Diabetes mellitus(DM) that occurs because of chronic liver disease(CLD) is known as hepatogenous diabetes(HD). Although the association of diabetes and liver cirrhosis was described forty years ago, it was scarcely st...Diabetes mellitus(DM) that occurs because of chronic liver disease(CLD) is known as hepatogenous diabetes(HD). Although the association of diabetes and liver cirrhosis was described forty years ago, it was scarcely studied for long time. Patients suffering from this condition have low frequency of risk factors of type 2 DM. Its incidence is higher in CLD of viral, alcoholic and cryptogenic etiology. Its pathophysiology relates to liver damage, pancreatic dysfunction, interactions between hepatitis C virus(HCV) and glucose metabolism mechanisms and genetic susceptibility. It associates with increased rate of liver complications and hepatocellular carcinoma, and decreased 5-year survival rate. It reduces sustained virological response in HCV infected patients. In spite of these evidences, the American Diabetes Association does not recognize HD. In addition, the impact of glucose control on clinical outcomes of patients has not been evaluated. Treatment of diabetes may be difficult due to liver insufficiency and hepatotoxicity of antidiabetic drugs. Notwithstanding, no therapeutic guidelines have been implemented up to date. In this editorial, authors discuss the reasons why they think that HD may be a neglected pathological condition and call attention to the necessity for more clinical research on different fields of this disease.展开更多
The diabetogenic potential of liver cirrhosis(LC)has been known for a long time,and the name"hepatogenous diabetes"(HD)was coined in 1906 to define the condition.Diabetes mellitus(DM)that develops as a conse...The diabetogenic potential of liver cirrhosis(LC)has been known for a long time,and the name"hepatogenous diabetes"(HD)was coined in 1906 to define the condition.Diabetes mellitus(DM)that develops as a consequence of LC is referred to as HD.In patients with LC,the prevalence rates of HD have been reported to vary from 21%to 57%.The pathophysiological basis of HD seems to involve insulin resistance(IR)and pancreaticβ-cell dysfunction.The neurohormonal changes,endotoxemia,and chronic inflammation of LC initially create IR;however,the toxic effects eventually lead toβ-cell dysfunction,which marks the transition from impaired glucose tolerance to HD.In addition,a number of factors,including sarcopenia,sarcopenic obesity,gut dysbiosis,and hyperammonemia,have recently been linked to impaired glucose metabolism in LC.DM is associated with complications and poor outcomes in patients with LC,although the individual impact of each type 2 DM and HD is unknown due to a lack of categorization of diabetes in most published research.In fact,there is much skepticism within scientific organizations over the recognition of HD as a separate disease and a consequence of LC.Currently,T2DM and HD are being treated in a similar manner although no standardized guidelines are available.The different pathophysiological basis of HD may have an impact on treatment options.This review article discusses the existence of HD as a distinct entity with high prevalence rates,a strong pathophysiological basis,clinical and therapeutic implications,as well as widespread skepticism and knowledge gaps.展开更多
Diabetes mellitus(DM)is common in liver cirrhosis(LC).The pathophysiological association is bidirectional.DM is a risk factor of LC and LC is a diabetogenic condition.In the recent years,research on different aspects ...Diabetes mellitus(DM)is common in liver cirrhosis(LC).The pathophysiological association is bidirectional.DM is a risk factor of LC and LC is a diabetogenic condition.In the recent years,research on different aspects of the association DM and LC has been intensified.Nevertheless,it has been insufficient and still exist many gaps.The aims of this review are:(1)To discuss the latest understandings of the association of DM and LC in order to identify the strategies of early diagnosis;(2)To evaluate the impact of DM on outcomes of LC patients;and(3)To select the most adequate management benefiting the two conditions.Literature searches were conducted using Pub Med,Ovid and Scopus