---
title: "Undiagnosed type 2 diabetes presenting as DKA with hypertriglyceridemia-induced acute pancreatitis"
id: "cmaj-1-undiagnosed-type-2-diabetes-presenting-as-diabetic-ketoacidosis-with"
canonical_url: "https://medichelpline.com/clinical-feed/cmaj-1-undiagnosed-type-2-diabetes-presenting-as-diabetic-ketoacidosis-with"
content_type: "clinical_feed_article"
specialty: "Endocrinology"
source_name: "CMAJ"
source_url: "http://www.cmaj.ca/cgi/content/short/198/29/E1153?rss=1"
published_at: "2026-08-24T04:05:24.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Undiagnosed type 2 diabetes presenting as DKA with hypertriglyceridemia-induced acute pancreatitis
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/cmaj-1-undiagnosed-type-2-diabetes-presenting-as-diabetic-ketoacidosis-with
- **Specialty:** [Endocrinology](https://medichelpline.com/clinical-feed/endocrinology.md)
- **Primary Source:** CMAJ
- **Source URL:** [Original Journal Publication](http://www.cmaj.ca/cgi/content/short/198/29/E1153?rss=1)
- **Published At:** 2026-08-24T04:05:24.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- A 27-year-old man with obesity (BMI 40) and undiagnosed diabetes presented with 24 hours of abdominal pain, vomiting, polyuria and lethargy and was found to have **diabetic ketoacidosis** (pH 7.24, bicarbonate 11 mmol/L, positive ketones) and biochemical hyperglycemia (random glucose 22.6 mmol/L). - Imaging (CT, ultrasound) showed acute pancreatitis with a swollen pancreas and peripancreatic fat stranding and no gallstones; serum amylase was elevated to 309 U/L, while lipase was not measured. - The laboratory noted a markedly lipemic sample and measured a triglyceride level of 41.5 mmol/L on admission, but these results were not acted on during the hospital stay and were retrospectively recognized. - The patient received IV fluids, insulin infusion, antibiotics and supportive care; symptoms and pancreatitis markers resolved within a week and he was discharged on insulin and referred to diabetes and gastroenterology clinics. - Diabetes autoantibodies (IA-2, ZnT8, islet cell) were negative; GAD antibody testing was initially not possible because of lipemia but was negative on repeat outpatient testing. The working diagnosis became **type 2 diabetes**. - Repeat fasting triglyceride remained high (15.0 mmol/L); the patient was started on atorvastatin and later fenofibrate after lipid clinic review, which diagnosed mixed hyperlipidemia with predominant hypertriglyceridemia. - Over 12 months with lifestyle measures and lipid-lowering therapy his triglycerides fell to 8.8 mmol/L, but glycemic control deteriorated (HbA1c 95 mmol/mol). The team started tirzepatide after shared decision-making despite prior pancreatitis; over 2 years his triglycerides normalized to 2.0 mmol/L, HbA1c improved to 53 mmol/mol and BMI decreased to 34.5, permitting insulin discontinuation. - The case illustrates pathophysiology linking insulin resistance, hypertriglyceridemia and pancreatitis; it emphasizes that **DKA** occurs in type 2 diabetes, that triglyceride measurement should be routine in acute pancreatitis, and that system errors in result communication can lead to missed diagnoses. - The authors note therapeutic considerations: IV insulin treats both DKA and severe hypertriglyceridemia; plasmapheresis is an option when insulin fails; novel APOC3-targeted agents exist for refractory hypertriglyceridemia; and incretin-based therapies (GLP-1 and dual GLP-1/GIP agonists such as **tirzepatide**) require individualized risk–benefit discussion in patients with prior pancreatitis.
