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American Diabetes Association Professional Practice Committee, ElSayed NA, McCoy RG, Aleppo G, Bajaj M, Balapattabi K, Beverly EA, Briggs Early K, Bruemmer D, Echouffo-Tcheugui JB, Ekhlaspour L, Gaglia JL, Garg R, Girotra M, Khunti K, Lal R, Lingvay I, Matfin G, Neumiller JJ, Pandya N, Pekas EJ, Pilla SJ, Polsky S, Segal AR, Seley JJ, Stanton RC, Bannuru RR. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2025. Diabetes Care 2025; 48:S181-S206. [PMID: 39651989 PMCID: PMC11635045 DOI: 10.2337/dc25-s009] [Citation(s) in RCA: 44] [Impact Index Per Article: 44.0] [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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Alessa T, Al Awadi F, Al Kaabi J, Al Mamari A, Al Ozairi E, Alromaihi D, Elhadd T, Gunaid AA, Hassanein M, Jayyousi AA, Kalimat R, Brand KMG. Modern-Day Management of the Dysglycemic Continuum: An Expert Viewpoint from the Arabian Gulf. Diabetes Metab Syndr Obes 2024; 17:4791-4802. [PMID: 39712240 PMCID: PMC11662629 DOI: 10.2147/dmso.s491591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 10/26/2024] [Indexed: 12/24/2024] Open
Abstract
Prediabetes is the first stage of a continuum that extends through the diagnosis of clinical type 2 diabetes towards long-standing diabetes with multiple comorbidities. The diagnosis of prediabetes provides an opportunity to interrupt the diabetes continuum at an early stage to ensure long-term optimization of clinical outcomes. All people with prediabetes should receive intervention to improve their lifestyles (quality of diet and level of physical activity), as this has been proven beyond doubt to reduce substantially the risk of conversion to diabetes. Additionally, a large base of clinical evidence supports the use of metformin in preventing or delaying the transition from prediabetes to clinical type 2 diabetes, for some people with prediabetes. For many years, guidelines for the management of type 2 diabetes focused on lowering blood glucose, with metformin prescribed first for those without contraindications. More recently, guidelines have shifted towards prevention of diabetes complications as the primary goal, with increased use of GLP-1 receptor agonists (or multi-agonist incretin peptides) or SGLT-2 inhibitors for patients with existing atherosclerotic cardiovascular disease, heart failure or chronic kidney disease. Access to these medications often remains challenging. Metformin remains a suitable option for initial pharmacologic intervention to manage glycemia for many people with prediabetes or type 2 diabetes along with other therapy to maintain control of blood glucose or to address specific comorbidities as the patient progresses along the diabetes continuum.
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Affiliation(s)
- Thamer Alessa
- Division of Endocrinology, Jaber Al-Ahmad Hospital, Kuwait City, Kuwait
| | - Fatheya Al Awadi
- Endocrine Department, Dubai Hospital, Dubai Academic Health Corporation (DAHC), Dubai, United Arab Emirates
| | - Juma Al Kaabi
- Department of Internal Medicine, College of Medicine and Health Sciences, The United Arab Emirates University, Al-Ain, United Arab Emirates
| | - Ali Al Mamari
- Department of Medicine, Sultan Qaboos University Hospital, Muscat, Oman
| | - Ebaa Al Ozairi
- Clinical Research Unit, Dasman Diabetes Institute, Dasman, Kuwait
| | - Dalal Alromaihi
- Internal Medicine Department, Royal College of Surgeons in Ireland-Medical University of Bahrain, Adliya, Kingdom of Bahrain
| | - Tarik Elhadd
- Endocrine Section, Department of Medicine, Hamad Medical Corporation, Doha, Qatar
| | - Abdallah A Gunaid
- Internal Medicine, Sana’a University Faculty of Medicine, Sanaa, Yemen
| | - Mohamed Hassanein
- Department of Endocrinology and Diabetes, Dubai Hospital, Dubai Academic Health Corporation (DAHC), Dubai, United Arab Emirates
| | - Amin A Jayyousi
- Department of Endocrinology, Hamad Medical Corporation, Doha, Qatar
| | - Raya Kalimat
- Medical Affairs, Merck Serono Middle East FZ-LLC, Dubai, United Arab Emirates
| | - Kerstin M G Brand
- Global Research & Development Medical – MU CM&E, Merck Healthcare KGaA, Darmstadt, Germany
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Atkinson M, Gharti P, Min T. Metformin Use and Vitamin B12 Deficiency in People with Type 2 Diabetes. What Are the Risk Factors? A Mini-systematic Review. TOUCHREVIEWS IN ENDOCRINOLOGY 2024; 20:42-53. [PMID: 39526048 PMCID: PMC11548349 DOI: 10.17925/ee.2024.20.2.7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 01/04/2024] [Indexed: 11/16/2024]
Abstract
Background and Aim: Metformin is recommended as the first-line agent for the management of type 2 diabetes following lifestyle and dietary changes. The long-term use of metformin has been associated with vitamin B12 deficiency. The aim of this review is to investigate the effect of metformin on vitamin B12 levels and identify any risk factors. Method: A literature search was conducted using MEDLINE, PubMed and ProQuest Central. Selected articles were peer-reviewed articles, written in English and published from 2015 and onwards. Excluded articles were case reports, reviews or meta-analyses, as well as those with no access to full text. Results: In total, 21 articles were included. There was a significant association between metformin use and vitamin B12 levels in 17 studies, while 4 studies found no such association. The risk factors examined were metformin dose, treatment duration, patient age and patient ethnicity. Conclusion: In summary, metformin use was associated with lower vitamin B12 concentrations, and higher doses and longer durations of treatment increase the risk of vitamin B12 deficiency. Routine vitamin B12 screening is recommended, prioritizing higher-risk patients. Further research is needed to identify when to initiate monitoring.
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Affiliation(s)
- Michael Atkinson
- Department of Diabetes and Endocrinology, Morriston Hospital, Swansea Bay University Health Board, Swansea, UK
| | - Prashamsa Gharti
- Diabetes Research Group, Swansea University Medical School, Swansea, UK
| | - Thinzar Min
- Diabetes Research Group, Swansea University Medical School, Swansea, UK
- Department of Diabetes and Endocrinology, Neath Port Talbot Hospital, Swansea Bay University Health Board, Swansea, UK
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Silverii GA. Optimizing metformin therapy in practice: Tailoring therapy in specific patient groups to improve tolerability, efficacy and outcomes. Diabetes Obes Metab 2024; 26 Suppl 3:42-54. [PMID: 38987983 DOI: 10.1111/dom.15749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 06/05/2024] [Accepted: 06/14/2024] [Indexed: 07/12/2024]
Abstract
Metformin is the first-line medication for type 2 diabetes. It is effective and safe, provided some caution is taken in specific populations. In patients with chronic kidney disease, metformin may provide long-term benefits, and it is a first-line therapy for diabetes, but the estimated glomerular filtration rate (eGFR) must be assessed regularly, to minimize the risk for metformin accumulation. When eGFR is 30-60 mL/min/1.73m2, the dose should be reconsidered, and sick-days education provided. Metformin should be discontinued when eGFR falls below 30 mL/min/1.73m2. Metformin accumulation may increase the risk for lactic acidosis if concomitant risk factors for hyperlactataemia (liver or respiratory insufficiency, sepsis, acute heart failure) are present; in these conditions, metformin is contraindicated, even although the available evidence is reassuring. Patients on metformin often complain of gastrointestinal side effects (mainly diarrhoea and nausea) during therapy initiation, but they may sometimes occur after years of stable therapy. These usually resolve if the dose is carefully titrated, or by switching to the extended-release formulation. Patients with obesity may benefit from the significant, although modest, metformin-associated weight loss and appetite reduction. During pregnancy, metformin is associated with a reduction of pregnancy complications, especially in obese women, but some concern remains, because metformin crosses the placenta, and it is associated with a significantly lower mean birth weight than insulin. In the elderly, gastrointestinal tolerability and renal function must be reassessed more often. Vitamin B-12 should be screened regularly in long-time metformin users because metformin may induce clinical vitamin B-12 deficiency.
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Affiliation(s)
- Giovanni Antonio Silverii
- Experimental and Clinical Biomedical Sciences "Mario Serio" Department, University of Florence, Florence, Italy
- Diabetology Unit, Central Tuscany Local Health Unit, Florence, Italy
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Mucha P, Kus F, Cysewski D, Smolenski RT, Tomczyk M. Vitamin B 12 Metabolism: A Network of Multi-Protein Mediated Processes. Int J Mol Sci 2024; 25:8021. [PMID: 39125597 PMCID: PMC11311337 DOI: 10.3390/ijms25158021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 07/12/2024] [Accepted: 07/19/2024] [Indexed: 08/12/2024] Open
Abstract
The water-soluble vitamin, vitamin B12, also known as cobalamin, plays a crucial role in cellular metabolism, particularly in DNA synthesis, methylation, and mitochondrial functionality. Its deficiency can lead to hematological and neurological disorders; however, the manifestation of these clinical outcomes is relatively late. It leads to difficulties in the early diagnosis of vitamin B12 deficiency. A prolonged lack of vitamin B12 may have severe consequences including increased morbidity to neurological and cardiovascular diseases. Beyond inadequate dietary intake, vitamin B12 deficiency might be caused by insufficient bioavailability, blood transport disruptions, or impaired cellular uptake and metabolism. Despite nearly 70 years of knowledge since the isolation and characterization of this vitamin, there are still gaps in understanding its metabolic pathways. Thus, this review aims to compile current knowledge about the crucial proteins necessary to efficiently accumulate and process vitamin B12 in humans, presenting these systems as a multi-protein network. The epidemiological consequences, diagnosis, and treatment of vitamin B12 deficiency are also highlighted. We also discuss clinical warnings of vitamin B12 deficiency based on the ongoing test of specific moonlighting proteins engaged in vitamin B12 metabolic pathways.
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Affiliation(s)
- Patryk Mucha
- Department of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, Poland; (P.M.); (F.K.); (R.T.S.)
| | - Filip Kus
- Department of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, Poland; (P.M.); (F.K.); (R.T.S.)
- Laboratory of Protein Biochemistry, Intercollegiate Faculty of Biotechnology of University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, Poland
| | - Dominik Cysewski
- Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland;
| | - Ryszard T. Smolenski
- Department of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, Poland; (P.M.); (F.K.); (R.T.S.)
| | - Marta Tomczyk
- Department of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, Poland; (P.M.); (F.K.); (R.T.S.)
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Yazidi M, Kammoun E, Oueslati I, Chihaoui M. Metformin-Induced Vitamin B12 Deficiency in Patients with Type 2 Diabetes: A Narrative Review with a Practical Approach for Screening, Diagnosing, and Managing Vitamin B12 Deficiency. Korean J Fam Med 2024; 45:189-198. [PMID: 39054838 PMCID: PMC11273170 DOI: 10.4082/kjfm.24.0090] [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: 04/24/2024] [Revised: 05/27/2024] [Accepted: 06/12/2024] [Indexed: 07/27/2024] Open
Abstract
Metformin is the most widely used antihyperglycemic drug in patients with type 2 diabetes (T2D). Over the past 2 decades, several studies have highlighted a substantial increase in the risk of vitamin B12 deficiency in patients with T2D on metformin therapy. This can lead to several complications and induce or exacerbate peripheral neuropathy. Despite these data, there are no definite guidelines for screening, diagnosing, and treating vitamin B12 deficiency in patients with T2D on metformin therapy. Therefore, in this narrative review, we aimed to suggest a practical diagnostic and therapeutic strategy to address vitamin B12 deficiency in patients with T2D receiving metformin treatment. Clinical evidence supporting an increased risk of vitamin B12 deficiency in patients with T2D on metformin therapy and its risk factors and potential complications are also discussed.
