vitamin-b-12 and Diabetes-Mellitus--Type-2

Type 2 diabetes mellitus is one of the most globally common chronic diseases. Metformin is the most popular prescribed medication for the treatment of diabetes. Studies suggest that metformin is associated with vitamin B12 deficiency, which may impart adverse health complications.. This review screens the literature to clarify the effect of metformin on vitamin B12 deficiency among type 2 diabetes mellitus patients.. Google Scholar, PubMed, Research Gate, and Semantic Scholar, were searched for the association between metformin intake and vitamin B12 deficiency in type 2 diabetes mellitus patients using relevant keywords and their combinations. Selected studies were those conducted on patients taking metformin with no vitamin B12 supplement. Nineteen studies (fifteen observational studies and four randomized controlled trials) met the inclusion criteria. These studies were assessed for design, setting, study population, and overall quality.. There is a positive correlation between metformin intake and vitamin B12 deficiency. This has been accompanied by increased homocysteine and decreased folate levels. Despite the refuting of the findings, most studies showed that higher doses of metformin were strongly associated with lower vitamin B12 levels, while the duration of treatment was not.. Regular measurement of vitamin B12 levels during long-term metformin treatment is recommended. A clear policy should be in place to illuminate the importance of this screening in preventing vitamin B12 deficiency complications. Taking therapeutic supplements or injections of vitamin B12 along with a vitamin B12-rich diet may decrease the incidence of its deficiency in diabetic patients taking metformin.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Vitamin B 12; Vitamin B 12 Deficiency

Previous studies have shown an association between low serum vitamin B12 levels and the risk of diabetic retinopathy (DR) in type 2 diabetes, but the conclusions from various studies were inconsistent. Therefore, we collected relevant data from various databases to perform a meta-analysis and address the inconsistencies in these studies.. We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang and CQVIP for eligible studies published up to April 10, 2022, and performed a meta-analysis using Stata software to assess the association between serum vitamin B12 levels and DR.. A total of 15 studies were included in this meta-analysis. Statistical analysis showed that serum vitamin B12 levels were significantly reduced in patients with type 2 diabetic retinopathy ,WMD 95% CI = -68.91 (-76.76, -61.06) (p <0.00001, I. This meta-analysis analyzed vitamin B12 in patients with type 2 diabetic retinopathy and emphasized the importance of monitoring serum vitamin B12 levels in patients with type 2 diabetic retinopathy, but this meta-analysis still has deficiencies and limitations, and more clinical studies are needed to confirm this conclusion in the future.

Topics: Asian People; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Ethnicity; Humans; Vitamin B 12

Alzheimer's disease is a prevalent form of dementia, particularly among the elderly population. It is characterized by progressive cognitive decline and neurodegeneration. Despite numerous studies, the exact cause of Alzheimer's disease remains uncertain, and various theories have been proposed, including Aβ amyloid deposition in the brain and tau protein hyper-phosphorylation. This review article explores the potential pathogenesis of Alzheimer's disease, focusing on the effects of derangements in the levels of vitamin B12, folate, and homocysteine, as well as the impact of oral bacteria causing periodontitis and insulin resistance, and their relationship to Alzheimer's. Studies have shown that high levels of homocysteine and low levels of vitamin B12 and folate, are associated with an increased risk of developing Alzheimer's disease. The article also explores the link between Alzheimer's disease and oral bacteria, specifically dental infections and periodontitis, which contribute to the inflammatory processes in the nervous system of Alzheimer's patients. There could be derangement in the insulin signaling further causing disruption in glucose metabolism within the brain, suggesting that Alzheimer's disease may represent a form of type 2 diabetes mellitus associated with the brain, commonly known as type 3 diabetes. Neuroimaging techniques, including MRI, PET, and tau PET, can identify the predictive characteristics of Alzheimer's disease, with amyloid PET being the most useful in ruling out the disease. The article concludes by stressing the importance of understanding genetic and neuroimaging factors in the diagnosing and treating Alzheimer's disease.

Topics: Aged; Alzheimer Disease; Biomarkers; Diabetes Mellitus, Type 2; Folic Acid; Humans; Insulin Resistance; Vitamin B 12

Metformin blocks the absorption of vitamin B12 through a mechanism that has not been established but could be because of interference with the calcium-dependent binding of the intrinsic factor vitamin B12 complex to the cubam receptor in the terminal ileum. The subsequent deficiency of vitamin B12 may cause or accelerate distal symmetrical and autonomic neuropathy in the patient with diabetes. Several observational studies and meta-analyses have reported a significant association between metformin utilization and vitamin B12 deficiency. Prospective studies have shown that not only do metformin utilizers have lower vitamin B12 levels but they also have higher frequencies of distal symmetrical polyneuropathy and autonomic neuropathy (including cardiac denervation, which is associated with increased incidences of cardiac arrhythmias, cardiac events and mortality). Therefore, periodic monitoring of vitamin B12 is recommended in all patients who utilize metformin, particularly if metformin has been used for over 5 years at which stage hepatic stores of vitamin B12 would probably be depleted. Factors that accelerate the loss of hepatic vitamin B12 stores are proton pump inhibitors, bariatric surgery, being elderly and having an increased turnover of red blood cells. If serum vitamin B12 levels are borderline, measurement of methylmalonic acid and homocysteine levels can detect vitamin B12 deficiency at its earliest stage. Therapies include prophylactic calcium and vitamin B12 supplements, metformin withdrawal, replenishing vitamin B12 stores with intramuscular or oral vitamin B12 therapy and regular monitoring of vitamin B12 levels and vitamin B12 supplements if metformin continues to be utilized. With adequate vitamin B12 replacement, while symptoms of neuropathy may or may not improve, objective findings of neuropathy stabilize but do not improve.

Topics: Aged; Calcium; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Peripheral Nervous System Diseases; Prospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

Metformin is a hypoglycemic drug widely used in the treatment of type 2 diabetes. It has been proven to have analgesic and neuroprotective effects. Metformin can reverse pain in rodents, such as diabetic neuropathic pain, neuropathic pain caused by chemotherapy drugs, inflammatory pain and pain caused by surgical incision. In clinical use, however, metformin is associated with reduced plasma vitamin B12 levels, which can further neuropathy. In rodent diabetes models, metformin plays a neuroprotective and analgesic role by activating adenosine monophosphate-activated protein kinase, clearing methylgloxal, reducing insulin resistance, and neuroinflammation. This paper also summarized the neurological adverse reactions of metformin in diabetic patients. In addition, whether metformin has sexual dimorphism needs further study.. 二甲双胍是一种广泛用于治疗2型糖尿病的降糖药物。它已被证明具有镇痛和神经保护作用。二甲双胍可以逆转啮齿类动物的疼痛，如糖尿病性神经痛、化疗药物引起的神经性疼痛、炎症性疼痛、手术切口引起的疼痛。然而，在临床使用中，二甲双胍与血浆维生素B12水平降低有关，这可能会进一步加剧神经病变。在啮齿动物糖尿病模型中，二甲双胍通过激活AMPK、清除MGO、降低胰岛素抵抗和神经炎症发挥神经保护和镇痛作用。本文还总结了二甲双胍对糖尿病患者的神经系统不良反应。此外，二甲双胍是否有两性区别还有待进一步研究。.

Topics: Adenosine Monophosphate; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Hypoglycemic Agents; Metformin; Neuroprotective Agents; Pain; Protein Kinases; Vitamin B 12

Metformin-treated type 2 diabetes mellitus (T2DM) patients are at higher risk of vitamin B. Studies reporting the efficacy of vitamin B. Seven clinical trials with a total of 506 participants were included. Using the Cochrane's Risk of Bias 2 tools for clinical trials, 4 studies were assessed to have high risk of bias and 3 studies had low risk of bias. There were 5 studies that measured changes in serum vitamin B. The results of this systematic review support the implementation of vitamin B

Topics: Diabetes Mellitus, Type 2; Dietary Supplements; Homocysteine; Humans; Hypoglycemic Agents; Metformin; Peripheral Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

The vitamin status of a child depends on many factors and most of the clinical studies do not take into account the different access to adequate nutrition of children coming from different countries and the consequent major differences in micronutrients or vitamin deficits between low-income and high-income countries. Vitamin supplements are included in the general field of dietary supplements. There is a large amount of not always factual material concerning vitamin supplements, and this may sometimes create confusion in clinicians and patients. Inadequate information may lead to the risk of attributing beneficial properties leading to their over-use or misuse in the paediatric field. Vitamin supplementation is indicated in all those conditions in which a vitamin deficiency is found, either because of a reduced intake due to reduced availability of certain foods, restrictive diets or inadequate absorption. The lack of guidelines in these fields may lead paediatricians to an improper use of vitamins, both in terms of excessive use or inadequate use. This is due to the fact that vitamin supplementation is often intended as a therapy of support rather than an essential therapeutic tool able to modify disease prognosis. In fact, various vitamins and their derivatives have therapeutic potential in the prevention and treatment of many diseases, especially in emerging conditions of paediatric age such as type 2 diabetes and the metabolic syndrome. The aim of the present article is to analyse the state of the art and consider new perspectives on the role of vitamin supplements in children.

Topics: Ascorbic Acid; Avitaminosis; Child; Databases, Factual; Diabetes Mellitus, Type 2; Dietary Supplements; Folic Acid; Humans; Micronutrients; Nutritional Status; Vitamin A; Vitamin B 12; Vitamin D; Vitamin E; Vitamins

Metformin is first-line therapy for patients with diabetes. However, it may lower vitamin B. PubMed, Web of Knowledge, Cochrane Library, and Embase were searched to identify all relevant studies published in English prior to March 2018. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for dichotomous outcomes and pooled mean differences (MDs) and 95% CIs were calculated for continuous outcomes.. Thirty-one studies were included in the meta-analyses. Compared with diabetic patients not taking metformin, patients taking metformin had a significantly higher risk of vitamin B. Metformin use led to significantly lowered vitamin B. 摘要: 背景 二甲双胍是糖尿病患者的一线治疗药物。然而, 二甲双胍的使用与维生素B

Topics: Anemia; Case-Control Studies; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Peripheral Nervous System Diseases; Prognosis; Vitamin B 12; Vitamin B Complex

Diabetic peripheral neuropathy (DPN) is a common and severe complication that affects 50% of people with diabetes. Painful DPN is reported to occur in 16% to 24% of people with diabetes. A complete and comprehensive management strategy for the prevention and treatment of DPN, whether painful or not, has not yet been defined.Research into treatment for DPN has been characterised by a series of failed clinical trials, with few noteworthy advances. Strategies that support peripheral nerve regeneration and restore neurological function in people with painful or painless DPN are needed. The amino acid acetyl-L-carnitine (ALC) plays a role in the transfer of long-chain fatty acids into mitochondria for β-oxidation. ALC supplementation also induces neuroprotective and neurotrophic effects in the peripheral nervous system. Therefore, ALC supplementation targets several mechanisms relevant to potential nerve repair and regeneration, and could have clinical therapeutic potential. There is a need for a systematic review of the evidence from clinical trials.. To assess the effects of ALC for the treatment of DPN.. On 2 July 2018, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. We checked references, searched citations, and contacted study authors to identify additional studies.. We included randomised controlled trials (RCTs) and quasi-RCTs of ALC compared with placebo, other therapy, or no intervention in the treatment of DPN. Participants could be of any sex and age, and have type 1 or type 2 diabetes mellitus, of any severity, with painful or painless DPN. We accepted any definition of minimum criteria for DPN, in accordance with the Toronto Consensus. We imposed no language restriction.Pain was the primary outcome, measured as the proportion of participants with at least 30% (moderate) or 50% (substantial) decrease in pain over baseline, or as the score on a visual analogue scale (VAS) or Likert scale for pain.. We followed standard Cochrane methods.. We included four studies with 907 participants, which were reported in three publications. Three trials studied ALC versus placebo (675 participants); in one trial the dose of ALC was 2000 mg/day, and in the other two trials, it was 1500 mg/day or 3000 mg/day. The fourth trial studied ALC 1500 mg/day versus methylcobalamin 1.5 mg/day (232 participants). The risk of bias was high in both trials of different ALC doses and low in the other two trials.No included trial measured the proportion of participants with at least moderate (30%) or substantial (50%) pain relief. ALC reduced pain more than placebo, measured on a 0- to 100-mm VAS (MD -9.16, 95% CI -16.76 to -1.57; three studies; 540 participants; P = 0.02; I² = 56%; random-effects; very low-certainty evidence; a higher score indicating more pain). At doses of 1500 mg/day or less, the VAS score after ALC treatment was little different from placebo (MD -0.05, 95% CI -10.00 to 9.89; two studies; 159 participants; P = 0.99; I² = 0%), but at doses greater than 1500 mg/day, ALC reduced pain more than placebo (MD -14.93, 95% CI -19.16 to -10.70; three studies; 381 participants; P < 0.00001; I² = 0%). This subgroup analysis should be viewed with caution as the evidence was even less certain than the overall analysis, which was already of very low certainty.Two placebo-controlled studies reported that vibration perception improved after 12 months. We graded this evidence as very low certainty, due to inconsistency and a high risk of bias, as the trial authors did not provide any numerical data. The placebo-controlled studies did not measure functional impairment and disability scores. No study used validated symptom scales. One study performed sensory testing, but the evidence was very uncertain.The fourth included study compared ALC with methylcobalamin, but did not report effects on pain. There was a reduction from baseline to 24 weeks in functional impairment and disability, based on the change in mean Neuropathy Disability Score (NDS; scale from zero to 10), but there was no important difference between the ALC group (mean score 1.66 ± 1.90) and the methylcobalamin group (mean score 1.35 ± 1.65) groups (P = 0.23; low-certainty evidence).One placebo-controlled study reported that six of 147 participants in the ALC > 1500 mg/day group (4.1%) and two of 147 participants in the placebo group (1.4%) discontinued treatment because of adverse events (headache, facial paraesthesia, and gastrointestinal disorders) (P. We are very uncertain whether ALC causes a reduction in pain after 6 to 12 months' treatment in people with DPN, when compared with placebo, as the evidence is sparse and of low certainty. Data on functional and sensory impairment and symptoms are lacking, or of very low certainty. The evidence on adverse events is too uncertain to make any judgements on safety.

Topics: Acetylcarnitine; Adult; Aged; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Neuralgia; Pain Measurement; Placebos; Randomized Controlled Trials as Topic; Sensation; Vibration; Vitamin B 12

Meat is an important food for human nutrition, by especially providing high-quality protein and also some essential micronutrients, in front iron, zinc, and vitamin B

Topics: Animals; Cardiovascular Diseases; Cattle; Colorectal Neoplasms; Diabetes Mellitus, Type 2; Diet, Healthy; Dietary Proteins; Evidence-Based Medicine; Food, Preserved; Humans; Iron, Dietary; Meat; Meat Products; Meta-Analysis as Topic; Mortality; Nutritive Value; Risk Factors; Sheep, Domestic; Sus scrofa; Vitamin B 12; Zinc

The association between serum folate and vitamin B12 levels and the risk of diabetic peripheral neuropathy (DPN) remains unclear. This meta-analysis included 16 studies of serum folate levels (1190 cases and 1501 controls) and 18 studies of serum vitamin B12 levels (1239 cases and 1562 controls) in patients with type 2 diabetes mellitus (T2DM). Reduced serum levels of folate and vitamin B12 were found in patients with T2DM and DPN compared with patients with T2DM but without DPN; weighted mean difference (WMD) = -1.64 (95% confidence interval [CI] = -2.46, -0.81) and WMD = -70.86 (95% CI = -101.55, -40.17), respectively. A subgroup analysis confirmed these associations in the Chinese population, but not in the Caucasian and mixed populations. In conclusion, these findings support the need for further controlled studies in defined patient populations and the importance of monitoring serum folate and vitamin B12 levels in patients with T2DM.

Topics: Aged; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Folic Acid; Humans; Male; Middle Aged; Publication Bias; Vitamin B 12

The present review evaluates the relationship between type 2 diabetes mellitus and individual or combined vitamins. Antioxidant vitamins A, C and E are found decreased in diabetic subjects, possibly due to an increased need to control the excessive oxidative stress produced by abnormalities in glucose metabolism. On the other hand, retinol binding protein exerts a modulating effect, as it has adipokine functions. With respect to the B group vitamins, thiamin, pyridoxine and biotin have been found decreased but the mechanisms are not clear, however supplementation has shown some improvement of the metabolic control in diabetic patients. The absorption of folic acid and vitamin B12 is importantly decreased by the prolongued use of metformin, which is the first choice drug in uncomplicated diabetes, thus these two nutrients have been found deficient in the disease and most probably need to be supplemented regularly. On the other hand, vitamin D is considered a risk factor for the development of diabetes as well as its complications, particularly cardiovascular ones. Although some studies have found an association of vitamin K intake with glucose metabolism further research is needed. Studies on the use of multivitamin supplements have shown unconclusive results. After reviewing the evidence, no real recommendation on the use of vitamin supplements in type 2 diabetes mellitus can be issued, however patients using metformin during prolongued periods may need folic acid and vitamin B12.

Topics: Animals; Antioxidants; Diabetes Mellitus, Type 2; Dietary Supplements; Folic Acid; Humans; Oxidative Stress; Vitamin B 12; Vitamins

Metformin is the only biguanide oral hypoglycemic drug, that is used to treat patients with type-2 diabetes mellitus. There are some reports of metformin being associated with decreased serum levels of vitamin B12 (VB12). The objective of this study is to systematically analyze the impact of metformin on the frequency of VB12 deficiency and serum levels of VB12. A search of various databases provided 18 retrospective cohort studies and 11 randomized controlled trials. Pooled estimates of odds ratio with 95% confidence interval using random effect model were conducted. Studies were examined for heterogeneity, publication bias and sensitivity analysis. Separate analysis of randomized control trials (RCTs) including both low-risk and high-risk bias was also conducted. 29 studies were selected with a total of 8,089 patients. 19 studies were rated intermediate or high quality. Primary outcome suggested increased incidence of VB12 deficiency in metformin group (OR = 2.45, 95% CI 1.74-3.44, P < 0.0001.) Heterogeneity was relatively high (I(2) = 53%), with minor publication bias. Secondary outcome suggested lower serum VB12 concentrations in metformin group (Mean difference = -65.8, 95% CI -78.1 to -53.6 pmol/L, P < 0.00001) with high heterogeneity (I(2) = 98%,) and low publication bias. RCTs analysis of low-and high-risk group revealed similar trends. We conclude that metformin treatment is significantly associated with an increase in incidence of VB12 deficiency and reduced serum VB12 levels.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Nutritional factors such as magnesium, folic acid, vitamins B12 and B6, L-arginine, and polyunsaturated fatty acids (PUFAs) appear to be significantly beneficial for patients with coronary artery disease (CAD), and in the prevention and arresting the progression of HF and cardiac arrhythmias. Additionally, ingestion of adequate amounts of protein and maintaining normal concentrations of plasma albumin seem to be essential for these patients. These nutrients closely interact with the metabolism of L-arginine-nitric oxide (NO) system, essential fatty acids, and eicosanoids such that beneficial products such as NO, prostaglandin E1, prostacyclin, prostaglandin I3, lipoxins, resolvins, and protectins are generated and synthesis of proinflammatory cytokines is suppressed that results in platelet anti-aggregation, vasodilation, angiogenesis, and prevention of CAD, cardiac arrhythmias, and stabilization of HF. This implies that individuals at high risk for CAD, cardiac arrhythmias, and HF and those who have these diseases need to be screened for plasma levels of magnesium, folic acid, vitamins B12 and B6, L-arginine, NO, various PUFAs, lipoxin A4, resolvins, protectins, asymmetrical dimethylarginine (an endogenous inhibitor of NO), albumin, and various eicosanoids and cytokines and correct their abnormalities to restore normal physiology.

Topics: Alprostadil; Anti-Inflammatory Agents; Arginine; CD59 Antigens; Coronary Artery Disease; Diabetes Mellitus, Type 2; Epoprostenol; Fatty Acids, Essential; Fatty Acids, Unsaturated; Female; Folic Acid; Heart Failure; Humans; Hypertension; Lipoxins; Magnesium; Male; Middle Aged; Nitric Oxide; Nutritional Status; Serum Albumin; Vasodilation; Vitamin B 12; Vitamin B 6

Vitamin B12 deficiency is common in certain populations, such as in India, where there is also a rising prevalence of Type 2 diabetes, obesity and their complications. Human cohorts and animal models provide compelling data suggesting the role of the one-carbon cycle in modulating the risk of diabetes and adiposity via developmental programming. Early mechanistic studies in animals suggest that alterations to the cellular provision of methyl groups (via the one-carbon cycle) in early developmental life may disrupt DNA methylation and induce future adverse phenotypic changes. Furthermore, replacement of micronutrient deficits at suitable developmental stages may modulate this risk. Current human studies are limited by a range of factors, including the accuracy and availability of methods to measure nutritional components in the one-carbon cycle, and whether its disruptions exert tissue-specific effects. A greater understanding of the causal and mechanistic role of the one-carbon cycle is hoped to generate substantial insights into its role in the developmental origins of complex metabolic diseases and the potential of targeted and population-wide prevention strategies.

Topics: Adiposity; Carbon Cycle; Diabetes Mellitus, Type 2; Environmental Exposure; Female; Fetal Development; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Infant, Newborn; Insulin Resistance; Male; Maternal Nutritional Physiological Phenomena; Methylmalonic Acid; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Vitamin B 12; Vitamin B 12 Deficiency

Randomized controlled trials and observational studies have yielded inconsistent results on the effects of metformin on vitamin B12 reduction. We therefore performed a systematic review to analyze the effects of metformin on vitamin B12 concentration.. PubMed, Medline, Embase, and the Cochrane central registry of controlled trials were searched to identify randomized controlled trials and observational studies exploring the association between metformin and vitamin B12 concentration in patients with type 2 diabetes mellitus or polycystic ovary syndrome. The main outcome measure was changes in serum vitamin B12 concentration after 6-208 weeks of treatment with metformin, as compared with placebo or other anti-hyperglycemic therapy.. Six randomized controlled trials met the inclusion criteria. Serum vitamin B12 concentrations were significantly lower in patients treated with metformin than in those who received placebo or rosiglitazone (mean difference [MD], -53.93 pmol/L; 95% confidence interval [CI], -81.44 to -26.42 pmol/L, P = 0.0001). Subgroup analysis identified four trials in which patients received a lower dose of metformin (<2000 mg/d) and two in which they received a higher dose (≥2000 mg/d), with MDs in vitamin B12 concentration after metformin treatment of -37.99 pmol/L (95% CI, -57.44 to -18.54 pmol/L, P = 0.0001) and -78.62 pmol/L (95% CI, -106.37 to -50.86 pmol/L, P<0.00001), respectively.. The reduction of vitamin B12 may be induced by metformin in a dose dependent manner.

Topics: Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Metformin; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin B 12

To assess the prior hypothesis that low blood vitamin B12, partly through hyperhomocysteinemia and partly through direct effects, increases the risk of cardiovascular diseases and diabetes. As background, we also extracted all-cause mortality from the studies that met our criteria.. A systematic review of prospective cohort studies identified through searching six electronic databases, screening of reference lists, and citation search. Included studies reported data on the association between vitamin B12 blood levels, or other appropriate surrogate biological markers e.g. holotranscobalamin or serum/urine methylmalonic acid, and fatal or non-fatal incident diabetes and cardiovascular events.. Seven studies were included. Studies differed regarding the population studied, length of follow-up, study outcomes, and data analysis--a narrative synthesis approach was performed to examine the results. Most studies met few of the quality assessment criteria which were adapted from the Scottish Intercollegiate Guidelines Network (SIGN). Only one high-quality study reported that low B12 increased the risk of incident cerebral ischaemia (RR = 1.76; 95% CI = 1.16-2.68). After controlling for homocysteine, the association persisted although weakened (RR = 1.57; 95% CI = 1.02-2.43), suggesting that the effects of low B12 were only partly mediated by homocysteine. In two studies, higher B12 levels were associated with a greater risk of total mortality (RR = 1.00; 95% CI = 1.00-1.00 and HR = 1.15; 95% CI = 1.08-1.22, respectively) and combined fatal and non-fatal coronary events (RR = 1.00; 95% CI = 1.00-1.00). No association between study outcomes and vitamin B12 levels was found in four other studies.. Surprisingly, there is only very limited evidence that vitamin B12 deficiency predisposes to the risk of mortality and morbidity from either cardiovascular diseases or diabetes in adults. Current data do not support vitamin B12 supplementation to reduce the risk of cardiovascular diseases or diabetes.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Homocysteine; Humans; Hyperhomocysteinemia; Incidence; Meta-Analysis as Topic; Risk Factors; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

BACKGROUND Acupoint injection is a therapeutic method that combines acupuncture and Western medicine and shows good curative effects for neuropathies. This study aimed to explore the efficacy of acupoint injection for treating diabetic peripheral neuropathy (DPN) by magnetic resonance neuroimaging (MRN). MATERIAL AND METHODS Forty patients with DPN were randomly divided into an acupoint injection group (AI; n=20) and intramuscular injection group (MI; n=20). The AI group received an acupoint injection of mecobalamin at acupoint Zusanli (S36); the MI group received intramuscular injection of mecobalamin. The curative effect was evaluated by the Toronto Clinical Neuropathy Score and diffusion tensor imaging (DTI). RESULTS The neuropathy scores of both groups decreased from baseline (AI 9.31±2.36; MI 9.34±2.54) to after the 2-week treatment (AI 7.12±1.87; MI 7.86±2.11); the differences were not significant. The fractional anisotropy (FA) value showed significant differences on the common peroneal nerve (AI 0.36±0.04; MI 0.31±0.05; P<0.05) and tibial nerve (AI 0.38±0.07; MI 0.34±0.06; P<0.05) after treatment. Likewise, apparent diffusion coefficient (ADC) values between groups showed significant differences for the common peroneal nerve (AI 1.44±0.17×10⁻³ mm²/s; MI 1.61±0.20×10⁻³ mm²/s; P<0.05) and tibial nerve (AI 1.54±0.22×10-3 mm²/s; MI 1.60±0.17 10⁻³ mm²/s; P<0.05). CONCLUSIONS Patients with DPN showed lower nerve FA and higher ADC in DTI-MRN. The acupoint injection of mecobalamin could treat DPN and repair the damaged nerves, which was shown by elevated FA and lowered ADC. Our study provides clinical evidence for the application of acupoint injection therapy and the evaluation of DPN by MRN.

Topics: Acupuncture Points; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diffusion Tensor Imaging; Humans; Injections, Intramuscular; Vitamin B 12

To investigate the effect of normalizing vitamin B12 (B12) levels with oral B12 (methylcobalamin) 1000 μg/day for one year in patients with diabetic neuropathy (DN).. In this prospective, double-blind, placebo-controlled trial, 90 patients with type 2 diabetes on metformin for at least four years and both peripheral and autonomic DN were randomized to an active treatment group (n = 44) receiving B12 and a control group (n = 46) receiving a placebo. All patients had B12 levels less than 400 pmol/L. Subjects underwent measurements of sural nerve conduction velocity (SNCV), sural nerve action potential (amplitude) (SNAP), and vibration perception threshold (VPT), and they performed cardiovascular autonomic reflex tests (CARTs: mean circular resultant (MCR), Valsalva test, postural index, and orthostatic hypotension). Sudomotor function was assessed with the SUDOSCAN that measures electrochemical skin conductance in hands and feet (ESCH and ESCF, respectively). We also used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE, respectively) and questionnaires to evaluate quality of life (QoL) and level of pain (pain score).. B12 levels increased from 232.0 ± 71.8 at baseline to 776.7 ± 242.3 pmol/L at follow-up,. The treatment of patients with DN with 1 mg of oral methylcobalamin for twelve months increased plasma B12 levels and improved all neurophysiological parameters, sudomotor function, pain score, and QoL, but it did not improve CARTS and MNSIE.

Topics: Cholesterol; Creatinine; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Linear Models; Male; Middle Aged; Prospective Studies; Quality of Life; Triglycerides; Vitamin B 12

Metformin has been shown to have both neuroprotective and neurodegenerative effects. The aim of this study was to investigate the effect of metformin in combination with insulin on cardiovascular autonomic neuropathy (CAN) and distal peripheral neuropathy (DPN) in individuals with type 2 diabetes (T2DM).. The study is a sub-study of the CIMT trial, a randomized placebo-controlled trial with a 2 × 3 factorial design, where 412 patients with T2DM were randomized to 18 months of metformin or placebo in addition to open-labelled insulin. Outcomes were measures of CAN: Changes in heart rate response to deep breathing (beat-to-beat), orthostatic blood pressure (OBP) and heart rate and vibration detection threshold (VDT) as a marker DPN. Serum levels of vitamin B12 and methyl malonic acid (MMA) were analysed.. After 18 months early drop in OBP (30 s after standing) was increased in the metformin group compared to placebo: systolic blood pressure drop increased by 3.4 mmHg (95% CI 0.6; 6.2, p = 0.02) and diastolic blood pressure drop increased by 1.3 mmHg (95% CI 0.3; 2.6, p = 0.045) compared to placebo. Beat-to-beat variation decreased in the metformin group by 1.1 beats per minute (95% CI - 2.4; 0.2, p = 0.10). Metformin treatment did not affect VDT group difference - 0.33 V (95% CI - 1.99; 1.33, p = 0.39) or other outcomes. Changes in B12, MMA and HbA. Eighteen months of metformin treatment in combination with insulin compared with insulin alone increased early drop in OBP indicating an adverse effect of metformin on CAN independent of vitamin B12, MMA HbA

Topics: Aged; Autonomic Nervous System Diseases; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Hypotension, Orthostatic; Insulin; Male; Metformin; Middle Aged; Peripheral Nervous System Diseases; Risk Factors; Standing Position; Vitamin B 12

This study was conducted to investigate and compare the effects of add-on folic acid and vitamin B12 supplementation on glycaemic control, insulin resistance and serum lipid profile in subjects with type 2 diabetes mellitus.. This study was a randomized, multi-arm, open-label clinical trial. 80 patients with type 2 diabetes and on stable oral antidiabetics were enrolled and 20 patients each were randomly allocated to one of the four groups - Group A: add-on Folic acid (5 mg/day); Group B: add-on Methylcobalamin (500 mcg/day); Group C: add-on Folic acid (5 mg/day) + Methylcobalamin (500 mcg/day) and Group D: Standard oral anti-diabetic drugs. The patients were followed up after 8 weeks.. HbA1c improved significantly in Groups B and C [median changes from baseline - 1.2 % (- 13 mmol/mol) and - 1.5 % (- 16 mmol/mol) respectively, p values 0.04 and 0.02 respectively] compared to Group D. Groups B and C also showed significant improvements in plasma insulin, insulin resistance and serum adiponectin compared to Group D. Serum homocysteine declined significantly in all three groups with add-on supplementation compared to standard treatment. No improvement in the lipid profile was noted in any of the groups.. Add-on supplementation with vitamin B12 improved glycaemic control and insulin resistance in patients with type 2 diabetes mellitus.

Topics: Adult; Diabetes Mellitus, Type 2; Dietary Supplements; Drug Therapy, Combination; Folic Acid; Glycemic Control; Humans; Insulin Resistance; Lipids; Middle Aged; Vitamin B 12

To investigate the efficacy of Superoxide Dismutase, Alpha Lipoic Acid, Acetyl L-Carnitine, and Vitamin B12 (B12) in one tablet in Diabetic Neuropathy (DN).. In this prospective, double-blind, placebo-controlled study, 85 patients with Diabetes Mellitus Type 2 (DMT2) were randomly assigned, either to receive the combination of four elements (active group,. At follow-up, BIO, MNSIQ, QL, PAIN, and SNCV, SNAP, and B12 levels had significantly improved inactive group (. The combination of the four elements in one tablet for 12 months in patients with DMT2 improved all indices of peripheral neuropathy, including SNAP and SNCV, pain, and Quality of Life perception, except CARTs and MNSIE.

