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Lin MH, Wu WT, Chen YC, Lin TK, Chou YC, Sun CA. Association between clinical use of lansoprazole and the risk of type 2 diabetes mellitus: a pharmacoepidemiological cohort study. Diabetol Metab Syndr 2023; 15:96. [PMID: 37165435 PMCID: PMC10170833 DOI: 10.1186/s13098-023-01051-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 03/31/2023] [Indexed: 05/12/2023] Open
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are common and widely used for gastrointestinal-related disorders. Lansoprazole is one of PPIs with potential benefits of anti-inflammation, reduced oxidative stress, and anti-diabetes. The aims of this study are to determine whether lansoprazole imparts differential risk of type 2 diabetes as compared with other PPIs. METHODS A population-based retrospective cohort study was conducted using the National Health Insurance Research Database in Taiwan. Patients who received lansoprazole more than 90 days and without records of use of other PPIs between January 1, 2000 and December 31, 2005 (the exposure period) were considered as the exposed cohort (n = 1668). In comparison, patients who received other PPIs more than 90 days and without use of lansoprazole in the exposure period were treated as the comparison cohort (n = 3336).The primary outcome was the new-onset of type 2 diabetes mellitus (T2DM). The association between use of lansoprazole and the risk of T2DM was determined by hazard ratios (HRs) and 95% confidence intervals (CIs) derived from multivariable Cox proportional hazards models. RESULTS The lansoprazole cohort showed a significantly reduced risk of T2DM with an adjusted HR of 0.65 (95% CI 0.56-0.76). Interestingly, the inverse association between use of lansoprazole and risk of T2DM was observed in both genders and in various age groups. CONCLUSION The present study findings suggest that lansoprazole was associated with a reduced risk of T2DM compared with other PPIs. Further studies are needed to determine the clinical implications of the present study.
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Affiliation(s)
- Ming-Hsun Lin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City, 114, Taiwan
| | - Wen-Tung Wu
- Department of Pharmacy, Tri-Service General Hospital, National Defense Medical Center, Taipei City, 114, Taiwan
| | - Yong-Chen Chen
- Department of Public Health, College of Medicine, Fu-Jen Catholic University, No.510, Zhongzheng Road, Xinzhuang District, New Taipei City, 242, Taiwan
- Department of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, 242, Taiwan
| | - Tsung-Kun Lin
- School of Pharmacy, National Defense Medical Center, Taipei City, 114, Taiwan
| | - Yu-Ching Chou
- School of Public Health, National Defense Medical Center, Taipei City, 114, Taiwan
| | - Chien-An Sun
- Department of Public Health, College of Medicine, Fu-Jen Catholic University, No.510, Zhongzheng Road, Xinzhuang District, New Taipei City, 242, Taiwan.
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Saboo B, Mulwani N, Petare AU, Veligandla KC, Pinto CS, Mane A, Rathod R, Kotak B. A real-world retrospective study of omeprazole-domperidone combination in managing acid peptic disease with PRoton-pump Inhibitors in patients with type 2 DiabEtes mellitus (PRIDE-2). Drugs Context 2023; 12:dic-2022-10-3. [PMID: 36816461 PMCID: PMC9933899 DOI: 10.7573/dic.2022-10-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 01/18/2023] [Indexed: 02/15/2023] Open
Abstract
Background Proton-pump inhibitors, along with a prokinetic agent, are widely used to provide symptomatic relief amongst patients with acid peptic disease (APD). This article evaluates the effectiveness and safety of the omeprazole-domperidone combination amongst patients with type 2 diabetes mellitus for the management of APD. Methods PRIDE-2 (PRoton-pump Inhibitor in patients with type 2 DiabEtes mellitus) is a retrospective study reviewing electronic medical records of patients with type 2 diabetes mellitus and APD who were receiving the omeprazole-domperidone combination and visiting multiple Indian healthcare settings between March 2018 and April 2021. The effectiveness outcome of the therapy was evaluated in terms of resolution of APD symptoms at visit 5 (120 days after baseline visit) compared with visit 1 (baseline visit). Safety was determined in terms of reported adverse events (AEs) during the treatment period (120 days). Results A total of 174 patients were included in the study. The mean age of the patients was 51.5±9.6 years, with the majority (59.8%) being men. A significant proportion of patients reported relief from APD symptoms, including abdominal pain (91.6%), epigastric burning (68.7%), nausea (89.5%), flatulence (100.0%), loss of appetite (93.6%), and altered bowel movements (94.7%) (p<0.001 for each) at visit 5 compared with visit 1. No serious AEs were reported. Conclusion Omeprazole-domperidone combination was beneficial in providing symptomatic relief to patients with diabetes and APD. The combination therapy was well tolerated, with few reports of minor AEs.
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Affiliation(s)
- Bharat Saboo
- Department of Diabetology, Prayas Diabetes Centre, Indore, Madhya Pradesh, India
| | - Nimmi Mulwani
- Department of Diabetology, Dr. Nimmi’s Diabetes Care, Chandkheda, Ahmedabad, Gujarat, India
| | - Anup Uttam Petare
- Medical Affairs, Dr. Reddy’s Laboratories Ltd, Hyderabad, Telangana, India
| | | | | | - Amey Mane
- Medical Affairs, Dr. Reddy’s Laboratories Ltd, Hyderabad, Telangana, India
| | - Rahul Rathod
- Medical Affairs, Dr. Reddy’s Laboratories Ltd, Hyderabad, Telangana, India
| | - Bhavesh Kotak
- Medical Affairs, Dr. Reddy’s Laboratories Ltd, Hyderabad, Telangana, India
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Muacevic A, Adler JR, Petare AU, Veligandla KC, Pinto CS, Mane A, Rathod R, Kotak B. An Evidence-Based Retrospective Study for the Management of Acid Peptic Disease With Omeprazole, a Proton Pump Inhibitor, in Indian Patients With Type 2 Diabetes Mellitus (PRIDE-1). Cureus 2022; 14:e32332. [PMID: 36627994 PMCID: PMC9825689 DOI: 10.7759/cureus.32332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/08/2022] [Indexed: 12/14/2022] Open
Abstract
Background In this study, we aimed to assess the effectiveness of omeprazole therapy in the management of acid peptic disease (APD) among type 2 diabetes mellitus (T2DM) patients. Methodology In this multicenter retrospective study, electronic medical records (EMRs) of T2DM patients with APD who were prescribed omeprazole between March 2018 and April 2021 at multiple Indian healthcare settings were reviewed. The resolution of APD symptoms was assessed at visit five (120 days after the index visit) and compared to visit one (index visit). Safety was established in terms of reported adverse events during the study period. Results Overall, 174 patients were included. The majority of patients (63.8%) were males with a mean age of 48.6 ± 11.03 years. After receiving omeprazole therapy, a significant number of patients reported improvement in symptoms such as abdominal pain (98.2%), epigastric burning (74.2%), altered bowel movements (62.1%), and nausea (80.5%) (p < 0.001 for each). Complete resolution was observed in all patients who complained about flatulence (100.0%) and loss of appetite (100.0%) (p < 0.001 for each). The drug was found to be well tolerated. Conclusions Omeprazole therapy was well tolerated and highly effective in resolving APD symptoms among T2DM patients receiving fixed oral hypoglycemic agents.
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Liu Y, Wu Y, Jiang M. The emerging roles of PHOSPHO1 and its regulated phospholipid homeostasis in metabolic disorders. Front Physiol 2022; 13:935195. [PMID: 35957983 PMCID: PMC9360546 DOI: 10.3389/fphys.2022.935195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 07/07/2022] [Indexed: 11/25/2022] Open
Abstract
Emerging evidence suggests that phosphoethanolamine/phosphocholine phosphatase 1 (PHOSPHO1), a specific phosphoethanolamine and phosphocholine phosphatase, is involved in energy metabolism. In this review, we describe the structure and regulation of PHOSPHO1, as well as current knowledge about the role of PHOSPHO1 and its related phospholipid metabolites in regulating energy metabolism. We also examine mechanistic evidence of PHOSPHO1- and phospholipid-mediated regulation of mitochondrial and lipid droplets functions in the context of metabolic homeostasis, which could be potentially targeted for treating metabolic disorders.
