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

The treatment of diabetes is still a problem more than a half-century after the discovery of insulin. Patients are now living significantly longer but until the development of oral hypoglycemic agents, the only direct treatment modalities were exercise, diet, and insulin. Before evaluating the effectiveness of treatment, a therapeutic goal must be determined. While there are no absolutely "hard" facts proving that "good control" is beneficial in preventing chronic complications of diabetes, increasing accumulation of "soft" data strongly suggests that normal blood glucose levels are most desirable, when possible, but not at the cost of severe or disabling hypoglycemic reactions. The development of the oral agents was a great public health advance in that many persons with early diabetes, but fearful of insulin injections, had less dread of "the pills" and sought treatment. The oral agents simplified care but this very simplification process often undermined the need for proper diet and good fundamental care. This often led to mediocre diabetes care. While useful, the oral agents have marked limitations and in some are effective only temporarily. The presently available oral agents are sulfonylureas and require a viable beta-cell system for success. This limits the number of diabetics responsive to such treatment. The general indications for tolbutamide, chlorpropamide, acetohexamide and tolazamide are in maturity-onset diabetics, generally beyond the age of 40 with diabetes of less than 10 years. They are contraindicated in juvenile-onset diabetics, in pregnant women, and usually in patients undergoing major surgery, and can become ineffective during periods of extreme stress or during severe infection. They can lower blood glucose levels if used in proper doses in properly selected patients. Contrary to several decades of documentation, it has become popular to suggest that the oral agents are not effective. They can be effective but for many reasons apparently were not in their use by the U.G.D.P. researchers. This might not be the fault of the oral agent used. If ineffective, they should be discontinued. Many, but not all, patients may respond to diet therapy, which is then the treatment of choice. Obviously insulin, though difficult to use for many persons and in itself able to induce several severe reactions if not used properly, is the only treatment (with diet) for the severe diabetic. There is a large spectrum of patients inbetween in whom the oral agents may be useful. The use of phenformin (phenethyl-biguanide) has been effectively curtailed because of many reported cases of lactic acidosis, and while it is doubtful that phenformin alone, in the absence of complicating factors, is the causative factor, it is capable of being an augmenting influence when other conditions, such as decreased kidney function, prevail...
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PMID:Oral hypoglycemic agent update. 9 75

The authors analyzed the effects of obesity/non-obesity in 162 epidoses of severe metabolic disturbances. Ketoacidosis and hypoglycaemics comas were more frequent in the non-obese group of diabetics, who were often insulin treated; whereas hyperosmolar coma and lactic acidosis were frequent in the obese group of diabetics, usually not treated with insulin. In the obese group both advanced age as well as a higher frequency of degenerative complications impaired the prognosis of these metabolic accidents. However the mortality rate was not significantly different in the two groups of patients. Despite the importance of the weight balance in the natural history of diabetes mellitus, it did not seem to influence the clinical aspects nor did it modify the therapeutic management of the major metabolic disturbances which occur in diabetes.
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PMID:[Major metabolic disturbances occur in diabetic patients whether they are obese or not (author's transl)]. 11 Dec 20

Sixteen cases of lactic acidosis are reported: 7 phenformin treated diabetes, 5 cardiovascular diseases (2 myocardial infractions, 2 pulmonary embolisms, 1 heart failure). In 2 patients no etiology was found. Concomittant renal failure or liver diseases were found in respectively 9 and 4 cases. Patients presented the usual criteria of lactic acidosis: clinical, polypnea, severe hypotension (9/16), peripheral symptoms of shock (12/16), hypothermia (9/16), abdominal pain (9/16): biologically, acidosis (pH = 6,99 +/- 0,01, HCO3- = 5,9 +/- 1,5 mmol), hyperlactatemia (14,1 +/- 3,6 mmol/l) with hig lactate/pyruvate ratio (105 +/- 73), and anion gap (24,3 +/- 4,2 mmol/l). Sodium bicarbonate infusion was performed in all cases (2,5 to 42 mmol/kg). Few cases required volhemic expansion or furosemid induced diuresis. One patient was treated with extrarenal dialysis. 13 patients were alkalinised with less than 185% of estimated deficit measured from alkalin reserve: 12 died. 3 patients received 185% more than this deficit, associated with furosemid (1,8 to 12,5 mg/kg): only one patient died ten days after by casual disease, with lactatemia of 3,2 mmol/l. In spite of the small number of patients, these findings suggest that an early and massive alkalinisation, with large doses of furosemid, can improve the severe lactic acidosis prognosis.
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PMID:[Lactic acidosis and intensive care. 16 cases (author's transl)]. 23 77

