Biguanides,such as metformin,have long been established as frontline medications for the management of type 2 diabetes due to their glucose-lowering effects and favorable safety profiles.However,concerns regarding the...Biguanides,such as metformin,have long been established as frontline medications for the management of type 2 diabetes due to their glucose-lowering effects and favorable safety profiles.However,concerns regarding the risk of lactic acidosis associated with biguanide use have sparked considerable debate and scrutiny.This research article aims to provide a comprehensive analysis of the relationship between biguanides,particularly metformin,and lactic acidosis.We delve into the underlying mechanisms,epidemiological evidence,risk factors,clinical manifestations,diagnostic considerations,and management strategies related to biguanide-induced lactic acidosis.Additionally,we explore recent research developments,controversies,and future directions in this critical area of pharmacovigilance and clinical practice.展开更多
Background:The transition period is a challenging period for high-producing dairy cattle.Cows in early lactation are considered as a group at risk of subacute ruminal acidosis(SARA).Variability in SARA susceptibility ...Background:The transition period is a challenging period for high-producing dairy cattle.Cows in early lactation are considered as a group at risk of subacute ruminal acidosis(SARA).Variability in SARA susceptibility in early lactation is hypothesized to be reflected in fecal characteristics such as fecal pH,dry matter content,volatile and odd-and branched-chain fatty acids(VFA and OBCFA,respectively),as well as fecal microbiota.This was investigated with 38 periparturient dairy cows,which were classified into four groups differing in median and mean time of reticular pH below 6 as well as area under the curve of pH below 6.Furthermore,we investigated whether fecal differences were already obvious during a period prior to the SARA risk(prepartum).Results:Variation in reticular pH during a 3-week postpartum period was not associated with differences in fecal pH and VFA concentration.In the postpartum period,the copy number of fecal bacteria and methanogens of unsusceptible(UN)cows was higher than moderately susceptible(MS)or susceptible(SU)cows,while the genera Ruminococcus and Prevotellacea_UCG-001 were proportionally less abundant in UN compared with SU cows.Nevertheless,only a minor reduction was observed in iso-BCFA proportions in fecal fatty acids of SU cows,particularly iso-C15:0and iso-C16:0,compared with UN cows.Consistent with the bacterial changes postpartum,the lower abundance of Ruminococcus was already observed in the prepartum fecal bacterial communities of UN cows,whereas Lachnospiraceae_UCG-001 was increased.Nevertheless,no differences were observed in the prepartum fecal VFA or OBCFA profiles among the groups.Prepartum fecal bacterial communities of cows were clustered into two distinct clusters with 70%of the SU cows belonging to cluster 1,in which they represented 60%of the animals.Conclusions:Inter-animal variation in postpartum SARA susceptibility was reflected in post-and prepartum fecal bacterial communities.Differences in prepartum fecal bacterial communities could alert for susceptibility to develop SARA postpartum.Our results generated knowledge on the association between fecal bacteria and SARA development which could be further explored in a prevention strategy.展开更多
Background Bovine milk is an important source of nutrition for human consumption,and its quality is closely associated with the microbiota and metabolites in it.But there is limited knowledge about the milk microbiome...Background Bovine milk is an important source of nutrition for human consumption,and its quality is closely associated with the microbiota and metabolites in it.But there is limited knowledge about the milk microbiome and metabolome in cows with subacute ruminal acidosis.Methods Eight ruminally cannulated Holstein cows in mid lactation were selected for a 3-week experiment.The cows were randomly allocated into 2 groups,fed either a conventional diet(CON;40%concentrate;dry matter basis)or a high-concentrate diet(HC;60%concentrate;dry matter basis).Results The results showed that there was a decreased milk fat percentage in the HC group compared to the CON group.The amplicon sequencing results indicated that the alpha diversity indices were not affected by the HC feeding.At the phylum level,the milk bacteria were dominated by Proteobacteria,Actinobacteria,Bacteroidetes,and Firmicutes both in the CON and HC groups.At the genus level,the HC cows displayed an improved proportion of Labrys(P=0.015)compared with the CON cows.Results of both the principal components analysis and partial least squares of discriminant analysis of milk metabolome revealed that samples of the CON and HC groups clustered separately.A total of 31 differential metabolites were identified between the two groups.Of these,the levels of 11 metabolites decreased(α-linolenic acid,prostaglandin E2,L-lactic acid,L-malic acid,3-hydroxysebacic acid,succinyladenosine,guanosine,pyridoxal,L-glutamic acid,hippuric acid,and trigonelline),whereas the levels of the other 20 metabolites increased in the HC group with respect to the CON group(P<0.05).Conclusion These results suggested that subacute ruminal acidosis less impacted the diversity and composition of milk microbiota,but altered the milk metabolic profiles,which led to the decline of the milk quality.展开更多