## Clinical Analysis & Structured Key Points
Undiagnosed type 2 diabetes presenting as diabetic ketoacidosis with hypertriglyceridemia-induced acute pancreatitis | CMAJ Skip to main content Log in Toggle navigation menu Open settings menu Open search Advanced Search Advanced Search Log in --> Undiagnosed type 2 diabetes presenting as diabetic ketoacidosis with hypertriglyceridemia-induced acute pancreatitis Sangeeth P.V. Rathakrishnan Sangeeth P.V. Rathakrishnan Department of Endocrinology and Diabetes (Rathakrishnan, Syed, Paisley, Kochhar), Salford Royal NHS Foundation Trust, Salford, UK; Faculty of Biology, Medicine and Health (Syed, Paisley, Kochhar), University of Manchester, Manchester, UK. MBBS Find this author on Google Scholar Find this author on PubMed Search for this author on this site Akheel A. Syed Akheel A. Syed Department of Endocrinology and Diabetes (Rathakrishnan, Syed, Paisley, Kochhar), Salford Royal NHS Foundation Trust, Salford, UK; Faculty of Biology, Medicine and Health (Syed, Paisley, Kochhar), University of Manchester, Manchester, UK. MBBS PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Angela N. Paisley Angela N. Paisley Department of Endocrinology and Diabetes (Rathakrishnan, Syed, Paisley, Kochhar), Salford Royal NHS Foundation Trust, Salford, UK; Faculty of Biology, Medicine and Health (Syed, Paisley, Kochhar), University of Manchester, Manchester, UK. MBChB MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site and Rupinder S. Kochhar Rupinder S. Kochhar Department of Endocrinology and Diabetes (Rathakrishnan, Syed, Paisley, Kochhar), Salford Royal NHS Foundation Trust, Salford, UK; Faculty of Biology, Medicine and Health (Syed, Paisley, Kochhar), University of Manchester, Manchester, UK. MBBS MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site CMAJ August 24, 2026 198 (29) E1153-E1155; DOI: https://doi.org/10.1503/cmaj.260244 PDF Help Article Figures & Tables Related Content Responses Metrics PDF Key points Diabetic ketoacidosis with severe hypertriglyceridemia-induced acute pancreatitis as the initial presentation of type 2 diabetes is a rare, severe metabolic emergency. Diabetic ketoacidosis is not exclusively associated with type 1 diabetes; it is increasingly recognized in patients with type 2 diabetes, particularly those who are young, those with obesity, and those with metabolic syndrome. Hypertriglyceridemia should be considered in all patients presenting with acute pancreatitis. Incretin-based therapies can be judiciously considered in patients with a history of pancreatitis, with careful patient assessment and counselling. A 27-year-old man presented to the emergency department with 24 hours of generalized abdominal pain, vomiting, polyuria, and lethargy. His medical history included depression (treated with citalopram) and obesity (body mass index 40). He reported minimal alcohol consumption of 0 to 4 units/week, and a family history of type 2 diabetes. He was alert, with a heart rate of 131 beats/min, a respiration rate of 20 breaths/min, oxygen saturation of 96% on room air, a temperature of 37°C, and blood pressure of 169/98 mm Hg. Laboratory investigations revealed a serum sodium level of 128 (reference 133 to 145) mmol/L, a random plasma glucose level of 22.6 (reference < 11.1) mmol/L, and an amylase level of 309 (reference 30 to 118) U/L; serum lipase was not measured. The serum sample was noted to be lipemic by the laboratory staff, who independently performed lipid testing; however, this additional observation was not reviewed by the clinical team during the admission. Venous blood gas analysis showed metabolic acidosis with a pH of 7.24 (reference 7.32 to 7.43) and a bicarbonate level of 11 (reference 22 to 29) mmol/L. Blood and urine dipstick tests were strongly positive for ketones. Abdominal computed tomography (CT) showed features of acute pancreatitis without evidence of biliary disease ( Figure 1 ). Abdominal ultrasonography confirmed a normal biliary tree with no gallstones. Download figure Open in new tab Download PowerPoint Figure 1: Abdominal computed tomography of a 27-year-old man with undiagnosed type 2 diabetes who presented in diabetic ketoacidosis with hypertriglyceridemia-induced acute pancreatitis showing a swollen pancreas (arrow) with peripancreatic fat stranding, characteristic of acute pancreatitis. The emergency department team diagnosed diabetic ketoacidosis (DKA) associated with acute pancreatitis. On admission to the medical ward, the patient received intravenous fluids, an insulin infusion, intravenous amoxicillin and metronidazole for coverage against intra-abdominal sepsis, and supportive care. His blood glucose control improved, and his symptoms and laboratory abnormalities from acute pancreatitis resolved within a week. He was reviewed by the inpatient diabetes