Skip to main content
SpringerLink
Log in

Clinical profile of patients with diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome in Japan: a multicenter retrospective cohort study

  • Original Article
  • Published:
Acta Diabetologica Aims and scope Submit manuscript

Abstract

Introduction

Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar syndrome (HHS) are life-threatening complications of diabetes mellitus. Their clinical profiles have not been fully investigated.

Methods

A multicenter retrospective cohort study was conducted in 21 acute care hospitals in Japan. Patients included were adults aged 18 or older who had been hospitalized from January 1, 2012, to December 31, 2016 due to DKA or HHS. The data were extracted from patient medical records. A four-group comparison (mild DKA, moderate DKA, severe DKA, and HHS) was performed to evaluate outcomes.

Results

A total of 771 patients including 545 patients with DKA and 226 patients with HHS were identified during the study period. The major precipitating factors of disease episodes were poor medication compliance, infectious diseases, and excessive drinking of sugar-sweetened beverages. The median hospital stay was 16 days [IQR 10–26 days]. The intensive care unit (ICU) admission rate was 44.4% (mean) and the rate at each hospital ranged from 0 to 100%. The in-hospital mortality rate was 2.8% in patients with DKA and 7.1% in the HHS group. No significant difference in mortality was seen among the three DKA groups.

Conclusions

The mortality rate of patients with DKA in Japan is similar to other studies, while that of HHS was lower. The ICU admission rate varied among institutions. There was no significant association between the severity of DKA and mortality in the study population.

Trial Registration

This study is registered in the UMIN clinical Trial Registration System (UMIN000025393, Registered 23th December 2016).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Kitabchi AE, Umpierrez GE, Murphy MB, Kreisberg RA (2006) Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American diabetes association. Diabetes Care 29:2739–2748. https://doi.org/10.2337/dc06-9916

    Article  CAS  PubMed  Google Scholar 

  2. French EK, Donihi AC, Korytkowski MT (2019) Diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: review of acute decompensated diabetes in adult patients. BMJ. https://doi.org/10.1136/bmj.l1114

    Article  PubMed  Google Scholar 

  3. Pasquel FJ, Umpierrez GE (2014) Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment. Diabetes Care 37:3124–3131. https://doi.org/10.2337/dc14-0984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dhatariya KK, Nunney I, Higgins K et al (2016) National survey of the management of diabetic ketoacidosis (DKA) in the UK in 2014. Diabet Med 33:252–260. https://doi.org/10.1111/dme.12875

    Article  CAS  PubMed  Google Scholar 

  5. Fathallah N, Slim R, Larif S et al (2015) Drug-induced hyperglycaemia and diabetes. Drug Saf 38:1153–1168. https://doi.org/10.1007/s40264-015-0339-z

    Article  CAS  PubMed  Google Scholar 

  6. Gibb FW, Teoh WL, Graham J, Lockman KA (2016) Risk of death following admission to a UK hospital with diabetic ketoacidosis. Diabetologia 59:2082–2087. https://doi.org/10.1007/s00125-016-4034-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Benoit SR, Zhang Y, Geiss LS, Gregg EW, Albright A (2018) Trends in diabetic ketoacidosis hospitalizations and in-hospital mortality—United States, 2000–2014. Morb Mortal Wkly Rep 67(12):362. https://doi.org/10.15585/mmwr.mm6712a3

    Article  Google Scholar 

  8. Barski L, Nevzorov R, Rabaev E et al (2012) Diabetic ketoacidosis: clinical characteristics, precipitating factors and outcomes of care. Isr Med Assoc J 14:298–302

    Google Scholar 

  9. Mekonnen GA, Gelaye KA, Gebreyohannes EA, Abegaz TM (2022) Treatment outcomes of diabetic ketoacidosis among diabetes patients in Ethiopia. Hosp Based Study PLoS One 17:1–15. https://doi.org/10.1371/journal.pone.0264626

    Article  CAS  Google Scholar 

  10. Siregar NN, Soewondo P, Subekti I, Muhadi M (2018) Seventy-two hour mortality prediction model in patients with diabetic ketoacidosis: a retrospective cohort study. J ASEAN Fed Endocr Soc 33:124–129. https://doi.org/10.15605/jafes.033.02.03

