Insulin pumps and other recent advances in the outpatient treatment of diabetes.
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Biomedical subjects
Publications and source records attributed to J E Loewenstein.
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To clarify the effect of aspirin on folate balance, we studied serum concentration, protein binding, and urinary excretion of endogenous folate. A healthy woman twice followed an 11-day protocol of constant diet, blood sampling twice daily, collection of all urine, and 650 mg of aspirin by mouth every 4 hours on the middle 3 days. As determined by equilibrium dialysis and Lactobacillus casei assay, aspirin induced a brisk, significant but reversible fall in total and bound serum folate and a small but insignificant rise in urinary folate excretion. Aspirin in vitro also displaced significant amounts of bound serum folate. Thus, aspirin in therapeutic doses can contribute to subnormal serum folate values, and if it increases urinary folate excretion even slightly, may impair folate balance.
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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.
All cases of lactic acidosis occurring during a 23-month period in a metropolitan teaching hospital were reviewed to ascertain the frequency of hyperamylasemia. Serum amylase activity had been measured in 12 of 26 patients and was elevated in eight (67%). Hyperamylasemia was not significantly more frequent in patients with phenformin-associated lactic acidosis than in patients with lactic acidosis who had not received phenformin. Serum amylase activity did not correlate with the severity of acidosis (arterial pH) or with renal function (serum creatinine).
All patients admitted with severe lactic acidosis to a university teaching hospital during a 17-month period were taking phenformin hydrochloride. Serum phenformin concentration was measured in one patient and found to be four to nine times the usual therapeutic concentration. Prerenal azotemia was present at the time of admission in all but one of these patients, but renal function was normal at the time of discharge in those patients with phenformin-associated lactic acidosis who survived. Phenformin-associated lactic acidosis accounted for 7% of the episodes of metabolic acidosis and 27% of deaths due to metabolic acidosis in diabetics.
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