AUCTORES
Globalize your Research
Review Article | DOI: https://doi.org/10.31579/2640-1045/028
Department of Diabetes, Endocrinology.
*Corresponding Author: David Spacey, Department of Diabetes, Endocrinology
Citation: David Spacey. Anti-Diabetic Agent: Involvement in Hepatic Fat Metabolism In Pioglitazone-Treated Type 2 Diabetic Patients. J. Endocrinology and Disorders, doi:10.31579/2640-1045/028
Copyright: © 2018: David Spacey. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Received: 01 April 2018 | Accepted: 19 April 2018 | Published: 26 April 2018
Keywords: lipid profile, liver enzyme, pioglitazone, type 2 diabetes mellitus.
Pioglitazone (brand name Actos) is a prescription drug of the thiazolidinedione (TZD) class with hypoglycemic (antihyperglycemic, antidiabetic) action to treat diabetes.
Pioglitazone is one of the antidiuretic agents used in the management of type 2 diabetes mellitus (DM). The effect of pioglitazone on blood glucose, lipid profile, liver enzymes and weight has been shown with conflicting results. In this study we aim to evaluate the effect of pioglitazone on the weight, lipid profile and liver enzymes in patients with DM.
Pioglitazone is used to lower blood glucose levels in the treatment of diabetes mellitus type 2 (T2DM) either alone or in combination with a sulfonylurea, metformin, or insulin.
Type 2 diabetes mellitus (T2DM) is a progressive disease characterized by raised glucose levels which is associated with macrovascular and microvascular complications as well as dyslipidaemia, that increase morbidity and mortality. There are various medications introduced to reduce glucose levels and improve DM patients’ clinical status. Pioglitazone, a thiazolidinedione derivative, is an insulin-sensitizing agent developed for the treatment of T2DM.Pioglitazone is a peroxisome proliferator activated receptor-gamma (PPAR-γ) agonist which can reduce insulin resistance in liver, muscle and adipose tissue] and improve glucose and lipid metabolism.
Pioglitazone treatment in T2DM results in improving lipid profile including decrease in triglycerides and low-density lipoprotein (LDL), increase in high-density lipoprotein (HDL) and decrease in serum fatty acids as well as improved liver function tests Unlike these findings, other studies were not able to demonstrate any significant improvement in liver function tests or lipid profile Unlike its beneficiary effects, weight gain is one major side effect of this medication.
Previous reports indicate that compared with glibenclamide or metformin, pioglitazone alone or in combination with any of these agents could reduce blood glucose further. However, there are controversies in reported effects of pioglitazone. So, it is important to define the exact role of pioglitazone on diabetes control, lipid profile, liver function and possible weight gain. In this study, we aim to evaluate the effect of pioglitazone in Iranian patients with T2DM.
THIAZOLIDINEDIONES, a new class of insulin-sensitizing agents, have recently been introduced for the treatment of patients with type 2 diabetic mellitus. Early studies showed that troglitazone ameliorates insulin resistance and improves hyperglycemia, hyperinsulinemia, and dyslipidemia in type 2 diabetic patients. Although the precise mechanism of action of the thiazolidinediones remains to be determined, their glucose-lowering effect seems to depend on the presence of insulin.It is known that thiazolidinediones activate specific receptors, termed PPARγ (6, 7). PPARγ activation causes preadipocytes to differentiate into mature fat cells and causes the induction of key enzymes involved in lipogenesis . Consistent with these observations, clinical studies have demonstrated that thiazolidinedione therapy in type 2 diabetic patients is associated with weight gain, yet glycemic control improves. The increase in body weight is positively related to the reduction in hemoglobin A1c (HbA1c). These results suggest that the improvement in glucose homeostasis after thiazolidinedione treatment may in some way be related to an alteration in fat metabolism and/or fat topography. With respect to the later, Adams et al reported that thiazolidinediones promote the differentiation of preadipocytes into mature fat cells in sc, but not visceral, fat depots in humans. Numerous studies have shown that increased visceral fat is associated with insulin resistance and the development of macrovascular complications (14–16). Several recent studies have demonstrated that the thiazolidinedione, troglitazone, decreases visceral fat content in type 2 diabetic patients (10, 17), but no previous study has examined whether the alterations in abdominal fat distribution after thiazolidinedione treatment are related to the improvement in glycemic control and/or insulin sensitivity.
Aim the Study
In the present study we have evaluated the effect of pioglitazone therapy on glucose tolerance, insulin secretion, and hepatic and peripheral tissue sensitivity to insulin, plasma lipid levels, and abdominal fat distribution in type 2 diabetic individuals. To the best of our knowledge, this represents the first study that has examined the relationship between changes in abdominal fat distribution and glucose homeostasis/insulin sensitivity after thiazolidinedione treatment in type 2 diabetic subjects.
