Vitamin B12 Deficiency In Metformin-treated Type-2 Diabetes Patients, Prevalence And Association With Peripheral Neuropathy
The association between long-term metformin use and low vitamin B12 levels has been proven. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed considerable variation among the studies. The potential of the deficiency to cause or worsen peripheral neuropathy in type-2 diabetes mellitus (T2DM) patients has been investigated with conflicting results. The aim of the study was to investigate: 1) the prevalence of vitamin B12 deficiency in T2DM patients on metformin; 2) the association between vitamin B12 and peripheral neuropathy; 3) and the risk factors for vitamin B12 deficiency in these patients. In this cross-sectional study, consecutive metformin-treated T2DM patients attending diabetes clinics of two public hospitals in South Africa were approached for participation. Participation included measuring vitamin B12 levels and assessing peripheral neuropathy using Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire. The prevalence of vitamin B12 deficiency (defined by concentrations <150 pmol/L) was determined. Those with NTSS-6 scores >6 were considered to have peripheral neuropathy. The relationship between vitamin B12 and peripheral neuropathy was investigated when the two variables were in the binary and continuous forms. Multiple logistic regression was used to determine risk factors for vitamin B12 deficiency. Among 121 participants, the prevalence of vitamin B12 deficiency was 28.1%. There was no difference in presence of neuropathy between those with normal and deficient vitamin levels (36.8% vs. 32.3%, P = 0.209). Vitamin B12 levels and NTSS-6 scores were not correlated (Spearmans rho =0.056, P = 0.54). HbA1c (mmol/mol) (OR = 0.97, 95% CI: 0.95 to 0.99, P = 0.003) and black race (OR = 0.34, 95% CI: 0.13 to 0.92, P = 0.033) wer Continue reading >>
Metformin Indirect Cause For Neuropathy
Home > English articles > Metformin indirect cause for neuropathy Metformin might be an indirect cause for neuropathy, cmlicating the issues in patients already suffering from neuropathy. The mechanism of this unsuspected long term side effect of metformin, is related to the fact that metformin can deplete the body storage of vitamine B12. Long-term use of metformin is associated with malabsorption of vitamin B(12) (cobalamin; Cbl) and elevated homocysteine (Hcy) and methylmalonic acid (MMA) levels, which may have deleterious effects on peripheral nerves. [ 1 ] Ina recent study (2009) patients using metformine for many years clearly had lower plasma levels of vitamine B12 compared to others not usinbg the bloodsuger lowering drug. Furthermore, the severity of neuropathy in these patients was mopre than could be suspected on the base of diabetes alone. Therefore it is recommended to look into the B12 levels in patients suffering from neuropatrhy and using metformin for a long time: Metformin exposure may be an iatrogenic cause for exacerbation of peripheral neuropathy in patients with type 2 diabetes. Interval screening for Cbl deficiency and systemic Cbl therapy should be considered upon initiation of, as well as during, metformin therapy to detect potential secondary causes of worsening peripheral neuropathy. From the Centre for the study and treatment of neuropathic pain and neuropathy in Soest, the Nertherlands This site helps patients and treating physicians, neurologists, anesthesiologists and other pain specialists to find the best and most up to date research findings related to neuropathy and neuropathic pain and the treatment thereof. In our centre we are specialised in treating patients suffering from neuropathic pain and neuropathy following an Integrated Me Continue reading >>
Metformin Linked To B12 Deficiency
