Correlation and causation of both diabetes and pancreatitis have stumped medical professionals for decades. These two seemingly similar conditions can be unpredictable in how they affect the body and interact with one another. Yet, countless studies and statistics show a relationship between diabetes and pancreatitis. And now, with the help of genetic testing, we’re closer than ever to uncovering the information we need to answer our most important questions about the pancreas and diseases affecting this vital organ.
Before we dive into pancreatitis, diabetes and how they’re related, there are a few essential facts you should know about these conditions and the organs they affect.
The pancreas and pancreatitis
The pancreas is a gland that works for both the digestive and endocrine systems. This organ secretes enzymes that helps the body digest food. These enzymes break down food and convert it to essential nutrients the body needs to function. The pancreas also releases two hormones, insulin and glucagon, to help regulate blood sugar. The pancreas is located behind the stomach in the upper left abdomen.
Pancreatitis is simply inflammation of the pancreas, but the disease is much more complex than that. The inflammation occurs when the digestive enzymes secreted by the pancreas become active while still in the pancreas. Instead of breaking down your food as designed, the enzymes break down the pancreas, leading to inflammation and possible organ damage.
Pancreatitis can be a progressive disease, and there are three main types or stages of pancreatitis:
- Acute Pancreatitis: This type of pancreatitis happens suddenly and can be caused by gallstones blocking a bile duct, among other causes. Acute pancreatitis requires emergency medical treatment and can be life-threatening.
- Recurrent Acute Pancreatitis: Patients who have more than one attack of acute pancreatitis have recurrent acute pancreatitis. This type of pancreatitis often leads to chronic pancreatitis.
- Chronic Pancreatitis: Chronic pancreatitis is long-term pancreas inflammation that diminishes pancreatic health and can result in permanent pancreas damage if left untreated. This painful condition can also interfere with digestion, insulin production and in severe and/or untreated cases, cause death.
Symptoms of acute pancreatitis include:
- Sudden, severe upper abdominal pain aggravated by eating
- Fever
- Nausea
- Vomiting
- Abdominal tenderness
Symptoms of chronic pancreatitis include:
- Upper abdominal pain, which may be constant or episodic
- Unintentional weight loss
- Oily, smelly stools that may or may not be diarrhea
There are several known risk factors for pancreatitis. The National Pancreas Foundation reports that chronic pancreatitis is most common in men age 30 to 40. Heavy alcohol consumption and genetic factors can also cause attacks of pancreatitis.
Overall, pancreatitis risk is low. The average person has between a 0.005 and 0.035% chance of getting acute pancreatitis in any given year. The chances of getting chronic pancreatitis are even lower; it’s between 0.005 and 0.012%.
Check out our educational webinar, Pancreatitis Facts and Fiction, to learn more about pancreatitis.
What is diabetes?
Diabetes is a group of diseases caused by elevated blood sugar levels, called hyperglycemia. Regulating glucose is extremely important because it provides energy for the cells that comprise muscles and tissues. Glucose is also the primary source of energy for the brain.
There are several types of diabetes, and the underlying cause of the blood sugar spike associated with this disease depends on the type. Here’s a breakdown of each type of diabetes:
Prediabetes:
Patients with higher than normal blood sugar have prediabetes. Their glucose levels aren’t high enough to be considered type 2, but without intervention, like diet change and weight loss, developing type 2 diabetes is a virtual certainty.
- Type 1: This chronic form of diabetes occurs when the pancreas produces little or no insulin. As a result, the pancreas fails to regulate blood sugar, causing dangerous
spikes. The cause of Type 1 diabetes is unknown, although thought to be largely
genetic. Type 1 diabetes is usually diagnosed in children, but it can be diagnosed at any age. - Type 2: Type 2, also called adult-onset diabetes, is when the body doesn’t produce enough or resists insulin. High body mass index (BMI), lack of exercise and poor dietary
choices, among other known and unknown factors, can contribute to the
development of this chronic form of diabetes. It may be partially reversed with
the proper diet. - Gestational: This form of diabetes is hyperglycemia caused by pregnancy. In most cases,
gestational diabetes reverses soon after giving birth. However, women with this
form of diabetes are at higher risk of developing type 2 diabetes for the rest
of their life. - Type 3c: Type 3c, also called pancreatogenic diabetes, causes high glucose levels in addition to disruptions in secreting critical digestive enzymes. Furthermore, damage to or
removal of the pancreas in Type 3c diabetes reduces or eliminates additional
hormones secreted by the pancreas that regulate blood sugar. This effect can
make Type 3c diabetes more difficult to control.
