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Metformin Toxicology

Fatal Metformin Overdose: Case Report And Postmortem Biochemistry Contribution

Fatal Metformin Overdose: Case Report And Postmortem Biochemistry Contribution

Abstract Metformin is an oral antihyperglycemic agent used in the management of type 2 diabetes mellitus. Lactic acidosis from metformin overdose is a rare complication of metformin therapy and occurs infrequently with therapeutic use. Fatal cases, both accidental and intentional, are extremely rare in clinical practice. Metformin is eliminated by the kidneys, and impaired renal function can result in an increased plasma concentration of the drug. In this report, we describe an autopsy case involving a 70-year-old woman suffering from diabetes mellitus and impaired renal function who received metformin treatment. Metformin concentrations in the peripheral blood collected during hospitalization and femoral blood collected during autopsy were 42 and 47.3 µg/ml, respectively. Lactic acidosis (29.10 mmol/l) was objectified during hospitalization. Furthermore, postmortem biochemistry allowed ketoacidosis to be diagnosed (blood β-hydroxybutyrate, 10,500 µmol/l). Death was attributed to lactic acidosis due to metformin intoxication. Increased plasma concentrations of the drug were attributed to severely impaired renal function. The case emphasizes the usefulness of performing exhaustive toxicology and postmortem biochemistry towards the more complete understanding of the pathophysiological mechanisms that may be involved in the death process. Discover the world's research 14+ million members 100+ million publications 700k+ research projects Join for free (500 mg at 8 a.m., 1,000 mg at 1 p.m., and 1,000 mg at 7 (500 mg at 8 a.m., 1,000 mg at 1 p.m., and 1,000 mg at 7 Tab l e 1 The results of biochemical antemortem and postmortem investigations Treatment Analyte and blood reference values Urea nitrogen Creatinine Lactate and pH K Na Cl BHB 65–105 mg/dl 5–6.6 % 8.1–17.9 Continue reading >>

Toxicity And Toxicokinetics Of Metformin In Rats

Toxicity And Toxicokinetics Of Metformin In Rats

Advanced HF (heart failure) is associated with altered substrate metabolism. Whether modification of substrate use improves the course of HF remains unknown. The antihyperglycaemic drug MET (metformin) affects substrate metabolism, and its use might be associated with improved outcome in diabetic HF. The aim of the present study was to examine whether MET would improve cardiac function and survival also in non-diabetic HF. Volume-overload HF was induced in male Wistar rats by creating ACF (aortocaval fistula). Animals were randomized to placebo/MET (300 mgkg(-1) of body weightday(-1), 0.5% in food) groups and underwent assessment of metabolism, cardiovascular and mitochondrial functions (n=6-12/group) in advanced HF stage (week 21). A separate cohort served for survival analysis (n=10-90/group). The ACF group had marked cardiac hypertrophy, increased LVEDP (left ventricular end-diastolic pressure) and lung weight confirming decompensated HF, increased circulating NEFAs (non-esterified 'free' fatty acids), intra-abdominal fat depletion, lower glycogen synthesis in the skeletal muscle (diaphragm), lower myocardial triacylglycerol (triglyceride) content and attenuated myocardial (14)C-glucose and (14)C-palmitate oxidation, but preserved mitochondrial respiratory function, glucose tolerance and insulin sensitivity. MET therapy normalized serum NEFAs, decreased myocardial glucose oxidation, increased myocardial palmitate oxidation, but it had no effect on myocardial gene expression, AMPK (AMP-activated protein kinase) signalling, ATP level, mitochondrial respiration, cardiac morphology, function and long-term survival, despite reaching therapeutic serum levels (2.20.7 g/ml). In conclusion, MET-induced enhancement of myocardial fatty acid oxidation had a neutral effect on ca Continue reading >>

