DIABETES MELLITUS TYPE 2 IN PANCREATIC CANCER

Surgical Clinics of North America June 2013

Introduction

• Pancreatic cancer – 4th leading cause of cancer deaths.

• Estimated OS – 5% at 5 years.• 15-20% have resectable disease at

presentation.• 5 year survival after resection – 25%.

Risk factors

• Modifiable1. Cigarette smoking2. Obesity3. Type 2 diabetes mellitus

Diagnosis of DM2

TEST CUT-OFF VALUE

Fasting plasma glucose

≥ 126 mg/dL

Glucose tolerance test

≥ 200 mg/dL

HbA1c ≥ 6.5 %

Random plasma glucose

≥ 200 mg/dL

Anatomy of islet cells

• Ellipsoid clusters of cells embedded in exocrine tissue.

• Receive 20-30% of the pancreatic blood flow.• Mostly concentrated in the tail

Relation between pancreatic cancer and diabetes

• 80% of patients will have DM2 or glucose intolerance.

• Inciting event unknown DM2 vs. Pancreatic cancer.

DM2 as a symptom

• Studies show that new onset DM2 was more common in patients with pancreatic cancer than controls.

• 50% greater risk of malignancy in recently diagnosed DM2 compared to long standing DM2.

• One percent of newly diagnosed DM2 will be diagnosed with pancreatic cancer within 3 years.

• Potential early tool for screening.• 71% of the glucose intolerance diagnosed was

unknown before pancreatic cancer was diagnosed.

Insulin resistance

Increased b cell mass

High local levels of insulin

Mitogenic action- tumor progression

Pancreatic cancer cells

Altered gene expression in skeletal muscles

Altered gene expression TCA cycle mediators and glucose metabolism

Aberrant metabolism leading to DM2

DM2 and pancreatic resection

• DM2 increases operative complications• Insulin dependent DM2 increased 90 day

mortality from 4.8% to 13 %.• Post operative pancreatic fistula- Odds ratio

4.3.• Reduced survival especially in new onset DM2

after resection

Diabetogenic carcinoma?

• In a study of 101 patients undergoing pancreatectomy with 41% preoperative DM2.

• Postoperatively 20 % developed DM2.• 35% had improvement in sugar control.

Summary

• Pathways of tumourogensis of and pathophysiology of DM2 are intertwined.

• Further studies required for better understanding.

• DM2 is a significant co-morbidity for pancreatic resection.

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