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

Epinephrine raises plasma lactate concentrations when infused intravenously in normal subjects. We studied a patient with non-insulin-dependent diabetes mellitus who developed lactic acidosis and marked insulin resistance when treated with epinephrine after open heart surgery.
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PMID:Lactic acidosis and insulin resistance associated with epinephrine administration in a patient with non-insulin-dependent diabetes mellitus. 363 50

Dichloroacetate (DCA) reduces blood glucose, lactate and lipids in diabetes or during fasting. Chronic use of DCA, however, is limited by toxicity, probably due in part to its rapid conversion to oxalate in vivo. In theory, therefore, DCA's efficacy may be retained and its toxicity minimized by controlling its rate of metabolism. We attempted to alter DCA pharmacokinetics and bioavailability by synthesizing various derivatives comprising DCA esters with polyols and DCA ionic complexes. Twenty-four hour fasted, nondiabetic rats received single, orogastric doses of saline (control) sodium DCA (100mg/kg) or the following derivatives (D1-4): the esters D1-D3: potassium tetra (dichloroacetyl) glucuronate (D1), inositol-monophosphate-tetradichloroacetate (D2), inositol-hexadichloroacetate (D3) and inositol-hexa [N-methylnicotinate] hexadichloroacetate salt (D4). Each derivative was administered at a dose that would ultimately provide 100 mg/kg DCA as the anion. All derivatives were orally effective in significantly decreasing blood glucose and lactate. D4 exerted the most potent and long-lasting glucose- and lactate-lowering effects, yet increased plasma DCA concentrations less than an equivalent dose of the sodium salt. When administered to reverse light-cycled rats, D4 markedly inhibited the incorporation of tritiated water into cholesterol and triglycerides. We conclude that derivatives of DCA retain the biological activity of the parent compound, but may exhibit different pharmacokinetics. They may eventually prove useful in the treatment of diabetes mellitus, hyperlipidemia and lactic acidosis in man.
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PMID:Dichloroacetate derivatives. Metabolic effects and pharmacodynamics in normal rats. 366 16

Dichloroacetate (DCA) is known to prevent the phosphorylation of the pyruvate dehydrogenase complex (PDHC) by blocking the action of PDH kinase. This action allows the active PDHC to exert its effect on the metabolism of glucose, lactate and alanine to acetyl CoA. DCA has been shown to reduce serum lactate levels in humans and animals in such conditions as diabetes, phenformin-induced hepatic failure, exercise, and endotoxin-induced shock. Lactic acidosis in the brain has often been postulated as a cause of neuronal damage following ischemia and hypoxia. Therefore, we examined the effect of intravenously administered DCA (100 mg/kg) in rats that were rendered hyperglycemic by intravenous glucose (2 g/kg), and then made to undergo 15 minutes of incomplete cerebral ischemia by bilateral carotid ligation and systemic hypotension (mean arterial pressure of 50 mm Hg). DCA significantly reduced serum lactate levels pre-ischemia, but had no effect on serum lactate levels after ischemia induction. Brain levels of lactate, ATP and PCr after 15 minutes of incomplete ischemia were unaffected by DCA. We conclude that in this in-vivo model the control of PDHC activity in the brain may be different than that in the periphery, and that DCA was not effective in reducing brain tissue lactate levels.
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PMID:The effect of dichloroacetate on brain lactate levels following incomplete ischemia in the hyperglycemic rat. 371 55

Effects of fructose feeding in moderate amounts on lipid metabolism of obese versus lean, and diabetic versus nondiabetic Zucker rats, were studied. Forty pairs of male lean and obese animals were assigned to two dietary groups, fructose and glucose. For each diet, one-half of lean and obese animals were injected with streptozotocin intraperitoneally (i.p.) to induce diabetes, and the other half were injected with buffer i.p. as a nondiabetic control group. After 9 wk of feeding, animals were fasted overnight, decapitated and exsanguinated. Organs were removed and weighed. Blood glucose, insulin, lactic acid, triglycerides, cholesterol, total liver lipids and urinary glucose were determined. Hyperphagia was observed in obese, non-diabetic and lean-diabetic animals. Streptozotocin injection drastically reduced insulin levels, and produced an impairment of growth, hyperglycemia, glucosuria, polydipsia and polyuria. Fructose feeding increased organ weights in kidney, liver and retroperitoneal adipose tissue, regardless of diabetic state. However, lactic acid levels were lower in fructose-fed groups than glucose-fed groups. In obese rats serum triglyceride levels were also lower in fructose-fed groups than in glucose-fed groups. Serum cholesterol was not affected by fructose feeding. The results indicated that fructose feeding did not produce hyperlipemia and lactic acidosis in the blood circulation in Zucker rats. However, fructose feeding did not improve glucose intolerance in diabetic animals, rather fructose feeding produced hyperinsulinemia in nondiabetic, obese animals.
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PMID:Effects of fructose feeding on lipid parameters in obese and lean, diabetic and nondiabetic Zucker rats. 390 Mar 13

