Abstract:
OBJECTIVES:To study the effects of metformin on the incidence of vitamin B-12 deficiency (<150 pmol/l), low concentrations of vitamin B-12 (150-220 pmol/l), and folate and homocysteine concentrations in patients with type 2 diabetes receiving treatment with insulin. DESIGN:Multicentre randomised placebo controlled trial. SETTING:Outpatient clinics of three non-academic hospitals in the Netherlands. PARTICIPANTS:390 patients with type 2 diabetes receiving treatment with insulin. INTERVENTION:850 mg metformin or placebo three times a day for 4.3 years. MAIN OUTCOME MEASURES:Percentage change in vitamin B-12, folate, and homocysteine concentrations from baseline at 4, 17, 30, 43, and 52 months. RESULTS:Compared with placebo, metformin treatment was associated with a mean decrease in vitamin B-12 concentration of -19% (95% confidence interval -24% to -14%; P<0.001) and in folate concentration of -5% (95% CI -10% to -0.4%; P=0.033), and an increase in homocysteine concentration of 5% (95% CI -1% to 11%; P=0.091). After adjustment for body mass index and smoking, no significant effect of metformin on folate concentrations was found. The absolute risk of vitamin B-12 deficiency (<150 pmol/l) at study end was 7.2 percentage points higher in the metformin group than in the placebo group (95% CI 2.3 to 12.1; P=0.004), with a number needed to harm of 13.8 per 4.3 years (95% CI 43.5 to 8.3). The absolute risk of low vitamin B-12 concentration (150-220 pmol/l) at study end was 11.2 percentage points higher in the metformin group (95% CI 4.6 to 17.9; P=0.001), with a number needed to harm of 8.9 per 4.3 years (95% CI 21.7 to 5.6). Patients with vitamin B-12 deficiency at study end had a mean homocysteine level of 23.7 micromol/l (95% CI 18.8 to 30.0 micromol/l), compared with a mean homocysteine level of 18.1 micromol/l (95% CI 16.7 to 19.6 micromol/l; P=0.003) for patients with a low vitamin B-12 concentration and 14.9 micromol/l (95% CI 14.3 to 15.5 micromol/l; P<0.001 compared with vitamin B-12 deficiency; P=0.005 compared with low vitamin B-12) for patients with a normal vitamin B-12 concentration (>220 pmol/l). CONCLUSIONS:Long term treatment with metformin increases the risk of vitamin B-12 deficiency, which results in raised homocysteine concentrations. Vitamin B-12 deficiency is preventable; therefore, our findings suggest that regular measurement of vitamin B-12 concentrations during long term metformin treatment should be strongly considered. Trial registration Clinicaltrials.gov NCT00375388.
journal_name
BMJjournal_title
BMJ (Clinical research ed.)authors
de Jager J,Kooy A,Lehert P,Wulffelé MG,van der Kolk J,Bets D,Verburg J,Donker AJ,Stehouwer CDdoi
10.1136/bmj.c2181subject
Has Abstractpub_date
2010-05-20 00:00:00pages
c2181eissn
0959-8138issn
1756-1833journal_volume
340pub_type
杂志文章,多中心研究,随机对照试验abstract:OBJECTIVE:To assess the effects of Helicobacter pylori treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer. DESIGN:Blinded randomized placebo controlled trial. SETTING:Linqu County, Shandong province, China. PARTICIPANTS:3365 residents of a high risk region for gastric ...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章,随机对照试验
doi:10.1136/bmj.l5016
更新日期:2019-09-11 00:00:00
abstract:OBJECTIVE:To determine the contribution of inheritance to the incidence of squamous cell carcinoma of the head and neck. DESIGN:Historical cohort study. First degree relatives of cases with squamous cell carcinoma of the head and neck made up the exposed cohort and first degree relatives of spouses of cases made up th...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
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abstract:OBJECTIVES:To assess the experiences of obstetricians in England and Wales of serum screening for Down's syndrome. DESIGN:Postal questionnaire survey. SUBJECTS:Questionnaires were sent to all practising obstetricians in England and Wales with nonacademic appointments who had not participated in an earlier (randomly s...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
doi:10.1136/bmj.309.6957.769
更新日期:1994-09-24 00:00:00
abstract:OBJECTIVE:To investigate differences between hospitals in clinical management of patients admitted with fractured hip and to relate these to mortality at 90 days. DESIGN:A prospective audit of process and outcome of care based on interviews with patients, abstraction from records with standard proforma, and follow up ...
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pub_type: 杂志文章
doi:10.1136/bmj.310.6984.904
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abstract:OBJECTIVE:To see whether the issue of AIDS has influenced the observed decline in blood donation in Scotland. DESIGN:Two methods: a quantitative survey using personal interviews based on a questionnaire and a qualitative survey based on group discussions. SETTING:Interviews based on the questionnaire were conducted i...
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abstract:OBJECTIVE:To describe the association between epithelial cell IgM, which has previously been associated with an increased incidence of loss of renal graft in children, with a novel cutaneous eruption and unexplained native renal disease. DESIGN:Observational study on children with epithelial cell antibody presenting w...
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abstract:OBJECTIVE:To determine whether women with atrial fibrillation have a higher risk of stroke than men. DESIGN:Nationwide retrospective cohort study. SETTING:Patients with a diagnosis of atrial fibrillation in the Swedish hospital discharge register between 1 July 2005 and 31 December 2008. Information about drug treatm...
