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Sini M, Dongmo F, Mvongo C, Fokam Tagne MA, Jidibe P, Foyet Fondjo A, Noubissi PA, Kamgang R. Antihyperglycemic and Antioxidative Stress Effects of Erythrophleum africanum (Fabaceae) Trunk Bark Powder Fractions on High-Calorie Diet-Induced Type 2 Diabetes in Rats. Food Sci Nutr 2025; 13:e70290. [PMID: 40370420 PMCID: PMC12076005 DOI: 10.1002/fsn3.70290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 04/16/2025] [Accepted: 05/04/2025] [Indexed: 05/16/2025] Open
Abstract
Diabetes mellitus is a persistent and chronic metabolic disease characterized by high blood glucose levels. The aim of this work was to evaluate the antihyperglycemic and antioxidative stress effects of Erythrophyllum africanum trunk bark powder fractions in diabetes-induced rats. 30 male rats subdivided into 6 groups of five rats each received daily a sweetened hypercaloric diet supplemented with sucrose (4 g/kg bw), except for the normal control, which received a normal diet. Normal and diabetic controls subsequently received distilled water (10 mL/kg bw per os), the positive control received metformin (20 mg/kg bw per os) and the test rats received powder fractions (≤ 50 μm ≤ 50-120 μm) or unsieved powder of E. africanum (300 mg/kg bw per os) for 7 weeks. Dexamethasone (0.2 mg/kg) was administered intraperitoneally once a week from the third week, except for the normal control, which received saline. Fasting blood glucose, lipid profile, and biochemical parameters of oxidative stress were assessed during and at the end of treatment. Blood glucose levels of the animals at the 7th week were 0.92 ± 0.03, 1.52 ± 0.08, 0.78 ± 0.04, 0.77 ± 0.03, 1.13 ± 0.03, and 0.40 ± 0.01 g/L in the normal control, diabetic control, metformin-treated animals, ≤ 50 μm fraction, 50-120 μm fraction, and unsieved powder, respectively. Powder fraction ≤ 50 μm significantly improved (p < 0.01) the lipid profile (decrease in triglyceride and LDL cholesterol levels, an increase in HDL cholesterol levels) by reducing the atherogenic index. E. africanum has antihyperglycemic and antioxidative stress effects and would be less toxic to the liver and kidneys. The fine powder (≤ 50 μm) of E. africanum could be used as a food additive to prevent the occurrence of diabetes in vulnerable patients.
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Affiliation(s)
- Mathieu Sini
- Department of Biological Sciences, Faculty of ScienceUniversity of NgaoundereNgaoundereCameroon
| | - Faustin Dongmo
- Department of Biological Sciences, Faculty of ScienceUniversity of NgaoundereNgaoundereCameroon
| | - Clemence Mvongo
- Department of Life SciencesHigher Teacher Training College, University of BertouaBertouaCameroon
| | | | - Pierre Jidibe
- Department of Biological Sciences, Faculty of ScienceUniversity of NgaoundereNgaoundereCameroon
| | - Angèle Foyet Fondjo
- Department of Applied Sciences for HealthHigher Institute of Applied Sciences, University Institute of Gulf of GuineaDoualaCameroon
| | - Paul Aimé Noubissi
- Department of Zoology and Animal Physiology, Faculty of ScienceUniversity of BueaBueaCameroon
| | - René Kamgang
- Laboratory of Endocrinology and RadioisotopesInstitute of Medical Research and Medicinal Plants Studies (IMPM)YaoundeCameroon
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Obeid R, Geisel J, Pietrzik K, Andres E. A Framework to Guide Defining an Upper Threshold of Crystalline Vitamin B12 in Foods and Food Supplements. Curr Nutr Rep 2025; 14:32. [PMID: 39939550 PMCID: PMC11821671 DOI: 10.1007/s13668-025-00622-7] [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: 01/28/2025] [Indexed: 02/14/2025]
Abstract
PURPOSE OF REVIEW To define an intake threshold of vitamin B12 from food supplements that is sufficient to maintain normal body functions, but it does not cause pharmacological effects. RECENT FINDINGS We used studies on the amount of B12 absorbed following oral B12 application and non-comparative case-series studies to synthesize evidence on pharmacological effects of oral B12 (between < 10 µg and 3000 µg) in people with manifested deficiency. There is a dose-dependent intestinal absorption of B12 and in the same time effects on body metabolism and functions. Food supplements providing ≤ 20 µg B12 daily are unlikely to cause pharmacological effects, while 50 µg might correct abnormal biochemical markers in some deficient patients. Foods for special medical purposes for people who cannot absorb B12 may contain 100 µg to 150 µg B12. This dose may ensure 1-4 µg of the vitamin reaching the circulation on a daily basis independent of intrinsic factor. Dosages ≥ 200 µg/d should be considered as drugs that can correct anemia, metabolic markers and clinical symptoms. The content of vitamin B12 in food supplements should not exceed 20 µg. In addition, people with deficiency should receive appropriate medical treatment with high dose B12.
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Affiliation(s)
- Rima Obeid
- Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, 66424, Homburg, Germany.
| | - Juergen Geisel
- Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, 66424, Homburg, Germany
| | - Klaus Pietrzik
- Department of Nutrition and Food Science, Rheinische Friedrich-Wilhelms University, Endenicher Allee 19B, 53115, Bonn, Germany
| | - Emmanuel Andres
- Department of Internal Medicine, Diabetes and Metabolic Diseases, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
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AlSaad SZ, AlHadlaq RK, Alaraik EF, Alnomany AO, AlSaif HI, Almigbal TH, Batais MA, Alrasheed AA. Evaluating Physician Knowledge, Attitudes, and Practices in Screening and Supplementation for Vitamin B12 Deficiency in Type 2 Diabetes Patients Treated with Metformin. Diabetes Metab Syndr Obes 2024; 17:3925-3934. [PMID: 39465124 PMCID: PMC11512529 DOI: 10.2147/dmso.s486059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 10/16/2024] [Indexed: 10/29/2024] Open
Abstract
Background and Aim Long-term metformin use in Type 2 Diabetes Mellitus (T2DM) patients is associated with Vitamin B12 deficiency. This study aims to evaluate physicians' knowledge, attitudes, and practices regarding Vitamin B12 screening and supplementation in this context. Methods A survey was administered to physicians across various specialties in government hospitals and primary care centers in Riyadh, Saudi Arabia, from January 2019 to January 2020. The survey assessed their knowledge, attitudes, and practices concerning Vitamin B12 deficiency screening and supplementation. Results Of the 402 participating physicians, 94.0% (378 respondents) demonstrated sufficient knowledge about Vitamin B12 deficiency. However, 26.1% believed that Vitamin B12 supplementation does not necessitate screening. 55.7% did not prescribe Vitamin B12 prophylactically, 41.5% omitted neurological examinations in patients presenting with neuropathy, and 22.4% were unaware of the recommended Vitamin B12 supplement dose. Only 49.8% routinely screened for Vitamin B12 deficiency in symptomatic patients. Physicians with more extended years of experience showed significantly better knowledge about Vitamin B12 screening and supplementation (p<0.001). Conclusion While most physicians were knowledgeable about Vitamin B12 deficiency and supplementation, a substantial gap in translating this knowledge into practice was observed. There is a critical need for institutional oversight to ensure adherence to American Diabetes Association (ADA) guidelines for Vitamin B12 screening and supplementation in T2DM patients on long-term metformin therapy.
