Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether metformin or troglitazone can delay the onset of diabetes in the Zucker diabetic fatty (ZDF) rat, lean control, fatty, and ZDF rats received metformin, troglitazone, or no treatment from 6 to 12 wk of age. Glucose, insulin, triglyceride (TG), and free fatty acid (FFA) levels and glucose stimulated insulin secretion by the perfused pancreas were measured. Metformin-treated rats gained significantly less weight. Both drugs prevented hyperglycemia by 12 wk in diabetic rats and significantly reduced TG and FFA levels. Insulin secretion at low glucose was elevated in untreated fatty and diabetic animals, and the increment in diabetic animals produced by glucose perfusion was attenuated compared with lean and fatty rats. Both drugs reduced basal insulin secretion in fatty and diabetic rats and improved glucose responsiveness in diabetic rats. Metformin and troglitazone delay the onset of diabetes in the ZDF rat. The significantly improved insulin secretory response of the pancreas undoubtedly contributes to the improved glucose tolerance.
 ...
PMID:Prevention of hyperglycemia in the Zucker diabetic fatty rat by treatment with metformin or troglitazone. 889 63

Since impaired glucose tolerance (IGT) is a major risk factor for non-insulin-dependent diabetes mellitus (NIDDM), some kinds of intervention aiming to prevent or to delay the onset of NIDDM in subjects with IGT might be considered. Besides life style modification, drug therapy which could correct insulin deficiency and insulin resistance, might prevent progression to NIDDM. One agent is an alpha-glucosidase inhibitor, which delays the absorption of glucose from the intestine. The resulting decrease in postprandial hyperglycemia and hyperinsulinemia could theoretically decrease insulin resistance in IGT subjects and, it is hoped, prevent or delay progression to NIDDM. Metformin, an antihyperglycemic drug of the biguanide class, may be effective in subjects with IGT by reducing hepatic glucose output, enhancing insulin sensitivity, or through other mechanisms such as weight loss. New insulin sensitizers, such as troglitazone and pioglitazone, improve insulin-mediated glucose disposal by enhancing tissue sensitivity to the actions of insulin and reversing the insulin resistance, characteristic of NIDDM. Sulfonylureas might be another candidates of drug intervention to IGT whose insulin secretory abilities are markedly reduced. As far as the question, "Can NIDDM be prevented or delayed?" is concerned, a prospective study using life style modification or above-mentioned drugs, should be performed on long-term basis.
 ...
PMID:[Drug therapy in subjects with impaired glucose tolerance]. 891 39

Metformin is a biguanide that has been shown to effectively lower plasma glucose levels in subjects with noninsulin-dependent diabetes mellitus (NIDDM). However, its mechanism of action remains unknown. Studies that have examined the effect of metformin on hepatic glucose production (HGP) and muscle glucose utilization in NIDDM have yielded conflicting results, and little information is available about the action of metformin on lactate turnover and gluconeogenesis from lactate in humans. We studied 20 NIDDM subjects and 8 nondiabetic controls in a randomized, double blind, placebo-controlled trial to determine the effect of 15 weeks of treatment with metformin or placebo on glucose and lactate metabolism. Before and after treatment, all participants received a 7-h infusion of [6-3H]glucose and [3-14C]lactate in combination with indirect calorimetry and estimation of lactate central vein specific activity. A euglycemic insulin clamp (20 mU/m2.min) was performed during the last 3 h of the tracer infusions. The study design allowed us to evaluate the effects of metformin vs. placebo treatment on glycemic control, plasma lipid profile, HGP, insulin-mediated glucose uptake, oxidative and nonoxidative glucose metabolism, and lactate turnover. Metformin treatment significantly reduced fasting plasma glucose (196 +/- 18 vs. 152 +/- 12 mg/dL; P < 0.01), hemoglobin A1 (12.5 +/- 0.6 vs. 9.2 +/- 0.3%; P < 0.01), and plasma triglyceride and low density lipoprotein cholesterol concentrations. When diabetics were compared to nondiabetic controls, basal HGP was higher (12.9 +/- 1.0 vs. 9.8 +/- 1.2 mumol/kg.min; P < 0.01) despite the presence of fasting hyperinsulinemia and insulin-mediated total body glucose disposal (10.9 +/- 0.9 vs. 20.2 +/- 3.3 mumol/kg.min; P < 0.01) was decreased. Metformin significantly reduced fasting HGP (from 12.9 +/- 0.7 to 11.0 +/- 0.5 mumol/kg.min; P < 0.01), but did not enhance total body glucose disposal during insulin stimulation (10.9 +/- 0.9 vs. 11.0 +/- 0.5 mumol/kg.min; P = NS). Neither oxidative nor nonoxidative glucose disposal was improved by metformin treatment. The fasting plasma lactate concentration (1.1 +/- 0.1 vs. 0.6 +/- 0.1 mmol/L) and lactate turnover (14.0 +/- 0.8 vs. 10.3 +/- 0.6 mumol/kg.min) were significantly increased in diabetics and strongly correlated (r = 0.68; P < 0.001). The percent gluconeogenesis derived from lactate was similar in diabetic and control subjects (17 +/- 2% vs. 15 +/- 2%; P = NS), but the estimated rate of gluconeogenesis from lactate was increased in the diabetic group (P < 0.01). Despite the significant reduction in HGP after metformin treatment, the percentage of gluconeogenesis from lactate and the rate of lactate-derived gluconeogenesis were unchanged from baseline. Basal lactate turnover (15.4 +/- 1.4 vs. 14.8 +/- 1.4 mumol/kg.min) and lactate oxidation (7.9 +/- 0.7 vs. 8.1 +/- 0.9 mumol/ kg.min) as well as total lactate turnover and lactate oxidation during the insulin clamp were similar before and after metformin treatment. There were no changes in any of the above metabolic parameters in the placebo-treated group. In poorly controlled NIDDM subjects, the primary mechanism by which metformin improves glycemic control is related to the suppression of accelerated basal HGP, and this most likely is secondary to an inhibition of hepatic glycogenolysis. Metformin has no effect on the rate of lactate turnover or gluconeogenesis from lactate in either the basal or insulin-stimulated states.
 ...
PMID:Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitus. 892 61