What are the symptoms of diabetes?
The symptoms of type 1 and type 2 diabetes are quite similar. Patients can experience increased thirst and hunger, frequent urination, fatigue, and blurred vision in both cases. Bear in mind that all symptoms of diabetes, regardless of type, depend on the severity of blood sugar elevation.
Type 3c diabetes is a unique as there are several symptoms with this condition that aren’t present in other forms of diabetes. Symptoms of type 3C diabetes include:
- Unintentional weight loss
- Stomach pain
- Frequent gas
- Diarrhea
- Fatty or oily stools
- Hypoglycemia, also called low blood sugar (i.e., getting “hangry”)
- Fatigue
Interestingly, many of the symptoms of type 3c diabetes are the same as those of chronic pancreatitis.
What are the risk factors of diabetes?
Modern medicine is still trying to understand the intricate inner workings of risk for this complex set of diseases. Type 1 diabetes is usually attributed to genetics, family history and childhood viral infections. Type 2, on the other hand, is primarily caused by poor dietary choices, excess weight and a sedentary lifestyle. Because not everyone with these risk factors will develop type 2 diabetes, the medical community believes genetics and family history play a prominent role in risk.
Once again, type 3c diabetes is very different from its type 1 and type 2 counterparts. Here are the known risk factors for type 3c diabetes:
- Smoking
- Complete or partial pancreatectomy (surgical removal of the
- pancreas)
- Chronic pancreatitis
- Cystic fibrosis
- Hemochromatosis (excessive iron)
This list of risk factors is by no means exhaustive. Every case of diabetes, including type 3c diabetes, is unique, and every patient carries an individual set of symptoms and risk factors.
How do diabetes and pancreatitis affect the pancreas?
When the pancreas fails to secrete essential hormones and enzymes needed for glucose regulation and digestion, the pancreas becomes inflamed. This inflammation is what causes the pain felt by many patients. However, prolonged inflammation of the pancreas is a known risk factor for type 3c diabetes and pancreatic cancer in the long-term.
Type 3c diabetes prevents patients’ pancreata from producing enough insulin to adequately control blood glucose levels. In about half of cases, patients need insulin injections to help the pancreas control blood sugar. This form of diabetes is also known to impair the digestive function of the pancreas. When the pancreas is affected this way, the patient often has
exocrine pancreatic insufficiency (EPI).
EPI is an common complication in patients with both chronic pancreatitis and diabetes. In addition to digestive issues, EPI can cause chronic diarrhea and bloating. Fortunately, taking replacement pancreatic enzymes is an effective treatment.
Does pancreatitis cause diabetes, or could diabetes cause pancreatitis?
Pancreatitis and diabetes are very similar in the way they affect the body, which begs the question: how are these conditions related? Here’s what you should know about the correlation between pancreatitis and diabetes.
Pancreatitis causes type 3c diabetes
Yes — pancreatitis is a known cause of type 3c diabetes; chronic pancreatitis causes nearly 80% of all type 3c cases. About 1.8% of patients with adult-onset diabetes have type 3c as a result of pancreatitis. However, far too many are misdiagnosed with type 1 or type 2 diabetes.
Studies have shown that more people have type 3c than type 1 diabetes. Of those hospitalized for their diabetes, about one in ten have type 3c. Patients with chronic pancreatitis have a 25 to 80% chance of developing type 3c diabetes. Twenty percent type 3c diabetes is not caused by pancreatitis. Instead, those cases are usually caused by pancreatic cancer, cystic fibrosis or hemochromatosis.
Diabetes is correlated to pancreatitis
There is no direct, causative link connecting diabetes to pancreatitis. There are, however, many correlations between these two conditions. Compared to healthy patients without diabetes, those with diabetes are 174% more likely to develop acute pancreatitis and 140% more likely to suffer from chronic pancreatitis.
But why is this? If diabetes isn’t a known cause of pancreatitis, why do so many patients with diabetes end up with pancreatitis, too? Because these two conditions share many of the same causes. So, if a patient suffers from gallstones and gallstones are known to cause diabetes and pancreatitis, it would stand to reason that the patient has a high likelihood of developing both conditions because of their gallstones. Here are the correlated causes of diabetes and pancreatitis:
- Gallstones
- High triglycerides
- Autoimmunity
- Medications
- Alcohol and tobacco use
Can pancreatitis and diabetes lead to pancreatic cancer?