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Affiliation(s)
- Yi Liu
- Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Yingting Wu
- Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Mengxi Jiang
- Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
- *Correspondence: Mengxi Jiang,
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5
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Peng CCH, Tu YK, Lee GY, Chang RHE, Huang Y, Bukhari K, Tsai YC, Fu Y, Huang HK, Munir KM. Effects of Proton Pump Inhibitors on Glycemic Control and Incident Diabetes: A Systematic Review and Meta-analysis. J Clin Endocrinol Metab 2021; 106:3354-3366. [PMID: 34170301 DOI: 10.1210/clinem/dgab353] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Indexed: 12/22/2022]
Abstract
CONTEXT Whether proton pump inhibitors (PPI) can improve glycemic control among individuals with diabetes or decrease the risk of incident diabetes in the general population is unclear. OBJECTIVE To evaluate the impact of PPI therapy on glycemic control among individuals with diabetes and the risk of diabetes among those without diabetes. RESULTS PubMed, Embase, Scopus, and ClinicalTrials.gov were searched from inception to November 21, 2020. We included studies comparing glycosylated hemoglobin (HbA1c) or fasting blood glucose (FBG) among individuals with diabetes treated with and without PPI therapy as an add-on to standard therapy. Studies evaluating the risk of incident diabetes among individuals taking PPI were assessed. We performed dual independent review, data extraction, and quality assessment. Weighted mean differences between groups or relative risks were imputed using random-effects models. RESULTS Seven studies (n = 342) for glycemic control and 5 studies (n = 244 439) for risk of incident diabetes were included. Compared with standard therapy, add-on PPI was associated with a significant decrease in HbA1c (WMD, -0.36 %; 95% CI, -0.68 to -0.05; P = 0.025) and FBG (WMD, -10.0 mg/dL; 95% CI, -19.4 to -0.6; P = 0.037). PPI use did not reduce the risk of incident diabetes (pooled RR, 1.10; 95% CI, 0.89 to 1.34; P = 0.385). CONCLUSION Add-on PPI improved glycemic indices among individuals with diabetes but did not alter the risk of incident diabetes. The effects of PPI on glycemic control should be considered when prescribing antacids to patients with diabetes.
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Affiliation(s)
- Carol Chiung-Hui Peng
- Department of Internal Medicine, University of Maryland Medical Center Midtown Campus, Baltimore, MarylandUSA
| | - Yu-Kang Tu
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, TaipeiTaiwan
- Department of Dentistry, National Taiwan University Hospital and School of Dentistry, National Taiwan University, TaipeiTaiwan
- Research Center of Big Data and Meta-analysis, Wan Fang Hospital, Taipei Medical University, TaipeiTaiwan
| | - Gin Yi Lee
- Department of Medicine, Danbury Hospital, Danbury, ConnecticutUSA
| | | | - Yuting Huang
- Department of Internal Medicine, University of Maryland Medical Center Midtown Campus, Baltimore, MarylandUSA
| | - Khulood Bukhari
- Department of Internal Medicine, University of Maryland Medical Center Midtown Campus, Baltimore, MarylandUSA
| | - Yao-Chou Tsai
- Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, TaipeiTaiwan
- Department of Urology, Taipei Medical University Hospital, Taipei Medical University, TaipeiTaiwan
| | - Yunting Fu
- Health Sciences and Human Services Library, University of Maryland, Baltimore, MDUSA
| | - Huei-Kai Huang
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, TaipeiTaiwan
- Departments of Family Medicine and Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, HualienTaiwan
| | - Kashif M Munir
- Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MarylandUSA
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DİK B, COŞKUN D, BAHÇİVAN E, ÜNEY K. Potential antidiabetic activity of benzimidazole derivative albendazole and lansoprazole drugs in different doses in experimental type 2 diabetic rats. Turk J Med Sci 2021; 51:1579-1586. [PMID: 33641315 PMCID: PMC8283501 DOI: 10.3906/sag-2004-38] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Accepted: 02/27/2021] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND/AIM The aim of this study is to determine the effects of different concentrations of albendazole and lansoprazole, which were benzimidazole derivatives, on endocrinologic and biochemical parameters in experimental type 2 diabetic (T2D) rats. MATERIALS AND METHODS In this study, 46 male Wistar Albino rats were used. Animals were divided as healthy control (0.1 mL/rat/day saline, s.c, n = 6), diabetes control (0.1 mL/rat/day saline, s.c, n = 8), diabetes+low-dose albendazole (5 mg/kg, oral, n = 8), diabetes+high- dose albendazole (10 mg/kg, oral n = 8), diabetes+low-dose lansoprazole (15 mg/kg, subcutaneous, n = 8), and diabetes+high-dose lansoprazole (30 mg/kg, subcutaneous, n = 8). All groups were treated for 8 weeks. The blood samples were analyzed by autoanalyzer and ELISA kits for biochemical and endocrinological parameters, respectively. RESULTS Glucose, HbA1c, triglyceride, low density cholesterol (LDL), leptin, and Homeostatic Model Assessment for insulin resistance (HOMA-IR) levels increased and insulin and HOMA-β levels decreased in the diabetic rats compared to the healthy control group. The glucose, HbA1c, and triglyceride levels were partially decreased; however, insulin and HOMA-β levels were increased by low-dose albendazole therapy. The high dose of lansoprazole treatment increased insulin level. CONCLUSION The lansoprazole and albendazole treatments can be a potential drug or combined with antidiabetic drugs in T2D treatment by Adenosine 5′-monophosphate activated protein kinase (AMPK), peroxisome proliferator-activated receptor (PPAR), incretin-like effect and other antidiabetic mechanisms. It may be beneficial to create an effective treatment strategy by developing more specific substances with benzimidazole scaffold.
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Affiliation(s)
- Burak DİK
- Department of Pharmacology and Toxicology, Veterinary Faculty, SelÇuk University, KonyaTurkey
| | - Devran COŞKUN
- Department of Pharmacology and Toxicology, Veterinary Faculty, Siirt University, SiirtTurkey
| | - Emre BAHÇİVAN
- Department of Pharmacology and Toxicology, Veterinary Faculty, Kafkas University, KarsTurkey
| | - Kamil ÜNEY
- Department of Pharmacology and Toxicology, Veterinary Faculty, SelÇuk University, KonyaTurkey
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7
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Suchacki KJ, Morton NM, Vary C, Huesa C, Yadav MC, Thomas BJ, Turban S, Bunger L, Ball D, Barrios-Llerena ME, Guntur AR, Khavandgar Z, Cawthorn WP, Ferron M, Karsenty G, Murshed M, Rosen CJ, MacRae VE, Millán JL, Farquharson C. PHOSPHO1 is a skeletal regulator of insulin resistance and obesity. BMC Biol 2020; 18:149. [PMID: 33092598 PMCID: PMC7584094 DOI: 10.1186/s12915-020-00880-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Accepted: 09/25/2020] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND The classical functions of the skeleton encompass locomotion, protection and mineral homeostasis. However, cell-specific gene deletions in the mouse and human genetic studies have identified the skeleton as a key endocrine regulator of metabolism. The bone-specific phosphatase, Phosphatase, Orphan 1 (PHOSPHO1), which is indispensable for bone mineralisation, has been recently implicated in the regulation of energy metabolism in humans, but its role in systemic metabolism remains unclear. Here, we probe the mechanism underlying metabolic regulation by analysing Phospho1 mutant mice. RESULTS Phospho1-/- mice exhibited improved basal glucose homeostasis and resisted high-fat-diet-induced weight gain and diabetes. The metabolic protection in Phospho1-/- mice was manifested in the absence of altered levels of osteocalcin. Osteoblasts isolated from Phospho1-/- mice were enriched for genes associated with energy metabolism and diabetes; Phospho1 both directly and indirectly interacted with genes associated with glucose transport and insulin receptor signalling. Canonical thermogenesis via brown adipose tissue did not underlie the metabolic protection observed in adult Phospho1-/- mice. However, the decreased serum choline levels in Phospho1-/- mice were normalised by feeding a 2% choline rich diet resulting in a normalisation in insulin sensitivity and fat mass. CONCLUSION We show that mice lacking the bone mineralisation enzyme PHOSPHO1 exhibit improved basal glucose homeostasis and resist high-fat-diet-induced weight gain and diabetes. This study identifies PHOSPHO1 as a potential bone-derived therapeutic target for the treatment of obesity and diabetes.
