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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral antidiabetic agents continue to play an important role in the treatment of type 2 diabetes. Of decisive importance is the timing of their use, together with a knowledge of their specific properties. Acarbose, which needs to be initiated at a low, slowly increasing dose, is noted for the fact that it has virtually no systemic side effects. Metformin reduces plasma glucose levels without inducing hyperinsulinemia, and carries virtually no risk of lactic acidosis. Glibenclamide can be used either alone to treat type 2 diabetes or in combination with other oral antidiabetics or insulin. Today, intensified insulin therapy represents the optimal standard of insulin replacement. It permits meal-oriented injection of normal insulin and the use of longer-acting insulin overnight. This form of treatment is now facilitated by the possibilities of plasma glucose selfmonitoring and the use of injection aids (pen). Intensified treatment should be initiated at the time type I diabetes is diagnosed. In the case of a particularly instable metabolic situation or neuropathy, it may become necessary to use insulin pumps.
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PMID:[Management of diabetes in general practice--current requirements. 2: Oral antidiabetics and insulin therapy]. 820 Jun 2

Metformin, an agent used in treatment of non-insulin-dependent diabetes mellitus, is believed to act by potentiating the effects of insulin on glucose metabolism. This study was designed to determine whether metformin affects the actions of insulin on ovarian steroidogenic capability. Rat thecal-interstitial (T-I) and granulosa (G) cells were cultured in chemically defined media for 144 h with or without gonadotrophins [luteinizing hormone (LH) at 100 ng/ml or follicle stimulating hormone (FSH) at 100 ng/ml], insulin (1 microgram/ml) and/or metformin (1 and 5 micrograms/ml). Production of testosterone and progesterone by T-I cells, and 17 beta-oestradiol and progesterone by G cells were assessed. Insulin potentiated LH-dependent stimulation of testosterone production by T-I cells and FSH-dependent stimulation of 17 beta-oestradiol production by G cells, but did not significantly affect progesterone production by T-I cells or G cells in the presence or absence of gonadotrophins. Metformin did not affect any of the actions of insulin on steroidogenesis. These results suggest that insulin may modulate ovarian steroidogenesis via a pathway separate from that modulating glucose metabolism. Actions of insulin on steroidogenesis are selective with regard to stimulation of specific aspects of steroidogenesis and do not simply amplify gonadotrophin effects.
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PMID:Insulin actions on ovarian steroidogenesis are not modulated by metformin. 840 16

Metformin (dimethylbiguanide) has been used for more than 30 years as an antihyperglycemic agent in the treatment of diabetes mellitus, but its effect on gluconeogenesis is still controversial. In isolated hepatocytes from fasted rats, a significant inhibition of glucose production from lactate/pyruvate (10:1, mol/mol), fructose, alanine or glutamine, following metformin addition, is observed. Moreover, in hepatocytes perifused with dihydroxyacetone as the gluconeogenic substrate and treated with 0.5 mM metformin, an inhibition of the glucose flux and a simultaneous stimulation of the lactate/pyruvate flux were observed. This enhancement of lactate/pyruvate formation appears to be due to an effect on the pyruvate-kinase enzyme. A direct effect of metformin on pyruvate kinase cannot explain this result, since pyruvate-kinase activity was not affected by metformin at this concentration. In contrast, the addition of metformin caused a significant decrease in the cellular ATP concentration, a known allosteric inhibitor of this enzyme. This could explain the stimulation of pyruvate-kinase activity following metformin addition and thus the inhibition of gluconeogenesis.
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PMID:Metformin decreases gluconeogenesis by enhancing the pyruvate kinase flux in isolated rat hepatocytes. 850 25

NIDDM is the result of concomitant defects in both insulin secretion and insulin action. Although plasma insulin concentration in NIDDM patients may be normal or even increased as compared to normal individuals, insulin secretion is always impaired when related to ambient hyperglycemia. Moreover, the loss of first-phase insulin secretion is always present and it occurs at the very early stage of the disease. The defect in the early release of insulin may have quite an impact in post-prandial glucose homeostasis, due to inadequate suppression of hepatic glucose production. Therefore, insulin releasers should be able; 1. to increase total insulin secretory capacity, and 2. to restore physiologic profile of insulin secretion. However, this is rarely achieved with the current therapeutical tools. Sulfonylureas may exert some suppressive action on the liver and may maintain a portal-peripheral venous insulin gradient. Metformin may improve insulin sensitivity but has no effect on the beta-cell. Exogenous insulin exerts an inhibitory effect on hepatic glucose production but it does not maintain the physiologic gradient, neither can it mimic first-phase insulin secretion. Therefore, more appropriate tools must be sought. Prompt stimulation of insulin secretion can be elicited by alpha 2-adrenoreceptor antagonists, but their clinical use is still under evaluation. New sulfonylureas are under development, though some of them may exert a better peripheral action than more potent stimulation of the beta-cell. Special interest has been focused on incretin peptides. Infusion of glucagon-like peptide 1 (GLP-1) in NIDDM patients improves glucose tolerance through enhancement of acute release of insulin, suppression of glucagon secretion, and improvement of peripheral glucose utilization.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res Clin Pract 1995 Aug
PMID:What therapy do our NIDDM patients need? Insulin releasers. 852 9

Metformin is an effective agent in the oral treatment of non-insulin-dependent diabetes mellitus and does not cause hypoglycemia like the sulfonylureas. This drug is safe provided the cautions and contraindications are followed and the patient is monitored for hepatic and renal function. Metformin is used extensively outside the United States in the treatment of type II diabetes and recently was approved by the FDA for marketing under the brand name of Glucophage.
Diabetes Educ
PMID:Metformin: a biguanide. 893 23

