Background: Metformin (M) is an effective first-line hypoglycemic agent in obese type 2 diabetes mellitus due to its low cost and safety profile. The Case: A 66-year-man presented with shock due to lactic acidosis ind...Background: Metformin (M) is an effective first-line hypoglycemic agent in obese type 2 diabetes mellitus due to its low cost and safety profile. The Case: A 66-year-man presented with shock due to lactic acidosis induced by M-supersaturation subsequent to acute renal failure following infective diarrhea. The drug has been used, by this patient, for >10 years without complication. Physical examination, laboratory tests, radiological investigations and blood cultures did not show evidence of new cardiac, hepatic and septic insult. Despite discontinuation of M and 2-days of aggressive hydration, bicarbonate infusions and pressors;toxic levels of the drug persisted and shock-state culminated in severe and oliguric renal failure with serum urea and creatinine up to 50 mmol/L and 1270 umol/L, respectively. Hence, continuous venovenous hemodiafiltration (CVVHDF) was used, for 16-hours, to remove the drug, correct his acidosis and support his severe renal complications. Hours after the procedure;drug level, lactic acidosis and its associated shock improved followed by gradual renal recovery. The patient was discharged after 6 days and serum creatinine reached his base line (180 umol/L) 2 weeks later. The drug was not recommended for his future use. Conclusion: M-induced lactic acidosis, should be considered in assessment of shock in M-treated patients and management of unstable patients indicates early-use of CVVHDF.展开更多
The first description of a syndrome including stroke-like episodes, lactic acidaemia, and ragged red fibres, was reported by Shapira et al in 1975. 1 Pavlakis et al 2 described further cases, introduced the acr...The first description of a syndrome including stroke-like episodes, lactic acidaemia, and ragged red fibres, was reported by Shapira et al in 1975. 1 Pavlakis et al 2 described further cases, introduced the acronym MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes), and suggested that this represented a distinct mitochondrial disease phenotype. In 1990, Goto et al 3 identified A3243G mutation in the transfer RNA (tRNA) leucine (UUR) gene in some patients with MELAS. Although this mutation has now been established to be the commonest mtDNA defect it is often misdiagnosed. Here we report a kindred of MELAS including a mother and a son. Clinical, pathological and genetic studies are proceeding.展开更多
BACKGROUND Type B lactic acidosis and hypoglycemia can occur in various pediatric conditions.In young children with a history of fasting preceding these metabolic derangements,inborn errors of metabolism should be pri...BACKGROUND Type B lactic acidosis and hypoglycemia can occur in various pediatric conditions.In young children with a history of fasting preceding these metabolic derangements,inborn errors of metabolism should be primarily considered.However,the Warburg effect,a rare metabolic complication,can also manifest in children with hematologic malignancies.Only a few reports of this condition in children have been published in the literature.AIM To identify the clinical course,treatment strategies,and outcomes of childhood hematologic malignancies with type B lactic acidosis.METHODS We performed a comprehensive search of the PubMed,Scopus,and Cochrane databases without any time restriction but limited to English language articles.The databases were last accessed on July 1st,2023.RESULTS A total of 20 publications were included in the analysis,all of which were case reports or case series.No higher quality evidence was available.Among children with hematologic malignancies and Warburg effect,there were 14 cases of acute lymphoblastic leukemia and 6 cases of non-Hodgkin’s lymphoma including our illustrative case.Lactic acidosis occurred in 55%of newly diagnosed cases and 45%of relapsed cases.The mean age was 10.3±4.5 years,and 80%of cases were male.The mean serum lactate was 16.9±12.6 mmol/L,and 43.8%of the cases had concomitant hypoglycemia.Lactic acidosis initially subsided in 80%of patients receiving chemotherapy compared to 60%in the contrast group.The mortality rate of newly diagnosed cases was 45.5%,while the relapsed cases represented a 100%mortality rate.All 8 patients reported before 2001 died from disease-related complications.However,patients described in reports published between 2003 and 2023 had a 54.5%rate of complete remission.CONCLUSION This complication has historically led to fatal outcome;however,patients who received chemotherapy showed a more favorable response.Therefore,it is crucial to promptly initiate specific treatment in this context.展开更多
