cholesterol removal were similar with both techniques, but the efficacy differed; DF removed both LDL and LP-X from plasma, whereas DSC selectively lowered the LDL content. Cascade filtration may therefore be considered as a first-choice treatment for patients with LP-X accumulation due to cholestasis.
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PMID:Impaired efficacy of selective LDL-apheresis in primary biliary cirrhosis. 206 Sep 91

According to the authors' clinical analysis, about half of the patients who suffer from arteriosclerotic obstruction (ASO) in the lower extremity(-ies) with clinical manifestation are dyslipidemic (total cholesterol > or = 220 mg/dL or LDL cholesterol > or = 140 mg/dL). As suggested by clinical success in regression of ASO in the coronary arteries as a result of aggressive removal of LDL, LDL adsorption utilizing an extracorporeal circulation technique with a dextran sulfate/cellulose adsorbent column was applied in 33 patients (22 men and 11 women) with ASO. Clinical results obtained after a series of 10 LDL adsorption procedures as a standard showed encouraging success. Improvement in subjective symptoms was achieved as follows: 88.5% for cold lower extremity, 87.1% for intermittent claudication, 53.8% for leg/toe pain at rest, and 60% for disappearance/size diminution of ulcer/necrosis. Improvements in objective examination findings supported subjective ones: 85.7% by plethysmography, 81% by thermography and 70% by ankle pressure index. No serious complications or untoward effects were observed during or after the adsorption procedures. In conclusion, LDL adsorption appears to be a useful and safe tool in treatment of ASO patients with dyslipidemia.
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PMID:Treatment of arteriosclerotic obstruction by LDL adsorption. 844 32

Hypertension is often accompanied by a host of metabolic defects. Investigations have shown an association between insulin resistance, hyperinsulinemia, central/visceral obesity, and hypertension. Recent interest has focused on the fact that untreated hypertensive individuals have compensatory hyperinsulinemia, are resistant to insulin-mediated glucose uptake, and frequently have coexisting lipid abnormalities. Data from prospective studies appear to indicate that fasting hyperinsulinemia is an independent predictor of coronary artery disease. Additionally, there is evidence that hyperinsulinemia and diabetes eliminate the normal sex differences in the prevalence of coronary artery disease. The salutary effects of ovarian hormones on the prevalence of hypertension and cardiovascular disease in postmenopausal women are well established. Hyperandrogenism, in particular elevated serum levels of dehydroepiandrosterone sulfate, is believed to be a risk factor promoting sex-specific impairments of glucose and lipid metabolism, obesity, and hypertension in women. Clinical and epidemiologic evidence have linked elevated blood pressure to disturbances in lipoprotein metabolism, fibrinolytic activity, plasminogen activation inhibitor levels, and dyslipidemia. This review briefly presents the current understanding of various metabolic disturbances associated with hypertension, the pathophysiologic mechanisms involved, and the significance of the interplay between them relative to the complications of this disease.
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PMID:Metabolic abnormalities in hypertension. 926 63