    Article  PubMed  PubMed Central  Google Scholar 

  11. Fadini GP, de Kreutzenberg SV, Rigato M et al (2011) Characteristics and outcomes of the hyperglycemic hyperosmolar non-ketotic syndrome in a cohort of 51 consecutive cases at a single center. Diabetes Res Clin Pract 94:172–179. https://doi.org/10.1016/j.diabres.2011.06.018

    Article  PubMed  Google Scholar 

  12. Venkatesh B, Pilcher D, Prins J et al (2015) Incidence and outcome of adults with diabetic ketoacidosis admitted to ICUs in Australia and New Zealand. Crit Care 19:1–12. https://doi.org/10.1186/s13054-015-1171-7

    Article  Google Scholar 

  13. Gershengorn HB, Iwashyna TJ, Cooke CR et al (2012) Variation in use of intensive care for adults with diabetic ketoacidosis. Crit Care Med 40:2009–2015. https://doi.org/10.1097/CCM.0b013e31824e9eae

    Article  PubMed  PubMed Central  Google Scholar 

  14. Mendez Y, Surani S, Varon J (2017) Diabetic ketoacidosis: Treatment in the intensive care unit or general medical/surgical ward? World J Diabetes 8:40. https://doi.org/10.4239/wjd.v8.i2.40

    Article  PubMed  PubMed Central  Google Scholar 

  15. Zhou VL, Shofer FS, Desai NG et al (2019) Predictors of short intensive care unit stay for patients with diabetic ketoacidosis using a novel emergency department-based resuscitation and critical care unit. J Emerg Med 56:127–134. https://doi.org/10.1016/j.jemermed.2018.09.048

    Article  CAS  PubMed  Google Scholar 

  16. George JT, Ajay Kumar Mishra RI (2018) Correlation between the outcomes and severity of diabetic ketoacidosis: a retrospective pilot study. J Fam Med Prim Care 7:787–790. https://doi.org/10.4103/jfmpc.jfmpc_116_18

    Article  Google Scholar 

  17. Efstathiou SP, Tsiakou AG, Tsioulos DI et al (2002) A mortality prediction model in diabetic ketoacidosis. Clin Endocrinol (Oxf) 57:595–601. https://doi.org/10.1046/j.1365-2265.2002.01636.x

    Article  PubMed  Google Scholar 

  18. Novida H, Setiyawan F, Soelistijo SA (2021) A prediction model of mortality in patients hospitalized with diabetic ketoacidosis in a tertiary referral hospital in Surabaya, Indonesia. Indian J Forensic Med Toxicol 15:2519–2526. https://doi.org/10.37506/ijfmt.v15i2.14751

    Article  CAS  Google Scholar 

  19. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN (2009) Hyperglycemic crises in adult patients with diabetes. Diabetes Care 32:1335–1343. https://doi.org/10.2337/dc09-9032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Haas NL, Whitmore SP, Cranford JA et al (2020) An emergency department-based intensive care unit is associated with decreased hospital and intensive care unit utilization for diabetic ketoacidosis. J Emerg Med 58:620–626. https://doi.org/10.1016/j.jemermed.2019.10.005

    Article  PubMed  Google Scholar 

  21. Braatvedt G, Kwan A, Dransfield W et al (2019) Differing protocols of managing adult diabetic ketoacidosis outside of the intensive care unit make no difference to the rate of resolution of hyperglycaemia and acidosis. N Z Med J 132:13–23

    PubMed  Google Scholar 

  22. Chang DW, Shapiro MF (2016) Association between intensive care unit utilization during hospitalization and costs, use of invasive procedures, and mortality. JAMA Intern Med 176:1492–1499. https://doi.org/10.1001/jamainternmed.2016.4298

    Article  PubMed  Google Scholar 

  23. Sato Y, Morita K, Okada A et al (2021) Factors affecting in-hospital mortality of diabetic ketoacidosis patients: a retrospective cohort study. Diabetes Res Clin Pract 171:108588. https://doi.org/10.1016/j.diabres.2020.108588

