OBJECTIVE: Diabetes frequently develops in patients with chronic pancreatitis. We examined the alterations in the glucagon response to hypoglycemia and to oral glucose administration in patients with diabetes due to chronic pancreatitis.

RESEARCH DESIGN AND METHODS: Ten patients with diabetes secondary to chronic pancreatitis were compared with 13 patients with type 2 diabetes and 10 healthy control subjects. A stepwise hypoglycemic clamp and an oral glucose tolerance test (OGTT) were performed.

RESULTS: Glucose levels during the OGTT were higher in patients with diabetes and chronic pancreatitis and lower in control subjects (P< 0.0001). Insulin and C-peptide levels were reduced, and the glucose-induced suppression of glucagon was impaired in both groups with diabetes (allP< 0.0001 vs. control subjects). During hypoglycemia, glucagon concentrations were reduced in patients with chronic pancreatitis and with type 2 diabetes (P< 0.05). The increase in glucagon during the clamp was inversely related to the glucose-induced glucagon suppression and positively related to β-cell function. Growth hormone responses to hypoglycemia were lower in patients with type 2 diabetes (P= 0.0002) but not in patients with chronic pancreatitis.

CONCLUSIONS: α-Cell responses to oral glucose ingestion and to hypoglycemia are disturbed in patients with diabetes and chronic pancreatitis and in patients with type 2 diabetes. The similarities between these defects suggest a common etiology.