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
Renal tubular acidosis(RTA)can lead to renal calcification in children,which can cause various complications and impair renal function.This review provides pediatricians with a comprehensive understanding of the relat...Renal tubular acidosis(RTA)can lead to renal calcification in children,which can cause various complications and impair renal function.This review provides pediatricians with a comprehensive understanding of the relationship between RTA and renal calcification,highlighting essential aspects for clinical manage-ment.The article analyzed relevant studies to explore the prevalence,risk factors,underlying mechanisms,and clinical implications of renal calcification in children with RTA.Results show that distal RTA(type 1)is particularly associated with nephrocalcinosis,which presents a higher risk of renal calcification.However,there are limitations to the existing literature,including a small number of studies,heterogeneity in methodologies,and potential publication bias.Longitudinal data and control groups are also lacking,which limits our understanding of longterm outcomes and optimal management strategies for children with RTA and renal calcification.Pediatricians play a crucial role in the early diagnosis and management of RTA to mitigate the risk of renal calcification and associated complications.In addition,alkaline therapy remains a cornerstone in the treatment of RTA,aimed at correcting the acid-base imbalance and reducing the formation of kidney stones.Therefore,early diagnosis and appropriate therapeutic interventions are paramount in preventing and managing renal calcification to preserve renal function and improve long-term outcomes for affected children.Further research with larger sample sizes and rigorous methodologies is needed to optimize the clinical approach to renal calcification in the context of RTA in the pediatric population.展开更多
Diabetic ketoacidosis (DKA) can cause significant morbidity and mortality in patient with both type 1 and type 2 diabetes mellitus. A subset of DKA cases termed euglycemic diabetic ketoacidosis (EDKA) is characterized...Diabetic ketoacidosis (DKA) can cause significant morbidity and mortality in patient with both type 1 and type 2 diabetes mellitus. A subset of DKA cases termed euglycemic diabetic ketoacidosis (EDKA) is characterized by euglycemic (<200 mg/dl), high anion gap metabolic acidosis, and increased plasma ketone concentration. This clinical syndrome is primary related to a general state of starvation, resulting in the development of ketosis while maintaining normoglycemia. It can lead to severe complication, such as extreme dehydration, altered mental status and coma. Early recognition and treatment are essential to avoid this life-threatening complication. EDKA represents approximately 2.6% to 3.2% of total DKA admissions, making it a rare condition. In this case report, a male patient was diagnosed with type 2 DM, 1 week prior to his symptoms and admission in hospital. Despite normal glucose levels at the time of presentation to the ED, he displayed severe acidemia and ketonemia, and was diagnosed with EDKA.展开更多
BACKGROUND Renal tubular acidosis(RTA)is a renal cause of non-anion-gap metabolic acidosis characterized by low urinary ammonia excretion.This condition has a low prevalence,and various congenital and acquired etiolog...BACKGROUND Renal tubular acidosis(RTA)is a renal cause of non-anion-gap metabolic acidosis characterized by low urinary ammonia excretion.This condition has a low prevalence,and various congenital and acquired etiologies.To date,only a few cases of idiopathic RTA uncovered during pregnancy have been reported.CASE SUMMARY A previously healthy 32-year-old Korean woman at 30 wk of gestation was admitted to Pusan National University Hospital with preterm labor.At admission,the patient presented with hypokalemia,non-anion-gap metabolic acidosis,and nephrocalcinosis.Distal RTA was diagnosed based on laboratory blood and urine findings and imaging examinations.Various tests,including next-generation gene sequencing panels for nephropathy,were performed to determine the etiology of the disease,which indicated that it was idiopathic.The patient received sodium bicarbonate and potassium chloride supplementation.After 3 wk,she delivered a baby who was subsequently diagnosed with corpus callosum agenesis and colpocephaly.During regular follow-ups for 6 mo postpartum,her hypokalemia and metabolic acidosis were gradually resolved,and medications eventually discontinued.CONCLUSION Herein we describe a case of idiopathic distal RTA discovered during pregnancy.Hypokalemia and metabolic acidosis resolved spontaneously after delivery.展开更多
文摘Biguanides,such as metformin,have long been established as frontline medications for the management of type 2 diabetes due to their glucose-lowering effects and favorable safety profiles.However,concerns regarding the risk of lactic acidosis associated with biguanide use have sparked considerable debate and scrutiny.This research article aims to provide a comprehensive analysis of the relationship between biguanides,particularly metformin,and lactic acidosis.We delve into the underlying mechanisms,epidemiological evidence,risk factors,clinical manifestations,diagnostic considerations,and management strategies related to biguanide-induced lactic acidosis.Additionally,we explore recent research developments,controversies,and future directions in this critical area of pharmacovigilance and clinical practice.