    Article  PubMed  Google Scholar 

  24. Yamada K, Nonaka K (1996) Diabetic ketoacidosis in young obese Japanese men. Diabetes Care 19:671

    Article  CAS  PubMed  Google Scholar 

  25. Tanaka K, Moriya T, Kanamori A, Yajima Y (1999) Analysis and a long-term follow up of ketosis-onset Japanese NIDDM patients. Diabetes Res Clin Pract 44:137–146. https://doi.org/10.1016/S0168-8227(99)00023-6

    Article  CAS  PubMed  Google Scholar 

  26. Wachtel TJ, Tetu-Mouradjian LM, Goldman DL et al (1991) Hyperosmolarity and acidosis in diabetes mellitus—a 3 year experience in Rhode Island. J Gen Intern Med 6:495–502. https://doi.org/10.1007/BF02598216

    Article  CAS  PubMed  Google Scholar 

  27. Randall L, Begovic J, Hudson M et al (2011) Recurrent diabetic ketoacidosis in inner-city minority patients: behavioral, socioeconomic, and psychosocial factors. Diabetes Care 34:1891–1896. https://doi.org/10.2337/dc11-0701

    Article  PubMed  PubMed Central  Google Scholar 

  28. Yoshida M, McKeown NM, Rogers G et al (2007) Surrogate markers of insulin resistance are associated with consumption of sugar-sweetened drinks and fruit juice in middle and older-aged adults. J Nutr 137:2121–2127. https://doi.org/10.1093/jn/137.9.2121

    Article  CAS  PubMed  Google Scholar 

  29. den Biggelaar LJCJ, Sep SJS, Mari A et al (2020) Association of artificially sweetened and sugar-sweetened soft drinks with β-cell function, insulin sensitivity, and type 2 diabetes: the Maastricht Study. Eur J Nutr 59:1717–1727. https://doi.org/10.1007/s00394-019-02026-0

    Article  CAS  Google Scholar 

  30. Hwang JL, Weiss RE (2014) Steroid-induced diabetes: a clinical and molecular approach to understanding and treatment. Diabetes Metab Res Rev 30:96–102. https://doi.org/10.1002/dmrr.2486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Sarafidis PA, Bakris GL (2006) Antihypertensive treatment with beta-blockers and the spectrum of glycaemic control. QJM 99:431–436. https://doi.org/10.1093/qjmed/hcl059

    Article  CAS  PubMed  Google Scholar 

  32. Lean MEJ, Pajonk F-G (2003) Patients on atypical antipsychotic drugs. Diabetes Care 26:1597–1605. https://doi.org/10.2337/diacare.26.5.1597

    Article  CAS  PubMed  Google Scholar 

  33. Shafi T, Appel LJ, Miller ER et al (2008) Changes in serum potassium mediate thiazide-induced diabetes. Hypertension 52:1022–1029. https://doi.org/10.1161/HYPERTENSIONAHA.108.119438

    Article  CAS  PubMed  Google Scholar 

  34. Chou HW, Wang JL, Chang CH et al (2013) Risk of severe dysglycemia among diabetic patients receiving levofloxacin, ciprofloxacin, or moxifloxacin in Taiwan. Clin Infect Dis 57:971–980. https://doi.org/10.1093/cid/cit439

    Article  CAS  PubMed  Google Scholar 

  35. Bonaventura A, Montecucco F (2018) Steroid-induced hyperglycemia: an underdiagnosed problem or clinical inertia? A narrative review. Diabetes Res Clin Pract 139:203–220. https://doi.org/10.1016/j.diabres.2018.03.006

    Article  CAS  PubMed  Google Scholar 

  36. Manu P, Correll CU, Van Winkel R et al (2012) Prediabetes in patients treated with antipsychotic drugs. J Clin Psychiatry 73:460–466. https://doi.org/10.4088/JCP.10m06822

    Article  CAS  PubMed  Google Scholar 

  37. Vuk A, Kuzman MR, Baretic M, Osvatic MM (2017) Diabetic ketoacidosis associated with antipsychotic drugs: case reports and a review of literature. Psychiatr Danub 29:121–135. https://doi.org/10.24869/psyd.2017.121

