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| ORIGINAL ARTICLE |
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| Year : 2018 | Volume
: 20
| Issue : 1 | Page : 1-5 |
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Study of the effect of pantoprazole on glycemic control of type-2 diabetes mellitus in tertiary care center and hospital in North India
Prabhat K Agrawal, Subhash Chandra, Arvind K Jaiswal, Ashish Gautam, Pradeep Kumar Maheshwari
PG Department of Medicine, Sarojini Naidu Medical College (SNMC), Agra, Uttar Pradesh, India
| Date of Web Publication | 29-May-2018 |
Correspondence Address:
Dr. Subhash Chandra
Assistant Professor, P.G. Department of Medicine, S.N. Medical College, Agra, Uttar Pradesh
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jomt.jomt_2_18
Context: Type 2 diabetes mellitus (type 2 DM) is a heterogeneous and complex combination of metabolic condition caused by high levels of blood glucose and insulin resistance or insulin deficiency. Some studies suggest the increased levels of gastrin following the administration of proton pump inhibitors (PPIs), which seek to improve glycemic status and increased pancreatic insulin content.
Aim: We determined the effect of pantoprazole on glycemic control in patients with type 2 DM.
Material and Methods: Two groups, each with 30 patients of type 2 DM under treatment with oral hypoglycemic agent, were considered for this study. Patients were treated for 24 weeks with placebo or 40 mg pantoprazole tablets twice daily. Fasting blood glucose (FBG), postprandial blood glucose (PP blood glucose), as well as glycated hemoglobin (HbA1C) before and after treatment were measured.
Study: Duration 1 year.
Statistical Analysis: A hospital-based, randomized, double-blind, placebo-controlled study was used. Data were expressed as mean with standard deviation, numbers, and percentage. Baseline parameters and laboratory safety parameters were compared using appropriate parametric and nonparametric tests. A P value <0.05 was considered as significant.
Results: The mean FBG readings at baseline in the intervention and control groups were 170.47 ± 16.65 and 163.39 ± 14.95 mg/dL, respectively, and those at the end of intervention were 157.95 ± 14.37 and 165.32 ± 12.40 mg/dL. The within-group changes in the intervention group were statistically significant (P = 0.003). The statistical analysis between groups after intervention showed a significant differences (P = 0.03). HbA1C changes in the intervention and control groups in the study were 0.53 ± 0.03% and 0.20 ± 0.08%, respectively, but a decrease in the intervention group was statistically significant (P = 0.005). In the end, the change between the two groups was also statistically significant (P = 0.005).
Conclusions: There is a significant reduction in FBG, PP blood glucose, and HbA1C after 24 weeks of pantoprazole (40 mg BID) administration, which improved glycemic control in type 2 DM patients. PPI such as pantoprazole may be a new therapeutic approach in type 2 DM in future.
Keywords: Beta cell neogenesis, proton pump inhibitor, raised gastrin level, type 2 diabetes mellitus
How to cite this article:
Agrawal PK, Chandra S, Jaiswal AK, Gautam A, Maheshwari PK. Study of the effect of pantoprazole on glycemic control of type-2 diabetes mellitus in tertiary care center and hospital in North India. J Med Trop 2018;20:1-5 |
How to cite this URL:
Agrawal PK, Chandra S, Jaiswal AK, Gautam A, Maheshwari PK. Study of the effect of pantoprazole on glycemic control of type-2 diabetes mellitus in tertiary care center and hospital in North India. J Med Trop [serial online] 2018 [cited 2023 Mar 24];20:1-5. Available from: https://www.jmedtropics.org/text.asp?2018/20/1/1/233419 |
| Introduction | |  |
Type 2 diabetes mellitus (type 2 DM) is a complex heterogeneous group of metabolic conditions characterized by increased level of blood glucose due to two defects − insulin resistance and insulin deficiency,[1] there are plethora of drugs targeting these two defects. Recently, the focus has been on strengthening the enteroinsular axis and incretins. Beta cell loss and dysfunction play important roles in the pathogenesis of both type 1 and type 2 DM. Recent studies have suggested that age-dependent deterioration of type 2 DM is associated with progressive loss of beta cell function.[2] Most medications being used to treat type 2 diabetes cannot prevent β-cell death or re-establish β-cell mass.[3]
Over the past few decades, various therapeutic options have been proposed to maintain β-cell function and mass.[2] Incretin-based therapies aim not only at promoting beta cell function, but also at decreasing apoptosis and increasing regeneration of beta cells. Beta cell turnover is affected by many factors including gastrointestinal hormones, like glucose-mimetic insulinotropic peptide, glucagon like peptide-1 (GLP-1), gastrin and cholecystokinin.[4],[5] GLP-1 and its mimetic compound, exendin-4, gastrin, epidermal growth factor, transforming growth factor a new class of diabetic agents (exert their functions through multiple pathways, acting on the brain to induce satiety, inhibiting gastric emptying and glucagon secretion, and potentiating glucose-stimulated insulin secretion, all together leading to improved glucose homeostasis).[2],[6]