The authors investigated the lactic acid levels in the blood of 57 type 2 diabetics treated with metformin. The mean lactate level before onset of metformin treatment was in the whole group 2.01 +/- 0.36 mmol/l and after 6 months of metformin administration it remained unchanged 2.00 +/- 0.42 mmol/l. Compensation of diabetes evaluated by HbAlc improved significantly (9.74 +/- 1.62% before treatment, and 8.52 +/- 1.36% after 6 months of treatment). The mean cholesterol levels declined significantly and the mean triacylglycerol levels were after two months of metformin administration significantly lower. Metformin treatment did not lead to an increase of the patients body weight.
 ...
PMID:[The effect of metformin on lactate levels in type II diabetes]. 901 21

Noninsulin-dependent diabetes mellitus has historically been treated with diet therapy alone or the addition of an oral hypoglycemic agent such as a sulfonylurea, or the two in combination with insulin. Although these medical interventions lower blood glucose concentrations, they may also potentiate hyperinsulinism through increased serum insulin concentrations. Insulin resistance and hyperinsulinism are associated with cardiovascular risk factors such as hypertriglyceridemia, decreased high-density lipoprotein cholesterol levels, hypertension, and hyperglycemia, among others. Therefore, a desirable therapeutic alternative would lower blood glucose, not result in hyperinsulinism, and have beneficial effects on lipid profiles. Metformin is a biguanide antihyperglycemic agent that provides these effects. When administered to carefully selected patients and monitored appropriately metformin may prove to be valuable in the treatment of diabetes mellitus and in altering its cardiovascular sequelae.
 ...
PMID:Metformin, a promising oral antihyperglycemic for the treatment of noninsulin-dependent diabetes mellitus. 901 66

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of metformin hydrochloride are reviewed. Metformin is an antihyperglycemic agent; it lowers the blood glucose concentration without causing hypoglycemia. Proposed mechanisms of action include decreased intestinal absorption of glucose, increased glucose uptake from the blood into the tissues, decreased glucose production in the liver, and decreased insulin requirements for glucose disposal. Metformin is slowly absorbed from the small intestine and does not undergo hepatic metabolism. The half-life is about five hours. The major route of elimination is renal; the drug is contraindicated in patients with impaired renal function. In double-blind, placebo-controlled trials, metformin has shown efficacy in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). The drug is as effective as sulfonylureas in patients with diabetes who are nonobese or obese and whose diabetes is uncontrolled by diet alone. Metformin may be useful as addon therapy in obese patients with diabetes uncontrolled by sulfonylureas and diet. Lipid profiles may be favorably influenced. The most common adverse effects are gastrointestinal. A rare but potentially fatal adverse effect is lactic acidosis. Metformin has the potential to interact with cationic drugs eliminated by the renal tubular pathway. The usual effective dosage is 1.5-2.5 g/day orally in two or three divided doses. Metformin hydrochloride is an effective alternative to sulfonylureas in obese and non-obese patients with NIDDM in whom diet alone has not achieved glycemic control, and it may be useful as addon therapy in patients whose diabetes has not responded adequately to sulfonylureas plus dietary measures.
 ...
PMID:Metformin hydrochloride: an antihyperglycemic agent. 911 21