    Article  CAS  PubMed  Google Scholar 

  38. Chinthapalli K, Newey A, Krause M (2015) Corticosteroid induced hyperosmolar hyperglycaemic state and hemiballismus. Oxford Med Case Rep 2015:320–322. https://doi.org/10.1093/omcr/omv051

    Article  Google Scholar 

  39. Peters AL, Buschur EO, Buse JB et al (2015) Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care 38:1687–1693. https://doi.org/10.2337/dc15-0843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Nasa P, Chaudhary S, Shrivastava PK, Singh A (2021) Euglycemic diabetic ketoacidosis: a missed diagnosis. World J Diabetes 12:514–523. https://doi.org/10.4239/wjd.v12.i5.514

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Not applicable

Funding

Not applicable.

Author information

Author notes

  1. Kyosuke Takahashi and Norimichi Uenishi are contributed equally as first authors.

Authors and Affiliations

  1. Department of Anesthesiology and Critical Care Medicine, Jichi Medical University Saitama Medical Center, 1-847 Amanumacho, Omiya-Ku, Saitama City, Saitama Prefecture, 330-0834, Japan

    Kyosuke Takahashi, Masamitsu Sanui & Shigehiko Uchino

  2. Department of Emergency and General Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan

    Norimichi Uenishi

  3. Department of Emergency and Critical Care Medicine, Yokohama City Minato Red Cross Hospital, Yokohama, Kanagawa, Japan

    Naoki Yonezawa & Tetsuhiro Takei

  4. Department of Preventive Services, Kyoto University Graduate School of Medicine, Sakyo, Kyoto, Japan

    Norihiro Nishioka

  5. Division of Nephrology, Department of Internal Medicine, Okinawa Prefectural Chubu Hospital, Uruma, Okinawa, Japan

    Norihiro Nishioka

  6. Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Hirotada Kobayashi

  7. Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada

    Hirotada Kobayashi

  8. Department of Intensive Care Medicine, Kameda Medical Center, Kamogawa, Chiba, Japan

    Hirotada Kobayashi

  9. Department of Emergency Medicine, International University of Health and Welfare Narita Hospital, Narita, Chiba, Japan