Peripheral Neuropathy Patients Who Take Diabetes Drug May Have Vitamin B12 Deficiency June 8, 2009 -- The popular diabetes drug metformin may contribute to vitamin B12 deficiency , according to a new study. Researchers found that 40% of type 2 diabetes patients using metformin had vitamin B12 deficiency or were in the low-normal range for the essential vitamin. And 77% of metformin users with vitamin B12 deficiency also had peripheral neuropathy , a common form of nerve damage associated with type 2 diabetes . Peripheral neuropathy is a type of nerve damage most often characterized by pain, tingling, and numbness in the hands and feet. Because peripheral neuropathy is such a major complication of diabetes , researchers say the results suggest that people using metformin be screened for vitamin B12 deficiency or supplemented with vitamin B12 . Also, anyone already diagnosed with peripheral neuropathy who uses metformin should be screened for vitamin B12 deficiency. Vitamin B12 is primarily found in meat and dairy products. In the body, it plays a critical role in making red blood cells and keeping the nervous system functioning properly. Symptoms of vitamin B12 deficiency include anemia (low red blood cell count), depression , or dementia ; but often there are no symptoms if the vitamin levels are just a little low. B12 deficiency can lead to nerve symptoms similar to that of diabetic peripheral neuropathy, although the researchers note that they cannot be certain that B12 deficiency contributed to the peripheral neuropathy seen in their study. Vitamin B12 Screening Urged for Metformin Users The study, presented this week at the American Diabetes Associations 69th Annual Scientific Sessions, looked at the prevalence of vitamin B12 deficiency in 76 people with type 2 dia Continue reading >>
Metformin-induced Vitamin B12 Deficiency Presenting As A Peripheral Neuropathy
Diabetic neuropathy is a common problem and can present various clinical presentations such as cranialneuropathy, radiculopathy, plexopathy, mononeuropathy, polyneuropathy and autonomic neuropathy. Clinicalevaluation and use of scoring systems for the evaluation of diabetic polyneuropathy is an important step to getcorrect diagnosis. New informations about the diagnosis of diabetic neuropathy continue to emerge, whichwill lead to correct diagnosis and treatment as well. Diabetic length-dependent sensorimotor polyneuropathy(DSPN) and carpal tunnel syndrome are the most common seen problems. While acute and painful situationswith motor weakness are mostly transient, sensory fibres are predominantly involved in chronic ones. Nerveconduction studies are needed to confirm diagnosis of any type of diabetic neuropathy, but they are normal incases with small fiber involvement. The early diagnosis is crucial because it is well-known that subclinicaldiabetic neuropathy may be reversed or significantly improved with diabetes control. Because neuropathy atthe stage in which only small fibers are affected can be reversed, it is important to diagnose DSPN in thesestages. Skin biopsy taken from the dermatomal area of sural nerve, laser-doppler-imager flare technique, cornealconfocal microscopy are used to assess small fibre dysfunction. The aim of the present review was to evaluateevidence-based diagnosis for any type of neuropathy seen in the patients with diabetes mellitus. Vitamin B12, also known as cobalamin, is a water-soluble vitamin essential for hematopoietic and neurological functions in the body. It is obtained primarily from animal sources such as meat and fish. Many breakfast cereals and nondairy beverages such as soymilk are fortified with vitamin B12. When vitamin B12 f Continue reading >>
Long-term Metformin Use And Vitamin B12 Deficiency In The Diabetes Prevention Program Outcomes Study
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. 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. 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. All parameters decreased to their respective nadir at 1 month and then gradually returned toward baseline values. White blood cells (WBCs) and platelets (PLTs) were the most significantly affected cells. At 1 month, the decrease was 29.6% (P < .0001) for WBCs and 25% (P < .0001) for PLTs, whereas at 12 months, the decrease was 15.5% (P < .0001) and 13% (P < .0001), respectively. Lymphocytes appeared to be more susceptible to I-131 than neutrophils (ANCs). The decreases were small in absolute numbers for red blood cells, hematocrit and hemoglobin not surpassing 10%. Multivariate analysis demonstrated that the ratio of administered prescribed activity-t Continue reading >>
