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

Rosiglitazone is a potent oral antidiabetic agent of the thiazolidinedione class that works through activation of the peroxisome proliferator-activated nuclear receptor. It improves insulin sensitivity in peripheral tissues and effectively lowers blood glucose in patients with type 2 diabetes. Metformin is a dimethyl-biguanide, also used in type 2 diabetes, that lowers fasting blood glucose primarily by decreasing hepatic glucose output. Rosiglitazone and metformin reduce plasma glucose concentrations via different mechanisms and thus could potentially be used in combination to optimize glycemic control. This study evaluated the effects of the coadministration of these two agents on the pharmacokinetics of both rosiglitazone and metformin. Sixteen male volunteers (22-55 years old) received oral metformin (500 mg every 12 hours), rosiglitazone (2 mg every 12 hours), or the combination each for 4 days. Plasma collected on day 4 of each regimen was assayed for rosiglitazone and metformin concentrations. Oral doses of rosiglitazone and metformin were safe and well tolerated when administered alone or in combination. There were no clinically significant episodes of hypoglycemia or increased blood lactic acid levels following treatment with any regimen. Coadministration of rosiglitazone and metformin had no significant effects on the steady-state pharmacokinetics (AUC(0-12 h), Cmax, tmax, or t1/2) of either drug. The authors conclude that rosiglitazone can be safely administered with metformin and, due to the different mechanisms of action of these agents, may offer a therapeutic advantage in patients with type 2 diabetes mellitus.
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PMID:Rosiglitazone does not alter the pharmacokinetics of metformin. 1107 14

To examine the mechanism by which metformin lowers endogenous glucose production in type 2 diabetic patients, we studied seven type 2 diabetic subjects, with fasting hyperglycemia (15.5 +/- 1.3 mmol/l), before and after 3 months of metformin treatment. Seven healthy subjects, matched for sex, age, and BMI, served as control subjects. Rates of net hepatic glycogenolysis, estimated by 13C nuclear magnetic resonance spectroscopy, were combined with estimates of contributions to glucose production of gluconeogenesis and glycogenolysis, measured by labeling of blood glucose by 2H from ingested 2H2O. Glucose production was measured using [6,6-2H2]glucose. The rate of glucose production was twice as high in the diabetic subjects as in control subjects (0.70 +/- 0.05 vs. 0.36 +/- 0.03 mmol x m(-2) min(-1), P < 0.0001). Metformin reduced that rate by 24% (to 0.53 +/- 0.03 mmol x m(-2) x min(-1), P = 0.0009) and fasting plasma glucose concentration by 30% (to 10.8 +/- 0.9 mmol/l, P = 0.0002). The rate of gluconeogenesis was three times higher in the diabetic subjects than in the control subjects (0.59 +/- 0.03 vs. 0.18 +/- 0.03 mmol x m(-2) min(-1) and metformin reduced that rate by 36% (to 0.38 +/- 0.03 mmol x m(-2) x min(-1), P = 0.01). By the 2H2O method, there was a twofold increase in rates of gluconeogenesis in diabetic subjects (0.42 +/- 0.04 mmol m(-2) x min(-1), which decreased by 33% after metformin treatment (0.28 +/- 0.03 mmol x m(-2) x min(-1), P = 0.0002). There was no glycogen cycling in the control subjects, but in the diabetic subjects, glycogen cycling contributed to 25% of glucose production and explains the differences between the two methods used. In conclusion, patients with poorly controlled type 2 diabetes have increased rates of endogenous glucose production, which can be attributed to increased rates of gluconeogenesis. Metformin lowered the rate of glucose production in these patients through a reduction in gluconeogenesis.
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PMID:Mechanism by which metformin reduces glucose production in type 2 diabetes. 1111 8

Results from the United Kingdom Prospective Diabetes Study showed that intensive treatment of type 2 (non-insulin-dependent) diabetes mellitus, with sulphonylureas or insulin, significantly reduced microvascular complications but did not have a significant effect on macrovascular complications after 10 years. Insulin resistance plays a key role in type 2 diabetes mellitus and is linked to a cluster of cardiovascular risk factors. Optimal treatment for type 2 diabetes mellitus should aim to improve insulin resistance and the associated cardiovascular risk factors in addition to achieving glycaemic control. Treatment with sulphonylureas or exogenous insulin improves glycaemic control by increasing insulin supplies rather than reducing insulin resistance. Metformin and the recently introduced thiazolidinediones have beneficial effects on reducing insulin resistance as well as providing glycaemic control. There is evidence that, like metformin, thiazolidinediones also improve cardiovascular risk factors such as dyslipidaemia and fibrinolysis. Whether these differences will translate into clinical benefit remains to be seen. The thiazolidinediones rosiglitazone and pioglitazone have been available in the US since 1999 (with pioglitazone also being available in Japan). Both products are now available to physicians in Europe.
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PMID:Antidiabetic drugs present and future: will improving insulin resistance benefit cardiovascular risk in type 2 diabetes mellitus? 1112 20

