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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two main classes of oral hypoglycaemic drugs, the sulphonylureas and the biguanides, are currently used in the therapy of type II, non-insulin-dependent diabetes mellitus (NIDDM). The basic pharmacokinetic properties of these agents are discussed with a view to efficient and safe treatment. Both first- and second-generation sulphonylureas are rapidly absorbed from the gastrointestinal tract. In the plasma compartment, these drugs are strongly bound to serum proteins. All sulphonylureas are metabolised in the liver, and the metabolites and the parent drugs are eliminated mainly in the urine, but also (second-generation derivatives) in the faces. Rapid- and short-acting sulphonylureas may improve early insulin release and promote better postprandial glucose control. Long-acting derivatives may ensure better control of overnight glycaemia. The elderly are at risk of developing severe sulphonylurea-induced hypoglycaemia, and in this population the agent chosen should have a short or intermediate duration of action and no active metabolites. Caution is needed when prescribing any sulphonylurea in patients receiving drugs known to affect sulphonylurea action, and in those with impaired liver and/or kidney function. The bioavailability of the biguanides ranges from 40 to 60%. Binding to plasma proteins is absent or very low. Metformin and buformin are not metabolised and are excreted in the urine; phenformin undergoes hepatic hydroxylation and is excreted in both urine and faeces. Metformin is the only agent of this class currently recommended for clinical use. The main indications of metformin treatment are NIDDM associated with obesity and/or hyperlipidaemia, and in combination with sulphonylurea both as primary treatment and when secondary failure occurs with sulphonylurea alone. Lactic acidosis may develop in patients receiving therapy with biguanides, especially in the presence of a preexisting contraindication to their use.
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PMID:Pharmacokinetic optimisation of oral hypoglycaemic therapy. 176 Sep 2

Nineteen obese patients with Type 2 diabetes mellitus were treated for periods of 3 months with placebo, guar gum (5 g three times daily) and metformin (500 mg three times daily) in a randomized double-blind, double-placebo, cross-over study. Both active agents decreased fasting blood glucose from 11.4 +/- 3.7 mmol l-1 (mean +/- SD) to 8.6 +/- 2.8 mmol l-1 on metformin (p less than 0.001) and to 9.5 +/- 3.9 mmol l-1 on guar gum (p less than 0.01). Metformin significantly reduced the very low density lipoprotein (VLDL) cholesterol concentration from 0.62 (+0.73, -0.34) mmol l-1 (geometric mean (+SD, -SD)) to 0.43 (+0.58, -0.25) mmol l-1, (p less than 0.02), but unless hyperlipidaemia was present there were no changes in other serum lipid or lipoprotein levels. In patients with serum cholesterol greater than 6.5 mmol l-1 decreases in serum triglycerides from 3.29 (+3.27, -1.64) to 2.46 (+2.55, -1.25) mmol l-1 (p less than 0.02) occurred with metformin. In these patients guar gum produced a reduction in serum cholesterol (from 7.70 +/- 0.90 to 6.41 +/- 1.11 mmol l-1, p less than 0.01) due to an effect on low density lipoproteins. These differential effects may be important in planning therapy when hyperlipidaemia accompanies Type 2 diabetes.
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PMID:Placebo-controlled trial of the effects of guar gum and metformin on fasting blood glucose and serum lipids in obese, type 2 diabetic patients. 215 10

Metformin, an antidiabetic biguanide derivative, prevents experimental atherosclerosis and induces structural changes in lipoproteins in experimental animals. In the present study we investigated the effect of metformin on serum lipoproteins and platelet function in 24 non-diabetic patients with type II B hyperlipidemia. The patients were randomly given metformin in two dosage levels (1.0 g/day and 2.0 g/day) and placebo for periods of nine weeks in a crossover trial. Metformin caused a dose dependent fall in the concentrations of total serum cholesterol and of LDL-cholesterol. The average concentration of total cholesterol was 8.54 +/- 0.22 (SE) mmol/l, 8.12 +/- 0.19 mmol/l and 7.79 +/- 0.15 mmol/l during placebo, metformin 1.0 g/day and 2.0 g/day treatments, respectively. Both metformin values differed significantly (P less than 0.05) from the placebo value. Thus there was an average fall of 8.1% in total cholesterol after the higher metformin dose. LDL-cholesterol was 5.25 +/- 0.23 mmol/l after placebo, falling by 3.1% and 9.6% after metformin doses of 1.0 g/day and 2.0 g/day, respectively. The concentrations of HDL-cholesterol and total serum triglycerides showed no significant changes. Body weight, blood glucose, plasma insulin, blood lactate, platelet function and urinary excretion of prostanoids remained unchanged during the study. The reduction of total- and LDL-cholesterol levels may be a welcome additional consequence of metformin during treatment of diabetic patients with hypercholesterolemia.
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PMID:Cholesterol lowering effect of metformin in combined hyperlipidemia: placebo controlled double blind trial. 229 38