Study Of Vitamin B 12 Deficiency And Peripheral Neuropathy In Metformin-treated Early Type 2 Diabetes Mellitus Roy Rp, Ghosh K, Ghosh M, Acharyya A, Bhattacharya A, Pal M, Chakraborty S, Sengupta N - Indian J Endocr Metab
Diabetes mellitus (DM) is associated with risk of cardiovascular diseases, which cannot be fully justified by important risk factors such as hyperglycemia, [1] hypertension, [2] and dyslipidemia. [3] Among all risk factors, homocysteine (Hcy) is recognized as an independent, [4] and potentially modifiable, [5] risk factor that may be strongly linked to cardiovascular prognosis in Type 2 diabetes. [6] It can also be a determinant of microalbuminuria and diabetic retinopathy. Hcy is produced during the demethylation of methionine. It is normally metabolized by two pathways, remethylation and transsulfuration. Remethylation acts as a catalyst for methionine synthase. In this reaction, 5-methyltetrahydrofolate is a methyl group donor and Vitamin B 12 is a cofactor. Several studies found decreased serum Vitamin B 12 level among metformin-treated diabetes patients [7] probably due to malabsorption. [8] Hence, during metformin treatment, Hcy level might increase, but data on this issue are contradictory. [9] , [10] With this idea in mind, we conducted a study at B.R. Singh Hospital, Kolkata, among the Type 2 diabetic patients who are on metformin for at least 2 years but not more than 3 years after they were first detected with diabetes and compared them with patients not on metformin for the same duration. The effects of metformin treatment on serum levels of Hcy, Vitamin B 12 and folate level in patients with Type 2 diabetes were studied. To study the blood level of Vitamin B 12 , folic acid, and Hcy in metformin-treated early Type 2 DM To study the evidence of peripheral neuropathy in metformin-treated early Type 2 DM. A hospital-based, comparative, descriptive study was conducted in the Department of Medicine, B.R. Singh Hospital, Kolkata, during August 2010-June 2012. A Continue reading >>
Can Metformin Use Increase The Risk Of Diabetic Neuropathy?
Allen Jacobs DPM FACFAS Metformin (Glucophage, Bristol-Myers Squibb) is a commonly utilized biguanide agent for the treatment of diabetes. Increasingly, it appears that metformin may paradoxically increase the risk of neuropathy in the patient with diabetes. Therefore, when you see a patient with diabetes who is taking metformin, greater surveillance may be necessary for the presence of sensory, autonomic and motor neuropathy. Wile and colleagues noted that metformin increases homocysteine levels as well as methylmalonic acid levels, both contributing factors to neuropathy.1 The study noted the increased frequency and severity of diabetic neuropathy in patients taking metformin, as well as reduced levels of B12. In a recent issue of Diabetes Care, Palomba and co-workers also affirmed that metformin raises serum homocysteine levels with resultant endothelial dysfuction.2 They suggested that folate supplementation may be helpful in reducing this effect. The suggestion that metformin may act to raise homocysteine levels is not new as others have suggested that more than six months of exposure to metformin results in rising homocysteine levels.3,4 Studies have previously suggested that elevated levels of homocysteine to be operative may play a role in the evolution of diabetic neuropathy.5 Metformin interferes with the absorption of vitamin Band, as a result, the chronic use of metformin may act to reduce vitamin B levels in the patient with diabetes. Vitamin B compounds are critical for normal nerve health and function. Accordingly, a reduction in the level of vitamin B may result in an increased incidence of neuropathy in those taking metformin.6 In addition, L-methyl folate (Metanx, Pamlab), the active form of folic acid, directly stimulates nitric oxide production, incr Continue reading >>
Can Metformin Cause Neuropathy?