Several new oral drugs have been approved for the management of type II diabetes. Metformin is an "antihyperglycemic agent" that decreases hepatic glucose production and improves insulin sensitivity. It may be used as monotherapy or in combination with a sulfonylurea. Acarbose slows carbohydrate absorption after a meal, giving endogenous or injected insulin more time to respond to ingested glucose. Glimepiride is an insulin-sparing sulfonylurea with a once-daily dosing schedule. How might these medications fit into the primary care of older diabetics?
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PMID:Type II diabetes: how to use the new oral medications. Interview by David B. Jack. 862 76

The effects of renal impairment and age on the pharmacokinetics of metformin were evaluated. The subjects, including 6 young, 12 elderly, and 3 middle-age healthy adults and 15 adults with various degrees of chronic renal impairment (CRI) each were given a single, 850-mg metformin HCl tablet. Multiple whole blood, plasma, and urine samples were collected and analyzed for metformin levels using a high-performance liquid chromatography (HPLC) method. In healthy elderly individuals, the plasma and whole blood clearance/absolute bioavailability values [CL/F and (CL/F)b], and corresponding renal clearance values (CLR and CLR,b) of metformin were 35-40% lower than the respective values in healthy young individuals. These two groups did not differ significantly with respect to volume of distribution (Vd), time to peak concentration (tmax), and parameters related to metformin's appearance in the urine. In the moderate and severe CRI groups, all clearance values were 74-78% lower than in the healthy young/middle-age group, and all other evaluable pharmacokinetic parameters (with the exception of tmax) differed significantly in this group. In the mild CRI group, clearance values of metformin, which were 23-33% lower than in the young/middle-age group, were the only parameters that differed significantly. Based on a regression analysis of the combined data, both creatinine clearance (CL*cr; corrected for body surface area) and age are predictors of metformin clearance, with the following model best fitting the data: CL/F [or (CL/F)b, CLR, CLR,b] = alpha + beta.CL*cr + gamma.CL*cr.age. Metformin should not be used in patients with moderate and severe CRI, or in patients with mild, but not absolutely stable, renal impairment. The initial and maximum doses in elderly patients and patients with stable mild CRI should be lowered to approximately one third that given to the general (i.e., patients without non-insulin-dependent diabetes) population.
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PMID:Kidney function and age are both predictors of pharmacokinetics of metformin. 862 83

Metformin is a biguanide that can used alone or in combination with sulfonylureas or insulin in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). Since biguanides do not increase pancreatic insulin secretion, they are referred to as antihyperglycemic agents, as opposed to hypoglycemic agents. Biguanides reduce hyperglycemia by increasing, insulin sensitivity, decreasing glucose absorption, and inhibiting hepatic gluconeogenesis. Advantages of metformin include achieving glycemic control without exacerbating weight gain or hyperinsulinemia and beneficially affecting serum cholesterol concentrations. Although metformin has the potential to cause lactic acidosis, the incidence is significantly lower compared with phenformin. Risk factors for lactic acidosis include renal serum creatinine > 1.5 mg/dL and cardiovascular, pulmonary, and hepatic disease. Metformin should be temporarily discontinued prior to surgery and before administration of radiologic intravenous contrast, and in patients with sepsis, severe gastrointestinal disease, trauma, and acute cardiovascular events.
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PMID:Metformin: a new treatment option for non-insulin-dependent diabetes mellitus. 865 73

Recently there has been growing interest in magnesium deficiency and its correlation with coronary artery disease, chronic complications of diabetes mellitus and antioxidant enzyme activity. Hypomagnesemia is a common association of diabetes mellitus, and the blood glutathione (GSH) level is significantly lower in both conditions. Metformin (Met), 'an oral antihyperglycemic drug' frequently used in the management of diabetes mellitus outside the USA, has been shown to have an insulin-like action. The purpose of this study was to investigate the effect of oral administration of Met (60 mg kg(-1)) for 14 days on GSH and magnesium levels in blood, liver and heart of normal and streptozotocin-induced diabetic Wistar rats. Diabetes was induced by an i.p. injection of streptozotocin (60 mg kg(-1)). Our results showed that Met did not affect fasting serum glucose concentration in non-diabetic animals but reduced it significantly in diabetic animals. Serum and liver magnesium levels were significantly decreased in the untreated diabetic group compared with the normal group. Treatment with Met improved liver magnesium concentration in the diabetic group only. It has no effect on serum magnesium in diabetic or non-diabetic rats. Heart magnesium levels showed non-significant changes in all groups. In diabetic animals a significant decrease of GSH in both blood and liver was observed. Treatment with Met increased these levels significantly, with a similar effect on GSH levels in non-diabetic rats. There were no significant changes in heart GSH levels in any of the groups. This study demonstrates that oral Met therapy improves the altered levels of magnesium and GSH in diabetic rats.
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PMID:Effect of metformin on glutathione and magnesium in normal and streptozotocin-induced diabetic rats. 866 22

We assessed the effect of adding low doses of metformin to sulfonylurea therapy in 76 elderly Type 2 diabetic patients by monitoring glycaemic control and blood lactate for one year. Metformin markedly improved glycaemic control. Fasting lactate concentrations were not affected and post-meal lactate peaks were minimally increased. Additional benefits included an improvement in some lipid parameters, a reduction in serum uric acid and a significant weight loss in overweight patients. Metformin was clinically well-tolerated. Instead of advanced age alone, renal function and/or any other age-related factor likely to contribute to lactate overproduction should be the basis for deciding on metformin therapy. No evidence indicated that metformin should be denied "a priori" to ageing Type 2 diabetic patients.
Diabetes Metab 1996 Feb
PMID:Is metformin safe enough for ageing type 2 diabetic patients? 869 95


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