Topics: Aged; Carnitine; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Neural Conduction; Pain Measurement; Prospective Studies; Quality of Life; Reflex; Superoxide Dismutase; Thioctic Acid; Treatment Outcome; Vitamin B 12

Diabetic hyperglycemia damages peripheral nerves by triggering ischemia, oxidative stress, and inflammation. Alpha-lipoic acid (ALA) and methylcobalamin (MC) are known to improve signs of diabetic peripheral neuropathy (DPN), possibly by enhancing neural and vascular endothelial cell metabolism and antioxidant capacity. We evaluated differences in efficacy following short-term MC or ALA treatment on DPN symptoms to guide clinical drug selection.. Forty DPN patients were randomly divided into MC and ALA treatment groups (both N.=20) and assessed by the Toronto Clinical Neuropathy Scoring System (TCSS), total symptom score (TSS), visual analog scale (VAS) of positive symptoms, and easy sensory test (EST) for negative symptoms before and after 2 weeks of treatment. Serum malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured.. Neuropathy as measured by TCSS, TSS, and VAS scores was significantly reduced by both treatments (P<0.05) but magnitude varied by symptom. The VAS score reductions for burning and pain were significantly greater following ALA (P<0.01), while MC reduced numbness and paresthesia VAS scores to a slightly greater extent than ALA (P>0.05). Numbers of abnormal (low-response) points for pressure and pinprick sensation were reduced by MC but not by ALA, while both treatments induced a significant reduction in vibratory perception threshold (P<0.01). Neither MC nor ALA improved temperature sensation or tendon reflexes (P>0.05). Alpha-lipoic acid, increased SOD and reduced MDA (P<0.05), indicating enhanced antioxidant capacity, while MC had no effect.. Due to differences in efficacy, MC or ALA should be chosen according to the symptoms of individual patients.

Topics: Aged; Antioxidants; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Pain Measurement; Peripheral Nervous System Diseases; Thioctic Acid; Treatment Outcome; Vitamin B 12

Low serum B12 level is a common occurrence in patients with type 2 diabetes (T2DM) treated with metformin. There is lack of evidence concerning blood testing of vitamin B12 and current clinical guidelines make no recommendations on the detection or prevention of vitamin B-12 deficiency during metformin treatment. Our objective was to examine the current practice and clinical determinants of vitamin B12 testing in metformin treated T2DM patients. Data were collected from health maintenance organization patients, and consisted of T2DM patients who were newly prescribed metformin from 2008 to 2013. Patients were randomly divided into two subgroups: referred for a vitamin B12 blood test, and did not receive a referral. The demographic data and medical characteristics were analyzed. 5131 patients began taking metformin during the study period. Of these 2332 (44.5 %) had vitamin B12 tested. Significant differences were found between the groups in regard to glycosylated hemoglobin, low density lipoprotein, systolic blood pressure, dyslipidemia, chronic renal failure, and disease duration. A significant positive association (p < .05) was found between vitamin B12 testing and insulin treatment, retinopathy, neuropathy and hypertension. Vitamin B12 in elderly (>75 years) patients was significantly lower (p < .01). Insulin treatment, hypertension, and chronic diabetic complications in metformin treated T2DM patients are associated with higher rates of vitamin B12 testing. T2DM patients 75 years and above were less likely to be tested for B12 deficiency.

Topics: Age Factors; Aged; Comorbidity; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Healthcare Disparities; Humans; Hypoglycemic Agents; Israel; Male; Metformin; Primary Health Care; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 deficiency may occur with metformin treatment, but few studies have assessed risk with long-term use.. To assess the risk of B12 deficiency with metformin use in the Diabetes Prevention Program (DPP)/DPP Outcomes Study (DPPOS).. Secondary analysis from the DPP/DPPOS. Participants were assigned to the placebo group (PLA) (n = 1082) or the metformin group (MET) (n = 1073) for 3.2 years; subjects in the metformin group received open-label metformin for an additional 9 years.. Twenty-seven study centers in the United States.. DPP eligibility criteria were: elevated fasting glucose, impaired glucose tolerance, and overweight/obesity. The analytic population comprised participants with available stored samples. B12 levels were assessed at 5 years (n = 857, n = 858) and 13 years (n = 756, n = 764) in PLA and MET, respectively.. Metformin 850 mg twice daily vs placebo (DPP), and open-label metformin in the metformin group (DPPOS).. B12 deficiency, anemia, and peripheral neuropathy.. Low B12 (≤ 203 pg/mL) occurred more often in MET than PLA at 5 years (4.3 vs 2.3%; P = .02) but not at 13 years (7.4 vs 5.4%; P = .12). Combined low and borderline-low B12 (≤ 298 pg/mL) was more common in MET at 5 years (19.1 vs 9.5%; P < .01) and 13 years (20.3 vs 15.6%; P = .02). Years of metformin use were associated with increased risk of B12 deficiency (odds ratio, B12 deficiency/year metformin use, 1.13; 95% confidence interval, 1.06–1.20). Anemia prevalence was higher in MET, but did not differ by B12 status. Neuropathy prevalence was higher in MET with low B12 levels.. Long-term use of metformin in DPPOS was associated with biochemical B12 deficiency and anemia. Routine testing of vitamin B12 levels in metformin-treated patients should be considered.

Topics: Adult; Aged; Anemia; Diabetes Mellitus, Type 2; Female; Homocysteine; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

To assess the efficacy and safety of acetyl-L-carnitine (ALC) on diabetic peripheral neuropathy compared with methylcobalamin (MC).. This was a multicenter, randomized, parallel-group, double-blind, double-dummy, positive-controlled, non-inferior phase II clinical trial. Diabetic patients with abnormal nerve conduction test results were randomized in a 1:1 ratio to receive oral ALC 500 mg t.i.d. or MC 0.5 mg t.i.d. for 24 weeks. The neuropathy symptom score, neuropathy disability score and neurophysiological parameters were measured during follow up.. A total of 232 patients were randomized (ALC n = 117, MC n = 115), 88% of which completed the trial. At week 24, patients from both groups had significant reductions in both neuropathy symptom score and neuropathy disability score with no significant difference between two groups (neuropathy symptom score reduction: ALC vs MC 2.35 ± 2.23, P < 0.0001 vs 2.11 ± 2.48, P < 0.0001, intergroup P = 0.38; neuropathy disability score reduction ALC vs MC 1.66 ± 1.90, P < 0.0001 vs 1.35 ± 1.65, P < 0.0001, intergroup P = 0.23). Neurophysiological parameters were also improved in both groups. No significant difference was found between groups in the development of adverse events.. ALC is as effective as MC in improving clinical symptoms and neurophysiological parameters for patients with diabetic peripheral neuropathy over a 24-week period with good tolerance.

Topics: Acetylcarnitine; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Female; Humans; Male; Middle Aged; Neural Conduction; Severity of Illness Index; Treatment Outcome; Vitamin B 12

MAIM: To compare a single 1mg intramuscular hydroxocobalamin injection with a 3-month course of 1mg/day sublingual methylcobalamin supplements on serum vitamin B12 concentrations in participants withtype 2 diabetes treated with metformin.. Participants on metformin treatment with vitamin B12 concentrations below 220pmol/L were recruited through hospital diabetes clinics and primary care practices. They were randomised to receive either the injection or sublingual treatment. The primary outcome was serum vitamin B12 level after 3 months adjusted for baseline assessed by analysis of covariance (ANCOVA). The trial was registered on the Australia New Zealand Clinical Trial registry (ACTRN12612001108808).. A total of 34 participants were randomised; 19 to the tablet, and 15 to the injection. The mean (SD) age, duration of diabetes, and duration of metformin use were, 64.2 (7.3) years, 13.7 (6.4) years, and 11.6 (5.0) years, respectively. After 3 months, the mean (SD) vitamin B12 was 372.1 (103.3) pmol/L in the tablet group (n=19) compared to 251.7 (106.8) pmol/L in the injection group (n=15), ANCOVA estimated difference -119.4 (95% CI -191.2 to -47.6), p=0.002. After 6 months, the mean (SD) serum B12 was 258.8 (58.7) pmol/L in the tablet group (n=17) and 241.9 (40.1) pmol/L in the injection group (n=15); ANCOVA estimated difference -15.2 (95% CI -50.3 to 19.8), p=0.38. Higher metformin dose was associated with lower serum B12 at 3 months, but not at baseline or 6 months.. Decreased serum vitamin B12 level in patients with type 2 diabetes who are treated with metformin can be corrected through treatment with either hydroxocobalamin injections or methylcobalamin sublingual supplements.

Topics: Administration, Sublingual; Aged; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Humans; Hypoglycemic Agents; Injections, Intramuscular; Male; Metformin; Middle Aged; New Zealand; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

To evaluate the efficacy of internal application of Qigui Mixture (QM) and external application of Qigui Huoxue Lotion (QHL) in treating type 2 diabetic peripheral neuropathy (DNP) patients of qi-yin deficiency complicated phlegm-dampness blocking collaterals syndrome (QYD-PDBCS), and to primarily discuss its mechanism.. Totally 62 DPN patients of QYD-PDBCS were randomly assigned to the treatment group (31 cases) and the control group (31 cases). All patients received routine comprehensive therapy. Patients in the control group took Mecobalamine Tablet, 500 microg each time, 3 times per day. Patients in the treatment group additionally took QM, 200 mL per day, twice daily. Besides, they had foot bath in QHL 10 - 15 min every evening for 3 months. The efficacy was assessed by Chinese medical symptom integrals and Toronto clinical scoring system (TCSS) before treatment, 2 and 3 months after treatment. The nerve conduction velocity was determined; the serum levels of total antioxidant capacity (T- AOC), malondialdehyde (MDA), and superoxide dismutase (SOD) were detected 2 and 3 months after treatment.. The total effective rates of Chinese medical symptom integrals and TCSS score were obviously higher in the treatment group than in the control group (P < 0.05). The nerve conduction velocity was significantly improved in the treatment group, when compared with before treatment (P < 0.01). There was statistical difference in the nerve conduction velocity difference of right median nerve motor branch, bilateral tibial nerve motor branches, bilateral common peroneal nerve motor branches, bilateral ulnar nerve sensory branches, and left tibial nerve sensory branch (P < 0.05). Compared with before treatment, serum levels of T-AOC and SOD significantly increased, and the level of MDA decreased significantly in the treatment group after 2 and 3 months of treatment (P < 0.01). But only the SOD level increased significantly in the control group (P < 0.01). There was no statistical difference in increased T-AOC level between the two groups after 2 months of treatment (P > 0.05), but there was statistical difference in increased SOD level and decreased MDA level (P < 0.05). There was statistical difference in increased T-AOC and SOD levels and decreased MDA level between the two groups after 3 months of treatment (P < 0.05). No adverse reaction occurred during the therapeutic course.. The internal application of QM and external application of QHL combined with Mecobalamine in treating DPN was safe and effective, with more significant efficacy than using Mecobalamine alone. Its mechanism might be associated with resistance to oxidative stress.

Topics: Adult; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Drugs, Chinese Herbal; Female; Humans; Male; Middle Aged; Qi; Treatment Outcome; Vitamin B 12; Yin Deficiency

To determine whether a combination of L-methylfolate, methylcobalamin, and pyridoxal-5'-phosphate (LMF-MC-PLP [Metanx; Pamlab LLC, Covington, La]) improves sensory neuropathy.. This multicenter, randomized, double-blind, placebo-controlled trial involved 214 patients with type 2 diabetes and neuropathy (baseline vibration perception threshold [VPT]: 25-45 volts), who were randomly assigned to 24 weeks of treatment with either L-methylfolate calcium 3 mg, methylcobalamin 2 mg, and pyridoxal-5'-phosphate 35 mg or placebo. The primary end point was effect on VPT. Secondary end points included Neuropathy Total Symptom Score (NTSS-6) and Short Form 36 (SF-36), as well as plasma levels of folate, vitamins B(6) and B(12), methylmalonic acid (MMA), and homocysteine.. There was no significant effect on VPT. However, patients receiving LMF-MC-PLP consistently reported symptomatic relief, with clinically significant improvement in NTSS-6 scores at week 16 (P=.013 vs placebo) and week 24 (P=.033). Improvement in NTSS scores was related to baseline MMA and inversely related to baseline PLP and metformin use. Quality-of-life measures also improved. Homocysteine decreased by 2.7±3.0 μmol/L with LMF-MC-PLP versus an increase of 0.5±2.4 μmol/L with placebo (P=.0001). Adverse events were infrequent, with no single event occurring in ≥2% of subjects.. LMF-MC-PLP appears to be a safe and effective therapy for alleviation of peripheral neuropathy symptoms, at least in the short term. Additional long-term studies should be conducted, as the trial duration may have been too short to show an effect on VPT. In addition, further research on the effects in patients with cobalamin deficiency would be useful.

Topics: Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Female; Folic Acid; Humans; Male; Middle Aged; Pyridoxal Phosphate; Treatment Outcome; Vitamin B 12

Recent studies suggest increased cancer risk in patients with type 2 diabetes mellitus (T2DM) compared with healthy individuals. The present study aims to assess whether T2DM is associated with increased genome instability and whether a healthy diet with natural foods can improve genome stability in peripheral blood lymphocytes (PBLs). Seventy-six diabetic and 21 non-diabetic individuals were randomly assigned to either an 'intervention' or an 'information only' group. All participants received information about the beneficial effects of a healthy diet, while subjects of the intervention group received additionally 300g of vegetables and 25ml of plant oil rich in polyunsaturated fatty acids per day for 8 weeks. Chromosomal damage was assessed using the cytokinesis-block micronucleus (MN) cytome assay. Levels of chromosomal damage did not differ between diabetic and non-diabetic individuals. However, diabetic individuals with MN frequency above the high 50th percentile had significantly higher levels of fasting plasma glucose, glycosylated haemoglobin and were at higher risk for cardiovascular disease (CVD), assessed by the Framingham general cardiovascular risk score. Non-diabetic individuals with MN frequency above the 50th percentile had significantly lower vitamin B12 levels. The intervention with vegetables and plant oil led to significant increases in folate, γ-tocopherol, α- and β-carotene while vitamin B12 was significantly reduced. Levels of chromosomal damage were not altered, only apoptosis was slightly increased. The results suggest interactions between glycaemic control, CVD risk and genome stability in individuals with T2DM. However, a healthy diet does not improve genome damage in PBLs.

Topics: Aged; Anthropometry; beta Carotene; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Carotenoids; Chromosome Aberrations; Diabetes Mellitus, Type 2; DNA Damage; Fatty Acids, Unsaturated; Female; Folic Acid; gamma-Tocopherol; Genome, Human; Genomic Instability; Glycated Hemoglobin; Humans; Lymphocytes; Male; Micronucleus Tests; Middle Aged; Plant Oils; Risk Factors; Vegetables; Vitamin B 12

Metformin is widely used in patients with type 2 diabetes, but it may decrease vitamin B12 and folate levels and increase levels of homocysteine (Hcy). Hyperhomocysteinemia (HHC) and hyperglycemia induce oxidative stress in type 2 diabetes. Thus, this study was performed to determine the effects of folate supplementation on the concentration of homocysteine, total antioxidant capacity (TAC), and malondialdehyde (MDA).. This was a double-blind randomized controlled clinical trial. Sixty-eight men with type 2 diabetes participated in the study with written consent. Patients were divided randomly into 2 groups: folic acid 5 mg/d and placebo. All patients received the tablets for 8 weeks. Anthropometric and nutrient intake data were obtained from each patient. Baseline and eighth-week homocysteine, total antioxidant capacity, malondialdehyde, folate, and B12 levels were measured.. After folate supplementation in the folic acid group, homocysteine was significantly decreased (15.1 ± 3.2 to 12.1 ± 3.1 μmol/L, p < 0.001) and folate and B12 levels were significantly increased (p < 0.001). A significant increase in total antioxidant capacity (0.96 ± 0.2 to 1.14 ± 0.3 mmol Fe2+/L, p < 0.001) and a significant decrease in malondialdehyde (2.6 ± 0.7 to 1.7 ± 0.2 μmol/L, p < 0.001) were observed in the folic acid group, whereas no significant changes occurred in the placebo group (p > 0.05).. Pharmacological doses of folate supplementation lowered plasma homocysteine and serum malondialdehyde levels and improved serum total antioxidant capacity and folate and B12 levels in patients with type 2 diabetes.

Topics: Administration, Oral; Aged; Antioxidants; Diabetes Mellitus, Type 2; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Folic Acid; Homocysteine; Humans; Male; Malondialdehyde; Metformin; Middle Aged; Oxidative Stress; Vitamin B 12

To study the effect of short term metformin therapy on plasma levels of cobalamin, cobalamin related metabolites and cobalamin binding proteins in elderly patients.. Twenty patients with type 2 diabetes were assigned to receive metformin or not for 3 months. Cobalamin and its metabolites were measured before and after metformin therapy.. As compared to baseline measures, there was a metformin therapy specific significant decrease in plasma levels of total cobalamin, total haptocorrin and haptocorrin bound cobalamin.. Plasma total cobalamin and haptocorrin bound cobalamin levels are reduced by short term metformin therapy in an elderly diabetic population. Larger scale, longer term studies are necessary to determine if there is an unequivocal decrease in functional measures of cobalamin status.

Topics: Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Down-Regulation; Female; Humans; Hypoglycemic Agents; Male; Metformin; Time Factors; Transcobalamins; Vitamin B 12

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.. Multicentre randomised placebo controlled trial.. Outpatient clinics of three non-academic hospitals in the Netherlands.. 390 patients with type 2 diabetes receiving treatment with insulin.. 850 mg metformin or placebo three times a day for 4.3 years.. Percentage change in vitamin B-12, folate, and homocysteine concentrations from baseline at 4, 17, 30, 43, and 52 months.. 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).. 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.

Topics: Aged; Diabetes Mellitus, Type 2; Female; Folic Acid; Homocysteine; Humans; Hypoglycemic Agents; Long-Term Care; Male; Metformin; Middle Aged; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

Low-fat vegetarian and vegan diets are associated with weight loss, increased insulin sensitivity, and improved cardiovascular health.. We compared the effects of a low-fat vegan diet and conventional diabetes diet recommendations on glycemia, weight, and plasma lipids.. Free-living individuals with type 2 diabetes were randomly assigned to a low-fat vegan diet (n = 49) or a diet following 2003 American Diabetes Association guidelines (conventional, n = 50) for 74 wk. Glycated hemoglobin (Hb A(1c)) and plasma lipids were assessed at weeks 0, 11, 22, 35, 48, 61, and 74. Weight was measured at weeks 0, 22, and 74.. Weight loss was significant within each diet group but not significantly different between groups (-4.4 kg in the vegan group and -3.0 kg in the conventional diet group, P = 0.25) and related significantly to Hb A(1c) changes (r = 0.50, P = 0.001). Hb A(1c) changes from baseline to 74 wk or last available values were -0.34 and -0.14 for vegan and conventional diets, respectively (P = 0.43). Hb A(1c) changes from baseline to last available value or last value before any medication adjustment were -0.40 and 0.01 for vegan and conventional diets, respectively (P = 0.03). In analyses before alterations in lipid-lowering medications, total cholesterol decreased by 20.4 and 6.8 mg/dL in the vegan and conventional diet groups, respectively (P = 0.01); LDL cholesterol decreased by 13.5 and 3.4 mg/dL in the vegan and conventional groups, respectively (P = 0.03).. Both diets were associated with sustained reductions in weight and plasma lipid concentrations. In an analysis controlling for medication changes, a low-fat vegan diet appeared to improve glycemia and plasma lipids more than did conventional diabetes diet recommendations. Whether the observed differences provide clinical benefit for the macro- or microvascular complications of diabetes remains to be established. This trial was registered at clinicaltrials.gov as NCT00276939.

Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Diet Records; Diet, Fat-Restricted; Diet, Vegetarian; Dietary Fats; Dietary Supplements; Glycated Hemoglobin; Humans; Lipoproteins, HDL; Lipoproteins, LDL; Time Factors; Vitamin B 12; Weight Loss

Type 2 diabetes mellitus (T2DM) is a worldwide pandemic that may lead to diabetic kidney disease (DKD), a complication which is the single most important and globally prevalent cause of chronic kidney disease. Microalbuminuria has been shown to be an early indicator of DKD and data suggest that angiotensin receptor blockers (ARBs) reduce urinary albumin excretion and retard the progression of renal disease in hypertensive T2DM patients. However, the effects of ARBs on preventing microalbuminuria and ensuing DKD in normotensive patients with T2DM is yet to be fully established. The objective of this study is to assess the anti-microalbuminuric effects of losar-tan therapy versus placebo in normotensive T2DM patients. This randomized single blinded controlled trial was performed at the Diabetic Clinic, Jinnah Hospital, Lahore over a period of 10 months. A total of 361 normotensive patients with T2DM and microalbuminuria were selected; of them, 171 patients were randomly allocated to the test group and 190 enrolled into the control group. The patients in the test group were started on losartan 50 mg/day for a six month period while those in the control group were put on vitamin B-12 500 mcg/day. The patients as well as the primary attending phy-sicians/lab evaluators were blinded to the study. All study patients were followed up on a monthly basis. Quantitative microalbuminuria was tested at the beginning and at the end of the study. Out of the 171 patients in the test group, 149 (87.1%) had significant reduction of albuminuria by > 30% of their baseline (mean 101.9 +/- 21.7 baseline and, 47.5 +/- 12.9 post-therapy). The corresponding values for albuminuria in the 190 patients in the control group was mean 104.7 +/- 26.3 baseline and post 6-month mean 103.9 +/- 22.9, with P< 0.0001. The anti-albuminuric effect of losartan was reversible as seen on re-checking the urinary albumin two months after discontinuation of treatment. Our study shows that losartan was well tolerated and demonstrated significant anti-proteinuric effects in patients with T2DM with early nephropathy independent of hypertension.

Topics: Adult; Aged; Albuminuria; Angiotensin II Type 1 Receptor Blockers; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Losartan; Male; Middle Aged; Single-Blind Method; Time Factors; Treatment Outcome; Vitamin B 12; Vitamins

Homocysteinemia may play an etiologic role in the pathogenesis of type 2 diabetes by promoting oxidative stress, systemic inflammation, and endothelial dysfunction. We investigated whether homocysteine-lowering treatment by B vitamin supplementation prevents the risk of type 2 diabetes.. The Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a randomized, double-blind, placebo-controlled trial of 5,442 female health professionals aged > or = 40 years with a history of cardiovascular disease (CVD) or three or more CVD risk factors, included 4,252 women free of diabetes at baseline. Participants were randomly assigned to either an active treatment group (daily intake of a combination pill of 2.5 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12) or to the placebo group.. During a median follow-up of 7.3 years, 504 women had an incident diagnosis of type 2 diabetes. Overall, there was no significant difference between the active treatment group and the placebo group in diabetes risk (relative risk 0.94 [95% CI 0.79-1.11]; P = 0.46), despite significant lowering of homocysteine levels. Also, there was no evidence for effect modifications by baseline intakes of dietary folate, vitamin B6, and vitamin B12. In a sensitivity analysis, the null result remained for women compliant with their study pills (0.92 [0.76-1.10]; P = 0.36).. Lowering homocysteine levels by daily supplementation with folic acid and vitamins B6 and B12 did not reduce the risk of developing type 2 diabetes among women at high risk for CVD.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Middle Aged; Placebos; Proportional Hazards Models; Risk Factors; Vitamin B 12; Vitamin B 6; Vitamin E

Homocysteine is a predictor of vascular disease and may have an important role in diabetes. In this study, we examined the effects of folic acid and methylcobalamin supplementation on changes in homocysteine (Hcy) levels and homocysteine thiolactonase/paraoxonase (HTase/PON) activity in a short-term trial.. Ninety patients with type 2 diabetes were randomly divided into three groups: Group I received no vitamin supplementation, group II received 5 mg/day folic acid (orally), group III received folic acid (5 mg/day) in combination with methylcobalamin (500 microg/day; intramuscularly, on prescription). All patients were treated for 2 weeks. Plasma Hcy, HTase/PON activity, vitamin B(12), and folic acid were measured before and after supplementation in each group. In addition, forty healthy (nondiabetic) controls were enrolled.. Serum HTase/PON activity was significantly higher in diabetics compared with controls, plasma Hcy levels were significantly lower (P<0.05). After vitamin supplementation there was a significant reduction in plasma Hcy levels. The mean percentage reduction in Hcy was 2.75% in group I, 14% in group II and 37.3% in group III. There was a significant inverse correlation between the changes in HTase/PON activity and Hcy levels (r=-0.29, P=0.004). A 2.72% increase in HTase/PON activity was seen in group I, an 8.03% increase was detected when folic acid was given in group II (P<0.001), and a 17.59% increase in HTase/PON activity was seen in group III (P<0.001).. Short-term oral folic acid (5 mg/day) supplementation with or without methylcobalamin appeared to be an effective approach to decrease Hcy levels and increase HTase/PON activity in patients with type 2 diabetes. A decrease in plasma Hcy levels may partly account for the elevation of serum HTase/PON activity. This could be a novel mechanism to protect against vascular diabetic complications.

Topics: Adult; Aged; Aryldialkylphosphatase; Carboxylic Ester Hydrolases; Diabetes Mellitus, Type 2; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Vitamin B 12; Vitamins

To study the effects of methylcobalamin and folic acid treatment on plasma homocysteine (Hcy) level and homocysteine thiolactonase/paraoxonase (HTase/PON) activity in patients with type 2 diabetes mellitus.. 120 patients with type 2 diabetes mellitus were randomly divided into four equal groups: Group I, receiving no intervention therapy as control group, Group II, given folic acid orally (5 mg/d), Group III, receiving intramuscular injection of methylcobalamin (500 microg qd), and Group IV, treated with methylcobalamin (500 microg qd) in addition to folic acid (5 mg/d). Forty healthy age-matched persons were used as normal controls. Before and 12 weeks after 2-week treatment, plasma total Hcy, vitamin B(12), folic acid, and HTase/PON activity were assayed.. After 12-week treatment the plasma folic acid and methylcobalamin, and Hcy levels decreased and serum HTase/PON activity increased significantly in the three groups receiving intervention treatment (all P < 0.05). The Hcy level decreased by 2.8% in Group I, 14.0% in Group II, 37.3% in Group III, and 21.7% in Group IV respectively (all P < 0.01). The HTase/PON activity increased by 2.7% in Group I, 8.0% in Group II, 3.4% in Group III, and 17.6% in Group IV respectively (all P < 0.05).. Methylcobalamin and folic acid treatment alone can decrease the Hcy level and increase the HTase/PON activity in the patients with type 2 diabetes mellitus, and the methylcobalamin and folic acid combination therapy is much more effective. Folic acid may affect the HTase/PON activity through its antioxidant ability.

Topics: Administration, Oral; Adult; Aged; Aryldialkylphosphatase; Carboxylic Ester Hydrolases; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Folic Acid; Homocysteine; Humans; Injections, Intramuscular; Middle Aged; Treatment Outcome; Vitamin B 12; Vitamin B Complex

To explore to what extent homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine, total folate, 5-methyltetrahydrofolate (5-MTHF), vitamin B12, and vitamin B6 are associated with endothelium-dependent, flow-mediated vasodilation (FMD), and whether these associations are stronger in individuals with diabetes or other cardiovascular risk factors.. In this population-based study of 608 elderly people, FMD and endothelium-independent nitroglycerin-mediated dilation (NMD) were ultrasonically estimated from the brachial artery (absolute change in diameter [mum]). High SAM and low 5-MTHF were significantly associated with high and low FMD, respectively (linear regression coefficient, [95% confidence interval]): 48.57 microm (21.16; 75.98) and -32.15 microm (-59.09; -5.20), but high homocysteine was not (-15.11 microm (-42.99; 12.78). High SAM and low 5-MTHF were also significantly associated with high and low NMD, respectively. NMD explained the association of 5-MTHF with FMD but not of SAM. No interactions were observed for diabetes or cardiovascular risk factors.. In this elderly population, both SAM and 5-MTHF are associated with endothelial and smooth muscle cell function. The effect of homocysteine on endothelial function is relatively small compared with SAM and 5-MTHF. The relative impact of SAM, 5-MTHF, and homocysteine, and the mechanisms through which these moieties may affect endothelial and smooth muscle cell function need clarification.

Topics: Aged; Brachial Artery; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelium, Vascular; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Nitroglycerin; Regional Blood Flow; Risk Factors; S-Adenosylmethionine; Tetrahydrofolates; Ultrasonography; Vasodilation; Vasodilator Agents; Vitamin B 12; Vitamin B 6

Hyperhomocysteinemia is a risk factor for atherothrombosis. Through unknown mechanisms, individuals with type 2 diabetes appear particularly susceptible. We determined whether components of homocysteine metabolism are associated with intima-media thickness in individuals with and without type 2 diabetes.. In a cross-sectional design, we studied 231 Caucasian individuals, 60.6% having type 2 diabetes. We measured fasting homocysteine, vitamin B6 and vitamin B12 in plasma, and folate, S-adenosylmethionine and S-adenosylhomocysteine in plasma and erythrocytes. A homocysteine concentration >12 micromol/l was associated with a greater intima-media thickness of +0.07 mm (95% CI, +0.01 to +0.13; P=0.03) among diabetic individuals and of -0.004 mm (95%CI, -0.08 to +0.07; P=0.92) among non-diabetic individuals. An erythrocyte S-adenosylmethionine concentration above >4000 nmol/l was associated with a smaller intima-media thickness of -0.04 mm (95%CI, -0.10 to +0.02; P=0.17) for diabetic individuals versus -0.12 mm (95%CI, -0.20 to -0.36; P=0.005) for non-diabetic individuals.. With regard to carotid intima-media thickness, individuals with diabetes appear more susceptible to the detrimental effects of homocysteine than non-diabetic individuals. In addition, diabetic individuals may lack the protective effect on the vascular wall conferred by high concentrations of S-adenosylmethionine. These findings may help explain why hyperhomocysteinemia is an especially strong risk factor for atherothrombosis among individuals with type 2 diabetes.

Topics: Aged; Arteriosclerosis; Carotid Arteries; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Erythrocytes; Female; Homocysteine; Humans; Male; Middle Aged; S-Adenosylmethionine; Tunica Intima; Tunica Media; Vitamin B 12; Vitamin B 6

Metformin is a key treatment option in type 2 diabetes. However, metformin may decrease vitamin B12 levels and increase levels of homocysteine, a cardiovascular risk factor. We investigated whether 16 weeks of treatment with metformin affects serum concentrations of homocysteine, folate and vitamin B12 in subjects with type 2 diabetes treated with insulin.. Placebo-controlled, randomized trial.. at baseline and 16 weeks later.. This trial was conducted in the outpatient clinics of three general hospitals in The Netherlands.. A total of 745 patients with type 2 diabetes, treated with insulin and not known with a contraindication for the use of metformin, were approached; 390 gave informed consent and entered the study. Thirty-seven subjects dropped out (12 placebo and 25 metformin users).. Addition of metformin or placebo to insulin therapy. PRIMARY OUTCOME PARAMETERS: Serum homocysteine, folate, vitamin B12, indices of glycaemic control and body weight.. Amongst those who completed 16 weeks of treatment, metformin use, as compared with placebo, was associated with an increase in homocysteine of 4% (0.2 to 8; P=0.039) and with decreases in folate [-7% (-1.4 to -13); P=0.024] and vitamin B12 [-14% (-4.2 to -24); P<0.0001]. In addition, the increase in homocysteine could be explained by the decreases in folate and vitamin B12.. In patients with type 2 diabetes, 16 weeks of treatment with metformin reduces levels of folate and vitamin B12, which results in a modest increase in homocysteine. The clinical significance of these findings remains to be investigated.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Administration Schedule; Female; Folic Acid; Homocystine; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Vitamin B 12

Topics: Calcium; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Intestinal Absorption; Metformin; Vitamin B 12

Elevated blood homocysteine is a risk factor for cardiovascular disease. A 5-micromol/L increase is associated with an approximately 70% increase in relative risk of cardiovascular disease in adults. For patients with established risk factors, this risk is likely even greater.. Effects of increased dietary folate and recommended intakes of vitamins B-12 and B-6 on serum total homocysteine (tHcy) were assessed in individuals at high risk of cardiovascular disease.. This trial was conducted at 10 medical research centers in the United States and Canada and included 491 adults with hypertension, dyslipidemia, type 2 diabetes, or a combination thereof. Participants were randomly assigned to follow a prepared meal plan (PMP; n = 244) or a self-selected diet (SSD; n = 247) for 10 wk, which were matched for macronutrient content. The PMP was fortified to provide >/=100% of the recommended dietary allowances for 23 micronutrients, including folate.. Mean folate intakes at 10 wk were 601 +/- 143 microgram/d with the PMP and 270 +/- 107 microgram/d with the SSD. With the PMP, serum tHcy concentrations fell from 10.8 +/- 5.8 to 9.3 +/- 4.9 micromol/L (P < 0.0001) between weeks 0 and 10 and the change was associated with increased intakes of folate, vitamin B-12, and vitamin B-6 and with increased serum and red blood cell folate and serum vitamin B-12 concentrations. tHcy concentrations did not change significantly with the SSD.. The PMP resulted in increased intakes and serum concentrations of folate and vitamin B-12. These changes were associated with reduced serum tHcy concentrations in persons at high risk of cardiovascular disease.