Patients diagnosed with adult-onset diabetes who are over age 50 have a 1 to 13.5% chance of eventually having pancreatic cancer. These numbers simply represent a correlation between diabetes and pancreatic cancer, not a cause or direct link. Much like the question of diabetes causing pancreatitis, diabetes and pancreatic cancer share many risk factors.
Are pancreatitis and diabetes genetic?
As the medical community has learned more about genes and their role in causing chronic conditions, genetic factors have become widely accepted risk factors for many ailments, including pancreatitis and diabetes. Here’s how genetics impacts risk for pancreatitis and diabetes.
Genetics of pancreatitis
Genetic factors are a known risk factor for pancreatitis. The medical community has identified several known gene variants responsible for increasing a patient’s risk for pancreatitis. Click here to learn more about the basics of genetics and genetic variants.
PRSS1
Internationally recognized physician-scientist Dr. David C. Whitcomb first discovered the PRSS1 gene in 1996. Identifying harmful changes in the PRSS1 gene as a leading cause of hereditary pancreatitis has revolutionized the way physicians treat and diagnose hereditary pancreatitis.
PRSS1-Hereditary pancreatitis is a highly penetrant form of pancreatitis, which often emerges in childhood or adolescence. It is an inherited disorder that often affects multiple related individuals in a family. However, most cases of pancreatitis aren’t hereditary. Harmful changes, or variants, in other genes can increase a person’s risk for pancreatitis. Several of these genes are associated with a small to moderate increased risk for pancreatitis, but they don’t cause pancreatitis in isolation. Instead, they act in concert with other genetic and environmental risk factors. For example, some variants in the SPINK1 gene are a common genetic risk factor for pancreatitis. Variants in other genes, such as CFTR, may cause a genetic disorder that can include pancreatitis as a symptom.
SPINK1
Several variants in the SPINK1 gene are established risk factors for acute and chronic pancreatitis. However, SPINK1 risk variants are common in the general population (1-2%), meaning that most individuals with a SPINK1 risk variant don’t develop pancreatitis. Still, a SPINK1 variant can influence the disease course in an individual with pancreatitis.
Patients with acute or recurrent acute pancreatitis and a SPINK1 risk variant have an increased for developing chronic pancreatitis. Furthermore, they have an increased risk of developing pancreatic exocrine insufficiency and diabetes compared to individuals with idiopathic pancreatitis What’s more, people with SPINK1-related pancreatitis experience more frequent episodes of acute pancreatitis and elevated pancreatic pain.
CFTR
Disease-causing variants in the CFTR gene can cause cystic fibrosis. Cystic fibrosis is an autosomal recessive disease (i.e. both copies of CFTR must be affected). It is characterized by several multisystem manifestations, including sinopulmonary disease, early-onset pancreatic exocrine insufficiency, pancreatitis, infertility, and more. Cystic fibrosis increases a person’s risk of developing chronic pancreatitis 40- to 80-fold. Individuals with a single harmful variant in CFTR may be asymptomatic CF carriers. However, a large matched case-control study found that CF carriers had a mild but significantly increased odds for several CF-related conditions, including pancreatitis and male infertility, as well as other conditions such as diabetes.
Variants in CFTR have also been proven to interact with other genetic risk factors to further increase a person’s risk for pancreatitis. In a recent National Center for Biotechnology Information study, researchers found that 9-21% of patients with SPINK1-related pancreatitis had a co- occurring harmful variant in the CFTR or CTRC genes.
Identifying genetic variants in these genes and several others as risk factors for pancreatitis is a giant leap forward in diagnosing and treating this condition. But genetics don’t paint the whole picture. About 30% of pancreatitis cases are unexplained with no known genetic or environmental risk factors.
Still, patients’ environment and lifestyle decisions are substantial contributing factors to pancreatitis risk and are often present in patients with genetic risk. Some of these environmental factors include alcohol and tobacco use.
Patients often carry multiple genetic risk variants, which may interact to increase their chances of developing pancreatitis. In some cases, the interaction of two known genetic factors increases a patient’s risk of future pancreatitis, similar to how genetic risk factors and environmental risk factors interact to elevate risk.
Genetics of diabetes
Like pancreatitis, diabetes has both genetic and environmental risk factors. Often, these elements interact to amplify a patient’s chances of developing diabetes. Single-gene disease-causing variants are responsible for about 4% of diabetes cases. And from a hereditary perspective, people with first-degree relatives (such as parents and full siblings) who have type 2 diabetes are three-times more likely to develop the condition.
