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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin resistance, defined as the inability of insulin to exert a normal biological action at the level of its target tissues, is one of the principal pathogenetic defects of type 2 diabetes. Metformin, the most widely-prescribed insulin-sensitizing agent in current clinical use, improves blood glucose control mainly by improving insulin-mediated suppression of hepatic glucose production, and by enhancing insulin-stimulated glucose disposal in skeletal muscle. Experimental studies show that metformin-mediated improvements in insulin sensitivity may be associated with several mechanisms, including increased insulin receptor tyrosine kinase activity, enhanced glycogen synthesis, and an increase in the recruitment and activity of GLUT4 glucose transporters. In adipose tissue, metformin promotes the re-esterification of free fatty acids and inhibits lipolysis, which may indirectly improve insulin sensitivity through reduced lipotoxicity. The improved glycaemia with metformin is not associated with increased circulating levels of insulin, and the risk of hypoglycaemia with metformin is minimal. The therapeutic profile of metformin supports its use for the control of blood glucose, in diabetic patients and for the prevention of diabetes in subjects with impaired glucose tolerance. Moreover, the improvement by metformin of cardiovascular risk factors associated with the dysmetabolic syndrome may account for the significant improvements in macrovascular outcomes observed in the UK Prospective Diabetes Study.
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PMID:Reducing insulin resistance with metformin: the evidence today. 1450 98

Establishing and maintaining control of glycaemia is a key step in the reduction of diabetic microvascular complications. By contrast, macrovascular disease which is the most important complication and shortens the lives of many people with type 2 diabetes is not reduced by glycaemic control alone. The landmark UK Prospective Diabetes Study (UKPDS) showed that intensive glycaemic management with metformin significantly reduced the risk of a range of debilitating and/or life-threatening macrovascular complications, compared with other oral agents, diet and insulin who achieved similar overall glycaemic control. The benefits observed included diabetes-related mortality (reduced by 42%, compared with diet treatment, p=0.017), all-cause mortality (reduced by 36%, p=0.011), myocardial infarction (reduced by 39%, p=0.01), and any diabetes-related endpoint (reduced by 32%, p=0.002). Other clinical and experimental studies have shown metformin to be associated with improved outcomes and support the conclusions from the UKPDS. In addition, a well-designed retrospective analysis has shown significantly lower mortality rates in patients receiving metformin compared with patients treated with sulphonylurea monotherapy. Metformin provides a greater degree of cardiovascular protection than would be expected from its antihyperglycaemic actions alone and is the first drug of choice for the treatment of type 2 diabetes unless there are contraindications in the individual patient.
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PMID:Improving survival with metformin: the evidence base today. 1450 99

Type 2 diabetes is characterised by insulin resistance in association with clustering of atherothrombotic risk factors (dysglycaemia, hyperinsulinaemia, hypertension, raised triglyceride, low HDL cholesterol and increased levels of plasminogen activator inhibitor-1 (PAI-1) and clotting factor VII). There is a 3-5 fold increase in risk of myocardial infarction rising to 10-20 fold in the presence of microalbuminuria and overall around 70-75% of subjects with type 2 diabetes die of cardiovascular disease. However, classical risk factors which associate with insulin resistance do not account for all the increased burden of vascular disease in diabetic subjects. Metformin is a biguanide compound which is antihyperglycaemic, reduces insulin resistance and has cardioprotective effects on lipids, thrombosis and blood flow. Metformin has a weight neutral/weight lowering effect and reduces hypertriglyceridaemia, elevated levels of PAI-1, factor VII and C-reactive protein. In addition recent studies indicate that metformin has direct effects on fibrin structure/function and stabilises platelets, two important components of arterial thrombus. The United Kingdom Prospective Diabetes Study (UKPDS) reported that metformin was associated with a 32% reduction in any diabetes related endpoint (p<0.002), a 39% reduction in myocardial infarction (p<0.01) and a non-significant 29% fall in microvascular complications. The figures for macrovascular complications compare favourably for those described for other cardioprotective agents such as ACE inhibitors and statins. These findings confirm metformin as first line therapy in the management of obese insulin resistant type 2 diabetes and in the prevention of the vascular complications of this common condition.
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PMID:Beneficial effects of metformin on haemostasis and vascular function in man. 1450

Cardiovascular disease (CVD) is the major determining factor of morbidity and mortality in type 2 diabetic patients. The established relationship between type 2 diabetes and atherosclerosis has fueled suggestions that anti-diabetic drugs with beneficial effects on CV risk factors may help attenuate the atherosclerotic process in diabetic patients. Metformin is a hypoglycaemic agent widely used in the management of type 2 diabetes. In addition to its insulin-sensitising action, this drug has favourable effects on various CV risk factors and reduces macrovascular complications in obese type 2 diabetic patients. This review summarises in vivo and in vitro experimental evidence on the antiatherogenic properties of metformin.
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PMID:Antiatherogenic properties of metformin: the experimental evidence. 1450 3