The Toxicology Takedown #2 January 2015

The Toxicology Takedown #2 January 2015

The Toxicology Takedown #2 January 2015 A 15-Year-old female presents to the hospital 4 hours after ingestion of her diabetic fathers medication following a family dispute. Her family is unable to account for 75 x 5 mg glipizide and 29 x 500 mg metformin tablets. On arrival, she is vomiting and appears anxious and slightly sweaty with Glasgow Coma Score of 14/15. Her vital signs are pulse rate 90 bpm, blood pressure 110/75 mmHg, respiratory rate 18/min, and temperature of 36.8 C. A bedside blood glucose level is 54 mg/dl. Whats the immediate threat to life for this patient? Whats the mechanism of action of sulfonylurea medications, and how is it problematic in the management in toxicity? What are the antidotes for sulfonylurea toxicity? Whats concerning about metformin toxicity? What is the name of the syndrome that can develop in overdose and how it is managed? With respect to the ingestion of a potentially toxic amount of sulfonylureas, the immediate threat to life for this patient is hypoglycemia with potential progression to seizures and coma. This patient requires an IV line and administration of a bolus of 50 ml of 50% dextrose solution for correction of hypoglycemia and administration of another medication of minimize recurrent hypoglycemia. Glipizide is one of many sulfonylurea oral hypoglycemic agents. It exerts its effect by stimulating insulin release from the beta islet cells of the pancreas. All sulfonylureas inhibit ATP-sensitive K+ channels. This inhibition increases the membrane potential and depolarizes the cell. A subsequent influx of extracellular calcium ions through voltage-dependent calcium channels Occurs. An increase in the free intracellular calcium level is the signal, or second messenger, that triggers exocytosis and the release of insulin. F Continue reading >>

Survival Following A Metformin Overdose Of 63 G: A Case Report

Survival Following A Metformin Overdose Of 63 G: A Case Report

Survival Following a Metformin Overdose of 63 g: A Case Report Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus Amtssygehus, DK8000 Aarhus C, Denmark Author for correspondence: Jrgen Rungby, Department of Endocrinology C, Aarhus University Hospital, Tage Hansensgade, DK8000 Aarhus C, Denmark (fax +45 8949 7659, Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus Amtssygehus, DK8000 Aarhus C, Denmark Author for correspondence: Jrgen Rungby, Department of Endocrinology C, Aarhus University Hospital, Tage Hansensgade, DK8000 Aarhus C, Denmark (fax +45 8949 7659, Please review our Terms and Conditions of Use and check box below to share full-text version of article. I have read and accept the Wiley Online Library Terms and Conditions of Use. Use the link below to share a full-text version of this article with your friends and colleagues. Learn more. Metformin is a biguanide used in the treatment of type 2 diabetes mellitus. It lowers hepatic glucose production and peripheral insulin resistance. Hypoglycaemia is seen only after intake of toxic doses or in combination with other antidiabetic drugs or after prolonged fasting. As metformin is excreted by the kidneys, care must be taken in renal insufficiency or liver disease because of risk of lactic acidosis. Large overdoses of metformin can lead to lactic acidosis as well. Suicide with metformin is rare. Intake of 35 g of metformin has been shown to be lethal ( Teale et al. 1998 ). In the present paper we report on the treatment and outcome of a 70 year old man after ingestion of 63 g of metformin. Previously, survival after intake of up to 50 g has been described. A 70 year old man with type 2 diabetes mellitus who was being treated with metformin 850 mg twice daily and glimepiride Continue reading >>

Emdocs.net Emergency Medicine Educationmetformin Associated Lactic Acidosis (mala): Ed-focused Management - Emdocs.net - Emergency Medicine Education

Emdocs.net Emergency Medicine Educationmetformin Associated Lactic Acidosis (mala): Ed-focused Management - Emdocs.net - Emergency Medicine Education