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Affiliation(s)
- Karla J Suchacki
- Roslin Institute, R(D)SVS, University of Edinburgh, Edinburgh, Scotland, UK. .,Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland, UK.
| | - Nicholas M Morton
- Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland, UK
| | - Calvin Vary
- Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA
| | - Carmen Huesa
- Roslin Institute, R(D)SVS, University of Edinburgh, Edinburgh, Scotland, UK.,MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, Scotland, UK
| | - Manisha C Yadav
- Sanford Burnham Prebys Medical Discovery Institute, La Jolla, USA
| | - Benjamin J Thomas
- Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland, UK
| | - Sophie Turban
- Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland, UK
| | - Lutz Bunger
- Scottish Rural College, Edinburgh, Scotland, UK
| | - Derek Ball
- Medical Sciences and Nutrition, School of Medicine, University of Aberdeen, Aberdeen, Scotland, UK
| | | | - Anyonya R Guntur
- Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA
| | - Zohreh Khavandgar
- Department of Medicine and Faculty of Dentistry, McGill University, Montreal, Canada
| | - William P Cawthorn
- Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland, UK
| | - Mathieu Ferron
- Molecular Physiology Research Unit, Institut de recherches cliniques de Montréal, Montreal, Canada
| | - Gérard Karsenty
- Department of Genetics and Development, Columbia University Medical Center, New York, USA
| | - Monzur Murshed
- Department of Medicine and Faculty of Dentistry, McGill University, Montreal, Canada
| | - Clifford J Rosen
- Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA
| | - Vicky E MacRae
- Roslin Institute, R(D)SVS, University of Edinburgh, Edinburgh, Scotland, UK
| | - Jose Luis Millán
- Sanford Burnham Prebys Medical Discovery Institute, La Jolla, USA
| | - Colin Farquharson
- Roslin Institute, R(D)SVS, University of Edinburgh, Edinburgh, Scotland, UK
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Bozkuş Y, Mousa U, İyidir ÖT, Kırnap N, Demir CÇ, Nar A, Tütüncü NB. Short-Term Effect of Hypergastrinemia Following Esomeprazole Treatment On Well-Controlled Type 2 Diabetes Mellitus: A Prospective Study. Endocr Metab Immune Disord Drug Targets 2020; 20:1090-1096. [DOI: 10.2174/1871530320666200129124555] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Revised: 11/16/2019] [Accepted: 11/18/2019] [Indexed: 02/08/2023]
Abstract
Objective:
Proton pump inhibitor (PPI) drugs reduce gastric acid secretion and lead to an
increase in serum gastrin levels. Many preclinical and some clinical researches have established some
positive effects of gastrin or PPI therapy on glucose regulation. The aim of this study was to prospectively
investigate the short term effects of esomeprazole on glycaemic control in patients with type 2
diabetes mellitus. In addition, the presence of an association between this effect and gastrin levels was
evaluated.
Methods:
Thirty-two subjects with type 2 diabetes mellitus were enrolled and grouped as intervention
(n=16) and control (n=16). The participants in the intervention group were prescribed 40 mg of esomeprazole
treatment for three months. At the beginning of the study and at the 3rd month, HbA1c level
(%) and gastrin levels (pmol/L) of participants were assessed. Then, the groups were compared in
terms of their baseline and 3rd month values.
Results:
In the intervention group, the mean gastrin level increased significantly from 34.3±14.4
pmol/L to 87.4±43.6 pmol/L (p<0.001). The mean HbA1c level was similar to the pre-treatment level
(6.3±0.7% vs. 6.4±0.9%, p=0.441). There were no statistically significant differences in all parameters
of the control group. The majority of individuals were on metformin monotherapy (65.6 %). The subgroup
analysis of metformin monotherapy revealed that, in intervention group, there was a significant
increase in gastrin levels (39.9±12.6 vs. 95.5±52.5, p=0.026), but the HbA1c levels did not change
(6.0±0.4 % vs. 5.9±0.6 %, p=0.288); and in control group, gastrin levels did not change (37.5 ± 26.7
vs. 36.1 ±23.3, p=0.367), but there was an increase in HbA1c levels (6.1 ± 0.50 vs. 6.4 ± 0.60, p=0.01).
Conclusion:
Our study demonstrates that esomeprazole has no extra benefit for the controlled diabetic
patient in three months. However, in only the metformin-treated subgroup, esomeprazole may prevent
the rise in HbA1c level.
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Affiliation(s)
- Yusuf Bozkuş
- Department of Endocrinology and Metabolism, Faculty of Medicine, Baskent University, Ankara, Turkey
| | - Umut Mousa
- Department of Endocrinology and Metabolism, Faculty of Medicine, Baskent University, Ankara, Turkey
| | - Özlem T. İyidir
- Department of Endocrinology and Metabolism, Faculty of Medicine, Baskent University, Ankara, Turkey
| | - Nazlı Kırnap
- Department of Endocrinology and Metabolism, Faculty of Medicine, Baskent University, Ankara, Turkey
| | - Canan Ç. Demir
- Department of Endocrinology and Metabolism, Faculty of Medicine, Baskent University, Ankara, Turkey
| | - Aslı Nar
- Department of Endocrinology and Metabolism, Faculty of Medicine, Baskent University, Ankara, Turkey
| | - Neslihan B. Tütüncü
- Department of Endocrinology and Metabolism, Faculty of Medicine, Baskent University, Ankara, Turkey
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Rajput MA, Ali F, Zehra T, Zafar S, Kumar G. The effect of proton pump inhibitors on glycaemic control in diabetic patients. J Taibah Univ Med Sci 2020; 15:218-223. [PMID: 32647517 PMCID: PMC7336010 DOI: 10.1016/j.jtumed.2020.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 03/07/2020] [Accepted: 03/10/2020] [Indexed: 11/20/2022] Open
Abstract
OBJECTIVE This study aimed to evaluate the effect of proton pump inhibitors on glycaemic control amongst diabetic patients taking anti-diabetic medications. METHODS This randomised interventional clinical study was conducted in Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi. Eighty patients of either sex (aged 30-60 years) with type 2 diabetes mellitus and without any known comorbidities were equally divided into two groups (i.e., n = 40 for each group) and were included in this study. Group A received metformin and glimepiride, while Group B, metformin and glimepiride plus omeprazole. The efficacy of the combination medications was evaluated based on fasting blood sugar (FBS) and glycosylated haemoglobin (HbA1c) levels. Serum creatinine and liver function tests were reviewed to evaluate patients' safety profile at the initial visit and after 12 weeks. RESULTS After 12 weeks of omeprazole therapy, we observed a more significant improvement in glycaemic control in group B compared to group A based on the patients' FBS (108 ± 2.37 vs. 126 ± 2.9, P = 0.001) and HbA1c levels (7.29 ± 0.07 vs. 7.47 ± 0.04, P = 0.030). CONCLUSION The addition of a proton pump inhibitor along with anti-diabetic medications was considered effective in achieving better glycaemic control.
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Affiliation(s)
- Muhammad Ali Rajput
- Department of Pharmacology, Multan Medical and Dental College, Multan, Pakistan
| | - Fizzah Ali
- Department of Pharmacology, Liaquat National Medical College, Karachi, Pakistan
| | - Tabassum Zehra
- Department of Pharmacology, Liaquat National Medical College, Karachi, Pakistan
| | - Shahid Zafar
- Department of Pathology, Liaquat College of Medicine & Dentistry, Karachi, Pakistan
| | - Gunesh Kumar
- Department of Pharmacology, Liaquat University of Medical & Health Sciences, Jamshoro, Pakistan
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10
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Dahabiyeh LA, Abu-Rish EY, Taha MO. Inhibition of monoglyceride lipase by proton pump inhibitors: investigation using docking and in vitro experiments. Pharmacol Rep 2020; 72:435-442. [PMID: 32048247 DOI: 10.1007/s43440-019-00013-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 08/26/2019] [Accepted: 10/18/2019] [Indexed: 12/24/2022]
Abstract
BACKGROUND Currently, there is overwhelming evidence linking elevated plasma free fatty acids with insulin resistance and inflammation. Monoglyceride lipase (MGL) plays a crucial metabolic role in lipolysis by mediating the release of fatty acids. Therefore, inhibiting MGL should be a promising pharmacological approach for treating type 2 diabetes and inflammatory disorders. Proton pump inhibitors (PPIs) have been reported to improve glycemic control in type 2 diabetes albeit via largely unknown mechanism. METHODS The anti-MGL bioactivities of three PPIs, namely, lansoprazole, rabeprazole, and pantoprazole, were investigated using docking experiments and in vitro bioassay. RESULTS The three PPIs inhibited MGL in low micromolar range with rabeprazole exhibiting the best IC50 at 4.2 µM. Docking experiments showed several binding interactions anchoring PPIs within MGL catalytic site. CONCLUSION Our study provides evidence for a new mechanism by which PPIs improve insulin sensitivity independent of serum gastrin. The three PPIs effectively inhibit MGL and, therefore, serve as promising leads for the development of new clinical MGL inhibitors.
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Affiliation(s)
- Lina A Dahabiyeh
- Department of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Queen Rania St, Amman, 11942, Jordan.
| | - Eman Y Abu-Rish
- Department of Clinical Pharmacy and Biopharmaceutics, School of Pharmacy, The University of Jordan, Amman, Jordan
| | - Mutasem O Taha
- Department of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Queen Rania St, Amman, 11942, Jordan.
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Ala M, Jafari RM, Dehpour AR. Diabetes Mellitus and Osteoporosis Correlation: Challenges and Hopes. Curr Diabetes Rev 2020; 16:984-1001. [PMID: 32208120 DOI: 10.2174/1573399816666200324152517] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 02/02/2020] [Accepted: 02/24/2020] [Indexed: 01/14/2023]
Abstract
Diabetes and osteoporosis are two common diseases with different complications. Despite different therapeutic strategies, managing these diseases and reducing their burden have not been satisfactory, especially when they appear one after the other. In this review, we aimed to clarify the similarity, common etiology and possible common adjunctive therapies of these two major diseases and designate the known molecular pattern observed in them. Based on different experimental findings, we want to illuminate that interestingly similar pathways lead to diabetes and osteoporosis. Meanwhile, there are a few drugs involved in the treatment of both diseases, which most of the time act in the same line but sometimes with opposing results. Considering the correlation between diabetes and osteoporosis, more efficient management of both diseases, in conditions of concomitant incidence or cause and effect condition, is required.
