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DEFINITION

• Endocrine pancreatic insufficiency occurring after surgical resection of the pancreas leading to development of new-onset diabetes, exacerbation of pre-existing diabetes, or progression of pre-existing glucose intolerance to overt diabetes.
• Important factors include: amount of pancreatic parenchymal tissue removed, resection vs "sparing" of adjacent organs, preoperative pancreatic function, peripheral insulin resistance, preoperative diabetes, and postoperative changes in nutrition.

EPIDEMIOLOGY

• Pancreatic resections in the United States have increased overall 15% in the last decade, with a 27% increase in resections for benign pancreatic disease alone.
• Indications for pancreatic surgery include: malignancies (curative or palliative resection); chronic pancreatitis (palliation, drainage of pseudocysts, or repair of obstruction or fistulas); and acute necrotizing pancreatitis (necrosectomy or lavage-pseudocyst drainage). 

CLINICAL TREATMENT

• Postoperatively, insulin requirements are affected by nutritional disruptions due to ileus, pancreatic leak, or chyle leak. Also consider pre-operative malnutrition; as well as parenteral nutrition required during periods of bowel or pancreatic rest.
• In setting glycemic goals with pancreatic malignancy, consider overall prognosis and nutritional instability from chemotherapy/ radiation therapy. Higher glycemic targets may be indicated in these settings.

• Total pancreatectomy results in total insulin deficiency and near-absent glucagon production.
• All patients will require exogenous basal and correctional insulin to treat hyperglycemia and mealtime rapid or short-acting insulin to cover ingested carbohydrates once diet is consistent. 
• Initial insulin requirements during immediate postoperative fasting period are usually low, possibly due to the lack of glucagon production causing less hepatic gluconeogenesis.
• IV insulin infusion along with a low level of IV dextrose while patient is NPO provides the greatest flexibility.
• Because of the exaggerated sensitivity to insulin postoperatively, transition from IV to SQ insulin regimens utilizing conservative doses.

• Near-total pancreatectomy: ~ 95% is removed,  may be offered to patients with intractable pain from pancreatitis. Postoperatively, ~ 60-75% of patients require insulin.
• Proximal pancreatectomy: most commonly the "classic Whipple" or pancreaticoduodenectomy; head of the pancreas, duodenum, distal stomach (often), common bile duct, and gallbladder are removed. Recent refinements may preserve the pylorus and/or duodenum. May have leaks from the pancreaticojejunostomy, other perioperative events, or delayed gastric emptying. New onset diabetes in ~ 20-50%.
• Distal pancreatectomy: for disease processes in the tail. Spleen may be removed and the flow of pancreatic secretions not normally interrupted. Diabetes from ~ 3-30% .
• Middle pancreatectomy: preserves pancreatic parenchyma, reducing the risk of exocrine and endocrine insufficiency.  Less diabetes but higher rates of fistulas and pancreatic leaks.
• During hospital stay, closely monitor glycemia, in particular as diet is advanced and implement insulin therapy if needed.
• Prior diabetes regimens will likely need to be increased after pancreas surgery, often requiring insulin. 
• Rarely, removal of diseased tissue and subsequent reduced inflammation brings improved glycemic control.

FOLLOW UP

• GI disturbances are common and sometimes prolonged, often requiring pancreatic enzymes.  Gastric emptying can be delayed, and nausea and diarrhea can occur.
• Oral intake may be irregular and sporadic for several months making insulin management challenging.
• Additional changes in nutrition and insulin requirements can occur during chemotherapy in cancer patients.
• After total and distal pancreatectomy, patients are at increased risk for rapid development of hypoglycemia due to deficiency of glucagon-secreting alpha cells.
• For total pancreatectomy patients, include basal and correctional insulin, with nutritional insulin once food intake is stabilized and consistent.
• Partial pancreatectomy patients show wide variability in postoperative insulin requirements. A preoperative A1C > 6 % can be predictive of patients who will require postoperative insulin therapy.
• Insulin requirements may be erratic for several months after surgery, until healing has progressed, perioperative inflammation has resolved, and nutritional intake has normalized. During this period of instability, more conservative glycemic targets may be indicated.
• Patients on insulin need outpatient follow up with an endocrinologist and/or diabetes educator, no longer than 1 month post discharge.
• For insulin-treated patients, include on discharge: syringes/vials, insulin pens/needles, and glucagon emergency kits.
• All patients with blood glucose elevations postoperatively should receive a glucose meter, prescriptions for glucose testing strips and instructions to monitor their blood glucose regularly until follow up with their primary care provider within 1 month of hospital discharge.
• Discharge instructions include: contact health care provider for blood glucose <70 mg/dL, glucose >300 mg/dL, or 3 consecutive glucose readings >250 mg/dL.

EXPERT COMMENTS

• Inpatient consults should be initiated as soon as possible with a dietician and diabetes care team.
• Patient instruction, including hands on practice with insulin self-administration and blood glucose monitoring, should begin as early as possible and continue with frequent reinforcement and practice throughout the hospital stay.
• After pancreatectomy, patients are under severe physical and emotional stress.  This impacts their ability to understand and retain safety related instructions.
• Patients, especially with total pancreatectomy, will require outpatient diabetes education follow-up having become rapidly and totally insulin-deficient in the context of simultaneous glucagon deficiency, often leading to brittle diabetes.

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