Metformin Associated Lactic Acidosis (MALA): ED-focused management Authors: Richard B. Moleno DO, MS (EM Resident Physician, UTSW/Parkland Memorial Hospital) and Ashley Haynes MD (Toxicology Fellow, UTSW/Parkland Memorial Hospital) // Edited by: Alex Koyfman MD (@EMHighAK) and Stephen Alerhand MD (@SAlerhand) A 43 year-old woman with a past medical history of depression, DM, and HTN presents to the Emergency Department 2.5 hours after a suicide attempt by prescription drug ingestion. She reports that feeling upset with her home situation and ingested a handful of Metformin 500mg tablets in addition to drinking three 40oz beers. Initial vitals are HR 109, BP 165/96, Temp 36.4 and SpO2 on RA of 98%. Review of pill count from the Metformin bottle provided by EMS is significant for 30 missing pills (15g of Metformin). Being the astute and vigilant resident physician that you are, you quickly ask the nurse to move the patient into a critical care booth, as you remember learning about the dangers of Metformin during your toxicology rotation. Nursing begrudgingly complies. What should be done next? Metformin, a biguanide derived from guanidine, was introduced in the 1950s as a treatment for diabetes, and remains widely used today with 40 million prescriptions filled worldwide in 2008 (1). Lactic acidosis is the primary toxicity of concern, with an estimated incidence of 0.03 per 1000 patients/year (2). Metformin-associated lactic acidosis may happen with therapeutic doses or after an acute overdose. Currently the data is mixed as to which situation leads to a more severe pattern of illness. Common initial symptoms are non-specific and include nausea, vomiting, diarrhea, abdominal pain, malaise, and decreased oral intake. In severe cases, altered mental status, tachypnea, hypo Continue reading >>

A Fatal Case Of Metformin Poisoning

A Fatal Case Of Metformin Poisoning

Click to increase image sizeClick to decrease image size Metformin hydrochloride, a biguanide medicine, is used to improve glucose tolerance in patients with type II noninsulin dependent diabetes mellitus. This medication is considered safe if not used in the presence of contraindications like renal failure, liver disease, alcohol abuse, or congestive heart failure [1] . Severe lactic acidosis, which carries a high potential mortality risk, has been reported in patients following overdoses [2] [3] . This letter is a reminder of the severe toxicity that can result from metformin overdose. A 42yrold male was admitted to the hospital with confusion and abdominal pain. He had a 10yr history of noninsulin dependent diabetes mellitus. One year ago, metformin was stopped and the patient was placed on insulin therapy. His current medications included insulin, clarithromycin, domperidone, ibuprofen, buflomedil (a peripheral vasodilator), and tiaprofenic acid (a nonsteroidal antiinflammatory drug). On the admission, the patient was conscious but confused. He mentioned attempting suicide the day before but could not specify the drug. His temperature was 35.5C, pulse was 70 beats per minute (bpm), blood pressure 100/45 mmHg, respiratory rate 38 bpm. He was oliguric and appeared dehydrated. His initial arterial blood gas results were pH 6.88, pO2 159 mmHg, pCO2 13.8 mmHg, SaO2 97%, and bicarbonate 2.9 mmol/L. The lactate concentration was 27 mmol/L. Other laboratory values were sodium 143 mmol/L, potassium 4.1 mmol/L, chloride 99 mmol/L, calcium 2.7 mmol/L, urea nitrogen 4.2 mmol/L, creatinine 163 mol/L, and glucose 16.4 mmol/L. The blood count was hemoglobin 18.7 g/dL, hematocrit 57.2%, white blood cells 19,260/mm3 (neutrophils 76%), and platelet count 336,000/mm3. Toxicologic scr Continue reading >>

6 Pearls About Metformin And Lactic Acidosis

6 Pearls About Metformin And Lactic Acidosis

Metformin accumulation: Lactic acidosis and high plasmatic metformin levels in a retrospective case series of 66 patients on chronic therapy. Vecchio S et al. Clin Toxicol 2014 Feb;52:129-135. Metformin is frequently used alone or in combination to treat type 2 diabetes. It lowers blood glucose by decreasing hepatic gluconeogenesis, predominantly by inhibiting mitochondrial respiratory chain complex I. The drug is eliminated mainly by the kidneys, and acute or chronic renal insufficiency may allow accumulation of the drug with increasing levels. A small percentage of patients on metformin develop severe lactic acidosis. There has been an ongoing controversy as whether this acidosis is metformin-associated or metformin-induced. This paper, from the Pavia Poison Control Centre in Northern Italy, helps shed light on this question. The authors retrospectively reviewed patients admitted to their toxicology unit over a 5-year period. Eligible patients were on chronic metformin therapy at the time of admission, had lactic acidosis (pH < 7.35, arterial lactate > 5 mmol/L), and elevated metformin levels (plasma metformin > 4 mcg/ml). Cases of acute overdose were excluded. The study objective was to correlate the metformin levels with measured pH, lactate levels, renal function, and mortality rate. Sixty-six eligible patients were identified. All patients presented with acute renal failure and severe lactic acidosis (mean pH 6.91, mean lactate 14.36 mmol/L). About half the patients had a pre-existing contraindication to metformin therapy, predominantly renal failure and/or heart disease. Approximately 75% presented after several days of a mild gastrointestinal prodrome with nausea, vomiting, and diarrhea; this may either have represented the initial manifestations of metformin po Continue reading >>

