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

Hyperglycemia may lead to atherosclerosis by different pathogenic mechanisms. Nonenzymatic glycation and oxidation of LDL may increase its atherogenicity. Glycation may modify some arterial wall structural proteins. Increased blood glucose leads to hypertriglyceridemia which results in decrease of HDL-cholesterol level and in increase of atherogenic dense LDL particles. Hyperglycemia also adversely affects processes of platelet aggregation, hemocoagulation and fibrinolysis. It accelerates the development of diabetic nephropathy--a condition with a high prevalence of macrovascular diseases. Prospective epidemiologic studies have shown that diabetic patients in worse metabolic control had an increased cardiovascular morbidity and mortality. Therapeutic randomized studies in type 1 (DCCT) and type 2 (UKPDS) diabetic patients have shown that better diabetes control had a preventive effect against development of microvascular complications. The incidence of macrovascular complications both in type 1 diabetic patients on intensive insulin or sulfonylurea treatment has been decreased on the level of borderline statistical significance. Metformin lead to a significant decrease in myocardial infarction incidence in the subgroup of obese type 2 diabetic patients. In conclusion, maximal possible metabolic control of diabetes prevents the development of microvascular complication, but more impressive decrease in macrovascular disease incidence probably requires to affect another important risk factors for atherosclerosis, such as dyslipidemia and hypertension.
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PMID:[Hyperglycemia and atherosclerosis. Causal relation or association?]. 1095 84

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

In nonobese girls with an adolescent variant of polycystic ovary syndrome, insulin-sensitizing treatment reduces hyperinsulinism, dyslipidemia, and hyperandrogenism and restores eumenorrhea; however, the effect on anovulation is unknown. We assessed whether metformin treatment is capable of inducing ovulation in nonobese adolescents with anovulatory hyperandrogenism after precocious pubarche. The study population consisted of 18 adolescents (mean age, 16 yr; body mass index, 21.4 kg/m2; 3-7 yr beyond menarche) with hyperinsulinemic hyperandrogenism. All girls received metformin for 6 months in a daily dose of 1275 mg. Before inclusion, persistent anovulation was documented by weekly serum progesterone measurements less than 4 ng/ml (months -3 and -1); the ovulation rate was assessed similarly after 2, 4 and 6 months on metformin; a premenstrual progesterone level greater than 8 ng/ml was used as ovulation marker. Regular menses were reported by 16 of 18 girls within 4 months on metformin, and all girls were eumenorrheic after 6 months on metformin. Of the 18 girls, 1 (6%) ovulated after 2 months on metformin, 7 (39%) after 4 months, and 14 (78%) after 6 months; ovulation induction failed in the girls with the lowest birth weight or most severe hyperandrogenism. Metformin treatment was well tolerated. In conclusion, sensitization to insulin was found to be an effective approach to induce ovulation in nonobese adolescents with anovulatory hyperandrogenism.
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PMID:Sensitization to insulin induces ovulation in nonobese adolescents with anovulatory hyperandrogenism. 1150 83

Obesity has been shown to be an independent risk factor for coronary heart disease. The insulin resistance associated with obesity contributes to the development of other cardiovascular risk factors, including dyslipidemia, hypertension, and type 2 diabetes. The coexistence of hypertension and diabetes increases the risk for macrovascular and microvascular complications, thus predisposing patients to cardiac death, congestive heart failure, coronary heart disease, cerebral and peripheral vascular diseases, nephropathy, and retinopathy. Body weight reduction increases insulin sensitivity and improves both blood glucose and blood pressure control. Metformin therapy also improves insulin sensitivity and has been associated with decreases in cardiovascular events in obese diabetic patients. Antihypertensive treatment in diabetics decreases cardiovascular mortality and slows the decline in glomerular function. However, pharmacological treatment should take into account the effects of the antihypertensive agents on insulin sensitivity and lipid profile. Diuretics and beta-blockers are reported to reduce insulin sensitivity and increase triglyceride levels, whereas calcium channel blockers are metabolically neutral and ACE inhibitors increase insulin sensitivity. For the high-risk hypertensive diabetic patients, ACE inhibition has proven to confer additional renal and vascular protection. Because hypertension and glycemic control are very important determinants of cardiovascular outcome in obese diabetic hypertensive patients, weight reduction, physical exercise, and a combination of antihypertensive and insulin sensitizers agents are strongly recommended to achieve target blood pressure and glucose levels.
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PMID:Treatment of obesity hypertension and diabetes syndrome. 1156 61