team; they noted a glycated hemoglobin (HbA 1c ) level of 116 mmol/mol (12.8%) and sent samples for diabetes-specific autoantibody tests. He was discharged on insulin therapy with referrals to the outpatient diabetes and gastroenterology clinics. Results from autoantibody tests, reviewed 3 weeks after discharge, were negative for islet antigen-2, zinc transporter 8, and islet cell antibodies. Testing for glutamic acid decarboxylase antibodies could not be performed on the initial sample because of lipemia, but results were negative when he was retested in the outpatient clinic. The patient was started on metformin (final dose 1 g, twice daily) and a basal-bolus insulin regimen comprising insulin detemir (22 units with breakfast, 24 units at bedtime), and insulin aspart (10 to 14 units, 3 times daily with meals). We saw the patient in our diabetes specialist clinic 6 months after discharge. Considering his phenotype and autoantibody results, we diagnosed type 2 diabetes. His HbA 1c level improved to 73 mmol/mol (8.8%) with insulin, metformin, and continuous glucose monitoring. Retrospective review of his admission laboratory results revealed a triglyceride level of 41.5 (reference < 1.7) mmol/L, unfortunately overlooked during hospitalization. We made a retrospective diagnosis of hypertriglyceridemia-induced acute pancreatitis with DKA. As his repeat fasting triglyceride level remained elevated at 15.0 mmol/L, we started atorvastatin (final dose 40 mg daily) and referred him to the specialist lipid clinic. His thyroid function was normal and apolipoprotein E2 homozygosity was absent, excluding familial dysbetalipoproteinemia. The lipid clinic’s clinicians diagnosed mixed hyperlipidemia with predominant hypertriglyceridemia, and advised dietary modifications, weight management, and fenofibrate (final dose 160 mg daily). At 12 months, the patient’s triglyceride level had decreased to 8.8 mmol/L (Appendix 1, Figure 1, available at www.cmaj.ca/lookup/doi/10.1503/cmaj.260244/tab-related-content ), his HbA 1c level had increased to 95 mmol/mol (10.8%), and his BMI was 38.4. To address suboptimal glycemic control, persistent obesity, and residual hypertriglyceridemia, we considered tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist with demonstrated efficacy across all 3 domains. As pancreatitis is a recognized potential adverse effect of incretin-based therapies, and given our patient’s history of acute pancreatitis, we discussed these risks with the patient and reached a shared decision to start tirzepatide. Together with the diabetes team, he titrated the doses of all diabetes medications gradually over the next few months. At follow-up 2 years after initial presentation, the patient demonstrated substantial improvement. His triglyceride level had normalized to 2.0 mmol/L, his HbA 1c level had decreased to 53 mmol/mol (7%), and his BMI had decreased to 34.5 (Appendix 1, Figure 2), with no evidence of diabetic retinopathy on clinical examination. During his most recent visit, we discontinued his insulin therapy, and continued his treatment regimen of tirzepatide, metformin, atorvastatin, and fenofibrate. Discussion Acute pancreatitis is a common, life-threatening medical emergency with a mortality of roughly 1%. 1 Gallstones and alcohol account for most cases, with hypertriglyceridemia the third most common cause (5% to 22% of episodes), yet hypertriglyceridemia-induced acute pancreatitis is frequently underdiagnosed. 2 , 3 Acute pancreatitis due to hypertriglyceridemia results from breakdown of high levels of triglyceride-rich lipoproteins by pancreatic lipase in the pancreatic capillaries to free fatty acids and lysophosphatidylcholine, causing pancreatic damage. Elevated chylomicron levels also increase plasma viscosity in the pancreatic capillaries, resulting in stasis and hypoxic injury in the pancreas. Triglyceride levels higher than 11.3 mmol/L (1000 mg/dL) are usually required for triggering acute pancreatitis. The lifetime risk increases progressively with rising triglyceride levels, from approximately 5% at a triglyceride level of 11.3 mmol/L to 10% to 20% with levels greater than 22.6 mmol/L (2000 mg/dL). 2 This case highlights a complex and potentially life-threatening metabolic emergency in which a young adult with obesity and undiagnosed diabetes presented in DKA associated with acute pancreatitis, likely caused by severe hypertriglyceridemia. The global rise of “diabesity” — a term referencing the combined adverse health effects of obesity and diabetes — is a growing public health concern. Historically, DKA has been linked with type 1 diabetes but is increasingly recognized in patients with type 2 diabetes. Infections, surgery, cardiovascular events, nonadherence to antidiabetic medications such as insulin and sulfonylurea medications, and the use of sodium–glucose cotransporter-2 inhibitors during acute illness can all trigger DKA in patients with type 2 diabetes. 