Diabetic ketoacidosis (DKA) with severe hypertriglyceridemia-induced acute pancreatitis is an uncommon but potentially life-threatening presentation of undiagnosed type 2 diabetes.
DKA is increasingly recognised in people with type 2 diabetes, particularly in those who are young, obese, or have metabolic syndrome; autoantibody testing helps clarify diabetes type.
Triglyceride measurement should be part of the workup for all patients presenting with acute pancreatitis, and systems must reliably communicate critical laboratory findings to clinical teams.
Intravenous insulin treats both DKA and severe hypertriglyceridemia by stimulating lipoprotein lipase; plasmapheresis and novel APOC3-targeted agents are considerations for refractory cases.
Incretin-based therapies (GLP-1 receptor agonists and dual GLP-1/GIP agonists such as tirzepatide) can be considered after careful, individualized discussion in patients with prior pancreatitis.
A 27-year-old man with a background of obesity (body mass index 40) and treated depression presented to the emergency department after 24 hours of generalized abdominal pain, vomiting, polyuria and lethargy. He reported minimal alcohol intake and a family history of type 2 diabetes. On arrival he was alert but tachycardic (heart rate 131 beats/min), hypertensive (169/98 mm Hg) and afebrile.
Laboratory testing demonstrated hyponatremia (sodium 128 mmol/L), marked hyperglycaemia (random plasma glucose 22.6 mmol/L), an elevated amylase (309 U/L), and a lipemic serum sample flagged by laboratory staff. Venous blood gas showed metabolic acidosis (pH 7.24, bicarbonate 11 mmol/L) and blood and urine dipsticks were strongly ketone-positive. CT abdomen revealed a swollen pancreas with peripancreatic fat stranding consistent with acute pancreatitis; abdominal ultrasound showed a normal biliary tree without gallstones. Serum lipase was not measured.
The emergency and medical teams diagnosed concurrent DKA and acute pancreatitis. Initial inpatient treatment included intravenous fluids, an insulin infusion, intravenous amoxicillin and metronidazole for suspected intra-abdominal sepsis, and supportive care. The patient’s glycaemia improved, and symptoms and laboratory features of pancreatitis resolved within a week.
Inpatient diabetes review noted a glycated haemoglobin (HbA1c) of 116 mmol/mol (12.8%). Samples for diabetes-specific autoantibodies were sent. He was discharged on insulin therapy with outpatient referrals to diabetes and gastroenterology clinics. Results returned negative for islet antigen-2, zinc transporter 8 and islet cell antibodies. Initial testing for glutamic acid decarboxylase (GAD) antibodies was not possible on the lipemic admission sample but was negative on repeat outpatient testing. On the basis of phenotype and antibody negativity, the team diagnosed type 2 diabetes.
A retrospective review revealed an admission triglyceride level of 41.5 mmol/L that had been measured by the laboratory but overlooked by the clinical team. This led to a retrospective diagnosis of hypertriglyceridemia-induced acute pancreatitis. A repeat fasting triglyceride remained elevated at 15.0 mmol/L. The patient was started on atorvastatin (final dose 40 mg daily) and referred to a specialist lipid clinic where clinicians diagnosed mixed hyperlipidaemia with predominant hypertriglyceridemia. Management included dietary advice, weight management and fenofibrate (160 mg daily). ApoE2 homozygosity was absent and thyroid function was normal.
At 12 months the triglyceride level had decreased to 8.8 mmol/L and the HbA1c had risen to 95 mmol/mol (10.8%); BMI remained elevated at 38.4. Given ongoing obesity, suboptimal glycaemic control and residual hypertriglyceridemia, the team considered tirzepatide, a dual GLP-1 and GIP receptor agonist with reported benefits across glycaemia, weight and triglycerides. After shared decision-making that discussed pancreatitis risk, tirzepatide was started alongside metformin, atorvastatin and fenofibrate. Over 2 years the patient’s triglyceride level normalized to 2.0 mmol/L, HbA1c fell to 53 mmol/mol (7%), BMI decreased to 34.5 and insulin therapy was discontinued. There was no recurrence of pancreatitis and no diabetic retinopathy on clinical exam.
Incretin-based agents (GLP-1 receptor agonists and dual GLP-1/GIP agonists such as tirzepatide) carry a labelled precaution regarding pancreatitis based on early postmarketing reports. Subsequent larger observational and trial-based analyses reported reassuring pancreatic safety for GLP-1 receptor agonists and comparable pancreatitis risk between tirzepatide and other comparators. The authors emphasise that evidence is evolving and that the decision to use these agents after a pancreatitis episode requires individualized risk–benefit assessment and shared decision-making. In this single case, tirzepatide was associated with sustained improvements in triglycerides, glycaemia and weight without pancreatitis recurrence; the authors caution that single-case outcomes should be interpreted cautiously.
The authors outline pathophysiologic links: worsening insulin resistance and glucotoxicity reduce β-cell function and insulin reserve, permitting lipolysis and ketogenesis and precipitating DKA in people with type 2 diabetes. Reduced lipoprotein lipase activity in insulin-resistant states raises plasma triglyceride levels. Extremely high triglyceride and chylomicron concentrations lead to pancreatic capillary lipolysis to free fatty acids, local cytotoxicity, increased plasma viscosity, stasis and ischemia, and can trigger hypertriglyceridemia-induced acute pancreatitis. Triglyceride thresholds for pancreatitis risk are typically >11.3 mmol/L, with lifetime risk rising at higher concentrations.
Intravenous insulin helps treat both processes by stimulating lipoprotein lipase and lowering circulating triglycerides; plasmapheresis may be considered when triglycerides remain critically elevated despite medical therapy. Novel therapies targeting apolipoprotein C-III for refractory hypertriglyceridemia are under investigation.
This case highlights preventable system errors: triglyceride measurement was not included in the initial clinical workup for acute pancreatitis, and abnormal lipid results generated by the laboratory were not flagged or acted on by the clinical team. The authors recommend routine triglyceride testing for all patients with acute pancreatitis, reliable communication of critical lab results, inpatient initiation of hypertriglyceridemia management when levels are high, multidisciplinary discharge planning, dietary counselling (very low-fat diet), initiation and titration of lipid-lowering therapy, postdischarge lipid monitoring, and timely referral to lipid or metabolic specialist clinics. For unexplained, recurrent or severe hypertriglyceridemia, familial evaluation and targeted genetic testing should be considered.
This case documents a severe metabolic emergency in which undiagnosed type 2 diabetes presented as DKA together with hypertriglyceridemia-induced acute pancreatitis. It underscores the need for routine triglyceride measurement in acute pancreatitis, careful diabetes phenotyping with autoantibody testing, coordinated systems for result communication, and individualized therapeutic decisions— including consideration of incretin-based therapies after shared decision-making—when managing patients with prior pancreatitis.