    Shunichi Otaka

  10. Department of Emergency Medicine, Kumamoto Red Cross Hospital, Higashi, Kumamoto, Japan

    Shunichi Otaka

  11. Department of Emergency Medicine, Musashino Red Cross Hospital, Musashino, Tokyo, Japan

    Kotaro Yamamoto & Hideto Yasuda

  12. Department of Emergency Medicine, Jichi Medical University Saitama Medical Center, Omiya, Saitama, Japan

    Hideto Yasuda

  13. Department of Medicine, Nerima Hikarigaoka Hospital, Nerima, Tokyo, Japan

    Shintaro Kosaka, Hidehiko Tokunaga & Naoki Fujiwara

  14. Department of Medicine, Taito Municipal Taito Hospital, Taito, Tokyo, Japan

    Naoki Fujiwara

  15. Department of Emergency and Critical Care Medicine, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan

    Takashiro Kondo

  16. Nanohana Clinic, Ikuno, Osaka, Japan

    Tomoki Ishida

  17. Department of Emergency Medicine, Yodogawa Christian Hospital, Higashi Yodogawa, Osaka, Japan

    Tomoki Ishida

  18. Department of Sports Medicine, Faculty of Medicine, Juntendo University, Bunkyo, Tokyo, Japan

    Takayuki Komatsu

  19. Department of Emergency and Critical Care Medicine, Juntendo University Nerima Hospital, Nerima, Tokyo, Japan

    Takayuki Komatsu

  20. Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Sakyo, Kyoto, Japan

    Koji Endo

  21. Department of General Internal Medicine, Tottori Prefectural Central Hospital, Tottori, Tottori, Japan

    Koji Endo

  22. Department of Emergency Medicine, Hyogo Emergency Medical Center, Kobe, Hyogo, Japan

    Taiki Moriyama

  23. Department of Emergency Medicine, Saiseikai Senri Hospital, Suita, Osaka, Japan

    Taiki Moriyama

  24. Department of Emergency Medicine, Hokkaido University Hospital, Sapporo, Hokkaido, Japan

    Takayoshi Oyasu & Mineji Hayakawa

  25. Department of Intensive Care Medicine, Tokyo Women’s Medical University Hospital, Shinjuku, Tokyo, Japan

    Atsumi Hoshino

  26. Department of Emergency and Critical Care Medicine, Toyooka Public Hospital, Toyooka, Hyogo, Japan

    Atsumi Hoshino

  27. Department of Emergency Medicine, Kyoto Prefectural University of Medicine, Kamigyo, Kyoto, Japan

    Tasuku Matsuyama & Yuki Miyamoto

  28. Department of Anesthesia, Gyoda General Hospital, Gyoda, Saitama, Japan

    Akihiro Yanagisawa

  29. Department of Anesthesiology and Intensive Care, Gunma University Hospital, Maebashi, Gunma, Japan

    Akihiro Yanagisawa

  30. Department of Medicine, Suwa Central Hospital, Chino, Nagano, Japan

    Tadamasa Wakabayashi

  31. Department of Cardiology, Suwa Central Hospital, Chino, Nagano, Japan

    Tadamasa Wakabayashi

  32. Department of Emergency and General Internal Medicine, Rakuwakai Marutamachi Hospital, Nakagyo, Kyoto, Japan

    Takeshi Ueda

  33. Department of Medicine, TMG Muneoka Central Hospital, Shiki, Saitama, Japan

    Tetsuya Komuro

  34. Department of Critical Care, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan

    Tetsuya Komuro

  35. Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan

    Toshiro Sugimoto

  36. Department of Medicine, National Hospital Organization Higashiohmi General Medical Center, Higashiohmi, Shiga, Japan

    Toshiro Sugimoto

  37. Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan

    Alan Kawarai Lefor

Authors
  1. Kyosuke Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Norimichi Uenishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masamitsu Sanui
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shigehiko Uchino
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Naoki Yonezawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tetsuhiro Takei
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Norihiro Nishioka
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hirotada Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shunichi Otaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kotaro Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hideto Yasuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shintaro Kosaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Hidehiko Tokunaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Naoki Fujiwara
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Takashiro Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Tomoki Ishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Takayuki Komatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Koji Endo
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Taiki Moriyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Takayoshi Oyasu
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Mineji Hayakawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Atsumi Hoshino
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Tasuku Matsuyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Yuki Miyamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Akihiro Yanagisawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Tadamasa Wakabayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Takeshi Ueda
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Tetsuya Komuro
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Toshiro Sugimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Alan Kawarai Lefor
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

KT collected and analyzed the data and wrote the manuscript. NU designed the study and collected and analyzed the data. MS designed and directed the project. SU analyzed the data and supervised the manuscript. NY, TT, NN, HK, SO, KY, HY, SK, HT, NF, TK, TI, TK, KE, TM, TO, MH, AH, TM, YM, AY, TW, TU, TK, and TS collected and analyzed the data. AKL supervised the manuscript and provided a reliable edit to correct English language errors. All authors checked and approved the final version of the manuscript.

Corresponding author

Correspondence to Kyosuke Takahashi.

Ethics declarations

Conflict of interest

None.

Ethical approval and consent to participate

The study design was approved by the ethics committee of Jichi Medical University (ID: RINS17-023. Registered 4th September 2017) and each institution with a waiver of informed consent prior to collecting the data. The study was performed in accordance with the Declaration of Helsinki.

Informed consent

Due to the nature of the retrospective study, informed consent is waived, which was approved by the ethics commitiy in each institution. Instead, we kept all data completely anonymous and provided opportunities for opting out of the study.

Additional information

Managed By Massimo Federici.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 14 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Takahashi, K., Uenishi, N., Sanui, M. et al. Clinical profile of patients with diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome in Japan: a multicenter retrospective cohort study. Acta Diabetol 61, 117–126 (2024). https://doi.org/10.1007/s00592-023-02181-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00592-023-02181-1

Keywords

Search

Navigation