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Massalha M, Iskander R, Hassan H, Spiegel E, Erez O, Nachum Z. Gestational diabetes mellitus - more than the eye can see - a warning sign for future maternal health with transgenerational impact. FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2025; 6:1527076. [PMID: 40235646 PMCID: PMC11997571 DOI: 10.3389/fcdhc.2025.1527076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 02/06/2025] [Indexed: 04/17/2025]
Abstract
Gestational diabetes mellitus (GDM) is regarded by many as maternal maladaptation to physiological insulin resistance during the second half of pregnancy. However, recent evidence indicates that alterations in carbohydrate metabolism can already be detected in early pregnancy. This observation, the increasing prevalence of GDM, and the significant short and long-term implications for the mother and offspring call for reevaluation of the conceptual paradigm of GDM as a syndrome. This review will present evidence for the syndromic nature of GDM and the controversies regarding screening, diagnosis, management, and treatment.
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Affiliation(s)
- Manal Massalha
- Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel
- Rappaport Faculty of Medicine, Technion, Institute of technology, Haifa, Israel
| | - Rula Iskander
- Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel
| | - Haya Hassan
- Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel
| | - Etty Spiegel
- Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel
| | - Offer Erez
- Department of Obstetrics and Gynecology, Soroka University Medical Center, Beer Sheva, Israel
- Faculty of Medicine, Ben Gurion University of the Negev, Beer Sheva, Israel
- Department of Obstetrics and Gynecology, Hutzel Women’s Hospital, Wayne State University, Detroit, MI, United States
| | - Zohar Nachum
- Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel
- Rappaport Faculty of Medicine, Technion, Institute of technology, Haifa, Israel
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Garvey ZP, Gupta A, Taylor N, Thirunavukkarasu M, Maulik N. Navigating Diabetes in Pregnancy: Critical Approaches to Mitigate Risks and Improve Outcomes for Mother and Child. Metabolites 2025; 15:180. [PMID: 40137145 PMCID: PMC11943762 DOI: 10.3390/metabo15030180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 02/05/2025] [Accepted: 02/14/2025] [Indexed: 03/27/2025] Open
Abstract
With the increasing prevalence of diabetes and its growing impact on maternal and fetal health, management during pregnancy has become critical. This review describes the pathophysiology of insulin resistance during pregnancy, adverse outcomes correlated with diabetic pregnancies, and current management strategies. We investigate two leading approaches to managing pregnant patients with diabetes-lifestyle intervention and drug treatment. Lifestyle intervention, including dietary counseling, exercise regimens, patient education, and self-administered blood glucose monitoring, has demonstrated promising results in the management and prevention of gestational diabetes mellitus (GDM). Early intervention and treatment of at-risk patients have been critical for positive outcomes. Drug treatment, focusing on the utilization of insulin, insulin analogs, and antihyperglycemic agents has shown efficacy in achieving glycemic control and improving maternal and neonatal outcomes. These findings indicate that a combination of early lifestyle intervention and targeted drug treatment yields the most benefit in managing diabetes in pregnancy. To augment treatment, continuous glucose monitoring and telemedicine have become valuable tools in managing diabetes during pregnancy. Future research should aim to develop more effective antihyperglycemic agents, improve telehealth accessibility, and enhance preconception care for women at risk of developing GDM. By addressing these areas, we can significantly reduce the adverse outcomes associated with diabetes in pregnancy and improve overall maternal and fetal health.
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Affiliation(s)
| | | | | | | | - Nilanjana Maulik
- Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, University of Connecticut School of Medicine, Farmington, CT 06030, USA; (Z.P.G.); (A.G.); (N.T.); (M.T.)
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Bodier L, Le Lous M, Isly H, Derrien C, Vaduva P. Efficacy and safety of pharmacological treatments for gestational diabetes: a systematic review comparing metformin with glibenclamide and insulin. DIABETES & METABOLISM 2025; 51:101622. [PMID: 39923989 DOI: 10.1016/j.diabet.2025.101622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 01/31/2025] [Accepted: 02/03/2025] [Indexed: 02/11/2025]
Abstract
AIM Gestational diabetes, characterized by impaired glucose tolerance occurring or diagnosed during pregnancy, is a significant public health concern. When lifestyle and dietary measures fail (30 % of women), insulin is the standard treatment. Oral antidiabetic agents, such as metformin (Glucophage) and glibenclamide, could provide a promising alternative. The aim here was to evaluate the effectiveness and safety of these treatments in gestational diabetes. METHODS This study is based on a systematic literature review. A keyword search for "metformin (Glucophage)," "glibenclamide," "pregnancy," and "gestational diabetes" was conducted in the PubMed and Google Scholar databases from 2013 to 2023. RESULTS A total of 45 studies were selected and analyzed. metformin (Glucophage) appears to offer a combination of effectiveness in glycemic control and maternal and neonatal safety. Compared to insulin, it reduces maternal weight gain, lowers maternal hypoglycemia rates, and shows a tendency to reduce gestational hypertension and preeclampsia. Additionally, infants born to mothers on metformin (Glucophage) are less likely to be macrosomic, experience fewer neonatal hypoglycemic episodes, and require fewer admissions to intensive care units. On the other hand, glibenclamide seems effective in glycemic control but is associated with higher rates of macrosomia and neonatal hypoglycemia. CONCLUSION Metformin (Glucophage) appears to be a promising alternative to insulin for treating gestational diabetes, while uncertainties remain regarding the safety of glibenclamide.
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Affiliation(s)
- Louise Bodier
- Department of Gynecology and Obstetrics, Rennes University Hospital, France
| | - Maela Le Lous
- Department of Gynecology and Obstetrics, Rennes University Hospital, France
| | - Hélène Isly
- Department of Gynecology and Obstetrics, Rennes University Hospital, France
| | - Christèle Derrien
- Department of Endocrinology - Diabetes - Nutrition, Rennes University Hospital, France
| | - Patricia Vaduva
- Department of Endocrinology - Diabetes - Nutrition, Rennes University Hospital, France.
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Mason T, Alesi S, Fernando M, Vanky E, Teede HJ, Mousa A. Metformin in gestational diabetes: physiological actions and clinical applications. Nat Rev Endocrinol 2025; 21:77-91. [PMID: 39455749 DOI: 10.1038/s41574-024-01049-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/03/2024] [Indexed: 10/28/2024]
Abstract
Metformin is an effective oral hypoglycaemic agent used in the treatment of type 2 diabetes mellitus; however, its use in pregnancy for the treatment of gestational diabetes mellitus (GDM) remains controversial owing to concerns around safety and efficacy. This comprehensive review outlines the physiological metabolic functions of metformin and synthesizes existing literature and key knowledge gaps pertaining to the use of metformin in pregnancy across various end points in women with GDM. On the basis of current evidence, metformin reduces gestational weight gain, neonatal hypoglycaemia and macrosomia and increases insulin sensitivity. However, considerable heterogeneity between existing studies and the grouping of aggregate and often inharmonious data within meta-analyses has led to disparate findings regarding the efficacy of metformin in treating hyperglycaemia in GDM. Innovative analytical approaches with stratification by individual-level characteristics (for example, obesity, ethnicity, GDM severity and so on) and treatment regimens (diagnostic criteria, treatment timing and follow-up duration) are needed to establish efficacy across a range of end points and to identify which, if any, subgroups might benefit from metformin treatment during pregnancy.
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Affiliation(s)
- Taitum Mason
- Monash Centre for Health Research and Implementation (MCHRI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Melbourne, Australia
| | - Simon Alesi
- Monash Centre for Health Research and Implementation (MCHRI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Melbourne, Australia
| | - Melinda Fernando
- Monash Centre for Health Research and Implementation (MCHRI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Melbourne, Australia
| | - Eszter Vanky
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Helena J Teede
- Monash Centre for Health Research and Implementation (MCHRI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Melbourne, Australia
- Department of Endocrinology and Diabetes, Monash Health, Clayton, Victoria, Melbourne, Australia
| | - Aya Mousa
- Monash Centre for Health Research and Implementation (MCHRI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Melbourne, Australia.
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American Diabetes Association Professional Practice Committee, ElSayed NA, McCoy RG, Aleppo G, Balapattabi K, Beverly EA, Briggs Early K, Bruemmer D, Echouffo-Tcheugui JB, Ekhlaspour L, Garg R, Khunti K, Lal R, Lingvay I, Matfin G, Pandya N, Pekas EJ, Pilla SJ, Polsky S, Segal AR, Seley JJ, Stanton RC, Bannuru RR. 15. Management of Diabetes in Pregnancy: Standards of Care in Diabetes-2025. Diabetes Care 2025; 48:S306-S320. [PMID: 39651985 PMCID: PMC11635054 DOI: 10.2337/dc25-s015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2024]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Xu J, Zhang F, Li H, Li P, Zeng J, Wu X, Zhou R, Yang C, Zhang J. Total Water-Soluble Flavonoids From Lithocarpus litseifolius (Hance) Chun (Sweet Tea) Improve Glucose Homeostasis Through Multitarget Signalling in GDM Mice. J Diabetes Res 2024; 2024:1518080. [PMID: 39568571 PMCID: PMC11578658 DOI: 10.1155/2024/1518080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 10/19/2024] [Accepted: 10/22/2024] [Indexed: 11/22/2024] Open
Abstract
Background: The oral safety of Lithocarpus litseifolius (Hance) Chun (sweet tea) that has antihyperglycemic potential has been verified. However, its specific application and action mechanism in the treatment of gestational diabetes mellitus (GDM) are still unclear. Methods: Total water-soluble flavonoids extracted from L. litseifolius (Hance) Chun (sweet tea) were applied to GDM mice. The glucose tolerance, insulin sensitivity, and histopathology of the GDM mice were evaluated through an intraperitoneal glucose tolerance test (IPGTT), an intraperitoneal insulin tolerance test (IPITT), and histochemistry. The possible mechanism was analysed through network pharmacology. Results: Compared with those in GDM model mice (MD group), blood glucose levels indicating both glucose tolerance and insulin sensitivity were improved in GDM mice treated with total water-soluble flavonoids (LLHC group) but were greater than those in normal control mice (NC group). The number of apoptotic liver cells was significantly lower in the LLHC group than in the MD group, but greater than that in the NC group. Multiple targets and signalling pathways that were acted by eight main active ingredients were involved in the process by which total water-soluble flavonoids protect against GDM. The main mechanism involved quercetin (10 targets) and luteolin (8 targets), which acted on the effector target of GAA through six main signalling pathways around the AKT1 core axis. Conclusion: Oral administration of total water-soluble flavonoids can alleviate glucose intolerance and insulin resistance via the inhibition of liver cell apoptosis. The main active ingredients act on GAA through the signalling pathways of the AKT1 core axis.
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Affiliation(s)
- Junfei Xu
- College of Biological and Food Engineering/Key Laboratory of Research and Utilization of Ethnicinal Plant Resources of Hunan Province/Hunan Provincial Higher Education Key Laboratory of Intensive Processing Research on Mountain Ecological Food, Huaihua University, Huaihua 418000, China
| | - Fenfang Zhang
- College of Biological and Food Engineering/Key Laboratory of Research and Utilization of Ethnicinal Plant Resources of Hunan Province/Hunan Provincial Higher Education Key Laboratory of Intensive Processing Research on Mountain Ecological Food, Huaihua University, Huaihua 418000, China
| | - Huanhuan Li
- College of Biological and Food Engineering/Key Laboratory of Research and Utilization of Ethnicinal Plant Resources of Hunan Province/Hunan Provincial Higher Education Key Laboratory of Intensive Processing Research on Mountain Ecological Food, Huaihua University, Huaihua 418000, China
| | - Pan Li
- College of Biological and Food Engineering/Key Laboratory of Research and Utilization of Ethnicinal Plant Resources of Hunan Province/Hunan Provincial Higher Education Key Laboratory of Intensive Processing Research on Mountain Ecological Food, Huaihua University, Huaihua 418000, China
| | - Junying Zeng
- College of Biological and Food Engineering/Key Laboratory of Research and Utilization of Ethnicinal Plant Resources of Hunan Province/Hunan Provincial Higher Education Key Laboratory of Intensive Processing Research on Mountain Ecological Food, Huaihua University, Huaihua 418000, China
| | - Xianjin Wu
- College of Biological and Food Engineering/Key Laboratory of Research and Utilization of Ethnicinal Plant Resources of Hunan Province/Hunan Provincial Higher Education Key Laboratory of Intensive Processing Research on Mountain Ecological Food, Huaihua University, Huaihua 418000, China
| | - Rong Zhou
- College of Biological and Food Engineering/Key Laboratory of Research and Utilization of Ethnicinal Plant Resources of Hunan Province/Hunan Provincial Higher Education Key Laboratory of Intensive Processing Research on Mountain Ecological Food, Huaihua University, Huaihua 418000, China
| | - Chunyan Yang
- Department of Obstetrics and Gynecology, Huaihua Second People's Hospital/Huaihua Cancer Hospital, Huaihua 418000, China
| | - Juzuo Zhang
- College of Biological and Food Engineering/Key Laboratory of Research and Utilization of Ethnicinal Plant Resources of Hunan Province/Hunan Provincial Higher Education Key Laboratory of Intensive Processing Research on Mountain Ecological Food, Huaihua University, Huaihua 418000, China
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Hsu CY, A Abbood M, Kadhim Abbood N, Hemid Al-Athari AJ, Shather AH, Talib Kareem A, Hassan Ahmed H, Yadav A. Mechanical quantum analysis on the role of transition metals on the delivery of metformin anticancer drug by the boron phosphide nanotube. Comput Methods Biomech Biomed Engin 2024; 27:1920-1930. [PMID: 37847195 DOI: 10.1080/10255842.2023.2267718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 09/12/2023] [Accepted: 09/30/2023] [Indexed: 10/18/2023]
Abstract
We scrutinized the impact of doping of X atoms (X = Fe, Co, Ni, Cu, and Zn) on the metformin (MF) drug delivery performance of a BP nanotube (BPNT) using density functional B3LYP calculations. The pristine BPNT was not ideal for the drug delivery of MF because of a weak interaction between the drug and nanotube. Doping of the Zn, Cu, Ni, Co, and Fe into the BPNT surface raised the adsorption energy of MF from -5.3 to -29.1, -28.7, -29.8, -32.1, and -26.9 kcal/mol, respectively, demonstrating that the sensitiveness of the metal-doped BPNT increased after increasing the radius atomic of metals. Ultimately, there was an increase in the adhesion performance and capacity of the MF after X (especially Co atom) doping, making the nanotube suitable for MF drug delivery. The mechanism of MF reaction with the BPNT changed from covalent bonding in the natural environment to hydrogen bonding in the cancerous cells with high acidity.
