Acute pancreatitis caused by severe hypertriglyceridemia in a 61-year-old man on a carnivore diet

Key points

• Acute pancreatitis is a complication of severe hypertriglyceridemia and should be managed with supportive measures, bowel rest, and in specific clinical settings, insulin infusion and plasmapheresis.

• High-fat diets can lead to severe hypertriglyceridemia for patients with genetic predisposition.

• Patients with severe hypertriglyceridemia require evaluation for secondary causes.

• Fibrates and apolipoprotein C inhibitors have shown the greatest triglyceride-lowering effect, while statins and icosapent ethyl have been shown to reduce risk for atherosclerotic cardiovascular disease risk reduction in hypertriglyceridemia.

A 61-year-old man presented to the emergency department with acute abdominal pain, nausea, and vomiting. He was hemodynamically stable and had normal vital signs. His weight was 141.5 kg with a corresponding body mass index of 43.7. His physical examination was otherwise unremarkable, including a normal neurologic examination and peripheral pulses. He had a nondistended abdomen with tenderness throughout the upper abdomen, particularly in the epigastric area, without guarding or rigidity. He had no eruptive xanthomas, xanthelasmas, or corneal arcus.

The patient had a history of type 2 diabetes, hypothyroidism, obesity, and dyslipidemia. His only medication was levothyroxine (225 μg daily). He had been on atorvastatin 5 years prior, which he had stopped because of an intolerance he was unable to recall. He had a family history of early acute coronary syndrome (his brother) and hyperlipidemia (his daughter).

Since the patient’s diagnosis of diabetes 2 years prior, he had made substantial dietary modifications. He initially started a low-carbohydrate ketogenic diet and eventually transitioned to a high-fat carnivore diet composed exclusively of meat, poultry, eggs, and dairy products, while excluding plant products such as vegetables, fruits, or grains. With these changes, he reported having lost 40 kg over 2 years. During this time, he was not monitoring his glucose and was not on any medication for diabetes.

Initial investigations revealed a serum lipase greater than 3000 (normal < 80) U/L and a triglyceride level greater than 50.0 (normal < 1.70) mmol/L. When centrifuged, the patient’s blood was lipemic and unsuitable for analysis of the rest of the lipid panel (Figure 1). His initial glucose level was elevated at 17.3 (normal 3.3 to 11.0) mmol/L, and glycated hemoglobin A_1c was elevated at 7.9%. Thyroid stimulating hormone level was elevated at 21.0 (normal 0.20 to 6.50) mIU/L, with a low free T4 of 9.6 (normal 10.0 to 25.0) pmol/L. Calcium level was normal at 2.14 mmol/L. Subsequent investigations revealed a lipoprotein( a) level below 7 (normal < 100) nmol/L and an apolipoprotein B (apoB) 100 level of 0.87 (normal < 1.05) g/L. Serial lipid profiles showed total cholesterol levels ranging from 12.90 to 20.60 (normal < 5.20) mmol/L. Abdominal ultrasonography revealed acute interstitial pancreatitis, hepatomegaly, and severe hepatic steatosis.

Figure 1:

Centrifuged plasma from a 61-year-old man with severe hypertriglyceridemia showing a floating, creamy, white chylomicron layer overlying an opaque layer rich in very low–density lipoprotein, consistent with multifactorial chylomicronemia (formerly, World Health Organization type V).

The patient was admitted to the general internal medicine service, put on bowel rest (nothing by mouth), and started on an insulin infusion at 15 units/h with the subsequent addition of an infusion of 10% dextrose in water at 100 mL/h. Both infusions were titrated to maintain euglycemia. At this point, we were consulted for guidance regarding the management of his hypertriglyceridemia. After 72 hours of bowel rest, the patient’s triglyceride level decreased to 9.59 mmol/L. We introduced a clear fluid diet, which was advanced to a low-fat diabetic diet. We then transitioned him to insulin glargine (10 units subcutaneously daily), oral microcoated fenofibrate (100 mg 3 times daily), an omega-3 supplement (containing 600 mg of eicosapentaenoic acid [EPA] and docosahexaenoic acid per 1000 mg), and metformin (250 mg twice daily, with a plan to titrate the dose). We increased his levothyroxine dose to 250 μg daily. He was discharged home in stable condition after 4 days of admission.

