Chapter 41
Acute Metabolic Complications of Diabetes
Diabetic Ketoacidosis and the Hyperosmolar Hyperglycaemic State in Adults
Philip Newland-Jones,
Mayank Patel,
Ketan Dhatariya,
Philip Newland-Jones
University Hospital Southampton NHS Foundation Trust, Southampton, UK
Search for more papers by this authorMayank Patel
University Hospital Southampton NHS Foundation Trust, Southampton, UK
Search for more papers by this authorKetan Dhatariya
Norfolk and Norwich University Hospitals NHS Foundation Trust and University of East Anglia, Norwich, UK
Search for more papers by this authorPhilip Newland-Jones,
Mayank Patel,
Ketan Dhatariya,
Philip Newland-Jones
University Hospital Southampton NHS Foundation Trust, Southampton, UK
Search for more papers by this authorMayank Patel
University Hospital Southampton NHS Foundation Trust, Southampton, UK
Search for more papers by this authorKetan Dhatariya
Norfolk and Norwich University Hospitals NHS Foundation Trust and University of East Anglia, Norwich, UK
Search for more papers by this authorBook Editor(s):Richard I.G. Holt MA, MB BChir, PhD, FRCP, FHEA,
Allan Flyvbjerg MD, DMSc,
Richard I.G. Holt MA, MB BChir, PhD, FRCP, FHEA
Professor in Diabetes & Endocrinology Faculty of Medicine Honorary Consultant Physician
Human Development and Health
University of Southampton, Southampton, UK
Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK
Search for more papers by this authorAllan Flyvbjerg MD, DMSc
Former CEO at Steno Diabetes Center Copenhagen (SDCC) Professor of Clinical Endocrinology
The Capital Region of Denmark
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorFirst published: 12 January 2024
Summary
Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS) are life-threatening emergencies in diabetes. Both are characterized by hyperglycaemia with insulinopaenia, with only the degree of hyperglycaemia, level of associated dehydration, and severity of the associated metabolic acidosis distinguishing them. This chapter reviews the pathogenesis and pathophysiology, precipitating factors, clinical presentation, management, complications, and prevention of DKA and HHS. Although the mechanisms for the development of DKA are multifactorial, there is always an undercurrent of absolute or relative insulin deficiency, often with a concomitant increase in counter-regulatory hormones. Insulin administration is an essential element of DKA management, as it both increases peripheral glucose utilization and decreases hepatic glucose output. Moreover, it inhibits the release of free fatty acid from adipose tissue and decreases ketogenesis. Improved education around awareness and risk factors for developing HHS are key to reducing future risk.
References
- Pasquel , F.J. and Umpierrez , G.E. ( 2014 ). Diab. Care 37 : 3124 – 3131 .
- Laine , C. , Williams , S. , Turner , B.J. , and Wilson , J.F. ( 2010 ). Ann. Intern. Med. 152 : ITC1-1 .
- Kitabchi , A.E. , Umpierrez , G.E. , Miles , J.M. , and Fisher , J.N. ( 2009 ). Diab. Care 32 : 1335 – 1343 .
- Dhatariya , K.K. , Glaser , N.S. , Codner , E. , and Umpierrez , G.E. ( 2020 ). Nat. Rev. Dis. Primers 6 : 40 .
- Dhatariya , K. , James , J. , Kong , M.-F. , and Berrington , R. ( 2020 ). Diab. Med. 37 : 1578 – 1589 .
- Kitabchi , A.E. and Wall , B.M. ( 1995 ). Med. Clin. N. Am. 79 : 9 – 37 .
- Kitabchi , A.E. , Umpierrez , G.E. , Murphy , M.B. et al. ( 2001 ). Diab. Care 24 : 131 – 153 .
- Umpierrez , G.E. , Smiley , D. , and Kitabchi , A.E. ( 2006 ). Ann. Intern. Med. 144 : 350 – 357 .
- Vellanki , P. and Umpierrez , G.E. ( 2017 ). Endocr. Pract. 23 : 971 – 978 .
- Peters , A.L. , Buschur , E.O. , Buse , J.B. et al. ( 2015 ). Diab. Care 38 : 1687 – 1693 .
- Wang , K.M. and Isom , R.T. ( 2020 ). Kidney Med. 2 : 218 – 221 .