Metformin - National Library Of Medicine Hsdb Database

Metformin - National Library Of Medicine Hsdb Database

For more information, search the NLM HSDB database. IDENTIFICATION AND USE: Metformin is antihyperglycemic, not hypoglycemic agent. It does not cause insulin release from the pancreas and does not cause hypoglycemia, even in large doses. HUMAN EXPOSURE AND TOXICITY: Metformin is believed to work by inhibiting hepatic glucose production and increasing the sensitivity of peripheral tissue to insulin. It does not stimulate insulin secretion, which explains the absence of hypoglycemia. Metformin also has beneficial effects on the plasma lipid concentrations and promotes weight loss. Accumulation of metformin may occur in patients with renal impairment, and such accumulation rarely can result in lactic acidosis, a serious, potentially fatal metabolic disease. Lactic acidosis constitutes a medical emergency requiring immediate hospitalization and treatment; lactic acidosis is characterized by elevated blood lactate concentrations, decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. Lactic acidosis also may occur in association with a variety of pathophysiologic conditions, including diabetes mellitus, and whenever substantial tissue hypoperfusion and hypoxemia exist. Approximately 50% of cases of metformin-associated lactic acidosis have been reported to be fatal. No evidence of mutagenicity or chromosomal damage was observed in in vitro test systems, including human lymphocytes assay. ANIMAL STUDIES: No evidence of carcinogenic potential was seen in a 104-week study in male and female rats receiving metformin hydrochloride dosages up to and including 900 mg/kg daily or in a 91-week study in male and female mice receiving metformin hydrochloride at dosages up to and including 1500 mg/kg daily. Cancer preventive e Continue reading >>

Toxicology Of Oral Antidiabetic Medications

Toxicology Of Oral Antidiabetic Medications

Toxicology of Oral Antidiabetic Medications Am J Health Syst Pharm.2006;63(10):929-938. In 1996, the Food and Drug Administration approved the labeling for metformin (dimethylbiguanide), the only biguanide currently available in the United States. Phenformin, the other previously available biguanide, was withdrawn from the market in 1977 because of an association with lactic acidosis. Buformin, another biguanide, is not available in the United States. The complex of mechanisms of action of metformin is multifaceted but appears to include delayed glucose absorption, increased intestinal glucose utilization, increased intestinal lactate production, inhibition of hepatic gluconeogenesis, decreased lipid oxidation, decreased free fatty acid concentration, and increased peripheral insulin-related glucose uptake.[ 70 ] Metformin absorption is incomplete, with 20-30% found in the feces. Oral bioavailability is 40-60%, depending on the dose ingested, with greater doses producing lower bioavailability.[ 71 ] The reduced bioavailability may result from the drug binding by the intestinal wall.[ 72 ] The rate of absorption is slower than the rate of elimination, which makes absorption a rate-limiting step in the elimination half-life.[ 73 , 74 ] Absorption, in therapeutic doses, is expected to be complete in 6 hours. In an overdose situation involving massive doses, absorption may be prolonged. About 90% of the absorbed metformin is eliminated through the kidneys within the first 24 hours in patients with normal renal function.[ 72 ] Metformin has no metabolites. Metformin is the second most commonly prescribed oral antidiabetic medication in both monotherapy and combination therapy.[ 11 ] In 2004, metformin had the highest number of reports to U.S. poison control centers and the Continue reading >>