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Affiliation(s)
- Samaher Z AlSaad
- Department of Family Medicine, Riyadh Third Cluster, Riyadh, Saudi Arabia
| | - Razan K AlHadlaq
- Department of Family medicine, King Saud Medical City, Riyadh, Saudi Arabia
| | - Enas Fahad Alaraik
- Department of Family medicine, King Saud Medical City, Riyadh, Saudi Arabia
| | | | - Haytham I AlSaif
- Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Turky H Almigbal
- Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed A Batais
- Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Abdullah A Alrasheed
- Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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Al Zoubi MS, Al Kreasha R, Aqel S, Saeed A, Al-Qudimat AR, Al-Zoubi RM. Vitamin B 12 deficiency in diabetic patients treated with metformin: A narrative review. Ir J Med Sci 2024; 193:1827-1835. [PMID: 38381379 PMCID: PMC11294377 DOI: 10.1007/s11845-024-03634-4] [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: 01/25/2024] [Accepted: 02/12/2024] [Indexed: 02/22/2024]
Abstract
Metformin is the most prescribed oral hypoglycemic drug and is considered by many health practitioners as the first-line treatment for non-insulin-dependent diabetes mellitus (T2DM). It is used either as a monotherapy or adjuvant to other anti-hyperglycemic agents. Most of its side effects are usually mild and self-limiting. However, several studies have shown an association between the use of metformin and low vitamin B12 levels in diabetic patients. The current review aimed to provide a literature review of the current published reports on the association, the possible mechanisms, and the related individualized risk factors that might lead to this incidence. The most accepted mechanism of the effect of metformin on vitamin B12 level is related to the absorption process where metformin antagonism of the calcium cation and interference with the calcium-dependent IF-vitamin B12 complex binding to the ileal cubilin receptor. In addition, many risk factors have been associated with the impact of metformin on vitamin B12 levels in diabetic patients such as dose and duration where longer durations showed a greater prevalence of developing vitamin B12 deficiency. Male patients showed lower levels of vitamin B12 compared to females. Black race showed a lower prevalence of vitamin B12 deficiency in metformin-treated patients. Moreover, chronic diseases including T2DM, hyperlipidemia, coronary artery disease, polycystic ovary disease (PCOD), obesity, and metformin therapy were significantly associated with increased risk of vitamin B12 deficiency.
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Affiliation(s)
- Mazhar Salim Al Zoubi
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, 211-63, Jordan
| | - Rasha Al Kreasha
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, 211-63, Jordan
| | - Sarah Aqel
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, 211-63, Jordan
| | - Ahmad Saeed
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, 211-63, Jordan
| | - Ahmad R Al-Qudimat
- Surgical Research Section, Department of Surgery, Hamad Medical Corporation, 3050, Doha, Qatar
| | - Raed M Al-Zoubi
- Surgical Research Section, Department of Surgery, Hamad Medical Corporation, 3050, Doha, Qatar.
- Department of Biomedical Sciences, College of Health Sciences, QU-Health, Qatar University, Doha, 2713, Qatar.
- Department of Chemistry, Jordan University of Science and Technology, P.O.Box 3030, Irbid, 22110, Jordan.
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Obeid R, Andrès E, Češka R, Hooshmand B, Guéant-Rodriguez RM, Prada GI, Sławek J, Traykov L, Ta Van B, Várkonyi T, Reiners K. Diagnosis, Treatment and Long-Term Management of Vitamin B12 Deficiency in Adults: A Delphi Expert Consensus. J Clin Med 2024; 13:2176. [PMID: 38673453 PMCID: PMC11050313 DOI: 10.3390/jcm13082176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 04/04/2024] [Accepted: 04/06/2024] [Indexed: 04/28/2024] Open
Abstract
Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker and methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing the diagnosis of B12 deficiency. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency, and the treatment goals govern decisions regarding the route and dose of B12 therapy.
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Affiliation(s)
- Rima Obeid
- Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, 66421 Homburg, Germany
| | - Emmanuel Andrès
- Department of Internal Medicine, Diabetes and Metabolic Diseases, Hôpitaux Universitaires de Strasbourg, 67091 Strasbourg, France
| | - Richard Češka
- IIIrd Department of Internal Medicine, Center of Preventive Cardiology, University General Hospital, Charles University in Prague, 110 00 Prague, Czech Republic
| | - Babak Hooshmand
- Aging Research Center, Karolinska Institute, 171 65 Stockholm, Sweden
- Department of Neurology, Benedictus Klinikum Tutzing, 82327 Tutzing, Germany
- Department of Psychiatry and Psychotherapy, Ludwig Maximillian University Hospital, 80539 Munich, Germany
| | - Rosa-Maria Guéant-Rodriguez
- INSERM, UMR_S1256, NGERE–Nutrition, Genetics, and Environmental Risk Exposure, Faculty of Medicine of Nancy, University of Lorraine, 54500 Vandoeuvre-lès-Nancy, France
- Department of Biochemistry, Molecular Biology, Nutrition, and Metabolism, University Hospital of Nancy, 54000 Vandoeuvre-lès-Nancy, France
| | - Gabriel Ioan Prada
- Clinical Department of the National Institute of Gerontology and Geriatrics “Ana Aslan”, University of Medicine and Pharmacy “Carol Davila”, 011241 Bucharest, Romania
| | - Jarosław Sławek
- Department of Neurology & Stroke, St. Adalbert Hospital, 80-462 Gdańsk, Poland
- Department of Neurological-Psychiatric Nursing, Faculty of Health Sciences, Medical University of Gdańsk, 80-210 Gdańsk, Poland
| | - Latchezar Traykov
- Department of Neurology, University Hospital “Alexandrovska”, Medical University, 1431 Sofia, Bulgaria
| | - Binh Ta Van
- Vietnam Institute of Diabetes and Metabolic Disorders, Hanoi Medical University, Hanoi 116001, Vietnam
| | - Tamás Várkonyi
- Department of Internal Medicine, University of Szeged, 6720 Szeged, Hungary
| | - Karlheinz Reiners
- Consultant in Neurology and Clinical Neurophysiology, 41844 Wegberg, Germany
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Reis da Silva T. Can supplementing vitamin B12 improve mental health outcomes?: a literature review. Br J Community Nurs 2024; 29:137-146. [PMID: 38421889 DOI: 10.12968/bjcn.2024.29.3.137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/02/2024]
Abstract
AIM This study reviews research into the effects of the supplementation of B12 in the prevention and recovery of mental illness, and the potentiation of psychotropic medication. METHODOLOGY This literature review follows a systematic approach to searching databases CINAHL, EMBASE, Medline, and PsycINFO where 287 non-duplicated articles results were received. Appropriate articles were identified through title and abstract screening and inclusion and exclusion criteria were applied. Five articles were chosen to address the research question following critical appraisal. Thematic analysis was then conducted. FINDINGS This review identified five randomised controlled trials into the supplementation of various doses of B12 in conjunction with folic acid and B6. The supplement was measured against post-stroke depression prevention, the reduction of symptoms of depression in woman with cardiovascular disease, the effect on negative symptoms in schizophrenia, the reduction and prevention of depression in older adults, and the potentiation of psychotropic interventions. The papers reviewed showed inconclusive results, but evidence to support sub-groups and specific high-risk groups. Strong evidence showed supplementation of B12, folic acid and B6 has high rates of preventing post-stroke depression. CONCLUSION The findings show that this area of research is still to be developed. The effects of B12 supplementation with other B vitamins on mental health have shown to be inconclusive. There is a case for its use to be considered within certain patient groups to aid recovery of mental health or in some high-risk patient groups. Recommendations are made for further research into high-risk groups of people that may have symptoms or symptoms that could be improved through the supplementation of B12.
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Affiliation(s)
- Tiago Reis da Silva
- Lecturer in Nursing Education Academic Education Pathways (AEP), Department of Adult Nursing, Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King's College London
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Berger MM, Shenkin A, Dizdar OS, Amrein K, Augsburger M, Biesalski HK, Bischoff SC, Casaer MP, Gundogan K, Lepp HL, de Man AME, Muscogiuri G, Pietka M, Pironi L, Rezzi S, Schweinlin A, Cuerda C. ESPEN practical short micronutrient guideline. Clin Nutr 2024; 43:825-857. [PMID: 38350290 DOI: 10.1016/j.clnu.2024.01.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 01/27/2024] [Indexed: 02/15/2024]
Abstract
BACKGROUND Trace elements and vitamins, named together micronutrients (MNs), are essential for human metabolism. The importance of MNs in common pathologies is recognized by recent research, with deficiencies significantly impacting the outcome. OBJECTIVE This short version of the guideline aims to provide practical recommendations for clinical practice. METHODS An extensive search of the literature was conducted in the databases Medline, PubMed, Cochrane, Google Scholar, and CINAHL for the initial guideline. The search focused on physiological data, historical evidence (for papers published before PubMed release in 1996), and observational and/or randomized trials. For each MN, the main functions, optimal analytical methods, impact of inflammation, potential toxicity, and provision during enteral or parenteral nutrition were addressed. The SOP wording was applied for strength of recommendations. RESULTS The limited number of interventional trials prevented meta-analysis and led to a low level of evidence for most recommendations. The recommendations underwent a consensus process, which resulted in a percentage of agreement (%): strong consensus required of >90 % of votes. Altogether the guideline proposes 3 general recommendations and specific recommendations for the 26 MNs. Monitoring and management strategies are proposed. CONCLUSION This short version of the MN guideline should facilitate handling of the MNs in at-risk diseases, whilst offering practical advice on MN provision and monitoring during nutritional support.