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Affiliation(s)
- Moein Ala
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, 13145-784, Tehran, Iran
| | - Razieh Mohammad Jafari
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmad Reza Dehpour
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, 13145-784, Tehran, Iran
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12
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Vandenberghe F, Challet C, Maitrejean M, Christin L, Schaad N. Impact of drugs on hypoglycaemia in hospitalised patients. Eur J Hosp Pharm 2019; 26:199-204. [PMID: 31338167 DOI: 10.1136/ejhpharm-2017-001375] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2017] [Revised: 02/01/2018] [Accepted: 02/20/2018] [Indexed: 11/04/2022] Open
Abstract
Objectives Hospital admission rates for hypoglycaemia now exceed those for hyperglycaemias among older adults. A growing number of reports associating hypoglycaemia with non-antidiabetic drugs have been published. Clinical pharmacists are often faced with hypoglycaemia in patients taking multiple medications. This study assessed the potential relationship between prescribed drugs and episodes of hypoglycaemia during hospitalisation. Methods Point-of-care blood glucose values and prescribed drugs were analysed in patients admitted to a regional hospital. Hypoglycaemia cases were defined as patients with at least one hypoglycaemic event (random glucose value ≤3.9 mmol/L), and normoglycaemic cases as those with random glucose concentrations within the range of 4.5-5.8 mmol/L. Analyses were carried out using multivariate logistic regressions and Cox proportional hazard models. Results 373 patients (53% males; median age=74 years) were included in the analysis and of these, 64 (17%) had at least one hypoglycaemic event. Patients who experienced a hypoglycaemic event had a longer length of stay (median=10 vs 7 days, p<0.01) and a higher rate of antidiabetic drugs prescription (83% vs 37%, p<0.01). The number of non-antidiabetic drugs was associated with an increased risk of hypoglycaemia during hospitalisation (HR 2.3, 95% CI 1.4 to 4, p<0.01). After adjusting by confounders, heparin and pantoprazole were found to be associated with hypoglycaemia. Conclusions The relationship between hypoglycaemia and polypharmacy reinforces the advice to limit polymedication as much as possible, especially in elderly patients. This result underlines the potential involvement of clinical pharmacists with the aim to reduce the risk of hypoglycaemia during hospitalisation.
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Affiliation(s)
| | | | - Mathias Maitrejean
- Medical Analysis Laboratory, Groupement Hospitalier de l'Ouest Lémanique, Nyon, Switzerland, Nyon, Switzerland
| | - Laurent Christin
- Department of Internal Medicine, Groupement Hospitalier de l'Ouest Lémanique, Nyon, Switzerland., Nyon, Switzerland
| | - Nicolas Schaad
- Pharmacie Interhospitalière de la Cote, Morges, Switzerland.,Department of Basic Neurosciences, Geneva University Hospital, Geneva, Switzerland.,Department of Anaesthetics, Pharmacology and Intensive Care, Geneva University Hospital, Geneva, Switzerland
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13
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Villegas K, Meier JL, Long M, Lopez J, Swislocki A. The Effect of Proton Pump Inhibitors on Glycemic Control in Patients with Type 2 Diabetes. Metab Syndr Relat Disord 2019; 17:192-196. [PMID: 30730235 DOI: 10.1089/met.2018.0138] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Affiliation(s)
- Kelly Villegas
- Pharmacy Service, VA Northern California Health Care System, Martinez, California
| | - Joy L. Meier
- Pharmacy Service, VA Northern California Health Care System, Martinez, California
| | - Maureen Long
- Pharmacy Service, VA Northern California Health Care System, Martinez, California
| | - Julio Lopez
- Pharmacy Service, VA Northern California Health Care System, Martinez, California
| | - Arthur Swislocki
- Medical Service, VA Northern California Health Care System, Martinez, California
- Department of Internal Medicine, UC Davis School of Medicine, Sacramento, California
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14
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Kruszelnicka O, Kuźma M, Pena IZ, Perera IB, Chyrchel B, Wieczorek-Surdacka E, Surdacki A. No Association of Proton Pump Inhibitor Use with Fasting or Postload Glycaemia in Patients with Cardiovascular Disease: A Cross-Sectional Retrospective Study. Int J Med Sci 2017; 14:1015-1021. [PMID: 28924374 PMCID: PMC5599926 DOI: 10.7150/ijms.19457] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Accepted: 06/20/2017] [Indexed: 12/23/2022] Open
Abstract
Background: Proton pump inhibitor (PPI) use was reportedly associated with an excess of adverse cardiovascular (CV) events, thus making their systemic effects relevant to public health. PPIs reduce gastric acid secretion, causing increased gastrin release. Gastrin stimulates β-cell neogenesis and enhances insulin release, exerting an incretin-like effect. Our aim was to assess, if PPI usage is associated with altered glycaemia in patients with CV disease. Methods: We retrospectively analyzed medical records of 102 subjects (80 with ischemic heart disease) who underwent a routine oral glucose tolerance test while hospitalized in a cardiology department. Fasting and 2-h postload glucose levels were compared according to PPI use for ≥1 month prior to admission. Results: Compared to 51 subjects without PPIs, those on a PPI were older, more frequently male, had a lower body-mass index and a tendency to a worse renal function. PPI users and non-users exhibited similar glucose levels at baseline (5.6 ± 0.9 vs. 5.5 ± 1.1 mmol/l, P = 0.5) and 2-hrs post glucose intake (9.8 ± 3.0 vs. 9.9 ± 3.4 mmol/l, P = 0.9). This was consistent across subgroups stratified by gender or diabetes status. The results were substantially unchanged after adjustment for different characteristics of subjects with and without PPIs. Conclusions: PPI use does not appear associated with altered glycaemia in subjects with CV disease. Unchanged glucose tolerance despite PPI usage may result from simultaneous activation of pathways that counteract the putative PPI-induced incretin-like effect.
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Affiliation(s)
- Olga Kruszelnicka
- Department of Coronary Artery Disease and Heart Failure, John Paul II Hospital, Cracow, Poland
| | - Marcin Kuźma
- Students' Scientific Group at the Second Department of Cardiology, School of Medicine in English, Jagiellonian University Medical College, Cracow, Poland
| | - Iwona Z Pena
- Students' Scientific Group at the Second Department of Cardiology, School of Medicine in English, Jagiellonian University Medical College, Cracow, Poland
| | - Ian B Perera
- Students' Scientific Group at the Second Department of Cardiology, School of Medicine in English, Jagiellonian University Medical College, Cracow, Poland
| | - Bernadeta Chyrchel
- Second Department of Cardiology, Jagiellonian University Medical College, Cracow, Poland
| | | | - Andrzej Surdacki
- Second Department of Cardiology, Jagiellonian University Medical College, Cracow, Poland
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15
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Breuer TGK, Borker L, Quast DR, Tannapfel A, Schmidt WE, Uhl W, Meier JJ. Impact of proton pump inhibitor treatment on pancreatic beta-cell area and beta-cell proliferation in humans. Eur J Endocrinol 2016; 175:467-76. [PMID: 27562401 DOI: 10.1530/eje-16-0320] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2016] [Accepted: 08/24/2016] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Gastrin has been shown to promote beta-cell proliferation in rodents, but its effects in adult humans are largely unclear. Proton pump inhibitors (PPIs) lead to endogenous hypergastrinaemia, and improved glucose control during PPI therapy has been reported in patients with diabetes. Therefore, we addressed whether PPI treatment is associated with improved glucose homoeostasis, islet cell hyperplasia or increased new beta-cell formation in humans. PATIENTS AND METHODS Pancreatic tissue specimens from 60 patients with and 33 patients without previous PPI therapy were examined. The group was subdivided into patients without diabetes (n = 27), pre-diabetic patients (n = 31) and patients with diabetes (n = 35). RESULTS Fasting glucose and HbA1c levels were not different between patients with and without PPI therapy (P = 0.34 and P = 0.30 respectively). Beta-cell area was higher in patients without diabetes than in patients with pre-diabetes or diabetes (1.33 ± 0.12%, 1.05 ± 0.09% and 0.66 ± 0.07% respectively; P < 0.0001). There was no difference in beta-cell area between patients with and without PPI treatment (1.05 ± 0.08% vs 0.87 ± 0.08%, respectively; P = 0.16). Beta-cell replication was rare and not different between patients with and without PPI therapy (P = 0.20). PPI treatment was not associated with increased duct-cell replication (P = 0.18), insulin expression in ducts (P = 0.28) or beta-cell size (P = 0.63). CONCLUSIONS These results suggest that in adult humans, chronic PPI treatment does not enhance beta-cell mass or beta-cell function to a relevant extent.