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Affiliation(s)
- Meriem Yazidi
- Department of Endocrinology, La Rabta Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Elyes Kammoun
- Department of Endocrinology, La Rabta Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Ibtissem Oueslati
- Department of Endocrinology, La Rabta Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Melika Chihaoui
- Department of Endocrinology, La Rabta Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
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Moon JS, Kang S, Choi JH, Lee KA, Moon JH, Chon S, Kim DJ, Kim HJ, Seo JA, Kim MK, Lim JH, Song YJ, Yang YS, Kim JH, Lee YB, Noh J, Hur KY, Park JS, Rhee SY, Kim HJ, Kim HM, Ko JH, Kim NH, Kim CH, Ahn J, Oh TJ, Kim SK, Kim J, Han E, Jin SM, Bae J, Jeon E, Kim JM, Kang SM, Park JH, Yun JS, Cha BS, Moon MK, Lee BW. 2023 Clinical Practice Guidelines for Diabetes Management in Korea: Full Version Recommendation of the Korean Diabetes Association. Diabetes Metab J 2024; 48:546-708. [PMID: 39091005 PMCID: PMC11307112 DOI: 10.4093/dmj.2024.0249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 06/20/2024] [Indexed: 08/04/2024] Open
Affiliation(s)
- Jun Sung Moon
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Shinae Kang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jong Han Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
| | - Kyung Ae Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
| | - Joon Ho Moon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Suk Chon
- Department of Endocrinology and Metabolism, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Dae Jung Kim
- Department of Endocrinology and Metabolism, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea
| | - Hyun Jin Kim
- Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Korea
| | - Ji A Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Mee Kyoung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jeong Hyun Lim
- Department of Food Service and Nutrition Care, Seoul National University Hospital, Seoul, Korea
| | - Yoon Ju Song
- Department of Food Science and Nutrition, The Catholic University of Korea, Bucheon, Korea
| | - Ye Seul Yang
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Hyeon Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - You-Bin Lee
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Junghyun Noh
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
| | - Kyu Yeon Hur
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Suk Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Youl Rhee
- Department of Endocrinology and Metabolism, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Hae Jin Kim
- Department of Endocrinology and Metabolism, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea
| | - Hyun Min Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Jung Hae Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Nam Hoon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Chong Hwa Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea
| | - Jeeyun Ahn
- Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Tae Jung Oh
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Soo-Kyung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Jaehyun Kim
- Department of Pediatrics, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Eugene Han
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Sang-Man Jin
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jaehyun Bae
- Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Korea
| | - Eonju Jeon
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Ji Min Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
| | - Seon Mee Kang
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea
| | - Jung Hwan Park
- Division of Endocrinology & Metabolism, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Jae-Seung Yun
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Bong-Soo Cha
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Min Kyong Moon
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Byung-Wan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Goglia U, Hasballa I, Teti C, Boschetti M, Ferone D, Albertelli M. Ianus Bifrons: The Two Faces of Metformin. Cancers (Basel) 2024; 16:1287. [PMID: 38610965 PMCID: PMC11011026 DOI: 10.3390/cancers16071287] [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: 01/18/2024] [Revised: 03/10/2024] [Accepted: 03/20/2024] [Indexed: 04/14/2024] Open
Abstract
The ancient Roman god Ianus was a mysterious divinity with two opposite faces, one looking at the past and the other looking to the future. Likewise, metformin is an "old" drug, with one side looking at the metabolic role and the other looking at the anti-proliferative mechanism; therefore, it represents a typical and ideal bridge between diabetes and cancer. Metformin (1,1-dimethylbiguanidine hydrochloride) is a drug that has long been in use for the treatment of type 2 diabetes mellitus, but recently evidence is growing about its potential use in other metabolic conditions and in proliferative-associated diseases. The aim of this paper is to retrace, from a historical perspective, the knowledge of this molecule, shedding light on the subcellular mechanisms of action involved in metabolism as well as cellular and tissue growth. The intra-tumoral pharmacodynamic effects of metformin and its possible role in the management of different neoplasms are evaluated and debated. The etymology of the name Ianus is probably from the Latin term ianua, which means door. How many new doors will this old drug be able to open?
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Affiliation(s)
- Umberto Goglia
- Endocrinology and Diabetology Unit, Local Health Authority CN1, 12100 Cuneo, Italy
| | - Iderina Hasballa
- Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy (M.B.); (D.F.); (M.A.)
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, 16132 Genoa, Italy
| | - Claudia Teti
- Endocrinology and Diabetology Unit, Local Health Autorithy Imperia 1, 18100 Imperia, Italy;
| | - Mara Boschetti
- Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy (M.B.); (D.F.); (M.A.)
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, 16132 Genoa, Italy
| | - Diego Ferone
- Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy (M.B.); (D.F.); (M.A.)
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, 16132 Genoa, Italy
| | - Manuela Albertelli
- Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy (M.B.); (D.F.); (M.A.)
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, 16132 Genoa, Italy
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Fituri S, Akbar Z, Ganji V. Impact of metformin treatment on cobalamin status in persons with type 2 diabetes. Nutr Rev 2024; 82:553-560. [PMID: 37167532 PMCID: PMC10925902 DOI: 10.1093/nutrit/nuad045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/13/2023] Open
Abstract
Over the last decades, low vitamin B12 status has been reported in individuals with type 2 diabetes mellitus (T2DM). Metformin, the first-line therapy for lowering blood glucose, is the main driving factor behind this association. Although the relationship between vitamin B12 deficiency and metformin is well established, results of studies on the exact effect of the dose and duration of the therapy remain inconsistent. Additionally, a lack of consensus on the definition of vitamin B12 deficiency adds to the conflicting literature. The objectives of this review were to analyze and synthesize the findings on the effects of metformin dose and duration on vitamin B12 status in patients with T2DM and to outline the potential mechanisms underlying metformin's effect on vitamin B12. Metformin therapy has adversely affected serum vitamin B12 concentrations, a marker of vitamin B12 status. The metformin usage index (a composite score of metformin dose and duration) might serve as a potential risk assessment tool for vitamin B12 screening in patients with T2DM. Considering the health implications of suboptimal vitamin B12 status, vitamin B12 concentrations should be monitored periodically in high-risk patients, such as vegans who are receiving metformin therapy for T2DM. Additionally, it is prudent to implement lifestyle strategies concurrent with metformin therapy in individuals with T2DM, promoting an overall synergistic effect on their glycemic control.
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Affiliation(s)
- Sundus Fituri
- Human Nutrition Department, College of Health Sciences, QU Health, Qatar University, Doha, Qatar
| | - Zoha Akbar
- Human Nutrition Department, College of Health Sciences, QU Health, Qatar University, Doha, Qatar
| | - Vijay Ganji
- Human Nutrition Department, College of Health Sciences, QU Health, Qatar University, Doha, Qatar
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10
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Cao B, Xue Y, Liu D. The association between methylmalonic acid, a biomarker of mitochondria dysfunction, and phenotypic age acceleration: A population-based study. Arch Gerontol Geriatr 2024; 117:105176. [PMID: 37713936 DOI: 10.1016/j.archger.2023.105176] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 07/16/2023] [Accepted: 08/30/2023] [Indexed: 09/17/2023]
Abstract
Phenotypic age acceleration (PAA) is a sensitive marker of biological aging. Circulating methylmalonic acid (MMA) is a novel biomarker of mitochondrial dysfunction and has been associated with age-related disorders. Our study aimed to investigate to what extent circulating MMA was associated with PAA, and whether the association was independent of vitamin B12 status and renal function in the general population. We analyzed cross-sectional data from 13,023 participants across a wide age range (mean age: 38.9 years, range: 12 - 85 years, 51.1% women) from the US National Health and Nutrition Examination Survey (NHANES). PAA was calculated based on the published algorithm. Linear regression models were performed to assess the association between circulating MAA and PAA. Only 31% of the variation in MMA levels was explained by age, sex, race/ethnicity, social economic status, vitamin B12 status, and renal function. Per unit increase in circulating MAA (1.0 nmol/L) was associated with 1.59 years increase in PAA (β = 1.59, 95% CI: 1.17, 2.00, p < 0.001) after adjusting for multiple confounders. Importantly, PAA increased with circulating MMA levels independent of vitamin B12, creatine, and homocysteine levels. The association was more pronounced in subgroups of age ≥ 65 years, women, underweight, vitamin B12 < 400 μmol/L, and homocysteine ≥ 10 μmol/L. The association was much stronger among participants with cardiovascular diseases (CVDs) than without CVDs. In conclusion, our current population-based study showed that mitochondria-derived circulating MMA was associated with increased phenotypic age acceleration in the general population.
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Affiliation(s)
- Bing Cao
- School of Psychology and Key Laboratory of Cognition and Personality (Ministry of Education), Southwest University, Chongqing, 400715, China
| | - Yu Xue
- Department of Clinical Nutrition, West China Hospital, Sichuan University, No.37 Guoxue Lane, Chengdu, Sichuan, China
| | - Dan Liu
- Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
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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, Gaglia JL, 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. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2024. Diabetes Care 2024; 47:S158-S178. [PMID: 38078590 PMCID: PMC10725810 DOI: 10.2337/dc24-s009] [Citation(s) in RCA: 290] [Impact Index Per Article: 290.0] [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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Spallone V. Diabetic neuropathy: Current issues in diagnosis and prevention. CHRONIC COMPLICATIONS OF DIABETES MELLITUS 2024:117-163. [DOI: 10.1016/b978-0-323-88426-6.00016-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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13
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Gao L, Ran X, Liu X, Shen X, Chen S, Liu F, Zhao D, Bi Y, Su Q, Lu Y, Lei M, Wang Y, Ji L. The effects of daily dose and treatment duration of metformin on the prevalence of vitamin B12 deficiency and peripheral neuropathy in Chinese patients with type 2 diabetes mellitus: A multicenter cross-sectional study. J Diabetes 2023; 15:765-776. [PMID: 37310028 PMCID: PMC10509512 DOI: 10.1111/1753-0407.13428] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 04/27/2023] [Accepted: 05/22/2023] [Indexed: 06/14/2023] Open
Abstract
AIMS To evaluate the prevalence of vitamin B12 deficiency in Chinese patients with type 2 diabetes mellitus receiving metformin treatment and to investigate the effects of metformin daily dose and treatment duration on the prevalence of vitamin B12 deficiency and peripheral neuropathy (PN). MATERIALS AND METHODS In this multicenter cross-sectional study, 1027 Chinese patients who had been taking ≥1000 mg/day metformin for ≥1 year were enrolled using proportionate stratified random sampling based on daily dose and treatment duration. Primary measures included the prevalence of vitamin B12 deficiency (<148 pmol/L), borderline B12 deficiency (148 pmol/L-211 pmol/L), and PN. RESULTS The prevalence of vitamin B12 deficiency, borderline deficiency, and PN were 2.15%, 13.66%, and 11.59%, respectively. Patients receiving ≥1500 mg/day metformin had significantly higher prevalence of borderline vitamin B12 deficiency (16.76% vs. 9.91%, p = .0015) and serum B12 ≤221 pmol/L (19.25% vs. 11.64%, p < .001) than patients receiving <1500 mg/day metformin. No difference was found in prevalence of borderline vitamin B12 deficiency (12.58% vs. 15.49%, p = .1902) and serum B12 ≤221 pmol/L (14.91% vs. 17.32%, p = .3055) between patients receiving metformin for ≥3 and <3 years. Patients with vitamin B12 deficiency had numerically higher PN prevalence (18.18% vs. 11.27%, p = .3192) than patients without it. Multiple logistic analyses revealed that HbA1c and metformin daily dose were associated with the prevalence of borderline B12 deficiency and B12 ≤221 pmol/L. CONCLUSIONS High daily dosage (≥1500 mg/day) played an important role in metformin-associated vitamin B12 deficiency while not contributing to the risk of PN.
