We report 18 consecutive phenformin-treated diabetic patients admitted to this Medical Service acutely ill with metabolic acidosis. Lactic acidosis was anticipated, and documented, in all. Also, however, though most of the patients had only weakly positive, or even negative, serum reactions with the nitroprusside reagent, all were found to have coexisting ketoacidosis, plasma 3-hydroxybutyrate averaging 7.1 mmol/L. +/- 3.9 (S.D.). This finding suggest that treatment of these patients should include insulin, and often also glucose, because most do not have marked hyperglycemia and some have hypoglycemia. The lactic acidosis in the nine patients who survivied was, on average, less severe than in the nine who died, but the difference was not statistically significant. Surivival correlated closely with the absence of shock on arrival. Only eight patients had a identifiable acute illness other than the metabolic acidosis. The other 10 patients had no discernible cause for the acute illness apart from their treatment with phenoformin. This finding raises serious doubts about whether phenformin should be used to treat patients with diabetes.

Acidosis↗

PubMed1976

Lactic acidosis in diabetic patients.

Plasma lactate and beta-hydroxybutyrate concentrations were measured during episodes of ketoacidosis and lactic acidosis in diabetics. In 39 patients with ketoacidosis, with a mean plasma beta-hydroxybutyrate concentration of 12.4 millimols/liter, the plasma lactate concentration was less than 3.6 millimols/liter in 28 and moderately elevated in 11. In seven of the latter, coexisting lactic acidosis had been suspected clinically. In these 39 patients, there was no correlation between plasma lactate and beta-hydroxybutyrate concentrations. In six of ten episodes of presumed and later proved lactic acidosis, despite negative or weakly positive serum reactions with sodium nitroprusside, the plasma beta-hydroxybutyrate concentration was elevated. Although positive, the serum reaction with nitroprusside was also misleadingly weak in five of 39 patients with ketoacidosis, including three with plasma lactate concentrations less than 3 millimols/liter.

Adult↗

PubMed1975

Alcoholic detosis.

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.

Acidosis↗

PubMed1975

Is there a role for mitochondrial genes in carcinogenesis?

Although defective respriration is not characteristic of all tumors, recent comparative studies on the ultrastructure of normal and tumor cell mitochondria indicate that in malignant cells mitochondria deviate from normal not only in relative abundance but also in the size, form, density, and frequency of appearance of lesions. Normal and abnormal mitochondria may populate the same cell, suggesting that there may be a gradation in respiratory deficiency depending on the proportion of normal to abnormal forms. Recent advances in mitochondrial genetics suggest that aberrant mitochondria may be formed as a result of the presence of an abnormal mitochondrial genome. In analogy with the petite mutant of certain strains of yeast, animal cells may be transformed by treatment with dyes that alter the structure of their mitochondrial DNA, so that their mitochondria also become deficient in enzymes of the respiratory chain. Whether nutritional or other deficiencies are mutagenic with respect to mitochondrial DNA of animal cells is not known; nor is it known whether mitochondrial mutagenesis is causally involved in carcinogenesis. New knowledge of cytoplasmic genetics and of mitochondrial DNA and membrane structure and dynamics should encourage investigations aimed at examining the possible role of mitochondrial genes in neoplastic transformation.

Animals↗