Acute Pancreatitis Risk
What if we could reduce the risk of acute pancreatitis for people with extremely high triglycerides despite standard of care?
Extremely high triglycerides can cause acute pancreatitis
Consistent fasting triglyceride levels >880 mg/dL could be a sign of an underlying genetic disease.
In some people, extremely high triglycerides that do not respond to traditional triglyceride-lowering therapies could be caused by familial chylomicronemia syndrome (FCS), a rare genetic disorder. Other people with extremely high triglycerides that do not respond to standard of care may display clinical characteristics similar to FCS, but have no clear genetic cause.
Regardless of the cause, people with extremely high triglycerides that do not respond to standard of care face a risk of acute pancreatitis, which is a serious complication that often requires hospitalization and can be fatal.
Guidelines consistently recommend maintaining triglycerides <500 mg/dL to reduce the risk of acute pancreatitis.

What is FCS?
FCS is a rare, autosomal recessive disorder caused by genetic variants that impair lipoprotein lipase (LPL) activity. In unaffected individuals, LPL clears circulating triglycerides and chylomicrons from the blood shortly after a meal. In people with FCS, the loss of LPL activity leads to the accumulation of triglycerides and chylomicrons, resulting in fasting levels at 10x-100x the normal level that do not respond to traditional treatments.
Clinical manifestations of FCS, including treatment resistance and acute pancreatitis, can also have a multifactorial, polygenic cause.
People with consistent fasting triglycerides >500 mg/dL are in an established acute pancreatitis-risk danger zone.
An increasing risk of acute pancreatitis
Acute pancreatitis caused by high triglycerides is often more severe and more deadly than acute pancreatitis caused by other factors.
Identifying those at risk of acute pancreatitis caused by high triglycerides is critical—even one acute pancreatitis event can dramatically increase the chance of a future one. Multiple episodes of acute pancreatitis can damage the pancreas, leading to chronic pancreatitis and insulin-dependent diabetes.
Among people with triglycerides >500 mg/dL to ≤880 mg/dL, how much more likely is it for someone to experience an acute pancreatitis event if they’ve had 1 acute pancreatitis event in the past year vs. someone who has not?*
*Data from a national, retrospective study analyzing anonymized outpatient records of ~76 million patient records in the US from 2006-2020.

This chart is for demonstration purposes only.
The risk of unseen spikes in triglyceride levels
Chylomicrons are large triglyceride-rich lipoprotein particles derived mostly from dietary fat. In healthy individuals, chylomicrons are generally cleared from circulation within 3 to 4 hours after a meal.
People with extremely high triglycerides despite standard of care are unable to clear dietary chylomicrons, which causes triglyceride clearance to become saturated. Once clearance is saturated, chylomicrons from additional dietary fats can rapidly and drastically increase overall triglyceride levels.
Just one meal can spike acute pancreatitis risk
Accumulation of chylomicrons from dietary fat can dramatically spike acute pancreatitis risk after just one meal.

chylomicrons.


chylomicrons.

The risk of acute pancreatitis
Imagine if we could get more people with extremely high triglycerides to the recommended goal.
Expert guidelines across specialties consistently establish triglyceride levels of <500 mg/dL as the goal for triglyceride management to reduce acute pancreatitis risk. For people with FCS or those with a similar clinical presentation, traditional treatments may not consistently keep triglycerides below this important guideline.
“When the triglyceride concentration is very high…reducing the concentration to <500 mg/dL to prevent pancreatitis becomes the primary goal of therapy.”
The National Lipid Association
Guidelines support the [500] goal
Several physician organizations have published guidelines that establish the <500 mg/dL goal.

We’ll get there [soon]
There are few options to keep triglycerides in check
For some people, the use of traditional triglyceride-lowering therapies and intensive dieting are not enough to lower levels and reduce acute pancreatitis risk.
siRNA may hold the key to managing extremely high triglycerides
Silencing genes with siRNA (small interfering RNA) could be in our future.
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Show References
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