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Affiliation(s)
- Thomas G K Breuer
- Diabetes DivisionSt. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | - Laura Borker
- Diabetes DivisionSt. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | - Daniel R Quast
- Diabetes DivisionSt. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | | | - Wolfgang E Schmidt
- Diabetes DivisionSt. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | - Waldemar Uhl
- Department of SurgerySt. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | - Juris J Meier
- Diabetes DivisionSt. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
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16
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Chen CB, Lin M, Eurich DT, Johnson JA. Safety of Concomitant Metformin and Proton Pump Inhibitor Use: A Population Retrospective Cohort Study. Clin Ther 2016; 38:1392-1400. [PMID: 27061884 DOI: 10.1016/j.clinthera.2016.03.024] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Revised: 03/04/2016] [Accepted: 03/14/2016] [Indexed: 01/08/2023]
Abstract
PURPOSE The purpose of this study was to investigate the effect of concomitant use on important clinical outcomes. METHODS In this retrospective cohort study, a cohort of new metformin users was identified between 2004 and 2010 and followed up until termination of insurance coverage, December 31, 2010, or the outcomes were reached. The primary outcome was a composite of time to all-cause mortality or hospitalization; our secondary outcome was time to cardiovascular hospitalization. Exposures to metformin, a proton pump inhibitor (PPI), and/or a histamine2 receptor antagonist (H2RA) were compared with a Cox proportional hazards model after adjustment. FINDINGS Relative to metformin-only users, metformin and PPI users were at increased risk of the primary outcome (adjusted hazard ratio [HR] = 1.55; 95% CI, 1.46-1.64); metformin and H2RA users also had an elevated risk (adjusted HR = 1.29; 95% CI, 0.97-1.70). Similar patterns were seen with cardiovascular-specific hospitalization. Compared with no drug use, metformin users had an increased risk of the primary outcome, but risk was substantially elevated when patients were taking PPIs or H2RAs, alone or in combination with metformin. IMPLICATIONS Concomitant use of metformin and a PPI or metformin and an H2RA were associated with an increased risk of death or hospitalization. This finding suggests that the harm observed may not be due to a specific drug interaction but uncontrolled confounding secondary to an increased risk in those patients using a PPI or H2RA.
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Affiliation(s)
- Christopher B Chen
- School of Public Health, University of Alberta, Edmonton, Alberta, Canada
| | - Mu Lin
- School of Public Health, University of Alberta, Edmonton, Alberta, Canada
| | - Dean T Eurich
- School of Public Health, University of Alberta, Edmonton, Alberta, Canada
| | - Jeffrey A Johnson
- School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
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17
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Gastrin Secretion After Bariatric Surgery—Response to a Protein-Rich Mixed Meal Following Roux-En-Y Gastric Bypass and Sleeve Gastrectomy: a Pilot Study in Normoglycemic Women. Obes Surg 2015; 26:1448-56. [DOI: 10.1007/s11695-015-1985-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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18
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Barchetta I, Guglielmi C, Bertoccini L, Calella D, Manfrini S, Secchi C, Pozzilli P, Cavallo MG. Therapy with proton pump inhibitors in patients with type 2 diabetes is independently associated with improved glycometabolic control. Acta Diabetol 2015; 52:873-80. [PMID: 25716766 DOI: 10.1007/s00592-015-0721-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2014] [Accepted: 02/02/2015] [Indexed: 02/08/2023]
Abstract
AIMS 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.
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Affiliation(s)
- Ilaria Barchetta
- Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | | | - Laura Bertoccini
- Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | - Damiano Calella
- Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | | | | | | | - Maria Gisella Cavallo
- Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
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19
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Punjabi P, Hira A, Prasad S, Wang X, Chokhavatia S. Review of gastroesophageal reflux disease (GERD) in the diabetic patient. J Diabetes 2015; 7:599-609. [PMID: 25706050 DOI: 10.1111/1753-0407.12279] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Revised: 12/18/2014] [Accepted: 02/07/2015] [Indexed: 12/13/2022] Open
Abstract
This article reviews the known pathophysiological mechanisms of comorbid gastroesophageal reflux disease (GERD) in the diabetic patient, discusses therapeutic options in care, and provides an approach to its evaluation and management. We searched for review articles published in the past 10 years through a PubMed search using the filters diabetes mellitus, GERD, pathophysiology, and management. The search only yielded a handful of articles, so we independently included relevant studies from these review articles along with related citations as suggested by PubMed. We found diabetic patients are more prone to developing GERD and may present with atypical manifestations. A number of mechanisms have been proposed to elucidate the connection between these two diseases. Studies involving treatment options for comorbid disease suggest conflicting drug-drug interactions. Currently, there are no published guidelines specifically for the evaluation and management of GERD in the diabetic patient. Although there are several proposed mechanisms for the higher prevalence of GERD in the diabetic patient, this complex interrelationship requires further research. Understanding the pathophysiology will help direct diagnostic evaluation. In our review, we propose a management algorithm for GERD in the diabetic patient.
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Affiliation(s)
- Paawan Punjabi
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
| | - Angela Hira
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
| | - Shanti Prasad
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
| | - Xiangbing Wang
- Division of Endocrinology, Department of Medicine, Rutgers, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
| | - Sita Chokhavatia
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
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Abstract
Immunotherapies for type 1 diabetes mellitus (T1DM) have been the focus of intense basic and clinical research over the past few decades. Restoring β-cell function is the ultimate goal of intervention trials that target the immune system in T1DM. In an attempt to achieve this aim, different combination therapies have been proposed over the past few years that are based on treatments tackling the various mechanisms involved in the destruction of β cells. The results of clinical trials have not matched expectations based on the positive results from preclinical studies. The heterogeneity of T1DM might explain the negative results obtained, but previous trials have not addressed this issue. However, novel promising combination therapies are being developed, including those that couple immunomodulators with drugs that stimulate β-cell regeneration in order to restore normoglycaemia. This strategy is an encouraging one to pursue the goal of finding a cure for T1DM. This Review summarizes the available data about combination immunotherapies in T1DM, particularly addressing their clinical importance. The available data supporting the use of registered drugs, such as proton pump inhibitors and incretin-based agents, that have been shown to induce β-cell regeneration will also be discussed.
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Affiliation(s)
- Paolo Pozzilli
- Department of Endocrinology and Diabetes, University Campus Bio-Medico, Via Álvaro del Portillo 21, Rome 00128, Italy
| | - Ernesto Maddaloni
- Department of Endocrinology and Diabetes, University Campus Bio-Medico, Via Álvaro del Portillo 21, Rome 00128, Italy
| | - Raffaella Buzzetti
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, Rome 00161 Italy
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21
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González-Ortiz M, Martínez-Abundis E, Mercado-Sesma AR, Álvarez-Carrillo R. Effect of pantoprazole on insulin secretion in drug-naïve patients with type 2 diabetes. Diabetes Res Clin Pract 2015; 108:e11-3. [PMID: 25704601 DOI: 10.1016/j.diabres.2015.01.039] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Revised: 01/14/2015] [Accepted: 01/29/2015] [Indexed: 02/09/2023]
Abstract
To evaluate the effect of pantoprazole during 45 days on insulin secretion in drug-naïve patients with type 2 diabetes, a randomized, double blind, placebo control clinical trial was performed in 14 drug-naïve volunteers. Significant increases in late insulin phase and total insulin secretion, and decreases in HbA1c levels were found.
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Affiliation(s)
- Manuel González-Ortiz
- Institute of Experimental and Clinical Therapeutics, Physiology Department, Health Science University Center, University of Guadalajara, Guadalajara, Mexico; Medical Research Unit in Clinical Epidemiology, Specialties Hospital, Medical Unit of High Specialty, West National Medical Center, Mexican Institute of Social Security, Guadalajara, Mexico.