HLA-DR3 or HLA-DR4
These genes are most often associated with autoimmune disease but are also linked to type 1 diabetes. Harmful variants in these genes are associated with an risk for developing juvenile diabetes.
IDDM1
Variants in the IDDM1 gene are the most common genetic cause of type 1 diabetes. Scientists believe this gene contributes 40-50% of the hereditary risk for developing juvenile diabetes.
DRB1-DQA1-DQB1
Variants in the HLA-DRB1, –DQA1, and –DQB1 genes are another known genetic risk factor for type 1 diabetes, especially in Caucasian populations. These genes are located near each other. The effect of variants in these genes is highly dependent on ancestry, as combinations of DRB1–DQA1–DQB1 variants affect individuals of some ancestries more than others.
PPARγ
PPARy assists with adipocyte and lipid (e.g., fat) metabolism. The PPARγ 12Pro variant is common and has been linked to decreased insulin sensitivity and significantly increases patients’ risk for type 2 diabetes. The less common alternate variant, PPARγ Pro12Ala, has a protective effect.
ABCC8
This gene provides the instructions for making a protein that helps regulate potassium in the body and is part of what’s called “the potassium channel.” ABCC8 plays a crucial role regulating hormones in the body, including insulin and glucagon. Harmful variants of this gene prevent the pancreas properly releasing hormones, which can contribute to the development of type 2 diabetes.
KCNJ11
This gene is located near the ABCC8 gene. Some variants in this gene decrease secretion of insulin, which increases risk for type 1 diabetes. Variations of this gene are correlated to type 2 diabetes, as well as other diabetes-related traits.
CAPN10
This gene was the first type 2 diabetes-associated gene discovered by linkage analysis in 1996. Since then, we’ve learned that CAPN10 encodes a cysteine protease to assist with intracellular remodeling, post-receptor signaling and other intracellular functions. Variants of this gene can cause insulin secretion problems. Scientists have observed that CAPN10 variants may disproportionately affect individuals of Mexican-American ancestry.
TCF7L2
Variants in the TCF7L2 gene are another significant risk factor in the Mexican-American population as well as the Icelandic population. Common variants in this gene represent the most potent type 2 diabetes risk over all other known common genetic risk factors (i.e., excluding rare single-gene causes of diabetes).
How can genetic testing help?
Pancreatitis and diabetes are complex diseases. A better understanding of these conditions’ genetic makeup has helped doctors make more accurate diagnoses and effective treatment plans, but we have a long way to go.
Problems with the past
Diseases like pancreatitis and diabetes used to be diagnosed by analyzing symptoms, doing a physical exam and considering lab work or imaging results. This is called evidence-based practice.
Although advances in diagnosis are being continuously made, evidence-based medicine frequently fails to identify the underlying cause of complex diseases. And when the source is unknown, it’s not addressed. This means the problem could easily become recurrent or even misdiagnosed. In both cases, the disease will likely progress.
Treatment of complex diseases in generally focused on alleviation of symptoms rather than the cause of disease. This is because traditional medicine has not been equipped to accurately identify the cause of complex diseases like pancreatitis and diabetes for most patients. However, insights in genetics, computational advances, and more provide the opportunity for precision medicine in the 21st century.
Complex diseases, like pancreatitis and diabetes, are rarely caused by symptoms readily identified by evidence-based medicine. Instead, they result from genetic, environmental and other factors that interact with one another to increase patient risk. The only way to accurately, consistently assess these factors is with genetic testing and precision medicine.
Hope For The Future
With recent developments in medical science, physicians can now access valuable genetic data to obtain a more complete view of a patient’s condition, and the cause.
The ADVANCE® Precision Medicine Platform supports the integration of this data for clinical care. This platform integrates the patient’s genetics, environment, and family and medical history to help doctors accurately diagnose and offer personalized treatment strategies for their
patients. It works by harnessing the power of deep genetic sequencing, advanced analytics and evidence-based expert knowledge to create a simple, actionable report.
ADVANCE® provides so much more than diagnostic information. It some cases, the information it provides can support:
- Earlier detection
- More effective treatment
- Improved family risk predictions
These are a few of the many treatment benefits realized by genetic testing for pancreatitis, diabetes and other chronic conditions. Precision medicine, guided by comprehensive genetic testing, brings all these variables together to improve diagnosis and treatment of conditions long before they inflict life-changing damage.
Download our patient-provider discussion guide to help you have a more informed discussion about genetic testing for pancreatitis.
