Early Alterations in Glycemic Control and Pancreatic Endocrine Function in Nondiabetic Patients With Chronic Pancreatitis

Abstract

Objectives: Diabetes mellitus is a frequent consequence of chronic pancreatitis (CP). Little is known about pancreatic endocrine function before the development of diabetes mellitus 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 FSIVGTT was 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.

Figure 1

From mixed meal tolerance tests in chronic pancreatitis (dark circle) and healthy control (grey diamonds): (a) glucose; (b) C-peptide; (c) glucagon levels, (d) GLP-1, and (e) GIP. AUC glucose and AUC glucagon were significantly higher in the CP cohort, but AUC C-peptide, GLP-1, and GIP did not differ between groups. * indicates p-value ≤0.05, ** p ≤0.01.

Figure 2

Results from the frequent sample intravenous glucose tolerance test in chronic pancreatitis and matched control patients: (a) Acute insulin response to glucose (n=20 pairs); (b) insulin sensitivity index (n=21 pairs); and (c) natural log of the disposition index (n=19 pairs).

Figure 3

Mixed meal tolerance test glucose (A), C-peptide (B), and glucagon levels (C) in patients with non-calcific chronic pancreatitis (n=18, open circles with dashed line) and calcific pancreatitis (n=7, grey circles, solid grey line). The AUCglucose was significantly higher in calcific chronic pancreatitis, while differences in C-peptide and glucagon were not statistically significant. Data are graphically represented as mean ± standard error.