Functional ovarian hyperandrogenism, a variant of polycystic ovary syndrome, is often associated with hyperinsulinism and dyslipidemia. The mechanisms interlinking this triad are poorly understood; both hyperandrogenism and hyperinsulinism have been proposed as factors involved in the pathogenesis of the dyslipidemia. Precocious pubarche (PP) in girls is a risk factor for subsequent anovulation, ovarian and adrenal hyperandrogenism, hyperinsulinism and dyslipidemia. Flutamide, a nonsteroidal antiandrogen, is known to be effective in reducing hirsutism in patients with ovarian hyperandrogenism. However, the effects of flutamide on the endocrine-metabolic correlates of hyperandrogenism are uncertain. We assessed the effects of low dose flutamide treatment (250 mg daily for 18 months) on hormonal and metabolic variables in 18 nonobese adolescent girls (age, 16.8 +/- 0.3 yr) with functional ovarian hyperandrogenism (diagnosis by GnRH agonist test) after PP. Flutamide treatment was accompanied by a marked decrease in the hirsutism score, free androgen index, and testosterone, androstenedione, and dehydroepiandrosterone levels and by an increase in sex hormone-binding globulin concentrations. However, there were no substantial changes in the pattern of menstrual cycles, gonadotropin, estradiol, or dehydroepiandrosterone sulfate concentrations, and there was no detectable effect on the 17-hydroxyprogesterone response to GnRH agonist. Serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels decreased markedly during flutamide therapy, whereas high-density lipoprotein cholesterol, fasting glycemia/insulinemia, and the insulin response to a glucose load remained unchanged. Flutamide was well tolerated. In conclusion, low dose flutamide treatment was found to be an effective and safe approach to reduce hirsutism and circulating androgen, low-density lipoprotein cholesterol, and triglyceride levels in girls with functional ovarian hyperandrogenism after PP. However, flutamide failed to increase high-density lipoprotein cholesterol levels or decrease hyperinsulinemia, i.e. to affect two major risk factors for subsequent cardiovascular disease.
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PMID:Treatment of hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism in nonobese, adolescent girls: effect of flutamide. 1099 17

Precocious pubarche in girls is often preceded by low weight at birth and followed by hirsutism, ovarian hyperandrogenism, and oligomenorrhea in adolescence, the latter usually being accompanied by dyslipidemia and hyperinsulinism, which are, in turn, two major risk factors for cardiovascular disease in later life. We hypothesized that insulin resistance may be a key pathogenetic factor in this sequence. We tested the hypothesis by assessing the effects of an insulin-sensitizing agent, metformin, given at a daily dose of 1275 mg for 6 months to 10 nonobese adolescent girls (mean age, 16.8 yr; body mass index, 21.9 kg/m2; birth weight, 2.7 kg) with hirsutism, ovarian hyperandrogenism (diagnosis by GnRH agonist test), oligomenorrhea, dyslipidemia, and hyperinsulinemia after precocious pubarche. Before the metformin trial, longitudinal studies in these girls had shown that hyperinsulinism was present at prepubertal diagnosis of precocious pubarche, and that it increased markedly in late puberty or early postmenarche. Metformin treatment was well tolerated and was accompanied by a marked drop in hirsutism score, insulin response to oral glucose tolerance test, free androgen index, and baseline testosterone, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate levels (all P < 0.01). During metformin treatment, the LH and 17-hydroxyprogesterone hyperresponses to GnRH agonist were attenuated (P < 0.01); serum triglyceride, total cholesterol, and low density lipoprotein cholesterol levels decreased; and high density lipoprotein cholesterol rose. All girls reported regular menses within 4 months. Withdrawal of metformin treatment was followed, within 3 months, by a consistent reversal toward pretreatment conditions. In conclusion, metformin treatment reduced hyperinsulinemia, hirsutism, and hyperandrogenism; attenuated the LH and 17-hydroxyprogesterone hyperresponses to GnRH agonist; improved the atherogenic lipid profile; and restored eumenorrhea in nonobese adolescent girls with a history of precocious pubarche. These observations corroborate the idea that insulin resistance may indeed be a prime factor underpinning the sequence from reduced fetal growth, through precocious pubarche, to adolescent endocrinopathies that are reminiscent of so-called polycystic ovary syndrome.
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PMID:Sensitization to insulin in adolescent girls to normalize hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism after precocious pubarche. 1106 94