Nine cases of severe acidosis occurring in patients with maturity onset diabetes who were receiving phenformin therapy were reviewed. All had evidence of renal disease. Lactic acidosis was diagnosed by elevated blood lactate levels in seven patients, and by the clinical manifestations and laboratory information in the other two. Contributing factors are discussed, as well as means of treatment and prevention. Although the specific etiology of renal disease is not emphasized in this paper, unrecognized progressive deterioration of renal function is implicated in the etiology of lactic acidosis.
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PMID:Lactic acidosis with phenformin therapy. 462 14

Sulfonylureas are the most potent and widely used oral antidiabetic agents. Despite the finding of possible side effects in a large multicenter trial (UGDP Study) demonstrating increased cardiovascular mortality during tolbutamide therapy, prescription of sulfonylureas has not declined in view of the inconclusive results of the study. In addition, new aspects of their mode of action have been discovered. Sulfonylureas may enhance insulin sensitivity of peripheral tissues, particularly by raising the decreased number of insulin receptors in type II diabetics. While this extrapancreatic effect appears to be quantitatively important, it is only present when insulin secretion is simultaneously stimulated. Insulin release is enhanced due to an increase in the sensitivity of the B-cell to glucose challenge. There is evidence to suggest that the extrapancreatic effect of sulfonylureas is secondary to their pancreatic effect. Pointers in the same direction emerged from our own results in a study on the influence of sulfonylureas added to insulin therapy on insulin sensitivity in type I diabetics. Sulfonylureas failed to increase insulin sensitivity and insulin requirements in these patients. The first generation compounds of sulfonylureas are associated with more side effects and drug interactions than the second generation preparations. However, the latter are more frequently associated with hypoglycemia since they are more potent and have a prolonged duration of action. Biguanides have almost fallen into disuse as therapeutic agents due to the potentially lethal complication of lactic acidosis. Only metformin may still be indicated in certain cases. Inhibitors of intestinal amylase and glucosidase represent a new therapeutic principle in diabetes therapy whose aim is to reduce postprandial hyperglycemia. Their value as therapeutic agents is not yet clearly established.
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PMID:[Oral antidiabetic agents: recent aspects]. 619 88

Despite the availability of oral hypoglycaemic agents for nearly 30 years, their precise mode of action and role in the management of diabetes mellitus remains poorly defined and controversial. They are regarded by many, though not all, clinicians as helpful adjuncts in the treatment of patients with non-insulin-dependent diabetes who have failed to respond satisfactorily to an adequate programme of dietary treatment. Their initial effectiveness is greatest in those patients who have had diabetes for less than 5 years, are overweight at the time of initiation of therapy, and whose fasting blood glucose levels are not unduly raised (less than 200 mg/dl). If they are receiving treatment with insulin and a shift to oral compounds is contemplated, success in the changeover is more likely if the daily dose has been less than 20 to 30 units daily. While their efficacy in maintaining adequate glycaemic control over the short term in responsive patients is unquestioned, the long term benefit of oral hypoglycaemic agents in reducing morbidity and mortality of late complications remains to be substantiated. In this regard, where long term efficacy is difficult to quantify, physician vigilance for chronic toxicity assumes a special importance. Notwithstanding the potential for interaction between sulphonylureas and numerous other drugs, significant adverse effects are uncommon. Hypoglycaemia is the major health concern associated with the use of sulphonylureas, and lactic acidosis has been the major problem with biguanides. Careful patient selection is thus the key to ensuring efficacy and avoiding toxicity. Recent evidence suggests that while the insulinotropic action of the sulphonylureas may explain the short term hypoglycaemic effect of these compounds, their reported action in enhancing insulin sensitivity, both at the receptor and post-receptor levels, more likely accounts for the long term maintenance of improved carbohydrate tolerance. The relatively new ('second generation') sulphonylurea compounds have not been shown to possess clearly defined advantages over the older preparations; the potentially beneficial effects of gliclazide on the microangiopathic changes of diabetes require considerable further evaluation.
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PMID:Oral hypoglycaemic agents. An update. 637 83

