What is type 3c (pancreatogenic) diabetes?

What is Type 3c Diabetes?

Type 3c diabetes (also called pancreatogenic or pancreatic diabetes) is a form of diabetes that develops when diseases of the exocrine pancreas damage the insulin-producing islet cells, resulting in loss of both insulin and glucagon secretion alongside pancreatic exocrine dysfunction. 1

Defining Characteristics

Type 3c diabetes is fundamentally different from type 1 and type 2 diabetes in its pathophysiology and clinical presentation:

• Dual hormonal deficiency: Patients lose both insulin secretion from β-cells and glucagon secretion from α-cells, along with reduced pancreatic polypeptide levels 1
• Concurrent exocrine dysfunction: The hallmark feature is simultaneous pancreatic exocrine insufficiency, typically confirmed by low fecal elastase or direct function tests 1
• Absence of autoimmunity: Unlike type 1 diabetes, patients lack diabetes-associated autoantibodies 1

Common Causes

The diverse etiologies of type 3c diabetes include 1:

• Pancreatitis (acute and chronic) - accounts for approximately 75% of cases 2
• Pancreatic surgery (pancreatectomy or trauma)
• Pancreatic neoplasia
• Cystic fibrosis
• Hemochromatosis
• Fibrocalculous pancreatopathy
• Rare genetic disorders

Clinical Presentation: "Brittle" Diabetes

The most distinctive clinical feature is characteristically unstable "brittle" diabetes with erratic swings between severe hypoglycemia and hyperglycemia. 1, 3

This occurs because:

• Reduced pancreatic polypeptide contributes to decreased hepatic insulin sensitivity and unsuppressed hepatic glucose production 1
• Loss of glucagon secretion impairs the body's ability to counter hypoglycemia 1, 4
• Patients often have higher-than-expected insulin requirements 1

Associated Complications

Patients with type 3c diabetes face unique challenges beyond glycemic control:

• Malnutrition and undernutrition: Due to pancreatic exocrine insufficiency causing malabsorption, chronic abdominal pain, anorexia, and symptom avoidance 1, 3
• Osteoporosis: Approximately two-thirds of chronic pancreatitis patients develop bone disease due to vitamin D and calcium malabsorption 1, 3
• Nutrient deficiencies: Particularly fat-soluble vitamins 1, 3
• Increased mortality risk: Higher likelihood of death related to hypoglycemic events compared to other diabetes types 5

Prevalence and Misdiagnosis

Type 3c diabetes accounts for approximately 5-10% of all diabetes cases but is frequently misclassified as type 2 diabetes. 5, 2

This misdiagnosis is problematic because:

• Type 3c diabetes requires different treatment approaches than type 2 diabetes 1, 4
• Patients are often inappropriately excluded from diabetes research studies 1
• The condition carries a high risk for pancreatic carcinoma, particularly in chronic pancreatitis cases 2

Diagnostic Approach

The American Diabetes Association recommends specific screening protocols 1:

• Screen within 3-6 months following acute pancreatitis, then annually thereafter
• Annual screening for chronic pancreatitis patients
• Use oral glucose tolerance test (OGTT) rather than A1C, which has low sensitivity for type 3c diabetes 3, 4

Key diagnostic features distinguishing type 3c from other diabetes types 1:

• Pathological pancreatic imaging (endoscopic ultrasound, MRI, or CT)
• Documented pancreatic exocrine insufficiency (fecal elastase testing)
• Absence of type 1 diabetes autoantibodies
• Evidence of structural pancreatic damage

Risk Factors for Development

Within chronic pancreatitis populations, risk is highest in 1:

• Heavy smokers
• Those who have undergone distal pancreatectomy (due to high concentration of islet cells in the pancreatic tail)
• Patients with longer disease duration
• Those with pancreatic calcifications

Important Clinical Caveat

Type 2 and type 3c diabetes can coexist in the same patient, complicating both diagnosis and management. 3 This overlap requires careful clinical assessment to ensure appropriate treatment strategies are employed.