Type 2 diabetes mellitus results from impaired insulin secretion and reduced peripheral insulin sensitivity. Treatment options include diet, oral antihyperglycemic agents, and insulin. Metformin, an oral biguanide, ameliorates hyperglycemia by improving peripheral sensitivity to insulin, and reducing gastrointestinal glucose absorption and hepatic glucose production. Unlike sulfonylureas, it does not stimulate insulin secretion, aggravate hyperinsulinemia, or cause hypoglycemia or weight gain (weight stabilizes or decreases). It also has beneficial effects on serum lipid profiles. In lean or overweight type 2 diabetic patients uncontrolled by diet, metformin monotherapy significantly improves glycemic control, compared with placebo, and to similar extents as sulfonylurea monotherapy. In secondary sulfonylurea failure, combination metformin-sulfonylurea treatment significantly improves glycemic control beyond that achieved with either agent along. Metformin-sulfonylurea also appears to be as effective as insulin or insulin plus sulfonylurea, suggesting that such combination therapy may obviate or substantially delay insulin therapy. Limited data suggest that metformin-insulin therapy may improve glycemic control, possibly reducing insulin requirements, in type 2 diabetic patients uncontrolled by insulin alone following secondary sulfonylurea failure. Gastrointestinal side effects are common, but usually tolerated. Lactic acidosis risk is minimal, provided that contraindications, particularly renal impairment, and prescribing guidelines are respected. Aside from elevated plasma metformin levels with cimetidine and synergistic hypoglycemia with sulfonylureas, few interactions occur. Thus, metformin is safe and effective both as monotherapy or in combination with other antihyperglycemic agents in type 2 diabetic patients requiring additional glycemic control and may be advantageous when weight control is desirable and/or hyperlipidemia exists.
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PMID:An overview of metformin in the treatment of type 2 diabetes mellitus. 920 6

1. Insulin resistance is an early and major feature in the development of non-insulin-dependent diabetes mellitus (NIDDM), but it is also associated with hyperlipidaemia, hypertension, obesity and cardiovascular disease, the so-called 'insulin-resistance syndrome' (Syndrome X). 2. There is a strong genetic determination of NIDDM and insulin resistance, but the environmental factors of calorie excess, reduced activity and obesity also make a major contribution. 3. Central (abdominal) obesity is much more strongly associated with insulin resistance than is overall obesity. From twin studies, there appears to be specific genetic determinants of central abdominal fat, independent of overall obesity. 4. Calorie restriction and weight loss improve insulin sensitivity in overweight humans. Isocaloric alteration of macronutrients substantially affects insulin sensitivity in rats but not, at least in the short-term, in humans. 5. Exercise training improves insulin sensitivity via increased oxidative enzymes, glucose transporters (GLUT4) and capillarity in muscle as well as by reducing abdominal fat. 6. Metformin has been the only available drug that has been used clinically to significantly improve insulin sensitivity, but the new 'glitazones' (thiazolidinediones) have a more specific effect via altered lipid metabolism.
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PMID:Pathogenesis of the insulin resistance syndrome (syndrome X). 931 89

Cardiovascular disease (CVD) risk associated with fat redistribution seen among HIV-infected individuals remains unknown, but may be increased due to hyperlipidemia, hyperinsulinemia, increased visceral adiposity, and a prothrombotic state associated with these metabolic abnormalities. In this study we characterized plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (tPA) antigen levels, markers of fibrinolysis and increased CVD risk, in HIV lipodystrophic patients compared to controls. Furthermore, we investigated the effect of treatment with metformin on PAI-1 and tPA antigen levels in patients with HIV-associated fat redistribution. Eighty-six patients (age 43 +/- 1 yr, BMI 26.1 +/- 0.5 kg/m(2)) with HIV and fat redistribution were compared to 258 age- and BMI-matched subjects from the Framingham Offspring study. In addition, 25 HIV-infected patients with fat redistribution and fasting insulin >15 microU/mL [104 pmol/L] or impaired glucose tolerance, but without diabetes mellitus were enrolled in a placebo-controlled treatment study of metformin 500 mg twice daily. PAI-1 and tPA antigen levels were significantly increased in patients with HIV related fat redistribution compared to Framingham control subjects (46.1 +/- 4 vs 18.9 +/- 0.9 microg/L PAI-1, 16.6 +/- 0.8 vs. 8.0 +/- 0.3 microg/L tPA, P = 0.0001). Among patients with HIV infection, a multivariate regression analysis including age, sex, waist-to-hip ratio, BMI, smoking status, protease inhibitor use and insulin area under the curve (AUC), found gender and insulin AUC were significant predictors of tPA antigen. Twelve weeks of metformin treatment resulted in decreased tPA antigen levels (-1.9 +/- 1.4 vs +1.4 +/- 1.0 microg/L in the placebo-treated group P = 0.02). Similarly, metformin resulted in improvement in PAI-1 levels (-8.7 +/- 2.3 vs +1.7 +/- 2.9 microg/L, P = 0.03). Change in insulin AUC correlated significantly with change in tPA antigen (r = 0.43, P = 0.03). PAI-1 and tPA antigen, markers of impaired fibrinolysis and increased CVD risk, are increased in association with hyperinsulinemia in patients with HIV and fat redistribution. Metformin reduces PAI-1 and tPA antigen concentrations in these patients and may ultimately improve associated CVD risk.
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PMID:Increased PAI-1 and tPA antigen levels are reduced with metformin therapy in HIV-infected patients with fat redistribution and insulin resistance. 1115 71