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Affiliation(s)
- Chou-Yi Hsu
- Department of pharmacy, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Manal A Abbood
- Division of Medical and Industrial Materials Science, Department of Applied Sciences, University of Technology, Iraq
| | - Nabeel Kadhim Abbood
- Chemical Engineering and Oil Refining Department, Basrah University for Oil and Gas, Oil and Gas Engineering College, Iraq
| | | | - A H Shather
- Department of Computer Engineering Technology, Al Kitab University, Altun Kopru, Kirkuk, Iraq
| | - Ashwaq Talib Kareem
- Collage of Pharmacy, National University of Science and Technology, Dhi Qa, Iraq
| | | | - Anupam Yadav
- Department of CEA, GLA University, Mathura, India
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Lu Y, Jia Y, Lu J, Liu J, Xu Y, Liu Y, Chen K. Progenies of gestational diabetes mellitus exhibit sex disparity in metabolism after respective therapies of insulin, glibenclamide, and metformin in dams during pregnancy. Arch Physiol Biochem 2024; 130:183-195. [PMID: 34689672 DOI: 10.1080/13813455.2021.1991957] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 09/28/2021] [Accepted: 10/06/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND The aim of this study was to compare the sex-dependent intergenerational effects of insulin, glibenclamide, and metformin on glucose and lipid metabolism in the offspring born to GDM mice. METHODS The murine GDM was induced by high fat diet. The offspring were grouped based on the treatments in maternal mice. ITT and GTT were performed at 4th and 8th weeks of age, respectively. Serum levels of TC, TG, HDL-C, and LDL-C plus hepatic levels of TG and TC, were respectively determined by enzymatic kits. Western blotting was conducted to detect related proteins in the livers from offspring. RESULTS The dyslipidaemia, hepatic lipid abnormality, and insulin insensitivity caused by GDM were persistently normalised in male adult offspring by the respective therapies of insulin, glibenclamide, and metformin during maternal pregnancy. Specifically, the decreases in plasma TC, TG, and LDL-C levels (29%, 37.8%, and 57.7%, respectively, p ˂ .05) and in hepatic lipid contents (TC 31.3% and TG 39.2%, p ˂ .05), the increases in hepatic phosphorylation levels of AKT, CPT1A, PPAR-α, and PPAR-γ (57.1%, 91.7%, 68%, and 173.3%, respectively, p ˂ .05) and the inhibition of G6Pase, PEPCK, and HMGCS1 (35.7%, 68.8%, and 77.3% respectively, p ˂ .05) were still observed in the male offspring born to treated GDM mice from 4th to 8th week of age. Unexpectedly, the aforementioned parameters in female progenies in different groups were not significantly changed compared with controls. CONCLUSIONS Respective treatments in GDM mice during pregnancy with insulin, glibenclamide, and metformin have the long-term persistent effects in male offspring, while female progenies born to untreated dams showed an autonomous inhibition of intergenerational relay of glucose and lipid dysregulation. Our current findings may imply a sex-dependent strategy of medical care for GDM mothers and their offspring.NoveltiesRespective interventions of insulin, glibenclamide, and metformin on dams exerted the persisted effects on male progenies.Therapies of three drugs on dams had the similarly improved effects in offspring.Female offspring autonomously corrected their dysregulated glucose-lipid metabolism caused by gestational diabetes mellitus (GDM) in dams.
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Affiliation(s)
- Yao Lu
- Department of Anesthesiology, the First Affiliated Hospital, Anhui Medical University, Hefei, PR China
| | - Yajing Jia
- Department of Health Inspection and Quarantine, School of Public Health, Anhui Medical University, Hefei, PR China
| | - Jing Lu
- Department of Nutrition and Food Science, School of Public Health, Anhui Medical University, Hefei, PR China
| | - Juan Liu
- Department of Health Inspection and Quarantine, School of Public Health, Anhui Medical University, Hefei, PR China
| | - Yuxin Xu
- Department of Ophthalmology of Second Affiliated Hospital, Anhui Medical University, Hefei, PR China
| | - Yong Liu
- AIER Hefei Eye Hospital Affiliated to Anhui Medical University, Hefei, PR China
| | - Keyang Chen
- Department of Health Inspection and Quarantine, School of Public Health, Anhui Medical University, Hefei, PR China
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Gayatri V, Krishna Prasad M, Mohandas S, Nagarajan S, Kumaran K, Ramkumar KM. Crosstalk between inflammasomes, inflammation, and Nrf2: Implications for gestational diabetes mellitus pathogenesis and therapeutics. Eur J Pharmacol 2024; 963:176241. [PMID: 38043778 DOI: 10.1016/j.ejphar.2023.176241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 11/21/2023] [Accepted: 11/28/2023] [Indexed: 12/05/2023]
Abstract
The role of inflammasomes in gestational diabetes mellitus (GDM) has emerged as a critical area of research in recent years. Inflammasomes, key components of the innate immune system, are now recognized for their involvement in the pathogenesis of GDM. Activation of inflammasomes in response to various triggers during pregnancy can produce pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and interleukin-18 (IL-18), contributing to systemic inflammation and insulin resistance. This dysregulation not only impacts maternal health but also poses significant risks to fetal development and long-term health outcomes. Understanding the intricate interplay between inflammasomes and GDM holds promise for developing novel therapeutic strategies and interventions to mitigate the adverse effects of this condition on both mothers and their offspring. Researchers have elucidated that targeting inflammasomes using anti-inflammatory drugs and compounds can effectively reduce inflammation in GDM. Furthermore, the addition of nuclear factor erythroid 2-related factor 2 (Nrf2) to this complex mechanism opens novel avenues for therapeutics. The antioxidant properties of Nrf2 may potentially suppress inflammasome activation in GDM. This comprehensive review investigates the intricate relationship between inflammasomes and GDM, emphasizing the pivotal role of inflammation in its pathogenesis. It also sheds light on potential therapeutic strategies targeting inflammasome activation and explores the role of Nrf2 in mitigating inflammation in GDM.
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Affiliation(s)
- Vijaya Gayatri
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India
| | - Murali Krishna Prasad
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India
| | - Sundhar Mohandas
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India
| | - Sanjushree Nagarajan
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India
| | - Kriya Kumaran
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India
| | - Kunka Mohanram Ramkumar
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.
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Nachum Z, Perlitz Y, Shavit LY, Magril G, Vitner D, Zipori Y, Weiner E, Alon AS, Ganor-Paz Y, Nezer M, Harel N, Soltsman S, Yefet E. The effect of oral probiotics on glycemic control of women with gestational diabetes mellitus-a multicenter, randomized, double-blind, placebo-controlled trial. Am J Obstet Gynecol MFM 2024; 6:101224. [PMID: 37956906 DOI: 10.1016/j.ajogmf.2023.101224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 10/29/2023] [Accepted: 11/08/2023] [Indexed: 11/21/2023]
Abstract
BACKGROUND Gestational diabetes mellitus should be treated adequately to avoid maternal hyperglycemia-related complications. Previously, probiotic supplements were suggested to improve fasting blood glucose in women with gestational diabetes mellitus. However, a major limitation of previous studies was that preprandial and especially postprandial glucose values, which are important predictors of pregnancy outcomes, were not studied. OBJECTIVE This study aimed to examine the effect of a mixture of probiotic strains on maternal glycemic parameters, particularly preprandial and postprandial glucose values and pregnancy outcomes among women with gestational diabetes mellitus. STUDY DESIGN A multicenter prospective randomized, double-blind, placebo-controlled trial was conducted. Women newly diagnosed with gestational diabetes mellitus were randomly allocated into a research group, receiving 2 capsules of oral probiotic formula containing Bifidobacterium bifidum, B lactis, Lactobacillus acidophilus, L paracasei, L rhamnosus, and Streptococcus thermophilus (>6 × 109/capsule), and a control group, receiving a placebo (2 capsules/day) until delivery. Glycemic control was evaluated by daily glucose charts. After 2 weeks, pharmacotherapy was started in case of poor glycemic control. The primary outcomes were the rate of women requiring medications for glycemic control and mean daily glucose charts after 2 weeks of treatment with the study products. RESULTS Forty-one and 44 women were analyzed in the treatment and placebo cohorts, respectively. Mean daily glucose during the first 2 weeks in the probiotics and placebo groups was 99.7±7.9 and 98.0±9.3 mg/dL, respectively (P=.35). The rate of women needing pharmacotherapy because of poor glycemic control after 2 weeks of treatment in the probiotics and placebo groups was 24 (59%) and 18 (41%), respectively (P=.10). Mean preprandial and postprandial glucose levels throughout the study period were similar between the groups (P>.05). There were no differences in maternal and neonatal outcomes, including birthweight and adverse effect profile between the groups. CONCLUSION The oral probiotic product tested in this study did not affect glycemic control of women with gestational diabetes mellitus.
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Affiliation(s)
- Zohar Nachum
- Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel (Dr Nachum); Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel (Drs Nachum, Vitner, and Zipori)
| | - Yuri Perlitz
- Department of Obstetrics and Gynecology, Tzafon Medical Center, Poriya, Israel (Drs Perlitz, Harel, Soltsman, and Yefet); Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel (Drs Perlitz and Yefet)
| | - Lilach Yacov Shavit
- Diabetes in Pregnancy Clinic, Tzafon Medical Center, Poriya, Israel (Ms Shavit)
| | - Galit Magril
- Nutrition Division, Tzafon Medical Center Poriya, Israel (Ms Magril)
| | - Dana Vitner
- Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel (Drs Nachum, Vitner, and Zipori); Department of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa, Israel (Drs Vitner and Zipori)
| | - Yaniv Zipori
- Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel (Drs Nachum, Vitner, and Zipori); Department of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa, Israel (Drs Vitner and Zipori)
| | - Eran Weiner
- Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel (Drs Weiner, Alon, and Ganor-Paz); Sackler Faculty of Medicine, Tel Aviv university, Tel Aviv, Israel (Drs Weiner, Alon, and Ganor-Paz)
| | - Ayala Shevach Alon
- Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel (Drs Weiner, Alon, and Ganor-Paz); Sackler Faculty of Medicine, Tel Aviv university, Tel Aviv, Israel (Drs Weiner, Alon, and Ganor-Paz)
| | - Yael Ganor-Paz
- Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel (Drs Weiner, Alon, and Ganor-Paz); Sackler Faculty of Medicine, Tel Aviv university, Tel Aviv, Israel (Drs Weiner, Alon, and Ganor-Paz)
| | - Meirav Nezer
- Department of Obstetrics and Gynecology, Samson Assuta Ashdod University Hospital, Ashdod, Israel (Dr Nezer)
| | - Noa Harel
- Department of Obstetrics and Gynecology, Tzafon Medical Center, Poriya, Israel (Drs Perlitz, Harel, Soltsman, and Yefet)
| | - Sofia Soltsman
- Department of Obstetrics and Gynecology, Tzafon Medical Center, Poriya, Israel (Drs Perlitz, Harel, Soltsman, and Yefet)
| | - Enav Yefet
- Department of Obstetrics and Gynecology, Tzafon Medical Center, Poriya, Israel (Drs Perlitz, Harel, Soltsman, and Yefet); Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel (Drs Perlitz and Yefet); Women's Health Center, Clalit Health Services, Afula, Israel (Dr Yefet).
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11
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American Diabetes Association Professional Practice Committee, ElSayed NA, Aleppo G, Bannuru RR, Bruemmer D, Collins BS, Ekhlaspour L, Hilliard ME, Johnson EL, Khunti K, Lingvay I, Matfin G, McCoy RG, Perry ML, Pilla SJ, Polsky S, Prahalad P, Pratley RE, Segal AR, Seley JJ, Stanton RC, Gabbay RA. 15. Management of Diabetes in Pregnancy: Standards of Care in Diabetes-2024. Diabetes Care 2024; 47:S282-S294. [PMID: 38078583 PMCID: PMC10725801 DOI: 10.2337/dc24-s015] [Citation(s) in RCA: 66] [Impact Index Per Article: 66.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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12
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Faraji A, Tahamtani L, Maharlouei N, Asadi N. Effects of oral glibenclamide versus subcutaneous insulin on perinatal outcome of patients with gestational diabetes mellitus: A randomized clinical trial. Obstet Med 2023; 16:98-103. [PMID: 37441660 PMCID: PMC10334033 DOI: 10.1177/1753495x221100167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 01/02/2022] [Indexed: 09/20/2023] Open
Abstract
Background The first-line treatment for gestational diabetes mellitus remains insulin, but oral hypoglycemic agents are easier and cheaper to use. The aim of the current study was to compare the efficacy and safety of oral glibenclamide and subcutaneous insulin on the serum glucose control and perinatal outcome of patients with gestational diabetes mellitus. Materials and methods This randomized clinical trial was conducted during a 2-year period from 2017 to 2019 in two tertiary healthcare centers in Shiraz, Iran. We included 84 singleton pregnancies between 24 and 34 weeks of gestation diagnosed with gestational diabetes mellitus. Patients were randomly assigned to oral glibenclamide (n = 44) or subcutaneous insulin (n = 40) according to a standard protocol and followed until delivery. The primary endpoint was to compare the glycemic level of patients, and the secondary outcomes included pregnancy adverse events and neonatal complications such as preeclampsia, preterm and premature rupture of membranes, preterm labor, placental abruption, maternal hypoglycemia, birth weight, neonatal hypoglycemia, hyperbilirubinemia, respiratory distress syndrome, and neonatal intensive care unit admission. Results The two study groups had comparable baseline characteristics. After treatment, the two study groups were comparable regarding fasting blood glucose (p = 0.398) and 2 h postprandial glucose (p = 0.085). There was no significant difference between the two groups regarding the rate of preeclampsia (p = 0.250), preterm rupture of membranes (p = 0.998), preterm labor (p = 0.495), hypoglycemia (p = 0.476), and abruption (p = 0.815). There was no significant difference between the two study groups in birth weight (p = 0.863) and the Apgar score at 1 (p = 0.190) and 5 min (p = 0.055). The rates of neonatal adverse events including hypoglycemia (p = 0.999), hyperbilirubinemia (p = 0.160), neonatal intensive care unit admission (p = 0.852), and respiratory distress syndrome (p = 0.665) were comparable between the two groups. Conclusion The results of the current study demonstrate that oral glibenclamide is as effective and safe as subcutaneous insulin in glycemic control and maternal and neonatal outcomes in women with gestational diabetes mellitus. Thus, it could be used as first-line treatment of gestational diabetes mellitus.