| | - Esperanza Martínez-Abundis
- Institute of Experimental and Clinical Therapeutics, Physiology Department, Health Science University Center, University of Guadalajara, Guadalajara, Mexico
| | - Arieh R Mercado-Sesma
- Medical Research Unit in Clinical Epidemiology, Specialties Hospital, Medical Unit of High Specialty, West National Medical Center, Mexican Institute of Social Security, Guadalajara, Mexico
| | - Rebeca Álvarez-Carrillo
- Medical Research Unit in Clinical Epidemiology, Specialties Hospital, Medical Unit of High Specialty, West National Medical Center, Mexican Institute of Social Security, Guadalajara, Mexico
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Han N, Oh M, Park SM, Kim YJ, Lee EJ, Kim TK, Kim TN, Kwon MJ, Kim MK, Lee SH, Rhee BD, Park JH. The effect of proton pump inhibitors on glycated hemoglobin levels in patients with type 2 diabetes mellitus. Can J Diabetes 2014; 39:24-8. [PMID: 25305802 DOI: 10.1016/j.jcjd.2013.10.008] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2013] [Revised: 10/28/2013] [Accepted: 10/28/2013] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Gastrin increases the growth and neogenesis of the islets of Langerhans. Oral proton pump inhibitors (PPIs) increase the circulating gastrin level in animals and humans, but the therapeutic benefit of PPIs for diabetes mellitus has not been resolved. We examined whether treatment with a PPI for ≥2 months affected the glycated hemoglobin (A1C) level in patients with type 2 diabetes. METHODS The electronic medical records of patients treated at the Busan Paik Hospital in South Korea were examined. The primary outcome measure was the change in A1C before and after PPI treatment for ≥2 months. We also tested if the primary outcome measure was affected by sex, age, duration of diabetes, body mass index, PPI molecule, duration of treatment with PPI or concurrent therapy with other antidiabetes agents. RESULTS In total, 43 patients (17 men and 26 women) were studied (mean age 63.8 years). Patients were treated with a PPI for a mean of 180 days. The A1C levels before and after treatment were not significantly different (6.86%±1.10% and 6.77%±1.07%, respectively; p=0.406). Metformin monotherapy did not lower A1C levels as compared with a combination therapy including metformin and antidiabetes medication not including metformin. CONCLUSIONS Proton pump inhibitor treatment of patients with type 2 diabetes did not reduce A1C levels. The data of this study were obtained from a retrospective chart review and included a small number of subjects. Furthermore, large randomized controlled studies are needed to define the effect of PPIs for type 2 patients with diabetes.
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Affiliation(s)
- Na Han
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, South Korea
| | - Minkyung Oh
- Department of Pharmacology and Clinical Trial Centre, Inje University, Busan Paik Hospital, Busan, South Korea
| | - Su Min Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, South Korea
| | - You Jeong Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, South Korea
| | - Eun Ju Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, South Korea
| | - Tae Kyoon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, South Korea
| | - Tae Nyun Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, South Korea
| | - Min Jeong Kwon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, South Korea.
| | - Mi-Kyung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, South Korea
| | - Soon Hee Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, South Korea
| | - Byoung Doo Rhee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, South Korea
| | - Jeong Hyun Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, South Korea
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Grong E, Arbo IB, Thu OKF, Kuhry E, Kulseng B, Mårvik R. The effect of duodenojejunostomy and sleeve gastrectomy on type 2 diabetes mellitus and gastrin secretion in Goto-Kakizaki rats. Surg Endosc 2014; 29:723-33. [PMID: 25106717 DOI: 10.1007/s00464-014-3732-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2014] [Accepted: 07/08/2014] [Indexed: 12/20/2022]
Abstract
BACKGROUND Bariatric surgery is a highly effective treatment of type 2 diabetes in patients with morbid obesity. The weight-loss independent improvement of glycemic control observed after these procedures has led to the discussion whether bariatric surgery can be introduced as treatment for type 2 diabetes in patients with a body mass index < 35 kg/m(2). We have studied the effects of two bariatric procedures on type 2 diabetes and on gastrointestinal hormone secretion in a lean diabetic animal model. METHODS Male Goto-Kakizaki rats, 17-18 weeks old, were randomized into three groups: duodenojejunostomy (DJ), sleeve gastrectomy (SG), or sham operation. During 36 postoperative weeks we evaluated body weight, fasting blood glucose, glucose tolerance, insulin, HbA1c, glucagon-like peptide 1, cholesterol parameters, triglycerides, total ghrelin, and gastrin. RESULTS Oral glucose tolerance was significantly improved for both DJ and SG at four weeks after surgery (p < 0.05). At the 34th postoperative week, SG had significantly lower area under the curve during oral glucose tolerance test compared to sham (p = 0.007). SG had significantly lower HbA1c compared to sham at 12 weeks; (mean ± SEM) 4.3 ± 0.1 % versus 5.2 ± 0.3 % (p < 0.05) and compared to both DJ and sham 34 weeks after surgery [median (75 %;25 %)] 5.2 (6.0; 4.3) % versus 7.0 (7.5; 6.7) % and 7.3 (7.6; 6.7) % (p = 0.009). Serum gastrin levels were markedly elevated for SG compared to DJ and sham; 188.0 (318.0; 121.0) versus 77.5 (114.0; 58.0) and 68.0 (90.0; 59.5) pmol/L (p = 0.004) at six weeks and 192.0 (587.8; 110.8) versus 65.5 (77.0; 59.0) and 69.5 (113.0; 55.5) (p = 0.001) 36 weeks after surgery. CONCLUSION Sleeve gastrectomy induces hypergastrinemia, lowers HbA1c, and improves glycemic control in Goto-Kakizaki rats. Sleeve gastrectomy is superior to duodenojejunostomy as treatment of type 2 diabetes mellitus in this animal model.
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Affiliation(s)
- Eivind Grong
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), PB 8905, 7491, Trondheim, Norway,
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Telfer SJ. Fluoroquinolone antibiotics and type 2 diabetes mellitus. Med Hypotheses 2014; 83:263-9. [PMID: 24947193 DOI: 10.1016/j.mehy.2014.05.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2013] [Accepted: 05/21/2014] [Indexed: 10/25/2022]
Abstract
Exposure to fluoroquinolone antibiotics is postulated as a risk factor for subsequent development of type 2 diabetes. It is hypothesized that fluoroquinolones induce an intracellular magnesium deficit that can lead to insulin resistance. A temporal correlation is reported between the rate of outpatient prescription of quinolones and the incidence of diabetes during the period 1980-2011 with a lag of approximately two years (R(2)=0.86, P<10(-9)). The increase in incidence of diabetes after 1990 and the recent decrease in the number of new cases are both reflected in the fluoroquinolone prescription rates. A geographical correlation is reported (adj. R(2)=0.7, P<0.0001) between rates of increase in prevalence of diabetes in each U.S. state and a model using only local rates of outpatient fluoroquinolone prescription, local rates of increase in the prevalence of obesity, and local rates of population growth as predictor variables. Prescription rates of non-quinolone antibiotics correlated less well with the local rates of increase in prevalence of diabetes. The data are consistent with fluoroquinolone exposure predisposing an individual to develop diabetes with a probability that strongly depends upon factors that also lead to an increase in obesity. According to the hypothesis, much of the increase in the incidence of type 2 diabetes in the U.S. from 1990 to the present can be attributed to fluoroquinolone exposure.
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Affiliation(s)
- Stephen J Telfer
- E Ink Corporation, 1000 Technology Park Drive, Billerica, MA 01821, USA.
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Inci F, Atmaca M, Ozturk M, Yildiz S, Koceroglu R, Sekeroglu R, Ipekci SH, Kebapcilar L. Pantoprazole may improve beta cell function and diabetes mellitus. J Endocrinol Invest 2014; 37:449-54. [PMID: 24682913 DOI: 10.1007/s40618-013-0040-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2013] [Accepted: 12/06/2013] [Indexed: 01/02/2023]
Abstract
BACKGROUND Proton pump inhibitors induce hypergastrinemia by suppressing gastric acidity. Gastrin has incretin-like stimulating actions on beta cells. Proton pump inhibitors have been shown to decrease glycosylated hemoglobin. AIM We aimed to observe changes in beta cell function in diabetic and non-diabetic subjects given pantoprazole for an acid-related ailment. METHODS Seventy-nine male patients (38 non-diabetic and 41 type-2 diabetic receiving only metformin therapy) were followed for 12 weeks after pantoprazole 40 mg/day was given. Fasting plasma glucose, HbA1c, fasting insulin, Pancreatic B cell function (HOMA-B), proinsulin and c-peptide levels were measured before and after the treatment. RESULTS In non-diabetic patients (n = 38), FPG decreased, whereas c-peptide, log-HOMA-B, increased significantly (p = 0.002, p = 0.03, p = 0.042, respectively) after 12 weeks of pantoprazole administration. In type 2 diabetic patients, FPG, HbA1c and weight decreased, whereas log-HOMA-B, c-peptide and log-proinsulin levels increased significantly after pantoprazole treatment (p = 0.003, p = 0.007, p < 0.001; p < 0.001; p = 0.017, p = 0.05, respectively). After pantoprazole treatment, pancreatic B-cell function was correlated with c-peptide and insulin and inversely with FBG and HbA1c levels in the whole group (r = 0.37, p = 0.001; r = 0.60, p < 0.001, r = -0.29, p = 0.011 and r = -0.28, p = 0.013, respectively). After pantoprazole treatment, HbA1c was correlated with FBG (r = 0.75, p < 0.001) and inversely with only log-HOMA-B level (r = -0.28, p = 0.013). CONCLUSIONS Pantoprazole administration seems to correlate with increased beta cell function. Pantoprazole administration improves HbA1c, HOMA-B, c-peptide and proinsulin levels. Since beta cell loss plays a significant role in the pathogenesis of type 2 diabetes, PPI-based therapies may be useful in the treatment of diabetes.
