Early alterations in glycemic control and pancreatic endocrine function in nondiabetic patients with chronic pancreatitis

Objectives: Diabetes mellitus is a frequent consequence of chronic pancreatitis (CP). Little is known about pancreatic endocrine function before the development of diabetesmellitus in CP, particularly in females, or those without calcific and/or alcoholic pancreatitis. Methods: Twenty-five nondiabetic adult patients with CP (19 female; mean [SE] age, 34.2 [2.4] years) were compared with 25 healthy controls matched for age, sex, and body mass index. Subjects underwent frequent sample intravenous glucose tolerance testing (FSIVGTT) and mixed meal tolerance testing (MMTT). Results: Mean (SE) fasting glucose was higher in patients with CP (89.5 [2.3] mg/dL) than in controls (84.4 [1.2] mg/dL, P = 0.04). On MMTT, patients with CP had a higher area under the curve (AUC) glucose and AUC glucagon compared with controls (P ≤ 0.01). The AUC C-peptide was equivalent (P = 0.6) but stimulated C-peptide at 30 minutes was lower in patients with CP (P = 0.04). Mean insulin sensitivity index calculated from the FSIVGTTwas lower in CP group, indicating reduced insulin sensitivity (P ≤ 0.01). Disposition index (insulin secretion adjusted for insulin sensitivity on FSIVGTT) was lower in patients with CP (P = 0.01). Conclusions: Patients with CP had higher fasting and MMTT glucose levels, without a compensatory increase in insulin secretion suggesting subtle early islet dysfunction. Our cohort had relative hyperglucagonemia and was less insulin sensitive than controls.