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Affiliation(s)
- Azam Faraji
- Maternal-Fetal Medicine Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Lida Tahamtani
- Department of Obstetrics and Gynecology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Najmeh Maharlouei
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nasrin Asadi
- Maternal-Fetal Medicine Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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13
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Moke EG, Omogbai EKI, Osagie-Eweka SE, Uchendu AP, Obayuwana OM, Okoro-Akpandu E, Ben-Azu B. Antihypertensive and antihyperglycemic effects of combinations of losartan with metformin and/or glibenclamide in desoxycorticosterone acetate and streptozotocin-induced hypertensive diabetic rats. Lab Anim Res 2023; 39:7. [PMID: 37055870 PMCID: PMC10103437 DOI: 10.1186/s42826-023-00159-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 03/29/2023] [Accepted: 04/10/2023] [Indexed: 04/15/2023] Open
Abstract
BACKGROUND Hypertension is a medical condition that often comorbidly exist in patients with type II diabetes. Therefore, it is very important to manage both conditions simultaneously to mitigate the complications and mortality connected with this comorbidity. Hence, this study investigated the antihypertensive and antihyperglycemic effects of combinations of losartan (LOS) with metformin (MET) and/or glibenclamide (GLB) in hypertensive diabetic rats. Hypertensive diabetic state was induced with desoxycorticosterone acetate (DOCA) and streptozotocin (STZ) in adult Wistar rats. The rats were divided into 5 groups (n = 5): control group (group 1), hypertensive diabetic (HD) control (group 2), treatment groups receiving LOS + MET (group 3), LOS + GLB (group 4), and LOS + MET + GLB (group 5). Group 1 comprised healthy rats while groups 2-5 were HD rats. The rats were treated orally once daily for 8 weeks. Fasted blood glucose (FBS) level, haemodynamic parameters, and some biochemical indices were thereafter assessed. RESULTS FBS level and blood pressure measurements were significantly (P < 0.05) increased following induction by DOCA/STZ. The drug treatment combinations, particularly combination of LOS + MET + GLB, significantly (P < 0.05) reduced the induced hyperglycemia and remarkably decreased systolic blood pressure and heart rate. There was significant (P < 0.05) reduction in raised lactate dehydrogenase and creatinine kinase levels by all drug treatment combinations except LOS + GLB. CONCLUSIONS Our findings suggest that LOS combinations with MET and/or GLB exhibited significant antidiabetic and antihypertensive effects against DOCA/STZ-induced hypertensive diabetic state in rats.
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Affiliation(s)
- Emuesiri Goodies Moke
- Department of Pharmacology, Faculty of Basic Medical Sciences, Delta State University, Abraka, Nigeria.
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Benin City, Nigeria.
| | - Eric Kelly Inanemo Omogbai
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
| | | | - Adaeze Phina Uchendu
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
| | - Odion Martha Obayuwana
- Department of Physiology, School of Basic Medical Sciences, University of Benin, Benin City, Nigeria
| | - Elizabeth Okoro-Akpandu
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
| | - Benneth Ben-Azu
- Department of Pharmacology, Faculty of Basic Medical Sciences, Delta State University, Abraka, Nigeria
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14
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Paschou SA, Bletsa E, Papazisi M, Mili N, Kanouta F, Kassi GN, Psaltopoulou T, Goulis DG, Lambrinoudaki I. Screening and management of major endocrinopathies during pregnancy: an update. Endocrine 2023; 80:10-19. [PMID: 36327019 PMCID: PMC10060311 DOI: 10.1007/s12020-022-03237-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 10/16/2022] [Indexed: 11/06/2022]
Abstract
Endocrinopathies during pregnancy constitute a challenging issue, being prevalent and requiring appropriate management to avoid maternal and fetal complications. This review aims to summarize and present major endocrine problems during pregnancy, the appropriate screening, maternal monitoring and management, fetal monitoring, and follow-up. Glucose metabolism, thyroid function, as well as calcium and vitamin D metabolism are the main endocrine domains that should be screened and monitored during pregnancy. Gestational diabetes mellitus (GDM) is the most prevalent endocrine disease during pregnancy, followed by thyroid disorders. Specific recommendations are provided for the optimal clinical care of pregnant women and their offspring for GDM, thyroid disorders, and calcium and vitamin D disorders.
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Affiliation(s)
- Stavroula A Paschou
- Endocrine Unit and Diabetes Center, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
| | - Evanthia Bletsa
- Third Department of Cardiology, Sotiria Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Papazisi
- School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Nikoletta Mili
- Second Department of Obstetrics and Gynecology, Aretaieion University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Fotini Kanouta
- Department of Endocrinology, Alexandra Hospital, Athens, Greece
| | - Georgia N Kassi
- Department of Endocrinology, Alexandra Hospital, Athens, Greece
| | - Theodora Psaltopoulou
- Endocrine Unit and Diabetes Center, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios G Goulis
- 1st Department of Obstetrics and Gynecology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Irene Lambrinoudaki
- Second Department of Obstetrics and Gynecology, Aretaieion University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
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15
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Arshad M, Arshad S, Majeed MK, Frueh J, Chang C, Bilal I, Niaz SI, Khan MS, Tariq MA, Yasir Mehboob M. Transition Metal-Decorated Mg 12O 12 Nanoclusters as Biosensors and Efficient Drug Carriers for the Metformin Anticancer Drug. ACS OMEGA 2023; 8:11318-11325. [PMID: 37008110 PMCID: PMC10061506 DOI: 10.1021/acsomega.3c00058] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 03/03/2023] [Indexed: 05/11/2023]
Abstract
Drug carriers have been designed and investigated remarkably due to their effective use in the modern medication process. In this study, the decoration of the Mg12O12 nanocluster has been done with transition metals (Ni and Zn) for effective adsorption of metformin (anticancer drug). Decoration of Ni and Zn on a nanocluster allows two geometries, and similarly, the adsorption of metformin also provides two geometries. Density functional theory and time-dependent density functional theory have been employed at the B3LYP with 6-311G(d,p) level. The decoration of Ni and Zn offers good attachment and detachment of the drug, which is observed from their good adsorption energy values. Further, the reduction in the energy band gap is noted in the metformin-adsorbed nanocluster, which allows high charge transfer from a lower energy level to a high energy level. The drug carrier systems show an efficient working mechanism in a water solvent with the visible-light absorption range. Natural bonding orbital and dipole moment values suggested that the adsorption of the metformin causes charge separation in these systems. Moreover, low values of chemical softness with a high electrophilic index recommended that these systems are naturally stable with the least reactivity. Thus, we offer novel kinds of Ni- and Zn-decorated Mg12O12 nanoclusters as efficient carriers for metformin and also recommend them to experimentalists for the future development of drug carriers.
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Affiliation(s)
- Muhammad Arshad
- Institute
of Chemical Sciences, Gomal University, 29050 Dera Ismail Khan, KPK, Pakistan
| | - Shafia Arshad
- University
College of Conventional Medicine, Faculty of Medicine and Allied Health
Sciences, The Islamia University Bahawalpur, Bahawalpur, Punjab 63100, Pakistan
| | - Muhammad K. Majeed
- Department
of Materials Science and Engineering, The
University of Texas at Arlington, Arlington 76019, Texas, United States
| | - Johannes Frueh
- Tomsk
Polytechnic University, 30 Lenin Avenue, 634050 Tomsk, Russian Federation
- Institute
of Medicine and Health, Harbin Institute of Technology, 150080 Harbin, P. R. China
| | - Chun Chang
- College of
Environment and Chemical Engineering, Dalian
University, Dalian, Liaoning 116622, China
| | - Ibtsam Bilal
- Faculty
of Life Sciences, Department of Biochemistry, University of Okara, Okara, Punjab 56300, Pakistan
| | - Shah Iram Niaz
- Institute
of Chemical Sciences, Gomal University, 29050 Dera Ismail Khan, KPK, Pakistan
| | - Muhammad Shahzeb Khan
- Sulaiman
Bin Abdullah Aba Al-Khail Centre for Interdisciplinary Research in
Basic Sciences (SA-CIRBS), Faculty of Basic and Applied Sciences, International Islamic University Islamabad, Islamabad 44000, Pakistan
| | | | - Muhammad Yasir Mehboob
- Department
of Chemistry, University of Okara, Okara, Punjab 56300, Pakistan
- . Tel.: +92-303-8670504
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16
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Lee SR, Jeong SH, Mukae M, Kim SY, Ko JW, Kwun HJ, Hong EJ. Dietary supplementation with nicotinamide riboside improves fetal growth under hypoglycemia. J Nutr Biochem 2023; 116:109310. [PMID: 36871839 DOI: 10.1016/j.jnutbio.2023.109310] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 09/18/2022] [Accepted: 02/27/2023] [Indexed: 03/07/2023]
Abstract
Nicotinamide riboside (NR) is considered a super-supplement that prevents obesity and diabetes. While NR has been investigated for various effects depending on nutritional conditions, metabolic research on women and pregnant women has rarely been discussed. In this study, we focused on the glycemic control of NR in females and found the protective role of NR in pregnant animals under hypoglycemic conditions. Metabolic-tolerance tests were performed in vivo under progesterone (P4) exposure after ovariectomy (OVX). NR enhanced resistance to energy deprivation and showed a slight increase in gluconeogenesis in naïve control mice. However, NR reduced hyperglycemia and significantly induced gluconeogenesis in OVX mice. While NR reduced hyperglycemia in the P4-treated OVX mice, it reduced insulin response and substantially increased gluconeogenesis. Similar to animal experiments, NR increased gluconeogenesis and mitochondrial respiration in Hep3B cells. The gluconeogenic function of NR is mediated by tricarboxylic acid cycle (TCA) cycle enrichment, as residual pyruvate could induce gluconeogenesis. NR recovered fetal growth by increasing blood glucose levels when hypoglycemia was induced by diet-restriction during pregnancy. Our study revealed the glucose-metabolic function of NR in hypoglycemic pregnant animals, suggesting NR as a dietary supplement to improve fetal growth. Because diabetic women suffer from hypoglycemia due to insulin therapy, NR has therapeutic potential for use as a glycemic control pill.
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Affiliation(s)
- Sang R Lee
- College of Veterinary Medicine, Chungnam National University, Daejeon Republic of Korea
| | - Su Hee Jeong
- College of Veterinary Medicine, Chungnam National University, Daejeon Republic of Korea
| | - Moeka Mukae
- College of Veterinary Medicine, Chungnam National University, Daejeon Republic of Korea
| | - Sang-Yun Kim
- College of Veterinary Medicine, Chungnam National University, Daejeon Republic of Korea; Reproductive Toxicology Research Group, Korea Institute of Toxicology, Daejeon, Republic of Korea
| | - Je-Won Ko
- College of Veterinary Medicine, Chungnam National University, Daejeon Republic of Korea
| | - Hyo-Jung Kwun
- College of Veterinary Medicine, Chungnam National University, Daejeon Republic of Korea
| | - Eui-Ju Hong
- College of Veterinary Medicine, Chungnam National University, Daejeon Republic of Korea.
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17
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ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Jeffrie Seley J, Stanton RC, Gabbay RA, on behalf of the American Diabetes Association. 15. Management of Diabetes in Pregnancy: Standards of Care in Diabetes-2023. Diabetes Care 2023; 46:S254-S266. [PMID: 36507645 PMCID: PMC9810465 DOI: 10.2337/dc23-s015] [Citation(s) in RCA: 172] [Impact Index Per Article: 86.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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18
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Abstract
Gestational diabetes mellitus (GDM) traditionally refers to abnormal glucose tolerance with onset or first recognition during pregnancy. GDM has long been associated with obstetric and neonatal complications primarily relating to higher infant birthweight and is increasingly recognized as a risk factor for future maternal and offspring cardiometabolic disease. The prevalence of GDM continues to rise internationally due to epidemiological factors including the increase in background rates of obesity in women of reproductive age and rising maternal age and the implementation of the revised International Association of the Diabetes and Pregnancy Study Groups' criteria and diagnostic procedures for GDM. The current lack of international consensus for the diagnosis of GDM reflects its complex historical evolution and pragmatic antenatal resource considerations given GDM is now 1 of the most common complications of pregnancy. Regardless, the contemporary clinical approach to GDM should be informed not only by its short-term complications but also by its longer term prognosis. Recent data demonstrate the effect of early in utero exposure to maternal hyperglycemia, with evidence for fetal overgrowth present prior to the traditional diagnosis of GDM from 24 weeks' gestation, as well as the durable adverse impact of maternal hyperglycemia on child and adolescent metabolism. The major contribution of GDM to the global epidemic of intergenerational cardiometabolic disease highlights the importance of identifying GDM as an early risk factor for type 2 diabetes and cardiovascular disease, broadening the prevailing clinical approach to address longer term maternal and offspring complications following a diagnosis of GDM.
