Atypical Feature of Diabetic Ketoacidosis with Low or Normal Plasma Glucose: a Narrative Review
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Abstract
Context: Diabetic Ketoacidosis (DKA) is a well-known emergency in diabetic patients. In a subgroup of patients ketoacidosis is present but is not accompanied by the marked hyperglycemia considered part of the diagnostic criteria for DKA. This is known as Euglycemic DKA (EuDKA).
Evidence acquisition: We searched the PubMed for the existing literature on the topic of normoglymic ketoacidosis, including its prevalence, pathogenesis, and treatment.
Results: The study showed that there are many reports of the cases in which diabetic patients developed ketoacidosis without experiencing hyperglycemia. Several predisposing factors have been proposed but the precise pathophysiologic mechanisms are still under investigation. Some pathways have been suggested. Timely diagnosis is of paramount importance. Treatment is similar to DKA.
Conclusion: EuDKA is a medical emergency that should be considered when evaluating a diabetic patient with ketoacidosis. It should be diagnosed and treated promptly.
1. Joseph F, Anderson L, Goenka N, Vora J. Starvation-induced true diabetic euglycemic ketoacidosis in severe depression. J Gen Intern Med. 2009;24(1):129-31.
2. Modi A, Agrawal A, Morgan F. Euglycemic Diabetic Ketoacidosis: A Review. Curr Diabetes Rev. 2017;13(3):315-21.
3. Lee K, Park IB, Yu SH, Kim SK, Kim SH, Seo DH, et al. Characterization of variable presentations of diabetic ketoacidosis based on blood ketone levels and major society diagnostic criteria: a new view point on the assessment of diabetic ketoacidosis. Diabetes Metab Syndr Obes. 2019;12:1161-71.
4. Poudel RR, Kafle NK. Closing anion gap without insulin in euglycaemic diabetic ketoacidosis. J Diabetol. 2017;8:92-3.
5. Thawabi M, Studyvin S. Euglycemic Diabetic Ketoacidosis, a Misleading Presentation of Diabetic Ketoacidosis. N Am J Med Sci. 2015;7(6):291-4.
6. Munro JF, Campbell IW, McCuish AC, Duncan LJ. Euglycaemic diabetic ketoacidosis. Br Med J. 1973;2(5866):578-80.
7. Rawla P, Vellipuram AR, Bandaru SS, Pradeep Raj J. Euglycemic diabetic ketoacidosis: a diagnostic and therapeutic dilemma. Endocrinol Diabetes Metab Case Rep. 2017; 2017:17-0081.
8. Joseph F, Anderson L, Goenka N, Vora J. Starvationtiontionvation N, Vora euglycemic ketoacidosis in severe depression. J Gen Intern Med. 2009;24:129‑31
9. Rosenstock J, Ferrannini E. Euglycemic diabetic ketoacidosis: A Predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes Care. 2015;38:1638‑42.
10. Barski L, Eshkoli T, Brandstaetter E, Jotkowitz A. Euglycemic diabetic ketoacidosis. Eur J Intern Med. 2019;63:9-14.
11. Goldenberg RM, Berard LD, Cheng AYY, Gilbert JD, Verma S, Woo VC, et al. SGLT2 inhibitor-associated diabetic ketoacidosis: clinical review and recommendations for prevention and diagnosis. Clin Ther. 2016;38(12):2654–64.
12. Hine J, Paterson H, Abrol E, Russell-Jones D, Herring R. SGLT inhibition and euglycaemic diabetic ketoacidosis. Lancet Diabetes Endocrinol. 2015;3(7):503–4.
13. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335-43.
14. Wolfe RR, Peters EJ, Klein S, Holland OB, Rosenblatt J, Gary H Jr. Effect of short-term fasting on lipolytic responsiveness in normal and obese human subjects. Am J Physiol. 1987;252(2 Pt 1):E189-96.
15. Jensen MD, Haymond MW, Gerich JE, Cryer PE, Miles JM. Lipolysis during fasting. Decreased suppression by insulin and increased stimulation by epinephrine. J Clin Invest. 1987;79(1):207-13.
16. Burge MR, Garcia N, Qualls CR & Schade DS. Differential effects of fasting and dehydration in the pathogenesis of diabetic ketoacidosis. Metabolism. 2001;50(2):171-7.