4 Glucotoxicity impairs β-cell function and reduces insulin reserve, while obesity-related inflammation, elevated free fatty acids, and insulin resistance further promote metabolic decompensation. When these acute stressors occur, residual insulin secretion may become insufficient to suppress lipolysis and ketogenesis, precipitating DKA. As insulin resistance worsens, plasma triglyceride levels rise because of diminished lipoprotein lipase activity, creating conditions for hypertriglyceridemia-induced acute pancreatitis, which carries a significantly higher risk of severe pancreatitis than other causes. 5 Clinicians should no longer associate DKA with type 1 diabetes alone, especially in patients with obesity and metabolic syndrome, and autoantibody testing should be performed before committing to a diabetes classification. We postulate that acute pancreatitis contributed to the development and severity of DKA in our patient. Systemic inflammation from acute pancreatitis induces stress-related insulin resistance which, coupled with potential direct β-cell injury, can exacerbate pre-existing relative insulin deficiency, leading to DKA. Intravenous insulin is a cornerstone of managing both DKA and severe hypertriglyceridemia-induced pancreatitis as it stimulates lipoprotein lipase activity, rapidly clearing circulating triglycerides and reducing free fatty acid toxicity on the pancreas. When triglyceride levels remain critically elevated despite insulin therapy, plasmapheresis may be considered, although evidence of improved outcomes remains uncertain. Novel therapies targeting apolipoprotein C-III — such as small interfering RNA–based plozasiran and antisense oligonucleotides olezarsen and volanesorsen — have shown promise in refractory cases. 6 Early recognition and management of hypertriglyceridemia are crucial for optimal outcomes. Reducing triglyceride levels below 2.26 mmol/L (approximately 200 mg/dL) in severe hypertriglyceridemia lowers the risk of pancreatitis and cardiovascular events. 7 For patients with diabetes, a history of or increased risk for acute pancreatitis may create treatment dilemmas when considering incretin-based therapies, despite their efficacy for type 2 diabetes and obesity. These therapies include GLP-1 receptor agonists (such as semaglutide and liraglutide), and dual GLP-1 and GIP receptor agonists (tirzepatide). Postmarketing surveillance identified pancreatic inflammation with GLP-1 receptor agonists, leading regulatory agencies to include pancreatitis warnings in prescribing information. Subsequent large-scale evidence, however, has been reassuring. For GLP-1 receptor agonists, a meta-analysis and large cohort studies have found no significant increase in risk of pancreatitis. 8 , 9 For tirzepatide at all doses, evidence shows comparable pancreatitis risk to placebo, insulin, and GLP-1 receptor agonists. 10 A cohort study showed tirzepatide was associated with the lowest recurrence rate for pancreatitis among all incretin-based therapies. 11 Beyond pancreatic safety, tirzepatide has demonstrated superiority over GLP-1 receptor agonists for glycemic control, weight loss, and triglyceride reduction. 12 In our patient, tirzepatide was associated with sustained improvements in glycemic control, weight, and triglyceride levels over 12 months without recurrence of pancreatitis. However, as a single case, these findings should be interpreted with caution, and clinicians should adopt an individualized risk–benefit assessment when considering incretin-based therapies in patients with a history of acute pancreatitis. This case exposes some critical oversights in acute care. First, triglyceride measurement was not included in the patient’s initial workup. Once gallstones and notable alcohol history are excluded, hypertriglyceridemia is the next probable cause of acute pancreatitis. Second, although the laboratory ran additional tests and released results on the electronic medical record, these were not flagged to the clinical team and were, unfortunately, overlooked. This case highlights the importance of reliable systems for comprehensive investigation ordering, effective communication of critical results, and systematic inpatient and postdischarge review of admission investigations. A structured, multidisciplinary approach is essential to prevent recurrence of acute pancreatitis in patients with hypertriglyceridemia as a contributing cause. This approach should include triglyceride measurement in all patients presenting with acute pancreatitis, aggressive management of hypertriglyceridemia initiated during hospitalization if levels are substantially elevated, comprehensive discharge planning that incorporates specific dietary