Diabetic ketoacidosis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]


Development of diabetic ketoacidosis (DKA) is the result of a relative or absolute deficiency of insulin and an excess of glucagon. In diabetic patients, this leads to a shift from an anabolic state to a catabolic state. This leads to activation of various enzymes that cause an increase in blood glucose levels (via glycogenolysis and gluconeogenesis) and blood ketone levels (via lipolysis). The severe hyperglycemia results in glucosuria and osmotic diuresis leading to a state of dehydration. Muscle wasting is a consequence of proteolysis due an excess of counter-regulatory hormones (glucagon, catecholamines and cortisol).


Diabetic ketoacidosis (DKA) is the result of insulin deficiency from new-onset diabetes (usually type 1 diabetes), insulin noncompliance, prescription or illicit drug use, and increased insulin need because of any condition. DKA features hyperglycemia, acidosis, and high levels of circulating ketone bodies. When there is no or minute amounts of circulating insulin, for example in type 1 diabetes or less commonly in type 2 diabetes, the consequence is an elevation of counter-regulatory hormones/stress hormones (glucagon, catecholamines, cortisol, and growth hormone). This process eventually leads to the development of DKA.[1]


Insulin deficiency

Increased lipolysis and ketogenesis

Basic enzymes involved

Ketosis and acedemia in DKA

Increased blood glucose level

Basic enzymes involved

Hyperglycemia in DKA

Muscle wasting

Pathophysiology of diabetic ketoacidosis at a glance

Profound insulin deficiency/stress/infection
Increased levels of counter-regulatory hormones (glucagon, catecholamines, cortisol)
Increased lipolysis
Increased proteolysis, decreased protein synthesis (increased availability of gluconeogenic substrates)
Increased glycogenolysis
Increased ketogenesis (acidosis)
Increased gluconeogenesis (hyperglycemia)
Glucosuria and dehydration
Glucosuria and dehydration

Associated Conditions

The following conditions are associated with diabetic ketoacidosis (DKA):


