Case history
A 20-year-old man is brought to the accident and emergency department with abdominal pain, nausea, and vomiting with increasing polyuria, polydipsia, and drowsiness since the previous day. He was diagnosed with type 1 diabetes 2 years previously. He mentions that he ran out of insulin 2 days ago. Vital signs on admission are: BP 106/67 mmHg, heart rate 123 beats per minute, respiratory rate 32 breaths per minute, temperature 37.1°C (98.8°F). He is drowsy. Physical examination reveals Kussmaul breathing (deep and rapid respiration due to ketoacidosis) with acetone odour and mild generalised abdominal tenderness without guarding or rebound tenderness. Initial laboratory data are: blood glucose 25 mmol/L, arterial pH 7.24, PCO2 25 mmHg, bicarbonate 12 mmol/L, WBC count 18.5 × 10⁹/L, sodium 128 mmol/L, potassium 5.2 mmol/L, chloride 97 mmol/L, serum urea 11.4 mmol/L, creatinine 150.3 micromol/L, blood ketones (beta-hydroxybutyrate) 4.8 mmol/L.
Other presentations
It is now well recognised that new-onset type 2 diabetes can present with diabetic ketoacidosis (DKA). These patients are typically individuals with obesity and undiagnosed hyperglycaemia, impaired insulin secretion, and insulin resistance. After treatment of the acute hyperglycaemic episode with insulin, beta-cell function and insulin sensitivity often improve, allowing discontinuation of insulin therapy. Many can subsequently be managed with oral agents or lifestyle modification alone, with approximately 40% remaining insulin-independent 10 years after the initial episode of DKA.[4]Mauvais-Jarvis F, Sobngwi E, Porcher R, et al. Ketosis-prone type 2 diabetes in patients of sub-Saharan African origin: clinical pathophysiology and natural history of beta-cell dysfunction and insulin resistance. Diabetes. 2004;53:645-653.
http://diabetes.diabetesjournals.org/content/53/3/645.full
http://www.ncbi.nlm.nih.gov/pubmed/14988248?tool=bestpractice.com
These patients do not exhibit the autoimmune laboratory findings characteristic of type 1 diabetes.[1]Umpierrez GE, Davis GM, ElSayed NA, et al. Hyperglycaemic crises in adults with diabetes: a consensus report. Diabetologia. 2024 Aug;67(8):1455-79.
https://link.springer.com/article/10.1007/s00125-024-06183-8
http://www.ncbi.nlm.nih.gov/pubmed/38907161?tool=bestpractice.com
[5]Umpierrez GE. Ketosis-prone type 2 diabetes: time to revise the classification of diabetes. Diabetes Care. 2006 Dec;29(12):2755-7.
https://diabetesjournals.org/care/article/29/12/2755/26306/Ketosis-Prone-Type-2-DiabetesTime-to-revise-the
This condition has been described as 'type 1 and 1/2' (or 'type 1 and a half') diabetes, 'Flatbush' diabetes, 'atypical diabetes', or 'ketosis-prone' diabetes.
Otherwise, it is rare for DKA to develop spontaneously in patients with type 2 diabetes. When it does occur, it is usually precipitated by missed or inadequate insulin doses or associated with infection, severe illness, trauma, surgery, or the use of certain drugs (e.g., sodium-glucose cotransporter-2 [SGLT2] inhibitors or the dual SGLT1/SGLT2 inhibitor sotagliflozin).[6]American Diabetes Association. Standards of care in diabetes -2025. Diabetes Care. 2025 Jan 1;48(Suppl 1): S1-343.
https://diabetesjournals.org/care/issue/48/Supplement_1
[7]Al-Hindi B, Mohammed MA, Mangantig E, et al. Prevalence of sodium-glucose transporter 2 inhibitor-associated diabetic ketoacidosis in real-world data: A systematic review and meta-analysis. J Am Pharm Assoc (2003). 2024 Jan-Feb;64(1):9-26.e6.
https://www.japha.org/article/S1544-3191(23)00317-5/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/37844733?tool=bestpractice.com
An extreme hyperosmolar state resembling hyperosmolar hyperglycaemic state (HHS) may also occur in combination with DKA, particularly in type 1 diabetes.[8]Umpierrez GE, Woo W, Hagopian WA, et al. Immunogenetic analysis suggests different pathogenesis for obese and lean African-Americans with diabetic ketoacidosis. Diabetes Care. 1999 Sep;22(9):1517-23.
http://www.ncbi.nlm.nih.gov/pubmed/10480519?tool=bestpractice.com
[4]Mauvais-Jarvis F, Sobngwi E, Porcher R, et al. Ketosis-prone type 2 diabetes in patients of sub-Saharan African origin: clinical pathophysiology and natural history of beta-cell dysfunction and insulin resistance. Diabetes. 2004;53:645-653.
http://diabetes.diabetesjournals.org/content/53/3/645.full
http://www.ncbi.nlm.nih.gov/pubmed/14988248?tool=bestpractice.com
[9]Umpierrez GE, Smiley D, Kitabchi AE. Narrative review: ketosis-prone type 2 diabetes mellitus. Ann Intern Med. 2006;144:350-357.
http://www.ncbi.nlm.nih.gov/pubmed/16520476?tool=bestpractice.com
[10]Kitabchi AE, Umpierrez GE, Fisher JN, et al. Thirty years of personal experience in hyperglycemic crises: diabetic ketoacidosis and hyperglycemic hyperosmolar state. J Clin Endocrinol Metab. 2008;93:1541-1552.
http://www.ncbi.nlm.nih.gov/pubmed/18270259?tool=bestpractice.com
It is estimated that one third of hyperglycaemic emergencies have a hybrid DKA-HHS presentation.[6]American Diabetes Association. Standards of care in diabetes -2025. Diabetes Care. 2025 Jan 1;48(Suppl 1): S1-343.
https://diabetesjournals.org/care/issue/48/Supplement_1