Over the following month, the patient made further dietary modifications, introducing plant-based complex carbohydrates, fibre, and vegetables. He lost 11 kg, and his triglycerides further decreased to 4.86 mmol/L. We started him on pravastatin (10 mg daily) to reduce the risk of atherosclerotic cardiovascular disease (ASCVD). His inherited lipid disorder panel did not identify any pathogenic variant gene for hypertriglyceridemia.

Discussion

Hypertriglyceridemia is a common metabolic disorder with a prevalence of around 25%.¹ Plasma triglyceride concentrations reflect the number of circulating triglyceride-rich lipoproteins, namely chylomicrons and very low–density lipoproteins (VLDLs). Higher triglyceride levels are also associated with qualitative differences in these particles that render them more resistant to degradation.²

Triglyceride concentrations of 1.7 to 9.9 mmol/L are generally considered mild to moderately elevated, while concentrations greater than 10 mmol/L are considered severely elevated. This classification is based exclusively on triglyceride concentration and does not capture the heterogeneity in triglyceride-rich particles, which may be clinically relevant. Pancreatitis is a complication of hypertriglyceridemia, which becomes increasingly prevalent with higher triglyceride levels. The 5-year risk of acute pancreatitis is 1.5% with triglyceride concentrations of 4.5 to 10.0 mmol/L and 3.5% at concentrations of 10.1 to 20.0 mmol/L.³

The association between hypertriglyceridemia and cardiovascular risk is unclear, given difficulties in isolating the effects of triglycerides from high-density liporoptein and other lipoproteins, since their concentrations are often codependent. Recent studies in triglyceride metabolism have strengthened the evidence for a potential causal relationship between hypertriglyceridemia and ASCVD, which is likely mediated by excess VLDL and chylomicron remnants.⁴

Etiologies of hypertriglyceridemia can be classified into primary genetic conditions and secondary acquired causes. Most cases of hypertriglyceridemia are thought to involve both acquired triggers and genetic predisposition. Severe hypertriglyceridemia is more likely to have an underlying genetic basis; however, most people with severe hypertriglyceridemia have no identifiable pathogenic variant gene.⁵

Obesity, hyperglycemia, and insulin resistance have all been shown to raise triglyceride levels, primarily through increased hepatic synthesis of VLDL.² Other acquired causes of hypertriglyceridemia include chronic liver and kidney disease, hypothyroidism, alcohol use, pregnancy, and medications (Table 1).⁴

Table 1:

Causes of hypertriglyceridemia

Type	Cause
Dietary factors	Excess caloric intake Processed carbohydrates Excess fructose intake Excess saturated fat intake (e.g., ketogenic or carnivore diet) Alcohol
Comorbidities	Obesity Hepatic steatosis Diabetes mellitus/insulin resistance CKD (nephrotic syndrome) Liver disease Hypothyroidism
Medications	β-blockers Thiazides Glucocorticoids Antipsychotics Antiretrovirals Estrogens and SERMs Retinoids Calcineurin inhibitors mTOR kinase inhibitors Bile acid sequestrants
Genetic	Polygenic hypertriglyceridemia Combined hyperlipoproteinemia Dysbetalipoproteinemia Multifactorial chylomicronemia Familial chylomicronemia syndrome

Note: CKD = chronic kidney disease, mTOR = mammalian target of rapamycin, SERM = selective estrogen receptor modulator.

Dietary factors that contribute to increased hepatic VLDL synthesis include excess intake of calories, carbohydrates (> 55% energy consumption), fructose, and saturated fat.² The evidence regarding ultra-low carbohydrate diets (e.g., ketogenic or carnivore diets) and hypertriglyceridemia is mixed. Many studies suggest improvement in triglyceride levels, while other cohorts and case reports show a detrimental effect.⁶ The degree of caloric deficit, the proportion of saturated and trans fats, protein and carbohydrate intake, ethnicity, and genetic variation are all suggested to mediate this mixed response.⁷