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes （MELAS） are common types of mitochondrial encephalomyopathy. The involved muscular pathology is characterized by typical changes of mitochon...Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes （MELAS） are common types of mitochondrial encephalomyopathy. The involved muscular pathology is characterized by typical changes of mitochondrial abnormalities. Gene screening has been the gold diagnostic standard for MELAS diagnosis. This study presents three primary MELAS patients, with an age of onset from 13 to 18 years, including one patient with seizure, and two with headache and vomiting. All patients had a family history of disease, with maternal inheritance. Cerebral magnetic resonance imaging revealed abnormally high signals in T2-weighted images： temporal lobe in three cases, occipital lobe in two cases, and parietal lobe in one case. Migrating stroke-like lesions were confirmed in one patient. Muscle biopsy revealed several strongly succinate dehydrogenase-reactive vessels scattered in muscle sections of three patients, but ragged-red fibers and cytochrome c oxidase-negative/dense （COX-/＋） fibers were not observed. Mitochondrial DNA A3243G mutation was identified in all three cases. MELAS syndrome has obvious clinical heterogeneity, and muscle weakness was not prominent in some of the cases. Muscle pathological changes did not accompany ragged-red fibers or COX-/＋ fibers, but succinate dehydrogenase- reactive vessels are important for MELAS diagnosis.展开更多
BACKGROUND Metformin is arguably the most commonly prescribed oral hypoglycemic agent for the management of diabetes.Due to the lack of randomized control trials,most of the data pertaining to the clinical course,ther...BACKGROUND Metformin is arguably the most commonly prescribed oral hypoglycemic agent for the management of diabetes.Due to the lack of randomized control trials,most of the data pertaining to the clinical course,therapeutic interventions and outcomes of patients with metformin induced toxicity has come from case reports or series.AIM To analyse the symptomology,clinical interventions and outcomes of patients presenting with severe metformin toxicity by reviewing the published case reports and series.METHODS We performed a systematic search from PubMed,Science Direct,Reference Citation Analysis(https://www.referencecitationanalysis.com/)and Google Scholar databases using the terms“metformin”AND“toxicity”OR“overdose”OR“lactic acidosis”OR“hyperlactatemia”.The inclusion criteria were:(1)Case reports or case series with individual patient details;and(2)Reported toxicity or overdose of metformin in adults,published in the English language.Data regarding baseline demographics,clinical presentation,therapeutic interventions,intensive care unit course and overall outcome were collected.RESULTS Two hundred forty-two individual cases were analysed,from 158 case reports and 26 case series,with a cumulative mortality of 19.8%.214(88.4%)patients were diabetics on metformin.57(23.6%)had acute ingestion,but a great majority(76.4%)were on metformin in therapeutic doses when they developed toxicity.Metformin associated lactic acidosis(MALA)was the most commonly reported adverse effect present in 224(92.6%)patients.Most of the patients presented with gastrointestinal and neurological symptoms and a significant number of patients had severe metabolic acidosis and hyperlactatemia.The organ support used was renal replacement therapy(RRT)(68.6%),vasopressors(58.7%)and invasive mechanical ventilation(52.9%).A majority of patients(68.6%)received RRT for toxin removal,renal dysfunction and correction of MALA.Patients with lowest pH and highest serum lactate and metformin levels also had favourable outcomes with use of RRT.CONCLUSION Most of the reported cases were on therapeutic doses of metformin but developed toxicity after an acute deterioration in renal functions.These patients may develop severe lactic acidosis,leading to significant morbidity and need for organ support.Despite severe MALA and the need for multiple organ support,they may have good outcomes,especially when RRT is used.The dose of metformin,serum pH,lactate and metformin levels may indicate the severity of toxicity and the need for aggressive therapeutic measures but may not necessarily indicate poor outcomes.展开更多
Objective To study the effect of metformin on lactate metabolism in hepatocytes in vitro under high glucose stress.In vitro LO2 cells,liver cells were randomly divided into blank control group,25 tendency/L glucose so...Objective To study the effect of metformin on lactate metabolism in hepatocytes in vitro under high glucose stress.In vitro LO2 cells,liver cells were randomly divided into blank control group,25 tendency/L glucose solution,27 tendency/L glucose solution,29 tendency/L glucose solution,31 tendency/L glucose solution,33 tendency/L glucose solution,35 tendency/L glucose solution treatment group,the optimal concentation of 31 tendency after L,use 30 tendency for L metformin solution,and then divided into blank control group,the optimal concentration of glucose solution,normal liver cells+metformin solution normal liver cells.The optimal concentration of glucose solution normal liver cells+metformin solution respectively in the 12h,24 h,48 h on cell count plate to calculate the mumber of liver