Remember your last annual foot check? They poke and prod your feet to check your sensation is normal. They ask you questions about your shoes and whether cuts and blisters heal properly. You’re hoping that they tell you everything is normal, right? The biggest worry of nearly every diabetic I talk to is amputation. It can’t even be called a phobia, a phobia is an irrational fear. It’s totally rational to be terrified of amputation if you are a type 2 diabetic. Amputations happen to 135 people a week in the UK, add a zero onto that number for the States. A diabetic is 25 times more likely to lose a foot than the general population and 70% of all amputations worldwide are in diabetics. Nerve damage is where it all starts, that’s the reason why you go for an annual foot check. The doctor is trying to pick up the early signs to protect you. High sugars are known to cause nerve damage. But what if the most commonly prescribed medication for diabetics could be adding to the problem? Metformin and B12 If you have type 2 diabetes you are more likely to be deficient in specific hormones and vitamins, like testosterone and vitamin D – that’s a topic for another time though. Metformin causes B12 deficiency in 30% of users. Metformin acts in your digestive tract and can reduce the absorption of B12 from the food you eat. Guess what B12 deficiency causes? Neuropathy! Yes, B12 deficiency on it’s own causes nerve damage. If you have diabetic neuropathy and B12 deficiency that is definitely going to accelerate the damage. The risk increases with a higher dose and the length of time you’ve been taking metformin for. In his article published in Medscape, Dr Bell states: “However, a common, potentially damaging, and well-documented complication of metformin—vitamin B12 Continue reading >>
Metformin Users Risk Vitamin Deficiency
European diabetes researchers warn that many people with diabetes might be at risk of health problems because of this side effect. A new report suggests that prolonged use of metformin could lead to a vitamin B12 deficiency. This vitamin deficiency could cause peripheral neuropathy (nerve damage in the hands and feet) if not properly treated, according to the European Association for the Study of Diabetes. However, there are B12 supplements one can take to offset a deficiency, if properly diagnosed with the deficiency. The recommendations come from data collected from several studies. In 2006, for example, a Netherlands-based study tracked 390 Type 2 patients who were taking 850 mg of metformin or a placebo three times daily for an average of 4.3 years. The study found that continued use of metformin increased the risk of a B12 deficiency by 19 percent, and the risk climbed higher for those over 50. The findings suggest that nearly one out of every five people taking metformin might have a B12 deficiency. Serious B12 deficiency can lead to a host of potential ailments, including weakness and pain caused by nerve damage, cognitive decline, depression, fatigue, and memory loss. These symptoms can be easily misdiagnosed as diabetes symptoms, or missed altogether. If a deficiency is left untreated, however, the symptoms have the potential to become irreversible, especially for people over 50. Vitamin B12 is essential in the body to make red blood cells, nerves, and DNA, and provides nutrients to the brain. B12 cannot be produced internally, but is absorbed from food. Metformin can hinder the bodys natural ability to absorb B12, so supplements should be taken to stop the deficiency from becoming symptomatic. There are many good B12 supplements on the market, particularly be Continue reading >>
An Observational Study Of Vitamin B12 Levels And Peripheral Neuropathy Profile In Patients Of Diabetes Mellitus On Metformin Therapy - Sciencedirect
Volume 12, Issue 1 , JanuaryMarch 2018, Pages 51-58 An observational study of vitamin b12 levels and peripheral neuropathy profile in patients of diabetes mellitus on metformin therapy Author links open overlay panel KameshGupta A descriptive, observational study was completed in a tertiary care hospital between November 2014 and March 2016. Fifty consecutive patients of Type 2-Diabetes Mellitus who had been on metformin therapy for at least three months were included in our study. Several Parameters were compared with vitamin B12 levels and severity of peripheral neuropathy (using Toronto Clinical Scoring System (TCSS) and Nerve Conduction Velocity). These included the duration of diabetes, duration of metformin usage, dietary history, and HbA1c levels. Definite B12 deficiency was defined as B12<150pg/ml and possible B12 deficiency as <220pg/ml. In our study, we found a negative correlation between duration of metformin use and Vitamin B12 levels(r=0.40). The mean Vitamin B12 levels seen in our study was 212.3pg/mL. There is a positive correlation between the duration of metformin therapy and peripheral neuropathy (r=0.40). The mean TCSS score was 6.8. The percentage of patients with mild neuropathy was 28%, with moderate neuropathy was 20% and severe neuropathy in 12% of the patients. The average duration of metformin use in patients without peripheral neuropathy was 5.5yrs whereas the average length of metformin use in patients with peripheral neuropathy was 10.4 yrs. Patients on long-term metformin therapy are at a high risk for Vitamin B12 deficiency and peripheral neuropathy. Interval Screening for peripheral neuropathy is recommended for patients on metformin even if Vitamin B12 levels appear to be normal. Continue reading >>
Metformin-induced Vitamin B12 Deficiency Presenting As A Peripheral Neuropathy.