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Affiliation(s)
- F Inci
- Department of Internal Medicine, University of Yuzuncu Yil, Van, Turkey
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Hao S, Sun J, Tian X, Sun X, Zhang Z, Gao Y. Lansoprazole enhances the antidiabetic effect of sitagliptin in mice with diet-induced obesity and healthy human subjects. ACTA ACUST UNITED AC 2014; 66:1133-9. [PMID: 24628303 DOI: 10.1111/jphp.12237] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2013] [Accepted: 02/02/2014] [Indexed: 12/20/2022]
Abstract
OBJECTIVES Proton pump inhibitors as adjunctive therapy would improve diabetes control and could enhance the hypoglycaemic activity of DPP-4 inhibitors. The aim of the study was to investigate the short-term effects of lansoprazole (LPZ), sitagliptin (SITA) and their combination therapy on glucose regulation and gut peptide secretion. METHODS Glucose and gut peptide were determined and compared after short-term administration of LPZ or SITA, or in combination to mice with diet-induced obesity (DIO) and to healthy human subjects (n = 16) in a 75 g oral glucose tolerance test (OGTT) by a crossover design. KEY FINDINGS In DIO mice, LPZ significantly improve glucose metabolism, increase plasma C-peptide and insulin compared with vehicle treatment. Furthermore, the combination of LPZ and SITA improved glucose tolerance additively, with higher plasma insulin and C-peptide levels compared with SITA-treated mice. Similarly, in human in the OGTT, the combination showed significant improvement in glucose-lowering and insulin increase vs SITA-treated group. However, no significant differences in area under curve (AUC) of insulin, glucose and C-peptide between the LPZ-treated group and baseline, except that mean AUCgastrin was significantly increased by LPZ. CONCLUSIONS LPZ and SITA combination therapy appears to have complementary mechanisms of action and additive antidiabetic effect.
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Affiliation(s)
- ShaoJun Hao
- Department of Pharmacy and Equipment, No. 371 Hospital of PLA, Xin'xiang, China
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Zaccardi F, Pitocco D, Martini F, Caputo S, Miele L, Grieco A, Ghirlanda G. A case of esomeprazole-induced transient diabetes and hepatitis: the role of liver inflammation in the pathogenesis of insulin resistance. Acta Diabetol 2014; 51:151-153. [PMID: 22389003 DOI: 10.1007/s00592-012-0382-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2011] [Accepted: 02/16/2012] [Indexed: 12/18/2022]
Abstract
We describe a case report of a patient who developed transient type 2 diabetes after a drug-induced (esomeprazole) sub-acute hepatitis. This case evidences the pathophysiological relevance, also in humans, of liver inflammation in the pathogenesis of type 2 diabetes.
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Affiliation(s)
- Francesco Zaccardi
- Diabetes Care Unit, Catholic University, A. Gemelli Hospital, L. Go A. Gemelli, 00168, Rome, Italy,
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Omeprazole and PGC-formulated heparin binding epidermal growth factor normalizes fasting blood glucose and suppresses insulitis in multiple low dose streptozotocin diabetes model. Pharm Res 2013; 30:2843-54. [PMID: 23793991 DOI: 10.1007/s11095-013-1112-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2013] [Accepted: 06/04/2013] [Indexed: 12/29/2022]
Abstract
PURPOSE Our objective was to develop novel nanocarriers (protected graft copolymer, PGC) that improve the stability of heparin binding EGF (HBEGF) and gastrin and then to use PGC-formulated HBEGF (PGC-HBEGF) and Omeprazole (+/- PGC-gastrin) for normalizing fasting blood glucose (FBG) and improving islet function in diabetic mice. METHODS HBEGF, PGC-HBEGF, Omeprazole, Omeprazole + PGC-HBEGF, Omeprazole + PGC-gastrin + PGC-HBEGF and epidermal growth factor (EGF) + gastrin were tested in multiple low dose streptozotocin diabetic mice. RESULTS Omeprazole + PGC-HBEGF normalized FBG and is better than EGF + gastrin at improving islet function and decreasing insulitis. Groups treated with Omeprazole, Omeprazole + PGC-HBEGF, or EGF + gastrin have significantly improved islet function versus saline control. All animals that received PGC-HBEGF had significantly reduced islet insulitis versus saline control. Non-FBG was lower for Omeprazole + PGC-gastrin + PGC-HBEGF but Omeprazole + PGC-HBEGF alone showed better FBG and glucose tolerance. CONCLUSIONS Omeprazole + PGC-HBEGF provides a sustained exposure to both EGFRA and gastrin, improves islet function, and decreases insulitis in multiple low dose streptozotocin diabetic mice. Although HBEGF or EGF elevates non-FBG, it facilitates a reduction of insulitis and, in the presence of Omeprazole, provides normalization of FBG at the end of treatment. The study demonstrates Omeprazole and PGC-HBEGF is a viable treatment for diabetes.
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Abstract
Diabetes mellitus is a complex chronic disease associated with an absolute insulin deficiency in type 1 diabetes (T1D) and a progressive deterioration of β-cell function in type 2 diabetes (T2D). T2D pathophysiology has numerous defects including incretin deficiency/resistance. Gastrin has demonstrated to be an islet growth factor (like glucagon-like peptide-1, epidermal growth factor, transforming growth factor-α,…) and be able to restore a functional β-cell mass in diabetic animals. This hormone is likely to stimulate insulin secretion during an ordinary protein-rich meal, this is, to have an incretin-like effect. Proton pump inhibitors (PPIs) can raise serum gastrin concentration significantly and therefore, affect to glucose metabolism through promoting β-cell regeneration/expansion and also enhancing insulin secretion. The present paper aims to review studies concerning the effect of PPIs on glucose metabolism. Several research groups have recently explored the potential role of this class of drugs on glycemic control, mainly in T2D. The results show antidiabetic properties for the PPIs with a global glucose-lowering power around 0.6-0.7 % points of HbA1c, but the level of evidence for the available literature is still not high. If these data start to become demonstrated in the ongoing clinical trials, PPIs could become a new antidiabetic agent with a good and safe profile for T2D and even useful for T1D, particularly in the area of islet transplantation to preserve β-cell mass.
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Affiliation(s)
- Diana Boj-Carceller
- Endocrinology and Nutrition Unit, Hospital Miguel Servet, Paseo Isabel La Católica, 1-3, 50009, Zaragoza, Spain.
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Hove KD, Brøns C, Færch K, Lund SS, Petersen JS, Karlsen AE, Rossing P, Rehfeld JF, Vaag A. Effects of 12 weeks' treatment with a proton pump inhibitor on insulin secretion, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes: a randomised double-blind prospective placebo-controlled study. Diabetologia 2013; 56:22-30. [PMID: 23011351 DOI: 10.1007/s00125-012-2714-y] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Accepted: 07/31/2012] [Indexed: 01/04/2023]
Abstract
AIMS/HYPOTHESIS Recent studies suggest that proton pump inhibitor treatment may increase insulin secretion and improve glucose metabolism in type 2 diabetes. In a randomised double-blind prospective placebo-controlled 2 × 2 factorial study, we examined the effect of esomeprazole on insulin secretion, HbA(1c) and cardiovascular risk factors in type 2 diabetes. METHODS Forty-one patients with type 2 diabetes using dietary control or oral glucose-lowering treatment were randomised to receive add-on esomeprazole 40 mg (n = 20) or placebo (n = 21) for 12 weeks. Randomisation was carried out prior to inclusion on the basis of a computer-generated random-number list. The allocation sequence was concealed in sealed envelopes from the researcher enrolling and assessing participants. The study was undertaken at Steno Diabetes Center, Gentofte, Denmark. The primary outcome was change in AUC for insulin levels during a meal test. Secondary outcomes were the levels of HbA(1c) and biochemical markers of cardiovascular risk, including lipids, coagulation factors, inflammation markers, markers of endothelial function and 24 h ambulatory BP measurements. RESULTS Forty-one participants were analysed. In the esomeprazole-treated group the AUC for insulin did not change (before vs after treatment: 28,049 ± 17,659 vs 27,270 ± 32,004 pmol/l × min (p = 0.838). In the placebo group AUC for insulin decreased from 27,392 ± 14,348 pmol/l × min to 22,938 ± 11,936 pmol/l × min (p = 0.002). Esomeprazole treatment (n = 20) caused a ninefold increase in the AUC for gastrin. HbA(1c) increased from 7.0 ± 0.6% (53 ± 5 mmol/mol) to 7.3 ± 0.8% (56 ± 6 mmol/mol) in the esomeprazole-treated group and from 7.0 ± 0.6% (53 ± 5 mmol/mol) to 7.4 ± 0.8% (57 ± 6 mmol/mol) in the placebo group (n = 21) (p for difference in change >0.05). Except for BP, there were no differences between the groups in the markers of cardiovascular risk (p > 0.05). Monitoring of 24 h ambulatory BP showed a significant decrease in daytime systolic BP, daytime diastolic BP and 24 h diastolic BP in the placebo group (p < 0.05). No change in BP was seen in the patients treated with esomeprazole. CONCLUSIONS/INTERPRETATION Treatment with esomeprazole over 12 weeks did not improve insulin secretion, glycaemic control or cardiovascular disease biomarkers in patients with type 2 diabetes.