cells,and using lactic acid determination kit the optimal concentration of glucose solution+normal liver cells and normal liver cells+the optimal concentration of glucose solution+metformin solution respectively in the 12 h,24 h,48 h of cell cultures of lactic acid value.There was no significant change in the lactic acid concentration but significant increase in the number of suviving hepatocytes in the high-glycemic control group compared with that in the high-glycemic control group without metformin.Metformin has no significant effect on lactic acid metabolism of hepatocytes under high glucose stess in vito,and has a protective effect on hepatocytes under high glucose stress.Based on this,it is preliminanily believed that metformin is not the direct factor leading to diabetic lactic acidosis.展开更多
文摘Background: Metformin (M) is an effective first-line hypoglycemic agent in obese type 2 diabetes mellitus due to its low cost and safety profile. The Case: A 66-year-man presented with shock due to lactic acidosis induced by M-supersaturation subsequent to acute renal failure following infective diarrhea. The drug has been used, by this patient, for >10 years without complication. Physical examination, laboratory tests, radiological investigations and blood cultures did not show evidence of new cardiac, hepatic and septic insult. Despite discontinuation of M and 2-days of aggressive hydration, bicarbonate infusions and pressors;toxic levels of the drug persisted and shock-state culminated in severe and oliguric renal failure with serum urea and creatinine up to 50 mmol/L and 1270 umol/L, respectively. Hence, continuous venovenous hemodiafiltration (CVVHDF) was used, for 16-hours, to remove the drug, correct his acidosis and support his severe renal complications. Hours after the procedure;drug level, lactic acidosis and its associated shock improved followed by gradual renal recovery. The patient was discharged after 6 days and serum creatinine reached his base line (180 umol/L) 2 weeks later. The drug was not recommended for his future use. Conclusion: M-induced lactic acidosis, should be considered in assessment of shock in M-treated patients and management of unstable patients indicates early-use of CVVHDF.
基金ThisworkwassupportedbythegrantsfromtheGuangdongNaturalScienceFoundationProgram (No 31694 )andtheGuangdongNaturalScienceFoundationKeyProgram (No21894)
文摘The first description of a syndrome including stroke-like episodes, lactic acidaemia, and ragged red fibres, was reported by Shapira et al in 1975. 1 Pavlakis et al 2 described further cases, introduced the acronym MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes), and suggested that this represented a distinct mitochondrial disease phenotype. In 1990, Goto et al 3 identified A3243G mutation in the transfer RNA (tRNA) leucine (UUR) gene in some patients with MELAS. Although this mutation has now been established to be the commonest mtDNA defect it is often misdiagnosed. Here we report a kindred of MELAS including a mother and a son. Clinical, pathological and genetic studies are proceeding.
文摘BACKGROUND Type B lactic acidosis and hypoglycemia can occur in various pediatric conditions.In young children with a history of fasting preceding these metabolic derangements,inborn errors of metabolism should be primarily considered.However,the Warburg effect,a rare metabolic complication,can also manifest in children with hematologic malignancies.Only a few reports of this condition in children have been published in the literature.AIM To identify the clinical course,treatment strategies,and outcomes of childhood hematologic malignancies with type B lactic acidosis.METHODS We performed a comprehensive search of the PubMed,Scopus,and Cochrane databases without any time restriction but limited to English language articles.The databases were last accessed on July 1st,2023.RESULTS A total of 20 publications were included in the analysis,all of which were case reports or case series.No higher quality evidence was available.Among children with hematologic malignancies and Warburg effect,there were 14 cases of acute lymphoblastic leukemia and 6 cases of non-Hodgkin’s lymphoma including our illustrative case.Lactic acidosis occurred in 55%of newly diagnosed cases and 45%of relapsed cases.The mean age was 10.3±4.5 years,and 80%of cases were male.The mean serum lactate was 16.9±12.6 mmol/L,and 43.8%of the cases had concomitant hypoglycemia.Lactic acidosis initially subsided in 80%of patients receiving chemotherapy compared to 60%in the contrast group.The mortality rate of newly diagnosed cases was 45.5%,while the relapsed cases represented a 100%mortality rate.All 8 patients reported before 2001 died from disease-related complications.However,patients described in reports published between 2003 and 2023 had a 54.5%rate of complete remission.CONCLUSION This complication has historically led to fatal outcome;however,patients who received chemotherapy showed a more favorable response.Therefore,it is crucial to promptly initiate specific treatment in this context.