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Affiliation(s)
- Arianne Sweeting
- Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, Australia
| | - Jencia Wong
- Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, Australia
| | - Helen R Murphy
- Diabetes in Pregnancy Team, Cambridge University Hospitals, Cambridge, UK
- Norwich Medical School, Bob Champion Research and Education Building, University of East Anglia, Norwich, UK
- Division of Women’s Health, Kings College London, London, UK
| | - Glynis P Ross
- Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, Australia
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19
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Kamali F, Ebrahimzadeh-Rajaei G, Mohajeri S, Shamel A, Khodadadi-Moghaddam M. A computational design of X24Y24 (X = B, Al, and Y = N, P) nanoclusters as effective drug carriers for metformin anticancer drug: A DFT insight. INORG CHEM COMMUN 2022. [DOI: 10.1016/j.inoche.2022.109527] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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20
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Teague TT, Payne SR, Kelly BT, Dempsey TM, McCoy RG, Sangaralingham LR, Limper AH. Evaluation for clinical benefit of metformin in patients with idiopathic pulmonary fibrosis and type 2 diabetes mellitus: a national claims-based cohort analysis. Respir Res 2022; 23:91. [PMID: 35410255 PMCID: PMC9004115 DOI: 10.1186/s12931-022-02001-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 03/21/2022] [Indexed: 12/27/2022] Open
Abstract
Background Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with high morbidity and limited treatment options. Type 2 diabetes mellitus (T2DM) is a common comorbid illness among patients with IPF and is often treated with metformin, the first-line agent in the management of T2DM. There is growing evidence demonstrating metformin’s anti-fibrotic properties; however, there is little real-world clinical data regarding its potential effectiveness in IPF. This study aims to evaluate the clinical benefit of metformin in patients with IPF and T2DM. Methods This nationwide cohort study used de-identified administrative claims data from OptumLabs® Data Warehouse to identify 3599 adults with IPF and concomitant T2DM between January 1, 2014 and June 30, 2019. Two cohorts were created: a cohort treated with metformin (n = 1377) and a cohort not treated with metformin (n = 2222). A final 1:1 propensity score-matched cohort compared 1100 patients with IPF and T2DM receiving metformin to those with both diagnoses but not receiving metformin; matching accounted for age, sex, race/ethnicity, residence region, year, medications, oxygen use, smoking status, healthcare use, and comorbidities. Outcomes were all-cause mortality (primary) and hospitalizations (secondary). Results Among 2200 patients with IPF and T2DM included in this matched analysis, metformin therapy was associated with a reduction in all-cause mortality (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.36–0.58; p < 0.001) and hospitalizations (HR, 0.82; 95% CI, 0.72–0.93; p = 0.003) compared to patients not receiving metformin. Conclusions Among patients with IPF and T2DM, metformin therapy may be associated with improved clinical outcomes. However, further investigation with randomized clinical trials is necessary prior to metformin’s broad implementation in the clinical management of IPF.
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21
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Li C, Gao C, Zhang X, Zhang L, Shi H, Jia X. Comparison of the effectiveness and safety of insulin and oral hypoglycemic drugs in the treatment of gestational diabetes mellitus: a meta-analysis of 26 randomized controlled trials. Gynecol Endocrinol 2022; 38:303-309. [PMID: 34907818 DOI: 10.1080/09513590.2021.2015761] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE Oral hypoglycemic drugs for the treatment of gestational diabetes mellitus (GDM) are still controversial because they can pass through the placenta. The purpose of this meta-analysis is to evaluate the safety and effectiveness of oral hypoglycemic drugs. METHODS PubMed, Ovid Embase, Web of Science, and Cochrane databases were systematically searched (inception to 20 April 2021). Rev Man 5.0 was used to analyze the data. A random-effects model was used to compute the summary risk estimates. RESULTS There were 26 randomized controlled trials (RCTs) involving 4921 GDM patients which were included in this meta-analysis. Compared with metformin, insulin had a significant increase in the risk of preeclampsia (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.06 to 2.45; I2=40%; p < .05), hypertension (OR, 1.42; 95% CI, 1.02 to 1.99; I2=0%; p < .05), hypoglycemia (OR, 3.93; 95% CI, 1.27 to 12.19; I2=0%; p < .05), neonatal hypoglycemia (OR, 1.92; 95% CI, 1.34 to 2.76; I2=41%; p < .0001), neonatal jaundice (OR, 2.70; 95% CI, 1.12 to 6.52; I2=0%; p < .05), and Neonatal Intensive Care Unit Admission (OR, 1.46; 95% CI, 1.09 to 1.95; I2=39%; p < .05), but the risk of neonatal macrosomia (OR, 1.67; 95% CI, 1.12 to 2.40; I2=0%; p < .05) and neonatal injury (OR, 0.70; 95% CI, 0.55 to 0.89; I2=0%; p < .01) is lower. CONCLUSIONS Metformin is comparable with insulin in glycemic control and neonatal outcomes and has the potential to replace insulin therapy in clinical practice. Glyburide is behind metformin and insulin, and more RCTs are needed to verify its safety.
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Affiliation(s)
- Chaolin Li
- Sichuan Chengdu Jinniu District Maternal and Child Healthcare Hospital, Chengdu, China
- Non-coding RNA and Drug Discovery Key Laboratory of Sichuan Province, Chengdu Medical College, Chengdu, China
| | - Can Gao
- Key Laboratory of Microbial Drugs Innovation and Transformation, Medical College, Yan'an University, Yan'an, China
| | - Xianqin Zhang
- Non-coding RNA and Drug Discovery Key Laboratory of Sichuan Province, Chengdu Medical College, Chengdu, China
- Basic Medical College, Chengdu Medical College, Chengdu, China
| | - Lin Zhang
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
- Department of Pharmacy, Shaoxing People's Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, China
| | - Hao Shi
- Sichuan Chengdu Jinniu District Maternal and Child Healthcare Hospital, Chengdu, China
| | - Xu Jia
- Non-coding RNA and Drug Discovery Key Laboratory of Sichuan Province, Chengdu Medical College, Chengdu, China
- Basic Medical College, Chengdu Medical College, Chengdu, China
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22
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Tocantins C, Diniz MS, Grilo LF, Pereira SP. The birth of cardiac disease: Mechanisms linking gestational diabetes mellitus and early onset of cardiovascular disease in offspring. WIREs Mech Dis 2022; 14:e1555. [PMID: 35304833 DOI: 10.1002/wsbm.1555] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Revised: 02/10/2022] [Accepted: 03/09/2022] [Indexed: 12/12/2022]
Abstract
Cardiovascular disease (CVD) is the biggest killer worldwide, composing a major economic burden for health care systems. Obesity and diabetes are dual epidemics on the rise and major risk factors predisposing for CVD. Increased obesity- and diabetes-related incidence is now observed among children, adolescents, and young adults. Gestational diabetes mellitus (GDM) is the most common metabolic pregnancy disorder, and its prevalence is rapidly increasing. During pregnancies complicated by GDM, the offspring are exposed to a compromised intrauterine environment characterized by hyperglycemic periods. Unfavorable in utero conditions at critical periods of fetal cardiac development can produce developmental adaptations that remodel the cardiovascular system in a way that can contribute to adult-onset of heart disease due to the programming during fetal life. Epidemiological studies have reported increased cardiovascular complications among GDM-descendants, highlighting the urgent need to investigate and understand the mechanisms modulated during fetal development of in utero GDM-exposed offspring that predispose an individual to increased CVD during life. In this manuscript, we overview previous studies in this area and gather evidence linking GDM and CVD development in the offspring, providing new insights on novel mechanisms contributing to offspring CVD programming by GDM, from the role of maternal-fetal interactions to their impact on fetal cardiovascular development, how the perpetuation of cardiac programming is maintained in postnatal life, and advance the intergenerational implications contributing to increased CVD premature origin. Understanding the perpetuation of CVD can be the first step to manage and reverse this leading cause of morbidity and mortality. This article is categorized under: Reproductive System Diseases > Molecular and Cellular Physiology Cardiovascular Diseases > Molecular and Cellular Physiology Metabolic Diseases > Genetics/Genomics/Epigenetics.
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Affiliation(s)
- Carolina Tocantins
- CNC-Center for Neuroscience and Cell Biology, CIBB-Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal
| | - Mariana S Diniz
- CNC-Center for Neuroscience and Cell Biology, CIBB-Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal
| | - Luís F Grilo
- CNC-Center for Neuroscience and Cell Biology, CIBB-Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal.,PhD Programme in Experimental Biology and Biomedicine (PDBEB), Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal
| | - Susana P Pereira
- CNC-Center for Neuroscience and Cell Biology, CIBB-Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal.,Laboratory of Metabolism and Exercise (LametEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, Porto, Portugal
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Zera CA, Seely EW. Controversies in Gestational Diabetes. TOUCHREVIEWS IN ENDOCRINOLOGY 2022; 17:102-107. [PMID: 35118455 DOI: 10.17925/ee.2021.17.2.102] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 02/23/2021] [Indexed: 11/24/2022]
Abstract
Gestational diabetes mellitus (GDM) complicates approximately 7% of pregnancies in the USA. Despite recognition of the benefits of diagnosing and treating GDM, there are several areas of controversy that remain unresolved. There is debate as to whether to screen for GDM with the one-step versus the two-step approach. While the former identifies more pregnancies with potential adverse outcomes, data are lacking as to whether treatment of these pregnancies will improve outcomes, while increasing costs by diagnosing more women. Though it is well established that the diagnosis of even mild GDM, and treatment with lifestyle recommendations and insulin, improves pregnancy outcomes, it is controversial as to which type and regimen of insulin is optimal, and whether oral agents can be used safely and effectively to control glucose levels. Finally, it is recommended that women with GDM get tested for type 2 diabetes within several months of delivery; however, many women do not undergo this testing and alternative approaches are needed. These controversies are discussed with data from both sides of the debate to enable clinicians to make patient-centered decisions until more definitive data are available.
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Affiliation(s)
- Chloe A Zera
- Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA, USA.,Harvard Medical School, Boston, MA, USA
| | - Ellen W Seely
- Harvard Medical School, Boston, MA, USA.,Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
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24
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Oliveira MMD, Andrade KFDO, Lima GHS, Rocha TC. Metformin versus glyburide in treatment and control of gestational diabetes mellitus: a systematic review with meta-analysis. EINSTEIN-SAO PAULO 2022; 20:eRW6155. [PMID: 35195193 PMCID: PMC8809654 DOI: 10.31744/einstein_journal/2022rw6155] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 04/09/2021] [Indexed: 12/22/2022] Open
Abstract
Objective Methods Results Conclusion
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25
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American Diabetes Association Professional Practice Committee. 15. Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes-2022. Diabetes Care 2022; 45:S232-S243. [PMID: 34964864 DOI: 10.2337/dc22-s015] [Citation(s) in RCA: 134] [Impact Index Per Article: 44.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc22-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc22-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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26
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Mercado-Méndez S, González-Sepúlveda L, Romaguera J, González-Rodríguez LA. The Use of Oral Hypoglycemic Agents during Pregnancy: An Alternative to Insulin? PUERTO RICO HEALTH SCIENCES JOURNAL 2021; 40:162-167. [PMID: 35077074 PMCID: PMC9048127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
OBJECTIVE Gestational Diabetes Mellitus (GDM) and Type 2 Diabetes Mellitus (DM2) are metabolic disorders characterized by increased insulin resistance. Although insulin is the treatment of choice in pregnant patients with DM, the prescription of oral hypoglycemic agents (OHA) has been increasing among practitioners. This study aimed to evaluate the maternal and neonatal outcomes when oral hypoglycemic agents were used in diabetic pregnant women. METHODS Medical records from the Maternal-Infant Care Unit Clinics SoM-UPR (n=149) were reviewed. Patients that were treated with metformin, sulfonylurea or insulin were included. Maternal and neonatal outcomes were compared between groups. RESULTS Patient's mean age was 28 ± 6 years. The majority had GDM (91%). The most common comorbidity was hypertension (9.9%). Lifestyle modification was used as treatment in 77% of patients during the second trimester, but its use decreased to 33% during the third trimester. Insulin was the treatment of choice. Among the OHA, sulfonylurea was preferred. Postprandial glucose levels were lower in patients who used insulin as compared to those without medications. CONCLUSION No significant differences were found in maternal outcomes such as C-section, induction of labor, episiotomy or preterm labor, or neonatal outcomes such as macrosomia, neonatal hypoglycemia or congenital abnormalities among treatment groups. OHA can be considered as an alternative to insulin for the treatment of DM during pregnancy in selected cases.