Topics: Adult; Aged; Analysis of Variance; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet; Female; Folic Acid; Food, Fortified; Homocysteine; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Pyridoxine; Risk Factors; Vitamin B 12

To investigate the effect of mecobalamin on diabetic neuropathies.. One hundred and eight patients with non-insulin dependent diabetes mellitus were involved in a randomized positive-control clinical trial. 62 cases were treated with mecobalamin 500 microg intramuscularly three times a week for four weeks then followed by 500 microg orally three times a day for additional eight weeks. 46 cases were treated with vitamin B(12) in the same way and served as controls.. Twelve weeks after the treatment, spontaneous pain and numbness of limbs were improved by 73% and 75% in the mecobalamin group, which were much higher than those in the controls (36% and 45% respectively). Hypoesthesia, hotness, coldness, oral dryness and dysuria showed better response in the mecobalamin group than in the controls (55% vs 25%, 52% vs 18%, 59% vs 30%, 53% vs 19%, 63% vs 20% respectively). Mecobalamin also benefited nerve reflection and conduction velocity to a certain extent. No obvious side effects were found.. Mecobalamin might be worthy of use as a safe agent in the treatment of diabetic neuropathies.

Topics: Administration, Oral; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Neuroprotective Agents; Vitamin B 12

Metformin treatment increases circulating homocysteine levels. We studied whether administration of folate reduces serum total homocysteine levels in patients on long-term metformin treatment.. A prospective, randomized, double-blind, placebo-controlled study lasting for 12 weeks and taking place in a university hospital setting.. Thirty patients treated with a metformin dose of at least 1000 mg day-1 for a minimum of 1 year were included. At baseline serum total homocysteine levels were within the reference range. One patient who withdrew and one who died were excluded from the statistical evaluation. Twenty-six of the remaining patients suffered from NIDDM, the other two from hyperlipidaemia.. Patients were randomized into two groups at week 0. The folate group received 0.25 mg day-1 of folate in addition to 60 mg day-1 of Fe2+, while the placebo group received only 60 mg day-1 of Fe2+.. Fasting homocysteine, cysteine, cysteinylglycine, vitamin B12 and folate were measured at week 0, 4 and 12. Changes from week 0 to week 4 and from week 0 to week 12 were calculated.. Folate administration reduced serum levels of total homocysteine in the folate group as compared with the placebo group by 13.9% (P < 0.01) and 21.7% (P < 0.001) at week 4 and 12, respectively. In the folate group versus the placebo group serum levels of vitamin B12 increased by 9.9% (P = 0.010) and 9.6% (P = 0.043) while folate levels increased by 96.9 and 89.9% at week 4 and 12, respectively.. The present study indicates that the homocysteine-increasing effect of metformin can be counteracted by folate administration.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptides; Double-Blind Method; Female; Folic Acid; Hematinics; Homocysteine; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vitamin B 12

Sulfonylurea drugs have been the only oral therapy available for patients with non-insulin-dependent diabetes mellitus (NIDDM) in the United States. Recently, however, metformin has been approved for the treatment of NIDDM.. We performed two large, randomized, parallel-group, double-blind, controlled studies in which metformin or another treatment was given for 29 weeks to moderately obese patients with NIDDM whose diabetes was inadequately controlled by diet (protocol 1: metformin vs. placebo; 289 patients), or diet plus glyburide (protocol 2: metformin and glyburide vs. metformin vs. glyburide; 632 patients). To determine efficacy we measured plasma glucose (while the patients were fasting and after the oral administration of glucose), lactate, lipids, insulin, and glycosylated hemoglobin before, during, and at the end of the study.. In protocol 1, at the end of the study the 143 patients in the metformin group, as compared with the 146 patients in the placebo group, had lower mean (+/- SE) fasting plasma glucose concentrations (189 +/- 5 vs. 244 +/- 6 mg per deciliter [10.6 +/- 0.3 vs. 13.7 +/- 0.3 mmol per liter], P < 0.001) and glycosylated hemoglobin values (7.1 +/- 0.1 percent vs. 8.6 +/- 0.2 percent, P < 0.001). In protocol 2, the 213 patients given metformin and glyburide, as compared with the 210 patients treated with glyburide alone, had lower mean fasting plasma glucose concentrations (187 +/- 4 vs. 261 +/- 4 mg per deciliter [10.5 +/- 0.2 vs. 14.6 +/- 0.2 mmol per liter], P < 0.001) and glycosylated hemoglobin values (7.1 +/- 0.1 percent vs. 8.7 +/- 0.1 percent, P < 0.001). The effect of metformin alone was similar to that of glyburide alone. Eighteen percent of the patients given metformin and glyburide had symptoms compatible with hypoglycemia, as compared with 3 percent in the glyburide group and 2 percent in the metformin group. In both protocols the patients given metformin had statistically significant decreases in plasma total and low-density lipoprotein cholesterol and triglyceride concentrations, whereas the values in the respective control groups did not change. There were no significant changes in fasting plasma lactate concentrations in any of the groups.. Metformin monotherapy and combination therapy with metformin and sulfonylurea are well tolerated and improve glycemic control and lipid concentrations in patients with NIDDM whose diabetes is poorly controlled with diet or sulfonylurea therapy alone.

Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Fasting; Female; Folic Acid; Glucose Tolerance Test; Glyburide; Glycated Hemoglobin; Humans; Insulin; Lactates; Lactic Acid; Male; Metformin; Middle Aged; Obesity; Treatment Failure; Vitamin B 12

We studied the effect of prostaglandin E1.alpha CD (PGE1) on diabetic peripheral neuropathy by evaluating subjective symptoms and vibration sensation using a new vibrometer (SMV-5). Patients with diabetic neuropathy (n = 38) were divided into three groups; group A received no drugs (control), group B was treated with 1500 micrograms/day of oral methyl vitamin B12 (VB12) for four weeks, and group C received 1.2 micrograms/kg/day PGE1 intravenously for four weeks. There was a close relationship between symptom scores and vibratory threshold (VT). The effect of PGE1 on subjective symptoms and VT were compared with those in groups A and B. Patients who received PGE1 showed a significant improvement rate in pain and hypesthesia compared to patients in groups A and B, and in numbness compared to group A. During the study period, there was no significant change in VT in groups A and B, whereas VT was significantly improved at styloid process (P < 0.05) and at medial malleolus (P < 0.001) in group C. Our results confirmed that PGE1 significantly improved both subjective symptoms and VT, indicating that PGE1 therapy may be useful in diabetic neuropathy.

Topics: Administration, Oral; Adult; Aged; Alprostadil; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Dose-Response Relationship, Drug; Female; Humans; Hypesthesia; Injections, Intravenous; Male; Middle Aged; Pain Threshold; Vitamin B 12

We studied the clinical and neurophysiological effects of methylcobalamin on patients with diabetic neuropathy. In a double-blind study, the active group showed statistical improvement in the somatic and autonomic symptoms with regression of signs of diabetic neuropathy. Motor and sensory nerve conduction studies showed no statistical improvement after 4 months. The drug was easily tolerated by the patients and no side effects were encountered.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Muscle Contraction; Neurologic Examination; Peripheral Nerves; Reaction Time; Reflex, Stretch; Sensation; Synaptic Transmission; Vitamin B 12

Emerging evidence suggests that dietary one-carbon metabolism-related B-vitamins are associated with the reduced risk of cardiovascular disease (CVD) in the general population. However, only a few studies have assessed their associations in patients with type 2 diabetes (T2D).. This study aimed to assess the associations between the intake of three one-carbon metabolism-related B-vitamins (folate, vitamin B6, and vitamin B12) and CVD risk in Chinese patients with T2D.. A hospital-based case-control study of 419 patients with T2D and newly diagnosed CVD and 419 age- (±5 years) and sex-matched T2D-only controls was carried out in China. A validated 79-item semi-quantitative food-frequency questionnaire administered in face-to-face interviews was used to measure dietary B-vitamin intake. Conditional logistic regression was used to assess associations, which were tested by estimating odds ratios (ORs) with 95% confidence intervals (CIs).. Compared with the lowest quartile, the multivariable-adjusted ORs and 95% CIs for highest quartile were 0.32 (95% CI: 0.20, 0.52; p trend <0.001) for folate, 0.47 (95% CI: 0.30, 0.76; p trend = 0.002) for vitamin B6, and 1.02 (95% CI: 0.67, 1.55; p trend = 0.841) for vitamin B12. Consistent inverse associations were found for folate intake from eggs, vegetables, fruits, soy, and other foods but not for folate intake from grains.. Findings suggest that the high consumption of folate and vitamin B6, but not that of vitamin B12, might be associated with the low risk of CVD in patients with T2D. This study suggests that dietary folate and vitamin B6 protect against CVD in patients with T2D.

Topics: Carbon; Cardiovascular Diseases; Case-Control Studies; Diabetes Mellitus, Type 2; Folic Acid; Humans; Risk Factors; Vitamin B 12; Vitamin B 6; Vitamins

MetforminHydrochloride is an antidiabetic used for many years, currently; it considered the first choice in treatment of type 2 diabetes (T2D). It decreases insulin resistance, does not induce hypoglycaemia, increases glucose utilization in the liver and skeletal muscle, and decreases hepatic glucose production. Its adverse effects (AE) are gastrointestinal, decrease in vitamin B12 absorption, abnormalities of hemogram and rarely skin reactions. The objective of this study was to report the type and frequency of AEs of Metformin Hydrochloride used in the therapeutic management of T2D patients admitted to the medical center and the diabetes home of Sidi Bel-Abbès in Algeria.. A cross-sectional descriptive study was carried out over a period of four months, from January 1st, 2017 to April 30th, 2017, involving 130 patients treated with Metformin Hydrochloride consulting at Mimoun City Diabetes Home and Gambetta Diabetes Center in the town of Sidi Bel-Abbès. The primary outcome measure was the determination of the type and frequency of AEs related to normal dosages or overdose use of Metformin Hydrochloride in T2D. Data were collected from patient records, using a questionnaire, and analyzed using Statistical Package for the Social Sciences, version 20 software.. 130 patients were included, including 82 women, with a mean age of 51.08±8.85 years (30-66). One hundred and ninety-eight (198) AEs were reported, an average of 1.52 AEs per patient. Among them, 95 (47.98%) AEs are digestive disorders (30.77% of patients suffered from diarrhea, 10.77% had nausea and vomiting, 8.46% suffered from abdominal pain and bloating, 3.85% lost their taste, 7.69% complained of epigastric cramps and 11.54% of anorexia), 29 (14.65%) AEs are hypoglycaemia, 73 (36.87%) AEs are other symptoms and 1 (0.50%) EI is vitamin B12 deficiency and no cases of lactic acidosis or allergic reaction were reported. Five (3.85%) patients had a total and lasting intolerance to Metformin Hydrochloride leading to its discontinuation following persistent diarrhoea.. AEs of Metformin Hydrochloride used in the management of T2D patients consulting at the medical center and the Diabetes home of Sidi Bel-Abbès are frequent. Digestive disorders were the most frequent, diarrhea was very frequent and led to discontinuation of treatment in 3.85% of T2D patients, followed by nausea and vomiting, then abdominal pain, bloating and epigastric cramps, and rarely taste metallic. Hypoglycaemia was frequent following its association with insulin, the onset of headaches and fatigue were frequent, but no case of lactic acidosis or allergic reaction was reported. Due to a lack of means, the dosage of homocysteine and methylmalonic acid had not been carried out to confirm the vitamin B12 deficiency in the patient whose level was less than 200ng/mL. A precise assessment of the imputability of reported AEs is necessary.

Topics: Acidosis, Lactic; Adult; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Hypersensitivity; Hypoglycemia; Hypoglycemic Agents; Metformin; Middle Aged; Muscle Cramp; Nuns; Vitamin B 12; Vitamin B 12 Deficiency

Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor used for the treatment of type 2 diabetes, with additional beneficial effects for the kidney. Treatment of mice with linagliptin revealed increased storage of cobalamin (Cbl, Vitamin B12) in organs if a standard Cbl diet (30 µg Cbl/kg chow) is given. In order to translate these findings to humans, we determined methylmalonic acid (MMA), a surrogate marker of functional Cbl homeostasis, in human plasma and urine samples (n = 1092) from baseline and end of trial (6 months after baseline) of the previously completed MARLINA-T2D clinical trial. We found that individuals with medium Cbl levels (MMA between 50 and 270 nmol/L for plasma, 0.4 and 3.5 µmol/mmol creatinine for urine, at baseline and end of trial) exhibited higher MMA values at the end of study in placebo compared with linagliptin. Linagliptin might inhibit the N-terminal degradation of the transcobalamin receptor CD320, which is necessary for uptake of Cbl into endothelial cells. Because we demonstrate that linagliptin led to increased organ levels of Cbl in mice, sustained constant medium MMA levels in humans, and inhibited CD320 processing by DPP-4 in-vitro, we speculate that linagliptin promotes intra-cellular uptake of Cbl by prolonging half-life of CD320.

Topics: Animals; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Endothelial Cells; Homeostasis; Humans; Hypoglycemic Agents; Linagliptin; Mice; Vitamin B 12

Years of use of the antidiabetic drug metformin has long been associated with the risk of vitamin B12 (B12) deficiency in type 2 diabetes (T2D) patients, although the underlying mechanisms are unclear. Accumulating evidence has shown that metformin may exert beneficial effects by altering the metabolism of the gut microbiota, but whether it induces human B12 deficiency via modulation of bacterial activity remains poorly understood. Here, we show that both metformin and the other biguanide drug phenformin markedly elevate the accumulation of B12 in E. coli. By functional and genomic analysis, we demonstrate that both biguanides can significantly increase the expression of B12 transporter genes, and depletions of vital ones, such as tonB, nearly completely abolish the drugs' effect on bacterial B12 accumulation. Via high-throughput screens in E. coli and C. elegans, we reveal that the TetR-type transcription factor RcdA is required for biguanide-mediated promotion of B12 accumulation and the expressions of B12 transporter genes in bacteria. Together, our study unveils that the antidiabetic drug metformin helps bacteria gather B12 from the environment by increasing the expressions of B12 transporter genes in an RcdA-dependent manner, which may theoretically reduce the B12 supply to T2D patients taking the drug over time.

Topics: Animals; Caenorhabditis elegans; Diabetes Mellitus, Type 2; Escherichia coli; Humans; Hypoglycemic Agents; Metformin; Vitamin B 12; Vitamin B 12 Deficiency

Type 2 diabetes mellitus (T2DM) is a known risk factor for cardiovascular disease and stroke. Metformin is an old, relatively safe, first line therapy for T2DM; however, it has been associated with stroke.. To study the effects of metformin use and vitamin B12 deficiency on stroke rate among patients with T2DM.. We conducted a prospective study of patients admitted with ischemic stroke within 12 months (starting March 2020). We studied the clinical impact of metformin on vitamin B12 deficiency and stroke evolution. Student's t-test and ANOVA were used to compare the groups of patients and to determine whether there was any direct or indirect effect of metformin use on vitamin B12 deficiency and stroke.. In total, 80 patients were admitted with ischemic stroke. Clinical status and biochemical data were collected and compared with healthy volunteers. There were 39 diabetic patients, 16 took metformin for at least 1 year. Among those who took metformin for at least 1 year, 9 had vitamin B12 level < 240 pg/ml (56.2%); 23 diabetic patients did not get metformin and only 4 had vitamin B12 level < 240 pg/ml (17.4%) (P = 0.014).. T2DM is a significant risk factor to the development of ischemic stroke. We found an association between metformin use and vitamin B12 deficiency and an association between vitamin B12 deficiency and stroke risk in patients with T2DM. Diabetic patients who are taking metformin should monitor their vitamin B12 level.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Ischemic Stroke; Metformin; Prospective Studies; Stroke; Vitamin B 12; Vitamin B 12 Deficiency

Metformin treatment is associated with vitamin B12 deficiency, which is a risk factor for neuropathy. However, few studies have examined the relationship between metformin treatment and diabetic peripheral neuropathy (DPN), and the available findings are contradictory. We aimed to assess whether metformin treatment is associated with DPN in patients with type 2 diabetes mellitus (T2DM) in Beijing, China.. All patients with newly diagnosed T2DM between January 2010 and September 2012 in the Medical Claim Data for Employees database were included. Metformin treatment was defined as any record of metformin prescription. The average daily dose of metformin during follow-up was calculated. DPN was defined as DPN admissions occurring after a diagnosis of T2DM in the database. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models.. Among 49,705 T2DM patients, 1,933 DPN events were recorded during a median follow-up of 6.36 years. The crude incidence rates were 7.12 and 3.91 per 1000 person-years for patients treated with metformin (N=37,052) versus those not treated (N=12,653). Patients treated with metformin had an 84% increased risk of DPN compared with patients not using metformin (HR, 1.84; 95% CI, 1.62, 2.10). The daily dose was positively associated with DPN risk (HR, 1.48; 95% CI, 1.46, 1.51; P for trend <0.001). The risk of DPN was 1.53-fold (1.30, 1.81) and 4.31-fold (3.76, 4.94) higher in patients with daily doses of 1.0-2.0 g and >2.0 g, respectively, than in patients who did not receive treatment. Patients aged less than 60 years had a higher risk of DPN (P<0.05 for interaction test). Among patients taking vitamin B12 at baseline, there was no increased risk of DPN in the metformin group (1.92: 0.79, 4.69).. In Chinese patients with T2DM, metformin treatment was associated with an increased risk of DPN admission and this risk responds positively to the daily dose of metformin. In particular, metformin use was a major risk factor for DPN in younger patients. Concomitant use of vitamin B12 may avoid the increased risk of DPN associated with metformin use.

Topics: Beijing; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Metformin; Middle Aged; Vitamin B 12

Diabetic retinopathy (DR) is one of the most important causes of preventable visual impairment among patients of working age and leading cause of blindness. Deficiency of vitamin B12 and folate has been associated with increased serum homocysteine (Hcy) levels. This study was done to find out the role of vitamin B12 and Hyperhomocysteine (HHcy) in Diabetic retinopathy. The present study is a hospital-based case-control study conducted during over a period of 12 months from January 2019 to December 2019 study conducted in the Department of Ophthalmology at BIRDEM General Hospital, Dhaka, Bangladesh consisting of 100 Type 2 DM patients either with or without retinopathy (DR, n=50 and DNR, n=50, respectively). Subjects with Type 2 DM with and without retinopathy were recruited from patients attending in the department of Ophthalmology at BIRDEM General Hospital, Dhaka and were matched for duration of diabetes. Diabetes subjects on nutritional supplements for the last 6 months and those with a history of nephropathy (based standard renal function tests) and complications other than DR were excluded. Homocysteine (Hcy) levels were inversely related (p<0.05) with Diabetes patients with retinopathy. Vitamin B12 also significant correlated with Diabetes patients with retinopathy. A statistically significant negative linear relationship was found between serum homocysteine and vitamin B12 levels (Pearson r = -0.918, p=0.001) Diabetes patients with retinopathy. Vitamin B12 significantly correlated with diabetes retinopathy and homocysteine levels were inversely related with diabetes patients with retinopathy.

Topics: Bangladesh; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Humans; Hyperhomocysteinemia; Vitamin B 12; Vitamin B 12 Deficiency

Like many developed nations, the prevalence of both older people and type-2 diabetes mellitus (T2DM) in Singapore is rising. This demographic shift predisposes the population to greater risks of both frailty and its complications that can be further aggravated by vitamin B12 deficiency -a highly prevalent associated variable that is potentially modifiable. Indeed, B12 deficiency adversely impacts the neuro-cognitive, haematological, and even the immune systems; jeopardizing our aspirations for successful aging. Despite this, many patients with T2DM in primary care remain unscreened due to a lack of clear guidelines for regular B12 screening. We therefore investigated the determinants of B12 deficiency in community-dwelling patients with T2DM, with the aim of profiling patients most in need of B12-deficiency screening.. B12 deficiency was evaluated using a retrospective cross-sectional cohort of 592 primary-care patients with T2DM, recruited from 2008 to 2011 from a Polyclinic in Singapore.. B12 deficiency (serum B12 < 150 pmol/L) was present in 164 (27.7%) patients and was associated with a higher "metformin daily dose" (OR = 2.79; 95% CI, 2.22-3.48, P < 0.001); "age ≥ 80 years" (OR = 2.86; 95% CI, 1.31-6.25, P = 0.008); "vegetarianism" (OR = 21.61; 95% CI, 4.47-104.44, P < 0.001); and "folate deficiency" (OR = 2.04; 95% CI, 1.27-3.28, P = 0.003). Conversely, "Prescribed B12 supplementation" was associated with a lower odds of B12 deficiency (OR = 0.37; 95% CI: 0.22-0.61, P < 0.001). The area under the receiver operating characteristic curve was 0.803 (95% CI: 0.765-0.842). "Metformin daily dose" correlated interchangeably with "Metformin 1-year cumulative dose" (r = 0.960; P < 0.01), and also associated linearly with "duration of diabetes" (B = 0.113, P < 0.0001). Independent of the duration of T2DM, 29.3% of the B12-deficient patients needed > 1 screening test before the detection of B12 deficiency.. Primary-care screening for B12 deficiency should be part of the annual laboratory review of patients with T2DM regardless of the duration of T2DM -especially when they are prescribed ≥ 1.5 g/day of metformin; ≥ 80 years old; vegetarian; and not prescribed B12 supplementation. Concurrent evaluation for associated folate (vitamin B9) deficiency is essential when addressing T2DM-associated B12 deficiencies. Current "Metformin daily dose" is an accurate proxy of both cumulative metformin exposure and duration of T2DM.

Topics: Aged; Aged, 80 and over; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Folic Acid; Humans; Hypoglycemic Agents; Metformin; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

Prevalence of diabetes was high and rose significantly in the US between 1999 and 2018. A healthy dietary pattern that provides micronutrient adequacy is one of the most important lifestyle choices for battling the progress of diabetes. Yet, the patterns and trends of diet quality of the US type 2 diabetes are understudied.. We aim to examine the patterns and trends of diet quality and major food sources of macronutrients of US type 2 diabetic adults.. The 24 h dietary recalls of 7789 type 2 diabetic adults, comprising 94.3% of total adults with diabetes from the US National Health and Nutrition Examination Survey cycles (1999-2018), were analyzed. Diet quality was measured by the total Healthy Eating Index (HEI)-2015 scores and 13 individual components. Trends of usual intakes of vitamin C (VC), vitamin B12 (VB12), iron, and potassium and supplements from two 24 h recalls were also examined for type 2 diabetic population.. Diet quality of type 2 diabetic adults worsened between 1999 and 2018 while that of US adults of general population improved based on the total HEI 2015 scores. For people with type 2 diabetes, consumption of saturated fat and added sugar increased while consumption of vegetables and fruits declined significantly, although consumption of refined grain declined and consumption of seafood and plant protein increased significantly. In addition, usual intakes of micronutrients VC, VB12, iron, and potassium from food sources declined significantly during this period.. Diet quality generally worsened for US type 2 diabetic adults between 1999 and 2018. Declining consumptions of fruits, vegetables, and non-poultry meat may have contributed to the increasing inadequacies of VC, VB12, iron, and potassium in the US type 2 diabetic adults.

Topics: Adult; Ascorbic Acid; Diabetes Mellitus, Type 2; Diet; Energy Intake; Humans; Iron; Micronutrients; Nutrition Surveys; Potassium; Vegetables; Vitamin B 12; Vitamins

The use of metformin in diabetic patients causes vitamin B12 deficiency, but there is not enough evidence about the existence of a correlation between different doses of metformin and vit B12 deficiency. Therefore, this study was conducted with the aim of investigating the correlation between different doses of metformin and vitamin B12 deficiency. This cross-sectional study was conducted on 200 patients with type 2 diabetes referred to the diabetes clinic of the central hospital of Sulaimani city in 2022. Demographic data were collected by a questionnaire and the serum level of Vit B12 data was by testing the blood samples. Data analysis was done using SPSS ver.23 and descriptive tests, chi-square, Pearson correlation and logistic regression. The results showed that 24% of patients had vitamin B12 deficiency. 45 (93.8%) patients with vitamin B12 deficiency have taken metformin. The mean vitamin B12, mean metformin consumption per year and metformin dose were significantly different between the two groups. Based on the regression model, it was shown that there was no significant relationship between the serum level of vitamin B12 and the duration of metformin medication (P=0.134). And the relationship between gender, occupation, alcohol and metformin dose (mg) was significant, so these factors have the ability to predict the serum level of vitamin B12. The results showed that vitamin B12 deficiency is common in diabetic patients who take metformin, and the vitamin deficiency will increase with the increase in the dosage.

Topics: Cross-Sectional Studies; Diabetes Mellitus, Type 2; Humans; Metformin; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 involves several physiological functions, and malabsorption is reported with medication use.. Studies have reported an inverse association between the use of metformin or acid-lowering agents (ALAs), such as proton pump inhibitors, histamine 2 receptor antagonists, and blood vitamin B12 concentration, because of malabsorption. The concomitant use of these medications is underreported. We sought to examine these associations in a cohort of Boston-area Puerto Rican adults.. This analysis was conducted within the Boston Puerto Rican Health Study (BPRHS), an ongoing longitudinal cohort that enrolled 1499 Puerto Rican adults aged 45-75 y at baseline. Our study comprised 1428, 1155, and 782 participants at baseline, wave2 (2.2 y from baseline), and wave3 (6.2 y from baseline), respectively. Covariate-adjusted linear and logistic regression was used to examine the association between baseline medication use and vitamin B12 concentration or deficiency (vitamin B12 <148 pmol/L or methylmalonic acid >271 nmol/L), and long-term medication use (continuous use for ∼6.2 y) and wave3 vitamin B12 concentration and deficiency. Sensitivity analyses were done to examine these associations in vitamin B12 supplement users.. At baseline, we observed an association between metformin use (β = -0.069; P = 0.03) and concomitant ALA and metformin use (β = -0.112; P = 0.02) and vitamin B12 concentration, but not a deficiency. We did not observe associations between ALA, proton pump inhibitors, or histamine 2 receptor antagonists, individually, with vitamin B12 concentration or deficiency.. These results suggest an inverse relationship between metformin, concomitant ALA, metformin use, and serum vitamin B12 concentration.

Topics: Adult; Diabetes Mellitus, Type 2; Histamine; Histamine H2 Antagonists; Humans; Hypoglycemic Agents; Metformin; Proton Pump Inhibitors; Vitamin B 12; Vitamin B 12 Deficiency

To evaluate the prevalence of vitamin B12 deficiency in Chinese patients with type 2 diabetes mellitus receiving metformin treatment and to investigate the effects of metformin daily dose and treatment duration on the prevalence of vitamin B12 deficiency and peripheral neuropathy (PN).. In this multicenter cross-sectional study, 1027 Chinese patients who had been taking ≥1000 mg/day metformin for ≥1 year were enrolled using proportionate stratified random sampling based on daily dose and treatment duration. Primary measures included the prevalence of vitamin B12 deficiency (<148 pmol/L), borderline B12 deficiency (148 pmol/L-211 pmol/L), and PN.. The prevalence of vitamin B12 deficiency, borderline deficiency, and PN were 2.15%, 13.66%, and 11.59%, respectively. Patients receiving ≥1500 mg/day metformin had significantly higher prevalence of borderline vitamin B12 deficiency (16.76% vs. 9.91%, p = .0015) and serum B12 ≤221 pmol/L (19.25% vs. 11.64%, p < .001) than patients receiving <1500 mg/day metformin. No difference was found in prevalence of borderline vitamin B12 deficiency (12.58% vs. 15.49%, p = .1902) and serum B12 ≤221 pmol/L (14.91% vs. 17.32%, p = .3055) between patients receiving metformin for ≥3 and <3 years. Patients with vitamin B12 deficiency had numerically higher PN prevalence (18.18% vs. 11.27%, p = .3192) than patients without it. Multiple logistic analyses revealed that HbA1c and metformin daily dose were associated with the prevalence of borderline B12 deficiency and B12 ≤221 pmol/L.. High daily dosage (≥1500 mg/day) played an important role in metformin-associated vitamin B12 deficiency while not contributing to the risk of PN.

Topics: Cross-Sectional Studies; Diabetes Mellitus, Type 2; Duration of Therapy; East Asian People; Humans; Hypoglycemic Agents; Metformin; Peripheral Nervous System Diseases; Prevalence; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 (VB12) deficiency, which may lead to hematologic and neurologic symptoms, has been associated with metformin use, but the underlying mechanism is unclear. Here we report the B. ovatus as an effective VB12 catcher which was enriched in the type 2 diabetes patients suffered from VB12 deficiency after 3 to 6 months of metformin treatment. Colonization of B. ovatus increased the plasma levels of methylmalonic acid and homocysteine in high-fat diet (HFD)-fed mice treated with metformin, and compromised the efficacy of metformin against the HFD-induced metabolic disorders. Mechanistically, metformin increased the intracellular accumulation of VB12 in B. ovatus via btuB upregulation and promoted ATP production for energy-dependent translocation of VB12 transporters at the inner membrane, leading to an enhanced colonization of B. ovatus to compete for VB12 with hosts and subsequently an aggravated VB12 deficiency in the host. Our findings illustrate a previously unappreciated mechanism of metformin leads to host VB12 deficiency by acting directly on gut bacteria to increase their VB12 uptake and consumption, and suggest that inter-host-microbe competition for nutrients may broadly impact human health and drug safety.

Topics: Animals; Diabetes Mellitus, Type 2; Homocysteine; Humans; Metformin; Mice; Vitamin B 12; Vitamin B 12 Deficiency

Diabetes mellitus type 2 is characterized by insulin resistance, which can be combined with relatively decrease secretion of insulin hormone in the body. Metformin is usually recommended as a first-line treatment for diabetes mellitus-type 2, as it has a significant role in decrease mortality. This study aims to evaluate the B12 levels in Iraqi patients with type 2 diabetes, who were using the metformin drug in short-, medium- and long-term periods. The study included 202 patients, who were classified into four groups, according to their use of the Metformin drug as a hypoglycemic agent, while the fourth group did not use metformin and was termed as 'the standard group'. The results showed that the levels of vitamin B12 in patients using Metformin drugs in short-, medium- and long-term periods were, (444.4±17.21)pg/ml, (403.0±20.34)pg/ml and (261.7±14.70)pg/ml, respectively, compared to the standard group (469.7±26.37)pg/ml. The conclusion of this study was that a significant reduction was seen in the level of vitamin B12 in patients using the Metformin drug for medium- and long-term periods compared to the standard group, who did not use the Metformin drug.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Iraq; Metformin; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Vitamin B 12

The primary objective of this study was to explore the impact of metformin and metformin/gliptin combination therapy on the serum concentrations of vitamin B12, ferritin, and folic acid in individuals diagnosed with type 2 diabetes.. This study included 118 patients, classified into two groups: 59 patients using only metformin and 59 patients using a combination of metformin/gliptin. Among the latter group, 35 patients used vildagliptin/metformin, and 24 used sitagliptin/metformin. The study recorded the demographic data such as the age and gender of the patients, as well as their initial and 1-year follow-up blood parameters.. Folic acid decreased significantly in the metformin group but not in the metformin/gliptin group. Vitamin B12 and ferritin decreased significantly in both groups. The decrease in vitamin B12 and ferritin was not significantly different between the two groups. The decrease in fasting plasma glucose was more significant in the metformin/gliptin group than in the metformin group.. After 1 year, both groups taking metformin and metformin/gliptin showed low serum ferritin and vitamin B12 levels. Therefore, vitamin B12 levels in patients using these drugs should be closely monitored. Ferritin levels can be used to indicate whether glycemic control has been achieved.

Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Ferritins; Folic Acid; Humans; Hypoglycemic Agents; Metformin; Vitamin B 12

Despite that periodical monitoring of cobalamin (vitamin B12) in metformin-treated patients with diabetes is recommended, cobalamin-associated mortality benefits or risks remain unclear. We investigated the association between cobalamin intake and related biomarkers and mortality risk in adults with diabetes using metformin or not.. This study included 3,277 adults with type 2 diabetes from the National Health and Nutrition Examination Survey (NHANES) and followed up until 31 December 2015. Weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for mortality risk.. Among 3,277 participants, 865 all-cause deaths occurred during a median follow-up of 7.02 years. There was no robust relationship between all-cause mortality and serum cobalamin or intake of foods or cobalamin supplements, regardless of metformin treatment (each P ≥ 0.120). The doubling of methylmalonic acid (MMA), a cobalamin-deficiency marker, was significantly associated with higher all-cause (HR 1.31 [95% CI 1.18-1.45], P < 0.001) and cardiac (HR 1.38 [95% CI 1.14-1.67], P = 0.001) mortality. Cobalamin sensitivity was assessed by the combination of binary B12low/high and MMAlow/high (cutoff values: cobalamin 400 pg/mL, MMA 250 nmol/L). Patients with decreased cobalamin sensitivity (MMAhighB12high) had the highest mortality risk. The multivariable-adjusted HRs (95% CIs) of all-cause mortality in MMAlowB12low, MMAlowB12high, MMAhighB12low, and MMAhighB12high groups were 1.00 (reference), 0.98 (0.75-1.28), 1.49 (1.16-1.92), and 1.96 (1.38-2.78), respectively. That association was especially significant in metformin nonusers.. Serum and dietary cobalamin were not associated with reduced mortality. Decreased cobalamin sensitivity was significantly associated with all-cause and cardiac mortality, particularly among metformin nonusers.

Topics: Adult; Biomarkers; Diabetes Mellitus, Type 2; Humans; Methylmalonic Acid; Nutrition Surveys; Vitamin B 12; Vitamin B 12 Deficiency

This study aimed to assess the role of plasma homocysteine (Hcy) in the development of nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes (T2DM) without chronic kidney disease.. This was a cross-sectional study that included 94 T2DM. Hcy, serum 25-hydroxy (25-OH) vitamin D, vitamin B12, and folate were determined by the CMIA method. NPDR was determined according to the EURODIAB retinal photography methodology and optical coherence tomography (OCT) of the macula.. Compared to patients without NPDR, patients with NPDR had longer diabetes duration (p < 0.001), higher Hcy (p < 0.001), lower vitamin B12 (p = 0.028) and lower estimated glomerular filtration rate (eGFR) (p = 0.004). NPDR was positively associated with diabetes duration (p < 0.001), HbA. Higher Hcy is associated with NPDR and may play a role as a risk factor for its development in T2DM. Vitamins B12 and D seem to modify this association.

Topics: Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Folic Acid; Homocysteine; Humans; Vitamin B 12

Insomnia is highly prevalent in patients with type 2 diabetes mellitus (T2DM). This study therefore evaluated the associations between various micronutrients and insomnia in patients with T2DM.. Between January 2018 and December 2020, a total of 418 T2DM patients with or without insomnia were recruited. Clinical and biochemical parameters, as well as micronutrient levels, were measured in each participant. Insomnia and sleep quality were assessed using the Athens Insomnia Scale and Pittsburgh Sleep Quality Index, respectively.. Insomnia was found in 24.16% of patients with T2DM. Compared with T2DM patients without insomnia, patients with insomnia had significantly higher levels of vitamin B12 (VitB12). Increased VitB12 was an independent risk factor for insomnia (OR 1.61 [1.06-2.45], P = 0.03). A cut-off value of 517.50 pg/ml VitB12 (P = 0.01, AUC 0.61, standard error 0.04) predicted insomnia risk. Moreover, increased VitB12 levels in patients with insomnia were closely correlated with the use of mecobalamin.. This study suggests that elevated serum VitB12 level is independently associated with the incidence of insomnia and predicts increased insomnia risk in Chinese patients with T2DM.

Topics: China; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Humans; Sleep Initiation and Maintenance Disorders; Vitamin B 12

The associations of serum folate and vitamin B12 levels with cardiovascular outcomes among patients with type 2 diabetes (T2D) remain unclear.. To investigate the associations of serum folate and vitamin B12 levels with risk of cardiovascular disease (CVD) mortality among individuals with T2D.. This prospective cohort study included 8067 patients with T2D who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 through 2014 and NHANES III (1988-1994). American Diabetes Association criteria were used to define T2D. Data were analyzed between October 1, 2020, and April 1, 2021.. Serum folate and vitamin B12 levels.. Multivariable Cox proportional hazards regression models were used to compute hazard ratios and 95% CIs for the associations of serum folate and vitamin B12 levels with risks of CVD and all-cause mortality. Two multivariable models were constructed. Restricted cubic spline analyses were used to examine the nonlinear association of serum folate levels and vitamin B12 levels with CVD mortality, and nonlinearity was assessed using the likelihood ratio test.. This cohort study included data from 7700 participants in the folate analysis (mean [SE] age, 57.8 [0.3] years; 3882 men [weighted, 50.5%]; median serum folate level, 12.1 ng/mL [IQR, 7.1-19.5 ng/mL]) and 4860 participants for the vitamin B12 analysis (mean [SE] age, 57.8 [0.3] years; 2390 men [weighted, 50.7%]; median serum vitamin B12 level, 506.1 pg/mL [IQR, 369.1-703.5 pg/mL]). During 72 031 person-years of follow-up, 799 CVD deaths were documented for the folate analysis, and during 43 855 person-years of follow-up, 467 CVD deaths were reported for the vitamin B12 analysis. Nonlinear associations were observed for serum levels of folate (P = .04 for nonlinearity) and vitamin B12 (P = .04 for nonlinearity) with risk of CVD mortality among patients with T2D. Compared with participants in the second quartile of serum folate levels (7.1-12.1 ng/mL), the hazard ratios for CVD mortality were 1.43 (95% CI, 1.04-1.98) for participants in the lowest serum folate level quartile (<7.1 ng/mL) and 1.03 (95% CI, 0.74-1.44) for participants in the highest quartile (≥19.5 ng/mL). In addition, compared with participants in the second quartile of serum vitamin B12 levels (369.1-506.0 pg/mL), the hazard ratios for CVD mortality were 1.74 (95% CI, 1.20-2.52) for participants in the lowest quartile (<369.1 pg/mL) and 2.32 (95% CI, 1.60-3.35) for participants in the highest quartile (≥703.5 pg/mL). Similar patterns of association were observed for all-cause mortality (nonlinearity: P = .01 for folate and P = .02 for vitamin B12).. This cohort study found that both low and high serum levels of vitamin B12 as well as low serum levels of folate were significantly associated with higher risk of CVD mortality among individuals with T2D.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Female; Folic Acid; Humans; Male; Middle Aged; Nutrition Surveys; Nutritional Status; Proportional Hazards Models; Prospective Studies; Vitamin B 12

There have been no studies to date examining the effect of metformin treatment on vitamin B12 status in children and adolescents. In this prospective study, the effects of metformin on blood vitamin B12, serum methylmalonic acid (MMA), homocysteine and holo-transcobalamin-II (holo-TC-II) levels were assessed in pediatric age group.. This prospective study was conducted at the Pediatric Endocrinology and Adolescent Department between January 2017 and March 2019. Metabolic syndrome and polycystic ovary syndrome diagnosed patients with insulin resistance and/or impaired glucose tolerance, patients with type 2 diabetes mellitus (DM) treated with metformin were enrolled in study. Blood vitamin B12, MMA, homocysteine, holo-TC-II levels and hemogram values were evaluated.. Twenty-four patients were enrolled in study. Among these, 15 (62.5%) were female. The mean age of patients was 13.7±2.3 (10-19) years. Sixteen patients were diagnosed with metabolic syndrome and 8 patients were type 2 DM. At 6-month follow-up of all patients, there was no statistically significant difference in terms of vitamin B12, homocysteine, MMA and holo-TC-II levels. A 0.6% decline in vitamin B12 levels were revealed. At 12-month follow-up of 11 patients (45.8%) (6 Type 2 DM, 5 metabolic syndrome), no statistically significant difference was determined in vitamin B12, homocysteine, MMA and holo-TC-II levels. There were 6% decline in vitamin B12 levels and 10.9% increase in homocysteine levels, 5.4% decrease was detected in holo-TC-II level.. Although no significant changes in the serum vitamin B12, homocysteine, MMA or holo-TC-II levels with metformin therapy were detected, long-term prospective studies with high-dose metformin treatment in pediatric population are needed to confirm our results.

Topics: Adolescent; Child; Diabetes Mellitus, Type 2; Female; Homocysteine; Humans; Male; Metabolic Syndrome; Metformin; Methylmalonic Acid; Prospective Studies; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Chronic axonal polyneuropathy is a common disease, but the etiology remains only partially understood. Previous etiologic studies have identified clinical risk factors, but genetic evidence supporting causality between these factors and polyneuropathy are largely lacking. In this study, we investigate whether there is a genetic association of clinically established important risk factors (diabetes, body mass index [BMI], vitamin B12 levels, and alcohol intake) with chronic axonal polyneuropathy.. This study was performed within the population-based Rotterdam Study and included 1565 participants (median age = 73.6 years, interquartile range = 64.6-78.8, 53.5% female), of whom 215 participants (13.7%) had polyneuropathy. Polygenic scores (PGSs) for diabetes, BMI, vitamin B12 levels, and alcohol intake were calculated at multiple significance thresholds based on published genome-wide association studies.. Higher PGSs of diabetes, BMI, and alcohol intake were associated with higher prevalence of chronic axonal polyneuropathy, whereas higher PGS of vitamin B12 levels was associated with lower prevalence of polyneuropathy. These effects were most pronounced for PGSs with lenient significance thresholds for diabetes and BMI (odds ratio [OR]. This study provides evidence for polygenic associations of diabetes, BMI, vitamin B12 level, and alcohol intake with chronic axonal polyneuropathy. This supports the hypothesis of causal associations between well-known clinical risk factors and polyneuropathy.

Topics: Aged; Diabetes Mellitus, Type 2; Female; Genome-Wide Association Study; Humans; Male; Polyneuropathies; Risk Factors; Vitamin B 12

Coronary heart disease and its complications remain the most common cause of morbidity and mortality throughout the world. In addition, its incidence among adults <45 years of age has also been steadily increasing in the past few decades. Besides the typical aetiology such as coronary artery abnormalities or autoimmune disorders, increasing rates can be attributed to escalating trends of obesity, type 2 diabetes mellitus, and illicit abuse of drugs such as cocaine and amphetamines in the younger population.

Topics: Amphetamines; Cocaine; Diabetes Mellitus, Type 2; Folic Acid; Humans; Male; Myocardial Infarction; Sprue, Tropical; Vitamin B 12; Young Adult

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

To evaluate the relationship between calciferol (vitamin D), cobalamin (vitamin-B12), and Stromelysin-1 (MMP-3) circulating levels in patients with diabetic peripheral neuropathy (DPN), patients with DM type 2 (T2DM) without neuropathy, and healthy control groups.. Cross-sectional descriptive study.. Department of Internal Medicine, Namik Kemal University of Medicine, Tekirdag, Turkey, between November 2020 and February 2022.. Healthy, age, and gender matched volunteers who were admitted to the hospital for a check-up with no health problem constituted the control group (n=30). Cases diagnosed with T2DM (n=30) and those with DPN (n=30) comprised the experimental group. Stromelysin-1, calciferol, and cobalamin levels were analysed from blood samples from all groups using enzyme-linked immunosorbent assay (ELISA) with a commercial kit. Tukey's Honest Significant Difference (HSD) test was performed after one-way analysis of variance (ANOVA) for intergroup comparisons. Alpha significance level was accepted as.

Topics: Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Ergocalciferols; Humans; Matrix Metalloproteinase 3; Vitamin B 12; Vitamin D; Vitamins

To describe the prevalence of vitamin B12 deficiency among Jordanian patients with type 2 diabetes mellitus treated with metformin and to compare the findings with those who did not receive metformin.. Total 155 patients with type 2 diabetes mellitus, aged between 48 and 82 years were enrolled in the current study. They were divided into two groups; the first (n = 120) was treated with metformin while the second (n = 35) was not. Patients' demographics (age, gender, duration of type 2 diabetes mellitus, smoking status), medication parameters (daily dosage and duration of metformin therapy), and biochemical parameters (hemoglobin level, mean corpuscular volume (MCV), serum vitamin B12, and folate level) were recorded. Definite deficiency was defined as serum vitamin B12 levels of < 150 pg/ml, whereas < 200 pg/ml indicated possible deficiency.. The mean serum ± standard deviation (SD) vitamin B12 level was significantly lower in patients who were treated with metformin (268.5 ± 35.8 vs. 389.5 ± 29.8 pg/ml, p = 0.029). The metformin group had significantly higher prevalence of definite deficiency (32% vs. 9%, p < 0.02) and possible deficiency (48% vs. 30%, p < 0.02). Within the metformin group, the mean serum ± SD vitamin B12 level was significantly lower in those on high dosage (175.2 ± 30.5 vs. 315.6 ± 37.8 pg/ml, p < 0.001). MCV (μm3) levels ± SD were higher in the metformin group (87.5 ± 2.9 vs. 83.7 ± 2.4) with no statistical significance.. There is a significant association between metformin intake and vitamin B12 deficiency. Serum vitamin B12 levels should be checked by physicians and serial monitoring is necessary in patients who are treated with metformin.

Topics: Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

Peripheral neuropathy caused by diabetes mellitus (DM) and vitamin B12 deficiency may produce overlapping clinical pictures. Metformin use is a known cause of B12 deficiency in patients with type 2 DM (T2DM). This cross-sectional comparative study was conducted at two specialized endocrine outpatient clinics in Mymensingh and Cumilla cities of Bangladesh over one year from July 2019 to June 2020. Non-pregnant adults (≥18 years of age) receiving drug treatment for T2DM for at least six months were included in this study. The study subjects were divided into two groups: those with ongoing treatment with metformin and those who never received metformin in their lifetime. Out of 99 subjects evaluated, 66 (66.7%) were in the metformin group, and 33 (33.3%) were in the non-metformin group. Subjects in the metformin group had significantly lower B12 levels compared to the non-metformin group [448.5 (343.0-570.9) vs. 549.0 (487.5-847.0) pg/mL, median (IQR), p<0.001]. None of the study subjects in the non-metformin group were either borderline deficient or deficient of B12 compared to five borderline deficient and three deficient subjects in the metformin group. Among the study subjects, 88.9% had peripheral neuropathy (PN) (43.4% mild, 21.2% moderate and 24.2% severe PN); the two groups had similar frequencies of PN. Though median serum B12 levels were lower in mild [483.0 (411.2-620.0) pg/mL], moderate [492.0 (366.5-680.0) pg/mL] and severe PN [524.5 (363.5-654.2) pg/mL] groups compared to absent PN group [540.0 (340.0-685.0) pg/mL]; the difference in B12 levels across the four groups was not statistically significant. B12 levels had weak negative correlation (r = -0.061, p = 0.624) with gram-years of metformin use. Periodic screening for serum vitamin B12 levels should be done to identify metformin-induced B12 deficiency in T2DM, especially those with PN.

Topics: Adult; Bangladesh; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Infant; Metformin; Vitamin B 12

The association of homocysteine metabolism-related nutrients along with renal function to homocysteine levels is not well known in patients with type 2 diabetes mellitus (T2DM). We investigated the relevance of kidney function, albuminuria, and nutritional factors to serum homocysteine in T2DM patients. This cross-sectional study enrolled 149 T2DM patients (96 men and 53 postmenopausal women), and patient characteristics and laboratory data including kidney-related data [glomerular filtration rate (eGFR), urinary albumin excretion (UACR), uric acid] and metabolism parameters (hemoglobin A1c and lipids) were collected from the medical record and serum levels of vitamin B12, folic acid, zinc, homocysteine and UACR were also acquired. In total subjects, serum levels of homocysteine, vitamin B12, and folic acid were within reference intervals, but zinc levels were close to lower limits of its reference interval. A multivariate-adjusted analysis showed that gender (β=-0.259, p<0.001), uric acid (β=0.267, p<0.001), eGFR (β=-0.188, p=0.001), log UACR (β=0.190, p=0.002), log folic acid (β=-0.259, p<0.001), log vitamin B12 (β=-0.224, p<0.001) and zinc (β=-0.169, p=0.006) were correlated to log homocysteine. In multiple regression analysis by gender, these correlations were found similarly in men, but neither log folic acid nor zinc showed correlations with log homocysteine in women. The present study suggests that renal function parameters and the certain nutritional factors have a possible influence on serum homocysteine, in T2DM patients including diabetes kidney disease.

Topics: Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Folic Acid; Homocysteine; Humans; Male; Vitamin B 12; Vitamin B Complex; Zinc

Studies have shown an association between metformin use and vitamin B. To determine the overall incidence and impact of the ADA Guideline on vitamin B. 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 B. Of 394 patients included for the primary outcome, 136 (34.5%) had at least 1 vitamin B. Vitamin B

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Retrospective Studies; Veterans; Vitamin B 12; Vitamins

Metformin-treated diabetics (MTD) showed a decrease in cobalamin, a rise in homocysteine, and methylmalonic acid, leading to accentuated diabetic peripheral neuropathy (DPN). This study aimed to determine whether or not metformin is a risk factor for DPN. We compared MTD to non-metformin-treated diabetics (NMTD) clinically using the Toronto Clinical Scoring System (TCSS), laboratory (methylmalonic acid, cobalamin, and homocysteine), and electrophysiological studies. Median homocysteine and methylmalonic acid levels in MTD vs. NMTD were 15.3 vs. 9.6 µmol/l; P < 0.001 and 0.25 vs. 0.13 µmol/l; P = 0.02, respectively with high statistical significance in MTD. There was a significantly lower plasma level of cobalamin in MTD than NMTD. Spearman's correlation showed a significant negative correlation between cobalamin and increased dose of metformin and a significant positive correlation between TCSS and increased dose of metformin. Logistic regression analysis showed that MTD had significantly longer metformin use duration, higher metformin dose > 2 g, higher TCSS, lower plasma cobalamin, and significant higher homocysteine. Diabetics treated with metformin for prolonged duration and higher doses were associated with lower cobalamin and more severe DPN.

Topics: Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Homocysteine; Humans; Male; Metformin; Methylmalonic Acid; Middle Aged; Peripheral Nervous System Diseases; Risk Factors; Vitamin B 12

The aim: To determine the peculiarities of changes in the homocysteine levels in the patients with chronic pancreatitis and type 2 diabetes blood serum depending on the vitamin status.. Materials and methods: We investigated 36 patients with chronic pancreatitis and type 2 diabetes, who were included in the first group of the patients examined; Group 2 consisted of 34 patients with chronic pancreatitis; and Group 3 of the patients examined consisted of 40 patients with type 2 diabetes.. Results: All patients examined were diagnosed with type 2 diabetes mellitus of moderate severity. Also, the diagnosis of chronic pancreatitis was confirmed in all patients with type 2 diabetes, which was manifested by exocrine pancreatic insufficiency according to the results of clinical, laboratory and instrumental methods of examination. There was a significant decrease in the level of all B vitamins and 25-(OH)D in patients with chronic pancreatitis and type 2 diabetes (Group I). An increase in the concentration of homocysteine in the serum in all examined groups of patients was established, with the maximum deviation from the norm in patients with chronic pancreatitis and type 2 diabetes (up to 32.7 ± 0.8 μmol / L <0.01). The correlation analysis revealed a strong direct relationship between the level of homocysteine and vitamins B12, B6, 25-(OH)D and an inverse correlation between vitamin B9 in the group of patients with chronic pancreatitis and type 2 diabetes.. Conclusions: Patients with chronic pancreatitis and type 2 diabetes have a decreased levels of B vitamins (B1, B6, B9, B12) and 25-(OH)D, which is accompanied by an increase in serum homocysteine. In patients with chronic pancreatitis and type 2 diabetes, the level of homocysteine in the blood serum directly depends on the decrease in the levels of vitamins B6, B12 and 25-(OH)D in blood serum, as well as inverse depends on vitamin B9 levels in these patients.

Topics: Diabetes Mellitus, Type 2; Folic Acid; Homocysteine; Humans; Pancreatitis, Chronic; Vitamin B 12

Metformin therapy has been associated with vitamin B. This cross-sectional study was carried out with type 2 diabetes mellitus patients treated (Met group, n = 122) or not treated (control group, n = 63) with metformin. The primary end-point was the difference in the serum concentration of homocysteine, a marker of VB12 activity, between the two groups. The serum concentrations of VB12, blood hemoglobin level and mean corpuscular volume were also compared between the groups. Subset analysis was carried out with individuals aged ≥70 years. The potential correlation between the daily dose or duration of metformin treatment and the other measured parameters was also examined.. The level of homocysteine, as well as the VB12 level, hemoglobin concentration and mean corpuscular volume, did not differ significantly between the control and treated with metformin groups. The level of homocysteine was positively and that of VB12 negatively correlated with the daily dose of metformin. Among elderly individuals, the hemoglobin level was significantly lower in the treated with metformin group than in the control group, although the mean corpuscular volume was similar in the two groups.. The risk of VB12 deficiency during metformin treatment appears to be low in Japanese type 2 diabetes mellitus patients. However, high doses of metformin might result in a moderate decrease in the circulating VB12 level, as well as in anemia in elderly individuals.

Topics: Aged; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Erythrocyte Indices; Female; Hemoglobins; Homocysteine; Humans; Hypoglycemic Agents; Japan; Male; Metformin; Middle Aged; Nutritional Status; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Prevalence; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Peripheral Nervous System Diseases; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

This study aimed to determine the prevalence of vitamin B12 deficiency amongst diabetic patients on metformin therapy.. This cross-sectional study was conducted at general clinics at the University Health Center and diabetes outpatient clinics at Sultan Qaboos University Hospital, Muscat, Oman, between January and December 2017. All Omani adults who were diagnosed with type 2 diabetes mellitus and took metformin were invited to participate in the study. The variables included in this study were age, gender, duration of diabetes, dose and duration of metformin therapy, haemoglobin and glycosylated haemoglobin level.. A total of 248 subjects were included (response rate = 95.4%) of which 26 (10.5%) were vitamin B12 deficient and 53 (21.4%) were borderline deficient. The mean daily dose of metformin was highest among vitamin B12 deficient group (1,981 ± 222 mg;. The prevalence of vitamin B12 deficiency is considerable among diabetic patients on metformin therapy. Further research is needed to confirm the need for routine screening and monitoring.

Topics: Adult; Aged; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Oman; Prevalence; Vitamin B 12; Vitamin B 12 Deficiency

The present study aimed to evaluate the combined effect of both dose and duration of metformin therapy on vitamin B12 levels in patients with type 2 diabetes mellitus (T2D).. We recruited 2887 patients with T2D between January 2018 and November 2019 and categorized them into two groups (metformin and non-metformin users) matched for age, mean duration of diabetes, and BMI. We calculated the "Metformin Usage Index" (MUI) which was defined as the product of the dose of metformin (mg) used and its duration divided by 1000. Vitamin B12 levels were compared between the two groups, and its association with MUI was assessed using correlation and multistep logistic regression analyses.. Vitamin B12 levels < 200 pg/ml and between 200 and 300 pg/ml were noted among 24.5% and 34.5% metformin users, respectively; this was significantly higher than among non-metformin users (17.3% and 22.6%, respectively) [P < 0.001]. Overall, a vitamin B12 level < 300 pg/ml was found in 52.2% of the subjects. There was a significant association between an MUI > 5 and a high risk of vitamin B12 deficiency [P < 0.01]. The highest risk was observed among patients with an MUI > 15 [odds ratio (OR) 6.74, 95% CI 4.39-10.4] followed by patients with an MUI > 10 (OR 5.12, 95% CI 3.12-8.38).. The MUI can be employed as a risk assessment tool for evaluation of vitamin B12 deficiency in patients with T2D. Further prospective studies are required to determine the MUI thresholds in populations with good nutritional statuses and low prevalence of vitamin B12 deficiency.

Topics: Adult; Case-Control Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Prevalence; Prospective Studies; Risk Assessment; Vitamin B 12; Vitamin B 12 Deficiency

Metformin is widely used for the treatment of type-2 diabetes (T2D) but was shown to cause vitamin-B. This descriptive cross-sectional study recruited T2D patients using metformin from a primary care center and examined their socioeconomic status, accompanying complaints, medication use, and hemogram parameters such as serum vitamin B. Study included 421 T2D patients on metformin regimen: 213 (50.6%) males and 208 (49.4%) females. The mean duration of diabetes was 9.88 ± 7.32 years, and the total metformin dose was 1925.5 ± 236.7 mg/d. Almost half of the participants (n = 199, 47.3%) had H pylori infection, and more than half (n = 222, 52.7%) had vitamin-B. This study supported the role of H pylori infection in vitamin-B

Topics: Aged; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metformin; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

A high intake of green leafy vegetables rich in antioxidative nutrients such as vitamin C and β-carotene may protect against the risk of type 2 diabetes. Measurement of the circulating nutrient concentrations can indicate the nutrient status more directly, and vitamin C and carotenoids are recognized as good biomarkers for the intake of fruits and vegetables. The aim of this study was to investigate the relationships between serum antioxidative vitamin concentrations and type 2 diabetes in Japanese subjects. The study subjects comprised 506 men and 493 women who first underwent anti-aging health checks at Tokai University Tokyo Hospital. Serum concentration of vitamin (V) A, VC, α-tocoferol, β-carotene, VB12, folate, ferritin and homocysteine, and fasting plasma glucose and HbA1c were used for analysis. Low levels of β-carotene and VC were significantly associated with dysglycemia. Diabetic subjects showed significantly decreased β-carotene and VC levels, and multivariate analyses suggested that low levels of β-carotene and VC were factors related to diabetes. Low levels of β-carotene and VC are significantly related to dysglycemia/type 2 diabetes, and encouraging people at a higher risk of diabetes to take more green vegetables may be useful as a dietary intervention to improve the antioxidative vitamin status and dysglycemia.

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Blood Glucose; Diabetes Mellitus, Type 2; Diet; Female; Folic Acid; Humans; Japan; Male; Middle Aged; Vitamin A; Vitamin B 12; Vitamins

Our objective was to assess whether increased duration of metformin therapy is associated with incident peripheral neuropathy (PN) in older Veterans with diabetes.. 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.. 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).. 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.

Topics: Aged; Alcoholism; Body Mass Index; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Hypoglycemic Agents; Logistic Models; Male; Metformin; Middle Aged; Retrospective Studies; Risk Factors; Smoking; Time Factors; Veterans; Vitamin B 12; Vitamin B 12 Deficiency

To assess the status of vitamin B12 in patients with type 2 diabetes, and to explore any association between its deficiency and diabetic peripheral neuropathy.. This cross-sectional observational study was conducted from August, 2017, to April, 2018, at the Specialized Centre for Endocrinology and Diabetes in Baghdad, Iraq. Type 2 diabetics using metformin were subjected to clinical examination for retinopathy using fundoscopy, and peripheral neuropathy using the Michigan Neuropathy Screening Instrument. Additionally, patients were asked to fill a questionnaire and their medical records were reviewed. Blood samples were obtained for the measurement of biomarkers. Vitamin B12 deficiency was recorded at ≤187 pg/ml. Data was analysed using SPSS 25.. Of the 66 patients, 39(59%) were males and 27(41%) were females. The overall mean age was 53.3}9.2 years and the mean duration of diabetes was 104}71.8 months. The mean dose of metformin was 1135}496 mg and the duration of metformin use was 72}62 months. Overall, 19(29%) patients suffered from vitamin B12 deficiency. However, no significant difference was found between normal and deficit groups regarding the parameters that may affect vitamin B12 level. Also, no significant correlations were found between vitamin B12 concentration and the dose (p=0.16) or the duration of metformin use (p=0.09).. High prevalence of vitamin B12 deficiency was observed in metformin-treated patients with type 2 diabetes. However, the deficiency had no correlation with the rate of peripheral neuropathy.

Topics: Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Hypoglycemic Agents; Incidence; Iraq; Male; Metformin; Middle Aged; Prevalence; Vitamin B 12; Vitamin B 12 Deficiency

Metformin can cause serum vitamin B12 deficiency, but studies on the influence of its duration and dose are lacking. We investigated vitamin B12 deficiency in patients with type 2 diabetes using metformin, in conjunction with other related factors.. This cross-sectional study included 1111 patients with type 2 diabetes who took metformin for at least 6 months. Serum vitamin B12 levels were quantified using a competitive-binding immunoenzymatic assay, and vitamin B12 deficiency was defined as serum B12 <300 pg/mL. Information on metformin use and confounding variables were collected from records or questionnaires and interviews.. Serum vitamin B12 deficiency occurred in 22.2% of patients (n = 247). After adjusting for confounders, a 1 mg increase in daily metformin dose was associated with a 0.142 pg/mL decrease in vitamin B12 (P < .001). Compared with a daily dose of <1000 mg, the adjusted odds ratios for 1000 to 1500, 1500 to 2000, and ≥2000 mg metformin were 1.72 (P = .080), 3.34 (P < .001), and 8.67 (P < .001), respectively. Vitamin B12 deficiency occurred less often in patients taking multivitamins (odds ratio 0.23; P < .001). After adjusting for confounding factors, there was no correlation between B12 deficiency and duration of metformin use. Serum homocysteine levels showed significant negative correlation with vitamin B12.. Metformin at ≥1500 mg/d could be a major factor related to vitamin B12 deficiency, whereas concurrent supplementation of multivitamins may potentially protect against the deficiency. Serum homocysteine levels were negatively correlated with vitamin B12 levels, suggesting that B12 deficiency due to metformin use may occur at the tissue level. However, this hypothesis will require further study.

Topics: Age Factors; Aged; Alcohol Drinking; Anemia; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Folic Acid; Homocysteine; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Odds Ratio; Republic of Korea; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

To explore the relationships between macular thickness and the plasma concentrations of homocysteine, vitamin B12, folate, and other known risk factors for patients with diabetes without diabetic macular edema (DME).. Fasting venous blood samples were collected from 252 subjects (126 relatively healthy subjects with type 2 diabetes without diabetic macular edema and 126 age- and gender-matched controls). Measurement of macular thickness and volume was performed for those subjects using SD-OCT. The plasma concentrations of homocysteine, vitamin B12, folate, and other known risk factors were analyzed in all the patients and controls using multiple linear regression models.. An increase in the serum levels of homocysteine was present within patients with type 2 diabetes compared to healthy individuals. The mean total plasma homocysteine levels were associated with a greater central subfield macular thickness (CSMT), average macular thickness (AMT), and average macular volume (AMV) in patients with type 2 diabetes without DME, after adjusting for age, sex, duration of diabetes, and HbA1c. Each 1 mmol/L increase in tHcy level was associated with a 6.57 µm greater CSMT (95% confidence interval [CI] 1.78, 11.36), a 4.51 µm greater AMT (95% CI 1.05, 7.98), and a 4.72 mm. Higher homocysteine levels were associated with an increased CSMT, AMT, and AMV in diabetic patients without DME. This link may indicate that patients with type 2 diabetes with increased levels of plasma tHcy are more prone to develop a clinical manifestation of DME.

