Fat accumulation in the pancreas is known as fatty pancreas. When it occurs without any significant consumption of alcohol, it is termed as non-alcoholic fatty pancreas disease (NAFPD) (1).
Metabolic problems such as obesity, especially central obesity, fatty liver, dyslipidemia, and diabetes are some of the risk factors which are related to non-alcoholic fatty pancreas disease. However, the heart of all these problems including the fatty pancreas is insulin resistance (2).
It can progress to chronic pancreatitis and possibly pancreatic cancer development if left untreated (3).
The reason behind the fatty pancreas is simple. When your blood sugar is high, you are in a hyperglycemic state. This causes free fatty acid circulation in the body and your body keeps stuffing it in your liver as fatty liver and pancreas as the fatty pancreas.
What are the Functions of the Pancreas?
The pancreas is a six-inch-long gland that is located in your abdomen, behind and below the stomach. It’s nestled slightly behind the stomach and in front of the spine. The head of the pancreas is along the curve of the duodenum, the first part of the small intestine just beyond the stomach.
The parenchymal cells of the pancreas are the functional cells that play dual functions.
- Endocrine function: Hormones such as insulin and glucagon is secreted from the pancreas that helps regulate your blood sugar levels
- Exocrine function: The pancreas secretes enzymes such as lipase, amylase, and chymotrypsin, and trypsin into your digestive tract through a duct into your duodenum.
In the fatty pancreas, there is a replacement of the pancreatic parenchyma by fat. It means the fat deposits in the adipocytes (fat cells) in the pancreatic tissue. In the fatty liver, the fatty accumulation occurs intracellularly, however, the fatty components in the pancreas are in the shape of adiposity cell infiltration (4).
Fatty Infiltration of the Pancreas
Fatty infiltration of the pancreas is the abnormal movement of fat in the pancreas and its deposition there. The infiltration of fat in the pancreas can be unevenly distributed or specifically deposited in one particular region.
Van Geenen et al. in 2010, came up with the hypothesis that obesity and its association with insulin resistance play a crucial role in pancreatic infiltration with adipocytes.
Insulin resistance also leads to peripheral lipolysis resulting in a flux of fatty acids and the onset of NAFLD.
It is prudent to understand here that fatty replacement and fatty infiltration are not the same things. The former is the death of the replacement of the acinar cells with adipocytes and the latter is infiltration with adipocytes due to obesity. Both of these states are succeeded by the presence of DM-T2, metabolic syndrome, and obesity.
Focal fatty infiltration of the pancreas is the fat deposition in the anterior aspect of the head of the pancreas. It spares the dorsal aspect of the head and uncinate the process (5).
Diffuse fatty infiltration of the pancreas is a common image finding that leads to the difficulty of assessing pancreas appearance.
Pancreatic fat is associated with systemic vascular complications and is associated with subclinical atherosclerosis (6). It also increases the prevalence of diabetic retinopathy. Kim et al. in their study stated that fatty pancreatic infiltration is associated with a higher risk of carotid atherosclerosis (7).
Multiple terms have been used to describe this fat accumulation such as the non-alcoholic fatty pancreas (NAFP), fatty infiltration (FI) of the pancreas, pancreatic steatosis, pancreatic lipomatosis, fatty replacement, and lipomatous pseudohypertrophy of the pancreas.
Medical History of Fatty Pancreas
The first description of pancreatic fat was made by Ogilvie in 1933. After more than 40 years, in 1978, Olsen performed a large study over 394 autopsies. He found a relationship between the content of fat and age and confirmed the relationship with obesity (8).
Causes of Fatty Pancreas
The fatty pancreas develops when your body produces way too much fat or isn’t able to metabolize fat efficiently. This excess fat starts getting deposited in the liver causing fatty liver. As the process continues, fat is accumulated in the pancreas as well causing a fatty pancreas.
There are at least two mechanisms that can lead to pancreatic fat accumulation (9)
- Death of acinar cells and replacement by adipocytes known as fatty replacement
- Fat accumulation associated with obesity and type-2 diabetes mellitus known as fatty infiltration or NAFPD
In people who do not drink excess alcohol, the cause of the fatty pancreas is not very clear. One or more factors may be the reason.
Pancreatic fat content increases with age and is the highest in the third and fourth decades. Pancreatic parenchymal volume declines beyond the sixth decade and as a result the fat to parenchymal ratio increases in that age group, although the total pancreatic fat volume remains stable (10).
Rare genetic syndromes that are associated with fatty pancreas are Shwachman-Diamond syndrome, Johanson-Blizzard syndrome, and heterozygous-carboxyl ester lipase (CEL) mutations. The reason being pancreatic exocrine insufficiency.