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Affiliation(s)
- Leili Gao
- Department of EndocrinologyPeking University People's HospitalBeijingChina
| | - Xingwu Ran
- Department of EndocrinologyWest China Hospital Sichuan UniversityChengduChina
| | - Xuejun Liu
- Department of EndocrinologyMetabolic Disease Hospital of Tianjin Medical UniversityTianjinChina
| | - Xingping Shen
- Department of EndocrinologyZhongshan Hospital Xiamen UniversityXiamenChina
| | - Shuchun Chen
- Department of EndocrinologyHebei General HospitalShijiazhuangChina
| | - Fuqiang Liu
- Department of EndocrinologyQilu Hospital of Shangdong UniversityJinanChina
| | - Dong Zhao
- Department of EndocrinologyBeijing Luhe Hospital Affiliated to Capital Medical UniversityBeijingChina
| | - Yan Bi
- Department of EndocrinologyNanjing Drum Tower HospitalNanjingChina
| | - Qing Su
- Department of EndocrinologyXinhua Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghaiChina
| | - Yao Lu
- Department of EndocrinologySecond Affiliated Hospital of Xinjiang Medical UniversityXinjiangChina
| | - Minxiang Lei
- Department of EndocrinologyXiangya Hospital Central South UniversityChangshaChina
| | - Yanfang Wang
- Department of EndocrinologyHenan Provincial People's HospitalZhengzhouChina
| | - Linong Ji
- Department of EndocrinologyPeking University People's HospitalBeijingChina
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14
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Rossmann C, Ranz C, Kager G, Ledinski G, Koestenberger M, Wonisch W, Wagner T, Schwaminger SP, Di Geronimo B, Hrzenjak A, Hallstöm S, Reibnegger G, Cvirn G, Paar M. Metformin Impedes Oxidation of LDL In Vitro. Pharmaceutics 2023; 15:2111. [PMID: 37631325 PMCID: PMC10459002 DOI: 10.3390/pharmaceutics15082111] [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: 06/22/2023] [Revised: 07/13/2023] [Accepted: 07/26/2023] [Indexed: 08/27/2023] Open
Abstract
Metformin is the most commonly prescribed glucose-lowering drug for the treatment of type 2 diabetes. The aim of this study was to investigate whether metformin is capable of impeding the oxidation of LDL, a crucial step in the development of endothelial dysfunction and atherosclerosis. LDL was oxidized by addition of CuCl2 in the presence of increasing concentrations of metformin. The extent of LDL oxidation was assessed by measuring lipid hydroperoxide and malondialdehyde concentrations, relative electrophoretic mobilities, and oxidation-specific immune epitopes. Cytotoxicity of oxLDL in the vascular endothelial cell line EA.hy926 was assessed using the alamarBlue viability test. Quantum chemical calculations were performed to determine free energies of reactions between metformin and radicals typical for lipid oxidation. Metformin concentration-dependently impeded the formation of lipid hydroperoxides, malondialdehyde, and oxidation-specific immune epitopes when oxidation of LDL was initiated by addition of Cu2+. The cytotoxicity of oxLDL was reduced when it was obtained under increasing concentrations of metformin. The quantum chemical calculations revealed that only the reaction of metformin with hydroxyl radicals is exergonic, whereas the reactions with hydroperoxyl radicals or superoxide radical anions are endergonic. Metformin, beside its glucose-lowering effect, might be a suitable agent to impede the development of atherosclerosis and associated CVD. This is due to its capability to impede LDL oxidation, most likely by scavenging hydroxyl radicals.
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Affiliation(s)
- Christine Rossmann
- Division of Medicinal Chemistry, Otto Loewi Research Centre, Medical University of Graz, 8010 Graz, Austria; (C.R.); (C.R.); (G.K.); (G.L.); (W.W.); (S.P.S.); (B.D.G.); (S.H.); (G.R.); (M.P.)
| | - Cornelia Ranz
- Division of Medicinal Chemistry, Otto Loewi Research Centre, Medical University of Graz, 8010 Graz, Austria; (C.R.); (C.R.); (G.K.); (G.L.); (W.W.); (S.P.S.); (B.D.G.); (S.H.); (G.R.); (M.P.)
| | - Gerd Kager
- Division of Medicinal Chemistry, Otto Loewi Research Centre, Medical University of Graz, 8010 Graz, Austria; (C.R.); (C.R.); (G.K.); (G.L.); (W.W.); (S.P.S.); (B.D.G.); (S.H.); (G.R.); (M.P.)
| | - Gerhard Ledinski
- Division of Medicinal Chemistry, Otto Loewi Research Centre, Medical University of Graz, 8010 Graz, Austria; (C.R.); (C.R.); (G.K.); (G.L.); (W.W.); (S.P.S.); (B.D.G.); (S.H.); (G.R.); (M.P.)
| | - Martin Koestenberger
- Department of Pediatrics and Adolescent Medicine, Division of General Pediatrics, Medical University of Graz, 8010 Graz, Austria;
| | - Willibald Wonisch
- Division of Medicinal Chemistry, Otto Loewi Research Centre, Medical University of Graz, 8010 Graz, Austria; (C.R.); (C.R.); (G.K.); (G.L.); (W.W.); (S.P.S.); (B.D.G.); (S.H.); (G.R.); (M.P.)
| | - Thomas Wagner
- Department of Blood Group Serology and Transfusion Medicine, Medical University of Graz, 8010 Graz, Austria;
| | - Sebastian P. Schwaminger
- Division of Medicinal Chemistry, Otto Loewi Research Centre, Medical University of Graz, 8010 Graz, Austria; (C.R.); (C.R.); (G.K.); (G.L.); (W.W.); (S.P.S.); (B.D.G.); (S.H.); (G.R.); (M.P.)
- BioTechMed Graz, 8010 Graz, Austria
| | - Bruno Di Geronimo
- Division of Medicinal Chemistry, Otto Loewi Research Centre, Medical University of Graz, 8010 Graz, Austria; (C.R.); (C.R.); (G.K.); (G.L.); (W.W.); (S.P.S.); (B.D.G.); (S.H.); (G.R.); (M.P.)
| | - Andelko Hrzenjak
- Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, 8010 Graz, Austria;
| | - Seth Hallstöm
- Division of Medicinal Chemistry, Otto Loewi Research Centre, Medical University of Graz, 8010 Graz, Austria; (C.R.); (C.R.); (G.K.); (G.L.); (W.W.); (S.P.S.); (B.D.G.); (S.H.); (G.R.); (M.P.)
- Division of Biomedical Research and Translational Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Gilbert Reibnegger
- Division of Medicinal Chemistry, Otto Loewi Research Centre, Medical University of Graz, 8010 Graz, Austria; (C.R.); (C.R.); (G.K.); (G.L.); (W.W.); (S.P.S.); (B.D.G.); (S.H.); (G.R.); (M.P.)
| | - Gerhard Cvirn
- Division of Medicinal Chemistry, Otto Loewi Research Centre, Medical University of Graz, 8010 Graz, Austria; (C.R.); (C.R.); (G.K.); (G.L.); (W.W.); (S.P.S.); (B.D.G.); (S.H.); (G.R.); (M.P.)
| | - Margret Paar
- Division of Medicinal Chemistry, Otto Loewi Research Centre, Medical University of Graz, 8010 Graz, Austria; (C.R.); (C.R.); (G.K.); (G.L.); (W.W.); (S.P.S.); (B.D.G.); (S.H.); (G.R.); (M.P.)
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15
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Dinesh D, Lee JS, Scott TM, Tucker KL, Palacios N. Association between Acid-Lowering Agents, Metformin, and Vitamin B12 among Boston-Area Puerto Ricans. J Nutr 2023; 153:2380-2388. [PMID: 37302714 PMCID: PMC10447618 DOI: 10.1016/j.tjnut.2023.05.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 05/11/2023] [Accepted: 05/23/2023] [Indexed: 06/13/2023] Open
Abstract
BACKGROUND Vitamin B12 involves several physiological functions, and malabsorption is reported with medication use. OBJECTIVES Studies have reported an inverse association between the use of metformin or acid-lowering agents (ALAs), such as proton pump inhibitors, histamine 2 receptor antagonists, and blood vitamin B12 concentration, because of malabsorption. The concomitant use of these medications is underreported. We sought to examine these associations in a cohort of Boston-area Puerto Rican adults. METHODS This analysis was conducted within the Boston Puerto Rican Health Study (BPRHS), an ongoing longitudinal cohort that enrolled 1499 Puerto Rican adults aged 45-75 y at baseline. Our study comprised 1428, 1155, and 782 participants at baseline, wave2 (2.2 y from baseline), and wave3 (6.2 y from baseline), respectively. Covariate-adjusted linear and logistic regression was used to examine the association between baseline medication use and vitamin B12 concentration or deficiency (vitamin B12 <148 pmol/L or methylmalonic acid >271 nmol/L), and long-term medication use (continuous use for ∼6.2 y) and wave3 vitamin B12 concentration and deficiency. Sensitivity analyses were done to examine these associations in vitamin B12 supplement users. RESULTS At baseline, we observed an association between metformin use (β = -0.069; P = 0.03) and concomitant ALA and metformin use (β = -0.112; P = 0.02) and vitamin B12 concentration, but not a deficiency. We did not observe associations between ALA, proton pump inhibitors, or histamine 2 receptor antagonists, individually, with vitamin B12 concentration or deficiency. CONCLUSIONS These results suggest an inverse relationship between metformin, concomitant ALA, metformin use, and serum vitamin B12 concentration.
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Affiliation(s)
- Deepika Dinesh
- Center for Population Health, University of Massachusetts Lowell, Lowell, MA, United States; Department of Biomedical and Nutritional Sciences, University of Massachusetts Lowell, Lowell, MA, United States.
| | - Jong Soo Lee
- Center for Population Health, University of Massachusetts Lowell, Lowell, MA, United States; Department of Mathematics and Statistics, University of Massachusetts Lowell, Lowell, MA, United States
| | - Tammy M Scott
- Center for Population Health, University of Massachusetts Lowell, Lowell, MA, United States; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, United States; Department of Psychiatry, School of Medicine, Tufts University, Boston, MA, United States
| | - Katherine L Tucker
- Center for Population Health, University of Massachusetts Lowell, Lowell, MA, United States; Department of Biomedical and Nutritional Sciences, University of Massachusetts Lowell, Lowell, MA, United States
| | - Natalia Palacios
- Center for Population Health, University of Massachusetts Lowell, Lowell, MA, United States; Department of Public Health, University of Massachusetts Lowell, Lowell, MA, United States; Department of Nutrition, Harvard University School of Public Health, Boston, MA, United States; Department of Veterans Affairs, Geriatric Research Education Clinical Center, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA, United States.
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16
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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, Seley JJ, Stanton RC, Gabbay RA, on behalf of the American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2023. Diabetes Care 2023; 46:S140-S157. [PMID: 36507650 PMCID: PMC9810476 DOI: 10.2337/dc23-s009] [Citation(s) in RCA: 514] [Impact Index Per Article: 257.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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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17
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Huber J, Smeikal M, Saely CH, Stingl H, Clodi M, Lechleitner M, Fasching P. [Geriatric aspects for the management of diabetes mellitus (Update 2023)]. Wien Klin Wochenschr 2023; 135:307-318. [PMID: 37101051 PMCID: PMC10133361 DOI: 10.1007/s00508-022-02124-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/09/2022] [Indexed: 04/28/2023]
Abstract
There is a high prevalence of diabetes mellitus in the elderly population of industrial countries. The present article provides recommendations for the screening, prevention and treatment of elderly diabetic patients according to current scientific evidence.
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Affiliation(s)
- Joakim Huber
- Abteilung für Innere Medizin mit Akutgeriatrie und Palliativmedizin, Franziskus Spital, Standort Landstraße, Landstraßer Hauptstraße 4a, 1030 Wien, Österreich
| | - Michael Smeikal
- Abteilung für Innere Medizin mit allgemeiner Geriatrie und Palliativmedizin, Haus der Barmherzigkeit, Wien, Österreich
| | - Christoph H. Saely
- Abteilung für Innere Medizin und Kardiologie/VIVIT-Institut, Landeskrankenhaus Feldkirch, Feldkirch, Österreich
| | - Harald Stingl
- Interne Abteilung, Landesklinikum Melk, Melk, Österreich
| | - Martin Clodi
- ICMR—Institute for Cardiovascular and Metabolic Research, Johannes Kepler Universität Linz (JKU Linz), 4040 Linz, Österreich
| | - Monika Lechleitner
- Interne Abteilung, Landeskrankenhaus Hochzirl – Natters, Hochzirl, Österreich
| | - Peter Fasching
- 5. Medizinische Abteilung mit Endokrinologie, Rheumatologie und Akutgeriatrie, Klinik Ottakring der Stadt Wien, Wien, Österreich
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18
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Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, Rosas SE, Del Prato S, Mathieu C, Mingrone G, Rossing P, Tankova T, Tsapas A, Buse JB. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2022; 65:1925-1966. [PMID: 36151309 PMCID: PMC9510507 DOI: 10.1007/s00125-022-05787-2] [Citation(s) in RCA: 453] [Impact Index Per Article: 151.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 08/18/2022] [Indexed: 01/11/2023]
Abstract
The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the previous consensus statements on the management of hyperglycaemia in type 2 diabetes in adults, published since 2006 and last updated in 2019. The target audience is the full spectrum of the professional healthcare team providing diabetes care in the USA and Europe. A systematic examination of publications since 2018 informed new recommendations. These include additional focus on social determinants of health, the healthcare system and physical activity behaviours including sleep. There is a greater emphasis on weight management as part of the holistic approach to diabetes management. The results of cardiovascular and kidney outcomes trials involving sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, including assessment of subgroups, inform broader recommendations for cardiorenal protection in people with diabetes at high risk of cardiorenal disease. After a summary listing of consensus recommendations, practical tips for implementation are provided.