Topics: Adult; Aged; Biomarkers; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Folic Acid; Homocysteine; Humans; Macula Lutea; Macular Edema; Male; Middle Aged; Regression Analysis; Vitamin B 12

B

Topics: Child; Diabetes Mellitus, Type 2; Dietary Supplements; DNA Methylation; Epigenomics; Female; Humans; Male; MicroRNAs; Vitamin B 12; Vitamin B Complex

Metformin treatment is associated with a decrease of serum vitamin B12, but whether this reflects tissue B12 deficiency is controversial. We studied the effects of metformin on serum levels of methylmalonic acid (MMA), a biomarker for tissue B12 deficiency, and on onset or progression of neuropathy.. In the HOME trial, 390 insulin-treated patients with type 2 diabetes were treated with metformin or placebo for 52months. In a post hoc analysis, we analyzed the association between metformin, MMA and a validated Neuropathy Score (NPS).. Metformin vs placebo increased MMA at the end of the study (95%CI: 0.019 to 0.055, p=0.001). Mediation analysis showed that the effect of metformin on the NPS consisted of a beneficial effect through lowering HbA1c (-0.020 per gram year) and an adverse effect through increasing MMA (0.042 per gram year), resulting in a non-significant net effect (0.032 per gram year, 95% CI: -0.121 to 0.182, p=0.34).. Metformin not only reduces serum levels of B12, but also progressively increases serum MMA. The increase of MMA in metformin users was associated with significant worsening of the NPS. These results provide further support that metformin-related B12 deficiency is clinically relevant. Monitoring of B12 in users of metformin should be considered.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Diabetes Mellitus, Type 2; Female; Humans; Male; Metformin; Methylmalonic Acid; Middle Aged; Randomized Controlled Trials as Topic; Retrospective Studies; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Endobarrier® is a minimally invasive, reversible endoscopic treatment for obesity. It provokes malabsorption along 60 cm of the small intestine, which can contribute to the development of vitamin deficiencies and to changes in bone mineral density (BMD). To determine the prevalence of nutrient deficiencies, changes in body composition and BMD during the first year after Endobarrier® placement. Twenty-one patients with type 2 diabetes met inclusion criteria. Levels of vitamins, micro and macronutrients were assessed prior and at 1, 3 and 12 months post-operatively. DEXA was performed before and 12 months after implant. Nineteen patients completed the 12 months follow-up. Vitamin D deficiency was the most prevalent finding before Endobarrier® implant. The percentage of patients with severe deficiency decreased from 19 to 5% at 12 months after supplementation. Microcytic anaemia was initially present in 9.5% of patients and increased to 26.3% at 12 months. Low ferritin and vitamin B12 levels were observed in 14.2 and 4.8% of patients before the implant and worsened to 42 and 10.5%. Low concentrations of magnesium and phosphorus were also common but improved along the study. A significant but not clinically relevant decrease in BMD of 4.14 ± 4.0% at the femoral neck was observed at 12 months without changes in osteocalcin levels. Vitamin deficiencies are common after Endobarrier® implant. It is therefore important to screen patients prior to and at regular intervals after the implant, and to encourage adherence to diet counselling and supplementation.

Topics: Anemia; Avitaminosis; Bone Density; Deficiency Diseases; Diabetes Mellitus, Type 2; Female; Femur Neck; Ferritins; Humans; Intestinal Absorption; Intestine, Small; Magnesium; Male; Middle Aged; Obesity; Phosphorus; Prostheses and Implants; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin D Deficiency

Assessment of the impact of type 2 diabetes (T2DM) and metformin use on vitamin B12 (VB12) associated biomarkers and their suitability to represent VB12 supply.. Differences of VB12, holotranscobalamine (HoloTc), the biologically active fraction  (%AB12)=HoloTc/VB12*100 and homocystein (Hcy) were analysed i) among diabetic outpatients with (DMMet+ ) and without metformin use (DMMet-) and ii) in comparison to an external non-diabetic reference group with low VB12 (<200 pmol/L).. VB12 associated biomarkers were distributed equally between DMMet+  (n=29, 58%) and DMMet- (n=21, 42%). Significant differences in %AB12 in diabetic patients with low VB12 (n=19) compared to the non-diabetic reference group (n=31) were found. Higher %AB12 was associated with diabetes. Hcy levels were significantly associated with age, folic acid level, renal function and HoloTc but not with VB12.. In T2DM patients with low VB12, %AB12 was confirmed as being higher in comparison to nondiabetic patients. The effect was not clearly attributable to metformin use. HoloTc was unaffected by the lowering of VB12 and significantly associated with the functional marker Hcy. Both findings support the use of HoloTc for the assessment of VB12 supply in diabetic patients.

Topics: Aged; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Male; Metformin; Middle Aged; Switzerland; Vitamin B 12; Vitamin B 12 Deficiency

Several observational studies have shown that low serum vitamin B-12 is associated with increased body mass index (BMI) and adverse cardiometabolic outcomes. However, it is unclear if these associations reflect a causal effect of vitamin B-12 on cardiometabolic risk factors and diseases, latent confounding, or reverse causality.. The aims of this study were to investigate 1) the possible causal relation between vitamin B-12 and indicators of body fat, lipid, and glucose variables; type 2 diabetes (T2D); and cardiovascular disease by using a 2-sample Mendelian randomization (MR) method and 2) the possible pleiotropic role of fucosyltransferase 2 (FUT2).. We selected 11 single nucleotide polymorphisms (SNPs) robustly associated with serum concentrations of vitamin B-12 in a previous genomewide association study (GWAS) in 45,576 individuals. We performed 2-sample MR analyses of the relation between vitamin B-12 and cardiometabolic risk factors and diseases with the use of publicly available GWAS summary statistics for 15 outcomes in ≤339,224 individuals. The robustness of results was tested with sensitivity analyses by using MR Egger regression and weighted-median estimation, and by performing additional analyses excluding a variant in the FUT2 gene, which may be pleiotropic.. We found a suggestive causal relation between vitamin B-12 and fasting glucose and β cell function [homeostatic model assessment (HOMA) of β cell function (HOMA-B)]. However, we found no evidence that serum concentrations of vitamin B-12 were causally related to BMI, waist-to-hip ratio, plasma leptin, body fat, fasting insulin, insulin resistance (from HOMA of insulin resistance), glycated hemoglobin, triglycerides, T2D, coronary artery disease, or HDL, LDL, or total cholesterol.. We found no evidence that serum concentrations of vitamin B-12 are causally related to body weight or the majority of cardiometabolic outcomes investigated. However, vitamin B-12 may have a causal effect on fasting glucose and HOMA-B, although these results will require replication in large independent data sets. This trialwas registered at http://www.isrctn.com/ISRCTN47414943 as ISRCTN47414943.

Topics: Blood Glucose; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Fucosyltransferases; Galactoside 2-alpha-L-fucosyltransferase; Genome-Wide Association Study; Humans; Insulin Resistance; Leptin; Lipids; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Risk Factors; Vitamin B 12

AMP-activated kinase (AMPK) is a major regulator of energy metabolism and a promising target for development of new treatments for type 2 diabetes and cancer. 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), an adenosine analog, is a standard positive control for AMPK activation in cell-based assays. Some broadly used cell culture media, such as minimal essential medium α (MEMα), contain high concentrations of adenosine and other nucleosides. We determined whether such media alter AICAR action in skeletal muscle and cancer cells. In nucleoside-free media, AICAR stimulated AMPK activation, increased glucose uptake, and suppressed cell proliferation. Conversely, these effects were blunted or completely blocked in MEMα that contains nucleosides. Addition of adenosine or 2'-deoxyadenosine to nucleoside-free media also suppressed AICAR action. MEMα with nucleosides blocked AICAR-stimulated AMPK activation even in the presence of methotrexate, which normally markedly enhances AICAR action by reducing its intracellular clearance. Other common media components, such as vitamin B-12, vitamin C, and α-lipoic acid, had a minor modulatory effect on AICAR action. Our findings show that nucleoside-containing media, commonly used in AMPK research, block action of the most widely used pharmacological AMPK activator AICAR. Results of cell-based assays in which AICAR is used for AMPK activation therefore critically depend on media formulation. Furthermore, our findings highlight a role for extracellular nucleosides and nucleoside transporters in regulation of AMPK activation.

Topics: Adenosine; Aminoimidazole Carboxamide; AMP-Activated Protein Kinase Kinases; Ascorbic Acid; Cell Line, Tumor; Culture Media; Diabetes Mellitus, Type 2; Energy Metabolism; Glucose; Humans; Muscle, Skeletal; Neoplasms; Nucleosides; Protein Kinases; Ribonucleotides; Thioctic Acid; Vitamin B 12

To compare the prevalence of vitamin B12 deficiency and peripheral neuropathy between two groups of type 2 diabetes mellitus (T2DM) patients treated with or without metformin, and to determine factors associated with vitamin B12 deficiency therapy and dietary intake of vitamin B12.. In this retrospective study, we recruited 412 individuals with T2DM: 319 taking metformin, and 93 non-metformin users. Demographics, dietary assessment for vitamin B12 intakes, and medical history were collected. Participants were assessed for peripheral neuropathy. Blood specimens were collected and checked for serum vitamin B12 levels. The differences between the two groups were analyzed using an independent t-test for continuous data, and the Chi-squared or Fisher's exact test was used for categorical data. The relationship of vitamin B12 deficiency with demographics and clinical characteristics was modeled using logistic regression.. The prevalence of B12 deficiency was 7.8% overall, but 9.4% and 2.2% in metformin users and non-metformin users, respectively. The odds ratio for serum vitamin B12 deficiency in metformin users was 4.72 (95% CI, 1.11-20.15, P = 0.036). There were no significant differences in a test of peripheral neuropathy between the metformin users and non-metformin users (P > 0.05). Low levels of vitamin B12 occurred when metformin was taken at a dose of more than 2,000 mg/day (AOR, 21.67; 95% CI, 2.87-163.47) or for more than 4 years (AOR, 6.35; 95% CI, 1.47-24.47).. Individuals with T2DM treated with metformin, particularly those who use metformin at large dosages (> 2,000 mg/day) and for a longer duration (> 4 years), should be regularly screened for vitamin B12 deficiency and metformin is associated with B12 deficiency, but this is not associated with peripheral neuropathy.

Topics: Diabetes Mellitus, Type 2; Diet; Female; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Peripheral Nervous System Diseases; Prevalence; Retrospective Studies; Risk Factors; Saudi Arabia; Vitamin B 12; Vitamin B 12 Deficiency

Gastric bypass has been thought to be associated with a risk of gastric cancer, particularly in Asia. Sleeve gastrectomy with duodenojejunal end-to-side anastomosis (SG-DJESA) was suggested to be a better-designed procedure to avoid this risk, and it also has other advantages.. We aimed to evaluate the clinical efficacy and feasibility of SG-DJESA in the treatment of nonobese patients with type 2 diabetes (T2D).. University Hospital, China.. We present prospective data from 7 consecutive T2D patients with gastric precancerosis who underwent SG-DJESA from December 15, 2011 to June 8, 2013. The group had a mean body mass index of 27.7 kg/m. Along with a decrease in antidiabetic medication requirements, body mass index, fasting plasma glucose, 2-hour postprandial plasma glucose, and glycated hemoglobin decreased significantly at each postoperative time point, compared with the preoperative baseline (P<.05, respectively). Four patients (4/7, 57.1%) achieved a complete remission of T2D at 12 months and maintained remission at the 4-year follow-up time; 1 patient (1/7, 14.3%) achieved a partial remission at 6 months but had recurrence at 12 months postoperatively; and the other 2 patients (2/7, 28.6%) achieved improvement during the follow-up time. There were no deaths during the follow-up period. One patient had a postoperative anastomotic bleed and recovered under conservative treatment. Another patient had iron deficiency anemia 8 weeks after surgery and recovered after taking an oral iron supplement for 1 month. No other serious perioperative complications or postoperative malnutrition occurred.. SG-DJESA is an effective and safe procedure for nonobese patients with T2D and could be recommended as a treatment option for T2D patients with gastric precancerosis. A larger sample size may be required for better evaluation.

Topics: Adolescent; Adult; Aged; Anastomosis, Surgical; Bariatric Surgery; Blood Glucose; China; Diabetes Mellitus, Type 2; Duodenum; Fasting; Feasibility Studies; Female; Folic Acid; Gastrectomy; Hemoglobins; Humans; Hypertension; Jejunum; Laparoscopy; Lipid Metabolism; Male; Middle Aged; Obesity; Postoperative Complications; Prospective Studies; Transferrin; Vitamin B 12; Young Adult

Current evidence linking vitamin B12 deficiency with metformin use is inconsistent. Hence, there is uncertainty regarding the diagnostic approach in this scenario. Furthermore, this possible association has not been studied in the complete spectrum of patients with diabetes.. We conducted a cross-sectional, controlled study with the objective of assessing differences in serum vitamin B12 levels among patients with and without diabetes with different metformin-treatment regimens. A total of 150 participants were recruited: patients with diabetes (group 1: metformin alone ≥850mg/day, group 2: patients with type 2 diabetes naive to treatment and group 3: metformin ≥850mg/day, in addition to any other oral glucose lowering agent or insulin, or both) and without diabetes (group 4: polycystic ovary syndrome or group 5: healthy individuals). Serum vitamin B12, folate levels and complete blood counts were obtained for the entire population. Methylmalonic acid and homocysteine were obtained for patients when vitamin B12 levels were found to be borderline or low.. When patients with or without diabetes were compared, no significant difference was found in relation to their vitamin B12 levels (517.62 versus 433.83; P = 0.072). No difference in vitamin B12 levels was found among participants with metformin use and metformin naive participants (503.4 versus 462.3; P = 0.380).. Irrespective of metformin use, no significant difference in the serum levels of vitamin B12 was observed, both in patients with and without diabetes. In the light of the body of evidence and the results of this study, a universal recommendation for vitamin B12 deficiency screening cannot be made.

Topics: Adolescent; Adult; Aged; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

Vitamin B12 deficiency could be associated with cardiovascular autonomic neuropathy (CAN) in diabetes patients. We aim to investigate the association between serum levels of vitamin B12 and CAN in type 2 diabetes patients.. 469 ambulatory type 2 diabetes patients (mean diabetes duration 10.0years (IQR 5.0;17.0), mean age 59.0years (SD 11.6), 63% men, mean B12 289.0pmol/l (IQR 217;390)) were screened for CAN using three cardiovascular reflex tests, five minute resting heart rate (5min RHR) and heart rate variability indices.. Serum levels of vitamin B12 were significantly lower in patients treated with metformin and/or proton pump inhibitors (PPIs) compared with patients not treated (p<0.001). A 25pmol/l higher level of vitamin B12 was associated with an odds ratio of the CAN diagnosis of 0.94 (95% CI 0.88; 1.00, p=0.034), an increase in E/I-ratio of 0.21% (95% CI 0.01; 0.43, p=0.038), and a decrease in 5min RHR of 0.25 beats per minute (95% CI -0.47; -0.03, p=0.025).. Vitamin B12 may be inversely associated with CAN in patients with type 2 diabetes. Confirmatory studies investigating a causal role of vitamin B12 for the development of diabetic CAN are warranted.

Topics: Antihypertensive Agents; Autonomic Nervous System Diseases; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Denmark; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Cardiomyopathies; Diabetic Neuropathies; Female; Heart Rate; Humans; Hypertension; Hypoglycemic Agents; Male; Mass Screening; Metformin; Middle Aged; Prevalence; Proton Pump Inhibitors; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

Little is known about arsenic and diabetes in youth. We examined the association of arsenic with type 1 and type 2 diabetes in the SEARCH for Diabetes in Youth Case-Control (SEARCH-CC) study. Because one-carbon metabolism can influence arsenic metabolism, we also evaluated the potential interaction of folate and vitamin B12 with arsenic metabolism on the odds of diabetes.. Six hundred eighty-eight participants <22 years of age (429 with type 1 diabetes, 85 with type 2 diabetes, and 174 control participants) were evaluated. Arsenic species (inorganic arsenic [iAs], monomethylated arsenic [MMA], dimethylated arsenic [DMA]), and one-carbon metabolism biomarkers (folate and vitamin B12) were measured in plasma. We used the sum of iAs, MMA, and DMA (∑As) and the individual species as biomarkers of arsenic concentrations and the relative proportions of the species over their sum (iAs%, MMA%, DMA%) as biomarkers of arsenic metabolism.. Median ∑As, iAs%, MMA%, and DMA% were 83.1 ng/L, 63.4%, 10.3%, and 25.2%, respectively. ∑As was not associated with either type of diabetes. The fully adjusted odds ratios (95% CI), rescaled to compare a difference in levels corresponding to the interquartile range of iAs%, MMA%, and DMA%, were 0.68 (0.50-0.91), 1.33 (1.02-1.74), and 1.28 (1.01-1.63), respectively, for type 1 diabetes and 0.82 (0.48-1.39), 1.09 (0.65-1.82), and 1.17 (0.77-1.77), respectively, for type 2 diabetes. In interaction analysis, the odds ratio of type 1 diabetes by MMA% was 1.80 (1.25-2.58) and 0.98 (0.70-1.38) for participants with plasma folate levels above and below the median (P for interaction = 0.02), respectively.. Low iAs% versus high MMA% and DMA% was associated with a higher odds of type 1 diabetes, with a potential interaction by folate levels. These data support further research on the role of arsenic metabolism in type 1 diabetes, including the interplay with one-carbon metabolism biomarkers.

Topics: Adolescent; Arsenic; Biomarkers; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Environmental Exposure; Female; Folic Acid; Humans; Male; Vitamin B 12; Young Adult

Diabetic retinopathy is the most common complication in diabetic patients relates to high expression of VEGF and microaneurysms. Scutellarin (Scu) turned out to be effective against diabetes related vascular endothelial cell dysfunction. However, its clinical applications have been limited by its low bioavailability. In this study, we formulated and characterized a novel intestinal target nanoparticle carrier based on amphiphilic chitosan derivatives (Chit-DC-VB12) loaded with scutellarin to enhance its bioavailability and then evaluated its therapeutic effect in experimental diabetic retinopathy model.. Chit-DC-VB12 nanoparticles showed low toxicity toward the human colon adenocarcinoma (Caco-2) cells and zebra fish within concentration of 250 μg/ml, owing to good biocompatibility of chitosan. The scutellarin-loaded Chit-DC-VB12 nanoparticles (Chit-DC-VB12-Scu) were then prepared by self-assembly in aqueous solution. Scanning electron microscopy and dynamic light scattering analysis indicated that the Chit-DC-VB12-Scu nanoparticles were spherical particles in the sizes ranging from 150 to 250 nm. The Chit-DC-VB12-Scu nanoparticles exhibited high permeation in Caco-2 cell, indicated it could be beneficial to be absorbed in humans. We also found that Chit-DC-VB12 nanoparticles had a high cellular uptake. Bioavailability studies were performed in Sprague-Dawley rats, which present the area under the curve of scutellarin of Chit-DC-VB12-Scu was two to threefolds greater than that of free scutellarin alone. Further to assess the therapeutic efficacy of diabetic retinopathy, we showed Chit-DC-VB12-Scu down-regulated central retinal artery resistivity index and the expression of angiogenesis proteins (VEGF, VEGFR2, and vWF) of retinas in type II diabetic rats.. Chit-DC-VB12 nanoparticles loaded with scutellarin have better bioavailability and cellular uptake efficiency than Scu, while Chit-DC-VB12-Scu nanoparticles alleviated the structural disorder of intraretinal neovessels in the retina induced by diabetes, and it also inhibited the retinal neovascularization via down-regulated the expression of angiogenesis proteins. In conclusion, the Chit-DC-VB12 nanoparticles enhanced scutellarin oral delivery efficacy and exhibited potential as small intestinal target promising nano-carriers for treatment of type II diabetes induced-retinopathy.

Topics: Administration, Oral; Animals; Apigenin; Biological Availability; Caco-2 Cells; Chitosan; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Drug Carriers; Drugs, Chinese Herbal; Erigeron; Glucuronates; Humans; Male; Nanoparticles; Rats, Sprague-Dawley; Retinal Vessels; Vascular Endothelial Growth Factor A; Vitamin B 12; Zebrafish

Diabetic Mellitus is the chronic metabolic disorder associated with various complications of heart, eyes, nerves, kidney etc. Diabetic Nephropathy is one of the leading causes of death in diabetic patient. We hypothesized that decrease Vitamin B. Our study population consist of 100 subjects out of which 50 cases of Diabetes Mellitus without Diabetic Nephropathy and 50 cases of Diabetes Mellitus with Diabetic Nephropathy. We measured various routine lab parameters, apart from it, we measured spot urinary albumin to creatinine ratio to assess diabetic nephropathy and in special investigation we measured serum Vitamin B. Our study points towards the decrease levels of serum Vitamin B

Topics: Albuminuria; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; India; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Diabetes Mellitus, Type 2; Humans; Intestinal Absorption; Metformin; Predictive Value of Tests; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

Hyperhomocysteinemia and vitamin B12 deficiency may be involved in the development of diabetic peripheral neuropathy (DPN). Metformin therapy may reduce vitamin B12 plasma levels, thus contributing to DPN.. The purposes of this cross-sectional study were to assess (1) the potential associations of DPN with serum levels of homocysteine (tHcy), B-vitamins, and/or the common methylenetetrahydrofolate reductase (MTHFR) C677T mutation; (2) the influence of chronic treatment with metformin on tHcy and B-vitamins concentrations and, finally, (3) to evaluate whether, by this influence, metformin is a risk factor for DPN in a group of type 2 diabetic outpatients.. Our data showed that fasting tHcy, folate, and vitamin B12 levels and the MTHFR C677T genotype distribution were comparable between subjects with (n = 79, 30 %) and without DPN (n = 184, 70 %). Metformin-treated subjects (n = 124, 47 %) showed significantly lower levels of vitamin B12 (P < 0.001), but the prevalence of DPN was not different when compared to those not treated with this drug (33 vs. 27 %, P = NS). At univariate regression analysis, DPN was associated with age, duration of diabetes, HbA1c, creatinine levels, and the presence of coronary heart disease (CHD), and negatively with HDL-C concentrations (P < 0.05 all), but at multivariate regression analysis, high creatinine levels (P = 0.06), low HDL-C levels (P = 0.013), and a higher prevalence of CHD (P = 0.001) were the only variables independently associated with DPN in this population.. In conclusion, in these type 2 diabetic outpatients circulating levels of tHcy, folate, and the MTHFR C677T mutation are not associated with DPN, which was predicted by creatinine levels, CHD, and dyslipidemia. Metformin therapy is associated with a mild vitamin B12 level reduction, but not with DPN.

Topics: Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Folic Acid; Follow-Up Studies; Genotype; Homocysteine; Humans; Hypoglycemic Agents; Male; Metformin; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Outpatients; Prognosis; Vitamin B 12

Elevated serum homocysteine has been shown to be a risk factor for hypertension, cardiovascular disease (CVD), and type-2 diabetes mellitus (T2DM).We characterized the relationships between the serum levels of homocysteine, folic acid, and vitamins D2, D3, and B12 in patients with T2DM, CVD, and hypertension in Shanghai, China. The levels of these serum biochemical markers were determined for 9311 Chinese patients (mean age: 79.50 ± 13.26 years) with T2DM (N = 839), hypertension (N = 490), or CVD (N = 7925). The demographic and serum biochemical data were compared using an analysis of variance. We performed stratified analyses using Pearson linear regression to investigate correlations between the different variables in the T2DM, CVD, and hypertension groups and in patients aged < 50, 50 to 64, 65 to 80, and ≥80 years. A subgroup analysis was also performed to identify correlations between the serum biochemical markers. Stratified chi-squared analyses were performed based on the levels of folic acid and total vitamin D.In all 3 patient groups, elevated levels of vitamin D2 and homocysteine were observed, whereas the levels of folic acid and vitamins D3 and B12 were lower than the reference range for each serum marker (P < 0.05 for all). The linear regression and stratified analyses showed that the highest levels of folic acid and vitamins D2 and D3 correlated with the lowest level of homocysteine in T2DM, CVD, and hypertension patients (P < 0.05 for all), whereas the highest level of vitamin B12 correlated with a lowest level of homocysteine in CVD patients only (P < 0.05).Our results indicate that the contributions of both vitamin D2 and vitamin D3 should be considered in investigations of the effects of vitamin D supplements in T2DM, CVD, and hypertension patients. Our findings warrant future studies of the benefits of vitamin D and folic acid supplements for reducing the risk of T2DM, CVD, and hypertension in elderly Chinese people, as well as the benefits of vitamin B12 supplements for reducing the risk of CVD alone.

Topics: Aged; Aged, 80 and over; Asian People; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Folic Acid; Homocysteine; Humans; Hypertension; Male; Vitamin B 12; Vitamin D

Diabetes is considered an oxidative stress and a chronic inflammatory disease. The purpose of this study was to investigate the correlations between vitamin B-12 status and oxidative stress and inflammation in diabetic vegetarians and omnivores. We enrolled 154 patients with type 2 diabetes (54 vegetarians and 100 omnivores). Levels of fasting glucose, glycohemoglobin (HbA1c), lipid profiles, oxidative stress, antioxidant enzymes activity, and inflammatory makers were measured. Diabetic vegetarians with higher levels of vitamin B-12 (>250 pmol/L) had significantly lower levels of fasting glucose, HbA1c and higher antioxidant enzyme activity (catalase) than those with lower levels of vitamin B-12 (≤ 250 pmol/L). A significant association was found between vitamin B-12 status and fasting glucose (r = -0.17, p = 0.03), HbA1c (r = -0.33, p = 0.02), oxidative stress (oxidized low density lipoprotein-cholesterol, r = -0.19, p = 0.03), and antioxidant enzyme activity (catalase, r = 0.28, p = 0.01) in the diabetic vegetarians; vitamin B-12 status was significantly correlated with inflammatory markers (interleukin-6, r = -0.33, p < 0.01) in diabetic omnivores. As a result, we suggest that it is necessary to monitor the levels of vitamin B-12 in patients with diabetes, particularly those adhering to a vegetarian diet.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diet, Vegetarian; Feeding Behavior; Female; Glycated Hemoglobin; Humans; Inflammation; Inflammation Mediators; Lipids; Male; Meat; Middle Aged; Nutritional Status; Oxidative Stress; Vegetarians; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Metformin, an insulin-sensitizing drug, is a first line treatment for type 2 diabetes. Long-term use of metformin has been associated with subsequent reductions in vitamin B12 concentrations. The objective of our study was to determine whether metformin use is associated with lower serum vitamin B12 concentrations in older adults, and whether concurrent use of multivitamins modifies this association. We examined 2,510 participants aged 50 years and over, participating in the national population-based Reasons for Geographic And Racial Differences in Stroke (REGARDS) Study. Multivariable linear and logistic regression models were used to assess associations between multivitamin use and serum vitamin B12 concentrations. We estimated adjusted odds ratios (aOR)s and confidence intervals (CI)s. Results were stratified by three metformin/diabetes sub-groups: 1) participants with diabetes who were metformin users; 2) participants with diabetes who were not metformin users; and 3) participants without diabetes. We found that diabetic metformin users had significantly lower geometric mean serum B12 concentrations (409 pmol/L) than the group with diabetes not taking metformin (485 pmol/L; P<0.01), and the group without diabetes (445 pmol/L; P = 0.02). The geometric mean serum B12 concentrations were greater for multivitamin users (509 pmol/L) compared to those who did not use multivitamins (376 pmol/L; p<0.01). Among the participants with diabetes who were on metformin therapy, multivitamin use was associated with geometric mean serum vitamin B12 concentrations that were 50% (or 161 pmol/L) higher, compared to those not using multivitamins. Among metformin users, multivitamin use was associated with lower prevalence of combined low and borderline vitamin B12 concentrations (aOR = 0.14; 95% CI = 0.04, 0.54) compared to those not using multivitamins. In conclusion, metformin use was associated with lower geometric mean serum vitamin B12 concentrations among diabetic older adults compared to their counterparts. Concurrent multivitamin use may potentially protect against low or borderline vitamin B12 concentrations in long-term metformin users. Additional research is needed to further examine this association as low or borderline vitamin B12 concentrations can be preventable, or treatable if detected at an early stage, in long-term metformin users.

Topics: Adult; Aged; Case-Control Studies; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Metformin use is associated with cobalamin (vitamin B12) deficiency. However, the influence of both duration and dose of metformin is unclear. Studies using holotranscobalamin, a marker for cellular cobalamin deficiency, are scarce. We therefore investigated the prevalence of cobalamin deficiency in type 2 diabetes patients using both markers, and its relation with duration and dose of metformin use. This cross-sectional study among 550 type 2 diabetes patients using metformin (mean daily dose 1,306 mg; mean duration 64 months) was conducted in four primary care centers in Utrecht, the Netherlands. Cobalamin and holotranscobalamin concentrations were measured at the annual diabetes check. Detailed information on metformin use and confounding variables was collected from medical records. The prevalence of a cobalamin deficiency was 28.1 %, while a holotranscobalamin deficiency occurred in 3.9 % of the patients. Adjusting for multiple confounders, a 1 mg/day increase in daily metformin dose was associated (p < 0.001) with 0.042 (95 % CI -0.060, -0.023) decrease in cobalamin concentrations. Similarly, a 10 g increase of cumulative metformin dose was associated (p = 0.006) with -0.070 (-0.12, -0.021) lower cobalamin concentrations after adjustment for confounders. Duration of metformin use was not associated with cobalamin concentrations after multivariable adjustment. Similar results were observed for holotranscobalamin. Cobalamin deficiency occurs frequently among diabetes patients using metformin. A higher daily and cumulative doses of metformin were strongly associated with lower cobalamin and holotranscobalamin concentrations, while duration was not. It is thus important to account for metformin dose in recommendations for screening for cobalamin deficiency.

Topics: Aged; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Time Factors; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Hyperhomocysteinemia (hHcy) is a risk factor in the progression of chronic kidney disease (CKD). In type 2 diabetes (T2D), hHcy is strongly associated with increased risk of cardiovascular disease. Vitamin B12 and folic acid supplementation have been reported to lower homocysteine (tHcy) levels, but no data on plasma tHcy, cysteine (Cys), folate and vitamin B12 levels in T2D-CKD patients are reported.. tHcy and Cys levels were analyzed in 178 T2D-CKD patients by high performance liquid chromatography (HPLC) with fluorescence detection. In addition, we determined folate and vitamin B12 levels using a chemiluminescence method.. tHcy and Cys levels were increased in T2D patients, and this rise positively correlated with the CKD stage (P < 0.001). Folate levels were comparable to controls at various CKD stages, whereas vitamin B12 levels were lower, except at stage IV. We did not find any correlation between B-vitamins and levels of tHcy and Cys, regardless of the CKD stage.. This is the first study reporting tHcy, Cys and B-vitamins status in T2D-CKD patients. Although limited to our cohort of 178 patients, our findings could be helpful in clarifying the conflicting literature regarding B-vitamins supplementation. Further studies are necessary before any Hcy-lowering therapy can be safely established in T2D-CKD subjects.

