Pancreatic Dysfunction: Diabetes, Pancreatitis, Malabsorption, and Cancer Risks

The pancreas has dual endocrine (insulin, glucagon) and exocrine (digestive enzymes) functions. Dysfunction causes distinct syndromes.

Endocrine Failure → Diabetes Mellitus

• Type 1: Autoimmune β-cell destruction → absolute insulin deficiency.
• Type 2: Insulin resistance + relative deficiency.
• Type 3c (Pancreatogenic): From chronic pancreatitis, cystic fibrosis, hemochromatosis, pancreatic resection.
• Symptoms: Polyuria, polydipsia, weight loss, fatigue, blurred vision, infections, neuropathy.

Exocrine Failure

• Acute Pancreatitis: Sudden inflammation (gallstones, alcohol, hypertriglyceridemia, ERCP). Severe epigastric pain radiating to back, nausea, vomiting, elevated lipase/amylase. Can be necrotizing, fatal.
• Chronic Pancreatitis: Progressive fibrosis → pain, exocrine/endocrine insufficiency. Alcohol, smoking, genetic (PRSS1, SPINK1, CFTR).
• Exocrine Pancreatic Insufficiency (EPI): Inadequate enzymes → malabsorption (steatorrhea, weight loss, fat-soluble vitamin deficiency). Treated with PERT (pancreatic enzyme replacement therapy).

Pancreatic Cancer

Adenocarcinoma (95%) — late presentation, poor prognosis. Risk: smoking, chronic pancreatitis, diabetes, family history, BRCA mutations. Symptoms: jaundice, weight loss, pain, new-onset diabetes.

When to Seek Care

Persistent abdominal pain, unexplained weight loss, jaundice, steatorrhea, new diabetes with weight loss → urgent evaluation (CT/MRI, EUS, CA 19-9).