Proton pump inhibitors (PPIs) are wildly used clinically for the therapy of gastro-esophageal reflex disease, gastritis due to excess stomach acid, and gastric ulcers. PPIs can be orally administrated as an inactive form and, enters the blood stream from the intestine, reaches the gastric parietal cells, and is activated by crossing the cell membrane into the intracellular compartment. After converting to the active form in the unique parietal cell environment, PPIs irreversibly block the proton pump and can strongly reduce the secretion of gastric acid promoted by either gastrin, acetylcholine, or histamine. It is well known that PPIs indirectly elevate serum gastrin levels via a negative feedback effect.[7],[8],[9],[10],[11],[12]
Gastrin is one of neurohormonal secretagogues, peptide hormone produced mainly in the G cells of the pyloric antrum of the stomach, the main role of gastrin is the promotion of gastric acid secretion from the parietal cells of the stomach. Gastrin can also act as a growth factor and stimulate gastric cell proliferation.[13],[14]
The secretion of gastrin is stimulated by various factors, such as considerable distension of the stomach, vagal stimulation, the presence of food (especially protein, peptides, and amino acids) in the stomach and high pH levels in the stomach cavity.[14],[15] The gastrin receptor, cholecystokinin B (CCK-B), binds to gastrin and to cholecystokinin with a similar high affinity.[16] CCK-B receptor/gastrin receptor is involved in glucose homeostasis in adult humans and mediates the autocrine effects of gastrin on islet differentiation and growth in the fetal pancreas.[17]
It is reported that gastrin promotes β cell neogenesis in pancreatic ductal complex, modest pancreatic β cell replication, and improvement of glucose tolerance in animal models, in which the remodeling of pancreatic tissue is promoted.[16],[17],[18],[19],[20],[21] A report suggesting that, in 95% of the pancreatectomized rats, gastrin treatment not only increased β cells neogenesis from ductal cells but also caused both a modest increase in replication and a decrease in apoptosis in β cells with the resultant improvement of glucose tolerance.[19]
Interestingly, in type 2 DM animal models, it has been reported that PPIs improved glycemic control, probably via possible effects on augmenting both serum levels of gastrin and β cell mass. Therefore, these agents appear to have the possibility of being a new approach for the therapy of diabetes.
| Material and methods | | |
The study was duly approved by the ethical committee of S.N. Medical College, Agra before study commencement. Written informed consent was obtained from every patient before study specific procedure. The study was conducted in S.N. Medical College and Hospital, Agra, India. Previously diagnosed type 2 DM patients and newly diagnosed patients attending out patient department (OPD)/diabetic OPD taking oral hypoglycemic agent (OHA) during the duration of the study were, included in the study. Excluded from the study are patients with malignancies, systemic or local infection, hepatic or renal disease (creatinine levels >1.5 mg/dL), coronary artery disease/inflammatory bowel syndrome/tuberculosis/collagen vascular disease, past and current users of insulin, pioglitazone, or incretin-based therapies. Patients receiving systemic glucocorticoids or immune-suppressants using supplemental vitamins, statins, antibiotics or those who smoked or used alcohol in the 12 weeks prior to the study were also excluded from participation. Pregnant or lactating women and patients treated with bismuth salts, H2 receptor blockers or PPIs in the preceding 3 months were also excluded.
Two groups: Group 1–placebo group − patient on OHA (metformin, or sulphonylurea or metformin + sulphonylurea) with placebo. Group 2–intervention group − patient on OHA (metformin, or sulphonylurea or metformin + sulphonylurea) with added therapy of pantoprazole 40 mg BID for 24 weeks.
All the patients were advised to follow dietary restriction and life style modification as recommended. No new change in drug/addition of new drugs or change in lifestyle and dietary habits were allowed. All the patients were examined, and weight of patient, body mass index (BMI), fasting blood glucose (FBG), postprandial blood glucose (PP blood glucose) and glycated hemoglobin (HbA1C) were estimated at baseline and 24 weeks. Blood glucose was measured by glucose hexokinase method and HbA1C was measured by high performance liquid chromatography method.
Statistical analysis
Patients were divided into two groups (1) intervention group and (2) placebo group, and a hospital-based randomized double-blind placebo-controlled study were used. Data were expressed as mean with standard deviation, numbers, and percentage. Baseline parameters and laboratory safety parameters were compared using appropriate parametric and nonparametric tests. A P value <0.05 was considered as significant.
| Results | | |
The study was conducted in S.N. Medical College and Hospital, Agra, India. In this study, 62 patients of type 2 DM were considered; out of which, 30 were randomly allotted in intervention (study group) and 30 were randomly allotted in placebo (control group). Two patients, one in intervention group and one in placebo group did not appear after first visit. There were 30 patients in intervention group with mean age 57.03 ± 9.25 years and 30 patients in placebo group with mean age 57.43 ± 8.2 years. There were no significant differences of age distribution of patients in these two groups (P = 0.8604). There were random distribution of male and female patients in both intervention and control groups, with no significant difference (P = 0.7745). In intervention group, there were 21 males (70%) and nine female (30%), and in control group, there were 22 males (73.3%) and eight female (26.7%). All the other baseline characteristics including duration of DM, blood pressure, weight, height, BMI, smoking, and type of OHA, alcohol intake do not differ in the two groups.