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Affiliation(s)
- Melanie J Davies
- Leicester Diabetes Research Centre, University of Leicester, Leicester, UK.
- Leicester National Institute for Health Research (NIHR) Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK.
| | - Vanita R Aroda
- Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Billy S Collins
- National Heart, Lung, and Blood Institute, Bethesda, MD, USA
| | | | - Jennifer Green
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA
| | - Nisa M Maruthur
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Sylvia E Rosas
- Kidney and Hypertension Unit, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Stefano Del Prato
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Chantal Mathieu
- Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
| | - Geltrude Mingrone
- Università Cattolica del Sacro Cuore, Rome, Italy
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Division of Diabetes and Nutritional Sciences, School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, London, UK
| | - Peter Rossing
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Tsvetalina Tankova
- Department of Endocrinology, Medical University - Sofia, Sofia, Bulgaria
| | - Apostolos Tsapas
- Diabetes Centre, Clinical Research and Evidence-based Medicine Unit, Aristotle University Thessaloniki, Thessaloniki, Greece
- Harris Manchester College, University of Oxford, Oxford, UK
| | - John B Buse
- University of North Carolina School of Medicine, Chapel Hill, NC, USA.
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19
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Muacevic A, Adler JR, Tehseen Z, Khemani V, J SK, Nousherwani MD, Saleem F, Abdelhameed AN. Effect of Metformin on Vitamin B12 Deficiency in Patients With Type 2 Diabetes Mellitus and Factors Associated With It: A Meta-Analysis. Cureus 2022; 14:e32277. [PMID: 36628003 PMCID: PMC9816920 DOI: 10.7759/cureus.32277] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/05/2022] [Indexed: 12/12/2022] Open
Abstract
The current meta-analysis aims to explore the effect of metformin use on vitamin B12 deficiency in patients with type 2 diabetes mellitus (T2DM) and the factors associated with it. This meta-analysis followed the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines and the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. We searched PubMed and EMBASE from January 1, 2010, to October 31, 2022, to collect the studies that reported the effect of metformin on the deficiency of vitamin B12 in patients with T2DM and the factors associated with it. A total of 17 studies were included in the current meta-analysis. Among all the included studies, 13 were cross-sectional studies, 3 were retrospective cohorts, and one was a case-control study. The pooled rate of deficiency of vitamin B12 in patients receiving metformin (23.16%) was significantly higher compared to patients who were not on metformin (17.4%) (OR: 2.95, 95% CI: 2.18-4.00, p-value: 0.001). Factors significantly associated with vitamin B12 deficiency in patients with T2DM and receiving metformin include the duration of metformin use and a greater dose of metformin. In conclusion, our meta-analysis found that the prevalence of vitamin B12 deficiency is greater in patients receiving metformin compared to patients who did not receive metformin. Given the importance of vitamin B12 in nutrition, metformin-induced B12 decrease may be harmful to patients with T2DM. Supplemental vitamin B12 may be advantageous for those on metformin.
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20
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Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, Rosas SE, Del Prato S, Mathieu C, Mingrone G, Rossing P, Tankova T, Tsapas A, Buse JB. Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2022; 45:2753-2786. [PMID: 36148880 PMCID: PMC10008140 DOI: 10.2337/dci22-0034] [Citation(s) in RCA: 775] [Impact Index Per Article: 258.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 08/04/2022] [Indexed: 02/07/2023]
Abstract
The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the previous consensus statements on the management of hyperglycemia in type 2 diabetes in adults, published since 2006 and last updated in 2019. The target audience is the full spectrum of the professional health care team providing diabetes care in the U.S. and Europe. A systematic examination of publications since 2018 informed new recommendations. These include additional focus on social determinants of health, the health care system, and physical activity behaviors, including sleep. There is a greater emphasis on weight management as part of the holistic approach to diabetes management. The results of cardiovascular and kidney outcomes trials involving sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists, including assessment of subgroups, inform broader recommendations for cardiorenal protection in people with diabetes at high risk of cardiorenal disease. After a summary listing of consensus recommendations, practical tips for implementation are provided.
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Affiliation(s)
- Melanie J. Davies
- Leicester Diabetes Research Centre, University of Leicester, Leicester, U.K
- Leicester National Institute for Health Research Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, U.K
| | - Vanita R. Aroda
- Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | | | | | - Jennifer Green
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC
| | - Nisa M. Maruthur
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Sylvia E. Rosas
- Kidney and Hypertension Unit, Joslin Diabetes Center, Harvard Medical School, Boston, MA
| | - Stefano Del Prato
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Chantal Mathieu
- Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
| | - Geltrude Mingrone
- Università Cattolica del Sacro Cuore, Rome, Italy
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Division of Diabetes and Nutritional Sciences, School of Cardiovascular and Metabolic Medicine and Sciences, King’s College London, London, U.K
| | - Peter Rossing
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | | | - Apostolos Tsapas
- Diabetes Centre, Clinical Research and Evidence-Based Medicine Unit, Aristotle University Thessaloniki, Thessaloniki, Greece
- Harris Manchester College, University of Oxford, Oxford, U.K
| | - John B. Buse
- University of North Carolina School of Medicine, Chapel Hill, NC
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21
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Pratama S, Lauren BC, Wisnu W. The efficacy of vitamin B 12 supplementation for treating vitamin B 12 deficiency and peripheral neuropathy in metformin-treated type 2 diabetes mellitus patients: A systematic review. Diabetes Metab Syndr 2022; 16:102634. [PMID: 36240684 DOI: 10.1016/j.dsx.2022.102634] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 09/20/2022] [Accepted: 09/25/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND AND AIMS Metformin-treated type 2 diabetes mellitus (T2DM) patients are at higher risk of vitamin B12 deficiency and more severe neuropathy symptoms. There is still no guideline suggesting vitamin B12 supplementation for this population. This study aimed to analyze the efficacy of vitamin B12 supplementation in this population. METHOD Studies reporting the efficacy of vitamin B12 supplementation in metformin-treated T2DM patients were systematically searched in PubMed, Cochrane, EBSCOHost, and Scopus following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Additional relevant studies were searched manually through citations. Study quality and risk of bias were assessed using suitable tools. RESULTS Seven clinical trials with a total of 506 participants were included. Using the Cochrane's Risk of Bias 2 tools for clinical trials, 4 studies were assessed to have high risk of bias and 3 studies had low risk of bias. There were 5 studies that measured changes in serum vitamin B12 level, all of which reported a statistically significant increase after supplementation. Significant reductions in homocysteine after supplementation were found in 2 studies. Its effect on neuropathy symptoms was still unclear, with 2 studies reporting a significant improvement and 1 study reporting no significant effect. CONCLUSIONS The results of this systematic review support the implementation of vitamin B12 supplementation for metformin-treated T2DM to prevent or treat vitamin B12 deficiency and neuropathy. More high-quality clinical studies are required to generate quantitative analysis and to encourage supplementation in available guidelines.
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Affiliation(s)
- Samuel Pratama
- Faculty of Medicine, University of Indonesia, Jakarta, 10430, Indonesia.
| | | | - Wismandari Wisnu
- Faculty of Medicine, University of Indonesia, Jakarta, 10430, Indonesia; Division of Endocrine, Metabolic and Diabetes, Internal Medicine Department, Dr. Cipto Mangunkusumo Hospital, Jakarta, 10430, Indonesia
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22
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Wang C, Deng H, Xu Y, Liu Y. Literature review of the clinical characteristics of metformin-induced hepatotoxicity. Front Pharmacol 2022; 13:969505. [PMID: 36147344 PMCID: PMC9486097 DOI: 10.3389/fphar.2022.969505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 08/16/2022] [Indexed: 11/29/2022] Open
Abstract
Background: Knowledge of metformin-induced hepatotoxicity is based on case reports. The aim of this study was to investigate the clinical features of metformin-induced hepatotoxicity. Methods: We collected relevant literature on metformin-induced hepatotoxicity published from January 1994 to February 2022 by searching Chinese and English databases. Results: Thirty patients (19 males and 11 females) from 29 articles were included, with a median age of 61 years (range 29-83). The median time to onset of liver injury was 4 weeks (range 0.3-648) after metformin administration. Clinical symptoms occurred in 28 patients, including gastrointestinal reactions (56.7%), jaundice (50.0%), fatigue (36.7%), anorexia (23.3%), pruritus (13.3%), dark urine (13.3%), and clay-colored stools (10.0%). Serum alanine transaminase, aspartate transaminase, γ-glutamyl transferase, total bilirubin and alkaline phosphatase were elevated to varying degrees. Liver imaging in 26 patients showed hepatic steatosis (6 cases, 23.1%) and gallbladder wall thickening (11.5%). Liver biopsies from 13 patients showed portal phlebitis (61.5%), cholestatic hepatitis (38.5%), and parenchymal inflammation (38.5%). After metformin discontinuation, liver function returned to normal levels at a median of 6 weeks (range 2-16). Conclusions: Metformin-induced hepatotoxicity is a rare adverse reaction. Physicians and patients should be alert to metformin-induced hepatotoxicity.
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Affiliation(s)
- Chunjiang Wang
- Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China
- Sepsis Translational Medicine Key Lab of Hunan Province, Changsha, Hunan, China
- Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Hongyi Deng
- Department of Pharmacy, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China
| | - Yunfei Xu
- Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China
- Sepsis Translational Medicine Key Lab of Hunan Province, Changsha, Hunan, China
| | - Ying Liu
- Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China
- Sepsis Translational Medicine Key Lab of Hunan Province, Changsha, Hunan, China
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Bell DSH. Metformin-induced vitamin B12 deficiency can cause or worsen distal symmetrical, autonomic and cardiac neuropathy in the patient with diabetes. Diabetes Obes Metab 2022; 24:1423-1428. [PMID: 35491956 DOI: 10.1111/dom.14734] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 04/15/2022] [Accepted: 04/28/2022] [Indexed: 11/29/2022]
Abstract
Metformin blocks the absorption of vitamin B12 through a mechanism that has not been established but could be because of interference with the calcium-dependent binding of the intrinsic factor vitamin B12 complex to the cubam receptor in the terminal ileum. The subsequent deficiency of vitamin B12 may cause or accelerate distal symmetrical and autonomic neuropathy in the patient with diabetes. Several observational studies and meta-analyses have reported a significant association between metformin utilization and vitamin B12 deficiency. Prospective studies have shown that not only do metformin utilizers have lower vitamin B12 levels but they also have higher frequencies of distal symmetrical polyneuropathy and autonomic neuropathy (including cardiac denervation, which is associated with increased incidences of cardiac arrhythmias, cardiac events and mortality). Therefore, periodic monitoring of vitamin B12 is recommended in all patients who utilize metformin, particularly if metformin has been used for over 5 years at which stage hepatic stores of vitamin B12 would probably be depleted. Factors that accelerate the loss of hepatic vitamin B12 stores are proton pump inhibitors, bariatric surgery, being elderly and having an increased turnover of red blood cells. If serum vitamin B12 levels are borderline, measurement of methylmalonic acid and homocysteine levels can detect vitamin B12 deficiency at its earliest stage. Therapies include prophylactic calcium and vitamin B12 supplements, metformin withdrawal, replenishing vitamin B12 stores with intramuscular or oral vitamin B12 therapy and regular monitoring of vitamin B12 levels and vitamin B12 supplements if metformin continues to be utilized. With adequate vitamin B12 replacement, while symptoms of neuropathy may or may not improve, objective findings of neuropathy stabilize but do not improve.
