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Management of adult diabetic ketoacidosis

Authors Rosival V

Received 7 September 2014

Accepted for publication 8 September 2014

Published 28 November 2014 Volume 2014:7 Pages 571—573

DOI https://doi.org/10.2147/DMSO.S73896

Editor who approved publication: Professor Ming-Hui Zou

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Viktor Rosival

SYNLAB, Department of Laboratory Medicine, Dérer's Hospital, Bratislava, Slovakia

In the article “Management of adult diabetic ketoacidosis” by Gosmanov et al1 there are some discrepancies with the literature. The authors write, “Insulin deficiency […] which underlie the pathophysiology of DKA [diabetic ketoacidosis]”, and on page 258, they write, “Insulin administration is essential in DKA treatment [...]”.1 Since the Nobel prize was awarded in 1977 to Rosalyn S Yalow for the development of new methods of biochemical analysis that make it possible to measure insulin concentration in human plasma, these methods have been used worldwide. In 1981, the monograph Diabetic Coma: Ketoacidotic and Hyperosmolar was published,2 and on page 67, Figure 6.3 has the names of 12 authors who have reported sufficient amounts of plasmatic insulin in patients with DKA.

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Dear editor

In the article “Management of adult diabetic ketoacidosis” by Gosmanov et al1 there are some discrepancies with the literature. The authors write, “Insulin deficiency […] which underlie the pathophysiology of DKA [diabetic ketoacidosis]”, and on page 258, they write, “Insulin administration is essential in DKA treatment […]”.1 Since the Nobel prize was awarded in 1977 to Rosalyn S Yalow for the development of new methods of biochemical analysis that make it possible to measure insulin concentration in human plasma, these methods have been used worldwide. In 1981, the monograph Diabetic Coma: Ketoacidotic and Hyperosmolar was published,2 and on page 67, Figure 6.3 has the names of 12 authors who have reported sufficient amounts of plasmatic insulin in patients with DKA. In contrast, absolute deficiency of plasmatic insulin has been reported in diabetic patients with hyperglycemic hyperosmolar syndrome,3 as well as in diabetic patients on routine control without subjective complaints.4 Where are published concrete reports on the deficiency of plasmatic insulin in patients with DKA? What is the “safe level” of plasmatic insulin concentration that makes development of DKA impossible?

On page 259, the authors write, “The use of bicarbonate in severe DKA is controversial […]”. On the same page, the authors also write that “severe acidosis […] can lead to impairment in sensorium […]”. Severe “impairment in sensorium” is a life-threatening coma. If intravenous sodium bicarbonate is also included in the treatment, however, the lethality of coma in DKA is zero.5 In contrast, without sodium bicarbonate, lethality can be up to 100%.6 What here is controversial? The glycolytic enzyme phosphofructokinase is pH-dependent, as its activity is decreasing with decreasing pH, and thus, glucose use in brain cells is impaired.7 This is the explanation of the life-saving effects of sodium bicarbonate in the treatment of coma in DKA.

Disclosure

The author reports no conflicts of interest in this communication.


References

1.

Gosmanov AR, Gosmanova EO, Dillard-Cannon E. Management of adult diabetic ketoacidosis. Diabetes Metab Syndr Obes. 2014;7:255–264.

2.

Schade DS, Eaton RP, Alberti KGMM, Johnston DG. Diabetic Coma: Ketoacidotic and Hyperosmolar. Albuquerque: University of New Mexico Press; 1981.

3.

Vinik A, Seftel H, Joffe BI. Metabolic findings in hyperosmolar, non-ketotic diabetic stupor. Lancet. 1970;2(7677):797–799.

4.

Matsuyama T, Hoffman WH, Dunbar JC, Fo[#x00E0;] NL, Fo[#x00E0;] PP. Glucose, insulin, pancreatic glucagon and glucagon-like immunoreactive materials in the plasma of normal and diabetic children. Effect of the initial insulin treatment. Horm Metab Res. 1975;7(6):452–456.

5.