17. Chico M, Levine SN, Lewis DF. Normoglycemic diabetic ketoacidosis in pregnancy. J Perinatol. 2008;28(4):310-2.
18. Modi A, Agrawal A, Morgan F. Euglycemic diabetic ketoacidosis. Current Diabetes Reviews. Curr Diabetes Rev. 2017;13(3):315-21.
19. Parker JA, Conway DL. Diabetic ketoacidosis in pregnancy. Obstet Gynecol Clin North Am. 2007;34(3):533-43.
20. Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care. 2015;38(9):1687-93.
21. Mostert M, Bonavia A. Starvation Ketoacidosis as a Cause of Unexplained Metabolic Acidosis in the Perioperative Period. Am J Case Rep. 2016;17:755-8.
22. Lulsegged A, Saeed E, Langford E, Duffield C, El-Hasani S, Pareek N. Starvation ketoacidosis in a patient with gastric banding. Clin Med (Lond). 2011;11(5):473-5
23. Sinha N, Venkatram S, Diaz-Fuentes G. Starvation ketoacidosis: a cause of severe anion gap metabolic acidosis in pregnancy. Case Rep Crit Care.2014;2014:906283.
24. Umpierrez GE, DiGirolamo M, Tuvlin JA, Isaacs SD, Bhoola SM, Kokko JP. Differences in metabolic and hormonal milieu in diabetic- and alcohol-induced ketoacidosis. J Crit Care. 2000;15(2):52-9.
25. McGuire LC, Cruickshank AM, Munro PT. Alcoholic ketoacidosis. Emerg Med J. 2006;23(6):417-20.
26. Tanaka M, Miyazaki Y, Ishikawa S, Matsuyama K. Alcoholic ketoacidosis associated with multiple complications: report of 3 cases. Intern Med. 2004;43(10):955-9.
27. Jenkins D, Close CF, Krentz AJ, Nattrass M, Wright AD. Euglycaemic diabetic ketoacidosis: does it exist? Acta Diabetol. 1993;30(4):251-3.
28. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335-43.
29. McNulty SJ, English PJ. Euglycaemic diabetic ketoacidosis. Practical Diabetes Int. 2002;19(2):63.
30. Umpierrez G, Korytkowski M. Diabetic emergencies — ketoacidosis, hyperglycaemic hyperosmolar state and hypoglycaemia. Nat Rev Endocrinol. 2016;12(4):222-32.
2. Modi A, Agrawal A, Morgan F. Euglycemic Diabetic Ketoacidosis: A Review. Curr Diabetes Rev. 2017;13(3):315-21.
3. Lee K, Park IB, Yu SH, Kim SK, Kim SH, Seo DH, et al. Characterization of variable presentations of diabetic ketoacidosis based on blood ketone levels and major society diagnostic criteria: a new view point on the assessment of diabetic ketoacidosis. Diabetes Metab Syndr Obes. 2019;12:1161-71.
4. Poudel RR, Kafle NK. Closing anion gap without insulin in euglycaemic diabetic ketoacidosis. J Diabetol. 2017;8:92-3.
5. Thawabi M, Studyvin S. Euglycemic Diabetic Ketoacidosis, a Misleading Presentation of Diabetic Ketoacidosis. N Am J Med Sci. 2015;7(6):291-4.
6. Munro JF, Campbell IW, McCuish AC, Duncan LJ. Euglycaemic diabetic ketoacidosis. Br Med J. 1973;2(5866):578-80.
7. Rawla P, Vellipuram AR, Bandaru SS, Pradeep Raj J. Euglycemic diabetic ketoacidosis: a diagnostic and therapeutic dilemma. Endocrinol Diabetes Metab Case Rep. 2017; 2017:17-0081.
8. Joseph F, Anderson L, Goenka N, Vora J. Starvationtiontionvation N, Vora euglycemic ketoacidosis in severe depression. J Gen Intern Med. 2009;24:129‑31
9. Rosenstock J, Ferrannini E. Euglycemic diabetic ketoacidosis: A Predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes Care. 2015;38:1638‑42.