Toxicity And Toxicokinetics Of Metformin In Rats

Toxicity And Toxicokinetics Of Metformin In Rats

Volume 243, Issue 3 , 15 March 2010, Pages 340-347 Toxicity and toxicokinetics of metformin in rats Get rights and content Metformin is a first-line drug for the treatment of type 2 diabetes (T2D) and is often prescribed in combination with other drugs to control a patient's blood glucose level and achieve their HbA1c goal. New treatment options for T2D will likely include fixed dose combinations with metformin, which may require preclinical combination toxicology studies. To date, there are few published reports evaluating the toxicity of metformin alone to aid in the design of these studies. Therefore, to understand the toxicity of metformin alone, Crl:CD(SD) rats were administered metformin at 0, 200, 600, 900 or 1200mg/kg/day by oral gavage for 13weeks. Administration of 900mg/kg/day resulted in moribundity/mortality and clinical signs of toxicity. Other adverse findings included increased incidence of minimal necrosis with minimal to slight inflammation of the parotid salivary gland for males given 1200mg/kg/day, body weight loss and clinical signs in rats given 600mg/kg/day. Metformin was also associated with evidence of minimal metabolic acidosis (increased serum lactate and beta-hydroxybutyric acid and decreased serum bicarbonate and urine pH) at doses 600mg/kg/day. There were no significant sex differences in mean AUC024 or Cmax nor were there significant differences in mean AUC024 or Cmax following repeated dosing compared to a single dose. The no observable adverse effect level (NOAEL) was 200mg/kg/day (mean AUC024=41.1g h/mL; mean Cmax=10.3g/mL based on gender average week 13 values). These effects should be taken into consideration when assessing potential toxicities of metformin in fixed dose combinations. Continue reading >>

Metformin-associated Lactic Acidosis Following Intentional Overdose Successfully Treated With Tris-hydroxymethyl Aminomethane And Renal Replacement Therapy

Metformin-associated Lactic Acidosis Following Intentional Overdose Successfully Treated With Tris-hydroxymethyl Aminomethane And Renal Replacement Therapy

Metformin-Associated Lactic Acidosis following Intentional Overdose Successfully Treated with Tris-Hydroxymethyl Aminomethane and Renal Replacement Therapy Ngan Lam ,1,2 Gurbir Sekhon ,3and Andrew A. House 1,3 1Division of Nephrology, Department of Medicine, Western University, London, ON, Canada N6A 3K7 2London Health Sciences Centre, Kidney Clinical Research Unit, Victoria Hospital, Westminster Tower 800 Commissioners Road East, London, ON, Canada N6A 4G5 3Department of Medicine, Western University, London, ON, Canada N6A 3K7 Received 19 February 2012; Accepted 6 May 2012 Academic Editors: Y.Fujigaki, D.Packham, A.Papagianni, and H.Schiffl Copyright 2012 Ngan Lam et al. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A 43-year-old woman was brought to the hospital with severe metabolic acidosis (pH 6.56, bicarbonate 3 mmol/L, and lactate 18.4 mmol/L) and a serum creatinine of 162 mol/L with a serum potassium of 7.8 mmol/L. A delayed diagnosis of metformin-associated lactic acidosis was made, and she was treated with tris-hydroxymethyl aminomethane (THAM) and renal replacement therapy (RRT). Following a complete recovery, she admitted to ingesting 180 tablets (90 grams) of metformin. Her peak serum metformin concentration was 170 g/mL (therapeutic range 1-2 g/mL). Our case demonstrates an intentional metformin overdose resulting in lactic acidosis in a nondiabetic patient who was successfully treated with THAM and RRT. Metformin is an oral antihyperglycemic agent that is the first-line therapy for noninsulin-dependent diabetes mellitus [ 1 ]. Although the adverse event rate is 2030%, the majority of the Continue reading >>

