ISLET HORMONE-SECRETION IN PANCREATIC-CANCER PATIENTS WITH DIABETES

The diabetes or impaired glucose tolerance that occurs in most patient s with pancreatic cancer is characterized by profound insulin resistan ce. Recent evidence suggests that the diabetes may result from the pre sence of the tumor rather than being a predisposing factor to developm ent of the malignancy. Some islet hormones have been shown to exhibit diabetogenic effects. To investigate the potential role of these hormo nes in the diabetic state associated with pancreatic cancer, we measur ed islet hormones during fasting in pancreatic cancer patients (n = 30 ), patients with other malignancies (n = 43), and healthy controls (n = 25). Preoperative pancreatic cancer patients were classified as norm al glucose tolerance (NGTT), impaired glucose tolerance (IGTT), non-in sulin-requiring diabetes (NIRD), and insulin-requiring diabetes (IRD). Nine pancreatic cancer patients were studied after tumor removal by s ubtotal pancreatectomy. Some preoperative pancreatic cancer patients ( n = 19), postoperative patients (n = 9), and controls (n = 8) were als o studied during hyperglycemia and following glucagon injection. Easti ng plasma C-peptide was elevated in NIRD pancreatic cancer patients co mpared to controls. Fasting levels of islet amyloid polypeptide (IAPP) , glucagon, and somatostatin were elevated in NIRD and IRD patients. I APP and glucagon, but not somatostatin, normalized following subtotal pancreatectomy. During hyperglycemia, increases in C-peptide and IAPP were seen only in controls and in NGTT and postoperative pancreatic ca ncer patients. After glucagon infusion, IAPP levels increased in contr ols and nondiabetic cancer patients; C-peptide levels increased in con trols, nondiabetic patients, and NIRD. Responses of C-peptide and IAPP to glucagon normalized after pancreatectomy. During hyperglycemia, gl ucagon levels fell in all groups except IGTT patients and a decrease i n somatostatin concentrations was seen in controls.