- Centre for Perioperative Care ( 2021 ). Perioperative care of people with diabetes undergoing surgery . https://cpoc.org.uk/guidelines-resources-guidelines-resources/guideline-diabetes (accessed 8 February 2023).
- Pasquel , F.J. , Tsegka , K. , Wang , H. et al. ( 2020 ). Diab. Care 43 : 349 – 357 .
- Davis , S.N. and Umpierrez , G.E. ( 2007 ). Nat. Clin. Pract. Endocrinol. Metab. 3 : 730 – 731 .
- English , P. and Williams , G. ( 2004 ). Postgrad. Med. J. 80 : 253 – 261 .
- Miles , J.M. , Rizza , R.A. , Haymond , M.W. , and Gerich , J.E. ( 1980 ). Diabetes 29 : 926 – 930 .
- Foster , D.W. and McGarry , J.D. ( 1983 ). N. Engl. J. Med. 309 : 159 – 169 .
- Hatting , M. , Tavares , C.D. , Sharabi , K. et al. ( 2018 ). Ann. N. Y. Acad. Sci. 1411 : 21 – 35 .
- Schade , D.S. and Eaton , R.P. ( 1980 ). J. Clin. Endocrinol. Metab. 50 : 131 – 136 .
- Gerich , J.E. , Lorenzi , M. , Bier , D.M. et al. ( 1976 ). J. Clin. Invest. 57 : 875 – 884 .
- Exton , J.H. ( 1987 ). Diab. Metab. Rev. 3 : 163 – 183 .
- Palmer , B.F. and Clegg , D.J. ( 2015 ). N. Engl. J. Med. 373 : 548 – 559 .
- Nurjhan , N. , Consoli , A. , and Gerich , J. ( 1992 ). J. Clin. Invest. 89 : 169 – 175 .
- Miles , J.M. , Haymond , M.W. , Nissen , S.L. , and Gerich , J.E. ( 1983 ). J. Clin. Invest. 71 : 1554 – 1561 .
- McGarry , J.D. and Foster , D.W. ( 1980 ). Annu. Rev. Biochem. 49 : 395 – 420 .
- Stephens , J.M. , Sulway , M.J. , and Watkins , P.J. ( 1971 ). Diabetes 20 : 485 – 489 .
-
Dhatariya , K.K.
et al. (
2022
).
Diab. Med.
39
: e14788.
10.1111/dme.14788 Google Scholar
- Dhatariya , K. ( 2016 ). Rev. Diabet. Stud. 13 : 217 – 225 .
- Kraut , J.A. and Madias , N.E. ( 2007 ). Clin. J. Am. Soc. Nephrol. 2 : 162 – 174 .
- Burnell , J.M. , Villamil , M.F. , Uyeno , B.T. , and Scribner , B.H. ( 1956 ). J. Clin. Invest. 35 : 935 – 939 .
- Taylor , S.I. , Blau , J.E. , and Rother , K.I. ( 2015 ). J. Clin. Endocrinol. Metab. 100 : 2849 – 2852 .
- Ferrannini , E. , Muscelli , E. , Frascerra , S. et al. ( 2014 ). J. Clin. Invest. 124 : 499 – 508 .
- Perry , R.J. , Rabin-Court , A. , Song , J.D. et al. ( 2019 ). Nat. Commun. 10 : 548 .
- Rosenstock , J. and Ferrannini , E. ( 2015 ). Diab. Care 38 : 1638 – 1642 .
- Umpierrez , G. and Korytkowski , M. ( 2016 ). Nat. Rev. Endocrinol. 12 : 222 – 232 .
- Dabelea , D. , Rewers , A. , Stafford , J.M. et al. ( 2014 ). Pediatrics 133 : e938 – e945 .
- Patel , M. ( 2021 ). Medicine 49 : 106 – 109 .
- Akturk , H.K. , Kahramangil , D. , Sarwal , A. et al. ( 2019 ). Diab. Med. 36 : 1075 – 1081 .
- Ooi , E. , Nash , K. , Rengarajan , L. et al. ( 2021 ). BMJ Open Diab. Res. Care 9 : e002451 .
- Morris , A.D. , Boyle , D.I. , McMahon , A.D. et al. ( 1997 ). Lancet 350 : 1505 – 1510 .