Gluconeogenesis from lactate and hepatic cell pH (pHi) were measured in the isolated perfused livers of starved guinea pigs in the presence and absence of phenformin (phenethylbiguanide). The observed decrease in lactate consumption and glucose output in the presence of phenformin was associated with a fall in pHi. The fall in glucose output observed was considerably greater than accountable for by the decrease in lactate consumption. A possible mechanism for the pathogenesis of clinical lactic acidosis due to phenformin therapy is suggested.
Diabetes 1975 Jul
PMID:Effect of phenformin on gluconeogenesis from lactate and intracellular pH in the isolated perfused guinea pig liver. 23 72

The paper presents an analysis of clinical symptoms, signs and laboratory data of 330 diabetic patients who developed lactic acidosis after having been treated with biguanides (phenformin, buformin, metformin). From the review of the literature an attempt is made to find special features that predisposed patients to develop lactic acidosis such as accompanying illnesses and additional medications, to describe the course of illness and also the factors that influenced the prognosis. Of the patients that developed lactic acidosis 50.3% died. These patients were older, they suffered more frequently from cardiovascular shock, their acidosis was more severe, the whole blood lactate concentration was higher, and the degree of renal insufficiency was more advanced. From our observations we conclude the the treatment of diabetes mellitus with biguanides should be reserved for specially selected patients.
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PMID:Lactic acidosis in biguanide-treated diabetics: a review of 330 cases. 34 19

In a survey, the pharmacological and clinical documentation of metformin is presented and discussed, and the present state of knowledge relating to metformin-associated lactic acidosis is reviewed. The use of metformin in the treatment of diabetes is based on clinical experience over twenty years. It has been well documented that metformin is effective in maturity-onset diabetes both as monotherapy and in combination with a sulphonylurea. An advantage of metformin treatment is the tendency to weight reduction and the absence of significant hypoglycaemia; blood glucose levels are reduced only to normal. The disadvantages are the gastro-intestinal side effects and the potential risk of vitamin B 12 and folic acid deficiency during long-term use. Metformin-associated lactic acidosis is a very rare complication, which has mainly occured in patients with serious renal insufficiency or other contra-indications to the use of metformin. The association between phenformin and lactic acidosis has led to withdrawal of this biguanide in several countries. Metformin differs from phenformin in certain important respects, and the normal use of metformin does not involve the risk of side effects disproportionate to the intended effect. Further experimental studies are required to substantiate pharmacokinetics and metabolic effects of metformin in man.
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PMID:Metformin: a review of its pharmacological properties and therapeutic use. 38 88

The present report describes a patient with insulin-dependent diabetes who developed simultaneously lactic acidosis and ketoacidosis following insulin deprivation. Administration of insulin at low doses rapidly corrected both ketosis and lactic acidosis. There had been neither circulatory collapse, nor phenformin intake, and hepatic function was normal. The development of lactic acidosis in this case was possibly precipitated by hyperthyroidism. A review of the literature indicates that lactic acidosis is a very rare complication of diabetic ketosis per se.
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PMID:Lactic acidosis complicating diabetic ketosis in a patient with hyperthyroidism. 40 2

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

The pharmacological properties and the mode of action of biguanides is presented. In Austria, the association of lactic acidosis with biguanide therapy has led to a cancellation of the registration of buformin and phenformin. Only, if all contraindications for biguanide therapy are strictly observed, metformin can be prescribed for the treatment of obese patients with type II diabetes.
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PMID:[Biguanides: reasons for withdrawal of drugs and remaining indications]. 75 19

Twenty-four chronic alcohol abusers hospitalized during a twenty-seven-month period were suspected of having "alcoholic ketoacidosis" because they had ketonuria or ketonemia with little or no glucosuria. Twenty-one had moderate or severe ketosis, with plasma 3-hydroxybutyrate of 5.2 to 22.5 mmol/L. Fifteen of this group were not diabetic, while six were later found to have mild postprandial hyperglycemia without glycosuria. Three patients who had continued to drink until shortly before admission, though at first suspected of having alcoholic ketosis, were found to have predominant lactic acidosis, with minor elevations of plasma 3-hydroxybutyrate. In contrast to previously reported patients with "alcoholic ketoacidosis", severe acidemia was uncommon in this series. Indeed, seven patients were alkalemic, because of coexisting respiratory or metabolic alkalosis. Most patients had eaten poorly for several days (and usually longer) and had allegedly decreased their alcohol intake during that period. That history, and the usual rapid clearing of ketosis simply by treatment with solutions of glucose and NaCl, suggested that acute starvation was an important factor in the pathogenesis of this disorder. Four patients were treated with insulin and four with NaHCO3 solutions. In retrospect, the need for either of these treatments was not clear. Two of the twenty-four patients died, one from circulatory failure secondary to hemorrhage and the other from pulmonary edema, but no patient died because of ketoacidosis per se.
Diabetes 1975 Sep
PMID:Alcoholic detosis. 80 36


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