Non-insulin-dependent diabetes mellitus is a metabolic disease that is common and is characterized by insulin insufficiency and resistance. Measures such as body weight reduction and exercise improve the metabolic defects, but pharmacological therapy is the most frequently used and successful therapy. The sulphonylureas stimulate insulin secretion. Metformin and troglitazone increase disposal and decrease hepatic glucose output without causing hypoglycemia. Acarbose is a dietary aid that spreads the dietary carbohydrate challenge to endogenous insulin over time. These pharmacological agents, either alone or in combination, can improve blood glucose regulation in patients with non-insulin-dependent diabetes mellitus.
 ...
PMID:Pharmacological regulation of blood glucose levels in non-insulin-dependent diabetes mellitus. 912 43

In insulin-dependent (type 1) diabetes mellitus, increasing peripheral insulin sensitivity might be a useful approach in controlling the process leading to beta cell destruction by reducing insulin output and thereby reducing the antigenicity associated with its release. The aim of this study was to investigate whether the use of a biguanide, Metformin, which has been suggested to increase insulin sensitivity, was capable of modifying the natural history of diabetes in a model of type 1 diabetes, the non-obese diabetic (NOD) mouse. Using age-, sex- and litter-matched groups, three groups of 32 animals each were treated with Metformin in their drinking water at a high dose of 200 mg/kg body weight and at a low dose of 20 mg/kg body weight; the third group of mice acted as controls. Diabetes incidence at 30 weeks of age was similar in all groups. No significant differences in the calculated index of insulitis were observed in treated or control animals. We conclude that Metformin does not affect the disease process leading to clinical diabetes in this animal model.
 ...
PMID:Metformin does not alter diabetes incidence in the NOD mouse. 923 Mar 45

The Diabetes Prevention Program is a new, 150 million dollar, NIH-sponsored study designed to determine whether non-insulin-dependent diabetes mellitus can be prevented or delayed in persons with impaired glucose tolerance. Four thousand subjects will be randomly assigned to one of four study groups and followed for 4.5 years. Study groups include intensive lifestyle intervention with diet and exercise; metformin (Glucophage) or troglitazone (an investigational drug) with standard diet and exercise; and a control group. Insulin resistance is an important pathogenic factor in impaired glucose tolerance. Trivalent chromium, a dietary supplement that potentiates the action of insulin, was not included in the program. Like metformin and troglitazone, trivalent chromium decreases insulin resistance and has an acceptable side-effect profile; furthermore, it is available at a fraction of their cost. Trivalent chromium should have been included in the Diabetes Prevention Program; it is unfortunate that it was omitted.
 ...
PMID:Trivalent chromium and the diabetes prevention program. 924 7

Impaired glycemic control in type II diabetes results from peripheral insulin resistance, hepatic insulin resistance, and a relative failure of beta cell function. Nutritional and pharmaceutical measures are now available for addressing each of these defects, presumably enabling a rational and highly effective clinical management of non-insulin-dependent diabetes mellitus. Peripheral insulin resistance, which usually responds to a very-low-fat diet, aerobic exercise training, and appropriate weight loss, can also treated with high-dose chromium picolinate, high-dose vitamin E, magnesium, soluble fiber, and possibly taurine; these measures appear likely to correct the diabetes-associated metabolic derangements of vascular smooth muscle, and thus lessen risk for macrovascular disease. Metformin's clinical efficacy is primarily reflective of reduced hepatic glucose output; this action should complement the benefits of peripheral insulin sensitizers. When these measures are not sufficient for optimal control, beta cell function can be boosted with second-generation sulfonylureas.
 ...
PMID:Exploiting complementary therapeutic strategies for the treatment of type II diabetes and prevention of its complications. 927 26


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>