Insulin resistance and type 2 diabetes are associated with elevated circulating levels of insulin, nonesterified fatty acids (NEFAs), and lipoprotein remnants. Extracellular matrix proteoglycan (PG) alterations are also common in macro- and microvascular complications of type 2 diabetes. In liver, extracellular heparan sulfate (HS) PGs contribute to the uptake of triglyceride-rich lipoprotein remnants. We found that HepG2 cells cultured with 10 or 50 nmol/l insulin or 300 micromol/l albumin-bound linoleic acid changed their PG secretion. The glycosaminoglycans (GAGs) of the secreted PGs from insulin-treated HepG2 cells were enriched in chondroitin sulfate (CS) PGs. In contrast, cells exposed to linoleic acid secreted PGs with decreased content of CS. Insulin caused a moderate increase in mRNA for versican (secreted CS PG), whereas linoleic acid markedly decreased mRNA for versican in HepG2 cells, as did the peroxisomal proliferator-activated receptor-alpha agonist bezafibrate. The effects of insulin or linoleic acid on syndecan 1, a cell surface HS PG, were similar to those on versican, but less pronounced. The livers of obese Zucker fa/fa rats, which are insulin-resistant and have high levels of insulin, NEFAs, and triglyceride-rich remnants, showed increased expression of CS PGs when compared with lean littermates. These changes in PG composition decreased the affinity of remnant beta-VLDL particles to PGs isolated from insulin-treated HepG2 cells and obese rat livers. The results indicated that insulin and NEFAs modulate the expression of PGs in hepatic cells. We speculate that in vivo this exchange of CS for HS may reduce the clearance of remnant beta-VLDLs and contribute to the dyslipidemia of insulin resistance.
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PMID:Changes in matrix proteoglycans induced by insulin and fatty acids in hepatic cells may contribute to dyslipidemia of insulin resistance. 1152 80

Patients with hypopituitarism have increased cardiovascular mortality. A high prevalence of conventional cardiovascular risk factors, including obesity, central fat distribution, insulin resistance, and dyslipidemia, have been described in these patients. The inflammatory markers C-reactive protein (CRP) and IL-6 are predictors of cardiovascular events, and high levels of CRP have been reported in men with hypopituitarism and GH deficiency. However, little is known about inflammatory cardiovascular risk markers in women with hypopituitarism. We therefore investigated whether inflammatory and traditional cardiovascular risk markers are elevated in women with hypopituitarism. Fifty-three women with hypopituitarism and 111 healthy control women were included in this cross-sectional study. Morning blood samples were drawn after an overnight fast. Serum was assayed for CRP, IL-6, glucose, insulin, IGF-I, triglycerides, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein (HDL) cholesterol, lipoprotein(a), E2, total testosterone (total T) and free testosterone (free T), and dehydroepiandrosterone sulfate. IL-6 and CRP levels were higher in women with hypopituitarism than in healthy controls (P < 0.0001 for comparison between groups). In a multivariate model, CRP levels depended on hypopituitarism, body mass index (BMI), and estrogen use. There was an interaction between the effect of BMI and hypopituitarism on CRP levels, such that the importance of hypopituitarism in determining CRP levels disappeared at high BMIs. In a similar multivariate model, IL-6 levels depended on hypopituitarism and BMI. Total cholesterol, the total to HDL cholesterol ratio, and triglycerides were higher in hypopituitary patients, but only triglycerides and the total to HDL cholesterol ratio depended on hypopituitarism when controlling for BMI. There was no significant difference in lipoprotein(a) levels between hypopituitary women and control subjects. However, when controlling for estrogen use, lipoprotein(a) levels showed a trend toward being lower in the hypopituitary group (P = 0.075). In patients with hypopituitarism, CRP correlated negatively with IGF-I (r = -0.35; P = 0.010), total T (r = -0.42; P = 0.0020), and free T (r = -0.30; P = 0.031). Similarly, IL-6 correlated negatively with total T (r = -0.39; P = 0.0040) and androstenedione (r = -0.27; P = 0.048) in hypopituitary patients. In conclusion, hypopituitary women have increased levels of IL-6 and CRP, both of which are inflammatory markers of atherosclerosis. GH deficiency and androgen deficiency may contribute to these findings. Chronic inflammation may contribute to the high cardiovascular risk seen in this population.
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PMID:Inflammatory cardiovascular risk markers in women with hypopituitarism. 1210 75