engines for DM and LC,diagnosis,outcomes and management.The authors also provided insight from their own published experience.Based on the published studies,two types of DM associated with LC have emerged:Type 2 DM(T2 DM)and hepatogenous diabetes(HD).High-quality evidences have determined that T2 DM or HD significantly increase complications and death pre and post-liver transplantation.HD has been poorly studied and has not been recognized as a complication of LC.The management of DM in LC patients continues to be difficult and should be based on drug pharmacokinetics and the degree of liver failure.In conclusion,the clinical impact of DM in outcomes of LC patients has been the most studied item recently.Nevertheless many gaps still exist particularly in the management.These most important gaps were highlighted in order to propose future lines for research.展开更多
Liver is an essential organ that maintains fasting and postprandial blood glucose response via various metabolic pathways. The liver function gradually deteriorates in chronic liver disease (CLD) due to inflammation a...Liver is an essential organ that maintains fasting and postprandial blood glucose response via various metabolic pathways. The liver function gradually deteriorates in chronic liver disease (CLD) due to inflammation and destruction of liver parenchyma. The development of glucose intolerance and hepatogenous diabetes (HD) in patients with CLD is an inevitable event. Diabetes and CLD can coexist, and function synergistically to cause unfavorable clinical consequences, including poor treatment outcomes and frequent hospitalization. The complications associated with liver disease (malnutrition, hypoglycemia, acute kidney injury, lactic acidosis, etc.) and lack of guidelines limit pharmacological management of HD. Dietary recommendations by The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines (2019), suggested weight reducing hypocaloric diet along with adequate branched-chain amino acid (BCAA) and micronutrient consumption to improve steatosis and insulin sensitivity in patients with CLD. Dietary glycemic index controls prognosis of obesity, non-alcoholic fatty liver disease (NAFLD) and diabetes. The importance of low GI diet in reducing fasting blood glucose, hepatic glucose influx and fat accumulation, thereby improving weight loss and NAFLD score, is being published in patients with diabetes or liver disease. Several countries have already incorporated GI into their national health policies, for identification of the nutrient value, resulting in establishment of worldwide GI and glycemic load tables for specific food items. However, the apparent complexity of GI and lack of low GI meal choices need to be resolved in order to enhance patient’s quality of life, health and well-being. Low GI nutritional supplements, comprising of balanced proportion of carbohydrate, protein, BCAAs, fibers and micronutrients, may reduce the complexity related to dietary management of HD. The review summarizes the importance of nutritional management in HD with focus on low GI diet in people with CLD.展开更多
AIM： To evaluate the presence of progenitor cells in healthy adult rat liver displaying the equivalent ad- vanced hepatogenic profile as that obtained in humans. METHODS： Rat fibroblastic-like liver derived cells （...AIM： To evaluate the presence of progenitor cells in healthy adult rat liver displaying the equivalent ad- vanced hepatogenic profile as that obtained in humans. METHODS： Rat fibroblastic-like liver derived cells （rFLDC） were obtained from collagenase-isolated liver cell suspensions and characterized and their phenotype profile determined using flow cytometry, immunocyto- chemistry, reverse transcription polymerase chain reac- tion and functional assays. RESULTS： rFLDC exhibit fibroblastoid morphology, ex- press mesenchymal （CD73, CD90, vimentin, m-smooth muscle actin）, hepatocyte （UGTIA1, CK8） and biliary （CK19） markers. Moreover, these cells are able to store glycogen, and have glucose 6 phosphatase activity, but not UGTIA1 activity. Under the hepatogenic differentia- tion protocol, rFLDC display an up-regulation of hepatocyte markers expression （albumin, tryptophan 2,3-di- oxygenase, G6Pase） correlated to a down-regulation of the expression of the biliary marker CK19. CONCLUSION： Advanced hepatic features observed in human liver progenitor cells could not be demonstrated in rFLDC. However, we demonstrated the presence of an original rodent hepato-biliary cell type.展开更多