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更新日期:2012-05-30 00:00:00
abstract:OBJECTIVE:To evaluate the outcome of liver transplantation in patients with alcoholic cirrhosis with respect to selection criteria, survival, and evidence suggesting a return to harmful drinking. DESIGN:Nine year retrospective study. SETTING:Cambridge and King's College Hospital liver transplant programme. SUBJECTS:...
journal_title:BMJ (Clinical research ed.)
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doi:10.1136/bmj.301.6742.15
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abstract:OBJECTIVE:To determine if trimethoprim use for urinary tract infection (UTI) is associated with an increased risk of acute kidney injury, hyperkalaemia, or sudden death in the general population. DESIGN:Cohort study. SETTING:UK electronic primary care records from practices contributing to the Clinical Practice Resea...
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abstract:OBJECTIVE:To determine whether the author's 20.9 lb (9.5 kg) carbon frame bicycle reduced commuting time compared with his 29.75 lb (13.5 kg) steel frame bicycle. DESIGN:Randomised trial. SETTING:Sheffield and Chesterfield, United Kingdom, between mid-January 2010 and mid-July 2010. PARTICIPANTS:One consultant in an...
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pub_type: 杂志文章,随机对照试验
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更新日期:2010-12-09 00:00:00
abstract:OBJECTIVE:To examine the extent of uptake of medication for secondary prevention of coronary heart disease in older British men and women before (1998-2001) and after (2003) the implementation of the national service framework. DESIGN:Two population based, longitudinal studies of men and women aged 60-79 in 1998-2001,...
journal_title:BMJ (Clinical research ed.)
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更新日期:2006-01-21 00:00:00
abstract:OBJECTIVE:To analyse the cost effectiveness of a national programme to screen blood donors for infection with the human T cell leukaemia/lymphoma virus. DESIGN:Three models for calculating the costs and benefits of screening were developed. The first model analysed the cost of continuously testing all donations; the s...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
doi:10.1136/bmj.316.7142.1417
更新日期:1998-05-09 00:00:00
abstract::A 40 year old man presents with a 1 cm tender soft swelling in the lateral neck region. This developed seven days after the onset of a tonsillitis episode that has now resolved. He has a 20 pack-year smoking history and consumes minimal alcohol. Examination is otherwise normal. ...
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doi:10.1136/bmj.f5473
更新日期:2013-10-28 00:00:00
abstract:OBJECTIVE:To determine the effects of perineal massage in the second stage of labour on perineal outcomes. DESIGN:Randomised controlled trial. PARTICIPANTS:At 36 weeks' gestation, women expecting normal birth of a singleton were asked to join the study. Women became eligible to be randomised in labour if they progres...
journal_title:BMJ (Clinical research ed.)
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2001-05-26 00:00:00
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doi:
更新日期:1998-04-04 00:00:00
abstract:OBJECTIVES:To determine whether informed consent introduces selection bias in prospective observational studies using data from medical records, and consent rates for such studies. DESIGN:Systematic review. DATA SOURCES:Embase, Medline, and the Cochrane Library up to March 2008, reference lists from pertinent article...
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pub_type: 杂志文章,评审
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更新日期:2009-03-12 00:00:00
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pub_type: 临床试验,杂志文章
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更新日期:2006-04-08 00:00:00
abstract:OBJECTIVES:To investigate trends in the incidence of acute pancreatitis resulting in admission to hospital, and mortality after admission, from 1963 to 1998. DESIGN:Analysis of hospital inpatient statistics for acute pancreatitis, linked to data from death certificates. SETTING:Southern England. SUBJECTS:5312 people...
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更新日期:2004-06-19 00:00:00
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pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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更新日期:2006-12-09 00:00:00
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abstract::This review summarises the literature on shift work and its relation to insufficient sleep, chronic diseases, and accidents. It is based on 38 meta-analyses and 24 systematic reviews, with additional narrative reviews and articles used for outlining possible mechanisms by which shift work may cause accidents and adver...
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更新日期:2016-11-01 00:00:00
abstract:OBJECTIVES:To describe the change in first day infant mortality during 1935-87. To examine the hypothesis that excess first day mortality in the 1950s and 1960s was attributable to restricting oxygen for sick newborn infants. DESIGN:Time series analysis of first day infant mortality and stillbirth rates. SETTING:Engl...
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abstract::A random sample of 133 elderly patients who had an unplanned readmission to a district general hospital within 28 days of discharge from hospital was studied and compared with a matched control sample of patients who were not readmitted. The total group was drawn from all specialties in the hospital, and by interviewi...
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abstract:OBJECTIVE:To confirm the findings of pilot studies that interferon alfa is an effective treatment of Europid men with chronic hepatitis B virus infection. DESIGN:Randomised controlled trial of three months treatment with interferon alfa followed by 12 months of observation. SETTING:Outpatient clinic of a tertiary ref...
journal_title:BMJ (Clinical research ed.)
pub_type: 临床试验,杂志文章,随机对照试验
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abstract:OBJECTIVE:To determine whether patients with unexpected prehospital cardiac arrest could be identified in whom ambulance resuscitation attempts would be futile. DESIGN:Review of ambulance and hospital records; detailed review of automated external defibrillator rhythm strips of patients in whom no shock was advised. ...
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pub_type: 杂志文章
doi:10.1136/bmj.311.6996.49
更新日期:1995-07-01 00:00:00
abstract:OBJECTIVE:To compare four potential screening strategies, and subsequent interventions, for the prevention and treatment of type 2 diabetes: (a) screening for type 2 diabetes to enable early detection and treatment, (b) screening for type 2 diabetes and impaired glucose tolerance, intervening with lifestyle interventio...
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doi:10.1136/bmj.39545.585289.25
更新日期:2008-05-24 00:00:00