Although diet and exercise remain the cornerstones of type 2 diabetes therapy, attempts at lifestyle changes seldom result in the achievement of glycaemic control. As a result, the addition of pharmacological agents is usually necessary. Currently available treatment options improve glycaemic control in the short term; however, maintaining long-term glycaemic control, halting disease progression, and preventing the complications of type 2 diabetes have all proven to be elusive therapeutic goals. For more than 30 years, sulphonylureas (SUs) have been first-line therapy for the management of type 2 diabetes. These compounds control hyperglycaemia by stimulating insulin release from pancreatic beta cells, and thus their benefits are limited to patients with preserved beta-cell function. Despite historic reliance on these agents to treat type 2 diabetes, long-term use of SUs may desensitize beta cells. The meglitinides (e.g. repaglinide) are a new class of non-sulphonylurea secretagogues that bind to a different receptor on the beta cell. Repaglinide has a short duration of action and may be useful for the treatment of postprandial hyperglycaemia. The biguanides (e.g. metformin) represent another class of antidiabetic agents and improve glycaemic control primarily by decreasing hepatic glucose output. Metformin and SUs provide similar glucose-lowering effects, and, in combination, may provide additional benefits in some patients. Reducing the rate of glucose absorption with alpha-glucosidase inhibitors (e.g. acarbose) has been explored as an alternative approach to the management of postprandial hyperglycaemia, but these agents do not address the primary defect in type 2 diabetes. Eventually, prolonged overproduction of insulin to compensate for hyperglycaemia leads to dramatically reduced beta-cell function, and exogenous insulin therapy is required.
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PMID:Effects of current therapeutic interventions on insulin resistance. 1122 Feb 86

Nuclear magnetic resonance (NMR) spectroscopy has made noninvasive and repetitive measurements of human hepatic glycogen concentrations possible. Monitoring of liver glycogen in real-time mode has demonstrated that glycogen concentrations decrease linearly and that net hepatic glycogenolysis contributes only about 50 percent to glucose production during the early period of a fast. Following a mixed meal, hepatic glycogen represents approximately 20 percent of the ingested carbohydrates, while only about 10 percent of an intravenous glucose load is retained by the liver as glycogen. During mixed-meal ingestion, poorly controlled type 1 diabetic patients synthesize only about 30 percent of the glycogen stored in livers of nondiabetic humans studied under similar conditions. Reduced net glycogen synthesis can be improved but not normalized by short-term, intensified insulin treatment. A decreased increment in liver glycogen content following meals was also found in patients with maturity-onset diabetes of the young due to glucokinase mutations (MODY-2). In patients with poorly controlled type 2 diabetes, fasting hyperglycemia can be attributed mainly to increased rates of endogenous glucose production, which was found by 13C NMR to be due to increased rates of gluconeogenesis. Metformin treatment improved fasting hyperglycemia in these patients through a reduction in hepatic glucose production, which could be attributed to a decrease in gluconeogenesis. In conclusion, NMR spectroscopy has provided new insights into the pathogenesis of hyperglycemia in type 1, type 2, and MODY diabetes and offers the potential of providing new insights into the mechanism of action of novel antidabetic therapies.
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PMID:Nuclear magnetic resonance studies of hepatic glucose metabolism in humans. 1123 14

Type 2 diabetes mellitus is characterized by insulin deficiency but in particular by insulin resistance. Patients where it is not possible to achieve positive results within 4-12 weeks by optimalization of the lifestyle are candidates for treatment with oral antidiabetics. At present the following main groups of oral antidiabetics are discussed: insulin secretagogues (SU derivatives and methiglinide derivatives), biguanides (Metformin), alpha-glucosidase inhibitors (acarbose, miglitol) and insulin sensitizers (thiazolindiones). Traditional SU therapy improves the insulin plasma levels by releasing insulin from the pancreas. This implies further stress on the b-cells and the function of these cells declines reversibly. Biguanides, such as metformin, are effective substances reducing the blood sugar level, they are however associated with the problem of tolerability and are contraindicated in some diabetics. A new approach to the treatment of type 2 diabetes are thiasolinediones, insulin-sensitizing substances, the molecular basis of their action being via activation of PPAR gamma-nuclear receptors with subsequent change in expression of genes participating in carbohydrate and lipid metabolism.
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PMID:[Current and future aspects of oral antidiabetic agents in type 2 diabetes]. 1139 69

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

Metformin should be regarded as a first-choice therapy of type 2 diabetes, showing an especially good efficacy in obese patients with hyperinsulinaemia. Reduction of blood glucose without hyperinsulinaemia and without hypoglycaemia, favourable influence on the lipid profile and inhibition of coagulation factors lead to an antidiabetic and antiatherogenic effect. Not only are these characteristics relevant to judging the value of the drug, but also the strict observation of contraindications is needed to avoid the dangerous complication of lactic acidosis.
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PMID:Metformin, the rebirth of a biguanide: mechanism of action and place in the prevention and treatment of insulin resistance. 1146 May 76

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

An obese patient, not diabetic, treated with metformin for some weeks, was referred to us with severe inferior digestive hemorrhage, diagnosed with Meckel's diverticulum. Metformin is described as a glucose-lowering agent for treatment of type 2 diabetes mellitus and as antiobesity drug, though results achieved with this last indication are not conclusive. But metformin has fibrinolytic features by means of diminished plasminogen activator inhibitor 1 activity. Although no coagulation study was done and the Meckel's diverticulum is normally associated with bleeding, the particular intensity of the following hemorrhage may have been favored by metformin.
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PMID:Digestive hemorrhage caused by a Meckel's diverticulum in a metformin-treated patient: is there any connection? 1146 78


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