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Affiliation(s)
- Sheila Mercado-Méndez
- University of Puerto Rico School of Medicine – Department of Medicine - Endocrinology, Diabetes and Metabolism Division
| | - Lorena González-Sepúlveda
- Puerto Rico Clinical and Translational Research Consortium, University of Puerto Rico Medical Sciences Campus
| | - Josefina Romaguera
- University of Puerto Rico School of Medicine – Department of Obstetrics and Gynecology
| | - Loida A. González-Rodríguez
- University of Puerto Rico School of Medicine – Department of Medicine - Endocrinology, Diabetes and Metabolism Division
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27
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Zhang L, Yu X, Wu Y, Fu H, Xu P, Zheng Y, Wen L, Yang X, Zhang F, Hu M, Wang H, Liu X, Qiao J, Peng C, Gao R, Saffery R, Fu Y, Qi H, Tong C, Kilby MD, Baker PN. Gestational Diabetes Mellitus-Associated Hyperglycemia Impairs Glucose Transporter 3 Trafficking in Trophoblasts Through the Downregulation of AMP-Activated Protein Kinase. Front Cell Dev Biol 2021; 9:722024. [PMID: 34796169 PMCID: PMC8593042 DOI: 10.3389/fcell.2021.722024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 10/08/2021] [Indexed: 12/25/2022] Open
Abstract
AMP-activated protein kinase (AMPK) is an important regulator of glucose metabolism, and glucose transporter 3 (GLUT3) is an efficient glucose transporter in trophoblasts. Whether placental AMPK and GLUT3 respond accordingly to gestational diabetes mellitus (GDM) remains uncertain. Here, we explored the regulatory role of AMPK in the GLUT3-dependent uptake of glucose by placental trophoblasts and the viability of the cells. In this study, the level of glycolysis in normal and GDM-complicated placentas was assessed by LC-MS/MS. The trophoblast hyperglycemia model was induced by the incubation of HTR8/SVneo cells with a high glucose concentration. GDM animal models were generated with db/ + mice and C57BL/6J mice fed a high-fat diet, and AMPK was manipulated by the oral administration of metformin. The uptake of glucose by trophoblasts was assessed using 2-NBDG or 2-deoxy-D-[3H] glucose. The results showed that GDM is associated with impaired glycolysis, AMPK activity, GLUT3 expression in the plasma membrane (PM) and cell survival in the placenta. Hyperglycemia induced similar changes in trophoblasts, and these changes were rescued by AMPK activation. Both hyperglycemic db/ + and high-fat diet-induced GDM mice exhibited a compromised AMPK–GLUT3 axis and suppressed cell viability in the placenta as well as excessive fetal growth, and all of these effects were partially alleviated by metformin. Taken together, our findings support the notion that AMPK activation upregulates trophoblast glucose uptake by stimulating GLUT3 translocation, which is beneficial for viability. Thus, the modulation of glucose metabolism in trophoblasts by targeting AMPK might ameliorate the adverse intrauterine environment caused by GDM.
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Affiliation(s)
- Li Zhang
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, China.,International Collaborative Laboratory of Reproduction and Development of the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Xinyang Yu
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, China.,International Collaborative Laboratory of Reproduction and Development of the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Yue Wu
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, China.,International Collaborative Laboratory of Reproduction and Development of the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Huijia Fu
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, China.,International Collaborative Laboratory of Reproduction and Development of the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Ping Xu
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,Department of Biochemistry and Molecular Biology, University of Texas McGovern Medical School, Houston, TX, United States
| | - Yangxi Zheng
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,Department of Biochemistry and Molecular Biology, University of Texas McGovern Medical School, Houston, TX, United States.,Department of Stem Cell Transplantation and Cell Therapy, MD Anderson Cancer Center, Houston, TX, United States
| | - Li Wen
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, China.,International Collaborative Laboratory of Reproduction and Development of the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Xiaotao Yang
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, China.,International Collaborative Laboratory of Reproduction and Development of the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Fumei Zhang
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, China.,International Collaborative Laboratory of Reproduction and Development of the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Mingyu Hu
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, China.,International Collaborative Laboratory of Reproduction and Development of the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Hao Wang
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, China.,International Collaborative Laboratory of Reproduction and Development of the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Xiyao Liu
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, China.,International Collaborative Laboratory of Reproduction and Development of the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Juan Qiao
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, China.,International Collaborative Laboratory of Reproduction and Development of the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Chuan Peng
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, China
| | - Rufei Gao
- International Collaborative Laboratory of Reproduction and Development of the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.,Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, China
| | - Richard Saffery
- International Collaborative Laboratory of Reproduction and Development of the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.,Department of Paediatrics, Cancer, Disease and Developmental Epigenetics, Murdoch Children's Research Institute, University of Melbourne, Parkville, VIC, Australia
| | - Yong Fu
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, China.,International Collaborative Laboratory of Reproduction and Development of the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Hongbo Qi
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, China.,International Collaborative Laboratory of Reproduction and Development of the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Chao Tong
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, China.,International Collaborative Laboratory of Reproduction and Development of the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Mark D Kilby
- International Collaborative Laboratory of Reproduction and Development of the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.,Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom
| | - Philip N Baker
- International Collaborative Laboratory of Reproduction and Development of the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.,College of Life Sciences, University of Leicester, Leicester, United Kingdom
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Hay H, Ivy D, Zolfaghari K. Prescribing patterns and outcomes among patients treated for gestational diabetes mellitus. Proc AMIA Symp 2021; 35:172-175. [DOI: 10.1080/08998280.2021.2000845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Affiliation(s)
- Heather Hay
- Department of Pharmacy Practice, Texas A&M University Irma Lerma Rangel College of Pharmacy and Baylor Scott and White Health, Georgetown, Texas
| | - Delaney Ivy
- Department of Pharmacy Practice, Texas A&M University Irma Lerma Rangel College of Pharmacy and Baylor Scott and White Health, Georgetown, Texas
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Yu DQ, Xu GX, Teng XY, Xu JW, Tang LF, Feng C, Rao JP, Jin M, Wang LQ. Glycemic control and neonatal outcomes in women with gestational diabetes mellitus treated using glyburide, metformin, or insulin: a pairwise and network meta-analysis. BMC Endocr Disord 2021; 21:199. [PMID: 34641848 PMCID: PMC8513183 DOI: 10.1186/s12902-021-00865-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 09/24/2021] [Indexed: 02/06/2023] Open
Abstract
AIMS We aimed to assess the comparative efficiency and safety of the use of glyburide, metformin, and insulin in gestational diabetes mellitus (GDM). METHODS We searched for randomized controlled trials that compared glyburide, metformin, and insulin in GDM. Data regarding glycemic control and neonatal safety were collected and analyzed in pairwise and network meta-analyses. RESULTS A total of 4533 individuals from 23 trials were included. Compared with glyburide, metformin reduced 2-h postprandial blood glucose (2HPG) to a greater extent (standard mean difference (SMD) 0.18; 95% credible interval (CI) 0.01, 0.34). There were significantly lower prevalence of neonatal hypoglycemia (risk difference (RD) - 0.07; 95%CI - 0.11, - 0.02) and preeclampsia (RD - 0.03; 95%CI - 0.06, 0) in the metformin group than in the insulin group. The metformin group had significantly lower birth weight (SMD - 0.17; 95%CI - 0.25, - 0.08) and maternal weight gain (SMD - 0.61; 95%CI - 0.86,- 0.35) compared with the insulin group. Network meta-analysis suggested that metformin had the highest probability of successfully controlling glycemia and preventing neonatal complications. CONCLUSIONS The present meta-analysis suggests that metformin may be as effective as insulin for glycemic control and is the most promising drug for the prevention of neonatal and maternal complications.
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Affiliation(s)
- Dan-Qing Yu
- The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Rd, Zhejiang, 310009, Hangzhou, China
| | - Guan-Xin Xu
- The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Rd, Zhejiang, 310009, Hangzhou, China
| | - Xin-Yuan Teng
- The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Rd, Zhejiang, 310009, Hangzhou, China
| | - Jing-Wei Xu
- The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Rd, Zhejiang, 310009, Hangzhou, China
| | - Liang-Fang Tang
- The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Rd, Zhejiang, 310009, Hangzhou, China
| | - Chun Feng
- The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Rd, Zhejiang, 310009, Hangzhou, China
| | - Jin-Peng Rao
- The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Rd, Zhejiang, 310009, Hangzhou, China
| | - Min Jin
- The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Rd, Zhejiang, 310009, Hangzhou, China
| | - Li-Quan Wang
- The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Rd, Zhejiang, 310009, Hangzhou, China.
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30
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Ouyang H, Wu N. Effects of Different Glucose-Lowering Measures on Maternal and Infant Outcomes in Pregnant Women with Gestational Diabetes: A Network Meta-analysis. Diabetes Ther 2021; 12:2715-2753. [PMID: 34482529 PMCID: PMC8479018 DOI: 10.1007/s13300-021-01142-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 08/09/2021] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION A network meta-analysis was conducted to compare and rank the effects of different glucose-lowering measures on maternal and infant outcomes in pregnant women with gestational diabetes mellitus (GDM). METHODS We searched the PubMed, CNKI, Embase, Cochrane Library, Wanfang, and Weipu databases for relevant studies published between database establishment and June 2021. Study retrieval involved subject-heading and keyword searches. Randomized controlled trials (RCTs) with different glucose-lowering treatments for GDM patients were included. The Cochrane tool was used to assess bias risk. Pairwise and network meta-analyses were used to compare and rank the effects of different hypoglycemic measures on maternal and infant outcomes in pregnant women with GDM. RESULTS We included 41 RCTs involving 6245 pregnant women with GDM. Patients treated with insulin had a higher incidence of neonatal intensive care unit (NICU) occupancy (1.3, 95% CI 1.0-1.7) than those treated with metformin. The insulin (1.5, 95% CI 1.1-2.1 and 1.8, 95% CI 1.0-3.3) and glyburide (2.0, 95% CI 1.2-3.2 and 2.5, 95% CI 1.1-8.4) groups exhibited higher incidences of neonatal hypoglycemia and large for gestational age (LGA) newborns than the metformin group. The glyburide group exhibited a lower probability of cesarean section than the metformin (0.76, 95% CI 0.55-1.0) and insulin (0.71, 95% CI 0.52-0.96) groups. Preeclampsia incidence in the diet and exercise groups was significantly lower than in the metformin (0.19, 95% CI 0.043-0.72) and insulin (0.15, 95% CI 0.032-0.52) groups. No intervention significantly reduced the incidences of macrosomia, preterm birth, gestational hypertension, or respiratory distress syndrome (RDS). The ranking results showed that the metformin group had the lowest rates of neonatal hypoglycemia, macrosomia, LGA, and NICU occupancy. The glyburide group had the lowest NICU occupancy and cesarean section rates and the highest neonatal hypoglycemia, LGA, preeclampsia, and gestational hypertension rates. The diet and exercise group had the lowest preterm delivery and preeclampsia rates and the highest NICU occupancy rate. CONCLUSION Metformin is a potentially superior choice for GDM treatment because it is associated with minimal incidences of multiple adverse pregnancy outcome indicators and does not lead to high values of certain adverse outcome indices. Other hypoglycemic agent or diet groups exhibit high incidences of certain adverse outcomes. Therefore, when selecting a GDM treatment strategy, the efficacies and risks of different treatment programs should be evaluated according to the scenario in hand.
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Affiliation(s)
- Hong Ouyang
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Na Wu
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, China.
- Clinical Skills Practice Teaching Center, Shengjing Hospital of China Medical University, Shenyang, China.
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31
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Tarry-Adkins JL, Ozanne SE, Aiken CE. Impact of metformin treatment during pregnancy on maternal outcomes: a systematic review/meta-analysis. Sci Rep 2021; 11:9240. [PMID: 33927270 PMCID: PMC8085032 DOI: 10.1038/s41598-021-88650-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 04/09/2021] [Indexed: 02/02/2023] Open
Abstract
We systematically assessed the impact of metformin treatment on maternal pregnancy outcomes. PubMed, Ovid Embase, Medline, Web of Science, ClinicalTrials.gov and Cochrane databases were systematically searched (inception-1st February 2021). Randomised controlled trials reporting pregnancy outcomes in women randomised to metformin versus any other treatment for any indication were included. Outcomes included gestational weight gain (GWG), pre-eclampsia, gestational hypertension, preterm birth, gestational age at delivery, caesarean section, gestational diabetes, glycaemic control, and gastrointestinal side-effects. Two independent reviewers conducted screening, with a third available to evaluate disagreements. Risk-of-bias and GRADE assessments were conducted using Cochrane Risk-of-Bias and GRADE-pro software. Thirty-five studies (n = 8033 pregnancies) met eligibility criteria. GWG was lower in pregnancies randomised to metformin versus other treatments (1.57 kg ± 0.60 kg; I2 = 86%, p < 0.0001), as was likelihood of pre-eclampsia (OR 0.69, 95% CI 0.50-0.95; I2 = 55%, p = 0.02). The risk of gastrointestinal side-effects was greater in metformin-exposed versus other treatment groups (OR 2.43, 95% CI 1.53-3.84; I2 = 76%, p = 0.0002). The risk of other maternal outcomes assessed was not significantly different between metformin-exposed versus other treatment groups. Metformin for any indication during pregnancy is associated with lower GWG and a modest reduced risk of pre-eclampsia, but increased gastrointestinal side-effects compared to other treatments.
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Affiliation(s)
- Jane L. Tarry-Adkins
- grid.5335.00000000121885934Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK ,grid.5335.00000000121885934Department of Obstetrics and Gynaecology, The Rosie Hospital and NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK
| | - Susan E. Ozanne
- grid.5335.00000000121885934Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK
| | - Catherine E. Aiken
- grid.5335.00000000121885934Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK ,grid.5335.00000000121885934Department of Obstetrics and Gynaecology, The Rosie Hospital and NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK
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Kousta E, Kontogeorgi A, Robinson S, Johnston DG. Long-Term Metabolic Consequences in Patients with a History of Gestational Diabetes. Curr Pharm Des 2021; 26:5564-5572. [PMID: 33155900 DOI: 10.2174/1381612826666201106092423] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 08/15/2020] [Indexed: 11/22/2022]
Abstract
Gestational diabetes mellitus is a common metabolic complication of pregnancy. Universal guidelines on gestational diabetes have been impeded by the long-term controversies on its definition and screening strategies. The prevalence of gestational diabetes is rising all over the world, is significantly influenced by ethnicity and its rise is mainly attributed to increasing maternal obesity and age. Gestational diabetes mellitus has important long-term implications, including gestational diabetes recurrence, increased risk for developing type 2 diabetes, metabolic syndrome and cardiovascular disease for the mother. Gestational diabetes mellitus may be viewed as a chronic metabolic disorder that is identified in women during gestation and may provide a unique opportunity for the early identification and primary prevention of type 2 diabetes mellitus and cardiovascular disease in these women. In this mini-review, the evolution of screening tests for gestational diabetes and guidelines are briefly described and metabolic and cardiovascular long-term consequences of women with a history of gestational diabetes are summarized. A summary of our own St. Mary's Hospital-UK Research series on long-term metabolic consequences of 368 women with a history of gestational diabetes of 3 different ethnic groups and 482 control women is also included. We found that approximately 2 years following delivery, 37% of women with a history of gestational diabetes had abnormal glucose concentrations, but, most importantly, even those who were normoglycaemic, postpartum displayed metabolic abnormalities on detailed testing. Future research needs to focus on the prevention of gestational diabetes long-term complications, but also in identification of pre-pregnancy predictors and risk reduction before conception.