South Med J. 2010 Mar;103(3):265-7. doi: 10.1097/SMJ.0b013e3181ce0e4d. Metformin-induced vitamin B12 deficiency presenting as a peripheral neuropathy. Southside Endocrinology and Division of Diabetes, Endocrinology, and Metabolism, University of Alabama Medical School, Birmingham, AL 35205, USA. [email protected] Chronic metformin use results in vitamin B12 deficiency in 30% of patients. Exhaustion of vitamin B12 stores usually occurs after twelve to fifteen years of absolute vitamin B12 deficiency. Metformin has been available in the United States for approximately fifteen years. Vitamin B12 deficiency, which may present without anemia and as a peripheral neuropathy, is often misdiagnosed as diabetic neuropathy, although the clinical findings are usually different. Failure to diagnose the cause of the neuropathy will result in progression of central and/or peripheral neuronal damage which can be arrested but not reversed with vitamin B12 replacement. To my knowledge, this is the first report of metformin-induced vitamin B12 deficiency causing neuropathy. Continue reading >>
Letters To The Editor
Use of Metformin Is a Cause of Vitamin B12 Deficiency Am Fam Physician.2004Jan15;69(2):264-266. to the editor: I read with great interest the superb review of vitamin B12 deficiency by Drs. Oh and Brown, 1 and I believe it is one of the most clinically useful papers written about this topic. However, I noticed that among the etiologies of food-cobalamin malabsorption, no mention was made of metformin use, which is an unfamiliar, yet increasingly common, cause of cobalamin deficiency in adults. Small studies and case reports have shown that 10 to 30 percent of patients who are prescribed metformin show signs of reduced vitamin B12 absorption leading to clinically significant abnormalities in about 30 percent of cases. A recent cohort study 2 conducted at the University Hospital of Strasbourg, France, examined patients with a diagnosis of metformin-associated cobalamin deficiency and concluded that metformin causes at least 6 percent of the incidence of vitamin B12 deficiency and that resulting hematologic abnormalities and peripheral neuropathy are quite common. Different mechanisms have been proposed, including alterations in intestinal mobility, bacterial overgrowth, and interactions with a complex of intrinsic-factor/vitamin B12 and cubilin, an endocytic receptor involved in the absorption of cobalamin. B12-intrinsic factor complex uptake by ileal cell surface, a calcium-dependent process, also is affected by metformin because of impaired calcium availability. 3 5 During the past five years, the increasing knowledge of the role of insulin resistance in type 2 diabetes has led to a linear widespread use of biguanides for the treatment of this condition and other conditions associated with insulin resistance, such as metabolic syndrome, nonalcoholic fatty liver disease Continue reading >>
Metformin Link To Vitamin B12 Deficiency, Neuropathy In Diabetes
Metformin Link to Vitamin B12 Deficiency, Neuropathy in Diabetes STOCKHOLM Metformin-related vitamin B12 deficiency might contribute to clinically significant peripheral neuropathy in diabetes patients, new research suggests. Guidelines from European Association for the Study of Diabetes (EASD) and the American Diabetes Association do mention vitamin B12 deficiency as a risk of metformin treatment for type 2 diabetes, but they don't make recommendations for screening or supplementation, said Mattijs Out, MD, an internist of vascular medicine at Bethesda Diabetes Research Center, Hoogeveen, the Netherlands, who presented the findings last week at the European Association for the Study of Diabetes 2015 Meeting . "This is important. The consequences of vitamin B12 deficiency, like neuropathy or mental changes, may be profound. Even more, they may be difficult to diagnose, because they may be ascribed to old age or diabetes itself and may be or become irreversible. On the other hand, vitamin B12 deficiency is relatively easy to diagnose, and treatment is easy, cheap, and effective," Dr Out commented. Previous research from Dr Out's group and others has linked metformin use to vitamin B12 deficiency (<150 pmol/L), raising concern that the drug may be contributing to peripheral neuropathy separate from the effect of the diabetes itself. In the current study, Dr Out and colleagues examined, for the first time, a very specific biomarker for tissue B12 deficiency, methylmalonic acid (MMA), and examinedthe impact of that on a validated neuropathy score; they found that the overall increase in MMA outweighed the benefit derived from metformin's glucose-lowering effect. But during the question-and-answer period, some doctors expressed skepticism, stating that they hadn't seen very Continue reading >>