Materials and Methods
In this single-arm clinical trial, 110 patients aged 35–75 years with uncontrolled diabetes mellitus and no previous history of taking thiazolidinediones, who were on maximum dose of metformin (1.5–2 g) and glibenclamide (15–20 mg) for at least 1 month, having HbA1c 7.5–11% and fasting blood sugar (FBS) ⩾140 mg/dl were enrolled. Patients with significant renal, cardiac, liver, lung, or neurological disease, anaemia, systemic glucocorticoid therapy patients receiving β-blockers, prior use of or known allergy to any type of available thiazolidinediones, patients currently pregnant, breastfeeding, smokers, and subjects who abused alcohol or drugs and those with a body mass index (BMI) greater than 40 kg/m2 were excluded from this study. Subjects were also excluded if they had been treated with insulin or had started treatment with a statin or any fibric acid derivative within 2 months of the beginning of the study. All patients underwent a complete laboratory survey including FBS, lipid profile including cholesterol, triglyceride, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), alkaline phosphatase (ALK-P), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and the weight of patients were assessed at the time of laboratory survey. Then the pioglitazone at a dose of 30 mg was added to the treatment protocol of all patients and they were followed up for 3 months. All above-mentioned laboratory investigations and weight assessing were repeated after 3 months and the obtained data before and after therapeutic intervention were studied.
Abdominal fat distribution
Visceral and sc fat area were measured by MRI, using previously described imaging procedures (18). Briefly, images were acquired on a 1.9 T Elscint Prestige MRI system using a T1-weighted spin echo pulse sequence with a TR of 500 msec and a TE of less than 20 msec. A sagittal localizing image was used to center transverse sections on the line through the space between L4 and L5. Ten 5.0-mm thick sections were acquired with a gap of 1.0 mm to prevent signal cross-over from adjacent sections. The field of view ranged from 30–50 cm, depending on body size. Phase encoding was in the antero-posterior direction to minimize the effects of motion-induced phase artifacts that might otherwise be distributed laterally through a large portion of the abdomen. The field of view was adjusted for body size to ensure 2-mm pixel spacing. Signal averaging (four signals averaged) were used to reduce the effects of motion-related artifacts. Additionally, respiratory gating was used to combat motion-induced artifacts and to reduce the blurring of fat boundaries in the anterior region of the abdomen. Images were processed using Alice software (Perceptive Systems, Inc., Boulder, CO) to determine abdominal sc and visceral fat areas. The sc fat area was analyzed by selecting the outer and inner margins of sc adipose tissue as region of interests from the cross-sectional images, and counting the number of pixels between the outer and inner margins of sc adipose tissue. The visceral (intraabdominal) fat area was determined using histograms specific to the visceral regions. The histograms were summed over a range of pixel values designated as fat by fitting two normal analysis distribution curves to them.
n this study, 110 patients with type 2 DM including 70 (63.6%) females and 40 (36.4%) males with a mean age of 54.26 ± 8.96 years were studied.
Table 1.
Demographic and anthropometric findings between groups.
Table 1 shows the laboratory findings before and after the intervention. As the table shows FBS, HbA1c, TG, ALT, ALK-P were significantly decreased and patients’ weight was increased following intervention. However, no significant differences were observed in the level of cholesterol, HDL, LDL and AST before and after the intervention. Mean percentage of increase in weight was 1.07 ± 0.29%.
FBS, fasting blood sugar; HbA1C, haemoglobin A1C; LDL, low-density lipoprotein; HDL, high-density lipoprotein; ALK-P, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase.
Table 2.
Hepatic and whole body glucose metabolism during the two-step insulin clamp (insulin infusion rates: 40 and 160 mU/m2 · min) performed before and after 16 wk of pioglitazone treatment Product of EGP and fasting plasma insulin concentration in the postabsorptive state.
Statistical analysis
Statistics were performed with StatView for Windows, version 5.0 (SAS Institute, Inc., Cary, NC). Values before and after treatment were compared using paired t test. Linear regression analysis was used to examine the relationships between hepatic/peripheral insulin sensitivity and abdominal/sc fat area before and after pioglitazone treatment. All data are presented as the mean ±se. P value less than 0.05 was considered statistically significant.
The beneficial effects of the thiazolidinediones on glucose metabolism are believed to be mediated by their binding to the nuclear receptor PPARγ (6). PPARγ receptors are most abundant in adipocytes and are present in low concentrations in muscle (24). PPARγ activation results in stimulation of adipogenesis (6, 8, 9, 25) and gene transcription of key enzymes involved in lipogenesis (6, 8). There is significant variability in the adipose tissue distribution of PPARγ.
It is concluded that pioglitazone is a good antidiabetic agent in patients with T2DM who do not respond properly to maximum dose of glibenclamide and metformin. This agent has no negative impact on lipid profile and liver function tests but carries a trivial risk of weight gain which would limit its utility.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