10. Barski L, Eshkoli T, Brandstaetter E, Jotkowitz A. Euglycemic diabetic ketoacidosis. Eur J Intern Med. 2019;63:9-14.
11. Goldenberg RM, Berard LD, Cheng AYY, Gilbert JD, Verma S, Woo VC, et al. SGLT2 inhibitor-associated diabetic ketoacidosis: clinical review and recommendations for prevention and diagnosis. Clin Ther. 2016;38(12):2654–64.
12. Hine J, Paterson H, Abrol E, Russell-Jones D, Herring R. SGLT inhibition and euglycaemic diabetic ketoacidosis. Lancet Diabetes Endocrinol. 2015;3(7):503–4.
13. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335-43.
14. Wolfe RR, Peters EJ, Klein S, Holland OB, Rosenblatt J, Gary H Jr. Effect of short-term fasting on lipolytic responsiveness in normal and obese human subjects. Am J Physiol. 1987;252(2 Pt 1):E189-96.
15. Jensen MD, Haymond MW, Gerich JE, Cryer PE, Miles JM. Lipolysis during fasting. Decreased suppression by insulin and increased stimulation by epinephrine. J Clin Invest. 1987;79(1):207-13.
16. Burge MR, Garcia N, Qualls CR & Schade DS. Differential effects of fasting and dehydration in the pathogenesis of diabetic ketoacidosis. Metabolism. 2001;50(2):171-7.
17. Chico M, Levine SN, Lewis DF. Normoglycemic diabetic ketoacidosis in pregnancy. J Perinatol. 2008;28(4):310-2.
18. Modi A, Agrawal A, Morgan F. Euglycemic diabetic ketoacidosis. Current Diabetes Reviews. Curr Diabetes Rev. 2017;13(3):315-21.
19. Parker JA, Conway DL. Diabetic ketoacidosis in pregnancy. Obstet Gynecol Clin North Am. 2007;34(3):533-43.
20. Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care. 2015;38(9):1687-93.
21. Mostert M, Bonavia A. Starvation Ketoacidosis as a Cause of Unexplained Metabolic Acidosis in the Perioperative Period. Am J Case Rep. 2016;17:755-8.
22. Lulsegged A, Saeed E, Langford E, Duffield C, El-Hasani S, Pareek N. Starvation ketoacidosis in a patient with gastric banding. Clin Med (Lond). 2011;11(5):473-5
23. Sinha N, Venkatram S, Diaz-Fuentes G. Starvation ketoacidosis: a cause of severe anion gap metabolic acidosis in pregnancy. Case Rep Crit Care.2014;2014:906283.
24. Umpierrez GE, DiGirolamo M, Tuvlin JA, Isaacs SD, Bhoola SM, Kokko JP. Differences in metabolic and hormonal milieu in diabetic- and alcohol-induced ketoacidosis. J Crit Care. 2000;15(2):52-9.
25. McGuire LC, Cruickshank AM, Munro PT. Alcoholic ketoacidosis. Emerg Med J. 2006;23(6):417-20.
26. Tanaka M, Miyazaki Y, Ishikawa S, Matsuyama K. Alcoholic ketoacidosis associated with multiple complications: report of 3 cases. Intern Med. 2004;43(10):955-9.
27. Jenkins D, Close CF, Krentz AJ, Nattrass M, Wright AD. Euglycaemic diabetic ketoacidosis: does it exist? Acta Diabetol. 1993;30(4):251-3.
28. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335-43.
29. McNulty SJ, English PJ. Euglycaemic diabetic ketoacidosis. Practical Diabetes Int. 2002;19(2):63.
30. Umpierrez G, Korytkowski M. Diabetic emergencies — ketoacidosis, hyperglycaemic hyperosmolar state and hypoglycaemia. Nat Rev Endocrinol. 2016;12(4):222-32.
| Files | ||
| Issue | Vol 4 No 4 (2020): Autumn (October) | |
| Section | Review article | |
| Keywords | ||
| Diabetic Ketoacidosis Euglycemic DKA Normoglycemic DKA Review | ||
| Rights and permissions | |
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Niroomand M, Jalili M. Atypical Feature of Diabetic Ketoacidosis with Low or Normal Plasma Glucose: a Narrative Review. Front Emerg Med. 2019;4(4):e91.
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