counselling (e.g., very low-fat diet), appropriate initiation and titration of lipid-lowering medications, postdischarge lipid monitoring, and timely referral to specialized clinics. When hypertriglyceridemia is unexplained, recurrent, or severe, clinicians should consider familial evaluation, including family history and, when indicated, targeted genetic testing (e.g., for familial hypertriglyceridemia or apolipoprotein E2 homozygosity). The section Cases presents brief case reports that convey clear, practical lessons. Preference is given to common presentations of important rare conditions, and important unusual presentations of common problems. Articles start with a case presentation (500 words maximum), and a discussion of the underlying condition follows (1000 words maximum). Visual elements (e.g., tables of the differential diagnosis, clinical features, or diagnostic approach) are encouraged. Consent from patients for publication of their story is a necessity. See information for authors at www.cmaj.ca . Footnotes Competing interests: Akheel Syed reports a speaker honorarium from the Endocrine Society and former honorary membership on the selection panel for the Leadership and Development Awards Programme at the Society for Endocrinology. No other competing interests were declared. This article has been peer reviewed. The authors have obtained patient consent. Contributors: All of the authors contributed to the conception and design of the work, drafted the manuscript, revised it critically for important intellectual content, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/ References 1 ↵ Iannuzzi JP King JA Leong JH . Global incidence of acute pancreatitis is increasing over time: a systematic review and meta-analysis . Gastroenterology 2022 ; 162 : 122 – 34 . Google Scholar OpenURL CrossRef PubMed 2 ↵ Yang AL McNabb-Baltar J . Hypertriglyceridemia and acute pancreatitis . Pancreatology 2020 ; 20 : 795 – 800 . Google Scholar OpenURL CrossRef PubMed 3 ↵ Olesen SS Harakow A Krogh K . Hypertriglyceridemia is often under recognized as an aetiologic risk factor for acute pancreatitis: a population-based cohort study . Pancreatology 2021 ; 21 : 334 – 41 . Google Scholar OpenURL PubMed 4 ↵ Umpierrez GE Davis GM El Sayed NA . Hyperglycaemic crises in adults with diabetes: a consensus report . Diabetologia . 2024 ; 67 : 1455 – 79 . Google Scholar OpenURL CrossRef PubMed 5 ↵ Mosztbacher D Hanák L Farkas N .; Hungarian Pancreatic Study Group . Hypertriglyceridemia-induced acute pancreatitis: a prospective, multicenter, international cohort analysis of 716 acute pancreatitis cases . Pancreatology 2020 ; 20 : 608 – 16 . Google Scholar OpenURL PubMed 6 ↵ Stitziel NO . Reducing the risk of pancreatitis by inhibiting APOC3 . N Engl J Med 2025 ; 392 : 197 – 9 . Google Scholar OpenURL PubMed 7 ↵ Christian JB Arondekar B Buysman EK . Determining triglyceride reductions needed for clinical impact in severe hypertriglyceridemia . Am J Med 2014 ; 127 : 36 – 44.e1 . Google Scholar OpenURL PubMed 8 ↵ Abd El Aziz M Cahyadi O Meier JJ . Incretin-based glucose-lowering medications and the risk of acute pancreatitis and malignancies: a meta-analysis based on cardiovascular outcomes trials . Diabetes Obes Metab 2020 ; 22 : 699 – 704 . Google Scholar OpenURL CrossRef PubMed 9 ↵ Ayoub M Chela H Amin N . Pancreatitis risk associated with GLP-1 receptor agonists, considered as a single class, in a comorbidity-free subgroup of type 2 diabetes patients in the United States: a propensity score-matched analysis . J Clin Med 2025 ; 14 : 944 . Google Scholar OpenURL PubMed 10 ↵ Kamrul-Hasan ABM Mondal S Dutta D . Pancreatic safety of tirzepatide and its effects on islet cell function: a systematic review and meta-analysis . Obes Sci Pract 2024 ; 10 : e70032 . Google Scholar OpenURL 11 ↵ Nassar M Nassar O Abosheaishaa H . Decreased risk of recurrent acute pancreatitis with semaglutide and tirzepatide in people with type 2 diabetes or obesity with a history of acute pancreatitis: a propensity matched global federated TriNetX database-based retrospective cohort study . Diabetes Metab Syndr 2024 ; 18 : 103116 . Google Scholar OpenURL PubMed 12 ↵ Sumithran P Russell AW Zoungas S . Cardiovascular effects of tirzepatide . J Endocrinol 2025 ; 264 : e240259 . Google Scholar OpenURL PubMed PDF Previous Next Back to top In This Issue CMAJ Vol. 198, Issue 29 24 Aug 2026 Table of Contents Index by author Article tools Respond to this article Print Download PDF Article Alerts Alerts for this Article User Name * Password * To sign up for email alerts or to access your current email alerts, enter your email address below: Email * Email Article Email This Article Thank you for your interest in spreading the word on CMAJ. NOTE: We only request your ema
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