Risk Factors Associated with Progression Toward Endocrine Insufficiency in Chronic Pancreatitis

Objective  Little data exist describing the change over time in islet function and glycemic control in patients with chronic pancreatitis (CP). Methods  In 325 CP patients who underwent 2 mixed meal tolerance tests and/or glycated hemoglobin (HbA1c) levels, we estimated the rate of change in metabolic measures per 6 months and assessed the association between potential risk factors for diabetes and rate of change using multivariate regression models. Results  Per 6-month time, HbA1c increased by 0.062% with a standard error of 0.029% (P = 0.037) and the ratio (area under the curve (AUC) C-peptide to AUC glucose from mixed meal tolerance testing) decreased by 0.0028 with a standard error of 0.0011 (P = 0.014). We observed more rapid decline in smokers (AUC C-peptide, P = 0.043) and patients with surgical drainage (AUC glucose, P = 0.001; ratio, P = 0.03) or with calcific pancreatitis (HbA1c, P = 0.003). In multivariate models, AUC C-peptide and ratio declined at a greater rate in smokers and HbA1c in those with pancreatic calcifications (both P < 0.05). Conclusions  We observed a measurable decline in β-cell function and glycemic control in patients with CP. Patients with a history of tobacco smoking, surgical drainage, or pancreatic calcification may be at highest risk.