Since the discovery that ketone acids are produced in the body and accumulate in the blood to excess in severe diabetes, general opinion has held that the accumulation of these chemical compounds is responsible for the syndrome known as diabetic coma. The general application of the term acidosis to the condition is in itself sufficient evidence of the importance which is attached to this disorder of metabolism. Difference of opinion seems to have been restricted chiefly to the question of the relative parts played by the ketone bodies as such and by the reduction of blood alkali and diminution of pH which they caused. With the appearance and application of accurate and practical methods for the determination of blood bicarbonate and pH it has become increasingly apparent that alkali deficits of the magnitude found in diabetic acidosis, when they are produced experimentally or occur in the course of other diseases, are not necessarliy attended by a syndrome resembling that of diabetic acidosis. This has, perhaps, given more weight to the arguments of those who would hold that acetone and diacetic acid, by their anesthetic and poisonous effects, are responsible for the symptoms and fatalities. On the other hand there is but the scantiest positive quantitative evidence to support such a theory. The anesthetic actions of acetone and diacetic acid are notoriously slight, but hard to ascertain with certainty because of the ease with which normal animals excrete or oxidize these compounds. Ketosis unassociated with the other metabolic disorders of diabetes never attains so great an intensity. The most convenient experimental animals when rendered diabetic by pancreatectomy or phlorizin do not develop ketosis comparable in severity to that seen in humans with diabetic coma. Chemical analyses have demonstrated no exact correlation between the concentration of ketones in the blood and the profundity of coma in diabetic patients (20).
Rowe (17), in 1917, reported observations of the serum proteins of 10 patients with diabetes. The only remarkable thing was the extreme variability of the findings. Both high and low values were obtained. In the majority of instances albumin and globulin preserved their normal proportions; but in some instances globulin appeared relatively high. Subsequent observers have confirmed Rowe and the general opinion. appears to be that there is nothing characteristic about the serum protein level in diabetes.In table 1 are shown the results of 52 observations of the plasma proteins of 31 patients with diabetes mellitus of varying degrees of severity, studied at different stages of the disease.
EXPERIMENTAL PROCEDUREWhenever there is no note to the contrary, the blood was taken in the morning, before the patient had breakfast and the morning dose of insulin. The blood was withdrawn in a syringe and coagulation prevented by the addition of enough neutral potassium oxalate to make an 0.2 per cent oxalate solution in the blood. The treatment of the blood is indicated in column 6 of the table. Those specimens marked cont. were obtained without stasis and immediately placed over mercury in a blood sampling tube of the type described by Austin, Cullen, Hastings, McLean, Peters and Van Slyke (1). Usually venous blood (ven.) was employed, but occasionally arterial (art.) was used instead. In specimens indicated as cap. the blood was withdrawn without precautions against air contact and brought into equilibrium with 40 mm. of CO2 in the air at 38°C. by the method previously described (16) before it was placed in the sampling tube over mercury. From the mercury sampling tube part of the blood was transferred to a centrifuge tube 451
The present paper represents an extension of the work outlined in number VII of this series, "Factors causing acidosis in nephritis" (1), with an attempt to explain in part the disturbances of the total acidbase equilibrium of the serum which were there described. The acidosis, a term applied to conditions in which the concentration of bicarbonate of serum is low, appeared to be due to several different types of electrolyte disturbances of which the chief were reduction of total base and increase of undetermined acid (i.e., acids other than bicarbonate, chloride, phosphate and protein). Phosphate increases seemed to play a less important r6le. Variable changes in the level of Cl, usually reductions in its concentration, were observed with great frequency.To the data then presented many observations have been added, and collateral studies, bearing especially on chloride metabolism, have been made.
EXPERIMENTAL METHODSSince the appearance of the first paper of this series (2) certain changes in the technique -and calculations used in the determination of the total acid-base equilibrium of the serum have ben adopted to increase accuracy. Although these changes in no way alter the conclusions reached in previous articles, they have necessitated a redetermination and restatement of normal values and recalculations of earlier data.
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