Several links relate mitochondrial metabolism and type 2 diabetes or chronic hyperglycaemia. Among them, ATP synthesis by oxidative phosphorylation and cellular energy metabolism (ATP/ADP ratio), redox status and reactive oxygen species (ROS) production, membrane potential and substrate transport across the mitochondrial membrane are involved at various steps of the very complex network of glucose metabolism. Recently, the following findings (1) mitochondrial ROS production is central in the signalling pathway of harmful effects of hyperglycaemia, (2) AMPK activation is a major regulator of both glucose and lipid metabolism connected with cellular energy status, (3) hyperglycaemia by inhibiting glucose-6-phosphate dehydrogenase (G6PDH) by a cAMP mechanism plays a crucial role in NADPH/NADP ratio and thus in the pro-oxidant/anti-oxidant cellular status, have deeply changed our view of diabetes and related complications. It has been reported that metformin has many different cellular effects according to the experimental models and/or conditions. However, recent important findings may explain its unique efficacy in the treatment of hyperglycaemia- or insulin-resistance related complications. Metformin is a mild inhibitor of respiratory chain complex 1; it activates AMPK in several models, apparently independently of changes in the AMP-to-ATP ratio; it activates G6PDH in a model of high-fat related insulin resistance; and it has antioxidant properties by a mechanism (s), which is (are) not completely elucidated as yet. Although it is clear that metformin has non-mitochondrial effects, since it affects erythrocyte metabolism, the mitochondrial effects of metformin are probably crucial in explaining the various properties of this drug.
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PMID:Mitochondrial metabolism and type-2 diabetes: a specific target of metformin. 1450 5

The timely series of state-of-the-art reviews contained within this supplement provide a valuable overview of the current state of diabetes care, and the pharmacological interventions we have available. Our experts agree that one of the most important lessons to emerge recently concerns the magnitude of the malign influence on clinical outcomes of the cardiovascular risk factors associated with the dysmetabolic (insulin resistance) syndrome. Metformin is unique in being not only as effective as any other oral antidiabetic therapy in controlling blood glucose, but also having an unparalleled clinical database relating to improved clinical outcomes in pre-diabetic subjects, and patients with established type 2 diabetes.
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PMID:Metformin: drug of choice for the prevention of type 2 diabetes and cardiovascular complications in high-risk subjects. 1450 10

Metformin belongs to a class of drugs known as the biguanides that are widely used in the treatment of type 2 diabetes mellitus. Its association with lactic acidosis is well established, although rare. Metformin-associated lactic acidosis is recognized as a potentially lethal condition that can occur in patients with contraindications to the drug, such as renal dysfunction, liver diseases, alcoholism, and cardiopulmonary diseases. In these cases, the plasma concentration of metformin is not necessarily abnormally high. We describe a 75-year-old diabetic woman with acute renal failure and life-threatening lactic acidosis due to metformin intoxication. Clinical manifestations included vomiting, diarrhea, hypothermia, hypotension and transitory blindness. Her initial renal function was recovered after hemodialysis and she was discharged 3 months after admission.
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PMID:Metformin-associated lactic acidosis and acute renal failure in a type 2 diabetic patient. 1460 17

Polycystic ovary syndrome (PCOS) is a common disorder among reproductive-age women, yet the diagnosis may be overlooked during adolescence. Although the clinical and metabolic features are similar to those found in adult women, it can be difficult to distinguish the young woman with PCOS from a normal adolescent. Irregular menses, anovulatory cycles, and acne are not uncommon in adolescent women. Adolescents with a history of premature pubarche, a family history of PCOS, Caribbean-Hispanic and African-American ancestry, and/or obesity are at risk for PCOS and deserve close surveillance. The laboratory evaluation of the adolescent with suspected PCOS or hyperandrogenism should be individualized based on the history, symptoms, and examination findings. The cornerstone of management of PCOS in adolescence includes either a combination oral contraceptive or progestin. Consideration of insulin-sensitizing agents, antiandrogens, topical treatments for acne, and various treatments for hair removal are dependent on the patient's symptoms and concerns. Healthy eating, regular exercise, and for the overweight adolescent, weight reduction, are encouraged to reduce the risk of cardiovascular disease and type II diabetes mellitus. Numerous studies have shown that weight loss and exercise decrease androgen levels, improve insulin sensitivity, and lead to the resumption of ovulation. Although initial studies suggest that Metformin may be particularly useful for treating the PCOS adolescent with insulin resistance and obesity, additional studies are needed to determine the efficacy and long-term outcome. Management of the adolescent with PCOS is challenging and requires a supportive, multidisciplinary team approach for optimal results.
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PMID:Polycystic ovary syndrome in adolescence. 1464 9

Metformin is a common treatment for women who have insulin resistance manifesting as type 2 diabetes or polycystic ovarian syndrome (PCOS). With an increasing number of these patients conceiving, it is expected that the use of metformin in and around the time of pregnancy will increase. This article reassesses the mechanisms, safety, and clinical experience of metformin use in obstetrics and gynecology. Metformin is an attractive therapeutic option because administration is simple, hypoglycemia rare, and weight loss promoted. There is a large volume of research supporting the use of metformin treatment in diabetes mellitus, androgenization, anovulation, infertility, and recurrent miscarriage. Although metformin is known to cross the placenta, there is, as yet, no evidence of teratogenicity. Metformin has an array of complex actions, accounting for the varied clinical roles, many of which are still to be fully evaluated. Much research is still needed.
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PMID:Metformin in obstetric and gynecologic practice: a review. 1475

A significant proportion of women with polycystic ovary syndrome (PCOS) suffer from insulin resistance and compensatory hyperinsulinemia. Growing evidence indicates that elevated serum insulin induces hyperandrogenism, which in turn leads to anovulation and infertility. Hyperinsulinemia also contributes to the increased risk for cardiovascular disorders and type 2 diabetes mellitus. These concepts provide a rationale for therapies focused on treatments of insulin resistance. Metformin is the most extensively studied insulin-sensitizing agent for the treatment of women with PCOS. Use of metformin leads to a decrease in serum insulin and androgen levels, as well as an improvement in ovulatory function. Other insulin-sensitizing agents studied in women with PCOS include troglitazone, rosiglitazone, pioglitazone, and D-chiro-inositol.
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PMID:Treatment of PCOS with metformin and other insulin-sensitizing agents. 1476 83


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