Ethnicity is an independent risk factor in the development of pancreatic steatosis. Hispanic and Caucasians are at increased risk of developing pancreatic fat infiltration than African Americans.
When compared with a lean person, obese persons have more intrapancreatic fat (IPF). This is independent of age and glycemic status. In a study by Saisho et al, it was demonstrated that a linear incremental relationship between body mass index and IPF in both diabetic and non-diabetic subjects exists. Studies showed that bariatric surgery helps improve glycemic outcomes associated with a decrease in IPF independent of postoperative change in body mass index (11).
Insulin is a hormone that is produced by the pancreas which helps to regulate sugar levels. It breaks down glucose into energy in the cells. In insulin resistance, this mechanism is obstructed as the cells lose their sensitivity to insulin.
This leads to the making of excess fat and deposited on the organs such as the liver and pancreas. This mechanism works on two sides. The fatty pancreas will cause the pancreas to stop producing enough insulin which is used to break down the glucose into energy in the cells. As this happens, the glucose turns into fats and gets accumulated in the viscera and in and around the pancreas.
Non-alcoholic Fatty Liver Disease (NAFLD)
Studies confirmed that people with NAFLD and fatty pancreas had a direct correlation with each other. In fact, a study on 60 patients reported a high prevalence of fatty pancreas in patients with NAFLD. More studies are needed to reach a firm understanding of the relationship.
It has been observed that the amount of intrapancreatic fat is greater in persons with diabetes mellitus than those with prediabetes. This increases with the duration of diabetes mellitus. Viceversa is also true. There has been a higher prevalence of DM in people with FP. However, the relationship between IPF and beta-cell dysfunction is unclear.
Human studies have shown a relationship between fatty infiltration and pancreatic beta-cell dysfunction.
In acute pancreatitis, there can be a reduction of parenchymal calls and is substituted with fat cells leading to a fatty pancreas.
Pancreatic fistula is a frequent complication after pancreatoduodenectomy. Several studies have found the fatty pancreas to be an independent predictor of postoperative pancreatic fistula. Studies have also observed that patients with pancreatic fistula have a greater amount of IPF than healthy individuals.
However, the role of the fatty pancreas is an independent risk factor for pancreatic fistula continues to be controversial. Studies with radiological and histologic evidence of FP would be useful.
Pancreatic Ductal Adenocarcinoma
Small case-control studies have found an association of fatty pancreas with pancreatic ductal adenocarcinoma (PDAC). Studies have also linked IPF to a higher risk of lymph node metastasis in patients with PDAC. the underlying mechanism needs to be more carefully examined.
Alcohol abuse is associated with abnormal mitochondrial function, which may account for the fat accumulation observed in pancreatic acinar cells. Alcohol abuse leads to pancreatic lipomatosis via acute and/or chronic pancreatitis and/or upregulation of transcription factors involved in the synthesis of cholesterol and triglycerides. Alcoholism is also associated with malnutrition which is again a big cause of fatty pancreas.
Toxic Agents and Medications
Steroid therapy and gemcitabine chemotherapy have been shown to be associated with the fatty pancreas. Some drugs may cause fatty pancreas and lead to acute pancreatitis. They are sulfonamides, sulindac, tetracycline, valproic acid, estrogens, octreotide, and many more.
Another rare cause is a reoviral infection that could cause pancreatic steatosis through a combination of malnutrition-related and viral-related effects and chronic hepatitis B infection. It leads to duct obstruction consequently leading to necrosis of the parenchyma and subsequent substitution with fatty tissue. In support of this pathogenic pathway, pancreatic duct ligation actually leads to fatty replacement.
The most important cause of iron overload is hereditary hemochromatosis which is a genetic disorder. It can also happen while transfusional iron overload which can result from repeated blood transfusions.
Iron mainly accumulates in the reticuloendothelial system, liver, heart, and endocrine or exocrine glands, pancreas included. When the pancreas is involved, iron leads to oxidative stress of acinar and islet cells, apoptosis, and substitution with adipocytes. Patients with transfusion-dependent diseases such as myelodysplastic syndrome and cooley’s anemia are prone to this process.
Medications can cause pancreatic tissue necrosis and subsequent substitution with fatty tissue. Even though it is rare, but not unheard of. Drugs include corticosteroids, gemcitabine, rosiglitazone, and more recently octreotide.
Malnutrition, as seen in alcoholism, kwashiorkor and AIDS is associated with changes in pancreatic structure, including pancreatic lipomatosis. However, the lack of solid evidence makes it unclear.
Metabolic Syndrome (MetS)
MetS is an ever-increasing clinical and social problem. High-calorie, high-fat, sedentary lifestyles with a lack of physical activity are the main cause. MetS is now associated with increased incidences of type-2 diabetes, cardiovascular disease, and stroke.