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Affiliation(s)
- Eleni Kousta
- Research in Female Reproduction Postgraduate Course, National and Kapodistrian University of Athens Medical School, Athens, Greece
| | - Adamantia Kontogeorgi
- Research in Female Reproduction Postgraduate Course, National and Kapodistrian University of Athens Medical School, Athens, Greece
| | - Stephen Robinson
- Division of Diabetes, Endocrinology and Metabolism, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom
| | - Desmond G Johnston
- Division of Diabetes, Endocrinology and Metabolism, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom
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Regassa LD, Tola A. Magnitude and predictors of hospital admission, readmission, and length of stay among patients with type 2 diabetes at public hospitals of Eastern Ethiopia: a retrospective cohort study. BMC Endocr Disord 2021; 21:74. [PMID: 33866969 PMCID: PMC8054433 DOI: 10.1186/s12902-021-00744-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 04/12/2021] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND Type 2 Diabetes (T2D) represents one of the leading causes for hospital admissions and outpatient visits. Hence, T2D continuously imposes a significant burden to healthcare systems. The aim of this study was to assess predictors of hospital admission, readmission rates, and length of hospital stay among T2D patients in government hospitals of Eastern Ethiopia from 2013 to 2017. METHODS This study utilized retrospective data from a cohort of T2D patients following their treatment in government hospitals in Harari regional state of Ethiopia. Predictor of hospital admission was determined using parametric survival analysis methods. The readmission rate and length of hospital stay were determined by Poisson regression and mixed effect Poisson regression, respectively. All association were performed at 95% confidence level. Significance of association with determinants was reported using the hazard rate for hospital admission, and the incidence rate for readmission and length of hospital stay. Optimal model for each outcome was selected by using information criteria after fitness was checked. RESULTS The hospital admission rate for T2D patients was 9.85 (95%CI: 8.32, 11.66) per 1000-person-year observation. Alcohol drinking, inactive lifestyle, being a rural resident, history of comorbidities, and experiencing chronic diabetes complications were predictors of hospital admission. Seventy-one (52.2%) of the admitted patients had a history of readmission. Readmission rate was increased by being female, duration of disease, inactive lifestyle, having BMI greater than 29.9 kg/m2, and higher blood glucose. The median time of hospital stay for admitted patients was 18 (IQR:7). The length of hospital stay was longer among females, patients with the history of insulin administration, and higher blood glucose. CONCLUSION Multiple and complex factors were contributing for high diabetes admission and readmission rates as well as for longer in-hospital duration among T2D patients in Harari regional state. Socio-demographic characteristics (sex, place of residence), behavioral factors (alcohol intake, lifestyle), and medical conditions (longer duration of disease, comorbidities, chronic diabetes complications, higher blood glucose level, and treatment modality) were significant determinants of hospital admission, readmission and longer hospital stay among T2D patients.
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Affiliation(s)
- Lemma Demissie Regassa
- Department of Epidemiology and Biostatistics, College of Health and Medical Sciences, Haramaya University, P. O. Box 135, Dire Dawa, Ethiopia
| | - Assefa Tola
- Department of Epidemiology and Biostatistics, College of Health and Medical Sciences, Haramaya University, P. O. Box 135, Dire Dawa, Ethiopia
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Musa OAH, Syed A, Mohamed AM, Chivese T, Clark J, Furuya-Kanamori L, Xu C, Toft E, Bashir M, Abou-Samra AB, Thalib L, Doi SA. Metformin is comparable to insulin for pharmacotherapy in gestational diabetes mellitus: A network meta-analysis evaluating 6046 women. Pharmacol Res 2021; 167:105546. [PMID: 33716167 DOI: 10.1016/j.phrs.2021.105546] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Revised: 03/07/2021] [Accepted: 03/09/2021] [Indexed: 12/13/2022]
Abstract
CONTEXT The comparative efficacy of gestational diabetes (GDM) treatments lack conclusive evidence for choice of first-line treatment. OBJECTIVES The aim of this study was to compare the efficacy of metformin and glibenclamide to insulin using a core outcome set (COS) to unify outcomes across trials investigating the treatment of gestational diabetes mellitus. STUDY DESIGN A network meta-analysis (NMA) was conducted. DATA-SOURCE PubMed, Embase, and Cochrane Controlled Register of Trials were searched from inception to January 2020. STUDY SELECTION RCTs that enrolled pregnant women who were diagnosed with GDM and that compared the efficacy of different pharmacological interventions for the treatment of GDM were included. META-ANALYSIS A generalized pairwise modelling framework was employed. RESULTS A total of 38 RCTs with 6046 participants were included in the network meta-analysis. Compared to insulin, the estimated effect of metformin indicated improvements for weight gain (WMD -2·39 kg; 95% CI -3·31 to -1·46), maternal hypoglycemia (OR 0.34; 95% CI 0.12 to 0·97) and LGA (OR 0.61; 95% CI 0.38 to 0·98). There were also improvements in estimated effects for neonatal hypoglycemia (OR 0.48; 95% CI 0.19 to 1·25), pregnancy induced hypertension (OR 0.63; 95% CI 0.37 to 1·06), and preeclampsia (OR 0.74; 95% CI 0.538 to 1·04), though with limited evidence against our model hypothesis of equivalence with insulin for these outcomes. CONCLUSION Metformin is, at least, comparable to insulin for the treatment of GDM. Glibenclamide appears less favorable, in comparison to insulin, than metformin.
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Affiliation(s)
- Omran A H Musa
- Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Asma Syed
- Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Aisha M Mohamed
- Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Tawanda Chivese
- Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Justin Clark
- The Center for Research into Evidence Based Practice, Bond University, Gold Coast, Australia
| | - Luis Furuya-Kanamori
- Research School of Population Health, Australian National University, Canberra, Australia
| | - Chang Xu
- Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Egon Toft
- Deans Office, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Mohammed Bashir
- Division of Endocrinology, Hamad General Hospital, Doha, Qatar
| | - Abdul Badi Abou-Samra
- Division of Endocrinology, Hamad General Hospital, Doha, Qatar; Qatar Metabolic Institute, Hamad General Hospital, Doha, Qatar
| | - Lukman Thalib
- Department of Public Health, College of Health Sciences, QU Health, Qatar University, Doha, Qatar
| | - Suhail A Doi
- Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, Qatar.
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Trends and associated maternal characteristics of antidiabetic medication use among pregnant women in South Korea. Sci Rep 2021; 11:4159. [PMID: 33603191 PMCID: PMC7892865 DOI: 10.1038/s41598-021-83808-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 02/08/2021] [Indexed: 01/11/2023] Open
Abstract
The prevalence of diabetes during pregnancy and the need for the treatment are increasing. We aimed to investigate antidiabetic medications (ADM) use among pregnant women and their characteristics. Using Korea’s nationwide healthcare database, we included women aged 15–49 years with births during 2004–2013. The prevalence and secular trend of ADM use were assessed in 3 periods: pre-conception period, first trimester, and second/third trimesters. To compare maternal characteristics between pregnancies with and without ADM prescription, we used the χ2 or Fisher’s exact test and Cochran-Armitage trend test. The prescription patterns analyzed by calendar year, age, insurance type, income, area, and medical institution. Of 81,559 pregnancies, 222 (0.27%) and 305 (0.37%) were exposed ADM during pre-conception and pregnancy periods, respectively. ADM prescriptions increased significantly by an 11.3-fold in second/third trimesters, while a 2.9-fold in first trimester. ADM use is more prevalent in women aged older and living in urban areas. Metformin was most used in the pre-conception period, while insulins were most during pregnancy. About 0.4% of women received ADM during pregnancy; a rate was lower than that in western countries. Non-recommended medications were more common in first trimester, which warrants pregnancy screening for women taking ADM.
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Sabbah N, Carles G, Demar M, Nacher M. Diabetes in French Guiana, adapting national standards of therapeutic education and care to the amazonian challenge. World J Diabetes 2021; 12:98-107. [PMID: 33594330 PMCID: PMC7839167 DOI: 10.4239/wjd.v12.i2.98] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 11/25/2020] [Accepted: 12/02/2020] [Indexed: 02/06/2023] Open
Abstract
French Guiana is a territory located more than 7000 km from France. It is also the largest French territory, with almost 84000 km2 and 90% of it is covered by forest. Some municipalities are isolated due to the scarcity of transportation and the poor road infrastructure. The population is extremely diverse ethnically and culturally, and includes more than thirty ethnic groups. Immigration is high because it is one of the richest countries in the area bordering northern Brazil, Suriname, Guyana, and as a result of socio-economic crises in some other countries such as Haiti, and it has permeable natural borders. Diabetes and obesity, are emerging issues, with double the prevalence of Mainland France, whereas infectious diseases, such as HIV, take second place. Therapeutic and educational management are challenging because they require the adaptation of tools and treatments to the mul-ticulturalism and precariousness often encountered in these populations. The French and European recommendations are unsuited to the needs of the territory and must take into account the epidemiological, sociological and cultural parameters of these populations in order to provide appropriate and graded management of diabetes in the French Amazon.
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Affiliation(s)
- Nadia Sabbah
- Endocrinology Diabetology Nutrition, Centre Hospitalier Andree Rosemon, Cayenne 97300, French Guiana
| | - Gabriel Carles
- Department of Obstetrics and Gynaecology, Centre Hospitalier Franck Joly, St Laurent Du Maroni 97320, French Guiana
| | - Magalie Demar
- Department of Laboratory, University of French Guiana, Cayenne 97300, French Guiana
| | - Mathieu Nacher
- Department of Medicine, COREVIH Centre Hospitalier Andree Rosemon, Cayenne 97300, French Guiana
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Hosni A, El-Twab SA, Abdul-Hamid M, Prinsen E, AbdElgawad H, Abdel-Moneim A, Beemster GTS. Cinnamaldehyde mitigates placental vascular dysfunction of gestational diabetes and protects from the associated fetal hypoxia by modulating placental angiogenesis, metabolic activity and oxidative stress. Pharmacol Res 2021; 165:105426. [PMID: 33453370 DOI: 10.1016/j.phrs.2021.105426] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 01/09/2021] [Accepted: 01/10/2021] [Indexed: 12/17/2022]
Abstract
Gestational diabetes mellitus (GDM) is a major pregnancy-related disorder with an increasing prevalence worldwide. GDM is associated with altered placental vascular functions and has severe consequences for fetal growth. There is no commonly accepted medication for GDM due to safety considerations. Actions of the currently limited therapeutic options focus exclusively on lowering the blood glucose level without paying attention to the altered placental vascular reactivity and remodelling. We used the fat-sucrose diet/streptozotocin (FSD/STZ) rat model of GDM to explore the efficacy of cinnamaldehyde (Ci; 20 mg/kg/day), a promising antidiabetic agent for GDM, and glyburide/metformin-HCl (Gly/Met; 0.6 + 100 mg/kg/day), as a reference drug for treatment of GDM, on the placenta structure and function at term pregnancy after their oral intake one week before mating onward. Through genome-wide transcriptome, biochemical, metabolome, metal analysis and histopathology we obtained an integrated understanding of their effects. GDM resulted in maternal and fetal hyperglycemia, fetal hyperinsulinemia and placental dysfunction with subsequent fetal anemia, hepatic iron deficiency and high serum erythropoietin level, reflecting fetal hypoxia. Differentially-regulated genes were overrepresented for pathways of angiogenesis, metabolic transporters and oxidative stress. Despite Ci and Gly/Met effectively alleviated the maternal and fetal glycemia, only Ci offered substantial protection from GDM-associated placental vasculopathy and prevented the fetal hypoxia. This was explained by Ci's impact on the molecular regulation of placental angiogenesis, metabolic activity and redox signaling. In conclusion, Ci provides a dual impact for the treatment of GDM at both maternal and fetal levels through its antidiabetic effect and the direct placental vasoprotective action. Lack of Gly/Met effectiveness to restore it's impaired functionality demonstrates the vital role of the placenta in developing efficient medications for GDM.