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24
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Gerardo González-González J, Cesar Solis R, Díaz González-Colmenero A, Raygoza-Cortez K, Moreno-Peña PJ, Sánchez AL, McCoy RG, Singh Ospina N, Maraka S, Brito JP, Rodriguez-Gutierrez R. Effect of metformin on microvascular outcomes in patients with type 2 diabetes: A systematic review and meta-analysis. Diabetes Res Clin Pract 2022; 186:109821. [PMID: 35247521 PMCID: PMC9064963 DOI: 10.1016/j.diabres.2022.109821] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 01/05/2022] [Accepted: 02/28/2022] [Indexed: 12/26/2022]
Abstract
AIMS Examine the efficacy of metformin compared to placebo or other glucose-lowering medications on microvascular outcomes in patients with Type 2 Diabetes Mellitus (T2DM). METHODS MEDLINE, EMBASE, Web of Science, and Scopus were searched from database inception to March 2020. We included randomized clinical trials of patients with T2DM receiving metformin compared with another active glucose-lowering treatment or placebo in which a microvascular outcome was assessed. The risk of bias was assessed using the Cochrane Risk of Bias tool. Microvascular complications included kidney-related outcomes, retinopathy, and peripheral neuropathy. An inverse-weighted variance random-effect meta-analysis was performed to estimate drugs effect over microvascular disease. PROSPERO (CRD42019120365). RESULTS Nineteen RCTs (n = 18,181) were included. Metformin increased estimated glomerular filtration rate (eGFR) by a mean difference (MD) of 1.08 (95% CI 0.84 to 1.33 ml/min/1.73 m2) after 24 weeks. No effect was found on urinary albumin-creatinine ratio, serum creatinine, and end-stage kidney disease; Patient-important outcomes regarding kidney disease, retinal outcomes, peripheral neuropathy or quality of life were not assessed by any of the included studies and could not be analyzed. CONCLUSIONS There is no evidence of clinically significant beneficial effect of metformin therapy as compared to other glucose-lowering medications or placebo on the examined microvascular complications.
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Affiliation(s)
- José Gerardo González-González
- Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico; Endocrinology Division, Department of Internal Medicine, University Hospital "Dr. José E. González", Universidad Autonoma de Nuevo León, Monterrey 64460, Mexico
| | - Ricardo Cesar Solis
- Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico
| | | | - Karina Raygoza-Cortez
- Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico
| | - Pablo J Moreno-Peña
- Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico
| | - Alicia L Sánchez
- Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico
| | - Rozalina G McCoy
- Division of Community Internal Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA; Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, MN, USA
| | - Naykky Singh Ospina
- Division of Endocrinology, Department of Medicine, University of Florida, FL 32610, USA
| | - Spyridoula Maraka
- Division of Endocrinology and Metabolism, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Central Arkansas Veterans Healthcare System, Medicine Service, Little Rock, AR, USA
| | - Juan P Brito
- Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN 55905, USA
| | - René Rodriguez-Gutierrez
- Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico; Endocrinology Division, Department of Internal Medicine, University Hospital "Dr. José E. González", Universidad Autonoma de Nuevo León, Monterrey 64460, Mexico; Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN 55905, USA.
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Prasathkumar M, Becky R, Anisha S, Dhrisya C, Sadhasivam S. Evaluation of hypoglycemic therapeutics and nutritional supplementation for type 2 diabetes mellitus management: An insight on molecular approaches. Biotechnol Lett 2022; 44:203-238. [PMID: 35119572 DOI: 10.1007/s10529-022-03232-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Accepted: 01/28/2022] [Indexed: 12/12/2022]
Abstract
OBJECTIVE This review aims to summarize the current management of type 2 diabetes principles, including oral hypoglycemic agents, types of insulin administration, diet maintenance, and various molecular approaches. METHODS A literature search was conducted in different databases such as Scopus, ScienceDirect, Google Scholar, and Web of Science by using the following keywords: type-2 diabetes mellitus (T2DM), first-line and second-line treatment, oral hypoglycemic agents, insulin administration, diet/nutritional therapy, gene and stem cell therapy, and diabetic complications. RESULTS The first-line treatment of T2DM includes administering oral hypoglycemic agents (OHAs) and second-line treatment by insulin therapy and some OHAs like Sulfonylurea's (SU). The oral hypoglycemic or oral antidiabetic drugs have the function of lowering glucose in the blood. Insulin therapy is recommended for people with A1C levels > 7.0, and insulin administration is evolved drastically from the syringe, pump, pen, inhalation, insulin jet, and patch. The use of OHAs and insulin therapy during glycemic control has a severe effect on weight gain and other side effects. Hence, diet maintenance (macro and micronutrients) and nutritional therapy guidelines were also reviewed/recommended for safe T2DM management. Besides, the recent progress in molecular approaches that focuses on identifying new targets for T2DM (i.e.) consisting of gene therapy, stem cell therapy, and the modulation of insulin signaling pathways for the regulation of glucose storage and uptake also discussed. CONCLUSION The analysis of all these key factors is necessary to develop a potential agent to cure T2DM and suggest that a combination of therapies will pave the way for advanced management of T2DM.
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Affiliation(s)
- Murugan Prasathkumar
- Bioprocess and Biomaterials Laboratory, Department of Microbial Biotechnology, Bharathiar University, Coimbatore, 641046, India
| | - Robert Becky
- Bioprocess and Biomaterials Laboratory, Department of Microbial Biotechnology, Bharathiar University, Coimbatore, 641046, India
| | - Salim Anisha
- Bioprocess and Biomaterials Laboratory, Department of Microbial Biotechnology, Bharathiar University, Coimbatore, 641046, India
| | - Chenthamara Dhrisya
- Bioprocess and Biomaterials Laboratory, Department of Microbial Biotechnology, Bharathiar University, Coimbatore, 641046, India
| | - Subramaniam Sadhasivam
- Bioprocess and Biomaterials Laboratory, Department of Microbial Biotechnology, Bharathiar University, Coimbatore, 641046, India.
- Department of Extension and Career Guidance, Bharathiar University, Coimbatore, 641046, India.
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American Diabetes Association Professional Practice Committee. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2022. Diabetes Care 2022; 45:S125-S143. [PMID: 34964831 DOI: 10.2337/dc22-s009] [Citation(s) in RCA: 473] [Impact Index Per Article: 157.7] [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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Ala M, Ala M. Metformin for Cardiovascular Protection, Inflammatory Bowel Disease, Osteoporosis, Periodontitis, Polycystic Ovarian Syndrome, Neurodegeneration, Cancer, Inflammation and Senescence: What Is Next? ACS Pharmacol Transl Sci 2021; 4:1747-1770. [PMID: 34927008 DOI: 10.1021/acsptsci.1c00167] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Indexed: 12/15/2022]
Abstract
Diabetes is accompanied by several complications. Higher prevalence of cancers, cardiovascular diseases, chronic kidney disease (CKD), obesity, osteoporosis, and neurodegenerative diseases has been reported among patients with diabetes. Metformin is the oldest oral antidiabetic drug and can improve coexisting complications of diabetes. Clinical trials and observational studies uncovered that metformin can remarkably prevent or alleviate cardiovascular diseases, obesity, polycystic ovarian syndrome (PCOS), osteoporosis, cancer, periodontitis, neuronal damage and neurodegenerative diseases, inflammation, inflammatory bowel disease (IBD), tuberculosis, and COVID-19. In addition, metformin has been proposed as an antiaging agent. Numerous mechanisms were shown to be involved in the protective effects of metformin. Metformin activates the LKB1/AMPK pathway to interact with several intracellular signaling pathways and molecular mechanisms. The drug modifies the biologic function of NF-κB, PI3K/AKT/mTOR, SIRT1/PGC-1α, NLRP3, ERK, P38 MAPK, Wnt/β-catenin, Nrf2, JNK, and other major molecules in the intracellular signaling network. It also regulates the expression of noncoding RNAs. Thereby, metformin can regulate metabolism, growth, proliferation, inflammation, tumorigenesis, and senescence. Additionally, metformin modulates immune response, autophagy, mitophagy, endoplasmic reticulum (ER) stress, and apoptosis and exerts epigenetic effects. Furthermore, metformin protects against oxidative stress and genomic instability, preserves telomere length, and prevents stem cell exhaustion. In this review, the protective effects of metformin on each disease will be discussed using the results of recent meta-analyses, clinical trials, and observational studies. Thereafter, it will be meticulously explained how metformin reprograms intracellular signaling pathways and alters molecular and cellular interactions to modify the clinical presentations of several diseases.
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Affiliation(s)
- Moein Ala
- School of Medicine, Tehran University of Medical Sciences (TUMS), 1416753955 Tehran, Iran
| | - Mahan Ala
- School of Dentistry, Golestan University of Medical Sciences (GUMS), 4814565589 Golestan, Iran
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28
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Phapale P. Pharmaco-metabolomics opportunities in drug development and clinical research. ANALYTICAL SCIENCE ADVANCES 2021; 2:611-616. [PMID: 38715865 PMCID: PMC10989535 DOI: 10.1002/ansa.202000178] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Revised: 08/15/2021] [Accepted: 08/24/2021] [Indexed: 07/18/2024]
Abstract
Pharmaco-metabolomics uses metabolic phenotypes for the prediction of inter-individual variations in drug response and helps in understanding the mechanisms of drug action. The field has made significant progress over the last 14 years with numerous studies providing clinical evidence for personalised medicine. However, discovered pharmaco-metabolomic biomarkers are not yet translated into clinics due to a lack of large-scale validation. Integration of targeted and untargeted metabolomics workflows into pharmacokinetic analysis and drug development can advance the field from bench to bedside. Also, Indian pharmaceutical research and its bioanalytical infrastructure are in a position to take on these opportunities by addressing challenges such as appropriate training and regulatory compliance.
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Affiliation(s)
- Prasad Phapale
- European Molecular Biology LabMetabolomics Core FacilityHeidelbergGermany
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29
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Abstract
Diabetes is one of the most common disease states in older adults and there are significant risks to the use of antidiabetic medications. The older adult population varies greatly in functional ability, independence, and cognition. These factors, along with increased risk of hypoglycemia, falls, and other comorbidities, add to the complexity of creating medication regimens to treat diabetes in older adults. In the current review, a person-centered approach to diabetes care in older adults is described to aid clinician decision making. By keeping the patient and their individual factors in the center of the decision, risks of over- or under-treating diabetes can be minimized. The review will discuss person-centered goal setting, practical approaches to diabetes medication management, and specific considerations for choosing medication classes based on patient characteristics. [Journal of Gerontological Nursing, 47(10), 7-13.].
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30
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Managing glucose-related adverse events of antipsychotics is worth the effort. DRUGS & THERAPY PERSPECTIVES 2021. [DOI: 10.1007/s40267-021-00856-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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31
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Cernea S, Dima L, Correll CU, Manu P. Pharmacological Management of Glucose Dysregulation in Patients Treated with Second-Generation Antipsychotics. Drugs 2021; 80:1763-1781. [PMID: 32930957 DOI: 10.1007/s40265-020-01393-x] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Fasting hyperglycemia, impaired glucose tolerance, prediabetes, and diabetes are frequently present in patients treated with second-generation antipsychotics (SGAPs) for schizophrenia, bipolar disorder, and other severe mental illnesses. These drugs are known to produce weight gain, which may lead to insulin resistance, glucose intolerance, and metabolic syndrome, which constitute important risk factors for the emergence of diabetes. The aim of this review was to formulate therapeutic guidelines for the management of diabetes in patients treated with SGAPs, based on the association between SGAP-induced weight gain and glucose dysregulation. A systematic search in PubMed from inception to March 2020 for randomized controlled trials (RCTs) of diabetes or prediabetes in patients treated with SGAPs was performed. PubMed was also searched for the most recent clinical practice guidelines of interventions for co-morbid conditions associated with diabetes mellitus (DM) (arterial hypertension and dyslipidemia), lifestyle interventions and switching from high metabolic liability SGAPs to safer SGAPs. The search identified 14 RCTs in patients treated with SGAPs. Drug therapy using metformin as first-line therapy and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or perhaps sodium-glucose cotransporter-2 (SGLT2) inhibitors as add-on therapy, might be preferred in these patients as well, as they favorably influence glucose metabolism and body mass index, and provide cardio-renal benefits in general to the DM population, although for the SGLT-2 inhibitors there are no RCTs in this specific patient category so far. Metformin is also useful for treatment of prediabetes. Arterial hypertension should be treated with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and statins should be used for correction of dyslipidemia. The outcome of lifestyle-changing interventions has been disappointing. Switching from clozapine, olanzapine, or quetiapine to lower cardiometabolic-risk SGAPs, like aripiprazole, brexpiprazole, cariprazine, lurasidone, or ziprasidone, has been recommended.
