What is the relationship between hypertriglyceridemia and pancreatitis?

From the Guidelines

High triglycerides cause pancreatitis primarily through the accumulation of triglyceride-rich chylomicrons in pancreatic capillaries, and management focuses on rapidly lowering triglyceride levels and addressing lifestyle factors. When triglyceride levels exceed 1,000 mg/dL, these large particles can obstruct small blood vessels in the pancreas, leading to ischemia and inflammation 1. Additionally, free fatty acids released from triglycerides by pancreatic lipase are directly toxic to pancreatic cells. The trapped triglycerides also activate trypsinogen prematurely within pancreatic cells, initiating autodigestion of the pancreas. This process triggers an inflammatory cascade involving cytokines and oxidative stress, further damaging pancreatic tissue.

Key Points

• The risk of pancreatitis increases significantly when triglyceride levels exceed 500 mg/dL, with levels above 1,000 mg/dL posing the highest risk 1.
• Management focuses on rapidly lowering triglyceride levels through fasting, intravenous fluids, insulin therapy, and plasmapheresis in severe cases, followed by long-term triglyceride control with diet, exercise, and medications like fibrates or omega-3 fatty acids 1.
• Hypertriglyceridemia should be addressed with nutritional and lifestyle changes, including weight loss and abstinence from alcohol, and severe hypertriglyceridemia may warrant pharmacologic therapy to reduce the risk of acute pancreatitis 1.
• The treatment goal for patients with moderate hypertriglyceridemia is a non–high-density lipoprotein cholesterol level of 30 mg per dL higher than the low-density lipoprotein goal, as recommended by the NCEP ATP III 1.

Recommendations

• For individuals with fasting triglyceride levels ≥500 mg/dL, evaluate for secondary causes of hypertriglyceridemia and consider medical therapy to reduce the risk of pancreatitis 1.
• In adults with hypertriglyceridemia, clinicians should address and treat lifestyle factors, secondary factors, and medications that raise triglycerides 1.
• In patients with atherosclerotic cardiovascular disease or other cardiovascular risk factors on a statin with controlled LDL cholesterol but elevated triglycerides, the addition of icosapent ethyl can be considered to reduce cardiovascular risk 1.

From the Research

Causes of Pancreatitis due to High Triglycerides

• High triglyceride levels can cause pancreatitis, with severely elevated triglyceride levels (500 mg per dL or higher) increasing the risk of pancreatitis 2, 3
• The exact mechanism is not fully understood, but it is thought that high levels of triglyceride-rich lipoproteins and their remnants can contribute to the development of pancreatitis 4, 5
• Hypertriglyceridemia is the third most common cause of acute pancreatitis, and it typically occurs in patients with an underlying disorder of lipoprotein metabolism and in the presence of a secondary condition such as uncontrolled diabetes, alcohol abuse, or medication use 4

Risk Factors for Hypertriglyceridemia-Induced Pancreatitis

• Obesity, metabolic syndrome, and type 2 diabetes mellitus are common risk factors for hypertriglyceridemia 3
• Excessive alcohol use, physical inactivity, being overweight, use of certain medications, and genetic disorders are less common risk factors for hypertriglyceridemia 3
• Patients with hypertriglyceridemia-induced pancreatitis are more likely to have severe disease courses and have a higher likelihood of persistent organ failure 4

Treatment and Management of Hypertriglyceridemia-Induced Pancreatitis

• The initial treatment of hypertriglyceridemia-induced pancreatitis is similar to acute pancreatitis from other causes and consists of aggressive fluid resuscitation, pain control, and nutritional support 4
• Hypertriglyceridemia is specifically treated with apheresis or insulin therapy when necessary 4
• Fibrates, omega-3 fatty acids, or niacin should be considered for patients with severely elevated triglyceride levels to reduce the risk of pancreatitis 3, 6
• Long-chain omega-3 fatty acids may be a well-tolerated and effective alternative to fibrates and niacin for reducing triglyceride levels 6