The blood content of lactic acid was measured in 186 patients with overt diabetes mellitus. The patients had normal or excess body weight and were placed on different treatment methods during decompensation, subcompensation and compensation stages. During diabetes mellitus compensation attained with different treatment methods as well as during treatment including biguanides in the presence of normoglycemia, the mean blood level of lactic acid did not differ significantly from its mean content in normal subjects. Patients with decompensated diabetes mellitus manifested a significant elevation of the mean blood content of lactic acid. There was a definite relationship between the glycemia and high lactic acid level in the blood. Based on an analysis of the reported data and own materials the conclusion is drawn that biguanides should not be used in the treatment of decompensated diabetes mellitus, since this may lead to an increase in blood lactic acid and to the growth of lactic acidosis risk. It is proposed that contraindications to the use of biguanides in diabetes mellitus patients should also include hyperglycemia. Indications to the use of biguanides in diabetes mellitus patients are provided as well as the table of diseases in which biguanides are contraindicated. A list of drugs incompatible with biguanides is also presented. It is recommended that biguanides should not be applied for over 4 to 6 months. It is also recommended that detection of blood lactic acid should be introduced into medical practice on a wider basis, since lactic acidosis cannot be diagnosed without using such a test.
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PMID:[Use of biguanide preparations in the treatment of diabetes mellitus]. 642 9

A perfused preparation of the hind limb of normal and diabetic rats was used to study the effects of lactic acidosis, alone or associated with hypoinsulinemic diabetes, on the incorporation of glucose and inorganic orthophosphate (Pi) into the skeletal muscle. A well oxygenated perfusate was recirculated for ninety minutes during which the lactic acid accumulated into the medium with the ensuing pH drop. The perfusions were practiced in the hind limb of alloxanized diabetic rats, in the hind limb of diabetic rats with perfusate containing 200 microU of insulin/ml, in the hind limb of 24 hour fasted rats, and on the hind limb of fed rats, and they were compared to similar groups with normalized pH perfusate with a sodium bicarbonate infusion. In the diabetic perfusions with lactic acidemia, it was observed that the addition of insulin increased the uptake of Pi and of glucose, and reduced the release of Pi by the muscular tissues. A smaller release of Pi by the preparations obtained from fed rats was observed when compared to the hind limb preparations of fasted rats. The diabetic preparations showed an increased glucose uptake when the pH was normalized, and a decrease of Pi released by the muscles, even in the absence of insulin, and at the same time, the administration of insulin associated with the normalization of pH increased the uptake of Pi and of glucose, and decreased the Pi released by the muscles. In all the groups, the administration of sodium bicarbonate significantly increased the lactate release into the medium. It was also found that the lactic acidosis reduced the uptake of Pi by the preparations inducing hyperphosphatemia. According to these results, muscular tissue plays a role in the hypophosphatemia that has been reported in the insulin treated diabetic ketoacidosis by increasing the incorporation of Pi and reducing its release by the same tissue.
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PMID:Glucose and orthophosphate incorporation and lactate release in the perfused hind limb of the rat during lactic acidemia. 667 May 67

Analysis of causes of death in a population of 3,113 diabetics was carried out for a period of eight years and those patients dying of some form of diabetic coma identified. Of 1,274 deaths, only 22 (1.73%) were primarily due to coma; 7 hypoglycaemia, 8 ketoacidosis, 3 hyperosmolar coma and 4 lactic acidosis. Three of the ketoacidosis patients may have died from other causes. Most deaths occurred in patients with long-standing diabetes. In the hypoglycaemic group all were on insulin and several had been difficult to control for many years. Infection was an important precipitating factor for ketoacidosis and hyperosmolar coma. Phenformin was the cause of all cases of fatal lactic acidosis. It is reassuring that death from coma is a comparatively rare event in known treated diabetic patients.
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PMID:Fatal coma in diabetes. 677 28


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