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Affiliation(s)
- Ahmed Hosni
- Molecular Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, 62511, Beni-Suef, Egypt; Laboratory for Integrated Molecular Physiology Research (IMPRES), Department of Biology, Faculty of Science, University of Antwerp, 2020, Antwerp, Belgium
| | - Sanaa Abd El-Twab
- Molecular Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, 62511, Beni-Suef, Egypt
| | - Manal Abdul-Hamid
- Histology and Cytology Division, Department of Zoology, Faculty of Science, Beni-Suef University, 62511, Beni-Suef, Egypt
| | - Els Prinsen
- Laboratory for Integrated Molecular Physiology Research (IMPRES), Department of Biology, Faculty of Science, University of Antwerp, 2020, Antwerp, Belgium
| | - Hamada AbdElgawad
- Laboratory for Integrated Molecular Physiology Research (IMPRES), Department of Biology, Faculty of Science, University of Antwerp, 2020, Antwerp, Belgium; Department of Botany, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt
| | - Adel Abdel-Moneim
- Molecular Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, 62511, Beni-Suef, Egypt.
| | - Gerrit T S Beemster
- Laboratory for Integrated Molecular Physiology Research (IMPRES), Department of Biology, Faculty of Science, University of Antwerp, 2020, Antwerp, Belgium
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Abstract
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc21-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc21-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Chen T, Liu D, Yao X. Progress of Clinical Trials for the Treatment of Gestational Diabetes Mellitus. Diabetes Metab Syndr Obes 2021; 14:315-327. [PMID: 33519220 PMCID: PMC7837562 DOI: 10.2147/dmso.s290749] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Accepted: 12/31/2020] [Indexed: 01/09/2023] Open
Abstract
Gestational diabetes mellitus (GDM) is one of the most common and severe complications of pregnancy, which is not only associated with perinatal complications but also has a long-term adverse effect on maternal and their offsprings. At present, the treatment of GDM focuses on the control of maternal blood glucose. Although lifestyle changes, hypoglycemic drugs, blood glucose monitoring, and other medicines that can improve maternal blood glucose to a certain extent, there are still some patients affected and have adverse pregnancy outcomes. The prevention of GDM and the treatment of improving pregnancy outcomes are urgently needed. This review summarized recently published clinical trials related with the treatment of GDM, aiming to provide additional options for the treatment of GDM.
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Affiliation(s)
- Tong Chen
- Department of Endocrinology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
| | - Dan Liu
- Department of Endocrinology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Correspondence: Dan Liu Department of Endocrinology, First Affiliated Hospital of Dalian Medical University, Zhongshan Str. 222, Dalian116011, People’s Republic of China Email
| | - Xiaofeng Yao
- Department of Preventive Medicine, Dalian Medical University, Dalian, Liaoning, People’s Republic of China
- Xiaofeng Yao Department of Preventive Medicine, Dalian Medical University, 9 W Lushun South Road, Dalian116044, People’s Republic of China Email
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Outcomes of Pregnancies Affected by Gestational Diabetes and Type 2 Diabetes in a Rural First Nations Obstetrical Program in Northwest Ontario. Can J Diabetes 2020; 44:624-627. [DOI: 10.1016/j.jcjd.2020.01.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Revised: 12/30/2019] [Accepted: 01/03/2020] [Indexed: 11/19/2022]
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Wei W, Zhang X. Expression of ADP and TNF-α in patients with gestational diabetes mellitus and its relationship with pregnancy outcomes. Exp Ther Med 2020; 20:2184-2190. [PMID: 32765694 DOI: 10.3892/etm.2020.8952] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Accepted: 04/16/2020] [Indexed: 12/26/2022] Open
Abstract
Expression of adiponectin (ADP) and tumor necrosis factor-α (TNF-α) in patients with gestational diabetes mellitus and its relationship with pregnancy outcomes was explored. A total of 78 patients with gestational diabetes mellitus admitted to Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University from June 2017 to December 2018 were enrolled as an experimental group, and further 70 healthy pregnant women in physical examination during the same period were enrolled as a control group. Concentrations of ADP and TNF-α were determined and compared between the two groups. The patients were divided into high ADP expression group (≥6.84), low ADP expression group (<6.84), high TNF-α expression group (≥6.17) and low TNF-α expression group (<6.17). Corresponding two groups were compared in terms of adverse pregnancy outcomes, respectively, and they were also compared with the control group. The clinical association between ADP and TNF-α was analyzed. TNF-α was highly expressed in the blood of patients with gestational diabetes mellitus, while ADP expression was low in the blood. The low expression of ADP was related to age, pregestational body mass index (BMI), gestational week, medical history and family history of diabetes mellitus (all P<0.05), and the high expression of TNF-α was related to age, pregestational BMI, gestational week, medical history, amniotic fluid volume, abortion history, and family history of diabetes mellitus (all P<0.05). The experimental group faced a higher risk of adverse pregnancy outcomes than the control group. Both ADP and TNF-α are abnormally expressed in the patients with gestational diabetes mellitus, and TNF-α is affected by more of the factors. The concentrations of ADP and TNF-α affect the pregnancy outcomes. It suggests that ADP and TNF-α can be used as indexes for predicating pregnancy outcomes, and for judging the disease conditions and treatment of patients.
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Affiliation(s)
- Wengong Wei
- Department of Obstetrics and Gynecology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai 201700, P.R. China
| | - Xiaoping Zhang
- Department of Obstetrics and Gynecology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai 201700, P.R. China
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Li Y, Kang L, Huang J, Zhang J, Liu C, Shen W. Effects of miR-152-Mediated Targeting of SOCS3 on Hepatic Insulin Resistance in Gestational Diabetes Mellitus Mice. Am J Med Sci 2020; 361:365-374. [PMID: 32718473 DOI: 10.1016/j.amjms.2020.06.032] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Revised: 05/07/2020] [Accepted: 06/29/2020] [Indexed: 11/19/2022]
Abstract
BACKGROUND The present study explored the effects of miR-152-mediated targeting of suppressor of cytokine signaling 3 (SOCS3) on hepatic insulin resistance (HIR) in mice with gestational diabetes mellitus (GDM). Healthy SPF C57BL/6J mice were selected to establish a GDM model. METHODS Mice were divided into seven groups as follows: Normal group, Model group, NC-mimic group, miR-152 mimic group, NC-pcDNA3.0 group, pcDNA3.0-SOCS group, and miR-152 mimic + pcDNA3.0-SOCS3 group. The relationship between miR-152 and SOCS3 expression was analyzed by a dual-luciferase reporter system. Islet cell morphology and expression of miR-152 and SOCS3 mRNA and protein in the islet tissue were detected by hematoxylin and eosin (HE) staining, reverse-transcription quantitative polymerase chain reaction (RT-qPCR), and western blot analysis. Fasting blood glucose (FBG) level was measured by a glucose meter while triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and insulin levels were determined by an automatic biochemical analyzer. Insulin resistance index (HOMA-IR) was calculated by the formula FBG × FINS/22.5. RESULTS The results showed that the levels of miR-152, SOCS3, FBG, fasting insulin (FINS), TG, and TC increased, and HDL-C content decreased in other groups as compared with those in the Normal group (all p < 0.05). Oral glucose tolerance test (OGTT), FBG, FINS, TG, TC, and HDL-C values showed an opposite trend in miR-152 mimic and pcDNA3.0-SOCS3 groups as compared with the Model group (all p < 0.05). CONCLUSIONS miR-152 can inhibit HIR in GDM mice by downregulating the expression of SOCS3.
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Affiliation(s)
- Yuanchun Li
- Department of Obstetrics, Baoji Maternal and Child Health Care Hospital, Baoji, Shaanxi, China
| | - Li Kang
- Department of Human Anatomy, Henan Vocational College of Nursing, Anyang, China
| | - Juanjuan Huang
- Department of Gynecology, Yan'an University Affiliated Hospital, Yanan, Shanxi, China
| | - Juan Zhang
- Department of Gynecology, Yan'an University Affiliated Hospital, Yanan, Shanxi, China
| | - Chunhua Liu
- Department of Obstetrics, Baoji Maternal and Child Health Care Hospital, Baoji, Shaanxi, China
| | - Wenjuan Shen
- Department of Obstetrics, Baoji High-tech People's Hospital, Baoji, Shaanxi, China.
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Saha S, Saha S. A Comparison of Apgar Scores and Changes in the Neonates of Gestational Diabetes Mellitus Patients Treated with Metformin versus Glyburide: A Systematic Review. DUBAI DIABETES AND ENDOCRINOLOGY JOURNAL 2020. [DOI: 10.1159/000507244] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
<b>Aims</b>: This study aims to compare the Apgar scores (at different time points after birth) and their changes between the newborns of gestational diabetes mellitus (GDM) patients treated with metformin and glyburide, respectively. <b>Methods:</b> Electronic databases were searched for randomized controlled trials that compared these outcomes between the above-depicted intervention groups. The data about the study design, the population characteristics, the interventions compared, and the outcomes of interest were extracted from the eligible trials. Then, these trials were critically appraised by the Cochrane tool. After that, the effect of the tested interventions on the respective outcomes of interest was reported narratively. <b><i>Results:</i></b> The literature search produced 4 single-center trials sourcing data from about 538 participants in the USA, Brazil, and Israel. The risk of detection and performance bias was unclear in the respective trials. The trials primarily reported about the Apgar scores at 1 and 5 min after birth. These scores were not different between glyburide- and metformin-treated GDM patients in any trial. No trial reported the Apgar score at 10 min after birth or the changes in Apgar score between 1, 5, or 10 min after birth. <b><i>Conclusion:</i></b> In all trials, the Apgar scores at 1 and 5 min after birth did not vary between the newborns of GDM mothers treated with metformin and glyburide, respectively.
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Webb HM. And Baby Makes 2. PHYSICIAN ASSISTANT CLINICS 2020. [DOI: 10.1016/j.cpha.2019.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Ng A, Liu A, Nanan R. Association between insulin and post-caesarean resuscitation rates in infants of women with GDM: A retrospective study. J Diabetes 2020; 12:151-157. [PMID: 31373771 DOI: 10.1111/1753-0407.12974] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Revised: 07/18/2019] [Accepted: 07/29/2019] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) and caesarean deliveries independently increase the risk of postoperative complications. There are limited data on the influence of insulin use on the outcomes of neonates who were delivered via caesarean section. We sought to investigate the impact of insulin use in women with GDM on resuscitation rates of infants post caesarean delivery. METHODS A retrospective database review of women with singleton term (≥ 37 weeks) pregnancies who were on insulin for GDM delivering between January 2005 and December 2014 at a major metropolitan hospital in Sydney. RESULTS One thousand eight hundred and fifty-seven women with GDM were identified. The mean age was 31.01 ± 5.63 years and mean gestational period of 39.07 ± 1.00 weeks. 31.0% received insulin treatment for GDM. Women who were on insulin were older (31.9 ± 5.7 vs 30.6 ± 5.6 years, P < 0.001), had a higher body mass index (BMI) (31.2 ± 7.7 vs 29.0 ± 7.4 kg/m2, P < 0.001), higher rates of preeclampsia (7.3% vs 4.1%, P = 0.004), lower rates of alcohol consumption (0.4% vs 1.7%, P = 0.014), and had infants with lower resuscitation rates (21.2% vs 28.6%, P = 0.001). Infants who required resuscitation had a lower gestational age, lower five-minute APGAR score, and lower birth weight, length, and head circumferences. On multivariate analysis, women with GDM treated with insulin (odds ratio [OR] = 0.69, CI = 0.54-0.89, P = 0.004), higher gestational age (OR = 0.88, CI = 0.78-0.99, P = 0.032), higher maternal BMI (OR = 1.02, CI = 1.01-1.04, P = 0.005), and emergency caesarean (OR = 2.33, CI = 1.74-3.12, P < 0.001) independently predicted incidence of resuscitation. CONCLUSIONS The findings suggest a relationship between insulin use and reduced resuscitation rates of infants born from mothers with GDM. Further studies investigating the role, dosage, and criteria for insulin use in women with GDM are required.
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Affiliation(s)
- Aloysius Ng
- Sydney Medical School - Nepean, Discipline of Pediatrics, University of Sydney, Sydney, New South Wales, Australia
| | - Anthony Liu
- Sydney Medical School - Nepean, Discipline of Pediatrics, University of Sydney, Sydney, New South Wales, Australia
- Charles Perkins Centre - Nepean, The University of Sydney, Sydney, New South Wales, Australia
| | - Ralph Nanan
- Sydney Medical School - Nepean, Discipline of Pediatrics, University of Sydney, Sydney, New South Wales, Australia
- Charles Perkins Centre - Nepean, The University of Sydney, Sydney, New South Wales, Australia
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Abstract
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc20-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc20-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Zhou Q, Ren D, Xiao Y, Yi L, Zhou Z. Plasma fatty acid metabolic profiling coupled with clinical research reveals the risk factors for atherosclerosis development in type 2 diabetes mellitus. RSC Adv 2019; 9:36162-36170. [PMID: 35540605 PMCID: PMC9074937 DOI: 10.1039/c9ra07634d] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 10/17/2019] [Indexed: 11/30/2022] Open
Abstract
Many publications have reported that the incidence of atherosclerotic cardiovascular diseases is higher in patients with type 2 diabetes mellitus (T2DM) than in the non-diabetic population; however, until now, the reason has been unclear. In this study, 25 males (25/64, 39.06%) and 19 females (19/54, 35.19%) had complications with atherosclerosis after two years. To reveal the risk factors for developing atherosclerosis in patients with T2DM, plasma fatty acid metabolic profiling based on gas chromatography-mass spectrometry was combined with the analysis of clinical biochemical indices. The results of partial least squares-discriminant and canonical correlation analyses suggested that C20:0, C22:6n-3, glycosylated hemoglobin, waist circumference, and waist-to-hip ratio are likely to be closely related to T2DM complicated with atherosclerosis. Metabolomic information is a beneficial supplement to existing clinical indices and is useful in predicting the development of a patient's disease and optimizing the treatment.
