title: Therapy with proton pump inhibitors in patients with type 2 diabetes is independently associated with improved glycometabolic control.
abstract: OBJECTIVE
  Experimental data demonstrated that gastrin has incretin-like stimulating actions on β-cells, resulting in a promotion of glucose-induced insulin secretion. As proton pump inhibitors (PPIs) consistently increase plasma gastrin levels, a possible effect of this treatment on glucose-insulin homeostasis may be hypothesized. Therefore, the aim of this study was to evaluate the effect of chronic PPIs treatment on glycemic control in patients affected by type 2 diabetes.
  
  
  METHODS
  This is an observational, retrospective study. A total of 548 consecutive patients with type 2 diabetes (mean age ± SD: 67.1 ± 10.9 years, M/F: 309/239, diabetes duration: 12.4 ± 9.8 years) referring to our diabetes outpatient clinics were enrolled; among them, 45 %were treated with PPIs longer than 2 years for preventive/therapeutic purposes. Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), serum lipids and transaminases were measured by standard laboratory methods. Major cardiovascular events and concomitant medications were recorded in all participants, and daily insulin requirement was calculated in insulin-treated subjects.
  
  
  RESULTS
  PPIs-treated patients had significantly lower HbA1c (7.1 ± 1.07 %-54.1 ± 12 vs 7.4 ± 1.4 %-57.4 ± 8 mmol/mol, p = 0.011) and FPG (127 ± 36.9 vs 147.6 ± 49.4 mg/dl, p < 0.001) levels than those untreated. These differences increased in patients under insulin therapy and in those with concomitant PPIs + GLP-1-based therapy. The multivariate regression analysis demonstrated that the association between chronic PPIs treatment and HbA1c was independent from possible confounders (p = 0.01).
  
  
  CONCLUSIONS
  PPIs treatment is associated with greater glycemic control in patients with type 2 diabetes, particularly in those on insulin- or GLP-1-based therapy. Our results suggest a role for PPIs in glucose-insulin homeostasis and may open a new scenario for diabetes therapy.
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Barchetta
authors.affiliation: University Campus Bio-Medico, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Guglielmi
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bertoccini
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
authors.forename: Damiano
authors.initials: D
authors.lastname: Calella
authors.affiliation: University Campus Bio-Medico, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Manfrini
authors.affiliation: University Campus Bio-Medico, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Secchi
authors.affiliation: University Campus Bio-Medico, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pozzilli
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy. gisella.cavallo@uniroma1.it.
authors.forename: Maria Gisella
authors.initials: MG
authors.lastname: Cavallo
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000032:analysis* / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005215:Fasting; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000032:analysis; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies
chemical_list: D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007328:Insulin; D054328:Proton Pump Inhibitors
keywords: Incretins; PPI; Therapy; Type 2 diabetes