Hypertriglyceridemia is associated with several phenotypic syndromes, with substantial overlap in the underlying genetic contributors. The most prevalent syndrome is polygenic hypertriglyceridemia, which is caused by polymorphisms associated with increased VLDL production, leading to moderately elevated triglyceride levels (generally < 10 mmol/L) with normal total cholesterol and apoB. In contrast, combined hyperlipoproteinemia is associated with elevated apoB, low-density lipoprotein cholesterol (LDL-C), and triglycerides. Multifactorial chylomicronemia is a heterogeneous syndrome caused by polygenic influences in chylomicron and VLDL remnant clearance, often resulting in variable severity of hypertriglyceridemia. Familial chylomicronemia syndrome is a group of rare disorders (1 in 300 000 people) that are commonly caused by pathogenic variants in lipoprotein lipase, resulting in persistent severe hypertriglyceridemia and recurrent pancreatitis.²

Our patient likely had multifactorial chylomicronemia that was exacerbated by insulin resistance, hypothyroidism, and a carnivore diet rich in saturated animal fat, which precipitated profound hypertriglyceridemia and subsequent acute pancreatitis. Other acute risks of severe hypertriglyceridemia are hyperviscosity syndrome, thrombosis, and neurocognitive changes, which our patient did not have.

The management of hypertriglyceridemia-induced pancreatitis includes supportive measures and bowel rest, with elimination of dietary fats to prevent further accumulation of chylomicrons. Insulin infusions or plasmapheresis are occasionally used as an adjunct treatment for rapid triglyceride lowering; however, evidence that rapid triglyceride lowering improves major clinical outcomes is limited.⁸ Insulin infusion should be used in the context of uncontrolled diabetes, and plasmapheresis can be considered in severe or refractory cases.⁸

Concurrent use of insulin and glucose infusions for euglycemic patients is not supported by evidence and can be counterproductive, given the triglyceride-raising effect of glucose infusion.⁸ Once triglyceride levels are consistently maintained below 10 mmol/L, a trial oral diet can be introduced with close monitoring.

The goal in managing chronic hypertriglyceridemia is to lower the risk of pancreatitis and ASCVD. The foundation of therapy is lifestyle modification. After addressing reversible risk factors, patients should be counselled on weight loss, aerobic exercise, minimizing alcohol intake, and dietary modifications. Weight loss of 5% to 10% can lower serum triglyceride levels by roughly 20%.⁹ Recommendations regarding dietary management of hypertriglyceridemia vary depending on the severity. For mild-to-moderate hypertriglyceridemia, reducing refined carbohydrate (total carbohydrates to < 50%, added sugars to < 10% of caloric intake) and saturated fat intake (total fat 30% to 35% of calorie intake) is effective.¹⁰ For severe hypertriglyceridemia, limiting total fat content to 10% to 15% of total caloric intake is recommended, as chylomicronemia related to dietary fats is more severe in these patients because of lipoprotein lipase saturation and resulting loss of activity.¹⁰

Pharmacologic treatments for patients with hypertriglyceridemia include fibrates, statins, and marine omega-3 fatty acids (high dose of 4 g/d), such as icosapent ethyl, a purified form of EPA.⁹ Fibrates are currently the mainstay of treatment for lowering triglyceride in patients with severe hypertriglyceridemia who are at risk of pancreatitis, as they can lower triglyceride levels by 50% to 70%. In patients with any degree of hypertriglyceridemia and elevated ASCVD risk, statin therapy and icosapent ethyl have the most evidence for risk reduction, with fibrate therapy as a third-line agent.⁹ Medications such as metformin, niacin, glucagon-like peptide-1 (GLP-1) analogues, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors also have modest triglyceride-lowering effects.

Emerging therapies include RNA interference agents designed to inhibit apolipoprotein C3, olezarsen and plozasiran, which have been shown to markedly reduce triglyceride levels and incidence of pancreatitis in patients with persistent chylomicronemia. ¹¹ In January 2026, Health Canada approved plozasiran for treatment of familial chylomicronemia syndrome, while olezarsen awaits approval. Evinacumab inhibits the angiopoietin-like 3 protein and has been shown to reduce both LDL-C and triglyceride levels.¹¹ Evinacumab is approved by Health Canada for treatment of homozygous familial hypercholesterolemia but not hypertriglyceridemia.

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.