The Effect of Proton Pump Inhibitors on Insulin-Glucose Homeostasis in Patients With Type 2 Diabetes Mellitus

Introduction: Gastrin release from G cells stimulates cholecystokinin (CCK2) receptors throughout the body, most of which promote gastric acid secretion. However, gastrin also stimulates CCK2 receptors located elsewhere, including the islet of the pancreas. In turn, gastrin increases insulin secretion(1). Gastrin also promotes pancreatic β cell neogenesis and replication. Proton pump inhibitors (PPIs) decrease the pH of the stomach and stimulate gastrin secretion, which may indirectly promote insulin secretion and improve hemoglobin A1c (HbA1c). Objective: To understand the effect of PPIs on insulin-glucose homeostasis (c-peptide, HbA1c, and glucose) in patients with type 2 diabetes mellitus (T2DM). Methodology: We retrospectively reviewed the charts of patients with T2DM at least 18 years of age who received care at AnMed Health facilities from Jan. 1, 2018 through Dec. 31, 2018 to compare HbA1c, C‐peptide, and glucose levels in patients with and without active PPI therapy. Slicer-dicer software was used to identify study population with diagnosis of T2DM and labs including both HbA1c and C-peptide. Out of total 215 patients satisfying inclusion criteria, 71 patients were on PPI. Statistical analyses were performed using SPSS version 20.0 (SPSS, Armonk, NY: IBM Corp). All values are presented as means ± SD. A p value of < 0.05 was considered to be significant. Independent T-test and chi-square test were performed to compare parameters in between groups. Results: The PPI and non‐PPI groups had no statistical difference regarding age, sex, race and BMI. There was no significant difference in HbA1c levels between PPI and non‐PPI groups (8.6% ± 2.1 vs 8.3% ± 2.0, respectively; p value = 0.37). However, we found a significant increase in C‐peptide levels (3.1 ng/mL ± 2.4 vs 2.4 ng/mL ± 2.3; p value = 0.037) and decrease in LDL levels (79.6 mg/dL ± 34.0 vs 89.73 mg/dL ± 32.9; p value = 0.046) in the PPI group compared to non-PPI group. In addition, there was a significantly greater prevalence of coronary artery disease in the PPI group (p = 0.01). Conclusion: PPI therapy in patients with T2DM was not associated with improved glycemic control. However, C-peptide levels were significantly higher in patients with T2DM who were on PPI therapy suggesting higher insulin secretion. The lack of difference in HbA1c levels may be a result of aggressive diabetic management by treating clinicians to achieve similar goal HbA1c in both groups. Further research is needed to understand the gastrin pathway as a potential option for improving glycemic control. References: 1. Rehfeld JF. Incretin physiology beyond glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide: cholecystokinin and gastrin peptides. Acta Physiol (Oxf). 2011 Apr;201(4):405–11.