Polycystic ovary syndrome (PCOS) is classically characterised by ovarian dysfunction (oligomenorrhoea, anovulation and infertility), androgen excess (hirsutism and acne), obesity, and morphological abnormalities of the ovaries (cystic enlargement and stromal expansion). More recently, insulin resistance has been found to be common in PCOS, along with an increased prevalence of other features of the "metabolic syndrome", namely glucose intolerance, type 2 diabetes mellitus, and hyperlipidaemia. Hyperinsulinaemia is likely to contribute to the disordered ovarian function and androgen excess of PCOS. Reducing insulin resistance by lifestyle modifications such as diet and exercise improves endocrine and menstrual function in PCOS. These lifestyle modifications are the best initial means of improving insulin resistance. Metformin, an oral hypoglycaemic agent that increases insulin sensitivity, has been shown to reduce serum concentrations of insulin and androgens, to reduce hirsutism, and to improve ovulation rates. The effect of metformin alone on fertility rates is unknown. Some studies suggest that metformin will reduce total body weight to a small extent, but with a predominant effect on visceral adipose reduction. The effects of metformin on lipid abnormalities, hypertension or premature vascular disease are unknown, but the relative safety, moderate cost, and efficacy in reducing insulin resistance suggest that metformin may prove to be of benefit in combating these components of the "metabolic" syndrome in PCOS. Further properly planned randomised controlled trials are required.
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PMID:Metformin and intervention in polycystic ovary syndrome. Endocrine Society of Australia, the Australian Diabetes Society and the Australian Paediatric Endocrine Group. 1145 23

In this review we present the agents that are in use in the treatment of type 2 diabetes. Sulfonylureas of the 1st and 2nd generation increase insulin secretion but can induce hyperinsulinemia and sometimes prolonged hypoglycemia. Glimepiride is a new 3rd generation sulfonylurea with some advantages over the other members of this group, such as a lower risk of hypoglycemia, no interaction with cardiovascular KATP-channels and a possibility that it may increase insulin sensitivity. There are also newer insulin secretagogues (such as neteglinide and repaglinide) with a rapid onset of action on the beta-cell, therefore inducing a more physiological profile of insulin secretion during meals. The category of insulin sensitizers includes metformin and thiazolidinediones. Metformin effectively reduces hyperglycemia, hyperlipidemia and macroangiopathy in patients with type 2 diabetes. This agent increases the sensitivity of the liver and peripheral tissues to insulin and, therefore, it could be considered as a drug of choice for the prevention of type 2 diabetes. Thiazolidinediones (rosiglitazone and pioglitazone) increase the sensitivity of the tissues to insulin. This mechanism of action makes them powerful therapeutic tools for the treatment of type 2 diabetes (and possibly other insulin resistant states) either alone or in combination with other oral agents. The category of agents that interfere with the absorption of glucose and lipids includes alpha-glucosidase inhibitors (acarbose and miglitol) and lipase inhibitors (or-listat). alpha-Glucocidase inhibitors improve the time relationship between plasma insulin and glucose increases after a meal. Therefore, these agents may be used in the treatment of patients with type 2 diabetes, either alone at a very early stage of this disease (when insulin secretion is still adequate), or in combination with insulin secretagogues. alpha-Glucosidase inhibition may also prove useful as a supplement to insulin therapy in patients with type 1 diabetes mellitus. The inhibitor of gastrointestinal lipase orlistat may prove a useful adjunct to hypocaloric diets in patients with type 2 diabetes and obesity.
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PMID:Oral hypoglycemic agents: insulin secretagogues, alpha-glucosidase inhibitors and insulin sensitizers. 1146 May 77

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

Type 2 diabetes is a serious, costly, and increasingly common disease. Several conditions commonly seen in family medicine settings confer increased risk of developing diabetes. Among these conditions are impaired glucose tolerance, impaired fasting glucose, obesity, gestational diabetes, hypertension, hyperlipidemia, and menopause. We here present the results of a systematic review of the literature examining the evidence for different strategies aimed at preventing type 2 diabetes in patients with these conditions. The strongest evidence supports an intensive lifestyle intervention designed to induce modest weight loss. The greatest degree of prevention, based on lesser quality evidence, may be imparted by bariatric surgery. Metformin and troglitazone have appreciable evidence in specific populations, and orlistat and acarbose have slightly less evidence among obese patients, for preventing diabetes. Ramipril, captopril, losartan, pravastatin, and estrogens show some very preliminary promise for preventing diabetes in patients treated for hypertension, hyperlipidemia, and menopause, but each needs a more rigorous evaluation. Although more questions remain to be answered, family physicians now have tools available to help our patients lead lives free of diabetes.
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PMID:Preventing type 2 diabetes mellitus. 1570 62


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