To confirm the existence of hepatic stem cells (HSCs), fetal liver cells isolated from mice on embryonic day 13 (ED13) were long-term cultured in vitro. Growth of the cells was observed intensively and characteristics...To confirm the existence of hepatic stem cells (HSCs), fetal liver cells isolated from mice on embryonic day 13 (ED13) were long-term cultured in vitro. Growth of the cells was observed intensively and characteristics were iden-tified by immunocytochemistry. The results showed that some of the cells grew as colonies, in which some cells ex-pressed AFP, CD34 and Albumin. Then the cells were trans-planted intravenously into irradiated syngeneic mice. At day 12 a number of small hyperplasia nodules were seen in the apparently enlarged spleens of recipient mice. Moreover, some nodules were positive for AFP and CD34 and consisted of various types of cells, suggesting the very existence of he-patic stem cells in the mouse fetal liver.展开更多
基金Supported by the Department of Endocrinology and Service of Gastroenterology of the Faculty of MedicineAutonomous University of Nuevo Leon
文摘Diabetes mellitus(DM) that occurs because of chronic liver disease(CLD) is known as hepatogenous diabetes(HD). Although the association of diabetes and liver cirrhosis was described forty years ago, it was scarcely studied for long time. Patients suffering from this condition have low frequency of risk factors of type 2 DM. Its incidence is higher in CLD of viral, alcoholic and cryptogenic etiology. Its pathophysiology relates to liver damage, pancreatic dysfunction, interactions between hepatitis C virus(HCV) and glucose metabolism mechanisms and genetic susceptibility. It associates with increased rate of liver complications and hepatocellular carcinoma, and decreased 5-year survival rate. It reduces sustained virological response in HCV infected patients. In spite of these evidences, the American Diabetes Association does not recognize HD. In addition, the impact of glucose control on clinical outcomes of patients has not been evaluated. Treatment of diabetes may be difficult due to liver insufficiency and hepatotoxicity of antidiabetic drugs. Notwithstanding, no therapeutic guidelines have been implemented up to date. In this editorial, authors discuss the reasons why they think that HD may be a neglected pathological condition and call attention to the necessity for more clinical research on different fields of this disease.
文摘The diabetogenic potential of liver cirrhosis(LC)has been known for a long time,and the name"hepatogenous diabetes"(HD)was coined in 1906 to define the condition.Diabetes mellitus(DM)that develops as a consequence of LC is referred to as HD.In patients with LC,the prevalence rates of HD have been reported to vary from 21%to 57%.The pathophysiological basis of HD seems to involve insulin resistance(IR)and pancreaticβ-cell dysfunction.The neurohormonal changes,endotoxemia,and chronic inflammation of LC initially create IR;however,the toxic effects eventually lead toβ-cell dysfunction,which marks the transition from impaired glucose tolerance to HD.In addition,a number of factors,including sarcopenia,sarcopenic obesity,gut dysbiosis,and hyperammonemia,have recently been linked to impaired glucose metabolism in LC.DM is associated with complications and poor outcomes in patients with LC,although the individual impact of each type 2 DM and HD is unknown due to a lack of categorization of diabetes in most published research.In fact,there is much skepticism within scientific organizations over the recognition of HD as a separate disease and a consequence of LC.Currently,T2DM and HD are being treated in a similar manner although no standardized guidelines are available.The different pathophysiological basis of HD may have an impact on treatment options.This review article discusses the existence of HD as a distinct entity with high prevalence rates,a strong pathophysiological basis,clinical and therapeutic implications,as well as widespread skepticism and knowledge gaps.
