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

Phenformin concentrations were measured in serum from seven patients with phenformin-associated lactic acidosis, and initial values ranging from 20 to 625 ng./ml. were obtained. Five of the seven patients had serum concentrations within the usual therapeutic range of up to 241 ng./ml. Serum phenformin concentrations were measured serially, and apparent half-lives of 5, 25, and 30 hours were obtained in three patients with serum creatinine concentrations of 1.7, 7.6, and 6.0 mg./dl., respectively. Although the half-life of phenformin was prolonged in azotemic patients, no correlation between serum creatinine concentration and serum phenformin could be demonstrated; furthermore, the severity of lactic acidosis as measured by arterial pH and lactate concentration did not correlate with the serum creatinine concentration.
Diabetes 1977 Jul
PMID:Serum phenformin concentrations in patients with phenformin-associated lactic acidosis. 40 57

It is shown that daily oral administration of 5--10 mg of an antidiabetic biguanide-phenformin (phenethyl-biguanide) for 2.5--5 months suppressed DMBA-induced mammary tumour development in rats considerably. Phenformin-treated rats revealed-a tendency towards a decrease in blood insulin level (radioimmunoassay). The obtained data are regarded as additional evidence for the proposed existence of the same metabolic background of diseases of compensation, i.e. adult-onset diabetes, artherosclerosis and cancer, and suggest studies on possible antitumour effect of phenformin in man.
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PMID:Inhibition of DMBA-induced carcinogenesis by phenformin in the mammary gland of rats. 41 48

Eighteen diabetic patients with lactic acidosis (L.A.) were analyzed for possible causal factors, metabolic changes, and efficacy of treatment. An antecedent phenformin therapy was performed in fifteen cases and was associated with renal insufficiency in ten cases and liver disease in eight cases. Tissular anoxia of primary hemodynamic or respiratory origin was absent in all cases. The severe metabolic acidosis (pH m.93 +/- 0,03; HCO3-= 6 +/- 1 MM; PaCO2 = 18 +/- 2 MM. Hg) and hyperlactatemia (14.2 +/- 0.3 mM) were associated with high lactate/pyruvate ration (70 +/- 22). High alanine levels (up to 4.6 mM) were measured in some of these patients. High beta-hydroxybutrate levels were sometimes measured (up to 7.6 mM), and substantial amounts of acetoacetate were also detected in twelve cases. Glucagon level was always increased (1,050 +/- 240 pg./ml.), and insulin/glucagon ratio was low. Cortisol (49 +/- 10 mug./100 ml.) and HGH (10.8 +/- 0.6 ng./ml.) were also elevated. Increased plasma levels of phenformin were measured in five L.A. diabetic subjects (50 +/- 5 mug./ml.) by comparison with other phenformin-treated diabetic subjects. The specificity of the assay was investigated, and phenformin metabolites were characterized by thin-layer chromatography. Por the treatment of L.A., adjunction of dialysis and furosemide improved the efficacy of early and massive sodium bicarbonate infusion. It is suggested that accumulation of phenformin via renal insufficiency plays a determinant role in causing L.A. through an impairment of lactate metabolism in the liver. An accelerated epuration of the drug may be helpful in therapy of L.A. Phenformin treatment should be avoided in case of renal and/or liver insufficiency.
Diabetes 1975 Sep
PMID:Phenformin-induced lactic acidosis in diabetic patients. 80 37

The activity of the succinate dehydrogenase-coenzyme Q10 reductase from 120 diabetic patients was significantly lower (P less than 0.001) and the per cent deficiency was significantly higher (P less than 0.001) than that of the controls. The diabetes of 37 patients was controlled by diet; the enzyme activity was lower (P less than 0.001) and the deficiency was higher (P less than 0.02) than for controls. In decreasing effectiveness, Dymelor, Glyburide, Phenformin and Tolazamide inhibited the COQ10-enzyme, NADH-oxidase. Tolbutamide, Glypizide, and Chlorpropamide were noninhibitory to succinoxidase and NADH-oxidase. Patients receiving Tolazamide and Phenformin showed a higher incidence (P less than 0.001 to P less than 0.05) of COQ10-deficiency than patients controlled by diet or normal controls. Certain diabetic patients controlled by diet may have a deficiency of COQ10 which may be enhanced by the inhibition by certain commonly used antidiabetic drugs of COQ10-enzymes. A deficiency of COQ10 in the pancreas could impair bioenergetics, the generation of ATP, and the biosynthesis of insulin.
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PMID:Bioenergetics in clinical medicine. XI. Studies on coenzyme Q and diabetes mellitus. 107 May 15

A patient with phenformin-associated lactic acidosis was treated with insulin and showed marked improvement coincident with the expected onset of action of the insulin administered. Relative insulin deficiency was demonstrated although several phenomena characteristic of phenformin-associated lactic acidosis obscured its reflection in the usual indices. From data presented and a review of the literature the following pathogenesis is proposed for the observed metabolic derangement. A background of relative insulin deficiency would permit enhanced pyruvate (and hence lactate) formation from protein sources. Insulin deficiency would also lead to inhibition of pyruvate dehydrogenase which slows pyruvate removal. Phenformin accumulation (cf impaired renal function) further reduces pyruvate removal by decreasing its conversion to glucose, but in addition alters the redox state. For the lactic acidosis which results, insulin administration may thus constitute specific therapy. Diabetes 24:28-35, January, 1975.
Diabetes 1975 Jan
PMID:Insulin therapy in phenformin-associated lactic acidosis; a case report, biochemical considerations and review of the literature. 112 May 43