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Affiliation(s)
- K D Hove
- Steno Diabetes Center A/S, Niels Steensens Vej 2, 2820 Gentofte, Denmark.
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Patel V, Joharapurkar A, Dhanesha N, Kshirsagar S, Detroja J, Patel K, Gandhi T, Patel K, Bahekar R, Jain M. Combination of omeprazole with GLP-1 agonist therapy improves insulin sensitivity and antioxidant activity in liver in type 1 diabetic mice. Pharmacol Rep 2013; 65:927-936. [PMID: 24145087 DOI: 10.1016/s1734-1140(13)71074-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2012] [Revised: 02/05/2013] [Indexed: 12/20/2022]
Abstract
BACKGROUND Combination with suitable pharmacological agents can improve the antiobesity and antidiabetic actions of glucagon like peptide-1 (GLP-1) based therapies. GLP-1 agonist exendin-4 may have insulin-independent effects on amelioration of insulin resistance and hepatic steatosis by virtue of its action on hepatic GLP-1 receptors, and these effects can be improved by combination with proton pump inhibitors. However, it was not assessed whether omeprazole can improve the peripheral actions of exendin-4 in the state of insulin deficiency. METHODS We investigated the effects of combination of omeprazole with GLP-1 agonist exendin-4 in multiple low-dose streptozotocin (STZ)-induced diabetes in C57BL/KsJ mice, a model of type 1 diabetes. Male diabetic mice were treated with exendin-4 and/or omeprazole for a period of 4 weeks. RESULTS Omeprazole treatment had no significant effect on lowering the blood glucose levels of diabetic mice, when compared to control, although it improved the antihyperglycemic actions of exendin-4. Similarly, serum triglycerides and total cholesterols levels were significantly lower in the combination treated mice compared to either exendin-4 and omeprazole alone. In addition, the combination treatment significantly ameliorated lipid peroxidation and hepatic triglycerides in diabetic mice compared to either exendin-4 and omeprazole alone. The improvement in hepatic insulin sensitivity, as indicated by insulin tolerance test (ITT) and pyruvate tolerance test (IPPTT), was correlated with the expression of nuclear factor erythroid-related factor 2 (Nrf2) and insulin receptor substrate-1 (IRS-1) and the combination treatment significantly improved the insulin sensitivity in comparison to vehicle control. CONCLUSION We conclude that combination with omeprazole improves the insulin sensitizing actions of GLP-1 therapy and these effects are partially mediated through the decrease in hepatic steatosis and improvement in antioxidant status in the liver.
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Affiliation(s)
- Vishal Patel
- Department of Pharmacology and Toxicology, Zydus Research Centre, Cadila Healthcare Limited, Sarkhej-Bavla N.H. No.8A, Moraiya, Ahmedabad 382210, India.
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Improved diabetes control and pancreatic function in a type 2 diabetic after omeprazole administration. Case Rep Endocrinol 2012; 2012:468609. [PMID: 22937295 PMCID: PMC3420592 DOI: 10.1155/2012/468609] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2011] [Accepted: 01/09/2012] [Indexed: 12/21/2022] Open
Abstract
A 43-year-old man with type 2 diabetes, opposed to insulin use and poorly responsive to oral agents added sequentially over 6 years, was placed on 40 mg omeprazole twice daily. A linear decline in daily fasting blood glucose was observed over the first two-month treatment, and his hemoglobin A1c was reduced from 11.9% to 8.2%, then sustained at 8.1% after four months. Glucose, insulin, and C-peptide response to a 2-hour glucose tolerance test were consistently improved across this time period, and calculated beta-cell mass increased by 67%. We believe these responses are consistent with activation or neogenesis of pancreatic beta cells, possibly through a gastrin-mediated mechanism.
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Boj-Carceller D, Bocos-Terraz P, Moreno-Vernis M, Sanz-Paris A, Trincado-Aznar P, Albero-Gamboa R. Are proton pump inhibitors a new antidiabetic drug? A cross sectional study. World J Diabetes 2011; 2:217-220. [PMID: 22174957 PMCID: PMC3238490 DOI: 10.4239/wjd.v2.i12.217] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2011] [Revised: 10/02/2011] [Accepted: 10/10/2011] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate the effect of proton pump inhibitors (PPIs) on glycemic control (HbA1c) in type 2 diabetic patients. METHODS A cross-sectional study of consecutive in-patients admitted to hospital in any department during the first semester of the year 2010 who had a recent HbA1c measurement. The study excluded those with a diagnosis of hyperglycemic decompensation, diabetic onset or pregnancy. It compared HbA1c levels of those taking PPIs and those not. RESULTS A total of 97 patients were recruited. The average HbA1C level was 7.0% ± 1.2%. Overall PPI consumption was 55.7%. HbA1c was significantly lower in individuals who took PPIs: -0.6%, 95% CI: -0.12 to -0.83. People who used PPIs with some type of insulin therapy had a HbA1c reduction by -0.8%, 95% CI: -0.12 to -1.48. For the rest of subgroup analysis based on the antidiabetic drug used, PPI consumption always exhibited lower HbA1c levels. CONCLUSION PPIs seems to be consistently associated with better glycemic control in type 2 diabetes. HbA1c reduction observed is similar to incretin-based therapies.
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Affiliation(s)
- Diana Boj-Carceller
- Diana Boj-Carceller, Alejandro Sanz-Paris, Pablo Trincado- Aznar, Ramón Albero-Gamboa, Endocrinology and Nutrition Unit, Hospital Miguel Servet, 50009 Zaragoza, Spain
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Hove KD, Færch K, Bödvarsdóttir TB, Karlsen AE, Petersen JS, Vaag A. Treatment with a proton pump inhibitor improves glycaemic control in type 2 diabetic patients - a retrospective analysis. Diabetes Res Clin Pract 2010; 90:e72-4. [PMID: 20888658 DOI: 10.1016/j.diabres.2010.09.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2010] [Revised: 08/19/2010] [Accepted: 09/02/2010] [Indexed: 12/16/2022]
Abstract
We retrospectively studied whether treatment with esomeprazole improved HbA₁(c) levels in type 2 diabetic patients. We selected 21 patients who had been treated with esomeprazole for 11 ± 3 months and 21 controls. HbA₁(c) levels decreased in the esomeprazole-treated group. Our data indicate that proton pump inhibitors may improve glycaemic control in type 2 diabetic patients.
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Affiliation(s)
- Karin D Hove
- Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark
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Bondar AN, Fischer S, Smith JC. Water Pathways in the Bacteriorhodopsin Proton Pump. J Membr Biol 2010; 239:73-84. [DOI: 10.1007/s00232-010-9329-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2010] [Accepted: 11/05/2010] [Indexed: 01/18/2023]
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Sanaka M, Yamamoto T, Kuyama Y. Effects of proton pump inhibitors on gastric emptying: a systematic review. Dig Dis Sci 2010; 55:2431-40. [PMID: 20012198 DOI: 10.1007/s10620-009-1076-x] [Citation(s) in RCA: 92] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2009] [Accepted: 11/25/2009] [Indexed: 12/26/2022]
Abstract
The proton pump inhibitor (PPI) is widely used for the treatment of gastroesophageal reflux disease, peptic ulcer diseases, and functional dyspepsia. The pathogenesis of these acid-related and/or functional upper gastrointestinal disorders is potentially associated with abnormal gastric emptying. To date, variable effects of PPIs on gastric emptying have been reported. Therefore, it is relevant to gather and analyze published information on this topic. A systematic literature search has been performed, showing that the delaying effect of PPIs on gastric emptying of solid meals is consistent, whereas the effect of PPIs on the emptying of liquids is inconsistent. The underlying mechanisms whereby PPIs may affect gastric emptying have been discussed, most of which still remain hypothetic. Gastric emptying of solids involves a process of peptic hydrolysis. PPIs impair the hydrolytic digestion by inhibiting acid-dependent peptic activity, thereby delaying the solid emptying. Gastric emptying of liquids largely depends on volume and energy density of intragastric contents. PPIs variably modify the volume and the energy density by reducing gastric fluid secretion, thereby modifying the liquid emptying in an unpredictable manner. Hypergastrinemia has been considered to delay gastric emptying, but it seems of minor importance in the regulation of gastric emptying during PPI use. The delayed emptying of solids due to PPI therapy may have clinical implications in the management of gastroesophageal reflux disease, functional dyspepsia, as well as diabetes.
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Affiliation(s)
- Masaki Sanaka
- Department of General Medicine and Emergency Care, Toho University School of Medicine, Omori Hospital, 6-11-1, Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan.
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