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Affiliation(s)
- Mette M Berger
- Faculty of Biology & Medicine, Lausanne University, Lausanne, Switzerland.
| | - Alan Shenkin
- Institute of Aging and Chronic Disease, University of Liverpool, Liverpool, UK.
| | - Oguzhan Sıtkı Dizdar
- Department of Internal Medicine and Clinical Nutrition Unit, University of Health Sciences Kayseri City Training and Research Hospital, Kayseri, Turkey.
| | - Karin Amrein
- Medical University of Graz, Department of Internal Medicine, Division of Endocrinology and Diabetology, Austria.
| | - Marc Augsburger
- University Centre of Legal Medicine Lausanne-Geneva, Lausanne University Hospital and University of Lausanne, Geneva University Hospital and University of Geneva, Lausanne-Geneva, Switzerland.
| | | | - Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Michael P Casaer
- KU Leuven, Department of Cellular and Molecular Medicine, Laboratory of Intensive Care Medicine, Leuven, Belgium.
| | - Kursat Gundogan
- Division of Intensive Care Medicine, Department of Internal Medicine, Erciyes University School of Medicine, Kayseri, Turkey.
| | | | - Angélique M E de Man
- Department of Intensive Care Medicine, Research VUmc Intensive Care (REVIVE), Amsterdam Cardiovascular Science (ACS), Amsterdam Infection and Immunity Institute (AI&II), Amsterdam Medical Data Science (AMDS), Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
| | - Giovanna Muscogiuri
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università di Napoli (Federico II), Naples, Italy; United Nations Educational, Scientific and Cultural Organization (UNESCO) Chair for Health Education and Sustainable Development, Federico II University, Naples, Italy.
| | - Magdalena Pietka
- Pharmacy Department, Stanley Dudrick's Memorial Hospital, Skawina, Poland.
| | - Loris Pironi
- Department of Medical and Surgical Sciences, University of Bologna, Italy; Centre for Chronic Intestinal Failure, IRCCS AOUBO, Bologna, Italy.
| | - Serge Rezzi
- Swiss Nutrition and Health Foundation, Epalinges, Switzerland.
| | - Anna Schweinlin
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Cristina Cuerda
- Departamento de Medicina, Universidad Complutense de Madrid, Nutrition Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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Guo J, Xie L, Zhang J, Cao H, Wang J, Wu X, Feng Y. Synthesis, Quality Control and Preliminary Activity Evaluation of a New Compound HM475. Molecules 2023; 28:molecules28093753. [PMID: 37175163 PMCID: PMC10180444 DOI: 10.3390/molecules28093753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 04/17/2023] [Accepted: 04/20/2023] [Indexed: 05/15/2023] Open
Abstract
Based on the principle of molecular splicing and theory of traditional Chinese medicine pairs, a new multi-active compound (HM475) was synthesized by connecting metformin with honokiol, and its structure was characterized, which not only reduced the toxicity of raw materials, but also maintained the original activity, and had a certain significance in research and innovation. At the same time, quality control and preliminary activity evaluation were carried out, and the effect of HM475 on neuroinflammation was further explored, which provided a new idea for drug development of neurodegenerative diseases.
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Affiliation(s)
- Jieqing Guo
- New Drug Research and Development Center, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Luming Xie
- New Drug Research and Development Center, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Jing Zhang
- New Drug Research and Development Center, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Han Cao
- New Drug Research and Development Center, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Juanxia Wang
- New Drug Research and Development Center, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Xia Wu
- New Drug Research and Development Center, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Yifan Feng
- New Drug Research and Development Center, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou 510006, China
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Luo A, Ning P, Lu H, Huang H, Shen Q, Zhang D, Xu F, Yang L, Xu Y. Association Between Metformin and Alzheimer's Disease: A Systematic Review and Meta-Analysis of Clinical Observational Studies. J Alzheimers Dis 2022; 88:1311-1323. [PMID: 35786654 DOI: 10.3233/jad-220180] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND As one of the widely used drugs for the management of type 2 diabetes mellites (T2DM), metformin is increasingly believed to delay cognitive deterioration and therapeutically for Alzheimer's disease (AD) patients especially those with T2DM. However, studies of the potential neuroprotective effects of metformin in AD patients have reported contradictory results. OBJECTIVE This study aimed to evaluate the association between metformin and the risk of developing AD. METHODS We systematically searched the PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases to identify clinical observational studies on the relationship between AD risk and metformin use published before December 20, 2021. Two investigators independently screened records, extracted data, and assessed the quality of the studies. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated using random-effect models. RESULTS After screening a total of 1,670 records, we included 10 studies involving 229,110 participants. The meta-analysis showed no significant association between AD incidence and metformin exposure (OR 1.17, 95% CI 0.88-1.56, p = 0.291). However, subgroup analysis showed that among Asians, the risk of AD was significantly higher among metformin users than those who did not (OR 1.71, 95% CI 1.24-2.37, p = 0.001). CONCLUSION The available evidence does not support the idea that metformin reduces risk of AD, and it may, in fact, increase the risk in Asians. Further well-designed randomized controlled trials are required to understand the role played by metformin and other antidiabetic drugs in the prevention of AD and other neurodegenerative diseases.
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Affiliation(s)
- Anling Luo
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, P.R. China
| | - Pingping Ning
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, P.R. China
| | - Haitao Lu
- Department of Neurology, Third People's Hospital of Chengdu, Chengdu, Sichuan Province, P.R. China
| | - Hongyan Huang
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, P.R. China
| | - Qiuyan Shen
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, P.R. China
| | - Dan Zhang
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, P.R. China
| | - Fang Xu
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, P.R. China
| | - Li Yang
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, P.R. China
| | - Yanming Xu
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, P.R. China
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10
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Berger MM, Shenkin A, Schweinlin A, Amrein K, Augsburger M, Biesalski HK, Bischoff SC, Casaer MP, Gundogan K, Lepp HL, de Man AME, Muscogiuri G, Pietka M, Pironi L, Rezzi S, Cuerda C. ESPEN micronutrient guideline. Clin Nutr 2022; 41:1357-1424. [PMID: 35365361 DOI: 10.1016/j.clnu.2022.02.015] [Citation(s) in RCA: 282] [Impact Index Per Article: 94.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 02/16/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND Trace elements and vitamins, named together micronutrients (MNs), are essential for human metabolism. Recent research has shown the importance of MNs in common pathologies, with significant deficiencies impacting the outcome. OBJECTIVE This guideline aims to provide information for daily clinical nutrition practice regarding assessment of MN status, monitoring, and prescription. It proposes a consensus terminology, since many words are used imprecisely, resulting in confusion. This is particularly true for the words "deficiency", "repletion", "complement", and "supplement". METHODS The expert group attempted to apply the 2015 standard operating procedures (SOP) for ESPEN which focuses on disease. However, this approach could not be applied due to the multiple diseases requiring clinical nutrition resulting in one text for each MN, rather than for diseases. An extensive search of the literature was conducted in the databases Medline, PubMed, Cochrane, Google Scholar, and CINAHL. The search focused on physiological data, historical evidence (published before PubMed release in 1996), and observational and/or randomized trials. For each MN, the main functions, optimal analytical methods, impact of inflammation, potential toxicity, and provision during enteral or parenteral nutrition were addressed. The SOP wording was applied for strength of recommendations. RESULTS There was a limited number of interventional trials, preventing meta-analysis and leading to a low level of evidence. The recommendations underwent a consensus process, which resulted in a percentage of agreement (%): strong consensus required of >90% of votes. Altogether the guideline proposes sets of recommendations for 26 MNs, resulting in 170 single recommendations. Critical MNs were identified with deficiencies being present in numerous acute and chronic diseases. Monitoring and management strategies are proposed. CONCLUSION This guideline should enable addressing suboptimal and deficient status of a bundle of MNs in at-risk diseases. In particular, it offers practical advice on MN provision and monitoring during nutritional support.