Adolescent girls born small for gestational age (SGA) are at risk for anovulation, hyperinsulinism, subclinical hyperandrogenism, dyslipidemia, and central adiposity. Hyperinsulinemic insulin resistance has been proposed as a key pathogenetic factor underpinning these associations. We have tested this hypothesis in an intervention study by assessing the effects of insulin sensitization (metformin treatment, 850 mg/d for 3 months) in eumenorrheic, nonobese, anovulatory SGA adolescents [n = 13; mean birth weight, 2.3 kg; age, 15 yr; body mass index (BMI), 20.5 kg/m(2); >or=3 yr post-menarche] who were in a steady state (over approximately 6 months) for BMI, hyperinsulinism, subclinical hyperandrogenism, and dyslipidemia, and who presented a deficit of lean body mass and an excess of (truncal and abdominal) fat mass. Metformin treatment was accompanied by a drop in fasting insulin and serum androgens and by a less atherogenic lipid profile (all P <or= 0.01). After 3 months on metformin, all identified aberrations in body composition were attenuated, the most marked changes (P < 0.0001) being a reduction of the excess in abdominal fat and of the deficit in lean body mass; BMI remained unaltered. Finally, 6 of 13 girls became ovulatory after about 6 wk on metformin, and 9 of 13 (69%) ovulated within 11 wk on metformin. In conclusion, these observations corroborate the notion that anovulation, an excess of abdominal fat mass, and a deficit of lean mass in nonobese SGA adolescents are essentially underpinned by hyperinsulinemic insulin resistance, and that sensitization to insulin is an effective approach to correct these abnormalities and, conceivably, to prevent them.
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PMID:Anovulation in eumenorrheic, nonobese adolescent girls born small for gestational age: insulin sensitization induces ovulation, increases lean body mass, and reduces abdominal fat excess, dyslipidemia, and subclinical hyperandrogenism. 1246 74

The etiology, natural history, and relationship of insulin resistance to type 2 diabetes mellitus and the effects of insulin-sensitizing agents are described. Insulin resistance results from a combination of genetic and environmental factors and contributes to type 2 diabetes mellitus, dyslipidemia, hypertension, central (abdominal) obesity, and cardiovascular disease. Insulin resistance does not necessarily progress to impaired glucose tolerance or diabetes because insulin secretion by normal pancreatic beta cells can increase to compensate for reduced physiological activity. Diabetes may develop in insulin-resistant persons with inherited secretory and glucose-sensing defects in beta cells. The pathogenesis of diabetes appears to involve a progressive decrease in beta-cell mass, potentially triggered by abnormalities in adipocytokine release from intraabdominal fat cells. Metformin and the thiazolidinediones are used to treat insulin resistance, but their actions differ. Metformin reduces free-fatty-acid efflux from fat cells, thereby suppressing hepatic glucose production, and indirectly improves peripheral insulin sensitivity and endothelial function. Thiazolidinediones improve peripheral insulin sensitivity by reducing circulating free fatty acids but also by suppressing adipocytokines, which increase insulin resistance. Thiazolidinediones also improve endothelial function and may prevent or delay the onset of diabetes. Insulin is intrinsically antiatherogenic but may mediate arterial inflammation in insulin-resistant patients. Unlike metformin, the thiazolidinediones suppress this inflammatory pathway and may indirectly help preserve beta-cell function. Insulin resistance, resulting from a combination of genetic and environmental factors, plays a central role in type 2 diabetes mellitus. Diabetes may develop in insulin-resistant persons with inherited secretory and glucose-sensing defects in beta cells. Metformin and thiazolidinediones are insulin-sensitizing agents with different mechanisms of action and effects in patients with type 2 diabetes mellitus.
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PMID:Insulin resistance, diabetes, and the adipocyte. 1248 80

The therapeutic goals in patients with type 2 diabetes mellitus and the mechanisms of insulin resistance and secretion are discussed. Sulfonylureas improve glycemic control, restore the acute insulin response, and help improve beta-cell function in the short term. Meglitinides and phenylalanine derivatives and alpha-glucosidase inhibitors may be useful for elderly patients and others with normal fasting blood glucose levels and postprandial hyperglycemia, but they are less effective in achieving goal HbA1c levels in patients with marked fasting hyperglycemia. Metformin and thiazolidinediones act on hepatic, muscle, and adipose tissue through different mechanisms to improve glycemic control, beta-cell function, and the lipid profile. Thiazolidinediones have a greater impact on free fatty acids than metformin. They may have an additive effect with sulfonylureas, metformin, or insulin in improving glycemic control and the lipid profile. Many patients require combination therapy with one or more insulin sensitizers and an insulin secretagogue to achieve therapeutic goals. Insulin therapy should be initiated in patients in whom an HbA1c level less than 7.0% cannot be maintained with other therapies. This is vital in preventing diabetes complications. Insulin sensitizers should be continued during insulin therapy to reduce insulin resistance and treat the insulin resistance syndrome. Therapeutic goals for patients with type 2 diabetes mellitus include improvement in glycemic control and prevention of diabetes complications. Elevated levels of fasting blood glucose should be addressed before postprandial levels to reduce HbA1c levels and glucotoxicity to the beta cell. Dyslipidemia, hypertension, and hypercoagulability should be treated to minimize the increased cardiovascular risk seen in people with diabetes, which is responsible for the majority of deaths.
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PMID:Treating dual defects in diabetes: insulin resistance and insulin secretion. 1248 81