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Affiliation(s)
- Qianyu Zhou
- Faculty of Agriculture and Food, Kunming University of Science and Technology Kunming Yunnan 650500 China +86 871 65920302
| | - Dabing Ren
- Faculty of Agriculture and Food, Kunming University of Science and Technology Kunming Yunnan 650500 China +86 871 65920302
- Yunnan Food Safety Research Institute, Kunming University of Science and Technology Kunming Yunnan 650500 China
| | - Yang Xiao
- Diabetes Center, Institute of Metabolism and Endocrinology, Department of Endocrinology, The Second Xiangya Hospital, Central South University Changsha Hunan 410011 China
| | - Lunzhao Yi
- Faculty of Agriculture and Food, Kunming University of Science and Technology Kunming Yunnan 650500 China +86 871 65920302
- Yunnan Food Safety Research Institute, Kunming University of Science and Technology Kunming Yunnan 650500 China
| | - Zhiguang Zhou
- Diabetes Center, Institute of Metabolism and Endocrinology, Department of Endocrinology, The Second Xiangya Hospital, Central South University Changsha Hunan 410011 China
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Lorenzo-Almorós A, Hang T, Peiró C, Soriano-Guillén L, Egido J, Tuñón J, Lorenzo Ó. Predictive and diagnostic biomarkers for gestational diabetes and its associated metabolic and cardiovascular diseases. Cardiovasc Diabetol 2019; 18:140. [PMID: 31666083 PMCID: PMC6820966 DOI: 10.1186/s12933-019-0935-9] [Citation(s) in RCA: 109] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 09/21/2019] [Indexed: 12/11/2022] Open
Abstract
Gestational diabetes mellitus (GDM) is defined as the presence of high blood glucose levels with the onset, or detected for the first time during pregnancy, as a result of increased insulin resistance. GDM may be induced by dysregulation of pancreatic β-cell function and/or by alteration of secreted gestational hormones and peptides related with glucose homeostasis. It may affect one out of five pregnancies, leading to perinatal morbidity and adverse neonatal outcomes, and high risk of chronic metabolic and cardiovascular injuries in both mother and offspring. Currently, GDM diagnosis is based on evaluation of glucose homeostasis at late stages of pregnancy, but increased age and body-weight, and familiar or previous occurrence of GDM, may conditionate this criteria. In addition, an earlier and more specific detection of GDM with associated metabolic and cardiovascular risk could improve GDM development and outcomes. In this sense, 1st-2nd trimester-released biomarkers found in maternal plasma including adipose tissue-derived factors such as adiponectin, visfatin, omentin-1, fatty acid-binding protein-4 and retinol binding-protein-4 have shown correlations with GDM development. Moreover, placenta-related factors such as sex hormone-binding globulin, afamin, fetuin-A, fibroblast growth factors-21/23, ficolin-3 and follistatin, or specific micro-RNAs may participate in GDM progression and be useful for its recognition. Finally, urine-excreted metabolites such as those related with serotonin system, non-polar amino-acids and ketone bodies, may complete a predictive or early-diagnostic panel of biomarkers for GDM.
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Affiliation(s)
- A Lorenzo-Almorós
- Renal, Vascular and Diabetes Laboratory, Instituto de Investigaciones Sanitarias-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Av. Reyes Católicos 2, 28040, Madrid, Spain
| | - T Hang
- Renal, Vascular and Diabetes Laboratory, Instituto de Investigaciones Sanitarias-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Av. Reyes Católicos 2, 28040, Madrid, Spain
| | - C Peiró
- Department of Pharmacology, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain
| | - L Soriano-Guillén
- Department of Paediatrics, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain
| | - J Egido
- Renal, Vascular and Diabetes Laboratory, Instituto de Investigaciones Sanitarias-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Av. Reyes Católicos 2, 28040, Madrid, Spain
- Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) Network, Madrid, Spain
| | - J Tuñón
- Department of Cardiology, Fundación Jiménez Díaz, Madrid, Spain
| | - Ó Lorenzo
- Renal, Vascular and Diabetes Laboratory, Instituto de Investigaciones Sanitarias-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Av. Reyes Católicos 2, 28040, Madrid, Spain.
- Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) Network, Madrid, Spain.
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Wexler DJ, Powe CE, Barbour LA, Buchanan T, Coustan DR, Corcoy R, Damm P, Dunne F, Feig DS, Ferrara A, Harper LM, Landon MB, Meltzer SJ, Metzger BE, Roeder H, Rowan JA, Sacks DA, Simmons D, Umans JG, Catalano PM. Research Gaps in Gestational Diabetes Mellitus: Executive Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop. Obstet Gynecol 2019; 132:496-505. [PMID: 29995731 DOI: 10.1097/aog.0000000000002726] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The National Institute of Diabetes and Digestive and Kidney Diseases convened a workshop on research gaps in gestational diabetes mellitus (GDM) with a focus on 1) early pregnancy diagnosis and treatment and 2) pharmacologic treatment strategies. This article summarizes the proceedings of the workshop. In early pregnancy, the appropriate diagnostic criteria for the diagnosis of GDM remain poorly defined, and an effect of early diagnosis and treatment on the risk of adverse outcomes has not been demonstrated. Despite many small randomized controlled trials of glucose-lowering medication treatment in GDM, our understanding of medication management of GDM is incomplete as evidenced by discrepancies among professional society treatment guidelines. The comparative effectiveness of insulin, metformin, and glyburide remains uncertain, particularly with respect to long-term outcomes. Additional topics in need of further research identified by workshop participants included phenotypic heterogeneity in GDM and novel and individualized treatment approaches. Further research on these topics is likely to improve our understanding of the pathophysiology and treatment of GDM to improve both short- and long-term outcomes for mothers and their children.
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Affiliation(s)
- Deborah J Wexler
- Diabetes Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; the Divisions of Endocrinology, Metabolism, and Diabetes and Maternal-Fetal Medicine, University of Colorado School of Medicine and Anschutz Medical Campus, Aurora, Colorado; the Division of Endocrinology and Diabetes, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; Women & Infants Hospital of Rhode Island and Warren Alpert Medical School of Brown University, Providence, Rhode Island; the Diabetes Unit, Hospital de la Santa Creu I Sant Pau, Universitat Autonoma de Barcelona, Bellaterra, Barcelona, CIBER-BBN, Spain; the Center for Pregnant Women with Diabetes, Department of Obstetrics, Rigshospitalet, Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; College Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland; the Diabetes & Endocrine in Pregnancy Program, Mount Sinai Hospital and University of Toronto, Toronto, Canada; the Division of Research, Kaiser Permanente Northern California, Oakland, California; the Department of Maternal-Fetal Medicine, Center for Women's Reproductive Health, University of Alabama at Birmingham, Birmingham, Alabama; the Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio; the Departments of Medicine and Obstetrics and Gynecology, McGill University Health Centre, Montreal, Quebec, Canada; Northwestern University Feinberg School of Medicine, Chicago, Illinois; Kaiser Permanente Southern California, San Diego, California; National Women's Health, Auckland, New Zealand; the Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California; Campbelltown Hospital and Western Sydney University, Sydney, Australia; MedStar Health Research Institute, Hyattsville, Maryland; Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC; and the Center for Reproductive Health, Case Western Reserve University at MetroHealth Medical Center, Cleveland, Ohio
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50
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de Wit L, Rademaker D, Voormolen DN, Akerboom BMC, Kiewiet-Kemper RM, Soeters MR, Verwij-Didden MAL, Assouiki F, Schippers DH, Vermeulen MAR, Kuppens SMI, Oosterwerff MM, Zwart JJ, Diekman MJM, Vogelvang TE, Gallas PRJ, Galjaard S, Visser W, Horree N, Klooker TK, Laan R, Heijligenberg R, Huisjes AJM, van Bemmel T, van Meir CA, van den Beld AW, Hermes W, Vidarsdottir S, Veldhuis-Vlug AG, Dullemond RC, Jansen HJ, Sueters M, de Koning EJP, van Laar JOEH, Wouters-van Poppel P, Sanson-van Praag ME, van den Akker ES, Brouwer CB, Hermsen BB, Potter van Loon BJ, van der Heijden OWH, de Galan BE, van Leeuwen M, Wijbenga JAM, de Boer K, van Bon AC, van der Made FW, Eskes SA, Zandstra M, van Houtum WH, Braams-Lisman BAM, Daemen-Gubbels CRGM, Wouters MGAJ, IJzerman RG, Mensing van Charante NA, Zwertbroek R, Bosmans JE, Evers IM, Mol BW, de Valk HW, Groenendaal F, Naaktgeboren CA, Painter RC, deVries JH, Franx A, van Rijn BB. SUGAR-DIP trial: oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial. BMJ Open 2019; 9:e029808. [PMID: 31427334 PMCID: PMC6701578 DOI: 10.1136/bmjopen-2019-029808] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 04/11/2019] [Accepted: 05/22/2019] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. METHODS The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. ETHICS AND DISSEMINATION The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER NTR6134; Pre-results.
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Affiliation(s)
- Leon de Wit
- Department of Obstetrics and Gynaecology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Doortje Rademaker
- Department of Obstetrics and Gynaecology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Daphne N Voormolen
- Department of Obstetrics and Gynaecology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Bettina M C Akerboom
- Department of Obstetrics and Gynaecology, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | | | - Maarten R Soeters
- Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | | | - Fahima Assouiki
- Department of Internal Medicine, Bernhoven Hospital, Uden, The Netherlands
| | - Daniela H Schippers
- Department of Obstetrics and Gynaecology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
| | - Mechteld A R Vermeulen
- Department of Internal Medicine, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
| | - Simone M I Kuppens
- Department of Obstetrics and Gynaecology, Catharina Hospital, Eindhoven, The Netherlands
| | | | - Joost J Zwart
- Department of Obstetrics and Gynaecology, Deventer Hospital, Deventer, The Netherlands
| | | | - Tatjana E Vogelvang
- Department of Obstetrics and Gynaecology, Diakonessenhuis Utrecht, Utrecht, The Netherlands
| | - P Rob J Gallas
- Department of Internal Medicine, Diakonessenhuis Utrecht, Utrecht, The Netherlands
| | - Sander Galjaard
- Department of Obstetrics and Prenatal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Willy Visser
- Department of Obstetrics and Prenatal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Nicole Horree
- Department of Obstetrics and Gynaecology, Flevoziekenhuis, Almere, The Netherlands
| | - Tamira K Klooker
- Department of Internal Medicine, Flevoziekenhuis, Almere, The Netherlands
| | - Rosemarie Laan
- Department of Obstetrics and Gynaecology, Gelderse Vallei Hospital, Ede, The Netherlands
| | - Rik Heijligenberg
- Department of Internal Medicine, Gelderse Vallei Hospital, Ede, The Netherlands
| | - Anjoke J M Huisjes
- Department of Obstetrics and Gynaecology, Gelre Hospitals, Apeldoorn, The Netherlands
| | - Thomas van Bemmel
- Department of Internal Medicine, Gelre Hospitals, Apeldoorn, The Netherlands
| | - Claudia A van Meir
- Department of Obstetrics and Gynaecology, Groene Hart Hospital, Gouda, The Netherlands
| | | | - Wietske Hermes
- Department of Obstetrics and Gynaecology, Haaglanden Medical Center, The Hague, The Netherlands
| | - Solrun Vidarsdottir
- Department of Internal Medicine, Haaglanden Medical Center, The Hague, The Netherlands
| | - Anneke G Veldhuis-Vlug
- Department of Internal Medicine, Medical Center Jan van Goyen, Amsterdam, The Netherlands
| | - Remke C Dullemond
- Department of Obstetrics and Gynaecology, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands
| | - Henrique J Jansen
- Department of Internal Medicine, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands
| | - Marieke Sueters
- Department of Obstetrics and Gynaecology, Leiden University Medical Center, Leiden, The Netherlands
| | - Eelco J P de Koning
- Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Judith O E H van Laar
- Department of Obstetrics and Gynaecology, Máxima Medical Center, Veldhoven, The Netherlands
| | | | | | | | | | - Brenda B Hermsen
- Department of Obstetrics and Gynaecology, OLVG, Amsterdam, The Netherlands
| | | | - Olivier W H van der Heijden
- Department of Obstetrics and Gynaecology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands
| | - Bastiaan E de Galan
- Department of Internal Medicine, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands
| | - Marsha van Leeuwen
- Department of Obstetrics and Gynaecology, Reinier de Graaf Hospital, Delft, The Netherlands
| | - Johanna A M Wijbenga
- Department of Internal Medicine, Reinier de Graaf Hospital, Delft, The Netherlands
| | - Karin de Boer
- Department of Obstetrics and Gynaecology, Rijnstate Hospital, Arnhem, The Netherlands
| | - Arianne C van Bon
- Department of Internal Medicine, Rijnstate Hospital, Arnhem, The Netherlands
| | - Flip W van der Made
- Department of Obstetrics and Gynaecology, Franciscus Gasthuis and Vlietland, Rotterdam, The Netherlands
| | - Silvia A Eskes
- Department of Internal Medicine, Franciscus Gasthuis and Vlietland, Rotterdam, The Netherlands
| | - Mirjam Zandstra
- Department of Obstetrics and Gynaecology, Spaarne Gasthuis, Haarlem, The Netherlands
| | | | | | | | - Maurice G A J Wouters
- Department of Obstetrics and Gynaecology, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
| | - Richard G IJzerman
- Department of Internal Medicine, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
| | | | - Rolf Zwertbroek
- Department of Internal Medicine, Dijklander Hospital, Hoorn, The Netherlands
| | - Judith E Bosmans
- Department of Health Sciences, Faculty of Science, VU University Amsterdam, Amsterdam, The Netherlands
| | - Inge M Evers
- Department of Obstetrics and Gynaecology, Meander Medical Center, Amersfoort, The Netherlands
| | - Ben Willem Mol
- Department of Obstetrics and Gynaecology, School of Medicine, Monash University, Melbourne, Australia, Melbourne, The Netherlands
| | - Harold W de Valk
- Department of Internal Medicine and Endocrinology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Floris Groenendaal
- Department of Neonatology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Christiana A Naaktgeboren
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
| | - Rebecca C Painter
- Department of Obstetrics and Gynaecology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - J Hans deVries
- Department of Internal Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Arie Franx
- Department of Obstetrics and Gynaecology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Bas B van Rijn
- Department of Obstetrics and Gynaecology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
- Department of Obstetrics and Prenatal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
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