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Affiliation(s)
- Mette M Berger
- Department of Adult Intensive Care, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
| | - Alan Shenkin
- Institute of Aging and Chronic Disease, University of Liverpool, Liverpool, UK.
| | - Anna Schweinlin
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Karin Amrein
- Medical University of Graz, Department of Internal Medicine, Division of Endocrinology and Diabetology, Austria.
| | - Marc Augsburger
- University Centre of Legal Medicine Lausanne-Geneva, Lausanne University Hospital and University of Lausanne, Geneva University Hospital and University of Geneva, Lausanne-Geneva, Switzerland.
| | | | - Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Michael P Casaer
- KU Leuven, Department of Cellular and Molecular Medicine, Laboratory of Intensive Care Medicine, Leuven, Belgium.
| | - Kursat Gundogan
- Division of Intensive Care Medicine, Department of Internal Medicine, Erciyes University School of Medicine, Kayseri, Turkey.
| | | | - Angélique M E de Man
- Department of Intensive Care Medicine, Research VUmc Intensive Care (REVIVE), Amsterdam Cardiovascular Science (ACS), Amsterdam Infection and Immunity Institute (AI&II), Amsterdam Medical Data Science (AMDS), Amsterdam UMC, Location VUmc, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands.
| | - Giovanna Muscogiuri
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università di Napoli (Federico II), Naples, Italy; United Nations Educational, Scientific and Cultural Organization (UNESCO) Chair for Health Education and Sustainable Development, Federico II, University, Naples, Italy.
| | - Magdalena Pietka
- Pharmacy Department, Stanley Dudrick's Memorial Hospital, Skawina, Poland.
| | - Loris Pironi
- Alma Mater Studiorum - University of Bologna, Department of Medical and Surgical Sciences, Italy; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Centre for Chronic Intestinal Failure - Clinical Nutrition and Metabolism Unit, Italy.
| | - Serge Rezzi
- Swiss Nutrition and Health Foundation (SNHf), Epalinges, Switzerland.
| | - Cristina Cuerda
- Departamento de Medicina, Universidad Complutense de Madrid, Nutrition Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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11
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Zhang Y, Zhang Y, Shi X, Han J, Lin B, Peng W, Mei Z, Lin Y. Metformin and the risk of neurodegenerative diseases in patients with diabetes: A meta-analysis of population-based cohort studies. Diabet Med 2022; 39:e14821. [PMID: 35213749 DOI: 10.1111/dme.14821] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 02/23/2022] [Indexed: 11/29/2022]
Abstract
AIMS The association between metformin use and neurodegenerative disease (ND) onset remains controversial. In this systematic review and meta-analysis, we aimed to determine the relationship between metformin use and ND risk based on data from population-based cohort studies. METHODS Articles were systematically searched in PubMed, EMBASE and Cochrane Library databases. Pooled relative risks (RRs) with 95% CIs were obtained using a random-effects model. Subgroup analyses, sensitivity analyses and meta-regression were performed to identify the sources of heterogeneity and strengthen the results. RESULTS Twelve population-based cohort studies involving 194,792 participants (94,462 metformin users and 100,330 metformin non-users) were eligible for inclusion in this meta-analysis. The pooled RR of NDs reached 0.77 (95% CI 0.67-0.88) when comparing metformin users with non-users. The effects were more prominent in long-term metformin users (≥4 years) (RR 0.29, 95% CI 0.13-0.44) and studies from Asian countries (RR 0.69, 95% CI 0.64-0.74). The effect estimates were stable when stratified by subtypes of NDs, study designs, and control definitions (p for interaction >0.05). Meta-regression did not identify the coefficients as the sources of heterogeneity (all p > 0.05). CONCLUSIONS This systematic review and meta-analysis found that metformin use, especially long-term use, was associated with lower ND risk. However, because there was substantial heterogeneity among studies, high-quality randomized controlled trials are still needed to confirm this finding.
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Affiliation(s)
- Yunnan Zhang
- Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- School of Pharmaceutical Sciences, Capital Medical University, Beijing, China
| | - Yi Zhang
- Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- School of Pharmaceutical Sciences, Capital Medical University, Beijing, China
| | - Xiujin Shi
- Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Jialun Han
- Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- School of Pharmaceutical Sciences, Capital Medical University, Beijing, China
| | - Baidi Lin
- Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- School of Pharmaceutical Sciences, Capital Medical University, Beijing, China
| | - Wenxing Peng
- Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Zubing Mei
- Department of Anorectal Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Anorectal Disease Institute of Shuguang Hospital, Shanghai, China
| | - Yang Lin
- Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- School of Pharmaceutical Sciences, Capital Medical University, Beijing, China
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12
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Vitamin B12 Deficiency in Patients with Diabetes on Metformin: Arab Countries. Nutrients 2022; 14:nu14102046. [PMID: 35631186 PMCID: PMC9144422 DOI: 10.3390/nu14102046] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 05/07/2022] [Accepted: 05/11/2022] [Indexed: 11/30/2022] Open
Abstract
Background: Diabetes is a global pandemic, especially in Arab countries. Aim: The goal of this study was to review the published studies that were conducted to determine the relationship between metformin treatment for type 2 diabetes mellitus (T2DM) and vitamin B12 deficiency and to identify possible complications in this relationship. Methods: I searched for all relevant studies published in English before 2020 on the PubMed and Web of Knowledge databases using the following terms: “metformin”, “vitamin B12”, “neuropathy”, “diabetes mellitus”, and Middle Eastern countries. Results: Eleven studies were included in this review which indicated an association between taking metformin and B12 deficiency in patients with T2DM in Arab countries. This B12 deficiency was found to be negatively associated with the dose and duration of metformin therapy. The physician’s knowledge of current ADA recommendations regarding supplementation with and screening of the B12 level for T2DM patients on metformin was also found to have an effect. Conclusion: Metformin therapy is associated with B12 deficiency among people with T2DM in Arabic countries. Thus, diabetes must be managed in compliance with current guidelines and recommendations, and B12 levels must be routinely monitored, particularly in those who have been long-term takers of metformin, to ensure the suitable management of diabetes and its complications.
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13
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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: 95] [Impact Index Per Article: 23.8] [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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14
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Serra MC, Kancherla V, Khakharia A, Allen LL, Phillips LS, Rhee MK, Wilson PWF, Vaughan CP. Long-term metformin treatment and risk of peripheral neuropathy in older Veterans. Diabetes Res Clin Pract 2020; 170:108486. [PMID: 33035597 PMCID: PMC8015419 DOI: 10.1016/j.diabres.2020.108486] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 09/09/2020] [Accepted: 09/25/2020] [Indexed: 12/16/2022]
Abstract
AIM Our objective was to assess whether increased duration of metformin therapy is associated with incident peripheral neuropathy (PN) in older Veterans with diabetes. METHODS Using national Veterans Affairs registry data from 2002 to 2015, we examined Veterans (50 + years) with diabetes. Long-term metformin therapy was defined as prescription ≥ 500 mg/day, filled for ≥ 6 consecutive months. Metformin therapy duration was examined both as continuous and categorical measures. Incident PN was defined by medical chart review. We estimated unadjusted and adjusted (variables selecteda priori)odds ratios (OR) and 95% confidence intervals (CI) using logistic regression. RESULTS The study included n = 210,004 individuals (mean ± SD: age: 66.2 ± 8.4 yrs, 96% male) prescribed metformin for 47.0 ± 34.0 months. Nineteen percent developed PN during follow-up. After adjusting for age, body mass index, duration of time receiving health care within the VA, smoking status, alcohol abuse, and vitamin B12 testing and treatment, the number of months of metformin treatment was associated with elevated odds for incident PN (aOR (metformin treatment - continuous) = 1.009 (95% CI = 1.009, 1.010); aOR (metformin treatment - categorical (ref: 6-<18 months): 18-<44.1 months = 1.57 (1.51-1.63), 44.1-<61 months = 2.05 (1.97-2.14), 61 + months = 2.69 (2.58-2.79), all p-values < 0.0001). CONCLUSION Our study suggests that Veterans treated for at least 18 months with metformin are approximately 2-3 times more likely to develop PN than those treated at least six, but<18 months. Future studies are needed to determine whether the association we found may be due to a decline in vitamin B12 status following metformin initiation.