- Butalia , S. , Johnson , J.A. , Ghali , W.A. , and Rabi , D.M. ( 2013 ). Diab. Med. 30 : 567 – 573 .
- Mays , J.A. , Jackson , K.L. , Derby , T.A. et al. ( 2016 ). Diab. Care 39 : 1671 – 1676 .
- Misra , S. , Khozoee , B. , Huang , J. et al. ( 2021 ). Diab. Care 44 : e29 – e31 .
- Umpierrez , G. and Freire , A.X. ( 2002 ). J. Crit. Care 17 : 63 – 67 .
- Umpierrez , G.E. , Kelly , J.P. , Navarrete , J.E. et al. ( 1997 ). Arch. Intern. Med. 157 : 669 – 675 .
- Dhatariya , K.K. and Umpierrez , G.E. ( 2017 ). Lancet Diab. Endocrinol. 5 : 321 – 323 .
- Modi , A. , Agrawal , A. , and Morgan , F. ( 2017 ). Curr. Diab. Rev. 13 : 315 – 321 .
- Macfarlane , J. and Dhatariya , K. ( 2019 ). Mayo Clin. Proc. 94 : 1909 – 1910 .
- Umpierrez , G.E. , DiGirolamo , M. , Tuvlin , J.A. et al. ( 2000 ). J. Crit. Care 15 : 52 – 59 .
- Munro , J.F. , Campbell , I.W. , McCuish , A.C. , and Duncan , J.P. ( 1973 ). Br. Med. J. 2 : 578 – 580 .
- Sheikh-Ali , M. , Karon , B.S. , Basu , A. et al. ( 2008 ). Diab. Care 31 : 643 – 647 .
- Adrogue , H.J. , Eknoyan , G. , and Suki , W.K. ( 1984 ). Kidney Int. 25 : 591 – 598 .
- Xu , W. , Wu , H.F. , Ma , S.G. et al. ( 2013 ). Int. J. Med. Sci. 10 : 758 – 765 .
- May , M.E. , Young , C. , and King , J. ( 1993 ). Am. J. Med. Sci. 306 : 287 – 294 .
- Moss , J.M. ( 1987 ). South Med. J. 80 : 875 – 881 .
- Umpierrez , G.E. , Latif , K. , Stoever , J. et al. ( 2004 ). Am. J. Med. 117 : 291 – 296 .
- Umpierrez , G.E. , Cuervo , R. , Karabell , A. et al. ( 2004 ). Diab. Care 27 : 1873 – 1878 .
- Kempegowda , P. , Chandan , J.S. , Coombs , B. et al. ( 2019 ). BMJ Open Diab. Res. Care 7 : e000695 .
- Kitabchi , A.E. , Murphy , M.B. , Spencer , J. et al. ( 2008 ). Diab. Care 31 : 2081 – 2085 .
- Rayman , G. , Lumb , A. , Kennon , B. et al. ( 2020 ). Diab. Med. 37 : 1214 – 1216 .
- Dhatariya , K.K. , Nunney , I. , Higgins , K. et al. ( 2016 ). Diab. Med. 33 : 252 – 260 .
- Lever , E. and Jaspan , J.B. ( 1983 ). Am. J. Med. 75 : 263 – 268 .
- Gamba , G. , Osequera , J. , Casterjon , M. , and Gomez-Perez , F.J. ( 1991 ). Rev. Invest. Clin. 43 : 234 – 238 .
- Latif , K.A. , Freire , A.X. , Kitabchi , A.E. et al. ( 2002 ). Diab. Care 25 : 2113 – 2114 .
- Kamel , K.S. and Halperin , M.L. ( 2015 ). N. Engl. J. Med. 372 : 546 – 554 .
- Wilson , H.K. , Keuer , S.P. , Lea , A.S. et al. ( 1982 ). Arch. Intern. Med. 142 : 517 – 520 .
- Choi , H.S. , Kwon , A. , Chae , H.W. et al. ( 2018 ). Ann. Pediatr. Endocrinol. Metab. 23 : 103 – 106 .
- Ditzel , J. and Lervang , H. ( 2019 ). Diab. Metab. Syndr. Obes. 3 : 319 – 324 .
- Shen , T. and Braude , S. ( 2012 ). Intern. Med. J. 42 : 1347 – 1350 .