Topics: Aged; Aged, 80 and over; Biomarkers; Chromatography, High Pressure Liquid; Cysteine; Diabetes Mellitus, Type 2; Disease Progression; Female; Folic Acid; Homocysteine; Humans; Male; Renal Insufficiency, Chronic; Vitamin B 12

To investigate the associations of vitamin B12 (cobalamin and holotranscobalamin) status with depression, cognition and neuropathy in patients with type 2 diabetes using metformin.. In an observational study, among 550 type 2 diabetes patients using metformin, cobalamin and holotranscobalamin (holoTCII) levels were measured at the annual diabetes checkup, and deficiencies were defined as <148 and <21 pmol/L, respectively. Depression and cognitive function were assessed with corresponding International Classification of Primary Care codes and questionnaires; neuropathy with medical record data and a questionnaire. Confounding variables were retrieved from medical records. Multivariable logistic and linear regressions were used with cobalamin status as independent variable; depression, cognition and neuropathy as dependent variables.. The mean duration of diabetes was 8.4 years (±5.8); mean duration of metformin use was 64.1 months (±43.2), with a mean metformin dose of 1,306 mg/day. A sufficient cobalamin level was independently associated with a decreased risk of depression (OR 0.42; 95 % CI 0.23-0.78) and better cognitive performance (β = 1.79; 95 % CI 0.07-3.52) adjusted for confounders. This indicates that cobalamin-deficient patients had a 2.4 times higher chance of depression and a 1.79 point lower cognitive performance score. HoloTCII was not associated with any outcome.. Cobalamin deficiency was associated with an increased risk of depression and worse cognitive performance, while holoTCII was not. Screening for cobalamin deficiency may be warranted in diabetes patients using metformin. Physicians should consider a cobalamin deficiency in diabetes patients using metformin with a depression or cognitive decline.

Topics: Adult; Aged; Cognition; Depressive Disorder; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Male; Metformin; Vitamin B 12; Vitamin B 12 Deficiency

To investigate the vitamin B status, with particular focus on vitamin B6, in adults with and without incipient nephropathy secondary to type 2 diabetes mellitus.. Plasma and/or urine concentrations of vitamins B₆, B₁, B₁₂, related vitamers and biomarkers (including total homocysteine, methylmalonic acid) were measured in 120 adults with type 2 diabetes (including 46 patients with microalbuminuria) and 52 non-diabetic control subjects.. Plasma concentrations of pyridoxal 5'-phosphate (PLP) were significantly lower in patients with type 2 diabetes than in control subjects (median: 22.7 nmol/L, diabetes with microalbuminuria; 26.8 nmol/L, diabetes without microalbuminuria; 39.5 nmol/L, non-diabetic control; p<0.0001). The prevalence of low PLP (<30 nmol/L) was 63%, 58%, and 25% in the diabetes groups with and without microalbuminuria and the control group, respectively. Plasma levels of pyridoxine and pyridoxal were also lower (p<0.0001), but levels of pyridoxamine, pyridoxamine 5'-phosphate, and pyridoxic acid were higher in both groups with diabetes compared to the control group (p<0.001). Thiamine deficiency was highly prevalent in all groups, whereas low vitamin B₁₂ and elevated methylmalonic acid were rare. Increased levels of C-reactive protein and soluble vascular cell adhesion molecule-1 were observed in the groups with diabetes (p<0.05, versus healthy control).. Deficiency of vitamin B₆ (PLP, pyridoxine, pyridoxal) and vitamin B₁ (thiamine) was prevalent in type 2 diabetes. Incipient nephropathy was associated with more pronounced alterations in vitamin B₆ metabolism and stronger indications of endothelial dysfunction and inflammation.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Biomarkers; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Inflammation; Male; Middle Aged; Pyridoxic Acid; Thiamine; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6; Vitamin B 6 Deficiency; Young Adult

Topics: Adult; Anemia, Megaloblastic; Delayed Diagnosis; Diabetes Mellitus, Type 2; Diagnosis, Differential; Female; Gout; Humans; Hypertension; Lichen Planus; Melanosis; Nail Diseases; Remission Induction; Vitamin B 12; Vitamin B 12 Deficiency

The conventional systemic corticosteroid treatment for acute peripheral facial nerve palsy in patients with type 2 diabetes mellitus can induce hyperglycemia, and an alternative local therapy may be necessary. Our purpose in this study is to evaluate therapeutic effects of stellate ganglion block (SGB) on facial nerve palsy in patients with type 2 diabetes mellitus.. A total of 361 cases of acute peripheral, chronic peripheral, acute central and chronic central facial nerve palsy treated with SGB or conventional therapy were included in this retrospective study. The facial nerve function score (Sunnybrook Facial Grading System) obtained at before and after treatment in non-SGB and SGB groups was used to assess the outcome. Furthermore, the blood glucose level in acute peripheral facial nerve palsy was measured.. The facial nerve function score in the SGB group was higher than that in the non-SGB group after treatment in peripheral facial nerve palsy, while the blood glucose level in the non-SGB group increased and was higher than that in the SGB group during the treatment in acute peripheral facial nerve palsy.. Our findings suggest that SGB has better therapeutic effect than conventional treatment on acute and chronic peripheral facial nerve palsy in patients with type 2 diabetes mellitus.

Topics: Adult; Anesthetics, Local; Antipyrine; Aspirin; Autonomic Nerve Block; Blood Glucose; Dexamethasone; Diabetes Mellitus, Type 2; Edaravone; Facial Nerve Diseases; Facial Paralysis; Female; Free Radical Scavengers; Glucocorticoids; Humans; Lidocaine; Male; Middle Aged; Phosphodiesterase Inhibitors; Platelet Aggregation Inhibitors; Prednisone; Retrospective Studies; Stellate Ganglion; Thiamine; Treatment Outcome; Vinca Alkaloids; Vitamin B 12; Vitamin B Complex

To describe the mortality and fatality of diabetes and assess their relationship with the level of red blood cell (RBC) folate.. We analyzed the data of 526 adults with diabetes who participated in the National Health and Nutrition Examination Survey (1991-1994) as the baseline examination, and were followed up through December 31, 2006. Estimates of the hazard ratios (HRs) of selected death causes for individuals with different levels of RBC folate were obtained from Cox proportional hazards regression. A total of 295 deaths were recorded by the end of a 15-year follow-up with a mortality rate of 58.48 per 1000 person year (py). Diabetes was listed as a contributing cause for 136 deaths, accounting for 46.1% of the total deaths with a fatality rate 26.96 per 1000 py. Mortality rate for all-cause in the group with upper quartile of RBC folate was almost twice as high as that among the group with lower quartile, 82.75 vs. 44.10 per 1000 py. After adjusting for covariates, including serum concentration of vitamin B12, cotinine, homocysteine and the history of cardio-cerebral vascular diseases assessed at the baseline, the HRs for dying from any causes were 1.00 (reference), 1.82 (95% CI = 1.25-2.66) and 2.10 (1.37-3.20) among diabetic adults with lower, intermediate, and upper quartiles of RBC folate.. Diabetes was listed as a contributing cause for less than half of the deaths among adults with diabetes after 15+ years of follow-up; high RBC folate concentration was associated with an elevated risk of death among adults with diabetes.

Topics: Aged; Cause of Death; Cerebrovascular Disorders; Cohort Studies; Cotinine; Diabetes Mellitus, Type 2; Dietary Supplements; Dose-Response Relationship, Drug; Erythrocytes; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Male; Middle Aged; Nutrition Surveys; Proportional Hazards Models; Risk Factors; Socioeconomic Factors; Vitamin B 12

The rising incidence of diabetes and its negative impact on quality of life highlights the urgent need to develop biomarkers of early nerve damage. Measurement of total vitamin B12 has some limitations. We want to determine the levels of urinary methylmalonic acid and its relationships with serum vitamin B12 and polyneuropathy. The 176 Chinese patients with Type 2 diabetes mellitus were divided into 3 groups according to the levels of vitamin B12. A gas chromatography mass spectrometric technique was used to determine blood methylmalonic acid and urinary methylmalonic acid. The diagnosis of distal diabetic polyneuropathy was based on the determination of bilateral limb sensory and motor nerve conduction velocity and amplitude with electromyogram. Multiple regression analysis revealed that urinary methylmalonic acid/creatinine, blood methylmalonic acid, and so forth were variables that influenced diabetic polyneuropathy significantly. Nerve sensory conduction velocity and nerve amplitude in the group of urinary methylmalonic acid/creatinine >3.5 mmol/mol decreased significantly. Superficial peroneal nerve sensory and motor conduction velocity and ulnar nerve compound motor active potential amplitude were inversely correlated with urinary methylmalonic acid/creatinine. Urinary methylmalonic acid correlates with serum vitamin B12 levels in person with diabetes and is a sensitive marker of early polyneuropathy.

Topics: Adult; Aged; Asian People; Biomarkers; China; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Male; Methylmalonic Acid; Middle Aged; Motor Neurons; Neural Conduction; Polyneuropathies; Prospective Studies; Sensory Receptor Cells; Severity of Illness Index; Vitamin B 12; Vitamin B 12 Deficiency

We investigated the association of serum homocysteine levels and vitamin status with type 2 diabetic retinopathy. This study included 65 patients with and 75 patients without diabetic retinopathy. Patients with diabetic retinopathy had significantly higher serum homocysteine levels (P < 0.001), higher prevalence of hyperhomocysteinemia (P < 0.001), lower serum folic acid (P < 0.001), and vitamin B12 (P = 0.014) levels than those without diabetic retinopathy. Regression analysis revealed that homocysteine was an independent risk factor for diabetic retinopathy and there was a threshold in its serum level (13.7  μ mol/L), above which the risk of diabetic retinopathy greatly increases (OR = 1.66, P = 0.001). Folic acid was associated with decreased odds for diabetic retinopathy (OR = 0.73, P < 0.001). There was a threshold in serum vitamin B12 level (248.4 pg/mL), below which serum homocysteine concentration significantly increases with decreasing serum vitamin B12 (P = 0.003). Our findings suggest that hyperhomocysteinemia is an independent risk factor for the development and progression of diabetic retinopathy. Decreased serum levels of folic acid and vitamin B12, through raising serum homocysteine concentrations, may also affect the diabetic retinopathy risk.

Topics: Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Odds Ratio; Prevalence; Regression Analysis; Risk Factors; Vitamin B 12; Vitamins

We evaluated the prevalence of vitamin B12 deficiency and associated factors in type 2 diabetes patients using metformin. A total of 799 type 2 diabetes patients using metformin was enrolled. Vitamin B12 and folate levels were quantified by chemiluminescent enzyme immunoassay. Vitamin B12 deficiency was defined as vitamin B12 ≤ 300 pg/mL without folate deficiency (folate > 4 ng/mL). The prevalence of vitamin B12 deficiency in metformin-treated type 2 diabetes patients was 9.5% (n = 76), and the mean vitamin B12 level was 662.5 ± 246.7 pg/mL. Vitamin B12 deficient patients had longer duration of metformin use (P < 0.001) and higher daily metformin dose (P < 0.001) than non-deficient patients. Compared with daily metformin dose of ≤ 1,000 mg, the adjusted odds ratio for 1,000-2,000 mg, and ≥ 2,000 mg were 2.52 (95% CI, 1.27-4.99, P = 0.008) and 3.80 (95% CI, 1.82-7.92, P < 0.001). Compared with metformin use of < 4 yr, the adjusted odds ratios for 4-10 yr, and ≥ 10 yr were 4.65 (95% CI, 2.36-9.16, P < 0.001) and 9.21 (95% CI, 3.38-25.11, P < 0.001), respectively. In conclusion, our study indicates that patients with type 2 diabetes treated with metformin should be screened for vitamin B12 deficiency, especially at higher dosages (> 1,000 mg) and longer durations (≥ 4 yr) of treatment.

Topics: Aged; Area Under Curve; Diabetes Mellitus, Type 2; Female; Folic Acid; Humans; Hypoglycemic Agents; Immunoassay; Male; Metformin; Middle Aged; Odds Ratio; Patients; Prevalence; ROC Curve; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Long-term and high-dose treatment with metformin is known to be associated with vitamin B12 deficiency in patients with type 2 diabetes. We investigated whether the prevalence of B12 deficiency was different in patients treated with different combination of hypoglycemic agents with metformin during the same time period. A total of 394 patients with type 2 diabetes treated with metformin and sulfonylurea (S+M group, n = 299) or metformin and insulin (I+M group, n = 95) were consecutively recruited. The vitamin B12 and folate levels were quantified using the chemiluminescent enzyme immunoassay. Vitamin B12 deficiency was defined as vitamin B12≤300 pg/mL without folate deficiency (folate>4 ng/mL). The mean age of and duration of diabetes in the subjects were 59.4±10.5 years and 12.2±6.7 years, respectively. The mean vitamin B12 level of the total population was 638.0±279.6 pg/mL. The mean serum B12 levels were significantly lower in the S+M group compared with the I+M group (600.0±266.5 vs. 757.7±287.6 pg/mL, P<0.001). The prevalence of vitamin B12 deficiency in the metformin-treated patients was significantly higher in the S+M group compared with the I+M group (17.4% vs. 4.2%, P = 0.001). After adjustment for various factors, such as age, sex, diabetic duration, duration or daily dose of metformin, diabetic complications, and presence of anemia, sulfonylurea use was a significant independent risk factor for B12 deficiency (OR = 4.74, 95% CI 1.41-15.99, P = 0.012). In conclusion, our study demonstrated that patients with type 2 diabetes who were treated with metformin combined with sulfonylurea require clinical attention for vitamin B12 deficiency and regular monitoring of their vitamin B12 levels.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Drug Combinations; Female; Folic Acid; Humans; Insulin; Male; Metformin; Middle Aged; Sulfonylurea Compounds; Vitamin B 12; Vitamin B 12 Deficiency

Aim of the study was to clarify the relationship between metformin-induced vitamin B12 (B12) deficiency, hyperhomocysteinemia and vascular complications in patients with type 2 diabetes. Serum B12 concentrations, homocysteine plasma levels, the presence of retinopathy and history of macroangiopathy (stroke or coronary heart disease) were analyzed in patients without renal dysfunction (serum creatinine<115 μmol/L). Firstly, B12 status was analyzed in 62 consecutive metformin-treated patients. Secondly, the relationship between B12, homocysteine and vascular complications was analyzed in 46 metformin-treated and 38 age- and sex-matched non-metformin-treated patients. Among the 62 consecutive metformin-treated patients, B12 was deficient (<150 pmol/L) in 8 (13%) and borderline-deficient (150-220 pmol/L) in 18 (29%): the larger the metformin dosage, the lower the B12 (P=0.02, Spearman's ρ=-0.30). There were independent correlations between metformin use and B12 lowering (P=0.02, r = -0.25), and B12 lowering and elevation of homocysteine (P<0.01, r=-0.34). Elevation of homocysteine was a risk for retinopathy (P=0.02, OR 1.26, 95%CI 1.04-1.52). There was no significant relation between homocysteine and macroangiopathy. Correlation between B12 and homocysteine was stronger in metformin-treated (P<0.01, r=-0.48) than non-metformin-treated (P=0.04, r=-0.38) patients. In ten B12 deficient patients, B12 supplementation (1,500 μg/day) for 2.2±1.0 months with continued use of metformin raised B12 levels: 152±42 and 299±97 pmol/L before and after treatment, respectively (P<0.01). Metformin-induced B12 lowering in diabetes was associated with elevation of homocysteine, and hyperhomocysteinemia was independently related to retinopathy. Metformin-induced B12 deficiency was correctable with B12 supplementation.

Topics: Aged; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Dietary Supplements; Dose-Response Relationship, Drug; Female; Homocysteine; Humans; Hyperhomocysteinemia; Hypoglycemic Agents; Japan; Male; Metformin; Middle Aged; Prevalence; Risk Factors; Severity of Illness Index; Stroke; Vitamin B 12; Vitamin B 12 Deficiency

To study vitamin B12 concentrations in patients with type 2 diabetes with and without metformin use and to identify risk factors and consequences of low vitamin B12 concentrations.. This study had a cross-sectional design. During eight weeks all patients with type 2 diabetes visiting the diabetic outpatient clinic of the Isala Clinics in Zwolle were approached for participation. Participation included measurement of haemoglobin, mean corpuscular volume and vitamin B12 levels. Data on neuropathy were retrospectively searched for in the patient records. Vitamin B12 deficiency was defined as serum B12 concentrations <150 pmol/l.. In the total cohort (n=298), the overall prevalence of vitamin B12 concentrations <150 pml/l was 9.7% (95% CI 6.6-13.7%). In type 2 diabetes patients not taking metformin (n=134), the prevalence was 4.4% (95% CI 1.6-9.4%) compared with 14.1% in metformin users (n=164) (95% CI 9.2-20.4%; p=0.006). Each 100 mg step in metformin dose increased (OR=1.081, p=0.014), whereas PPI use lowered (OR=0.322, p=0.037) the odds of having a vitamin B12 deficiency in logistic regression. Nevertheless, metformin use did not predict the chance on having anaemia or neuropathy.. Among patients with type 2 diabetes using metformin, the prevalence of vitamin B12 deficiency is higher than compared with patients not using metformin. However, metformin use did not predict the chance of having anaemia or neuropathy.

Topics: Aged; Anemia; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Erythrocyte Indices; Female; Hemoglobins; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Prevalence; Vitamin B 12; Vitamin B 12 Deficiency

A 73-year-old Japanese man with Hashimoto's disease and diabetes mellitus received regular medical checkups for type 2 diabetes care. Blood tests indicated macrocytic anemia (red blood cell count, 279×104 /μL; hemoglobin, 12.2 g/dL; hematocrit, 34.0%; mean corpuscular volume, 121.9 fL). The laboratory data demonstrated a normal folic acid level with a low vitamin B12 level. An endoscopic examination indicated no signs of gastric or intestinal bleeding. Positive results for anti-intrinsic factor antibodies were strongly suggestive of pernicious anemia. The patient refused cobalamin injections to treat the anemia. However, the oral administration of mecobalamin for the treatment of diabetic neuropathy was simultaneously initiated. Subsequently, the anemia gradually improved. Oral mecobalamin was presumably effective for pernicious anemia management. Anemia is frequently observed in elderly patients, and the incidence of pernicious anemia increases with age. Anemia is conventionally treated with cobalamin injections. Currently, the oral administration of mecobalamin is not the typical treatment for anemia. However, as in our case, a few reports have documented positive results following oral mecobalamin treatment. Moreover, oral mecobalamin is a fairly recent, novel, noninvasive mode of treatment, making it ideal for elderly patients, who are generally frail. This case suggests the efficacy of mecobalamin for the treatment of pernicious anemia.

Topics: Administration, Oral; Aged; Anemia, Pernicious; Diabetes Mellitus, Type 2; Hashimoto Disease; Humans; Male; Vitamin B 12

Contradictory results for concentrations of vitamin B12, holotranscobalamin (holoTC), and methylmalonic acid (MMA) have been reported. We tested the hypothesis that the extracellular vitamin B12 markers are not reflecting the intracellular vitamin B12-dependent biochemical reactions in individuals with type 2 diabetes. The study included 92 patients with diabetes and 72 controls with similar age and sex distribution. We measured vitamin B12 markers [MMA, total serum vitamin B12, holoTC, total homocysteine (tHcy)], red blood cell (RBC)-B12, and the plasma concentrations of the methylation markers [S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH)]. In comparison to controls, diabetic patients showed significantly higher concentrations of plasma SAH (median 15.1 vs. 11.8 nmol/L; p < 0.001) and lower SAM/SAH ratio (9.1 vs. 8.2; p = 0.006). Concentrations of total vitamin B12 and holoTC did not differ significantly between the groups, but plasma MMA concentrations were significantly higher in diabetics (250 vs. 206 nmol/L). However, RBC-B12 was lower in diabetics compared to controls (median 230 vs. 260 pmol/L; p = 0.001). The inverse correlation between MMA and RBC-B12 was stronger in the controls compared to that in the patients (correlation coefficient in controls R = -0.446, p = 0.001; in patients R = -0.289, p = 0.022). Metformin treatment was associated with a lower total serum vitamin B12, but a comparable RBC-B12 and a slightly lower MMA and better methylation index. In conclusion, patients with type 2 diabetes showed normal extracellular vitamin B12, but disturbed intracellular B12-dependent biochemical reactions. Metformin treatment was associated with low serum vitamin B12 and improved intracellular vitamin B12 metabolism despite low serum vitamin B12.

Topics: Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

Plasma cobalamin is requested in order to diagnose cobalamin deficiency and low levels confirm a deficient state. Here, we present three family members with unexpected high levels of cobalamin.. We included a patient referred for cobalamin measurement due to neurological symptoms, her son and her daughter. Mother and son both suffered from myotonic dystrophy type II, while the daughter tested negative for this disease. Blood samples were analyzed for cobalamin, haptocorrin, transcobalamin, holoTC, and sCD320. We employed gel filtration and antibody precipitation for further characterization. The protein coding region of the TCN2 gene, encoding transcobalamin, was sequenced.. The patient, her {son} and [daughter] all had cobalamin levels above the measurement range of the routine method employed (>1476 pmol/L). Total transcobalamin and (holoTC) were 5980 (1500), {5260 (2410)} and [5630 (1340)] pmol/L, which is well above the upper reference limits of 1500 (160) pmol/L. The sCD320 concentration was also well above the upper reference limit of 97 arb.u.: 1340, {1510} and [1090] arb.u. Haptocorrin levels were within the reference range and no signs of cobalamin deficiency were found. DNA sequencing of the TCN2 gene revealed several known polymorphisms not associated with highly elevated transcobalamin levels. Upon gel filtration, sCD320 eluted as a larger molecule than previously reported. By incubation with anti-transcobalamin antibodies, we precipitated both transcobalamin and part of sCD320.. The high cobalamin levels were mainly explained by high levels of holoTC, possibly caused by complex formation with its soluble receptor, sCD320. The family occurrence points to a genetic explanation.

Topics: Adult; Antigens, CD; Chromatography, Gel; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Heterozygote; Humans; Male; Middle Aged; Myotonic Disorders; Myotonic Dystrophy; Obesity; Promoter Regions, Genetic; Receptors, Cell Surface; Sequence Analysis, DNA; Transcobalamins; Vitamin B 12; Young Adult

Clearing the way: Glucagon-like peptide-1 (GLP-1) receptor agonists are proving a potent weapon in the treatment of type II diabetes. A new vitamin B(12)-GLP-1 conjugate is investigated and shown to have insulinotropic properties similar to the unmodified peptide. These results are critical to the exploitation of the vitamin B(12) oral uptake pathway for peptide delivery.

Topics: Calcium; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; HEK293 Cells; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Islets of Langerhans; Receptors, Glucagon; Vitamin B 12

Topics: Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Folic Acid; Humans; Male; Pyridoxal Phosphate; Vitamin B 12

Few modifiable risk factors are known to be associated with the presence and progression of diabetic polyneuropathy (DPN).. We have analyzed in 405 type 2 diabetic (T2DM) subjects (169 women) the association of plasma homocysteine with the presence of DPN measured with the Semmes-Weinstein (SW) monofilament test. A score below 4 was considered an altered SW monofilament test. Plasma homocysteine, vitamin B12 and folic acid were measured using standard procedures (ELISA).. Patients with T2DM with altered SW test have significantly higher age, evolution of disease, HbA1c and lower creatinine clearance values. In addition, plasma homocysteine values were independently and significantly higher in T2DM with DPN measured as altered SW test (13.64 ± 4.93 vs. 12.22 ± 4.48 μmol/l, P<.01) with similar vitamin B12 and folic acid values comparing the 2 groups.. Plasma homocysteine and HbA1c values are the 2 modifiable biological factors associated with the presence of DPN evaluated as an altered SW monofilament test in T2DM subjects.

Topics: Age Factors; Aged; Alcohol Drinking; Cardiovascular Diseases; Case-Control Studies; Creatinine; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Disease Progression; Female; Folic Acid; Glycated Hemoglobin; Homocysteine; Humans; Hyperhomocysteinemia; Hypesthesia; Hypoglycemic Agents; Hypolipidemic Agents; Male; Middle Aged; Overweight; Physical Examination; Risk Factors; Severity of Illness Index; Smoking; Vitamin B 12

Topics: Aged; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Retrospective Studies; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

To study the correlation of homocysteine (Hcy) in plasma with nitric oxide synthetase (NOS) and endogenous carbon monoxide (CO) in the penile corpus cavernosum of type 2 diabetic rats.. This study included 40 male Wistar rats, 10 as controls (Group A) and the other 30 as diabetes mellitus (DM) models. Four weeks after the model establishment, the model rats were divided into a DM group (Group B, n = 10), an insulin treated group (Group C, n = 10), and a folic acid and vitamin B12 treated group (Group D, n = 10). All the rats were injected with apomorphine and observed for penile erection at 8 and 12 weeks, and the levels of total plasma Hcy (tHcy), NOS and CO in the penile corpus cavernosum were measured at 12 weeks.. Compared with Group A, the level of tHcy was significantly increased, while NOS and CO activities in the penile cavernous tis-sue and erectile function remarkably decreased in Group B (P < 0.01). The incidence rate of high Hcy was 55% in the DM rats. In comparison, the level of tHcy was obviously decreased, and the NOS activity and erectile function markedly increased in Groups C and D (P < 0.01). The Hcy level showed a significant negative correlation with NOS activity (rA = -0.89, rB = -0.76, rc = -0.91, rD = -0.91) and CO content (TA = -0.82, r, = -0.77, rc = -0.93, rD = -0.81).. High plasma Hcy can decrease NOS and CO activities in the penile corpus cavernosum, and consequently induce erectile dysfunction in DM rats, while insulin, folic acid and vitamin B12 can improve their penile erectile function by increasing NOS and CO activities.

Topics: Animals; Carbon Monoxide; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Folic Acid; Homocysteine; Insulin; Male; Nitric Oxide Synthase; Penis; Rats; Rats, Wistar; Vitamin B 12

The purpose of this study was to examine the status of folate and vitamin B12 (B12) in relation to serum homocysteine (HCY) and oxidative stress indices in patients with type 2 diabetes (T2DM).. This case-control study involved 100 Omani adults (50 patients newly diagnosed with T2DM and 50 age- and gender-matched healthy controls). Several parameters were investigated, including dietary intake and biochemical assessments of folate, B12, HCY, oxidative stress markers (glutathione and total antioxidant status), and antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and catalase).. Low serum levels of folate, B12, and hyperhomocysteinemia were prevalent in patients with T2DM compared with controls. Oxidative stress was evident in patients with T2DM as indicated by low serum levels of glutathione, total antioxidant status, and impaired antioxidant enzymatic activities (superoxide dismutase, glutathione peroxidase, and catalase).. The low intake of folate and B12 is associated with low serum levels of these two nutrients and hyperhomocysteinemia in Omani adults with T2DM.

Topics: Adult; Antioxidants; Case-Control Studies; Diabetes Mellitus, Type 2; Diet; Female; Folic Acid; Folic Acid Deficiency; Glutathione; Hospitals, University; Humans; Hyperhomocysteinemia; Male; Middle Aged; Oman; Outpatient Clinics, Hospital; Oxidative Stress; Oxidoreductases; Prevalence; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

The main aim of the present study was to investigate the plasma phospholipids (PL) fatty acids status and its association with plasma Hcy in patients with type 2 diabetes mellitus (T2DM). One hundred and four T2DM (aged 57.3±13.4 y) and 150 healthy subjects (aged 48.4±8.7 y) were recruited. Plasma Hcy and PL fatty acids were determined by standard methods. Plasma Hcy concentration in T2DM was significantly higher than that in healthy subjects (p<0.001). The prevalence of hyperhomocysteinemia was significantly higher in T2DM (36.54%) than that in healthy subjects (17.32%) (p=0.012). Plasma PL 20:4n-6 (r=0.303, p=0.012), 22:5n-3 (r=0.312, p=0.01), total PUFA (r=0.303, p=0.012), n-6 PUFA (r=0.261, p=0.032) were significantly positively associated with plasma Hcy concentration in T2DM. While, plasma PL n-3:n-6 PUFA (r=-0.400, p=0.046) was negatively associated with plasma Hcy in T2DM. In healthy subjects, plasma PL 22:6n-3 (r=-0.201, p=0.042) was negatively associated with plasma Hcy. In addition, plasma PL 22:6n-3 (r=0.193, p=0.044) and 22:5n-6 (r=0.234, p=0.038) were significantly negatively associated with plasma vitamin B-12 in healthy subjects. Our results suggested that increased plasma Hcy levels in T2DM associated with low n-3:n-6 ratio intake. We suggest that T2DM increase their long chain n-3 PUFA intake from fish or fish oil while decrease n-6 PUFA intake.

Topics: Adult; Aged; Algorithms; China; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Outpatient Clinics, Hospital; Phospholipids; Prevalence; Vitamin B 12

Metanx is a product containing L-methylfolate, pyridoxal 5'-phosphate, and methylcobalamin for management of endothelial dysfunction. Metanx ingredients counteract endothelial nitric oxide synthase uncoupling and oxidative stress in vascular endothelium and peripheral nerve. This study evaluates Metanx on diabetic peripheral neuropathy in ZDF rats, a model of type 2 diabetes. Metanx was administered to 15-week-old ZDF and ZDF lean rats at either 4.87 mg ⋅ kg(-1) ⋅ day(-1) (a body weight-based equivalent of human dose) or 24.35 mg ⋅ kg(-1) ⋅ day(-1) by oral gavage two times a day for 4 weeks. Both doses alleviated hind limb digital sensory, but not sciatic motor, nerve conduction slowing and thermal and mechanical hypoalgesia in the absence of any reduction of hyperglycemia. Low-dose Metanx increased intraepidermal nerve fiber density but did not prevent morphometric changes in distal tibial nerve myelinated fibers. Metanx treatment counteracted endothelial nitric oxide synthase uncoupling, inducible nitric oxide synthase upregulation, and methylglyoxal-derived advanced glycation end product, nitrotyrosine, and nitrite/nitrate accumulation in the peripheral nerve. In conclusion, Metanx, at a body weight-based equivalent of human dose, increased intraepidermal nerve fiber density and improved multiple parameters of peripheral nerve function in ZDF rats. Clinical studies are needed to determine if Metanx finds use in management of diabetic peripheral neuropathy.

Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Disease Models, Animal; Folic Acid; Hyperalgesia; Male; Nerve Fibers; Neural Conduction; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Pyridoxal Phosphate; Rats; Rats, Zucker; Sciatic Nerve; Tibial Nerve; Tyrosine; Vitamin B 12

According to the ADA guidelines, metformin and lifestyle modifications are the first line therapies in the treatment of type 2 diabetes mellitus. Metformin does, however, cause vitamin B-12 malabsorption, which may increase the risk of developing vitamin B-12 deficiency--a clinically important and treatable condition. Here we report a case of 60 year old diabetic male presenting with clinical features of Vitamin B-12 deficiency on long term metformin therapy, which was confirmed on investigations. Patient showed symptomatic improvement with change in treatment.

Topics: Diabetes Mellitus, Type 2; Humans; Hydroxocobalamin; Hypoglycemic Agents; Malabsorption Syndromes; Male; Metformin; Middle Aged; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

To test vitamin B12 plasma levels in type 2 diabetic patients treated with metformin in our area.. A cross-sectional, observational study of consecutive type 2 diabetic patients on drug treatment attending an internal medicine outpatient clinic.. One hundred and nine patients (81 treated with metformin) were enrolled into the study. Mean time on metformin treatment was 43.5 months and mean drug dose was 1,779 mg/day. Patients treated with metformin had significantly lower vitamin B(12) plasma levels (393.5 vs. 509 pg/mL, P = .0008). Seven (8.6%) of 81 patients treated with metformin and none of the 28 patients not treated with the drug had vitamin B(12) plasma levels lower than 197 pg/mL. No correlation was found between vitamin B12 plasma levles and metformin treatment time or dosage.. In type 2 diabetic patients, treatment with metformin is associated to lower vitamin B12 plasma levels. Vitamin B12 deficiency associated with metformin is relatively common in our area.