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Affiliation(s)
- Monica C Serra
- Division of Geriatrics, Gerontology & Palliative Medicine and the Sam & Ann Barshop Institute for Longevity & Aging Studies, UT Health San Antonio, San Antonio, TX, USA; Department of Veterans Affairs, San Antonio Geriatric Research Education and Clinical Center, South Texas VA Health Care System, San Antonio, TX, USA.
| | - Vijaya Kancherla
- Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA
| | - Anjali Khakharia
- Division of General Medicine and Geriatrics, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Latricia L Allen
- Division of General Medicine and Geriatrics, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Department of Veterans Affairs, Birmingham/Atlanta Geriatric Research Education and Clinical Center, Decatur, GA, USA
| | - Lawrence S Phillips
- Atlanta VA Health Care System, Decatur, GA, USA; Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Mary K Rhee
- Atlanta VA Health Care System, Decatur, GA, USA; Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Peter W F Wilson
- Atlanta VA Health Care System, Decatur, GA, USA; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Camille P Vaughan
- Division of General Medicine and Geriatrics, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Department of Veterans Affairs, Birmingham/Atlanta Geriatric Research Education and Clinical Center, Decatur, GA, USA
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15
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Runeberg HA, Higbea AM, Weideman RA, Alvarez CA. Evaluation of Vitamin B 12 Monitoring in Veterans With Type 2 Diabetes on Metformin Therapy. J Pharm Pract 2020; 34:715-720. [PMID: 31955662 DOI: 10.1177/0897190019899260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Studies have shown an association between metformin use and vitamin B12 deficiency. Since 2017, the American Diabetes Association (ADA) Standards of Medical Care in Diabetes Guideline has included a recommendation for periodic vitamin B12 measurements in metformin-treated patients, especially those with anemia or peripheral neuropathy. OBJECTIVE To determine the overall incidence and impact of the ADA Guideline on vitamin B12 monitoring in a veteran population on long-term metformin therapy. METHODS Retrospective chart review was performed for patients on metformin who started therapy prior to 2005 at the VA North Texas Health Care System (VANTXHCS). The primary outcome was the proportion of patients with at least 1 vitamin B12 level drawn during 2016 versus 2018. Metformin dose and duration, vitamin B12 supplementation, and incident neuropathy prescriptions or diagnosis were also analyzed. RESULTS Of 394 patients included for the primary outcome, 136 (34.5%) had at least 1 vitamin B12 level in 2016 versus 198 (50.3%) patients in 2018 (odds ratio: 1.94, P < .001). Of the 394 patients, 157 were diagnosed with neuropathy or prescribed a medication for neuropathy without a vitamin B12 level in the previous year or with a low level that was not supplemented. CONCLUSION Vitamin B12 monitoring significantly increased between 2016 and 2018, aligning with the release of the 2017 ADA guidelines. However, a large proportion of patients were identified who were diagnosed with or treated for neuropathy without adequate vitamin B12 monitoring.
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Affiliation(s)
| | - Ashley M Higbea
- Texas Tech University Health Sciences Center, Jerry H. Hodge School of Pharmacy, Dallas, TX, USA
| | | | - Carlos A Alvarez
- Texas Tech University Health Sciences Center, Jerry H. Hodge School of Pharmacy, Dallas, TX, USA
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16
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Herbert L, Ribar A, Mitchell S, Phillips C. Discovering metformin-induced vitamin B12 deficiency in patients with type 2 diabetes in primary care. J Am Assoc Nurse Pract 2019; 33:174-180. [PMID: 31651584 DOI: 10.1097/jxx.0000000000000312] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2019] [Accepted: 07/19/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Although metformin is the preferred initial pharmacological choice in type 2 diabetes, there is evidence that reveals a link between metformin use and vitamin B12 deficiency. The American Diabetes Association (ADA) has recently recommended periodic measurement of B12 levels for all patients on metformin. LOCAL PROBLEM Medical record data collected for the preintervention period showed that only 5% (n = 23) of patients diagnosed with diabetes and on metformin had B12 levels checked at an internal medicine primary care practice. METHODS This was a quasi-experimental project of preintervention and postintervention design using a checklist containing important measures of diabetes control. The project sample population consisted of data of adults with type 2 diabetes aged 18 years and older who were prescribed metformin in the previous year at the primary care practice. INTERVENTIONS The intervention focused on revising an existing diabetes measures checklist to include a prompt for an annual measurement of B12 levels. RESULTS There was significant improvement in monitoring vitamin B12 levels and discovery of low vitamin B12 levels. These data show that the number of B12 levels checked increased from 23 during the preintervention to 155 during the intervention (p ≤ 0.0000). CONCLUSIONS This project supports a conclusion that including a prompt to check B12 levels to an existing checklist increases B12 monitoring in this patient population. Results may encourage other providers to follow the ADA guidelines for monitoring vitamin B12 levels for patients taking metformin.
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Affiliation(s)
- Laura Herbert
- Midlands Internal Medicine, Columbia, South Carolina
- University of South Carolina, College of Nursing, Columbia, South Carolina
| | - Alicia Ribar
- University of South Carolina, College of Nursing, Columbia, South Carolina
| | - Sheryl Mitchell
- University of South Carolina, College of Nursing, Columbia, South Carolina
| | - Cynthia Phillips
- Midlands Internal Medicine, Columbia, South Carolina
- University of South Carolina, College of Pharmacy, Columbia, South Carolina
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17
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Porter KM, Ward M, Hughes CF, O'Kane M, Hoey L, McCann A, Molloy AM, Cunningham C, Casey MC, Tracey F, Strain S, McCarroll K, Laird E, Gallagher AM, McNulty H. Hyperglycemia and Metformin Use Are Associated With B Vitamin Deficiency and Cognitive Dysfunction in Older Adults. J Clin Endocrinol Metab 2019; 104:4837-4847. [PMID: 30920623 DOI: 10.1210/jc.2018-01791] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2018] [Accepted: 03/22/2019] [Indexed: 02/02/2023]
Abstract
CONTEXT Emerging evidence suggests that deficiencies of folate-related B vitamins can arise with metformin treatment and are independently linked with cognitive dysfunction, a comorbidity of diabetes. OBJECTIVE To determine the impact of hyperglycemia and metformin use on relevant B vitamin biomarkers and cognitive outcomes in older adults. SETTING AND PARTICIPANTS Community-dwelling older adults (74.1 ± 8.3 years, n = 4160) without dementia, recruited to the Trinity, Ulster and Department of Agriculture cohort study in 2008 to 2012, were classified as normoglycemic (n = 1856) or hyperglycemic, based on HbA1c ≥5.7% (39 mmol/mol), either with (n = 318) or without (n = 1986) metformin treatment. MAIN OUTCOME MEASURES Biomarkers of folate, vitamin B12, vitamin B6, and riboflavin were measured. Cognitive assessments included the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) and the Frontal Assessment Battery (FAB). RESULTS Metformin use was associated with higher risk of deficiency of vitamin B12 (combined B12 index ≤-1; OR 1.45; 95% CI, 1.03 to 2.02) and vitamin B6 (plasma pyridoxal 5-phosphate <30.0 nmol/L; OR 1.48; 95% CI, 1.02 to 2.15). Fortified foods when eaten regularly had a positive impact on all relevant B vitamin biomarkers, even with hyperglycemia. After adjustment for relevant covariates, metformin use was associated with an increased risk of cognitive dysfunction as assessed with the RBANS (OR 1.36; 95% CI, 1.03 to 1.80) and FAB (OR 1.34; 95% CI, 1.03 to 1.74). CONCLUSIONS Use of metformin by older adults is associated with poorer cognitive performance; B vitamin deficiency may be implicated. Fortified foods can optimize B vitamin status and may be beneficial for maintaining better cognitive health in older people with or at risk for diabetes.