Polycystic ovary syndrome (PCOS) is a frequent disease, characterized by disturbed ovarian function with hyperandrogenism. Anovulation is secondary to an absence of follicular dominance. Apart from a primary ovarian defect, insulin resistance is observed in PCOS women, even in the absence of overweight. This insulin resistance could be secondary to a defect in the insulin transduction pathway, mainly by a defect in receptor phosphorylation. It enhances hyperandrogenism as it increases ovarian androgen production. Therefore treating insulin resistance by weight loss or drugs reducing insulin resistance might improve fertility of PCOS women. Metformin has been shown to reduce ovarian production, enhance ovulatory cycles and in some cases increase fertility. However, there are few randomized studies on large numbers of patients to prove an effect on pregnancies as well as on the occurrence of early pregnancy loss. There are currently no recommendation on dose and duration of metformin treatment. It is noteworthy that metformin has no authorization in France to be prescribed apart from diabetic patients' care. Considering the medical care of PCOS women, the cardiovascular risk needs to be taken into account. Therefore hypertension, dyslipidemia and diabetes must be treated in those women who need to be followed carefully all over their life.
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PMID:[Insulin resistance and polycystic ovary syndrome]. 1271 82

A number of metabolic disorders, including hypercholesterolemia, hypertriglyceridemia, insulin resistance, elevated fasting glucose and diabetes mellitus, were reported in a high proportion of HIV-infected patients receiving highly active antiretroviral therapy (HAART). Less frequently, coagulative disorders were described in patients receiving HAART. Since all these metabolic disorders may predispose to coronary heart disease, an early evaluation and treatment is advisable. Existing guidelines for uninfected patients may be applied, taking into account, however, the potential for drug interactions and accumulated toxicity. It may be helpful to stratify all patients in three risk groups to plan regular diagnostic screening. Treatment of dyslipidemia and diabetes mellitus should include a first-line approach with non-pharmacological interventions. Statins and fibrates are proposed for HIV-infected patients with HAART-related hyperlipidemia, but concern has been raised on their potential for interaction with antiretrovirals and hepatic and muscle toxicity. Metformin and thiazolidenediones (or glitazones), hypoglycemic agents that increase insulin sensitivity, are presently under evaluation in diabetic and glucose-intolerant HIV-infected patients treated with HAART. Glitazones also have a potential for ameliorating the lipodystrophic syndrome. The routine evaluation of coagulative parameters is probably not advisable until a benefit of widespread screening is assessed in prospective studies. A heightened awareness of the possiblity of coagulative disorders, together with controlled trials and basic research, is needed.
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PMID:Evaluation and management of metabolic and coagulative disorders in HIV-infected patients receiving highly active antiretroviral therapy. 1287 May 43

Patients with diabetes have a greatly increased relative risk of developing cardiovascular disease when compared with patients without diabetes. Much of this risk is related to insulin resistance and is associated with both traditional and nontraditional cardiovascular risk factors. Therapy for diabetes must address these risk factors in an attempt to prevent and adequately treat cardiovascular disease. Pharmacologic therapy directed toward dyslipidemia and hypertension has a beneficial effect on risk factors and has been shown to decrease cardiovascular events. The effects of insulin and oral hypoglycemic agents on insulin resistance are variable, and their direct effect on cardiovascular disease is less clear. Metformin is the only oral hypoglycemic agent shown to decrease cardiovascular events independent of glycemia. The thiazolidinediones directly improve insulin resistance, decrease plasma insulin concentration, and have the potential to decrease the risk of cardiovascular disease in patients with diabetes. A number of studies have demonstrated that the thiazolidinediones produce changes in several cardiovascular risk factors associated with the insulin resistance syndrome, including lowering blood pressure, correcting diabetic dyslipidemia, improving fibrinolysis, and decreasing carotid artery intima-medial thickness. These agents bind a newly described class of receptors, peroxisome proliferator-activated receptors, which may have implications for atherosclerosis. Although these drugs increase low-density lipoprotein (LDL) cholesterol, they induce a favorable change in the LDL particle size and susceptibility to oxidation. Long-term clinical trials are being conducted to determine the effect that thiazolidinediones have on cardiovascular events in individuals with type 2 diabetes.
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PMID:Management of diabetes mellitus and insulin resistance in patients with cardiovascular disease. 1295 27


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