Topics: Aged; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Male; Metformin; Vitamin B 12

Metformin can result in vitamin B(12) deficiency, potentially leading to complications such as neuropathy. Annual monitoring of vitamin B(12) has been suggested; however, it is unknown whether current practice reflects this recommendation.. To identify vitamin B(12) monitoring patterns in patients on long-term, high-dose metformin. Secondary objective was to determine the frequency of new vitamin B(12) deficiency, anemia, and neuropathy documented after initiation of high-dose metformin.. Electronic medical records of veterans treated at the Veterans Affairs Maryland Healthcare System with high-dose metformin (≥2000 mg/day) as of November 1, 2010, were reviewed. Data regarding metformin treatment, vitamin B(12) measurements, and documentation of vitamin B(12) deficiency, cyanocobalamin supplementation, anemia, and neuropathy were collected. Subjects treated with metformin for less than 1 year or those with documented peripheral neuropathy, megaloblastic anemia, vitamin B(12) deficiency, or a condition associated with vitamin B(12) malabsorption prior to metformin initiation were excluded.. Subjects (N = 235) had a mean metformin dose of 2050 mg/day and mean duration of treatment of 5.2 years. Sixty percent did not have vitamin B(12) measured. Of subjects receiving metformin for 10 years or more, nearly half (46%) never had vitamin B(12) measured. New documentation of vitamin B(12) deficiency or cyanocobalamin supplementation was found in 5.5% of the population, and anemia was found in 12%. Of the 14% with new neuropathy, 42% did not have vitamin B(12) measured.. Vitamin B(12) was not routinely monitored in patients on high-dose metformin, even in those at highest risk (≥10 years of therapy), or in those with potential manifestations of vitamin B(12) deficiency (neuropathy). Cases of vitamin B(12) deficiency and resulting anemia or neuropathy may be undiagnosed and untreated because of lack of monitoring. Prospective studies examining the effect of increased vitamin B(12) monitoring on identification and treatment of vitamin B(12) deficiency in patients on metformin are warranted.

Topics: Anemia; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Drug Monitoring; Humans; Hypoglycemic Agents; Metformin; Middle Aged; Veterans; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Diabetes Complications; Diabetes Mellitus, Type 2; Disease Progression; Female; Humans; Insulin; Ischemia; Male; Metformin; Models, Biological; Models, Theoretical; Polycystic Ovary Syndrome; Prostatic Neoplasms; Vitamin B 12

Agents used to treat symptoms of diabetic peripheral neuropathy (DPN) are only palliative, not disease modifying. Although studies of monotherapy with L-methylfolate, methylcobalamin, or pyridoxal 5'-phosphate suggest that each of these bioavailable B vitamins may reverse the pathophysiology and symptoms of DPN, data on the efficacy of this combination therapy are limited. Therefore, we assessed the efficacy of an oral combination of L-methylfolate, methylcobalamin, and pyridoxal 5'-phosphate for improving epidermal nerve fiber density (ENFD) in the lower extremity of patients with DPN. Eleven consecutive patients with type 2 diabetes with symptomatic DPN were assessed for ENFD at the calf by means of skin punch biopsy and then placed on twice daily oral-combination L-methylfolate, methylcobalamin, and pyridoxal 5'-phosphate. After approximately 6 months of treatment, patients underwent follow-up biopsy. At the end of their treatment, 73% of patients showed an increase in calf ENFD, and 82% of patients experienced both reduced frequency and intensity of paresthesias and/or dysesthesias. This preliminary study suggests that combination L-methylfolate, methylcobalamin, and pyridoxal 5'-phosphate increases ENFD in patients with DPN.

Topics: Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Drug Combinations; Epidermis; Female; Humans; Male; Middle Aged; Nerve Fibers; Paresthesia; Skin; Vitamin B 12

Topics: Aged; Anemia; Diabetes Mellitus, Type 2; Drug Synergism; Female; Folic Acid; Humans; Hyperhomocysteinemia; Hypoglycemic Agents; Intestinal Absorption; Male; Metformin; Middle Aged; Proton Pump Inhibitors; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Hypoglycemic Agents; Metformin; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

Evaluate the effect of lipopenic and hypotensive treatment on homocysteine levels.. We recruited 145 type 2 diabetics and 130 control subjects. Thirty-seven diabetics had no complications, 54 had microvascular complications and 54 had macrovascular complications. We determined the parameters homocysteine of lipid, vitamin B12, triglycerides, and folates for all subjects. Associated treatments used one or more of the following drugs, statin, fibrate, angiotensin-converting enzyme inhibitor and beta-blockers.. Hyperhomocysteinemia was present in 35.6% of patients. Diabetics had elevated serum levels of triglycerides (P < 0.001), homocysteine (P < 0.01), folates (P < 0.01) and vitamin B12 (P < 0.001). A strong association was found between type 2 diabetes and hyperhomocysteinemia (P < 0.001). Diabetics with associated treatment had elevated homocysteine, vitamin B12 and folate levels when compared to diabetes-free controls. For diabetics with macrovascular complications, we found significant differences in homocysteine (P = 0.010) and folate (P = 0.014) between those taking associated drugs and those who did not. For diabetics with microvascular complications, a significant difference was found in folate only (P = 0.012).. Drugs used for hypertension and hyperlipidemia may have an effect on homocysteine levels, for this reason the interaction between drug action and homocysteine levels should be taken into consideration.

Topics: Aged; Antihypertensive Agents; Biomarkers; Case-Control Studies; Chi-Square Distribution; Diabetes Mellitus, Type 2; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Hypolipidemic Agents; Male; Middle Aged; Odds Ratio; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Triglycerides; Vitamin B 12

Topics: Diabetes Mellitus, Type 2; Folic Acid; Health Knowledge, Attitudes, Practice; Humans; Hypoglycemic Agents; Metformin; Vitamin B 12; Vitamin B 12 Deficiency

Studies of monotherapy with L-methylfolate, methylcobalamin, or pyridoxal 5'-phosphate suggest that these B vitamins may reverse both the symptoms and the pathophysiology of diabetic peripheral neuropathy (DPN). The efficacy of oral-combination L-methylfolate, 3 mg; methylcobalamin, 2 mg; and pyridoxal 5'-phosphate, 35 mg (LMF-MC-PP) in restoring cutaneous sensitivity in patients with type 2 diabetes with DPN was evaluated in 20 type 2 diabetic patients who were given LMF-MC-PP twice daily for 4 weeks and then once daily for an additional 48 weeks. Statistically significant improvement in 1-point (tactile) and 2-point (discriminatory) static testing at the right and left great toe and heel in the patients was observed in all 3 follow-up periods: 1) baseline to 6 months, 2) baseline to 1 year, and 3) 6 months to 1 year. The greatest improvement occurred between baseline and 1 year of treatment. Treatment with oral LMF-MC-PP appears to promote restoration of lost cutaneous sensation in DPN.

Topics: Diabetes Mellitus, Type 2; Diabetic Neuropathies; Drug Therapy, Combination; Follow-Up Studies; Humans; Pilot Projects; Pyridoxal Phosphate; Sensory Thresholds; Tetrahydrofolates; Touch; Treatment Outcome; Vitamin B 12

Topics: Diabetes Mellitus, Type 2; Disease Progression; Folic Acid; Glucose Intolerance; Humans; Obesity; Placebos; Primary Prevention; Randomized Controlled Trials as Topic; Risk Factors; Vitamin B 12; Vitamin B 6

Low plasma concentrations of vitamin B-12 are common in Indians, possibly due to low dietary intakes of animal-source foods. Whether malabsorption of the vitamin contributes to this has not been investigated. A rise in the plasma holotranscobalamin (holo-TC) concentration after a standard dose of oral vitamin B-12 has been proposed as a measure of gastrointestinal absorption in people with normal plasma vitamin B-12 concentrations. We studied 313 individuals (children and parents, 109 families) in the Pune Maternal Nutrition Study. They received 3 doses of 10 microg (n = 191) or 2 microg (n = 122) of cyanocobalamin at 6-h intervals. A rise in plasma holo-TC of > or =15% and >15 pmol/L above baseline was considered normal vitamin B-12 absorption. The baseline plasma vitamin B-12 concentration was <150 pmol/L in 48% of participants; holo-TC was <35 pmol/L in 98% and total homocysteine was high in 50% of participants (>10 micromol/L in children and >15 micromol/L in adults). In the 10 microg group, the plasma holo-TC concentration increased by 4.8-fold from (mean +/- SD) 9.3 +/- 7.0 pmol/L to 53.8 +/- 25.9 pmol/L and in the 2 microg group by 2.2-fold from 11.1 +/- 8.5 pmol/L to 35.7 +/- 19.3 pmol/L. Only 10% of the participants, mostly fathers, had an increase less than the suggested cut-points. Our results suggest that an increase in plasma holo-TC may be used to assess vitamin B-12 absorption in individuals with low vitamin B-12 status. Because malabsorption is unlikely to be a major reason for the low plasma vitamin B-12 concentrations in this population, increasing dietary vitamin B-12 should improve their status.

Topics: Adult; Body Height; Body Weight; Cardiovascular Diseases; Child; Diabetes Mellitus, Type 2; Fathers; Female; Folic Acid; Hemoglobins; Homocysteine; Humans; Intestinal Absorption; Male; Maternal Nutritional Physiological Phenomena; Mother-Child Relations; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

This study investigated the role of homocysteine thiolactone (HcyT) in the development of macrovascular complications in Chinese patients with type 2 diabetes. HcyT has been proposed as a possible molecular basis for homocysteine (Hcy)-induced vascular damage.. One hundred and sixty subjects were recruited into this study: 40 healthy controls and 120 patients with type 2 diabetes. Plasma Hcy levels were measured by polarization immunoassay and HcyT concentrations were monitored using high-performance liquid chromatography on a reversephase C18 column with ultraviolet detection. Plasma folic acid and vitamin B(12) levels were measured using radioimmunoassay methods.. Plasma Hcy and HcyT concentrations in patients with type 2 diabetes were significantly higher than in healthy controls (Hcy [25th and 75th quartiles]: 9.28 [7.51-11.82] vs. 5.64 [5.17-8.00] micromol/L, P=0.01; HcyT: 3.38 [2.94-4.73] vs. 2.91 [2.77-3.08] nmol/L, P<0.05). Plasma Hcy and HcyT levels in patients with macrovasculopathy (MAVP) were significantly higher compared with patients without MAVP (Hcy: 10.36 [7.67-12.45] vs. 7.85 [6.76-10.52] micromol/L, P<0.05; HcyT: 4.27 [3.02-5.11] vs. 3.12 [2.63-3.77] nmol/L, P<0.05). Plasma HcyT concentrations were positively correlated with urinary excretion of albumin/creatinine (Alb/Cr; r=0.285, P=0.007), duration of diabetes (r=0.249, P=0.019), age (r=0.233, P=0.028), and fibrinogen levels (r=0.289, P=0.034). Plasma HcyT concentrations were negatively correlated with high-density lipoprotein levels (r=-0.223, P=0.037). Binary logistic regression showed that HcyT, Hcy, smoking, serum triglyceride, and urine Alb/Cr were significantly associated with the risk of diabetic MAVP (P<0.05).. Hcy and HcyT levels were associated with the development and progression of diabetic MAVP. HcyT may provide a plausible chemical mechanism for explaining Hcy toxicity in the human vascular endothelium.

Topics: Age Factors; Asian People; Body Mass Index; China; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Folic Acid; Homocysteine; Humans; Lipids; Male; Middle Aged; Risk Factors; Smoking; Time Factors; Vitamin B 12

Previous studies have shown conflicting results regarding circulating homocysteine levels in patients with type 2 diabetes.. This observational study included 2121 patients with angiographically proven coronary artery disease (507 patients with type 2 diabetes and 1614 patients without diabetes). Circulating homocysteine levels, methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, renal function, presence of coronary artery disease (CAD) diagnosed by coronary angiography, and circulating folate and vitamin B12 status were assessed. Plasma homocysteine levels [median (25th; 75th percentile)] were significantly higher in patients with diabetes than in those without [12.4 micromol/L (9.9 micromol/L; 15.9 micromol/L) versus 11.7 micromol/L (9.6 micromol/L; 14.5 micromol/L), P=0.011]. Diabetes affected homocysteine levels only in patients with a glomerular filtration rate <90 mL/min [13.0 micromol/L (10.5 micromol/L; 16.7 micromol/L) in patients with diabetes versus 12.2 micromol/L (10.1 micromol/L; 15.2 micromol/L) in patients without diabetes, P=0.006] but not in those with a glomerular filtration rate > or = 90 mL/min [10.1 micromol/L (8.1 micromol/L; 12.4 micromol/L) versus 10.2 micromol/L (8.8 micromol/L; 12.3 micromol/L), P=0.267]. Multivariable analysis did not show an independent association between diabetes and homocysteine level (P=0.342).. Circulating homocysteine levels are increased in patients with type 2 diabetes compared with non-diabetic patients due to a more diabetes-associated adverse risk profile rather than to diabetes itself.

Topics: Aged; Blood Glucose; Coronary Angiography; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Folic Acid; Genotype; Glomerular Filtration Rate; Glycated Hemoglobin; Homocysteine; Humans; Linear Models; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Multivariate Analysis; Polymorphism, Genetic; Up-Regulation; Vitamin B 12

To assess the role of homocysteine as a risk factor for mortality in diabetic subjects.. Homocysteine, vitamin B(12), and folate concentrations were measured in stored sera of 396 diabetic Pima Indians aged > or = 40 years when examined between 1982 and 1985. Vital status was assessed through 2001.. Over a median follow-up of 15.7 years, there were 221 deaths-76 were due to cardiovascular disease (CVD), 36 to diabetes/nephropathy and 34 to infections. Homocysteine was positively associated with mortality from all causes (hazard rate ratio (HRR) for highest versus lowest tertile of homocysteine = 1.70, 95% confidence interval (CI) 1.18-2.46), from diabetes/nephropathy (HRR = 2.39, 95% CI 0.94-6.11) and from infectious diseases (HRR = 3.39, 95% CI 1.19-9.70), but not from CVD (HRR = 1.16, 95% CI 0.62-2.17) after adjustment for age, sex and diabetes duration. Homocysteine correlated with serum creatinine (r = 0.50), and the relationships with mortality rates were not significant after adjustment for creatinine. Vitamin B(12) was positively associated with all-cause mortality (HRR for 100 pg/mL difference adjusted for age, sex and diabetes duration = 1.15, 95% CI 1.08-1.22) and death from diabetes/nephropathy (HRR = 1.27, 95% CI 1.10-1.46). The association between homocysteine and mortality in type 2 diabetes is not causal, but is confounded by renal disease in Pima Indians.

Topics: Adult; Aged; Aged, 80 and over; Arizona; Cardiovascular Diseases; Cause of Death; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Folic Acid; Homocysteine; Humans; Indians, North American; Infections; Longitudinal Studies; Male; Middle Aged; Proportional Hazards Models; Serum Albumin; Vitamin B 12

We analyzed the association between beer and other type of ethanol consumption and tHcy levels among type 2 diabetic patients. Male type 2 diabetic patients without overt nephropathy were studied (n=242). Ethanol consumptions of the patients were 35.1+/-37.8mL/day for total ethanol, 13.9+/-15.2mL/day for beer ethanol and 21.2+/-32.1mL/day for non-beer ethanol. Both, total and non-beer ethanol consumption correlated with tHcy, whereas beer ethanol consumption showed a trend to inverse association with tHcy (standard regression coefficient, 0.184, 0.283 and -0.110, respectively). Each intake of 30mL/day ethanol consumption was associated with an increase of tHcy of 0.6micromol/L for total ethanol and 1.1micromol/L for non-beer ethanol and a decrease of tHcy of 0.7micromol/L for beer ethanol. Similar trend was observed in the analysis model which included only drinkers, and also in an adjusted analysis model. Plasma tHcy of beer only drinkers was lower than that of non-beer alcohol only drinkers (8.9+/-1.9micromol/L versus 11.5+/-5.5micromol/L, P=0.003). Non-beer ethanol consumption might be less healthy compared with beer ethanol consumption among type 2 diabetic patients in terms of the effects on tHcy.

Topics: Alcohol Drinking; Beer; Diabetes Mellitus, Type 2; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Regression Analysis; Vitamin B 12

Topics: Aged; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Metformin; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Contraindications; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Risk Factors; Vitamin B 12

Individuals with Type 2 diabetes are at increased risk of stroke. Plasma homocysteine (tHcy) is an independent risk factor for cardiovascular (CV) disease. The methylene-tetrahydrofolate reductase (MTHFR) gene polymorphism (thermolabile variant C(677)T) is associated with CV risk, partly as a result of increased Hcy, especially in homozygous subjects.. To relate the occurrence of the MTHFR polymorphism with stroke prevalence by examining allelic frequency and genotype distribution in 165 subjects with Type 2 diabetes studied for the presence of thermolabile C(677)T MTHFR mutation.. Mean age was 67.7 years, and tHcy 18.2 micromol/l. T allele frequency was 38.5%. MTHFR genotypes were: normal (CC) 40%; heterozygous (CT) 43%; homozygous (TT) 17%. Serum levels of folic acid and B12 vitamin were within normal limits. Stroke prevalence was 14%. Sixty-four per cent of stroke-free subjects had the normal C allele vs. 46% in stroke subjects. The frequencies of genotypes (CC-CT-TT) were (%): 44-41-15 in stroke-free vs. 17-57-26 in stroke patients. Coronary (CAD) and peripheral artery disease (PAD) were common in all groups, with no differences according to genotypes. Stroke prevalence was markedly higher in genotypes CT and TT (18 and 21%) compared with CC (6%). Mean tHcy levels were higher in TT subjects.. The allelic frequency of C(677)T MTHFR mutation in Type 2 diabetes subjects with stroke is markedly different from that of subjects without stroke. Genotypic characteristics suggest that C(677)T MTHFR mutation confers a higher risk for stroke to both homozygous and heterozygous T allele carriers that cannot be ascribed solely to raised tHcy and/or lower folate status in CT subjects, nor to phenotypic expression of conventional risk factors for stroke. The impact of the MTHFR polymorphism on stroke may result from T allele-linked deleterious effects, or C allele-linked protection. Confirmatory studies are warranted, as this cohort was not randomly selected, and a type 1 error cannot be ruled out.

Topics: Aged; Cohort Studies; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Folic Acid; Gene Frequency; Heterozygote; Homozygote; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Mutation; Peripheral Vascular Diseases; Polymorphism, Genetic; Risk Factors; Stroke; Vitamin B 12

A moderate increase of total homocysteine (tHcy) plasma levels seems to increase cardiovascular disease (CVD) risk in Type 2 diabetic subjects, but its relationship with diabetes and insulin-resistance is still controversial. We examined whether mild hyperhomocysteinemia and its major genetic determinant would cluster with the metabolic syndrome (MS) in Type 2 diabetes. One hundred Type 2 diabetic subjects with and without MS were enrolled in the study. Fasting tHcy, vitamin B12, and folate plasma levels, insulin-resistance [assessed by homeostasis model assessment, (HOMAIR)] and the methylene tetrahydrofolate reductase (MTHFR) C677T genotype were assessed in all the participants. Geometric mean tHcy concentration and the prevalence of mild hyperhomocysteinemia, as commonly defined by tHcy >/=15 micromol/l, were comparable in diabetic subjects with and without MS, even after adjustment for age, sex, vitamin B12, folate and creatinine levels. In both groups, the MTHFR C677T genotype distribution was not significantly different from the Hardy-Weinberg equilibrium, with a TT homozygous frequency of 21% in subjects with and 18% in those without the syndrome (p=ns). tHcy plasma levels and the degree of insulin-resistance did not differ across MTHFR genotypes in both groups, even after multivariable adjustment. Overall, tHcy significantly correlated with creatinine (r=0.25; p=0.009) and trygliceride concentrations (r=0.24; p=0.02), but not with HOMAIR. At multivariate analysis, only creatinine was significantly correlated with tHcy levels (beta=0.42; p=0.001). In conclusion, hyperhomocysteinemia and the common C677T variant of MTHFR gene are not associated with MS in Type 2 diabetic subjects.

Topics: Adult; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Folic Acid; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Insulin Resistance; Linear Models; Male; Metabolic Syndrome; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Obesity; Polymorphism, Genetic; Triglycerides; Vitamin B 12

Mutations or polymorphisms in the gene of the enzyme methylenetetrahydrofolate (MTHFR) are associated with hyperhomocysteinemia and possibly with an elevated risk for vascular diseases. A study was conducted on 83 individuals with type 2 diabetes in order to determine the allelic and genotypic frequencies of the G1793A mutation and to assess the effect of folic acid supplementation on plasma homocysteine concentrations. The patients were attended by the Diabetes and Hypertension Program--Balneario Camboriu/SC and received daily supplements containing 1 mg of folic acid for 3 months. DNA was previously extracted from leukocytes and the G1793A mutation was detected by PCR-RFLP. Blood samples were collected during the basal period and after supplementation for the determination of homocysteine by HPLC, and of folic acid and vitamin B(12) by RIA. The allele frequency for the G1793A mutation was 3.01% and no homozygous individuals with mutant alleles were detected. Hyperhomocysteinemia was diagnosed in 27.71% of the patients, folic acid deficiency in 15.66%, and vitamin B(12) deficiency in 7.23%. Plasma homocysteine concentrations were inversely correlated with folic acid (r = -0.27, p = 0.01) and vitamin B(12) (r = -0.21; p = 0.05) concentrations. The individuals with a heterozygous genotype for the G1793A mutation showed borderlines or deficient values in folic acid and vitamin B(12) concentrations compared to individuals with a normal genotype. Hyperhomocysteinemia and the vitamin deficiencies presented by type 2 diabetic individuals, included with a heterozygous genotype for the G1793A mutation in the MTHFR gene, reached normal values by daily folic acid supplementation.

Topics: Adult; Aged; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Folic Acid; Gene Frequency; Heterozygote; Homocysteine; Humans; Hyperhomocysteinemia; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Vitamin B 12

Previous studies have suggested that hyperhomocysteinaemia (Hcy) could be a strong and independent cardiovascular risk factor. Many factors could influence the serum concentration of Hcy such as vitamin B 12, folic acid, renal failure, hypothyroid status, ovarian failure and cancers. So the aim of our study was to evaluate the prevalence of hyperhomocysteinaemia among 54 type 2 diabetic patients and to study, its relationship with vitamin B12, folic acid and Metformin. Were excluded all patients with an evident cause of hyperhomocysteinaemia. Mean age of patients was 52.8 years. Mean Hcy was 11.7 + 6.9 micromol/l. The prevalence of hyperhomocysteinaemia was 27.8% in our group. There were eight (14%) patients with vitamin B12 deficiency and three among them had hyperhomocysteinaemia. There was no folic acid deficiency and no relationship with Metformin treatment. We suggest a wide screening of hyperhomocysteinaemia in type 2 diabetic patients and folic acid or vitamin B12 supplements if necessary.

Topics: Diabetes Mellitus, Type 2; Female; Folic Acid; Glycated Hemoglobin; Homocysteine; Humans; Hyperhomocysteinemia; Hypoglycemic Agents; Male; Metformin; Middle Aged; Obesity; Prospective Studies; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

There are only very few epidemiological data about homocysteine levels in patients suffering from cardiovascular (CV) disease in Hungary, however, homocysteine is a newly recognized, independent risk factor of CV diseases.. Therefore, in the present study, data of 1010 East-Hungarian patients with signs of CV disease were analyzed retrospectively for correlation between the level of homocysteine and CV diseases, laboratory parameters, as well as genetic differences.. From the studied patient population a control ("healthy") group has been selected according to the following criteria: lack of previous stroke or stenosis of the carotid arteries or the lower extremities, lack of coronary artery stenosis more than 50%, no previous coronary intervention or an angiography diagnosed progression of the coronary atherosclerosis.. The level of homocysteine showed statistically significant negative linear correlation with HDL-cholesterol and the anti-atherogenic ApoAI, and showed a positive correlation with CRP and FXIII activities in the entire patient population. When compared to the control group, homocysteine level was significantly higher in patients with previous stroke or acute myocardial infarction, coronary stenosis, progressive coronary disease, physical inactivity, MTHFR gene polymorphism, low folate or vitamin B12 level in both men and women. In patients with type II diabetes the level of homocysteine was significantly higher only in women.. It can be concluded that the level of homocysteine in patients suffering from various CV diseases is high in Hungary. This may have a prognostic value, and shows that reduction of homocysteine level in these patients may be beneficial.

Topics: Adult; Aged; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; COUP Transcription Factor II; Diabetes Mellitus, Type 2; Factor XIII; Female; Folic Acid; Homocysteine; Humans; Hungary; Hyperhomocysteinemia; Linear Models; Male; Middle Aged; Patient Selection; Polymorphism, Genetic; Retrospective Studies; Risk Factors; Vitamin B 12

Diabetic nephropathy is a common complication in patients with type 2 diabetes that may increase atherothrombotic risk. Hyperhomocysteinemia (HHcy) further increases the risk in those patients. We studied concentrations of total homocysteine (tHcy) and its related metabolites S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy) in relation to B-vitamin status and renal function in patients with type 2 diabetes who developed diabetic nephropathy.. The study included 93 patients with renal failure and type 2 diabetes. Chronic kidney disease was classified into four subgroups according to the National Kidney Foundation based on glomerular filtration rate plus pathologic abnormalities or markers of kidney damage.. Serum or plasma concentrations of the metabolites increased significantly with worsening of renal function, whereas serum concentrations of the B vitamins (folate, vitamins B12 and B6) did not differ appreciably between the groups. Moreover, plasma concentrations of AdoHcy and AdoMet were markedly increased in patients with kidney failure compared with those in stage 2 (median AdoHcy, 112.7 vs 10.5 nmol/L; median AdoMet, 162.0 vs 80.0 nmol/L). The AdoMet/AdoHcy ratio was more than 80% lower in patients with renal failure compared with stage 2. Vitamin B12 was a significant determinant of concentrations of AdoMet, tHcy, methylmalonic acid (MMA), and cystathionine.. Increased plasma concentrations of tHcy and methionine cycle intermediates (AdoMet, AdoHcy) are related to disturbed renal function in patients with type 2 diabetes. Vitamin B12 and/or folate are significant predictors of tHcy, cystathionine, MMA, and AdoMet. The effect of therapeutic doses of the B vitamins on AdoMet, AdoHcy, and their ratio should be tested in renal patients.

Topics: Aged; Cystathionine; Cysteine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Folic Acid; Homocysteine; Humans; Kidney; Kidney Failure, Chronic; Male; Methionine; Methylmalonic Acid; Middle Aged; S-Adenosylhomocysteine; S-Adenosylmethionine; Transcobalamins; Vitamin B 12; Vitamin B 6

Increased concentration of plasmatic homocysteine (tHcy) and decreased vitamin B 12 (B12) and folate (FOL) are associated with Alzheimer's (AD) and vascular (VaD) dementias, with type II diabetes mellitus (DM), and reported as risk factors of these diseases.. The sample (n=122; males=60; mean age=73+/-7 years) comprised AD and VaD patients without DM, with a concomitant DM (AD+DM, VaD+DM), DM alone and controls (CTR), resulting in 6 groups. tHcy, B12 and FOL were determined in duplicate.. The one-way ANOVA yielded significant differences between groups for all variables: tHcy p<10(-12); B12 p<10(-3); FOL p<10(-4). Significance for comparisons between groups was set at alpha=0.05, using the Bonferroni's statistic. The comparisons: DM vs. CTR, AD+DM vs. AD, VaD+DM vs. VaD, and DM demented vs. DM non-demented resulted significant for all variables, except for B12 in 2 comparisons.. In demented and control subjects, tHcy and FOL exhibit extreme differences, not so marked between DM and controls. Demented patients with concomitant diabetes are closer to controls than their non-diabetic counterparts. Diabetes affects tHcy and FOL values, which are changed with opposite sign to non-demented. These results suggests a paradoxical phenomenon when diabetes is superimposed to dementias.

Topics: Aged; Alzheimer Disease; Analysis of Variance; Dementia, Vascular; Diabetes Mellitus, Type 2; Female; Folic Acid; Homocysteine; Humans; Male; Vitamin B 12

Although moderate alcohol intake is associated with reduced risk of atherosclerotic disease in both the general population and in diabetic patients, a recent report suggests that heavy alcohol intake facilitates the development of atherosclerosis exclusively in diabetic individuals. We studied cross-sectionally the effects of the interaction between ethanol consumption category and the prevalence of diabetes on plasma total homocysteine (tHcy), a risk factor for atherosclerotic disease, in middle-aged men. Heavy drinking was associated with elevated tHcy levels only in diabetic subjects but not in non-diabetic subjects. Plasma tHcy of heavy drinkers (average ethanol consumption > 30 ml/day) was higher than that of abstainers in the diabetic subgroup (10.25 +/- 3.39 vs. 8.88 +/- 1.94 micromol/l, P < 0.05), whereas tHcy levels in heavy drinkers were comparable with that of abstainers in the non-diabetic subgroup (9.36 +/- 2.52 vs. 9.12 +/- 2.10 micromol/l, NS). In a two-factor anova, significant interaction was observed on the effects of ethanol consumption category and diabetes prevalence on tHcy levels (P < 0.01). Confounding factors including folate, vitamin B(12), creatinine, age or cigarette smoking did not contribute to the interaction. These findings may partly explain the reported association between heavy drinking and atherosclerosis in diabetic subjects.

Topics: Alcohol Drinking; Arteriosclerosis; Blood Glucose; Creatinine; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Folic Acid; gamma-Glutamyltransferase; Homocysteine; Humans; Male; Middle Aged; Prevalence; Risk Factors; Vitamin B 12

Patients with diabetic nephropathy are at elevated cardiovascular risk. C-reactive protein (CRP) has been used to successfully predict cardiovascular events.. We identified clinical and biochemical characteristics that correlate with CRP levels in diabetic nephropathy patients.. Baseline data obtained from 722 patients in the Irbesartan Diabetic Nephropathy Trial included age, sex, body mass index (BMI), systolic blood pressure (BP), serum creatinine, plasma low- and high-density cholesterol, triacylglycerol, serum albumin, hemoglobin A1C, 24h urinary protein excretion, plasma total homocysteine (tHcy), folate, B12, pyridoxal 5'-phosphate (PLP, active form of Vitamin B(6)), and plasma CRP levels.. In univariate analyses CRP was positively associated with female sex (r=0.08; P=0.04), BMI (r=0.34; P<0.01), serum creatinine (r=0.21; P<0.01), hemoglobin A1C (r=0.08; 0.04), and inversely associated with PLP (r=-0.17; P<0.01) and folate (r=-0.09; P=0.02). A stepwise multiple regression model found CRP directly correlated with BMI (P<0.01) and serum creatinine (P<0.01), and inversely correlated with PLP (P<0.01). The final model explained 16% of the total variance of CRP.. These results extend previous findings of an inverse relationship between Vitamin B(6) and CRP. The lack of association between CRP and certain established or emerging cardiovascular risk factors offers novel information regarding cardiovascular risk in this population.