Metformin Litfl Life In The Fast Lane Medical Blog

Metformin Litfl Life In The Fast Lane Medical Blog

Metformin rarely causes hypoglycaemia but it can cause a profound lactic acidosis in overdose and in patients with renal failure. Used therapeutically to inhibit glucogenogenesis and stimulate peripheral glucose uptake, in toxic doses it causes a profound lactaemia. All the mechanisms are unclear but it is in part due to the inhibition of gluconeogenesis (which lactate is required). Therefore in healthy individuals there is some build up of lactate, this is normally excreted in the urine but at impaired renal function or an acute overdose there is excess lactate. It is not metabolised and excretion relies solely on renal excretion A lactic acidosis in the context of therapeutic metformin has a high mortality rate and an underlying cause (sepsis) needs to be managed Metformin overdose is usually benign but doses > 10 grams are concerning Lactic acidosis will occur in these individuals who are susceptible (renal, cardiac, respiratory failure) or in patients who have ingested co-ingestants or are on medications that impair cardiac and renal function Severe lactic acidosis usually manifests with non-specific symptoms several hours later but can progress to coma, shock and death Children: Unintentional ingestion of up to 1700mg is benign. Hypoglycaemia, if present can be managed with dextrose . Severe acidosis and hyperkalaemia may require the administration of sodium bicarbonate (1 2 mmol/kg). However, it is likely the patient is already hyperventilating to compensate for the metabolic acidosis, haemodialysis is the ultimate priority. If in a patient on therapeutic metformin, stop further administration and seek the underlying cause for their deterioration (sepsis, acute kidney injury) Screening: 12 lead ECG, BSL, Paracetamol level 50 grams of charcoal to the co-operative Continue reading >>

Metformin Scavenges Methylglyoxal To Form A Novel Imidazolinone Metabolite In Humans

Metformin Scavenges Methylglyoxal To Form A Novel Imidazolinone Metabolite In Humans

Metformin Scavenges Methylglyoxal To Form a Novel Imidazolinone Metabolite in Humans Southwest Environmental Health Sciences Center, Department of Pharmacology and Toxicology, College of Pharmacy, Department of Chemical & Environmental Engineering, Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, United States *E-mail: [emailprotected] . Tel: (313) 577-1574. Fax: (313) 577-0457. Cite this: Chem. Res. Toxicol. 2016, 29, 2, 227-234 Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days. Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts. The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Methylglyoxal (MG) is a highly reactive dicarbonyl compound involved in the formation of advanced glycation endproducts (AGE). Levels of MG are elevated in patients with type-2 diabetes mellitus (T2DM), and AGE have been implicated in the progression of diabetic complications. The antihyperglycemic drug metformin (MF) has been suggested to be a scavenger of MG. The present work examined and characterized unequivocally the resulting scavenged product from the metforminMG reaction. The primary product was characterized by 1H, 13C, 2D-HSQC, and HMBC NMR and tan Continue reading >>

Vitamin B12 Deficiency In Metformin-treated Type-2 Diabetes Patients, Prevalence And Association With Peripheral Neuropathy

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 Overdosage

Metformin Overdosage

Metformin is a biguanide used to treat type 2 diabetes mellitus and most commonly prescribed oral hypoglycemic agent. Metformin is now also used to treat polycystic ovary syndrome and some malignancies. Despite a good safety profile in a majority of patients with diabetes, the risk of metformin-associated lactic acidosis is genuine when safety guidelines are ignored. Overdoses with metformin are rare, but may result in serious consequences. Case reports and small case series of serious toxicity from metformin overdosage can be found in the medical literature, often with the portrayal of extracorporeal methods for the management of the subsequent severe lactic acidosis. Lactic acidosis can defined as a metabolic acidosis with a blood pH less than 7.35 and a serum lactate more than 2 mmol per liter. It can occur either with therapeutic metformin dosing (which is rare) or in overdose situations. 0.03 cases of lactic acidosis per 1000 patient-years occur within therapeutic dosing, with a majority of these cases among patients that have contraindications to metformin (such as renal insufficiency). In overdose situations, lactic acidosis is seen much more habitually, even though the precise incidence is unclear. Lactic acidosis has been observed in 1.6% of metformin exposures reported to poison control centers; nevertheless, merely 10% of these exposures were due to deliberate overdoses. The incidence of metformin-associated lactic acidosis was 12.8% in a review of poison control center inquiries from Germany. The minimum reported lethal dose was found in a 42 year-old patient who had a blood metformin level of 188 µg/ml (e.g. therapeutic range level is usually between 0.5–2.5 µg/ml). Although the intake of 35 g of metformin has shown to be lethal, the maximum reported to Continue reading >>

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