  1. Chiasson JL, Aris-Jilwan N, Bélanger R, Bertrand S, Beauregard H, Ekoé JM, Fournier H, Havrankova J (2003). "Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state". CMAJ. 168 (7): 859–66. PMC 151994. PMID 12668546.
  2. van Belle TL, Coppieters KT, von Herrath MG (2011). "Type 1 diabetes: etiology, immunology, and therapeutic strategies". Physiol. Rev. 91 (1): 79–118. doi:10.1152/physrev.00003.2010. PMID 21248163.
  3. Leahy JL (2005). "Pathogenesis of type 2 diabetes mellitus". Arch. Med. Res. 36 (3): 197–209. doi:10.1016/j.arcmed.2005.01.003. PMID 15925010.
  4. Gelfand RA, Matthews DE, Bier DM, Sherwin RS (1984). "Role of counterregulatory hormones in the catabolic response to stress". J. Clin. Invest. 74 (6): 2238–48. doi:10.1172/JCI111650. PMC 425416. PMID 6511925.
  5. "Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes - Laffel - 1999 - Diabetes/Metabolism Research and Reviews - Wiley Online Library".
  6. 6.0 6.1 Holm C (2003). "Molecular mechanisms regulating hormone-sensitive lipase and lipolysis". Biochem. Soc. Trans. 31 (Pt 6): 1120–4. doi:10.1042/ Check |doi= value (help). PMID 14641008.
  7. Duncan RE, Ahmadian M, Jaworski K, Sarkadi-Nagy E, Sul HS (2007). "Regulation of lipolysis in adipocytes". Annu. Rev. Nutr. 27: 79–101. doi:10.1146/annurev.nutr.27.061406.093734. PMC 2885771. PMID 17313320.
  8. Brownsey RW, Boone AN, Elliott JE, Kulpa JE, Lee WM (2006). "Regulation of acetyl-CoA carboxylase". Biochem. Soc. Trans. 34 (Pt 2): 223–7. doi:10.1042/BST20060223. PMID 16545081.
  9. Tong L (2005). "Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target for drug discovery". Cell. Mol. Life Sci. 62 (16): 1784–803. doi:10.1007/s00018-005-5121-4. PMID 15968460.
  10. Choi SM, Tucker DF, Gross DN, Easton RM, DiPilato LM, Dean AS, Monks BR, Birnbaum MJ (2010). "Insulin regulates adipocyte lipolysis via an Akt-independent signaling pathway". Mol. Cell. Biol. 30 (21): 5009–20. doi:10.1128/MCB.00797-10. PMC 2953052. PMID 20733001.
  11. 11.0 11.1 Foster DW, McGarry JD (1982). "The regulation of ketogenesis". Ciba Found. Symp. 87: 120–31. PMID 6122545.
  12. Liljenquist JE, Bomboy JD, Lewis SB, Sinclair-Smith BC, Felts PW, Lacy WW, Crofford OB, Liddle GW (1974). "Effects of glucagon on lipolysis and ketogenesis in normal and diabetic men". J. Clin. Invest. 53 (1): 190–7. doi:10.1172/JCI107537. PMC 301453. PMID 4808635.
  13. 13.0 13.1 Halestrap AP, Denton RM (1973). "Insulin and the regulation of adipose tissue acetyl-coenzyme A carboxylase". Biochem. J. 132 (3): 509–17. PMC 1177615. PMID 4146798.
  14. Holland R, Hardie DG, Clegg RA, Zammit VA (1985). "Evidence that glucagon-mediated inhibition of acetyl-CoA carboxylase in isolated adipocytes involves increased phosphorylation of the enzyme by cyclic AMP-dependent protein kinase". Biochem. J. 226 (1): 139–45. PMC 1144686. PMID 2858203.
  15. Serra D, Casals N, Asins G, Royo T, Ciudad CJ, Hegardt FG (1993). "Regulation of mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase protein by starvation, fat feeding, and diabetes". Arch. Biochem. Biophys. 307 (1): 40–5. doi:10.1006/abbi.1993.1557. PMID 7902069.
  16. "www.niddk.nih.gov" (PDF).
  17. Schreurs M, Kuipers F, van der Leij FR (2010). "Regulatory enzymes of mitochondrial beta-oxidation as targets for treatment of the metabolic syndrome". Obes Rev. 11 (5): 380–8. doi:10.1111/j.1467-789X.2009.00642.x. PMID 19694967.
  18. DiMarco JP, Hoppel C (1975). "Hepatic mitochondrial function in ketogenic states. Diabetes, starvation, and after growth hormone administration". J. Clin. Invest. 55 (6): 1237–44. doi:10.1172/JCI108042. PMC 301878. PMID 124319.
  19. 19.0 19.1 "Diabetic Ketoacidosis: Evaluation and Treatment - American Family Physician".
  20. Ruderman NB, Goodman MN (1974). "Inhibition of muscle acetoacetate utilization during diabetic ketoacidosis". Am. J. Physiol. 226 (1): 136–43. PMID 4203779.
  21. Féry F, Balasse EO (1985). "Ketone body production and disposal in diabetic ketosis. A comparison with fasting ketosis". Diabetes. 34 (4): 326–32. PMID 3918903.
  22. Bulman GM, Arzo GM, Nassimi MN (1979). "An outbreak of tropical theileriosis in cattle in Afghanistan". Trop Anim Health Prod. 11 (1): 17–20. PMID 442206.
  23. Pilkis SJ, El-Maghrabi MR, McGrane M, Pilkis J, Claus TH (1982). "Regulation by glucagon of hepatic pyruvate kinase, 6-phosphofructo 1-kinase, and fructose-1,6-bisphosphatase". Fed. Proc. 41 (10): 2623–8. PMID 6286362.
  24. Chiasson JL, Aris-Jilwan N, Bélanger R, Bertrand S, Beauregard H, Ekoé JM, Fournier H, Havrankova J (2003). "Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state". CMAJ. 168 (7): 859–66. PMC 151994. PMID 12668546.
  25. Chiasson JL, Aris-Jilwan N, Bélanger R, Bertrand S, Beauregard H, Ekoé JM, Fournier H, Havrankova J (2003). "Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state". CMAJ. 168 (7): 859–66. PMC 151994. PMID 12668546.

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