Umpierrez GE, Kelly JP, Navarrete JE, Casals MMC, Kitabchi AE. Hyperglycemic crises in urban blacks. Arch Intern Med. 1997;157(6):669–675.

6.

Basu A, Close CF, Jenkins D, Krentz AJ, Nattrass M, Wright AD. Persisting mortality in diabetic ketoacidosis. Diabet Med. 1993;10(3):282–284.

7.

Nyenwe EA, Razavi LN, Kitabchi AE, Khan AN, Wan JY. Acidosis: the prime determinant of depressed sensorium in diabetic ketoacidosis. Diabetes Care. 2010;33(8):1837–1839.


Authors’ reply

Aidar R Gosmanov1, Elvira O Gosmanova2

1Division of Endocrinology, Diabetes and Metabolism, 2Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA

Correspondence: Aidar R Gosmanov, Division of Endocrinology, 920 Madison Avenue, Suite 300A, Memphis, TN 38163, USA, Fax +1 901 448 5940, Email [email protected]

Dear editor

We appreciate Dr Rosival’s interest and comments raised after reading the review “Management of adult diabetic ketoacidosis”.1 The author raises several interesting points that warrant further discussion. Insulin has two important metabolic roles: suppression of lipolysis, ketogenesis, and unrestrained hepatic glucose production via inhibition of gluconeogenesis and glycogenolysis; and activation of glucose uptake and metabolism by insulin-sensitive tissues.2 When these insulin-mediated processes are active, diabetic patients do not develop ketoacidosis and severe hyperglycemia. When we stated that patients with diabetic ketoacidosis (DKA) have absolute insulin deficiency, we referred to the functional inability or deficiency of insulin to inhibit ketone body formation, suppress endogenous glucose production, and activate glucose utilization by peripheral tissues. Indeed, patients with DKA may not have an absolute deficiency of the hormone; previous studies have shown that development of a ketotic state is possible in subjects with a plasma insulin level of 5 μU/mL.3

Bicarbonate therapy is not indicated in mild and moderate forms of DKA because metabolic acidosis will correct with insulin therapy.2,4 Clinicians should exercise clinical judgment in deciding to use bicarbonate therapy in patients with severe DKA.5 We agree that it is tempting to use bicarbonate infusion in patients with DKA who are comatose and have severe acidosis. However, in the absence of randomized trials we should be cautious in that decision because while treating acidosis as a symptom, we may inadvertently cause harm through the development of peripheral hypoxemia, worsening of hypokalemia, paradoxical central nervous system acidosis, cerebral edema, and an increase in intracellular acidosis. We believe that in DKA patients with severe acidosis and a pH <7.0, it may be prudent to administer two ampules of bicarbonate in parallel with ongoing efforts to provide insulin and fluids, followed by repeated measurement of metabolic parameters and clinical reassessment of the patient. It is unclear if the provision of bicarbonate to the DKA patients with a pH >7.0 could offer any clinical advantage over routine DKA therapy.6

Disclosure

The authors report no conflicts of interest in this communication.


References

1.

Gosmanov AR, Gosmanova EO, Dillard-Cannon E. Management of adult diabetic ketoacidosis. Diabetes Metab Syndr Obes. 2014;7:255–264.

2.

Kitabchi AE, Umpierrez GE, Murphy MB, Kreisberg RA. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes care. 2006;29(12):2739–2748.

3.

Miles JM, Haymond MW, Nissen SL, Gerich JE. Effects of free fatty acid availability, glucagon excess, and insulin deficiency on ketone body production in postabsorptive man. J Clin Invest. 1983;71(6):1554–1561.

4.

Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes care. 2009;32(7):1335–1343.

5.

Latif KA, Freire AX, Kitabchi AE, Umpierrez GE, Qureshi N. The use of alkali therapy in severe diabetic ketoacidosis. Diabetes care. 2002;25(11):2113–2114.

6.

Viallon A, Zeni F, Lafond P, et al. Does bicarbonate therapy improve the management of severe diabetic ketoacidosis? Crit Care Med. 1999;27(12):2690–2693.

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