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.
Bibliographical noteFunding Information:
This study was supported in part by the American Diabetes Association (No. 1-11-CT-06) and the National Pancreas Foundation. M.D.B and R.P.R received support from the National Institute for Diabetes, Digestive, and Kidney diseases (1K23DK084315 and R01-39994, respectively). The authors would like to thank the Clinical Translational Sciences Institute and their staff for their contributions to conducting the study. The Clinical Translational Sciences Institute is supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114.
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- Total pancreatectomy and islet autotransplantation
- β cell