Causes of Pancreas Atrophy and Risk Factors of NAFPD (Fatty Pancreas)

A male patient in his mid-thirties is being examined by a female doctor in her office. The patient is expressing his discomfort with pancreatic pain. The female doctor explains the causes of pancreas atrophy

The pancreas is a vital organ. It is not very big, only about the size of a person’s hand, and it is tucked behind the abdomen. It has two major roles: it produces digestive enzymes that are released into the intestine to digest food, and it produces hormones that are released into the bloodstream and regulate blood sugar level, appetite, the production of stomach acids, and the rate of stomach emptying. In this article, we’ll discover what is pancreas atrophy and what are the causes of pancreas atrophy. Let’s dive in.

Pancreatic atrophy

Most causes of pancreas atrophy involve the gradual replacement of the normal pancreatic tissue by fatty tissues, which has in the past been called pancreatic lipomatosis, pancreatic steatosis, or fatty pancreas. More recently, this condition has been officially renamed nonalcoholic fatty pancreas disease (NAFPD). The process of developing NAFPD involves the infiltration of fatty tissues into the pancreas and the death of the normal acinar pancreatic cells.

A completely different form of pancreatic atrophy, lobular atrophy, is a symptom of pancreatic cancer and is not discussed in this article.

Causes of Pancreas Atrophy

Some causes of pancreas atrophy occur in individuals with metabolic syndrome. Metabolic syndrome is characterized by obesity, type II diabetes, hyperlipidemia, and nonalcoholic fatty liver disease (NAFLD). NAFPD has recently been added to the conditions associated with metabolic syndrome. Like NAFLD, its exact etiology is unclear, but chronic inflammation and abnormal fatty tissue infiltration are major aspects of its pathology.

Symptoms of NAFPD

There are no overt symptoms of NAFPD until extensive destruction of the pancreas has occurred. Most cases of NAFPD never reach this point. However, if it does, the following symptoms of pancreatic exocrine dysfunction may manifest:

  • Chronic diarrhea
  • Weight loss
  • Fatty stools

Pancreatic exocrine dysfunction is treated by the administration of pancreatic digestive enzymes. These enzymes are taken orally with food and assist with digestion.

Diagnosis of NAFPD

NAFPD is usually incidentally diagnosed on medical imaging. On ultrasound, MRI, and CT, a fatty pancreas looks very different from a healthy pancreas. In some cases, the radiologist may suspect a fatty pancreas is some form of pancreatic cancer and order a biopsy.

Imaging methods based on MRI, such as magnetic resonance spectroscopy (MRS) and magnetic resonance elastography (MRE), are being investigated and may be better approaches to diagnosing and monitoring the progression of NAFPD. MRE non-invasively measures the stiffness and texture of tissues and has proven very useful in studying NAFLD. MRE can detect the amount of fatty tissue infiltration and the extent of fibrosis in the pancreas, which directly reflect the degree of severity of pancreatic tissue atrophy and its replacement by fatty tissues.

NAFPD and type II diabetes

There is a clear association between type II diabetes and NAFPD. Individuals with type II diabetes are likely to have NAFPD, and individuals with NAFPD are likely to develop type II diabetes in the future. However, it is not clear if the association is causal. Some experts speculate that the causal pathway starts with obesity, which causes NAFPD, which then causes type II diabetes. Alternatively, all of the many manifestations of metabolic syndrome may be caused by a single underlying etiology, which has yet to be identified.

Weight loss can alleviate the symptoms of diabetes and reduce the amount of fatty tissue in the pancreas, supporting the theory that obesity is a key factor in the development of both NAFPD and type II diabetes.

NAFPD and pancreatitis

NAFPD is also associated with both acute and chronic pancreatitis. Long-standing chronic pancreatitis seems to induce the development of NAFPD, and severe NAFPD can trigger or worsen chronic pancreatitis, suggesting a vicious feedback cycle. However, the nature of the association between NAFPD and acute pancreatitis is not straightforward. Acute pancreatitis is a risk factor for type II diabetes. NAFPD is a risk factor for acute pancreatitis and type II diabetes. Obesity is a risk factor for acute pancreatitis, type II diabetes, and NAFPD. Thus, as for type II diabetes, the causal pathway is either obesity causing NAFPD, which then causes pancreatitis, or alternatively, a single underlying etiology, which has yet to be identified, causes both NAFPD and pancreatitis.

NAFPD and pancreatic cancer

The causes of pancreas atrophy have long been a mystery because studies attempting to identify environmental factors associated with an increased risk of pancreatic cancer mostly find nothing. Exposure to tobacco smoke and dry-cleaning chemicals are the only firmly established environmental risk factors.

NAFLD, a liver condition that has many similarities to NAFPD, drives the development of liver cancer through chronic inflammation, fibrosis, and disruption of the normal functioning of the liver tissue. Similarly, NAFPD seems to drive the development of pancreatic cancer. An association between obesity, diabetes, and pancreatic cancer has been noted, and NAFPD may be the direct link between obesity/diabetes and pancreatic cancer, and the ultimate driver of pancreatic cancer development. Unfortunately, the presence of NAFPD also increases the risk of pancreatic cancer metastasis and the development of severe, potentially fatal complications of pancreatic cancer treatment, such as post-surgical pancreatic fistula.

Treatment of NAFPD

The primary treatment of NAFD involves reversing the process of metabolic syndrome. Weight loss mediated through lifestyle changes, bariatric surgery, or one of the glucagon-like peptide-1 receptor antagonists (e.g., semaglutide, brand name Wegovy) can stop and even reverse the progression of NAFPD. Drugs that block the absorption of fat from the intestine (e.g., orlistat) have a similar effect. A combination of the anti-diabetic drug sitagliptin and the angiotensin II receptor antagonist telmisartan was also proven effective in stopping the progression of NAFPD.


Although the study of NAFPD is in its infancy, it mimics NAFLD in many ways. Thus, knowledge of NAFLD can be extrapolated to help understand the cause, complications, and treatment of NAFPD. NAFPD should be thought of as another manifestation of metabolic syndrome and be placed alongside NAFLD, obesity, hyperlipidemia, and type II diabetes as yet another manifestation of this poorly understood, yet very common condition.

NAFPD generally has no overt symptoms, but since it increases the risk of pancreatic cancer, aggressive cancer with few treatment options, and an abysmal outcome, it should be taken very seriously. In fact, the discovery that NAFPD may be the major driver of pancreatic cancer brings new hope to the field of pancreatic cancer. If NAFPD can be diagnosed early and treated, perhaps many cases of pancreatic cancer can be prevented.