Topics: Adult; Aged; Blood Pressure; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Creatinine; Depsipeptides; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Folic Acid; Glycated Hemoglobin; Humans; Male; Middle Aged; Peptides, Cyclic; Proteinuria; Pyridoxal Phosphate; Risk Factors; Serum Albumin; Triglycerides; Vitamin B 12

A high prevalence of hyperhomocysteinemia has been reported in type II diabetic patients with documented vascular disease; hence the hypothesis that hyperhomocysteinemia may contribute to overall mortality in diabetic patients. The link between insulin and homocysteine metabolism has not been completely clarified yet; in particular, only few data are available on the effects of insulin in vivo on homocysteine metabolism in the presence of abnormalities of sulphur amino acid metabolism (methionine intolerance).. To establish whether methionine intolerance and which of its determinants could influence total plasma homocysteine in response to insulin infusion in vivo in type II diabetic patients, we submitted 18 patients (Group A) with normal and 18 patients with abnormal (hyperhomocysteinemia) (Group B) response to oral methionine load to a glucose/clamp study. At time 0, and 30, 60 and 120 minutes after hyperinsulinemia, homocysteine and methionine plasma levels were assessed. In order to evaluate the cause of methionine intolerance, all patients were assayed for fasting homocysteine-cysteine ratio (as a marker of suspected heterozygosis for cystathionine-beta-synthase deficit), MTHFR C (677)T status and homocysteine-related vitamin status (serum vitamin B (6) [PLP], vitamin B (12) and folate).. After hyperinsulinemia, plasma methionine was reduced (by about - 30 % at 120 minutes vs. basal values) within both groups, whereas tHcy tend to decrease in group A following insulin administration (up to - 6.6 +/- 3.6 % vs. basal values at 120 minutes) with a significantly higher variability, while in patients with "methionine intolerance" (group B) tHcy tended to increase (up to + 29.05 +/- 8.3 % vs. basal values at 120 min from the clamp). Serum folic acid (7.45 +/- 2.8 vs. 4.82 +/- 2.5 nmol/L, p < 0.05), Vit. B (12) (348 +/- 78 vs. 242 +/- 65 pmol/L, p < 0.05) and PLP (84.1 +/- 23.6 vs. 50.6 +/- 32.4 nmol/L; p < 0.01) were significantly higher in group A than in group B; PLP levels significantly correlated with homocysteine after 4 h methionine load (n = 36; r = - 0.327, p < 0.05); group A showed also a significantly lower prevalence of suspected heterozygosis for cystathionine-beta-synthase deficit (1/18 [11.1 %] vs. 5/18 [33.3 %], p < 0.05) and MTHFR T allele presence (4/18 [22.2 %] vs. 11/18 [61.1 %], p < 0.01). A stepwise regression analysis with tHcy plasma level variations (event A = reduction; event B = increase) as the dependent variable showed that low serum folate and PLP levels and presence of MTHFR T allele were the variables associated with insulin-induced tHcy increase.. Methionine intolerance may influence the effect of insulin administration on plasma homocysteine in patients affected by type 2 diabetes. To prevent a possible acute (and repeated) hyperhomocysteinemia due to insulin administration in cases of methionine intolerance, it may be useful to assess the presence of methionine intolerance (tHcy after oral methionine loading) and Hcy-related vitamin status in all patients due to be subjected to insulin therapy.

Topics: Blood Glucose; Cysteine; Diabetes Mellitus, Type 2; DNA; Female; Folic Acid; Glucose Clamp Technique; Homocysteine; Humans; Hyperhomocysteinemia; Insulin; Male; Methionine; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Point Mutation; Polymerase Chain Reaction; Vitamin B 12; Vitamin B 6

Topics: Administration, Oral; Controlled Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Drug Therapy, Combination; Humans; Placebos; Prodrugs; Pyridoxine; Thiamine; Time Factors; Vitamin B 12; Vitamin B 6

To determine the effect of metformin on the levels of plasma homocysteine (Hcy), serum vitamin B12 and folic acid in patients with type 2 diabetes mellitus and the relationship between cumulative metformin exposure and levels of plasma homocysteine (Hcy).. The cross sectional study was conducted to assess the effect of metformin treatment on plasma homocysteine (Hcy), serum vitamin B12 and folic acid in 152 type 2 diabetic out-patients aged between 35-65 years old at the Diabetes Clinic of The Makaruk Hospital, Kanchanaburi, Thailand Among those, 88 and 64 patients were categorised to the metformin and non-metformin group according to their records of receiving metformin treatment for a period of a minimal 6 consecutive months before the study. Fasting blood was drawn from each patient and analysed for plasma homocysteine using the Fluorescence Polarization Immunoassay (FPIA) method (IMX Analyzer), and serum vitamin B12 and folic acid using the radioimmunoassay method. The plasma Hcy levels showed no significant difference (p = 0.544) among patients in the metformin group compared with those in the non-metformin group (10.6+/-5.8 mol/L vs 10.4+/-4.0 mol/L). There was a significant difference (p = 0.011) in the levels of serum vitamin B12 among patients in the metformin group and among those in the non-metformin group (318.0+/-192.2 pg/mL vs 434.3+/-300.7 pg/mL). However, there was no significant difference (p = 0.090) in serum folic acid levels between patients in the metformin and those in the non-metformin group (8.8+/-5.1 ng/mL vs 7.7+/-3.8 ng/mL). The plasma Hcy levels showed a significant correlation with the duration of metformin treatment (p = 0.014) and the amount of metformin received (p = 0.015) with the Spearman correlation coefficient of 0.260 and 0.258 respectively.. Even though the direct effect of metformin treatment on the plasma Hcy could not be concluded from the present study, it was found that there was a significant depletion of level of serum vitamin B12 among patients who had been on long-term metformin treatment. Therefore, vitamin B12 supplement is suggested for diabetic patients who are receiving metformin medication.

Topics: Adult; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Folic Acid; Homocysteine; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Vitamin B 12

The aim of this study was to examine the relation between serum total homocysteine concentrations and microvascular complications in Pima Indians with Type 2 diabetes.. Homocysteine concentrations were measured in frozen sera of 396 diabetic participants in a longitudinal study who were 40 years of age or older and who had attended one or more examinations between 1982 and 1985. Retinopathy was assessed by fundoscopy and nephropathy by an albumin:creatinine ratio greater than 300 mg/g. The incidence rate ratio for a 5 micro mol/l difference in homocysteine was calculated using proportional hazard regression.. The incidence of each complication was assessed in subjects without that complication at baseline and with more than one follow-up examination: 229 for nephropathy, 212 for retinopathy and 266 for proliferative retinopathy. There were 101 incident cases of nephropathy, 113 of retinopathy and 40 of proliferative retinopathy during a mean follow-up of 8.6, 7.5 and 8.9 years, respectively. Incidence of nephropathy was associated with homocysteine concentrations: IRR=1.42 (95% CI, 1.09-1.84, p=0.01); this remained statistically significant controlled for age, sex and duration of diabetes (p=0.03), but not when controlled for baseline renal function (p=0.4). Homocysteine concentrations were not associated with the incidence of any retinopathy IRR=1.14 (95%CI 0.89-1.46, p=0.3) but were associated with the incidence of proliferative retinopathy IRR=1.62 (95% CI 1.16-2.28, p=0.005); this association remained statistically significant when controlled for baseline renal function and diabetes duration (p=0.02).. Increased homocysteine concentrations are associated with an increased risk for incidence of nephropathy and proliferative retinopathy; the relation with incidence of nephropathy seems to be explained by an association with baseline albuminuria status concentrations, whereas the relation with incidence of proliferative retinopathy does not.

Topics: Age Factors; Analysis of Variance; Arizona; Biomarkers; Blood Glucose; Creatinine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Female; Folic Acid; Homocysteine; Humans; Incidence; Indians, North American; Longitudinal Studies; Male; Middle Aged; Vitamin B 12

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Arteriosclerosis; Cardiovascular Diseases; Chlamydia Infections; Controlled Clinical Trials as Topic; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Folic Acid; Humans; Hypercholesterolemia; Hyperhomocysteinemia; Hypertension; Hypolipidemic Agents; Infections; Male; Middle Aged; Multicenter Studies as Topic; Obesity; Randomized Controlled Trials as Topic; Risk Factors; Vitamin B 12; Vitamin B Complex

Topics: Calcium, Dietary; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

The aim of this study was to investigate the relationship between total homocysteine levels in people with Type 2 diabetes and cognitive status. Fifty patients from our diabetes unit (30 females/20 males) with diabetes were enrolled. All patients had fasting blood samples taken for measurement of cardiovascular risk factors; total cholesterol and triglyceride concentrations and other lipid fractions (lipoprotein (a), low density lipoprotein (LDL-cholesterol), high density lipoprotein (HDL-cholesterol)), glucose, HbA(1c) and homocysteine. 24-h urine collection was used to measure creatinine clearance and microalbuminuria. Vitamin B-12 and folate were measured to assess vitamin status. All diabetic patients were assessed for late complications and a Mini-Mental State Examination (MMSE) was performed. The patients were 64.6 (49-78) years old with body mass index (BMI) of 29.6 +/- 6.3 kg/m(2), and duration of diabetes of 8.9 +/- 6.7 years. A univariant correlation analysis was performed among cardiovascular risk factors and vitamins with total MMSE score. Total homocysteine was inverse by correlated with MMSE score (r=-0.38; P<0.05) of the other measures of cardiovascular risk, microalbuminuria showed an inverse correlation with MMSE score (r=-0.51:P<0.01). Lipoproteins, glucose control and vitamin status were not correlated MMSE score. In the multiple regression model only microalbuminuria remained in the model, showing a decrease of one point in the MMSE result with each milligram of microalbuminuria, adjusted for confounding factors. Cognitive status in type 2 diabetic was correlated with homocysteine levels and microalbuminuria, this last endothelial damage marker remaining as an independent risk factor of cognitive deterioration.

Topics: Aged; Albuminuria; Cholesterol; Cognition; Cognition Disorders; Diabetes Mellitus, Type 2; Female; Folic Acid; Glycated Hemoglobin; Homocysteine; Humans; Lipoproteins; Male; Middle Aged; Triglycerides; Vitamin B 12

To observe the clinical effect of combined treatment of prostaglandin E1 and mecobalamin on diabetic peripheral neuropathy(DPN).. Seventy two patients of DPN were divided into 3 groups, they were given the drug of prostaglandin E1 (PGE1), mecobalamin, PGE1 plus mecobalamin (combined therapeutic group) and compared the therapeutic effects respectively.. The improvement of DPN symptoms and nerve conducting speeds of combined therapeutic group was obviously better than that of the single PGE1 group or mecobalamin group(P < 0.01).. Combined therapy of PGE1 and mecobalamin is better than each of single drug for improvement of DPN symptoms.

Topics: Adult; Aged; Alprostadil; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Vitamin B 12

Limited data are available on determinants of diabetic neuropathy as its pathogenesis is multifactorial. Since homocysteine exhibits toxic effects on vascular endothelial cells, the association between homocysteine and the prevalence of neuropathy in Type 2 diabetes mellitus was investigated.. A total of 65 Type 2 diabetic patients were consecutively enrolled into the study. Neuropathy was diagnosed according to clinical symptoms, clinical examination, electrophysiological sensory testing and autonomic function testing. With regard to homocysteine-related parameters, plasma homocysteine, folate, vitamin B12, vitamin B6 and renal function (creatinine, ceratinine clearance, cystatin C) were measured, and the C677T polymorphism of the methylenetetrahydrofolate reductase gene was determined.. Forty-three of the Type 2 diabetic patients were classified as suffering from neuropathy. Both patient groups were comparable with regard to demographic data, blood pressure, glucose metabolism, renal function and homocysteine-related vitamins. In contrast, homocysteine levels (P = 0.04) and the frequency of hyperhomocysteinemia (>or= 15 micromol/l) (P = 0.01) were significantly increased in neuropathic patients. In a logistic regression model with neuropathy as dependent variable, homocysteine (adjusted for creatinine, homocysteine-related vitamins, HbA1c and duration of diabetes) was the only significant variable associated with the prevalence of neuropathy (odds ratio for homocysteine per 5 micromol/l increase: 2.60 (95% confidence interval 1.07-6.33)).. The data indicate that homocysteine is independently associated with the prevalence of diabetic neuropathy in a collective of Type 2 diabetic patients. A larger, prospective study would be desirable to clarify the role of homocysteine in the pathogenesis of diabetic neuropathy.

Topics: Adult; Aged; Biomarkers; Blood Glucose; Blood Pressure; Creatinine; Cystatin C; Cystatins; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Folic Acid; Glomerular Filtration Rate; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Pyridoxine; Vitamin B 12

Although it is accepted that elevated plasma homocysteine (tHcy) levels occur in end-stage renal disease and type 2 diabetes, the changes with milder renal dysfunction (e.g., microalbuminuria) are less clearly established. This study explores the relationship among tHcy, creatinine clearance (Ccr), and albumin excretion rate (AER) in a population with type 2 diabetes.. A total of 260 patients with type 2 diabetes were screened in our outpatient clinic during 10 months. Fasting blood samples were collected, and AER was calculated from an overnight timed urine sample. Ccr was calculated using the Cockroft-Gault formula.. A total of 198 subjects (76%) had normoalbuminuria (<20 microg/min), 50 subjects (19%) had microalbuminuria (20-200 microg/min), and 12 subjects (5%) had macroalbuminuria (>or=200 microg/min). Those with microalbuminuria had higher levels of tHcy than those with normoalbuminuria (13.2 +/- 7.8 vs. 11.3 +/- 4.6 micromol/l, P < 0.05). Patients were then subdivided based on low Ccr (<80 ml x min(-1) x 1.73 m(-2)) and normal Ccr (>or=80 x min(-1) x 1.73 m(-2)). None of the patients with macroalbuminuria had normal Ccr. In those with normoalbuminuria, tHcy levels were higher than in those with low Ccr than in those with normal Ccr (12.0 +/- 4.6 vs. 10.0 +/- 4.4 micromol/l, P < 0.01). The same was found for those with microalbuminuria (low Ccr versus normal Ccr: 14.6 +/- 9.0 vs. 10.2 +/- 2.8 micromol/l, P < 0.02). For normal Ccr, tHcy was similar irrespective of AER (normoalbuminuria versus microalbuminuria: 10.0 +/- 4.4 vs. 10.2 +/- 2.8 micromol/l, NS). For low Ccr, tHcy was higher in those with microalbuminuria versus normoalbuminuria (14.6 +/- 9.0 vs. 12.0 +/- 4.6 micromol/l, P = 0.01). Using multivariate regression, Ccr, but neither AER nor the presence of albuminuria, was an independent predictor of tHcy.. These data strongly suggest that in patients with type 2 diabetes, the relationship between plasma tHcy and AER is largely due to associated changes in renal function, as defined by Ccr.

Topics: Aged; Albuminuria; Creatinine; Diabetes Mellitus, Type 2; Female; Folic Acid; Homocysteine; Humans; Male; Metabolic Clearance Rate; Middle Aged; Regression Analysis; Vitamin B 12

Elevated plasma total homocysteine (tHcy) has been suggested to be an additional risk factor for cardiovascular disease in subjects with impaired glucose tolerance (IGT) and Type 2 diabetes (T2D). In order to investigate whether an insulin resistant/chronic hyperinsulinemic situation in male diabetic and prediabetic subjects directly influences the tHcy metabolism, fasting tHcy and post-methionine load tHcy plasma levels (PML-tHcy) were determined in 15 men with IGT, 13 men with newly diagnosed T2D, and 16 normoglycemic controls (NGT). Fasting tHcy (IGT, 13.1 +/- 4.6; T2D, 12.8 +/- 4.0; NGT, 10.7 +/- 4.4 micromol/L) and PML-tHcy (IGT, 46.5 +/-17.39; T2D, 41.1 +/- 6.8; NGT, 38.0 +/- 9.7 micromol/L) showed no differences between the groups. Fasting tHcy and PML-tHcy correlated with fasting proinsulin (r = 0.395, p < 0.05; r = 0.386, p< 0.05) and creatinine (r = 0.489, p < 0.01; r = 0.339, p < 0.05), resp. Multiple regression analysis showed only a relationship between fasting tHcy and creatinine. No relationships have been found between fasting tHcy and PML-tHcy, resp., and indicators of an insulin resistant state, e.g., insulin and proinsulin, as well as serum cobalamin and folate concentrations. In conclusion, our data suggest that the degree of glucose intolerance has no direct impact on the metabolism of homocysteine. However, tHcy levels tend to be elevated with the development of nephropathy, indicating an association between tHcy and renal function in these subjects.

Topics: Blood Glucose; Cardiovascular Diseases; Creatinine; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Fasting; Folic Acid; Homocysteine; Humans; Insulin; Male; Methionine; Middle Aged; Proinsulin; Risk Factors; Time Factors; Vitamin B 12

The aim of this study was to determine the distribution of plasma total homocysteine (tHcy) concentrations in type 2 diabetic patients and to assess whether high tHcy values were related to chronic complications (particularly macroangiopathy and nephropathy) and/or the degree of insulin resistance.. Fasting tHcy levels were measured in 122 type 2 diabetic patients in whom the presence of chronic complications (e.g., macroangiopathy, microalbuminuria, macroproteinuria, decreased creatinine clearance, hypertension, retinopathy, and neuropathy) was recorded alongside an assessment of insulin resistance by the homeostasis model assessment (HOMA).. We found that 31% of the cohort (group 1) had raised tHcy (mean +/- 1 SD) values (20.8 +/- 5.1 micromol/l), whereas 69% (group 2) had normal values (10.2 +/- 2.0 micromol/l). The prevalence of macroangiopathy was higher in group 1 than in group 2 subjects (70 vs. 42%, P < 0.01); the prevalence of coronary artery disease was particularly higher in group 1 (46 vs. 21%, P < 0.02). The prevalence of impaired renal function, evidenced by decreased creatinine clearance, was higher in group 1 (32 vs. 10%, P < 0.005). Other clinical and biological characteristics of both groups were comparable, although group 1 had lower levels of folic acid than group 2 (5.2 +/- 2.9 vs. 7.0 +/- 3.4 ng/ml, P < 0.01). No differences were found for microalbuminuria (33 vs. 31%), retinopathy (45 vs. 42%), or neuropathy (70 vs. 59%) between groups 1 and 2, respectively The degree of insulin resistance was similar in groups 1 and 2 (46 +/- 21 and 42 +/- 20% of HOMA-insulin sensitivity) as was the assessment of beta-cell function (63 +/- 28 and 65 +/- 46%, respectively). No differences in tHcy levels were found between subjects receiving metformin and those not receiving metformin. In contrast, the plasma tHcy level was higher in diabetic patients treated with fibrates (P = 0.0016).. Elevated plasma tHcy levels in type 2 diabetes is associated with a higher prevalence of macroangiopathy and nephropathy when assessed from creatinine clearance indexes and is not associated with different degrees of insulin resistance.

Topics: Aged; Cohort Studies; Creatinine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Female; Folic Acid; Homeostasis; Homocysteine; Humans; Hyperhomocysteinemia; Hypoglycemic Agents; Insulin; Insulin Resistance; Logistic Models; Male; Metabolic Clearance Rate; Metformin; Middle Aged; Vitamin B 12

The plasma concentrations of total homocysteine (tHcy) and total cysteine (tCys) are determined by intracellular metabolism and by renal plasma clearance, and we hypothesized that glomerular filtration is a major determinant of plasma tHcy and tCys. We studied the relationships between the glomerular filtration rate (GFR) and plasma tHcy and tCys in populations of diabetic patients with particularly wide ranges of GFR.. We measured GFR, urine albumin excretion rate (UAER), plasma tHcy, tCys, methionine, vitamin B12, folate, C-peptide, and routine parameters in 50 insulin-dependent diabetes mellitus (IDDM) and 30 non-insulin-dependent diabetes mellitus (NIDDM) patients. All patients underwent intensive insulin treatment and had a serum creatinine concentration below 115 micromol/liter.. Mean plasma tHcy in diabetic patients (0.1 micromol/liter) was lower than in normal persons (11.1 micromol/liter, P = 0.0014). Mean plasma tCys in diabetic patients (266.1 micromol/liter) was also lower than in normal persons (281.9 micromol/liter, P = 0.0005). Seventy-three percent of the diabetic patients had relative hyperfiltration. Plasma tHcy and tCys were closely and independently associated with GFR, serum folate, and serum B12. However, plasma tHcy was not independently associated with any of the 22 other variables tested, including age, serum creatinine concentration, UAER, total daily insulin dose, and glycemic control.. Glomerular filtration rate is an independent determinant of plasma tHcy and tCys concentrations, and GFR is rate limiting for renal clearance of both homocysteine and cysteine in diabetic patients without overt nephropathy. Declining GFR explains the age-related increase in plasma tHcy, and hyperfiltration explains the lower than normal mean plasma tHcy and tCys concentrations in populations of diabetic patients.

Topics: Adult; Aged; Aged, 80 and over; Aging; Creatinine; Cysteine; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Folic Acid; Glomerular Filtration Rate; Homocysteine; Humans; Insulin; Middle Aged; Vitamin B 12

The increased cardiovascular risk in subjects with NIDDM is partly explained by an association with established risk factors like hypertension, dyslipidemia, and obesity. Mild hyperhomocysteinemia has emerged as a new risk factor for cardiovascular disease. The purpose of this study was to assess its role in NIDDM.. We studied predictors of homocysteine levels and correlations between homocysteine and (micro-)albuminuria, retinopathy, and history of cardiovascular disease in normotensive NIDDM subjects under stable metabolic control. This was done in 85 NIDDM subjects by measuring fasting and post-methionine-loading homocysteine levels together with blood pressure, BMI, serum cholesterol, triglyceride, HDL cholesterol, folate, vitamin B12, pyridoxal-5-phosphate, HbA1c, and (micro-)albuminuria and creatinine clearance in triplicate 24-h urine samples. The relationship between micro- and macrovascular complications and fasting homocysteine only was studied in an additional 65 subjects, giving a total of 150 subjects.. In multiple regression analysis, significant (P < 0.05) predictors of fasting homocysteine were low-normal values of creatinine clearance (threshold effect at < 80 ml.min-1 .1.73 m-2), folate (< 20 nmol/l), and vitamin B12 (< 350 pmol/l), and postmenopausal status in women. Determinants of post-methionine homocysteine were pyridoxal-5-phosphate levels < 80 nmol/l, creatinine clearance, and sex (higher levels in women). Hyperhomocysteinemia did not cluster with other cardiovascular risk factors, like hypertension, obesity, or dyslipidemia. Regarding cardiovascular complications, fasting homocysteine, but not post-methionine homocysteine, was higher in subjects with a history of cardiovascular disease. There was a stepwise increase in the prevalence of subjects with cardiovascular disease with increasing fasting homocysteine. The prevalence of cardiovascular disease was 19.4% in the bottom quartile of fasting homocysteine, versus 55.0% in the top quartile (P for trend < 0.01). Neither fasting homocysteine nor post-methionine homocysteine correlated with (micro-)albuminuria or with retinopathy.. The findings suggest that homocysteine levels in NIDDM rise even with modest deterioration of renal function and when vitamin status is in the low to low-normal range. Fasting homocysteine correlates with macrovascular disease, but we found no evidence of a correlation with retinopathy or (micro-)albuminuria. Post-methionine homocysteine levels do not show a correlation with micro- or macrovascular complications.

Topics: Administration, Oral; Adult; Aged; Albuminuria; Analysis of Variance; Blood Pressure; Cardiovascular Diseases; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Retinopathy; Fasting; Female; Folic Acid; Homocysteine; Humans; Male; Methionine; Middle Aged; Postmenopause; Premenopause; Pyridoxal Phosphate; Regression Analysis; Risk Factors; Vitamin B 12

This study was undertaken to examine the effects of aldose reductase inhibitor (ARI) and vitamin B12 (VB12) on myocardial uptake of iodine-123 metaiodobenzylguanidine (MIBG) in patients with diabetic autonomic disorder. Myocardial scintigraphy using 123I-MIBG was performed on 20 healthy volunteers (controls) and 56 patients with non-insulin-dependent diabetes mellitus (NIDDM), in order to obtain the heart/mediastinum ratio in the initial (HMi) and the delayed images (HMd), and the washout rate (%WR). Thirty-four of the 56 NIDDM patients could be diagnosed as having diabetic autonomic disorder by evaluating their scintigraphic findings in comparison with the controls. Seventeen of these 34 patients received 150 mg/day of doses before meals, and the other 17 received 1.5 mg/day of mecobalamin (VB12 group) in three divided doses after meals, for 3-5 months. According to the presence or absence of clinical symptoms of autonomic or peripheral somatic nerve disorder, the patients were subclassified into four groups. group 1=patients, with autonomic symptoms or somatosensory disorder in the ARI group; group 2=patients without autonomic symptoms or somatosensory disorder in the ARI group; group 3=patients with autonomic symptoms or somatosensory disorder in the VB12 group; and group 4=patients without autonomic symptoms or somatosensory disorder in the VB12 group. After completion of the treatment, myocardial scintigraphy was performed again. Comparing the results obtained before and after the treatment, it was seen that ARI improved only the HMi in group 1 (P=0.046), whereas VB12 significantly improved HMi in the group 3 (P=0.018) and HMi, HMd and %WR in group 4 (P=0.043, P=0.018 and P=0.043, respectively). We conclude that VB12 is more efficacious than ARI in the treatment of diabetic cardiovascular autonomic disorder.

Topics: 3-Iodobenzylguanidine; Adult; Aged; Aged, 80 and over; Aldehyde Reductase; Autonomic Nervous System Diseases; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Enzyme Inhibitors; Female; Heart; Heart Diseases; Humans; Male; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Rhodanine; Thiazolidines; Vitamin B 12

Metformin is contraindicated in patients with renal failure because of the risk of lactic acidosis. This study assessed the complications of metformin treatment in patients with non-insulin-dependent diabetes mellitis with normal and raised serum creatinine. Subjects using metformin with serum creatinine above the upper reference range (120 mu mol/l) were identified (n = 17) from a hospital diabetes register; those with abnormal liver function, cardiac failure, peripheral vascular disease or recent severe illness were excluded. Reference plasma lactate levels were established, mean 1.742 mu mol/l (SD 0.819) using age-matched non-diabetic subjects. Age-matched patients treated with metformin with normal serum creatinine levels formed the control group (n = 24). Details of gastrointestinal disturbance were recorded, and plasma lactic acid and vitamin B12 levels measured. The median total daily dose of metformin in both groups was 1700 mg. The mean plasma lactate in subjects with serum creatinine 80-120 mu mol/l (2.640 mmol/l (SD 1.434) p < 0.02) was higher than non-diabetic control levels while diabetic subjects with serum creatinine 120-160 mumol/l had a mean of 2.272 mmol/l (SD 0.763) p < 0.05. There was no significant difference between the two groups taking metformin, nor any significant difference in the reporting of gastrointestinal symptoms between the groups on metformin (11.76% vs 12.5%). Plasma lactic acid levels are higher in diabetic subjects taking metformin compared with healthy volunteers but, within the diabetic groups, the small elevation of serum creatinine was not associated with higher plasma lactate levels.

Topics: Aged; Case-Control Studies; Creatinine; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Lactates; Male; Metformin; Middle Aged; Renal Insufficiency; Vitamin B 12

Serum vitamin B12, folic acid and haematological data from 147 elderly people (55 males and 92 females) who visited the special clinic for the elderly at Rajvithi Hospital, Bangkok between July and November 1989 were investigated. The individuals studied came from a health-conscious group of the middle socio-economic class in Bangkok. All of them were fairly well except for minor ailments and typical diseases of elderly people such as hypertension, mild to moderate degree coronary heart diseases and non-insulin dependent diabetes mellitus. There was a statistically significant difference in haemoglobin concentrations between males and females. According to the standard haemoglobin cut-off point values of 13 g/dl for males and 12 g/dl for females, anaemia was detected in 22 (15%) of the 147 subjects. The percentage of folic acid deficiency was found to be 20.6 per cent (30 of the 147 cases). Vitamin B12 insufficiency was found in only 6.9 per cent (10 of the 147 cases). No statistically significant correlation between haemoglobin, folic acid and vitamin B12 was found. However, when the data were grouped according to different intervals of increasing haemoglobin concentrations, for females there was a tendency for serum vitamin B12 to decrease, and serum folic acid to increase in both males and females. The results of this study suggest that folate deficiency may play a role in the occurrence of anaemia in elderly people, and therefore, dietary counselling and supplementation of folic acid are recommended.

Topics: Aged; Blood Cell Count; Cardiovascular Diseases; Developing Countries; Diabetes Mellitus, Type 2; Erythrocyte Indices; Female; Folic Acid; Folic Acid Deficiency; Hematocrit; Hemoglobinometry; Humans; Hypertension; Male; Middle Aged; Thailand; Vitamin B 12; Vitamin B 12 Deficiency

It has been postulated that the accumulation of homocysteine in plasma may induce arteriosclerosis. In order to explore the possible contribution of homocysteine to the occurrence of macroangiopathy in patients with non-insulin-dependent diabetes mellitus, the concentrations of total homocysteine in plasma were determined in 52 diabetic patients with clinical macroangiopathy, 84 diabetic patients without macroangiopathy, and 57 non-diabetic control subjects. The levels of total homocysteine in plasma were significantly higher in diabetic patients with macroangiopathy (10.8 +/- 3.8 nmol/ml) than in those without macroangiopathy (8.3 +/- 3.1 mmol/ml, P < 0.001) or non-diabetic subjects (7.5 +/- 2.1 nmol/ml, P < 0.001). Among all diabetic patients, multiple logistic regression analysis after adjustment for age, sex, and systolic blood pressure revealed that high levels of plasma homocysteine were significantly associated with the presence of diabetic macroangiopathy (P = 0.01). By an intramuscular injection of 1000 micrograms methylcobalamin daily for 3 weeks, the plasma levels of homocysteine in 10 diabetic patients were significantly decreased (14.7 +/- 7.5 vs. 10.2 +/- 6.0 nmol/ml, P < 0.01). Our results suggest that plasma homocysteine levels could be one of a number of independent risk factors for macroangiopathy in patients with diabetes mellitus and that they can be reduced by parenteral treatment with methylcobalamin.

Topics: Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Homocysteine; Humans; Injections, Intramuscular; Male; Middle Aged; Risk Factors; Vitamin B 12

The present study was aimed to determine the vitamin status of vitamins A, E, beta-carotene, B1, B2, B6, B12 and folate in plasma using HPLC and vitamins B1, B2 and B6 in erythrocytes using the apoenzyme stimulation test with the Cobas-Bio analyzer in 29 elderly type II diabetic women with (G1: n = 17, age: 68.6 +/- 3.2 years) and without (G2: n = 12, age: 71.8 +/- 2.7 years) diabetic polyneuropathy. The basic parameters as age, hemoglobin A1c, fructosamine and duration of the disease did not differ in both groups. Furthermore, retinopathy was assessed with fundoscopy and nephropathy with creatinine clearance. The creatinine clearance (G1: 50.6 +/- 3.4 vs. G2: 63.6 +/- 3.7 ml/min, 2p < 0.025) and the percentage of retinopathy (G1: 76.5% vs. G2: 16.7%, 2p = 0.002) were different indicating that G1 had significantly more severe late complications than G2. Current plasma levels of all measured vitamins (A, E, beta-carotene, B1, B2, B6, B12 and folate) and the status of B1, B2 and B6 in erythrocytes did not vary between the two groups (2p > 0.1). In summary, we found a lack of association between the actual vitamin condition in plasma and erythrocytes and diabetic neuropathy.

Topics: Aged; Avitaminosis; beta Carotene; Carotenoids; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Folic Acid; Glycated Hemoglobin; Humans; Male; Middle Aged; Neurologic Examination; Pyridoxine; Riboflavin; Thiamine; Vitamin A; Vitamin B 12; Vitamin E; Vitamins

Topics: Aged; Anemia, Pernicious; Diabetes Mellitus, Type 2; Humans; Hypotension, Orthostatic; Male; Recurrence; Vitamin B 12

The most important side-effect of sulfonylureas is hypoglycaemia. According to surveys in Switzerland and in Sweden it occurs at a frequency of about 2 cases per 10,000 treatment years. Mortality is high, about 10%. The syndrome of inappropriate ADH-secretion has been observed almost exclusively during treatment with chlorpropamide. Asymptomatic cases of SIADH-syndrome are quite frequent, hyponatraemia has been observed in 6-10% of diabetics treated with chlorpropamide. The most dangerous side-effect of biguanides is lactic acidosis. It occurs significantly more frequent during treatment with phenformin compared to metformin. Metformin has been reported to lead to lactic acidosis in 0.4 cases per 10,000 treatment years; mortality is about 30%. Mortality of phenformin-associated lactic acidosis is even higher, 70%. Both biguanides, phenformin and metformin, cause relatively frequently vitamin B12-malabsorption (in about 1/3 of the cases). However, symptomatic vitamin B12-deficiency is extremely rare.

Topics: Acidosis; Biguanides; Chlorpropamide; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Inappropriate ADH Syndrome; Malabsorption Syndromes; Male; Middle Aged; Sulfonylurea Compounds; Sweden; Switzerland; Vitamin B 12