文摘Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes （MELAS） are common types of mitochondrial encephalomyopathy. The involved muscular pathology is characterized by typical changes of mitochondrial abnormalities. Gene screening has been the gold diagnostic standard for MELAS diagnosis. This study presents three primary MELAS patients, with an age of onset from 13 to 18 years, including one patient with seizure, and two with headache and vomiting. All patients had a family history of disease, with maternal inheritance. Cerebral magnetic resonance imaging revealed abnormally high signals in T2-weighted images： temporal lobe in three cases, occipital lobe in two cases, and parietal lobe in one case. Migrating stroke-like lesions were confirmed in one patient. Muscle biopsy revealed several strongly succinate dehydrogenase-reactive vessels scattered in muscle sections of three patients, but ragged-red fibers and cytochrome c oxidase-negative/dense （COX-/＋） fibers were not observed. Mitochondrial DNA A3243G mutation was identified in all three cases. MELAS syndrome has obvious clinical heterogeneity, and muscle weakness was not prominent in some of the cases. Muscle pathological changes did not accompany ragged-red fibers or COX-/＋ fibers, but succinate dehydrogenase- reactive vessels are important for MELAS diagnosis.
文摘BACKGROUND Metformin is arguably the most commonly prescribed oral hypoglycemic agent for the management of diabetes.Due to the lack of randomized control trials,most of the data pertaining to the clinical course,therapeutic interventions and outcomes of patients with metformin induced toxicity has come from case reports or series.AIM To analyse the symptomology,clinical interventions and outcomes of patients presenting with severe metformin toxicity by reviewing the published case reports and series.METHODS We performed a systematic search from PubMed,Science Direct,Reference Citation Analysis(https://www.referencecitationanalysis.com/)and Google Scholar databases using the terms“metformin”AND“toxicity”OR“overdose”OR“lactic acidosis”OR“hyperlactatemia”.The inclusion criteria were:(1)Case reports or case series with individual patient details;and(2)Reported toxicity or overdose of metformin in adults,published in the English language.Data regarding baseline demographics,clinical presentation,therapeutic interventions,intensive care unit course and overall outcome were collected.RESULTS Two hundred forty-two individual cases were analysed,from 158 case reports and 26 case series,with a cumulative mortality of 19.8%.214(88.4%)patients were diabetics on metformin.57(23.6%)had acute ingestion,but a great majority(76.4%)were on metformin in therapeutic doses when they developed toxicity.Metformin associated lactic acidosis(MALA)was the most commonly reported adverse effect present in 224(92.6%)patients.Most of the patients presented with gastrointestinal and neurological symptoms and a significant number of patients had severe metabolic acidosis and hyperlactatemia.The organ support used was renal replacement therapy(RRT)(68.6%),vasopressors(58.7%)and invasive mechanical ventilation(52.9%).A majority of patients(68.6%)received RRT for toxin removal,renal dysfunction and correction of MALA.Patients with lowest pH and highest serum lactate and metformin levels also had favourable outcomes with use of RRT.CONCLUSION Most of the reported cases were on therapeutic doses of metformin but developed toxicity after an acute deterioration in renal functions.These patients may develop severe lactic acidosis,leading to significant morbidity and need for organ support.Despite severe MALA and the need for multiple organ support,they may have good outcomes,especially when RRT is used.The dose of metformin,serum pH,lactate and metformin levels may indicate the severity of toxicity and the need for aggressive therapeutic measures but may not necessarily indicate poor outcomes.
文摘Objective To study the effect of metformin on lactate metabolism in hepatocytes in vitro under high glucose stress.In vitro LO2 cells,liver cells were randomly divided into blank control group,25 tendency/L glucose solution,27 tendency/L glucose solution,29 tendency/L glucose solution,31 tendency/L glucose solution,33 tendency/L glucose solution,35 tendency/L glucose solution treatment group,the optimal concentation of 31 tendency after L,use 30 tendency for L metformin solution,and then divided into blank control group,the optimal concentration of glucose solution,normal liver cells+metformin solution normal liver cells.The optimal concentration of glucose solution normal liver cells+metformin solution respectively in the 12h,24 h,48 h on cell count plate to calculate the mumber of liver cells,and using lactic acid determination kit the optimal concentration of glucose solution+normal liver cells and normal liver cells+the optimal concentration of glucose solution+metformin solution respectively in the 12 h,24 h,48 h of cell cultures of lactic acid value.There was no significant change in the lactic acid concentration but significant increase in the number of suviving hepatocytes in the high-glycemic control group compared with that in the high-glycemic control group without metformin.Metformin has no significant effect on lactic acid metabolism of hepatocytes under high glucose stess in vito,and has a protective effect on hepatocytes under high glucose stress.Based on this,it is preliminanily believed that metformin is not the direct factor leading to diabetic lactic acidosis.