Fatty pancreas and fatty liver is just a hepatic manifestation of MetS. The high levels of free fatty acids (FFA) and insulin resistance are considered key pathogenic factors in the development of fat accumulation in the pancreas.
The Development of Pancreas Disease
Insulin resistance results in hyperinsulinemia that stimulates de novo lipogenesis transforming excess dietary carbohydrates into new fat. The liver packages and exports this new fat as VLDL making it widely available for other organs (12).
The new fat deposits in skeletal muscles take up much of this fat, as do fat cells in and around the abdominal organs leading to central obesity that is an important component of metabolic syndrome.
The fat starts depositing within the organs especially the liver and muscles. This leads to a further increase in insulin resistance that results in rising blood glucose. The body responds by secreting even more insulin to bring this blood glucose down.
Also known as the overflow phenomenon, even though the extra insulin overcomes the rising insulin resistance, it does set up a vicious cycle.
The mounting insulin resistance produces a long slow rise in blood glucose. And if you keep having excess carbohydrates, it will provoke excessive insulin secretion, leading to de novo lipogenesis.
High insulin generates fatty liver which in turn increases insulin resistance and vice-versa. This, in turn, increases insulin production which only increases fat synthesis. The fat starts accumulating in and around the organs especially the liver. The liver starts exporting this fat as VLDL to other organs including the pancreas resulting in a fatty pancreas.
Stages of Fatty Pancreas
The fatty pancreas is divided into four stages (13):
- Non-fatty pancreas
- Light fatty pancreas
- Severe fatty pancreas and
- Highly fatty pancreas
Symptoms of Fatty pancreas
People with fatty pancreas often suffer from a fatty liver as well. The most common symptoms are:
- Upper abdominal pain
- Nausea and vomiting
- Changes in bowel habit
- Abdominal pain that radiates to your back
- Loss of appetite and nausea
- Fatigue and extreme tiredness
- Mental confusion
- Weight loss
Diagnosis of Fatty Pancreas
Most people with fatty pancreas are asymptomatic. This makes diagnosis very difficult. Most of them are diagnosed by abnormal imaging studies of the pancreas. The fatty pancreas is a common incidental finding during a transabdominal ultrasound examination (14).
Rarely cases such as pancreatic bulging or mass-like lesions or abnormal pancreatic imaging studies after surgery have been reported (15). The difficulty of visualizing the pancreas has also become another reason to ignore the symptoms of asymptomatic patients. But recently with advanced imaging, fatty pancreas diagnosis has become easier (16).
Diagnosis of the fatty pancreas or pancreatic steatosis mainly depends on noninvasive imaging studies using transabdominal ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and recently endoscopic ultrasound (EUS) (17), (18).
EUS is known as the most sensitive method for the pancreas and biliary system.
Other common ways of diagnosing fatty infiltration in the pancreas are (19):
- Anatomical pathology
- Ultrasonography in diagnosis of fatty pancreas
- Computed tomography (CT) in the diagnosis of pancreatic steatosis
- Endoscopic ultrasonography in the diagnosis of pancreatic steatosis
- Magnetic resonance imaging (MRI) for the diagnosis of fatty pancreas
- Pathological classification
- Chemical shift imaging
Amongst these, MRI is considered the most accurate, non-invasive method of identifying fat accumulation in the visceral organs. However, more sensitive method of detecting fat component in the tissue includes:
- T2-weighted imaging shows a prominent reduction in the intensity of the fast replacement of the pancreas
The blood test that is done to understand the condition of your pancreas is
- Amylase which is more sensitive and
- Lipase which is more specific
With a fatty pancreas, both your serum amylase and serum lipase will be high. In case your fatty pancreas coexists with fatty liver, your blood ALT (SGPT) and AST (SGOT) is done. This along with GGT and alanine makes the diagnosis accurate. Fatty liver has all these markers high.
- Alanine aminotransferase (ALT)
- Aspartate transaminase (AST)
- Gamma-glutamyl transferase (GGT)
Normally these tests are recommended if you have developed signs and symptoms of liver disease. The liver enzymes and their high blood values can help detect a liver problem along with the pancreas.
Studies have stated that the fatty pancreas is associated with higher levels of visceral fat, waist circumference, AST, ALT, total cholesterol, triglyceride, free fatty acids, and insulin resistance (20).
Treatment for Fatty Pancreas
Treatment of fatty pancreas is based on its etiology. Once that is identified, corrective actions can be taken to help reduce pancreatic fat infiltration (21). There has not been any guideline for the treatment of fatty pancreas, but it is believed to be a reversible condition.
Efforts for treatment include lifestyle modifications to reduce the risk factors and treatment of metabolic syndrome. More research is needed to develop and test medications to treat this condition.