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Affiliation(s)
- Simona Cernea
- Faculty of Medicine/Department M4/Internal Medicine IV, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Târgu Mureș, Romania.,Diabetes, Nutrition and Metabolic Diseases Outpatient Unit, Emergency County Clinical Hospital, Târgu Mureş, Romania
| | - Lorena Dima
- Department of Fundamental Disciplines and Clinical Prevention, Faculty of Medicine, Universitatea Transilvania, Nicolae Balcescu Str 59, Brașov, 500019, Romania.
| | - Christoph U Correll
- Charite Universitaetsmedizin, Department of Child and Adolescent Psychiatry, Berlin, and Campus Virchow-Klinikum, Mittelallee 5A, Berlin, 13353, Germany.,Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.,Department of Psychiatry and Molecular Medicine, Zucker Hillside Hospital, Northwell Health System, Glen Oaks, NY, USA
| | - Peter Manu
- Department of Psychiatry, Hofstra Northwell School of Medicine, Hempstead, NY, USA.,Department of Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA.,South Oaks Hospital, Northwell Health System, Amityville, NY, USA
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Infante M, Leoni M, Caprio M, Fabbri A. Long-term metformin therapy and vitamin B12 deficiency: An association to bear in mind. World J Diabetes 2021; 12:916-931. [PMID: 34326945 PMCID: PMC8311483 DOI: 10.4239/wjd.v12.i7.916] [Citation(s) in RCA: 97] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 03/21/2021] [Accepted: 04/29/2021] [Indexed: 02/06/2023] Open
Abstract
To date, metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and efficacy profile. Indeed, metformin is the most widely used oral insulin-sensitizing agent, being prescribed to more than 100 million people worldwide, including patients with prediabetes, insulin resistance, and polycystic ovary syndrome. However, over the last decades several observational studies and meta-analyses have reported a significant association between long-term metformin therapy and an increased prevalence of vitamin B12 deficiency. Of note, evidence suggests that long-term and high-dose metformin therapy impairs vitamin B12 status. Vitamin B12 (also referred to as cobalamin) is a water-soluble vitamin that is mainly obtained from animal-sourced foods. At the cellular level, vitamin B12 acts as a cofactor for enzymes that play a critical role in DNA synthesis and neuroprotection. Thus, vitamin B12 deficiency can lead to a number of clinical consequences that include hematologic abnormalities (e.g., megaloblastic anemia and formation of hypersegmented neutrophils), progressive axonal demyelination and peripheral neuropathy. Nevertheless, no definite guidelines are currently available for vitamin B12 deficiency screening in patients on metformin therapy, and vitamin B12 deficiency remains frequently unrecognized in such individuals. Therefore, in this "field of vision" article we propose a list of criteria for a cost-effective vitamin B12 deficiency screening in metformin-treated patients, which could serve as a practical guide for identifying individuals at high risk for this condition. Moreover, we discuss additional relevant topics related to this field, including: (1) The lack of consensus about the exact definition of vitamin B12 deficiency; (2) The definition of reliable biomarkers of vitamin B12 status; (3) Causes of vitamin B12 deficiency other than metformin therapy that should be identified promptly in metformin-treated patients for a proper differential diagnosis; and (4) Potential pathophysiological mechanisms underlying metformin-induced vitamin B12 deficiency. Finally, we briefly review basic concepts related to vitamin B12 supplementation for the treatment of vitamin B12 deficiency, particularly when this condition is induced by metformin.
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Affiliation(s)
- Marco Infante
- UniCamillus, Saint Camillus International University of Health Sciences, Rome 00131, Italy
- Diabetes Research Institute Federation (DRIF), Division of Endocrinology and Diabetes, CTO Alesini Hospital, Department of Systems Medicine, University of Rome Tor Vergata, Rome 00145, Italy
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Rome 00145, Italy
| | - Martina Leoni
- Diabetes Research Institute Federation (DRIF), Division of Endocrinology and Diabetes, CTO Alesini Hospital, Department of Systems Medicine, University of Rome Tor Vergata, Rome 00145, Italy
| | - Massimiliano Caprio
- Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, Rome 00166, Italy
- Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele Pisana, Rome 00166, Italy
| | - Andrea Fabbri
- Diabetes Research Institute Federation (DRIF), Division of Endocrinology and Diabetes, CTO Alesini Hospital, Department of Systems Medicine, University of Rome Tor Vergata, Rome 00145, Italy
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Daniels MS, Park BI, McKay DL. Adverse Effects of Medications on Micronutrient Status: From Evidence to Guidelines. Annu Rev Nutr 2021; 41:411-431. [PMID: 34111363 DOI: 10.1146/annurev-nutr-120420-023854] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Recent dietary reference intake workshops focusing on nutrient requirements in chronic disease populations have called attention to the potential adverse effects of chronic medication use on micronutrient status. Although this topic is mostly ill defined in the literature, several noteworthy drug-nutrient interactions (DNIs) are of clinical and public health significance. The purpose of this narrative review is to showcase classic examples of DNIs and their impact on micronutrient status, including those related to antidiabetic, anticoagulant, antihypertensive, antirheumatic, and gastric acid-suppressing medications. Purported DNIs related to other drug families, while relevant and worthy of discussion, are not included. Unlike previous publications, this review is primarily focused on DNIs that have sufficient evidence supporting their inclusion in US Food and Drug Administration labeling materials and/or professional guidelines. While the evidence is compelling, more high-quality research is needed to establish clear and quantitative relationships between chronic medication use and micronutrient status. Expected final online publication date for the Annual Review of Nutrition, Volume 41 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Affiliation(s)
- Michael S Daniels
- Jean Mayer USDA Human Nutrition Research Center on Aging, Boston, Massachusetts 02111, USA; , .,Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts 02111, USA;
| | - Brian I Park
- Jean Mayer USDA Human Nutrition Research Center on Aging, Boston, Massachusetts 02111, USA; , .,Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts 02111, USA;
| | - Diane L McKay
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts 02111, USA;
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Luo YC, Huang SH, Pathak N, Chuang YH, Yang JM. An integrated systematic approach for investigating microcurrent electrical nerve stimulation (MENS) efficacy in STZ-induced diabetes mellitus. Life Sci 2021; 279:119650. [PMID: 34048807 DOI: 10.1016/j.lfs.2021.119650] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 05/13/2021] [Accepted: 05/18/2021] [Indexed: 11/24/2022]
Abstract
Diabetes mellitus (DM) is a major metabolic disorder and an increasing health problem worldwide. Effective non-invasive therapies for DM are still lacking. Here, we have developed Microcurrent electrical nerve stimulation (MENS), a non-invasive therapy, and tested on 46 mice clustered into five groups, such as control, STZ-induced DM, and MENS treatment groups. Experimental results show that MENS treatment is able to improve seven biochemical indexes (e.g., hemoglobin A1c and glucose level). To investigate the mechanisms of MENS treatment on STZ-induced DM, we selected six representative samples to perform microarray experiments for several groups and developed an integrated Hierarchical System Biology Model (HiSBiM) to analyze these omics data. The results indicate that MENS can affect fatty acid metabolism pathways, peroxisome proliferator-activated receptor (PPAR) signaling pathway and cell cycle. Additionally, the DM biochemical indexes and omics data profiles of MENS treatment were found to be consistent. We then compared the therapeutic effects of MENS with anti-diabetic compounds (e.g., quercetin, metformin, and rosiglitazone), using the HiSBiM four-level biological functions and processes of multiple omics data. The results show MENS and these anti-diabetic compounds have similar effect pathways highly correlated to the diabetes processes, such as the PPAR signaling pathway, bile secretion, and insulin signaling pathways. We believe that MENS is an effective and non-invasive therapy for DM and our HiSBiM is an useful method for investigating multiple omics data.
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Affiliation(s)
- Yong-Chun Luo
- Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan
| | - Sing-Han Huang
- Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan
| | - Nikhil Pathak
- Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan
| | - Yi-Hsuan Chuang
- Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan
| | - Jinn-Moon Yang
- Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan; Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan; Center for Intelligent Drug Systems and Smart Bio-devices, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan.
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Akinci G, Savelieff MG, Gallagher G, Callaghan BC, Feldman EL. Diabetic neuropathy in children and youth: New and emerging risk factors. Pediatr Diabetes 2021; 22:132-147. [PMID: 33205601 PMCID: PMC11533219 DOI: 10.1111/pedi.13153] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 11/02/2020] [Accepted: 11/12/2020] [Indexed: 12/23/2022] Open
Abstract
Pediatric neuropathy attributed to metabolic dysfunction is a well-known complication in children and youth with type 1 diabetes. Moreover, the rise of obesity and in particular of type 2 diabetes may cause an uptick in pediatric neuropathy incidence. However, despite the anticipated increase in neuropathy incidence, pathogenic insights and strategies to prevent or manage neuropathy in the setting of diabetes and obesity in children and youth remain unknown. Data from adult studies and available youth cohort studies are providing an initial understanding of potential diagnostic, management, and preventative measures in early life. This review discusses the current state of knowledge emanating from these efforts, with particular emphasis on the prevalence, clinical presentation, diagnostic approaches and considerations, and risk factors of neuropathy in type 1 and type 2 diabetes in children and youth. Also highlighted are current management strategies and recommendations for neuropathy in children and youth with diabetes. This knowledge, along with continued and sustained emphasis on identifying and eliminating modifiable risk factors, completing randomized controlled trials to assess effectiveness of strategies like weight loss and exercise, and enhancing awareness to support early detection and prevention, are pertinent to addressing the rising incidence of neuropathy associated with diabetes and obesity in children and youth.
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Affiliation(s)
- Gulcin Akinci
- Department of Neurology, University of Michigan Medicine, Ann Arbor, MI
| | | | - Gary Gallagher
- Department of Neurology, University of Michigan Medicine, Ann Arbor, MI
| | | | - Eva L. Feldman
- Department of Neurology, University of Michigan Medicine, Ann Arbor, MI
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Al Saeed RR, Baraja MA. Vitamin B12 deficiency in patients with type 2 diabetes mellitus using metformin and the associated factors in Saudi Arabia. Saudi Med J 2021; 42:161-165. [PMID: 33563734 PMCID: PMC7989282 DOI: 10.15537/smj.2021.2.25693] [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] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Accepted: 12/30/2020] [Indexed: 12/05/2022] Open
Abstract
OBJECTIVES To assess the presence of vitamin B12 deficiency among metformin users and associated factors in patients with type 2 diabetes mellitus. METHODS An observational cross-sectional study was conducted with 307 diabetic patients in the primary health care centers at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia between October 2017 and January 2018. Face-to-face interviews were conducted with the participants, using a designed checklist. RESULTS The prevalence of vitamin B12 deficiency was (3.6%) and the majority of the sample had borderline B12 levels (66.1%). The vitamin B12 deficiency and borderline levels were strongly associated with the dose of metformin. Patients taking doses of metformin more than 1000 mg had lower levels of vitamin B12. The use of multivitamin and vitamin B complex was assessed, and it was found that there was a marked decrease in the prevalence of vitamin B12 deficiency in patients using vitamin B complex containing more than 200 mcg vitamin B12. CONCLUSION Our findings show a low prevalence of vitamin B12 deficiency in type 2 diabetic patients taking metformin. The majority of the sample had borderline deficiency; therefore, additional investigation and management are required.
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Affiliation(s)
- Roqaih R. Al Saeed
- From the Department of Family Medicine (Al Saeed, Baraja), King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia.
| | - Muneera A. Baraja
- From the Department of Family Medicine (Al Saeed, Baraja), King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia.