Effects of phenformin on blood sugar, serum triglyceride, thrombin time, euglobulin clot lysis time and cardiovascular complications were studied in maturity onset diabetes and in atherosclerotic patients with or without diabetes, for a period of 14-18 months. Phenformin has shown the characteristic properties of an antifibrinopathic agent in that it prolongs thrombin time and enhances fibrinolysis. The hypoglycaemic effect of phenformin was found to be directly related to its antifibrinopathic action. Plasma lipids fell in all cases. Absence of fresh cardiovascular complications and improvement in anginal symptoms were observed. The metabolic, haematological and clinical benefits of phenformin and its limitations in maturity onset diabetes and atherosclerosis may be explained by the effects of the drug upon the thrombin-fibrinogen reaction. These results lend support to the hypothesis of a primary fibrinopathic pathogenesis in maturity onset diabetes mellitus and atherosclerosis.
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PMID:Antifibrin action of phenformin. 114 44

Under strict balance conditions we studied the effect of phenformin in 5 patients with diabetes mellitus. In all cases phenformin lowered the blood glucose values, and all patients showed a reduction of glycosuria. Contrary to other reports body weight increased during phenformin treatment. This was accompanied by positive nitrogen, phosphorus and calcium balances. The weight gain can be explained by the positive caloric balance, mainly caused by the diminished glycosuria. No change in B.M.R. or R.Q. was seen. During phenformin treatment there was a drop in cholesterol and total lipid levels in 4 patients. No conclusions could be drawn about the effect of phenformin on triglycerides, phospholipids and lipoprotein spectra. Phenformin treatment did not affect the disappearance of glucose, nor the insulin levels after intravenous glucose loading. During oral glucose loading phenformin caused a significant fall in blood glucose levels, accompanied by an increased insulin response in one patient. In the other 4 patients phenformin had no effect on either parameter.
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PMID:The effect of phenformin-HCl on patients with diabetes mellitus, studied under strict balance conditions. 118 70

The main biguanides, metformin and phenformin, were introduced in 1957 as oral glucose-lowering agents to treat non-insulin-dependent diabetes mellitus (NIDDM). Phenformin was withdrawn in many countries because of an association with lactic acidosis, but metformin does not have the same risk if appropriately prescribed. Metformin is now widely used as a monotherapy and in combination with a sulfonylurea. Unlike sulfonylureas, metformin is not bound to plasma proteins, is not metabolized, and is eliminated rapidly by the kidney. The glucose-lowering effect occurs without stimulation of insulin secretion and results mainly from increased glucose utilization. The presence of insulin is required, and enhancement of insulin action at the postreceptor level occurs in peripheral tissues such as muscle. In peripheral tissues metformin increases insulin-mediated glucose uptake and oxidative metabolism. Metformin also increases glucose utilization by the intestine, primarily via nonoxidative metabolism. The extra lactate produced is largely extracted by the liver and serves as a substrate to sustain gluconeogenesis. This limits the extent to which metformin reduces hepatic glucose production but provides a safeguard against excessive glucose lowering. Because metformin does not cause clinical hypoglycemia, it is actually an antihyperglycemic drug. It does not cause weight gain, it helps combat hypertriglyceridemia, and it has been ascribed some vasoprotective properties. Metformin offers a useful treatment for insulin-resistant overweight NIDDM patients.
Diabetes Care 1992 Jun
PMID:Biguanides and NIDDM. 160 Aug 35

Forty-one diabetic patients on insulin were given 100mg. of phenformin daily for six weeks, either before or after a period of six weeks of inert capsules, in a double-blind cross-over trial. Eleven patients while on phenformin noticed hypoglycaemic effects and reduced their insulin on average by almost 20% without resultant rise in blood sugar levels. Twenty-eight patients felt no untoward effects and maintained their usual insulin dose. Phenformin led to improved control of the diabetes, with a significant decrease in blood sugar levels and a significant reduction in the variability of the weekly blood sugar readings. There was no increased ketosis, no change in cholesterol, and no significant loss of weight.
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PMID:Pheniformin in insulin-dependent diabetics. 491 12

Effect of phenformin on [125I]insulin binding with the liver plasma membrane of normal and alloxan diabetic rats was studied in vitro. Diabetic rats showed a decreased binding of [125I]insulin with liver plasma membrane indicating thereby a decreased binding affinity of insulin with its receptors. Phenformin caused an increased binding of [125I]insulin with liver plasma membrane in normal as well as in diabetic rats. Results of this study indicate that the control of diabetes by phenformin is possibly affected by increasing the binding of insulin with plasma membrane receptors which in turn promotes insulin dependent metabolic reactions at the cellular level.
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PMID:Effect of alloxan diabetes and phenformin on insulin binding with liver plasma membrane receptors. 639 35


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