Canicola fever in man and animals.
Authors: J. H. Lawson, S. W. Michna
Journal: BMJ (1966)

above our accepted upper limit of normal, and the range was wide.The use of the intravenous tolbutamide-tolerance test added little more of value.Here we found so many abnormal results, judged by the criteria originally laid down by Unger and Madison (1958), that it would appear as if these criteria are too strict for older people.The mean curves within the three groups, however, correspond very well indeed with the glucose-tolerance tests, being normal in the normal group and distinctly diabetic in the diabetic group (Fig. 2).Effect of Diuretics on Carbohydrate Metabolism.-Shapiro et al. (1961) found no change in glucose tolerance after two weeks on chlorothiazide in those patients whose control glucose tolerance was normal, but a worsening in those who were originally mildly diabetic.We found almost the oppositecertainly no worsening in the abnormal and diabetic groups, and a higher mean two-hour level in the normal group, but individually only one normal curve became abnormal.Over a longer period of time, of course, more changes might have been seen.On frusemide there was an apparent improvement in mean glucose tolerance in the abnormal and diabetic groups, but we do not claim statistical significance for this.Two of the normal subjects became diabetic after three months of frusemide, yet repeat tests were normal in one and only slightly abnormal in the other.This indicates the possible degree of individual variability and danger of relying on a single glucose- tolerance test, though we must emphasize that in general the glucose tolerance is remarkably closely reproducible (Jackson, 1964).In summary we found no clear evidence in our patients that chlorothiazide in a three-week course, or frusemide over three months, caused deterioration in glucose tolerance or in response to intravenous tolbutamide.The conditions of our trial differed from those of other workers mentioned above, who reported upon individual cases or experiments in animals.We certainly do not deny that chlorothiazide can be diabetogenic in certain patients, but in pharmacological doses this effect would appear to be comparatively infrequent.We do not know why our results with chlorothiazide differed from those reported by Shapiro et al. (1961), in that the carbohydrate metabolism of our " subclinical diabetics " did not worsen on therapy.Effect of Diuretics on Other Blood Levels.-Ourpatients showed no change in levels of circulating platelets, serum potas- sium, alkaline phosphatase, or S.G.O.T.In only one subject was there a rise in serum uric acid level.Effect of Diuretics on Blood-pressure.-Ingeneral this was very slight, with a mean fall of only 4-5 mm.Hg in the dia- stolic pressure, though rather more in the systolic-a mean of about 19 mm.Hg. SummaryOf 19 selected moderately hypertensive subjects six were found to have diabetes by oral glucose-tolerance tests, pre- viously unsuspected, and a further six gave " abnormal" results.Intravenous tolbutamide-tolerance tests were also frequently abnormal.There was good correspondence between the results of these two tests.Chlorothiazide given for three weeks and frusemide given for three months produced no remarkable deterioration of carbo- hydrate tolerance in these subjects, nor was any substantial effect on serum potassium, S.G.O.T., uric acid, alkaline phosphatase, or platelet count observed.The serum uric acid rose in one patient only.The drop in blood-pressure with both diuretics was very small.There was a mean fall of about 4-5 mm.Hg in the diastolic pressure and about 19 mm.Hg in the systolic.We are pleased to acknowledge the great assistance provided by Professor J.