In the intervention group, there were 17 patients on metformin therapy alone, three patients were on sulphonylurea (glimipride), and 10 patients were on metformin and sulphonylurea (glimipride). In the control group, there were 16 patients on metformin therapy alone, five patients were on sulphonylurea (glimipride), and nine patients were on metformin and sulphonylurea (glimipride). There were, no significant difference in between these groups (P = 0.75).
[Table 1] is showing the weight and BMI of the patients before and after intervention and placebo. There were no significant change in weight and BMI of the patients observed before and after intervention (P = 0.94) and placebo (P = 0.70).
In intervention group, the mean FBG of patients before intervention 170.47 ± 16.65 mg/dL and after intervention (24 weeks of PPI administration), mean FBG of patients were 157.95 ± 14.37 mg/dL. There noted a change of 12.52 ± 2.28 mg/dL in FBG before and after PPI administration, and it is statistically highly significant (P = 0.0028). In placebo group, the mean FBG of patients before placebo were 163.39 ± 14.95 mg/dL and after placebo, mean FBG of patients were 165.32 ± 12.40 mg/dL. There are change of 1.93 ± 2.55 mg/dL in FBG before and after placebo, and it is not statistically significant (P = 0.5890) [Table 2]. | Table 2: Evaluation of fasting blood glucose, postprandial blood glucose, and HbA1C of patients in two groups
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In intervention group, the mean PP blood glucose of patients before intervention 242.83 ± 26.98 mg/dL and after intervention (24 weeks of PPI administration), mean PP blood glucose of patients were 219.58 ± 24.83 mg/dL. There are change of 23.83 ± 2.15 mg/dL in PP blood glucose before and after PPI administration, and it is statistically significant (P = 0.001). In placebo group, the mean PP blood glucose of patients before placebo were 225.30 ± 23.88 mg/dL and after placebo, mean PP blood glucose of patients were 232.08 ± 19.16 mg/dL. There are change of 6.78 ± 4.72 mg/dL in PP blood glucose before and after placebo and it is not statistically significant (P = 0.23) [Table 2].
In intervention group, the mean HbA1C of patients before intervention 7.90 ± 0.70% and after intervention (24 weeks of PPI administration), mean HbA1C of patients were 7.37 ± 0.73%. There were change of 0.53 ± 0.03% in HbA1C before and after PPI administration and it is statistically significant (P = 0.005). In placebo group, the mean HbA1C of patients before placebo were 7.63 ± 0.56% and after placebo, mean HbA1C of patients were 7.83 ± 0.48%. There were changes of 0.20 ± 0.08% in HbA1C before and after placebo, and it is not statistically significant (P = 0.15) [Table 2].
| Discusions | | |
In type 2 DM, there is a gradual deterioration in β-cell function in patients with type 2 DM. Type 2 diabetes is a progressive disease characterized by increasing dysfunction of pancreatic β-cell either through inactivation or apoptosis.
The effect of pantoprazole on glycemic control, that is, a decrease in HbA1C, FBG, and PP blood glucose may be due to incretin like effects of gastrin, because gastrointestinal peptides stimulate β cell insulin secretion and/or proliferation, resulting in enhanced glucose-dependent insulin release.[22],[23],[24],[25],[26],[27],[28],[29],[30],[31] In pancreatic duct-ligated rat model of diabetes, iv-infused gastrin enhanced β-cell neogenesis and insulin secretion, resulting in improved blood glucose control.[4] Administration of lansoprazole resulted in similar findings in the Psammomys obesus model of type 2 DM,[21] thus establishing the relationship among PPIs, gastrin, and glucose-insulin homeostasis. PPIs also delay gastric emptying, which could result in timely exposure of glucose to ileum, thereby providing conducive ambience for incretin hormones secretion, and thereby resulting into a decrease in postprandial glucose levels.[32],[33] The other possibility may be a direct effect of gastrin on glucose dependent insulinotropic peptide and glucagon like peptide-1 secretion from the K and L cells of the small intestine, respectively; however, it remains conjectural.
In the previous study, there observed a significant reduction in HbA1C, FBG, PP blood sugar, and increase in serum gastrin and serum insulin level was also found.[24],[27],[28],[29] There is a 2–3 fold increase in serum gastrin level occurs after 24–32 weeks of PPI therapy.[34]
HbA1C is considered the best parameter for evaluating the glycemic control, and for assessing the efficacy of ant diabetic medications, PPIs were shown to decrease HbA1C. In our study, the reduction in HbA1C is in concordance with earlier reports, where it was 0.5–0.7% with PPIs.
This study lasted for a longer duration of 24 weeks compared to a previous study, and has more advantage in increasing serum gastrin level, but the limitation of our study is that we could not measure serum gastrin and serum insulin level, because these tests are not available in our college. Sample size of this study is also larger than the previous study.
| Conclusion | | |
There is a significant reduction in FBG, PP blood glucose, and HbA1C after 24 weeks of pantoprazole administration, which improved glycemic control in type 2 DM patients. PPI (pantoprazole) may be a new therapeutic approach in type 2 DM in future.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]
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