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Affiliation(s)
- Kirsty M Porter
- Nutrition Innovation Centre for Food and Health, Biomedical Sciences Research Institute, Ulster University, Coleraine, Northern Ireland, United Kingdom
| | - Mary Ward
- Nutrition Innovation Centre for Food and Health, Biomedical Sciences Research Institute, Ulster University, Coleraine, Northern Ireland, United Kingdom
| | - Catherine F Hughes
- Nutrition Innovation Centre for Food and Health, Biomedical Sciences Research Institute, Ulster University, Coleraine, Northern Ireland, United Kingdom
| | - Maurice O'Kane
- Clinical Chemistry Laboratory, Western Health and Social Care Trust, Altnagelvin Hospital, Londonderry, Northern Ireland, United Kingdom
| | - Leane Hoey
- Nutrition Innovation Centre for Food and Health, Biomedical Sciences Research Institute, Ulster University, Coleraine, Northern Ireland, United Kingdom
| | | | - Anne M Molloy
- School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - Conal Cunningham
- Mercers Institute for Research on Aging, St James's Hospital, Dublin, Ireland
| | - Miriam C Casey
- Mercers Institute for Research on Aging, St James's Hospital, Dublin, Ireland
| | - Fergal Tracey
- Causeway Hospital, Northern Health and Social Care Trust, Coleraine, Northern Ireland, United Kingdom
| | - Sean Strain
- Nutrition Innovation Centre for Food and Health, Biomedical Sciences Research Institute, Ulster University, Coleraine, Northern Ireland, United Kingdom
| | - Kevin McCarroll
- Mercers Institute for Research on Aging, St James's Hospital, Dublin, Ireland
| | - Eamon Laird
- School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - Alison M Gallagher
- Nutrition Innovation Centre for Food and Health, Biomedical Sciences Research Institute, Ulster University, Coleraine, Northern Ireland, United Kingdom
| | - Helene McNulty
- Nutrition Innovation Centre for Food and Health, Biomedical Sciences Research Institute, Ulster University, Coleraine, Northern Ireland, United Kingdom
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18
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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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19
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Alshammari AN, Iqbal R, Baksh IP. Vitamin B12 deficiency and the knowledge and practice of physicians regarding screening for vitamin B12 deficiency among type 2 diabetic patients on metformin in selected hospitals in Riyadh, Saudi Arabia. J Family Med Prim Care 2019; 8:2306-2311. [PMID: 31463247 PMCID: PMC6691434 DOI: 10.4103/jfmpc.jfmpc_416_19] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Background/Aim: The worldwide prevalence of diabetes is high including Saudi Arabia. One standard first-line treatment for diabetes is metformin, which was reported to increase the risk for vitamin B12 deficiency. We wanted to determine the prevalence of vitamin B12 deficiency in metformin-treated type 2 diabetes mellitus patients. Methods: We conducted a cross-sectional study at the diabetic clinics of four hospitals in Riyadh, Saudi Arabia. Type 2 diabetes mellitus patients who were on metformin for at least 1 year were included in the study. Associations between B12 deficiency and age, duration of type 2 diabetes mellitus (T2DM), duration of use and dosage of metformin, and use of proton pump inhibitors (PPIs) were determined. Results: Of 363 T2DM patients, 206 (56.7%) were males and 157 (43.3%) were females, mean age was 53.72 ± 11.31 years, the mean duration of T2DM was 9.89 ± 7.32 years, and the mean duration of metformin use was 9.84 ± 7.29 years. There were 205 patients 56.5% who had a daily dose of 750 mg of metformin. The most commonly used oral hypoglycemic agent was gliclizide only in 138 (38.4%) of patients. There were 107 patients (29.5%) who were on PPIs. There were 210 patients (57.9%) who were on vitamin B12 supplementation, of which 111 (30.6%) had a daily dose of 200 mcg. The use of vitamin B12 supplement, duration of T2DM and duration of metformin use was significantly higher among females. The use of vitamin B12 supplement was significant among patients who were 46 years old and above. There were only 16 patients (4.4%) who had available serum vitamin B12 levels. Only 44.0% of the physician respondents know the current recommendation of American Diabetes Association on vitamin B12 screening and supplementation among diabetic patients, and 21.0% never prescribe vitamin B12 to their patients. Conclusion: Routine testing for serum vitamin B12 level is not practiced in our institution. A large percentage of physicians are not aware of the current recommendations of the American Diabetic Association (ADA) regarding vitamin B12 supplementation and screening. Thus, there is a need for doctors involved in the management of diabetes to keep abreast with guidelines and current recommendations and routinely monitor vitamin B12 levels particularly those who were on long-term takers of metformin and the elderly patients to optimize management of diabetes and its complications.
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Affiliation(s)
- Amal N Alshammari
- Department of Family and Community Medicine, Joint Program, Riyadh, Saudi Arabia
| | - Rafay Iqbal
- Department of Family and Community Medicine, Joint Program, Riyadh, Saudi Arabia
| | - Iqra Peer Baksh
- Department of Dermatology, General Practitioner, Riyadh, Saudi Arabia
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Soysal P, Smith L, Capar E, Kalan U, Arik F, Isik AT. Vitamin B12 and folate deficiencies are not associated with nutritional or weight status in older adults. Exp Gerontol 2018; 116:1-6. [PMID: 30550763 DOI: 10.1016/j.exger.2018.12.007] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 11/25/2018] [Accepted: 12/10/2018] [Indexed: 12/22/2022]
Abstract
It is not known whether undernutrition causes vitamin B12 and folate deficiencies. The present study aimed to determine whether nutritional status, measured using the Mini Nutritional Assessment (MNA) scale, and body mass index (BMI) are indicators of lower level serum vitamin B12 and folate in older adults. 1007 outpatients aged 65 years or over were included the study. MNA scores >23.5, 17-23.5, <17, were categorized as normal nutritional status, risk of malnutrition, and malnutrition, respectively. Weight status was assessed using BMI and categorized as under or normal weight (<25 kg/m2), overweight (25-30 kg/m2), class I obese (30.0-35 kg/m2), class II obese (35-40 kg/m2), and class III obese (≥40 kg/m2). Vitamin B12 and folate deficiencies were defined as <200 pg/ml and <3 ng/ml, respectively. Among 1007 patients with an average age of 74.3 ± 8.2 years, 6.9% were categorized as having malnutrition and 31.2% were categorized as at risk of malnutrition. While 45.7% of patients were categorized as having vitamin B12 deficiency and 0.9% folate deficiency. There were no differences between patients with malnutrition, at risk of malnutrition, and good nutrition in serum vitamin B12 or folate levels, or the presence of vitamin B12 or folate deficiency after adjustment for age, gender, and education (p > 0.05). The results were the same across BMI classifications (p > 0.05). Vitamin B12 and folate levels are not associated with nutritional or weight status and these should be evaluated independently of BMI and MNA values.