基金the financial support of Flanders Innovation&Entrepreneurship(VLAIOBelgium+3 种基金LA170830)the European Union’s Horizon 2020 research and innovation programme under grant agreement 101000213-Holo RuminantThe PhD research of Hong Yang and Xiaoping Jing was the Chinese Scholarship Council(CSC,China)the PhD research of Stijn Heirbaut was funded by a Ph D grant from the Special Research Fund of the Ghent University(Bijzonder Onderzoeksfonds,BOF,Belgium)。
文摘Background:The transition period is a challenging period for high-producing dairy cattle.Cows in early lactation are considered as a group at risk of subacute ruminal acidosis(SARA).Variability in SARA susceptibility in early lactation is hypothesized to be reflected in fecal characteristics such as fecal pH,dry matter content,volatile and odd-and branched-chain fatty acids(VFA and OBCFA,respectively),as well as fecal microbiota.This was investigated with 38 periparturient dairy cows,which were classified into four groups differing in median and mean time of reticular pH below 6 as well as area under the curve of pH below 6.Furthermore,we investigated whether fecal differences were already obvious during a period prior to the SARA risk(prepartum).Results:Variation in reticular pH during a 3-week postpartum period was not associated with differences in fecal pH and VFA concentration.In the postpartum period,the copy number of fecal bacteria and methanogens of unsusceptible(UN)cows was higher than moderately susceptible(MS)or susceptible(SU)cows,while the genera Ruminococcus and Prevotellacea_UCG-001 were proportionally less abundant in UN compared with SU cows.Nevertheless,only a minor reduction was observed in iso-BCFA proportions in fecal fatty acids of SU cows,particularly iso-C15:0and iso-C16:0,compared with UN cows.Consistent with the bacterial changes postpartum,the lower abundance of Ruminococcus was already observed in the prepartum fecal bacterial communities of UN cows,whereas Lachnospiraceae_UCG-001 was increased.Nevertheless,no differences were observed in the prepartum fecal VFA or OBCFA profiles among the groups.Prepartum fecal bacterial communities of cows were clustered into two distinct clusters with 70%of the SU cows belonging to cluster 1,in which they represented 60%of the animals.Conclusions:Inter-animal variation in postpartum SARA susceptibility was reflected in post-and prepartum fecal bacterial communities.Differences in prepartum fecal bacterial communities could alert for susceptibility to develop SARA postpartum.Our results generated knowledge on the association between fecal bacteria and SARA development which could be further explored in a prevention strategy.
基金the National Key R&D Program of China(2022YFD1301001)Jiangsu Province Special Project for Carbon Peak&Carbon Neutral Science and Technology Innovation(BE2022309).
文摘Background Bovine milk is an important source of nutrition for human consumption,and its quality is closely associated with the microbiota and metabolites in it.But there is limited knowledge about the milk microbiome and metabolome in cows with subacute ruminal acidosis.Methods Eight ruminally cannulated Holstein cows in mid lactation were selected for a 3-week experiment.The cows were randomly allocated into 2 groups,fed either a conventional diet(CON;40%concentrate;dry matter basis)or a high-concentrate diet(HC;60%concentrate;dry matter basis).Results The results showed that there was a decreased milk fat percentage in the HC group compared to the CON group.The amplicon sequencing results indicated that the alpha diversity indices were not affected by the HC feeding.At the phylum level,the milk bacteria were dominated by Proteobacteria,Actinobacteria,Bacteroidetes,and Firmicutes both in the CON and HC groups.At the genus level,the HC cows displayed an improved proportion of Labrys(P=0.015)compared with the CON cows.Results of both the principal components analysis and partial least squares of discriminant analysis of milk metabolome revealed that samples of the CON and HC groups clustered separately.A total of 31 differential metabolites were identified between the two groups.Of these,the levels of 11 metabolites decreased(α-linolenic acid,prostaglandin E2,L-lactic acid,L-malic acid,3-hydroxysebacic acid,succinyladenosine,guanosine,pyridoxal,L-glutamic acid,hippuric acid,and trigonelline),whereas the levels of the other 20 metabolites increased in the HC group with respect to the CON group(P<0.05).Conclusion These results suggested that subacute ruminal acidosis less impacted the diversity and composition of milk microbiota,but altered the milk metabolic profiles,which led to the decline of the milk quality.