- Weight reduction
- Exercise to improve insulin sensitivity
- Reduce your alcohol consumption
- Dietary restrictions such as low carb diet
- Lifestyle modifications
- Intermittent fasting
- Eat smaller meals. Chew properly and eat slowly
- Quit smoking
- Remove grains that increase inflammation
- Take an N-Acetyl Cysteine (NAC) supplement to increase glutathione production that in turn will help reduce inflammation in the pancreas
- Take a liver tonic to strengthen and detoxify your liver and pancreas. St Mary’s milk thistle, selenium, taurine, and B-vitamins supplements can be highly effective.
- Eat more plant-based food that includes vegetables, legumes, and seasonal fruits.
- Avoid trans fats which are mostly present in processes snack goods
- Take selenium supplements
- Take supplements containing ALA (alpha-lipoic acid)
- Avoid high fructose corn syrup that is present in sweetened fruit drinks and soft drinks. They are also found in canned fruits, breakfast cereals, flavored yogurt, and baked goods.
- Avoid excess alcohol
- Say no to deep-fried foods and reduce your intake of industrial seed oils such as corn oil, soybean oil, cottonseed oil, rice bran oil, etc.
- Reduce your consumption of refined, processed, and sugary products
Your doctor or dietician may advise you to limit your calorie intake for weight loss.
- High consumption of vitamin C that comes from fresh fruits and vegetables helps reduce inflammation. Citrus fruits such as oranges and grapefruit are excellent for that purpose.
- Drink raw juices of citrus fruits, apple, carrot, cabbage, kale, ginger, celery, mint, and parsley which are anti-inflammatory and help cleanse your organs.
- Drink ginger tea which can help reduce inflammation and detoxify the body
- A cup of green tea every day can be a great way to start your day
- Licorice infusion
- Keep hydrating yourself with pure drinking water
- Eat green leafy vegetables which are rich in vitamins and minerals
- Eat fruits that are rich in antioxidants
- Reduce your stress levels
- Practice yoga for a healthy pancreas
Statin: The use of statin is a commonly accepted treatment for the fatty pancreas and has been known to reduce the risk of pancreatic cancer. However, recently some studies have also stated statin to be a risk factor for inducing diabetes (22).
A study on mice with pancreas fatty formation showed a reversal of pancreas fatty filtration with the treatment of simvastatin.
Acalypha indica Linn. as an alternative for the lipid-lowering agent: The possibility of beta-cell dysfunction from the use of statin urges the emergence of other alternatives for dyslipidemia treatment for NAFPD which also includes herbal-derived-alternative. Acalypha indica Linn (AI), is a plant found in tropical and subtropical climates.
It comes from the Euphorbiaceae family. Several studies have shown promising effects from the use of this AI extract for metabolic syndrome. It has been known to decrease free fatty acids and serum glucose levels, an effect believed to be derived from its flavonoid content. More research is needed to understand its potential.
The Correlation Between Non-Alcoholic Fatty Liver and Non-Alcoholic Fatty Pancreas
A strong association between the presence of NAFLD and NAFPD has been shown in many studies. This is as high as 50% in both Asian and Western countries.
Let’s have a look at the table and understand (23)
|Non-alcoholic fatty liver disease (NAFLD)||Non-alcoholic fatty pancreas (NAFP)|
|Etiology||Obesity, Metabolic syndrome, Diabetes mellitus, Medications such as steroids, Chronic viral hepatitis, congenital syndrome||Obesity, Metabolic syndrome, congenital syndrome, viral infection, others|
|Definite risk factors||MetS, Diabetes mellitus,||Obesity|
|Clinical presentation||Asymptomatic abnormal liver chemistries, Abnormal imaging studies, Histopathology,||Asymptomatic Abnormal imaging studies|
|Diagnosis||Imaging studies only|
|Clinical significance||Related to metabolic syndrome,||Increased severity of acute pancreatitis, chronic pancreatitis, increase mortality, increased complication after pancreatic surgery, may increase the stage of pancreatic cancer|
|Treatment||Lifestyle modification, Bodyweight reduction, medication||No data|
The Final Note
The fatty pancreas has been observed to be the risk factor of pancreatic cancer development. It is the fat accumulation in the pancreas. People with high-risk factors such as obesity, especially central obesity, metabolic disorder, genetic syndrome, insulin resistance, diabetes mellitus, and non-alcoholic fatty liver disease are at risk of the fatty pancreas.
Mostly it is possible to reverse the fatty pancreas through lifestyle modifications such as diet, weight loss, and an active lifestyle to prevent weight regain.
To get the best outcome, follow your doctor’s recommended treatment plan and practice a healthy lifestyle overall.