This Top Prescribed Diabetes Medication Could Be Causing Your Pain (and The One Supplement That Can Stop It)
This Top Prescribed Diabetes Medication Could Be Causing Your Pain (and the One Supplement That Can Stop It) Oh, yes. It feels like theres lightning shooting through my hands and feet. Huh? Whats going on with your extremities? Eh, I am not really sure my doctor says its neuropathy. I think its just a part of having diabetes. This is a conversation I once had while doing a patient assessment. I will never forget how she described her pain. I could almost see little lightning bolts flashing through her fingers and toes as she described the ever-present buzzing and electric feelings in her extremities. At the time, I was working at an inpatient mental health unit, but since some anti-psychotic medications increase the risk of diabetes, many of the patients I saw were diabetic.1 It was all too common to hear them complain of numbness, shooting and stabbing pains, tingling in their hands and feet, loss of balance and reflexes, and even extreme skin sensitivity all symptoms of neuropathy. Some patients even had to rely on wheelchairs to get around during especially painful bouts. It was difficult to watch this seemingly matter-of-fact situation. But as it turns out, suffering from neuropathy may not be a consequence of just diabetes. This painful and debilitating condition maybe be due to a side effect of a diabetic medication vitamin B-12 deficiency. And not just any diabetic medication, the most prescribed diabetic medication: metformin. 2 In fact, a study found 40 percent of metformin users to be B-12 deficient. And of those metformin users, three-quarters experienced neuropathy .3 Plus, 22 percent of diabetics are already B-12 deficient, regardless of their medication regimes, making the metformin related B12 deficiency statistics even more significant.4 So that leaves Continue reading >>
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Could This Be A Simple Fix For A Daily Source Of Torment?
There’s no doubt that diabetic nerve pain is agonizing. It’s a form of nerve damage that can cause numbness and a shooting, burning sensation — like pins and needles — especially in your hands and feet. You can become so sensitive that even having a bed sheet touch you is excruciating. And if you have diabetes, you’ll be told that’s just another side effect of the disease. But what if it isn’t? What if this agony was actually a side effect of the medication you’re taking for diabetes? And even more importantly, what if the difference between sleepless nights and days filled with pain could be stopped with an inexpensive, easy-to-find vitamin? Well, some new research has found that very well may be the case. The power of BThe consequences of vitamin B12 deficiency, (such as) neuropathy (nerve pain) or mental changes, may be profound.” That’s how Mattijs Out, MD, an internist of vascular medicine at Bethesda Diabetes Research Center in the Netherlands, described what his group found in some brand new research. And yes, he’s talking about vitamin B12 — that inexpensive supplement you can find just about everywhere. A B12 deficiency can range from memory loss and depression to heart palpitations, shortness of breath and digestive ailments. And they also can include peripheral neuropathy — that horrible nerve pain said to be frequently caused by type 2 diabetes. But what the Dutch researchers blamed for a very common cause of B12 depletion wasn’t diabetes, but rather one of the world’s most commonly used drugs for treating it — metformin. The study was actually done to support earlier work by Dr. Out and his team. Research they did five years ago that led them to conclude that long-term use of metformin increased the risk of B12 deficiency by Continue reading >>