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Affiliation(s)
- Pinar Soysal
- Department of Geriatric Medicine, Bezmialem Vakif University, Faculty of Medicine, Istanbul, Turkey.
| | - Lee Smith
- The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge, United Kingdom
| | - Emre Capar
- Kayseri Education and Research Hospital, Geriatric Center, Department of Internal Medicine, Kayseri, Turkey
| | - Ugur Kalan
- Kayseri Education and Research Hospital, Geriatric Center, Department of Internal Medicine, Kayseri, Turkey
| | - Ferhat Arik
- Kayseri Education and Research Hospital, Geriatric Center, Department of Internal Medicine, Kayseri, Turkey
| | - Ahmet Turan Isik
- Unit for Aging Brain and Dementia, Department of Geriatric Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
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Wang M, Liu Y, Ren G, Wang W, Wu S, Shen J. Bioinspired carbon quantum dots for sensitive fluorescent detection of vitamin B12 in cell system. Anal Chim Acta 2018; 1032:154-162. [DOI: 10.1016/j.aca.2018.05.057] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Revised: 05/02/2018] [Accepted: 05/22/2018] [Indexed: 12/12/2022]
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Meneilly GS, Knip A, Miller DB, Sherifali D, Tessier D, Zahedi A. Diabetes in Older People. Can J Diabetes 2018; 42 Suppl 1:S283-S295. [PMID: 29650107 DOI: 10.1016/j.jcjd.2017.10.021] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Indexed: 12/15/2022]
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Valencia WM, Botros D, Vera-Nunez M, Dang S. Diabetes Treatment in the Elderly: Incorporating Geriatrics, Technology, and Functional Medicine. Curr Diab Rep 2018; 18:95. [PMID: 30187176 DOI: 10.1007/s11892-018-1052-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE OF REVIEW The current approach to diabetes in the elderly incorporates components from the comprehensive geriatric approach. The most updated guidelines from the American Diabetes Association reflect influence from the consensus made in 2012 with the American Geriatrics Society. Notably, the framework included the evaluation for geriatric syndromes (falls and urinary incontinence), functional and cognitive abilities. The goal for this review is to provide an updated summary of treatment strategies for community-dwelling older adults. We identified the need to expand our approach by addressing innovative approaches and scientific concepts from telemedicine, functional medicine, and geriatrics. RECENT FINDINGS Findings on cardiovascular protection with sodium-glucose co-transporter 2 inhibitors (SGLT-2i) and some glucagon-like peptide 1 receptor agonists (GLP-1RA) support their use for older patients with diabetes. However, careful consideration for agent selection must incorporate the presence of geriatric issues, such as geriatric syndromes, or functional and cognitive decline, as they could increase the risk and impact adverse reactions. Telemedicine interventions can improve communication and connection between older patients and their providers, and improve glycemic control. Functional medicine concepts can offer additional adjuvant strategies to support the therapeutic interventions and management of diabetes in the elderly. A systematic review confirmed the efficacy and safety of metformin as first-line therapy of type 2 diabetes in the older adult, but multiple reports highlighted the risk for vitamin B12 deficiency. Randomized controlled trials showed the efficacy and safety of antihyperglycemic agents in the elderly, including some with longer duration and lesser risk for hypoglycemia. Randomized clinical trials showed cardiovascular protection with SGLT-2i (empagliflozin, canagliflozin) and GLP-1RA (liraglutide, semaglutide). The most current guidelines recommend addressing for geriatric syndromes, physical and cognitive function in the elderly, in order to individualize targets and therapeutic strategies. Clinicians managing diabetes in the elderly can play a major role for the early detection and evaluation of geriatric issues in their patients. Telemedicine interventions improve glycemic control, and certain functional medicine strategies could be adjuvant interventions to reduce inflammation and stress, but more studies focused on the elderly population are needed.
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Affiliation(s)
- Willy Marcos Valencia
- Geriatric Research, Education and Clinical Center (GRECC), Miami VA Healthcare System, 1201 NW 16th St. (11 GRC), Miami, FL, 33125, USA.
- Department of Humanities, Health and Society, Florida International University Herbert Wertheim College of Medicine, Miami, FL, USA.
- Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
| | - Diana Botros
- Jackson Memorial Hospital, University of Miami Miller School of Medicine, 1611 NW 12th Ave, Miami, FL, 33136, USA
| | - Maria Vera-Nunez
- Institute for NeuroImmune Medicine (INIM), Nova Southeastern University College of Osteopathic Medicine, 3301 College Ave, CCR 4th Floor, Fort Lauderdale, FL, 33314, USA
| | - Stuti Dang
- Geriatric Research, Education and Clinical Center (GRECC), Miami VA Healthcare System, 1201 NW 16th St. (11 GRC), Miami, FL, 33125, USA
- Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
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Marsman D, Belsky DW, Gregori D, Johnson MA, Low Dog T, Meydani S, Pigat S, Sadana R, Shao A, Griffiths JC. Healthy ageing: the natural consequences of good nutrition-a conference report. Eur J Nutr 2018; 57:15-34. [PMID: 29799073 PMCID: PMC5984649 DOI: 10.1007/s00394-018-1723-0] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Many countries are witnessing a marked increase in longevity and with this increased lifespan and the desire for healthy ageing, many, however, suffer from the opposite including mental and physical deterioration, lost productivity and quality of life, and increased medical costs. While adequate nutrition is fundamental for good health, it remains unclear what impact various dietary interventions may have on prolonging good quality of life. Studies which span age, geography and income all suggest that access to quality foods, host immunity and response to inflammation/infections, impaired senses (i.e., sight, taste, smell) or mobility are all factors which can limit intake or increase the body's need for specific micronutrients. New clinical studies of healthy ageing are needed and quantitative biomarkers are an essential component, particularly tools which can measure improvements in physiological integrity throughout life, thought to be a primary contributor to a long and productive life (a healthy "lifespan"). A framework for progress has recently been proposed in a WHO report which takes a broad, person-centered focus on healthy ageing, emphasizing the need to better understand an individual's intrinsic capacity, their functional abilities at various life stages, and the impact by mental, and physical health, and the environments they inhabit.
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Affiliation(s)
- D Marsman
- Procter & Gamble, Cincinnati, OH, USA
| | - D W Belsky
- Duke University, Raleigh-Durham, NC, USA
| | | | | | - T Low Dog
- Integrative Medicine Concepts, Tucson, AZ, USA
| | | | - S Pigat
- Creme Global, Dublin, Ireland
| | - R Sadana
- World Health Organization, Geneva, Switzerland
| | - A Shao
- Amway/Nutrilite, Buena Park, CA, USA
| | - J C Griffiths
- Council for Responsible Nutrition-International, Washington, DC, USA.
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26
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Gómez-Huelgas R, Gómez Peralta F, Rodríguez Mañas L, Formiga F, Puig Domingo M, Mediavilla Bravo JJ, Miranda C, Ena J. [Treatment of type 2 diabetes mellitus in elderly patients]. Rev Esp Geriatr Gerontol 2018; 53:89-99. [PMID: 29439834 DOI: 10.1016/j.regg.2017.12.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Accepted: 12/18/2017] [Indexed: 06/08/2023]
Abstract
The prevalence of type 2 diabetes mellitus (DM2) increases markedly with age. Antidiabetic treatment and the objectives of glycaemic control in elderly patients with DM2 should be individualised according to their biopsychosocial characteristics. In elderly patients for whom the benefits of intensive antidiabetic treatment are limited, the basic objectives should be to improve the quality of life, preserve functionality and avoid adverse effects, especially hypoglycaemia. Treatment of DM2 in the elderly was the subject of a consensus document published in 2012 and endorsed by several Spanish scientific societies. Since then, new therapeutic groups and evidence have emerged that warrant an update to this consensus document. The present document focuses on the therapeutic aspects of DM2 in elderly patients, understood as being older than 75 years or frail.