The endocrine-metabolic hallmarks of polycystic ovary syndrome are hyperinsulinism, hyperandrogenism, dyslipidemia, and anovulation. We hypothesized that dyslipidemia and anovulation in nonobese women with polycystic ovary syndrome are essentially secondary to the concerted effects of hyperandrogenism and insulin resistance. We tested this hypothesis by comparing the efficacy of anti-androgen (flutamide) or insulin-sensitizing (metformin) monotherapy to that of combined therapy in normalizing the endocrine-metabolic and anovulatory status of nonobese, young women with hyperinsulinemic hyperandrogenism. Thirty-one young women (mean age, 18.7 yr; body mass index, 21.9 kg/m(2); hirsutism score, 16; monthly ovulation rate monitored by weekly serum progesterone, 10%) were randomly assigned to receive once daily flutamide (250 mg; n = 10), metformin (1275 mg; n = 8), or combined flutamide- metformin therapy (n = 13) for 9 months. At baseline, there were no endocrine-metabolic differences among treatment groups. Compared with monotherapy, combined flutamide-metformin therapy resulted in greater improvements in insulin sensitivity, in testosterone, androstenedione, dehydroepiandrosterone sulfate, and triglyceride levels, and in low-density lipoprotein/high-density lipoprotein-cholesterol ratio (all P < 0.005). Monthly ovulation rates increased after 9 months to 75 and 92%, respectively, with metformin alone or with combined therapy, but were unimproved with flutamide alone. All treatments were well tolerated. In conclusion, combined anti-androgen and insulin-sensitizing treatment in young, nonobese women with hyperinsulinemic hyperandrogenism had additive benefits on insulin sensitivity, hyperandrogenemia, and dyslipidemia. The data from this small study suggest that dyslipidemia is secondary to excess androgen action in concert with the hyperinsulinemia associated with insulin resistance. In contrast, anovulation seems to be mainly attributable to insulin resistance and hyperinsulinemia.
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PMID:Additive effects of insulin-sensitizing and anti-androgen treatment in young, nonobese women with hyperinsulinism, hyperandrogenism, dyslipidemia, and anovulation. 1205 Feb 66

Hyperandrogenemia and low levels of sex hormone binding globulin (SHBG) are frequently found in women with metabolic syndrome, which is characterized by low high-density lipoprotein cholesterol, hypertriglyceridemia, obesity, and hyperinsulinemia. The specific contribution of these various factors to coronary heart disease (CHD) is controversial. The coronary angiograms of 87 consecutive postmenopausal women were evaluated using 2 semiquantitative scoring systems to estimate the extent of focal and diffuse vessel wall alterations. Fasting sera were analyzed for levels of glucose, lipids, insulin, leptin, dehydroepiandrosterone sulfate, testosterone, and SHBG. Obesity was assessed by measuring body mass index, waist-to-hip ratio, skinfold thicknesses, and body impedance. After adjusting for age, there were significant differences in 55 women with CHD compared with 32 women without CHD: higher levels of low-density lipoprotein cholesterol (159 +/- 51 vs 132 +/- 39 mg/dl), apolipoprotein B (121 +/- 33 vs 102 +/- 29 mg/dl), triglycerides (115 vs 91 mg/dl), and basal insulin (7.5 vs 4.6 mU/L), as well as lower levels of high-density lipoprotein cholesterol (59.9 +/- 18.0 vs 69.0 +/- 17.1 mg/dl), SHBG (44.6 vs 68.1 nmol/L) and the quantitative insulin sensitivity check index (0.66 +/- 0.41 vs 0.93 +/- 0.73). Multivariate analysis by logistic regression identified age (odds ratio [OR] 1.22, 95% confidence intervals [CI] 1.09 to 1.37), smoking (OR 11.46, 95% CI 2.56 to 51.39), SHBG (OR 0.98, 95% CI 0.96 to 0.99), and apolipoprotein B (OR 1.02, 95% CI 1.01 to 1.04) as independently associated with the presence of CHD. Thus, low plasma levels of SHBG are associated with CHD in women independently of insulin, obesity markers, and dyslipidemia.
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PMID:Relation of serum levels of sex hormone binding globulin to coronary heart disease in postmenopausal women. 1216 Dec 23


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