- Kutlu , A.O. , Kara , C. , and Cetinkaya , S. ( 2011 ). Pediatr. Emerg. Care 27 : 537 – 538 .
- Ionescu-Tîrgovişte , C. , Bruckner , I. , Mihalache , N. , and Ionescu , C. ( 1981 ). Med. Int. 19 : 63 – 68 .
- Pham , P.-C. , Pham , P.-M. , Pham , S.V. et al. ( 2007 ). Clin. J. Am. Soc. Nephrol. 2 : 366 – 373 .
- Wolfsdorf , J. , Glaser , N. , and Sperling , M.A. ( 2006 ). Diab. Care 29 : 1150 – 1159 .
- Edge , J.A. , Jakes , R.W. , Roy , Y. et al. ( 2006 ). Diabetologia 49 : 2002 – 2009 .
- Lin , S. and Chien , Y.W. ( 2002 ). J. Pharm. Pharmacol. 54 : 791 – 800 .
- Hsia , E. , Seggelke , S. , Gibbs , J. et al. ( 2012 ). J. Clin. Endocrinol. Metab. 97 : 3132 – 3137 .
- George , S. , Dale , J. , and Stanisstreet , D. ( 2015 ). Diab. Med. 32 : 706 – 713 .
- Dashora , U. , Levy , N. , Dhatariya , K. et al., for The Joint British Diabetes Society for Inpatient Care group ( 2022 ). Diab. Med. 39 : e14744 .
- Frankel , A.H. , Wahba , M. , Ashworth , V . et al. ( 2023 ). Diab. Med. 40 : e15027 .
-
Evans , N.R.
,
Richardson , L.
,
Dhatariya , K.K.
, and
Sampson , M.J.
(
2012
).
Pract. Diab.
29
:
25
–
28
.
10.1002/pdi.1652 Google Scholar
- Zadkar , S.R. ( 2019 ). Res. Inno. in Anesth. 4 : 32 – 35 .
- Scott , A.R. and Joint British Diabetes Societies (JBDS) for Inpatient Care; JBDS Hyperosmolar Hyperglycaemic Guidelines Group ( 2015 ). BJD 15 ( 2 ): 75 .
- Mustafa , O.G. , Haq , M. , Dashora , U. et al. ( 2023 ). Diab. Med. 40 : e15005 .
- Karslioglu French , E. , Donihi , A.C. , and Korytkowski , M.T. ( 2019 ). BMJ 365 : l1114 .
- Chupin , M. , Charbonnel , B. , and Chupin , F. ( 1981 ). Acta Diabetol. Lat. 18 : 123 – 128 .
- Misra , S. , Barron , E. , Vamos , E. et al. ( 2021 ). Lancet Diab. Endocrinol. 9 : 671 – 680 .
- Tittel , S.R. , Sondern , K.M. , Weyer , M. et al. ( 2020 ). Acta Diabetol. 57 : 1245 – 1253 .
- Klingensmith , G.J. , Connor , C.G. , Ruedy , K.J. et al. ( 2016 ). Pediatr. Diab. 17 : 266 – 273 .
- Wachtel , T.J. ( 1990 ). Clin. Geriatr. Med. 6 : 797 – 806 .
- Wachtel , T.J. , Tetu-Mouradijian , L.M. , Goldman , D.L. et al. ( 1991 ). J. Gen. Intern. Med. 6 : 495 – 502 .
- Lorber , D. ( 1995 ). Med. Clin. N. Am. 79 : 39 – 52 .
- De Hert , M. , Detraux , J. , van Winkel , R. et al. ( 2012 ). Nat. Rev. Endocrinol. 8 : 114 – 126 .
-
Halmos , P.B.
,
Nelson , J.K.
, and
Lowry , R.C.
(
1966
).
Lancet
287
:
675
–
679
.
10.1016/S0140-6736(66)91626-6 Google Scholar
- Dhatariya , K. and Weston , P. ( 2021 ). BJD 21 : 282 – 283 .
- Singhal , P.C. , Abramovici , M. , and Venkatesan , J. ( 1990 ). Am. J. Med. Sci. 88 : 9 – 12 .
- Rumpf , K.W. , Kaiser , H. , Gröne , H.J. et al. ( 1981 ). Dtsch. Med. Wochenschr. 106 : 708 – 711 .
