Importance of low Blood pH in DKA

To the Editor of “Experimental and Clinical Endocrinology and Diabetes”.

In the very detailed paper [2] the authors have "found a slight but significant difference, in the time to normalization of acidosis" (p 276) of the treatment with 0.1 units/kg/h insulin as compared with 0.025 units/kg/h. However, "Implications of this earlier normalization of pH remains unclear" (p 273).

Therefore, the impression of the reader is that the higher dosage of insulin has resulted in the "earlier normalization of acidosis". According to the (Table 1) (p 274), the patients were treated with "fluids" which included also ringer lactate. This is an alkalizing solution. According to p 273, "For the first 12 h patients in center B (administering 0.1 units/kg/h insulin) got twice as much fluid as in center A (administering 0.025 units/kg/h)". Thus, patients in center B received greater amounts of alkalizing ringer lactate as patients in center A. The logical consequence is that their acidosis (= low blood pH) normalized faster. To attribute earlier normalization of the acidosis to higher dosage of insulin would be valid only in absence of ringer lactate treatment.

"Implications of this earlier normalization of pH remain unclear": these implications are known and are very interesting. According to Edge et al. [1] and Nyenwe et al. [3] very low blood pH is the immediate cause of coma: the glycolytic enzyme phosphofructokinase is pH dependent [4], as its activity is decreasing with decreasing pH and, thus, glucose utilization in brain cells is impaired [5]. Therefore, implication of normalization of the very low blood pH in comatose patients is recovery to normal consciousness. With other words, zero lethality of coma in diabetic ketoacidosis, e g. [6].

Among the 64 patients reported by the authors is also 1 comatose patient ((Table 2) on p 274); it would be interesting to know his blood pH value on admission and at recovery to full alertness.

• References

• 1 Edge JA, Roy Y, Bergomi A et al. Conscious level in children with diabetic ketoacidosis is related to severity of acidosis and not to blood glucose concentration. Pediatr Diabetes 2006; 7: 11-15
• 2 Kapellen T, Vogel C, Telleis D et al. Treatment of Diabetic Ketoacidosis (DKA) with 2 Different Regimens Regarding Fluid Substitution and InsuIin Dosage (0.025 vs. 0.1 units/kg/h). Exp Clin Endocrinol Diabetes 2012; 120: 273-276
• 3 Nyenwe EA, Razavi LN, Kitabchi AE et al. Acidosis: The Prime Determinant of Depressed Sensorium in Diabetic Ketoacidosis. Diabetes Care 2010; 33: 1837-1839
• 4 Trivedi B, Danforth WH. Effect of pH on the Kinetics of Frog Muscle Phosphofructokinase. J biol Chem 1966; 241: 4110-4112
• 5 Van Nimmen D, Weyne J, Demeester G et al. Local cerebral glucose utilization in systemic acidosis. Am J Physiol 1984; 247: R639-R645
• 6 Wagner A, Risse A, Brill H-L et al. Therapy of Severe Diabetic Ketoacidosis. Zero-mortality under very-low-dose insulin application. Diabetes Care 1999; 22: 674-677