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.
文摘Renal tubular acidosis(RTA)can lead to renal calcification in children,which can cause various complications and impair renal function.This review provides pediatricians with a comprehensive understanding of the relationship between RTA and renal calcification,highlighting essential aspects for clinical manage-ment.The article analyzed relevant studies to explore the prevalence,risk factors,underlying mechanisms,and clinical implications of renal calcification in children with RTA.Results show that distal RTA(type 1)is particularly associated with nephrocalcinosis,which presents a higher risk of renal calcification.However,there are limitations to the existing literature,including a small number of studies,heterogeneity in methodologies,and potential publication bias.Longitudinal data and control groups are also lacking,which limits our understanding of longterm outcomes and optimal management strategies for children with RTA and renal calcification.Pediatricians play a crucial role in the early diagnosis and management of RTA to mitigate the risk of renal calcification and associated complications.In addition,alkaline therapy remains a cornerstone in the treatment of RTA,aimed at correcting the acid-base imbalance and reducing the formation of kidney stones.Therefore,early diagnosis and appropriate therapeutic interventions are paramount in preventing and managing renal calcification to preserve renal function and improve long-term outcomes for affected children.Further research with larger sample sizes and rigorous methodologies is needed to optimize the clinical approach to renal calcification in the context of RTA in the pediatric population.
文摘Diabetic ketoacidosis (DKA) can cause significant morbidity and mortality in patient with both type 1 and type 2 diabetes mellitus. A subset of DKA cases termed euglycemic diabetic ketoacidosis (EDKA) is characterized by euglycemic (<200 mg/dl), high anion gap metabolic acidosis, and increased plasma ketone concentration. This clinical syndrome is primary related to a general state of starvation, resulting in the development of ketosis while maintaining normoglycemia. It can lead to severe complication, such as extreme dehydration, altered mental status and coma. Early recognition and treatment are essential to avoid this life-threatening complication. EDKA represents approximately 2.6% to 3.2% of total DKA admissions, making it a rare condition. In this case report, a male patient was diagnosed with type 2 DM, 1 week prior to his symptoms and admission in hospital. Despite normal glucose levels at the time of presentation to the ED, he displayed severe acidemia and ketonemia, and was diagnosed with EDKA.
基金Supported by Clinical Research Grant from Pusan National University Hospital in 2022.
文摘BACKGROUND Renal tubular acidosis(RTA)is a renal cause of non-anion-gap metabolic acidosis characterized by low urinary ammonia excretion.This condition has a low prevalence,and various congenital and acquired etiologies.To date,only a few cases of idiopathic RTA uncovered during pregnancy have been reported.CASE SUMMARY A previously healthy 32-year-old Korean woman at 30 wk of gestation was admitted to Pusan National University Hospital with preterm labor.At admission,the patient presented with hypokalemia,non-anion-gap metabolic acidosis,and nephrocalcinosis.Distal RTA was diagnosed based on laboratory blood and urine findings and imaging examinations.Various tests,including next-generation gene sequencing panels for nephropathy,were performed to determine the etiology of the disease,which indicated that it was idiopathic.The patient received sodium bicarbonate and potassium chloride supplementation.After 3 wk,she delivered a baby who was subsequently diagnosed with corpus callosum agenesis and colpocephaly.During regular follow-ups for 6 mo postpartum,her hypokalemia and metabolic acidosis were gradually resolved,and medications eventually discontinued.CONCLUSION Herein we describe a case of idiopathic distal RTA discovered during pregnancy.Hypokalemia and metabolic acidosis resolved spontaneously after delivery.