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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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Demaré S, Kothari A, Calcutt NA, Fernyhough P. Metformin as a potential therapeutic for neurological disease: mobilizing AMPK to repair the nervous system. Expert Rev Neurother 2020; 21:45-63. [PMID: 33161784 PMCID: PMC9482886 DOI: 10.1080/14737175.2021.1847645] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Introduction: Metformin is currently first line therapy for type 2 diabetes (T2D). The mechanism of action of metformin involves activation of AMP-activated protein kinase (AMPK) to enhance mitochondrial function (for example, biogenesis, refurbishment and dynamics) and autophagy. Many neurodegenerative diseases of the central and peripheral nervous systems arise from metabolic failure and toxic protein aggregation where activated AMPK could prove protective. Areas covered: The authors review literature on metformin treatment in Parkinson’s disease, Huntington’s disease and other neurological diseases of the CNS along with neuroprotective effects of AMPK activation and suppression of the mammalian target of rapamycin (mTOR) pathway on peripheral neuropathy and neuropathic pain. The authors compare the efficacy of metformin with the actions of resveratrol. Expert opinion: Metformin, through activation of AMPK and autophagy, can enhance neuronal bioenergetics, promote nerve repair and reduce toxic protein aggregates in neurological diseases. A long history of safe use in humans should encourage development of metformin and other AMPK activators in preclinical and clinical research. Future studies in animal models of neurological disease should strive to further dissect in a mechanistic manner the pathways downstream from metformin-dependent AMPK activation, and to further investigate mTOR dependent and independent signaling pathways driving neuroprotection.
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Affiliation(s)
- Sarah Demaré
- Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre , Winnipeg, MB, Canada.,Department of Pharmacology and Therapeutics, University of Manitoba , Winnipeg, MB, Canada
| | - Asha Kothari
- Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre , Winnipeg, MB, Canada.,Department of Pharmacology and Therapeutics, University of Manitoba , Winnipeg, MB, Canada
| | - Nigel A Calcutt
- Department of Pathology, University of California San Diego , La Jolla, CA, USA
| | - Paul Fernyhough
- Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre , Winnipeg, MB, Canada.,Department of Pharmacology and Therapeutics, University of Manitoba , Winnipeg, MB, Canada
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Kleinaki Z, Kapnisi S, Theodorelou-Charitou SA, Nikas IP, Paschou SA. Type 2 diabetes mellitus management in patients with chronic kidney disease: an update. Hormones (Athens) 2020; 19:467-476. [PMID: 32500461 DOI: 10.1007/s42000-020-00212-y] [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: 02/23/2020] [Accepted: 05/14/2020] [Indexed: 02/07/2023]
Abstract
Diabetes mellitus (DM) is a chronic multisystem disease. Diabetic nephropathy (DN) is one of its significant microvascular complications, associated with increased morbidity and mortality. The aim of this article is to review the literature regarding the latest advances in the management of type 2 DM (T2DM) in patients with chronic kidney disease (CKD). We initially refer to the screening guidelines, the diagnostic tests used, the need for novel biomarkers in DN, the recent advances in high-risk patient identification, the recommended glycemic targets, and concerns regarding the accuracy of HbA1c in these patients. Then, a detailed explanation of the appropriate medical management based on evidence from recent trials is presented, analyzed, and discussed. All patients with T2DM should be screened for albuminuria at initial diagnosis and annually thereafter. Proteomics and metabolomics today represent promising diagnostic tools. Optimal glycemic control, with individualized HbA1c targets, is fundamental for reduced onset or delayed progression of DN and microvascular complications, in general. This can be enhanced by lifestyle modifications and pharmacological interventions when needed. Metformin represents the first pharmacological step, with, recently, a broadened indication for patients with impaired renal function. If HbA1c remains above the target in patients with established CKD, SGLT2i or GLP-1 RA are the preferred second-line agents, as introduced in all new guidelines. This change was the result of recent landmark trials that highlighted the superiority of the two aforementioned medication categories in terms of both renal and cardiovascular outcomes.
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Affiliation(s)
- Zoi Kleinaki
- School of Medicine, European University Cyprus, Nicosia, Cyprus
| | - Stella Kapnisi
- School of Medicine, European University Cyprus, Nicosia, Cyprus
| | | | - Ilias P Nikas
- School of Medicine, European University Cyprus, Nicosia, Cyprus
| | - Stavroula A Paschou
- School of Medicine, European University Cyprus, Nicosia, Cyprus.
- Division of Endocrinology and Diabetes, "Aghia Sophia" Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
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Tay J, Thompson CH, Luscombe-Marsh ND, Noakes M, Buckley JD, Wittert GA, Brinkworth GD. Nutritional adequacy of very low- and high-carbohydrate, low saturated fat diets in adults with type 2 diabetes: A secondary analysis of a 2-year randomised controlled trial. Diabetes Res Clin Pract 2020; 170:108501. [PMID: 33058957 DOI: 10.1016/j.diabres.2020.108501] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Revised: 09/27/2020] [Accepted: 10/06/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND Growing evidence supports use of very low-carbohydrate (LC) diets for glycaemic control in type 2 diabetes. However, limited data on the micronutrient adequacy of LC diets exist. OBJECTIVE This study compared the long-term effects of a very low-carbohydrate, high unsaturated/low saturated fat (LC) diet to a high-carbohydrate, low-fat (HC) diet on micronutrient biomarkers in adults with obesity and type 2 diabetes. METHODS 115 adults with type 2 diabetes (mean[SD]; BMI:34.6[4.3]kg/m2, age:58[7]yrs, HbA1c:7.3[1.1]%, 56[12]mmol/mol) were randomized to one of two planned, nutritionally-replete, energy-matched, hypocaloric diets (500-1000 kcal/day deficit): (1) LC:14% energy carbohydrate, 28%protein, 58%fat[<10% saturated fat]) or (2) HC:53%carbohydrate, 17%protein, 30%fat [<10%saturated fat]) for 2 years. Nutritional biomarkers- folate, β-carotene, vitamin B12, D, E, copper, zinc, selenium, calcium, magnesium, sodium, potassium, iron, ferritin, transferrin and transferrin saturation were measured in fasting blood at baseline, 24, 52 and 104 weeks. RESULTS 61 participants completed the study with similar dropouts in each group (P = 0.40). For all biomarkers assessed, there were no differential response between groups overtime (P ≥ 0.17 time × diet interaction). Mean vitamin and mineral levels remained within normal (laboratory-specific) reference ranges without any reported cases of clinical deficiencies. CONCLUSION In free-living individuals with type 2 diabetes, nutrition biomarkers within normal ranges at baseline did not change significantly after 2 years on a prescribed LC or HC diet. These results demonstrate the feasibility of delivering a nutritionally replete LC diet and the importance of considering nutritional factors in planning LC diets that have strong public health relevance to the dietary management of type 2 diabetes. TRIAL REGISTRATION http://www.anzctr.org.au/, ANZCTR No. ACTRN12612000369820.
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Affiliation(s)
- Jeannie Tay
- Commonwealth Scientific and Industrial Research Organisation (CSIRO) - Health and Biosecurity, Adelaide, Australia; Discipline of Medicine, University of Adelaide, Adelaide, Australia; Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore.
| | | | - Natalie D Luscombe-Marsh
- Commonwealth Scientific and Industrial Research Organisation (CSIRO) - Health and Biosecurity, Adelaide, Australia
| | - Manny Noakes
- Commonwealth Scientific and Industrial Research Organisation (CSIRO) - Health and Biosecurity, Adelaide, Australia
| | - Jonathan D Buckley
- Alliance for Research in Exercise, Nutrition and Activity (ARENA), University of South Australia, Adelaide, Australia
| | - Gary A Wittert
- Discipline of Medicine, University of Adelaide, Adelaide, Australia
| | - Grant D Brinkworth
- Commonwealth Scientific and Industrial Research Organisation (CSIRO) - Health and Biosecurity, Sydney, Australia
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Doyle-Delgado K, Chamberlain JJ, Shubrook JH, Skolnik N, Trujillo J. Pharmacologic Approaches to Glycemic Treatment of Type 2 Diabetes: Synopsis of the 2020 American Diabetes Association's Standards of Medical Care in Diabetes Clinical Guideline. Ann Intern Med 2020; 173:813-821. [PMID: 32866414 DOI: 10.7326/m20-2470] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
DESCRIPTION The American Diabetes Association (ADA) updates the Standards of Medical Care in Diabetes annually to provide clinicians, patients, researchers, payers, and other interested parties with evidence-based recommendations for the diagnosis and management of diabetes. METHODS To develop the 2020 Standards, the ADA Professional Practice Committee, comprising physicians, adult and pediatric endocrinologists, diabetes educators, registered dietitians, epidemiologists, pharmacists, and public health experts, continuously searched MEDLINE (English language only) from 15 October 2018 through August-September 2019 for pertinent studies, including high-quality trials that addressed pharmacologic management of type 2 diabetes. The committee selected and reviewed the studies, developed the recommendations, and solicited feedback from the larger clinical community. RECOMMENDATIONS This synopsis focuses on guidance relating to the pharmacologic treatment of adults with type 2 diabetes. Recommendations address oral and noninsulin injectable therapies, insulin treatment, and combination injectable therapies. Results of recent large trials with cardiovascular and renal outcomes are emphasized.
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Affiliation(s)
- Kacie Doyle-Delgado
- St. Mark's Hospital and St. Mark's Diabetes Center, Salt Lake City, Utah (K.D., J.J.C.)
| | - James J Chamberlain
- St. Mark's Hospital and St. Mark's Diabetes Center, Salt Lake City, Utah (K.D., J.J.C.)
| | - Jay H Shubrook
- Touro University California, College of Osteopathic Medicine, Vallejo, California (J.H.S.)
| | - Neil Skolnik
- Abington Family Medicine, Jenkintown, Pennsylvania (N.S.)
| | - Jennifer Trujillo
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado (J.T.)
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Current Concepts in Pharmacometabolomics, Biomarker Discovery, and Precision Medicine. Metabolites 2020; 10:metabo10040129. [PMID: 32230776 PMCID: PMC7241083 DOI: 10.3390/metabo10040129] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 03/19/2020] [Accepted: 03/20/2020] [Indexed: 02/07/2023] Open
Abstract
Pharmacometabolomics (PMx) studies use information contained in metabolic profiles (or metabolome) to inform about how a subject will respond to drug treatment. Genome, gut microbiome, sex, nutrition, age, stress, health status, and other factors can impact the metabolic profile of an individual. Some of these factors are known to influence the individual response to pharmaceutical compounds. An individual’s metabolic profile has been referred to as his or her “metabotype.” As such, metabolomic profiles obtained prior to, during, or after drug treatment could provide insights about drug mechanism of action and variation of response to treatment. Furthermore, there are several types of PMx studies that are used to discover and inform patterns associated with varied drug responses (i.e., responders vs. non-responders; slow or fast metabolizers). The PMx efforts could simultaneously provide information related to an individual’s pharmacokinetic response during clinical trials and be used to predict patient response to drugs making pharmacometabolomic clinical research valuable for precision medicine. PMx biomarkers can also be discovered and validated during FDA clinical trials. Using biomarkers during medical development is described in US Law under the 21st Century Cures Act. Information on how to submit biomarkers to the FDA and their context of use is defined herein.