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Affiliation(s)
- R Gómez-Huelgas
- Servicio de Medicina Interna, Hospital Regional Universitario de Málaga, Málaga, España; Instituto de Investigación Biomédica de Málaga (IBIMA); CIBER de Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III; Sociedad Española de Medicina Interna (SEMI).
| | - F Gómez Peralta
- Unidad de Endocrinología y Nutrición, Hospital General de Segovia, Segovia, España; Sociedad Española de Diabetes (SED)
| | - L Rodríguez Mañas
- Servicio de Geriatría, Hospital Universitario de Getafe, Madrid, España; CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III; Sociedad Española de Medicina Geriátrica (SEMEG)
| | - F Formiga
- Unidad de Geriatría, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, España; Sociedad Española de Geriatría y Gerontología (SEGG)
| | - M Puig Domingo
- Servicio de Endocrinología y Nutrición, Hospital Germans Trias i Pujol, Badalona, Barcelona, España; Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, España; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III; Sociedad Española de Endocrinología y Nutrición (SEEN)
| | - J J Mediavilla Bravo
- Centro de Salud Burgos Rural, Burgos, España; Sociedad Española de Medicina General (SEMERGEN)
| | - C Miranda
- Centro de Salud Buenavista, Toledo, España; Sociedad Española de Médicos Generales y de Familia (SEMG)
| | - J Ena
- Servicio de Medicina Interna, Hospital Marina Baixa, La Vila Joiosa, Alicante, España; Sociedad Española de Medicina Interna (SEMI)
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Gómez-Huelgas R, Gómez Peralta F, Rodríguez Mañas L, Formiga F, Puig Domingo M, Mediavilla Bravo JJ, Miranda C, Ena J. Treatment of type 2 diabetes mellitus in elderly patients. Rev Clin Esp 2018; 218:74-88. [PMID: 29366502 DOI: 10.1016/j.rce.2017.12.003] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Accepted: 12/03/2017] [Indexed: 02/06/2023]
Abstract
The prevalence of type 2 diabetes mellitus (DM2) increases markedly with age. Antidiabetic treatment and the objectives of glycaemic control in elderly patients with DM2 should be individualised according to their biopsychosocial characteristics. In elderly patients for whom the benefits of intensive antidiabetic treatment are limited, the basic objectives should be to improve the quality of life, preserve functionality and avoid adverse effects, especially hypoglycaemia. Treatment of DM2 in the elderly was the subject of a consensus document published in 2012 and endorsed by several Spanish scientific societies. Since then, new therapeutic groups and evidence have emerged that warrant an update to this consensus document. The present document focuses on the therapeutic aspects of DM2 in elderly patients, understood as being older than 75 years or frail.
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Affiliation(s)
- R Gómez-Huelgas
- Servicio de Medicina Interna, Hospital Regional Universitario de Málaga, Málaga, España; Instituto de Investigación Biomédica de Málaga (IBIMA); CIBER de Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III; Sociedad Española de Medicina Interna (SEMI).
| | - F Gómez Peralta
- Unidad de Endocrinología y Nutrición, Hospital General de Segovia, Segovia, España; Sociedad Española de Diabetes (SED)
| | - L Rodríguez Mañas
- Servicio de Geriatría, Hospital Universitario de Getafe, Madrid, España; CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III; Sociedad Española de Medicina Geriátrica (SEMEG)
| | - F Formiga
- Unidad de Geriatría, Hospital Universitari de Bellvitge, ĹHospitalet de Llobregat, Barcelona, España; Sociedad Española de Geriatría y Gerontología (SEGG)
| | - M Puig Domingo
- Servicio de Endocrinología y Nutrición, Hospital Germans Trias i Pujol, Badalona, Barcelona, España; Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, España; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III; Sociedad Española de Endocrinología y Nutrición (SEEN)
| | - J J Mediavilla Bravo
- Centro de Salud Burgos Rural, Burgos, España; Sociedad Española de Medicina General (SEMERGEN)
| | - C Miranda
- Centro de Salud Buenavista, Toledo, España; Sociedad Española de Médicos Generales y de Familia (SEMG)
| | - J Ena
- Servicio de Medicina Interna, Hospital Marina Baixa, La Vila Joiosa, Alicante, España; Sociedad Española de Medicina Interna (SEMI)
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Abstract
PURPOSE OF REVIEW The purpose of this mini review is to evaluate the literature on B vitamins and chemotherapy-induced peripheral neuropathy. RECENT FINDINGS One hundred and five journal articles were evaluated and nine manuscripts were included. There was one in vitro, one was an animal and seven were human studies. The in vitro study was a safety study on vitamin B6 and oxaliplatin which was not directly related to CIPN. The animal study evaluated vitamin B3 on paclitaxel administration with positive results. The human studies varied using a vitamin B complex, vitamin B12 only and vitamin B6. Chemotherapy-induced peripheral neuropathy (CIPN) continues to plague patients and the medical fraternity. Currently, there are still no conclusive protective or treatment options. B vitamins have been found to play a role in CIPN prevention, but further studies are required to ascertain possible protection and treatment options.
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Affiliation(s)
- Janet Schloss
- Office of Research, Endeavour College of Natural Health, Brisbane, 4006, Australia.
| | - Maree Colosimo
- Medical Oncology Group of Australia, Clinical Oncology Society of Australia, Queensland Clinical Oncology Group, Brisbane, 4000, Australia
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Kuan YC, Huang KW, Lin CL, Hu CJ, Kao CH. Effects of metformin exposure on neurodegenerative diseases in elderly patients with type 2 diabetes mellitus. Prog Neuropsychopharmacol Biol Psychiatry 2017; 79:77-83. [PMID: 28583443 DOI: 10.1016/j.pnpbp.2017.06.002] [Citation(s) in RCA: 121] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 05/26/2017] [Accepted: 06/02/2017] [Indexed: 01/18/2023]
Abstract
Epidemiological evidence reveals that patients with type 2 diabetes mellitus (T2DM) have an increased risk of neurodegenerative diseases (NDs), including dementia and Parkinson's disease (PD). The effects of metformin exposure on dementia and PD risk in patients with T2DM are unknown. We evaluated the effects of metformin exposure on the risk of dementia and PD in patients with T2DM. We performed a cohort study by using Taiwan's National Health Insurance Research Database. We recruited 4651 patients in the metformin cohort and a comparable number of nonmetformin controls by using propensity score matching. Multivariate Cox proportional hazards regression was used to estimate the effects of metformin on the risk of dementia and PD after adjustment for several confounding factors. During the 12-year follow-up, the metformin cohort exhibited a higher risk of PD than the nonmetformin cohort (hazard ratio [HR]: 2.27, 95% confidence interval [CI]=1.68-3.07). The metformin cohort had an increased risk of all-cause dementia (HR: 1.66, 95% CI=1.35-2.04). Moreover, metformin exposure increased the risk of Alzheimer's disease (HR: 2.13, 95% CI=1.20-3.79) and vascular dementia (HR: 2.30, 95% CI=1.25-4.22). The effects of exposure duration and dosage on dementia and PD occurrence were also observed. Long-term metformin exposure in patients with T2DM may lead to the development of NDs, including dementia and PD. Additional large-scale, prospective controlled trials are required to confirm the observed association in patients with T2DM.
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Affiliation(s)
- Yi-Chun Kuan
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan
| | - Kuang-Wei Huang
- Division of Gastroenterology, Department of Internal Medicine, Taipei Beitou Health Management Hospital, Taipei, Taiwan
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan
| | - Chaur-Jong Hu
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan
| | - Chia-Hung Kao
- Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan; Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan.
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Banihani SA. Vitamin B 12 and Semen Quality. Biomolecules 2017; 7:biom7020042. [PMID: 28598359 PMCID: PMC5485731 DOI: 10.3390/biom7020042] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Revised: 05/12/2017] [Accepted: 06/07/2017] [Indexed: 12/22/2022] Open
Abstract
Various studies have revealed the effects of vitamin B12, also named cobalamin, on semen quality and sperm physiology; however, these studies collectively are still unsummarized. Here, we systematically discuss and summarize the currently understood role of vitamin B12 on semen quality and sperm physiology. We searched the Web of Science, PubMed, and Scopus databases for only English language articles or abstracts from September 1961 to March 2017 (inclusive) using the key words “vitamin B12” and “cobalamin” versus “sperm”. Certain relevant references were included to support the empirical as well as the mechanistic discussions. In conclusion, the mainstream published work demonstrates the positive effects of vitamin B12 on semen quality: first, by increasing sperm count, and by enhancing sperm motility and reducing sperm DNA damage, though there are a few in vivo system studies that have deliberated some adverse effects. The beneficial effects of vitamin B12 on semen quality may be due to increased functionality of reproductive organs, decreased homocysteine toxicity, reduced amounts of generated nitric oxide, decreased levels of oxidative damage to sperm, reduced amount of energy produced by spermatozoa, decreased inflammation-induced semen impairment, and control of nuclear factor-κB activation. However, additional research, mainly clinical, is still needed to confirm these positive effects.
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Affiliation(s)
- Saleem Ali Banihani
- Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan.
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