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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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Longo SL, Ryan JM, Sheehan KB, Reid DJ, Conley MP, Bouwmeester CJ. Evaluation of vitamin B12 monitoring in patients on metformin in urban ambulatory care settings. Pharm Pract (Granada) 2019; 17:1499. [PMID: 31592289 PMCID: PMC6763298 DOI: 10.18549/pharmpract.2019.3.1499] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 09/01/2019] [Indexed: 01/31/2023] Open
Abstract
Background: Previous studies linked metformin use to vitamin B12 deficiency and demonstrated that the prevalence of vitamin B12 monitoring remains low. Objective: This study aimed to assess the occurrence of monitoring vitamin B12 levels in a diverse population. Methods: This was a retrospective chart review of adult patients with type 2 diabetes on metformin doses ≥ 1000 mg for ≥ 6 months at five Federally Qualified Health Centers (FQHC) and one Program of All-Inclusive Care for the Elderly (PACE). Charts were reviewed for occurrence of monitoring vitamin B12 levels in the past 5 years. Data collected included patient demographics, laboratory data, other potential vitamin B12 level lowering agents, active prescription for vitamin B12 supplementation, concomitant diabetes medications and metformin total daily dose. Results: Of the 322 patients included, 25% had a vitamin B12 level measured in the previous five years. Among the patients with a vitamin B12 level, 87.7% were within the normal range (>350 pg/mL), 11.1% were low (200-300 pg/mL), and only one patient (1.2%) was deficient (<200 pg/mL). These patients were older (69.2 vs. 56.4, p<0.001); more likely to be white (56.8% vs. 37.8%, p=0.04); and more likely to use proton pump inhibitors (34.6% vs. 20.7%, p=0.02) and vitamin B12 supplementation (27.2% vs. 4.6%, p<0.001). Vitamin B12 monitoring differed between the FQHC (15.2%) and PACE (97.4%) sites (p<0.001). Each greater year of age was associated with a 5% increased odds of vitamin B12 monitoring (a OR: 1.05; 95% CI: 1.02-1.08). Conclusions: The majority of patients seen at the FQHC sites did not have vitamin B12 levels monitored, however, most of the patients who were monitored had normal vitamin B12 levels, which may warrant extending the monitoring time. This finding may also support monitoring patients who have additional risk factors for vitamin B12 deficiency such as concurrent medication use with other vitamin B12 lowering agents or clinical symptoms of deficiency such as peripheral neuropathy. Future studies are needed to determine appropriate frequency of monitoring.
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Affiliation(s)
- Stacy L Longo
- Clinical Pharmacist. The Dimock Center, Roxbury, MA (United States).
| | - Jessica M Ryan
- Clinical Pharmacist. Harbor Health Services Community Health Centers, Boston, MA (United States).
| | - Kelsey B Sheehan
- Clinical Pharmacist. Harbor Health Services Elder Service Plan, Mattapan, MA (United States).
| | - Debra J Reid
- Associate Clinical Professor. School of Pharmacy, Bouvé College of Health Sciences, Northeastern University. Boston, MA (United States).
| | - Michael P Conley
- School of Pharmacy, Bouvé College of Health Sciences, Northeastern University. Boston, MA (United States).
| | - Carla J Bouwmeester
- School of Pharmacy, Bouvé College of Health Sciences, Northeastern University. Boston, MA (United States).
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Yang W, Cai X, Wu H, Ji L. Associations between metformin use and vitamin B 12 levels, anemia, and neuropathy in patients with diabetes: a meta-analysis. J Diabetes 2019; 11:729-743. [PMID: 30615306 DOI: 10.1111/1753-0407.12900] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 12/11/2018] [Accepted: 01/03/2019] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Metformin is first-line therapy for patients with diabetes. However, it may lower vitamin B12 concentrations, which could have hematological or neurological implications. This meta-analyses reviewed all available studies on associations between metformin use and vitamin B12 levels, anemia, and neuropathy in diabetic patients. METHODS PubMed, Web of Knowledge, Cochrane Library, and Embase were searched to identify all relevant studies published in English prior to March 2018. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for dichotomous outcomes and pooled mean differences (MDs) and 95% CIs were calculated for continuous outcomes. RESULTS Thirty-one studies were included in the meta-analyses. Compared with diabetic patients not taking metformin, patients taking metformin had a significantly higher risk of vitamin B12 deficiency (RR 2.09; 95% CI 1.49, 2.93; P < 0.0001; I2 = 64%) and significantly lower serum vitamin B12 concentrations (MD -63.70; 95% CI -74.35, -53.05] pM; P < 0.00001; I2 = 87%), which depended on dose and duration of treatment. Metformin use was also associated with significantly greater percentage decrease in serum vitamin B12 concentrations from baseline in diabetic patients (MD -14.68%; 95% CI -17.98%, -11.39%; P < 0.00001; I2 = 33%). Analyses revealed no significant association between metformin use and the prevalence of anemia or neuropathy. CONCLUSIONS Metformin use led to significantly lowered vitamin B12 concentrations and significantly higher risk of vitamin B12 deficiency in diabetic patients. More quality studies are needed to explore the associations between metformin use and anemia and neuropathy in these patients. Annual vitamin B12 assessment in diabetic patients taking metformin is recommended.
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Affiliation(s)
- Wenjia Yang
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Xiaoling Cai
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Haiya Wu
- Eisai China Inc., Shanghai, China
| | - Linong Ji
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
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Sharma A, Kim JW, Ku SK, Choi JS, Lee HJ. Anti-diabetic effects of blue honeyberry on high-fed-diet-induced type II diabetic mouse. Nutr Res Pract 2019; 13:367-376. [PMID: 31583055 PMCID: PMC6760985 DOI: 10.4162/nrp.2019.13.5.367] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 01/02/2019] [Accepted: 04/02/2019] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND/OBJECTIVE The blue honeysuckle berry (Lonicera caerulea var. edulis L.) is a small deciduous shrub belonging to the Caprifoliaceae family that is native to Russia, China, Japan, and Korea. The berry of this shrub is edible, sweet and juicy and is commonly known as the blue honeyberry (BHB). This study examined the anti-diabetic potential of BHB on high-fat-diet-induced mild diabetic mice. The hypoglycemic, and nephroprotective effects of the 12-week oral administration of blue honeyberry extract were analyzed. MATERIALS/METHODS The hypoglycemic effects were based on the observed changes in insulin, blood glucose, and glycated hemoglobin (HbA1c). Furthermore, the changes in the weight of the pancreas, including its histopathology and immunohistochemical investigation were also performed. Moreover, the nephroprotective effects were analyzed by observing the changes in kidney weight, its histopathology, blood urea nitrogen (BUN), and serum creatinine levels. RESULTS The results showed that the high-fat diet (HFD)-induced control mice showed a noticeable increase in blood glucose, insulin, HbA1c, BUN, and creatinine levels. Furthermore, growth was observed in lipid droplet deposition related to the degenerative lesions in the vacuolated renal tubules with the evident enlargement and hyperplasia of the pancreatic islets. In addition, in the endocrine pancreas, there was an increase in the insulin-and glucagon-producing cells, as well as in the insulin/glucagon cell ratios. On the other hand, compared to the HFD-treated mice group, all these diabetic and related complications were ameliorated significantly in a dose-dependent manner after 84 days of the continuous oral administration of BHBe at 400, 200 and 100 mg/kg, and a dramatic resettlement in the hepatic glucose-regulating enzyme activities was observed. CONCLUSIONS By assessing the key parameters for T2DM, the present study showed that the BHBe could act as a potential herbal agent to cure diabetes (type II) and associated ailments in HFD-induced mice.
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Affiliation(s)
- Anshul Sharma
- Department of Food and Nutrition, College of BioNano Technology, Gachon University, 1342 Seongnamdaero, Sujeong-gu, Seongnam, Gyeonggi 13120, Republic of Korea
| | - Joo Wan Kim
- Aribio Co. Ltd., #2-301, Pangyo Seven Venture Valley, Gyeonggi 13487, Republic of Korea
| | - Sae-Kwang Ku
- Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongbuk 38610, Republic of Korea
| | - Jae-Suk Choi
- Major in Food Biotechnology, Division of Bioindustry, College of Medical and Life Sciences, Silla University, 140, Baegyang-daero 700beon-gil, Sasang-gu, Busan 46958, Republic of Korea
| | - Hae-Jeung Lee
- Department of Food and Nutrition, College of BioNano Technology, Gachon University, 1342 Seongnamdaero, Sujeong-gu, Seongnam, Gyeonggi 13120, Republic of Korea
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Wolffenbuttel BH, Wouters HJ, Heiner-Fokkema MR, van der Klauw MM. The Many Faces of Cobalamin (Vitamin B 12) Deficiency. Mayo Clin Proc Innov Qual Outcomes 2019; 3:200-214. [PMID: 31193945 PMCID: PMC6543499 DOI: 10.1016/j.mayocpiqo.2019.03.002] [Citation(s) in RCA: 124] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Although cobalamin (vitamin B12) deficiency was described over a century ago, it is still difficult to establish the correct diagnosis and prescribe the right treatment. Symptoms related to vitamin B12 deficiency may be diverse and vary from neurologic to psychiatric. A number of individuals with vitamin B12 deficiency may present with the classic megaloblastic anemia. In clinical practice, many cases of vitamin B12 deficiency are overlooked or sometimes even misdiagnosed. In this review, we describe the heterogeneous disease spectrum of patients with vitamin B12 deficiency in whom the diagnosis was either based on low serum B12 levels, elevated biomarkers like methylmalonic acid and/or homocysteine, or the improvement of clinical symptoms after the institution of parenteral vitamin B12 therapy. We discuss the possible clinical signs and symptoms of patients with B12 deficiency and the various pitfalls of diagnosis and treatment.
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Affiliation(s)
- Bruce H.R. Wolffenbuttel
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, NL-9700 RB, The Netherlands
| | - Hanneke J.C.M. Wouters
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, NL-9700 RB, The Netherlands
- Department of Haematology, University of Groningen, University Medical Center Groningen, Groningen, NL-9700 RB, The Netherlands
| | - M. Rebecca Heiner-Fokkema
- Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, NL-9700 RB, The Netherlands
| | - Melanie M. van der Klauw
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, NL-9700 RB, The Netherlands
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Huber J, Smeikal M, Saely CH, Stingl H, Lechleitner M, Fasching P. Geriatrische Aspekte bei Diabetes mellitus (Update 2019). Wien Klin Wochenschr 2019; 131:236-245. [DOI: 10.1007/s00508-019-1463-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Abstract
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes 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, please refer to the Standards of Care Introduction Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Adeva-Andany MM, Rañal-Muíño E, Fernández-Fernández C, Pazos-García C, Vila-Altesor M. Metabolic Effects of Metformin in Humans. Curr Diabetes Rev 2019; 15:328-339. [PMID: 30306875 DOI: 10.2174/1573399814666181009125348] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 09/26/2018] [Accepted: 10/02/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND Both insulin deficiency and insulin resistance due to glucagon secretion cause fasting and postprandial hyperglycemia in patients with diabetes. INTRODUCTION Metformin enhances insulin sensitivity, being used to prevent and treat diabetes, although its mechanism of action remains elusive. RESULTS Patients with diabetes fail to store glucose as hepatic glycogen via the direct pathway (glycogen synthesis from dietary glucose during the post-prandial period) and via the indirect pathway (glycogen synthesis from "de novo" synthesized glucose) owing to insulin deficiency and glucagoninduced insulin resistance. Depletion of the hepatic glycogen deposit activates gluconeogenesis to replenish the storage via the indirect pathway. Unlike healthy subjects, patients with diabetes experience glycogen cycling due to enhanced gluconeogenesis and failure to store glucose as glycogen. These defects raise hepatic glucose output causing both fasting and post-prandial hyperglycemia. Metformin reduces post-prandial plasma glucose, suggesting that the drug facilitates glucose storage as hepatic glycogen after meals. Replenishment of glycogen store attenuates the accelerated rate of gluconeogenesis and reduces both glycogen cycling and hepatic glucose output. Metformin also reduces fasting hyperglycemia due to declining hepatic glucose production. In addition, metformin reduces plasma insulin concentration in subjects with impaired glucose tolerance and diabetes and decreases the amount of insulin required for metabolic control in patients with diabetes, reflecting improvement of insulin activity. Accordingly, metformin preserves β-cell function in patients with type 2 diabetes. CONCLUSION Several mechanisms have been proposed to explain the metabolic effects of metformin, but evidence is not conclusive and the molecular basis of metformin action remains unknown.
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Affiliation(s)
- María M Adeva-Andany
- Internal Medicine Department, Hospital General Juan Cardona, c/ Pardo Bazan s/n, 15406 Ferrol, Spain
| | - Eva Rañal-Muíño
- Internal Medicine Department, Hospital General Juan Cardona, c/ Pardo Bazan s/n, 15406 Ferrol, Spain
| | | | - Cristina Pazos-García
- Internal Medicine Department, Hospital General Juan Cardona, c/ Pardo Bazan s/n, 15406 Ferrol, Spain
| | - Matilde Vila-Altesor
- Internal Medicine Department, Hospital General Juan Cardona, c/ Pardo Bazan s/n, 15406 Ferrol, Spain
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