文摘Diabetes mellitus(DM)is common in liver cirrhosis(LC).The pathophysiological association is bidirectional.DM is a risk factor of LC and LC is a diabetogenic condition.In the recent years,research on different aspects of the association DM and LC has been intensified.Nevertheless,it has been insufficient and still exist many gaps.The aims of this review are:(1)To discuss the latest understandings of the association of DM and LC in order to identify the strategies of early diagnosis;(2)To evaluate the impact of DM on outcomes of LC patients;and(3)To select the most adequate management benefiting the two conditions.Literature searches were conducted using Pub Med,Ovid and Scopus engines for DM and LC,diagnosis,outcomes and management.The authors also provided insight from their own published experience.Based on the published studies,two types of DM associated with LC have emerged:Type 2 DM(T2 DM)and hepatogenous diabetes(HD).High-quality evidences have determined that T2 DM or HD significantly increase complications and death pre and post-liver transplantation.HD has been poorly studied and has not been recognized as a complication of LC.The management of DM in LC patients continues to be difficult and should be based on drug pharmacokinetics and the degree of liver failure.In conclusion,the clinical impact of DM in outcomes of LC patients has been the most studied item recently.Nevertheless many gaps still exist particularly in the management.These most important gaps were highlighted in order to propose future lines for research.
文摘Liver is an essential organ that maintains fasting and postprandial blood glucose response via various metabolic pathways. The liver function gradually deteriorates in chronic liver disease (CLD) due to inflammation and destruction of liver parenchyma. The development of glucose intolerance and hepatogenous diabetes (HD) in patients with CLD is an inevitable event. Diabetes and CLD can coexist, and function synergistically to cause unfavorable clinical consequences, including poor treatment outcomes and frequent hospitalization. The complications associated with liver disease (malnutrition, hypoglycemia, acute kidney injury, lactic acidosis, etc.) and lack of guidelines limit pharmacological management of HD. Dietary recommendations by The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines (2019), suggested weight reducing hypocaloric diet along with adequate branched-chain amino acid (BCAA) and micronutrient consumption to improve steatosis and insulin sensitivity in patients with CLD. Dietary glycemic index controls prognosis of obesity, non-alcoholic fatty liver disease (NAFLD) and diabetes. The importance of low GI diet in reducing fasting blood glucose, hepatic glucose influx and fat accumulation, thereby improving weight loss and NAFLD score, is being published in patients with diabetes or liver disease. Several countries have already incorporated GI into their national health policies, for identification of the nutrient value, resulting in establishment of worldwide GI and glycemic load tables for specific food items. However, the apparent complexity of GI and lack of low GI meal choices need to be resolved in order to enhance patient’s quality of life, health and well-being. Low GI nutritional supplements, comprising of balanced proportion of carbohydrate, protein, BCAAs, fibers and micronutrients, may reduce the complexity related to dietary management of HD. The review summarizes the importance of nutritional management in HD with focus on low GI diet in people with CLD.
基金Supported by Fonds pour la formation à la recherche dans l’industrie et dans l’agriculture (FRIA)
文摘AIM： To evaluate the presence of progenitor cells in healthy adult rat liver displaying the equivalent ad- vanced hepatogenic profile as that obtained in humans. METHODS： Rat fibroblastic-like liver derived cells （rFLDC） were obtained from collagenase-isolated liver cell suspensions and characterized and their phenotype profile determined using flow cytometry, immunocyto- chemistry, reverse transcription polymerase chain reac- tion and functional assays. RESULTS： rFLDC exhibit fibroblastoid morphology, ex- press mesenchymal （CD73, CD90, vimentin, m-smooth muscle actin）, hepatocyte （UGTIA1, CK8） and biliary （CK19） markers. Moreover, these cells are able to store glycogen, and have glucose 6 phosphatase activity, but not UGTIA1 activity. Under the hepatogenic differentia- tion protocol, rFLDC display an up-regulation of hepatocyte markers expression （albumin, tryptophan 2,3-di- oxygenase, G6Pase） correlated to a down-regulation of the expression of the biliary marker CK19. CONCLUSION： Advanced hepatic features observed in human liver progenitor cells could not be demonstrated in rFLDC. However, we demonstrated the presence of an original rodent hepato-biliary cell type.
基金This work was supported bythe program issued by the Ministry of Science and Technology of China (Grant No. TJ99-LA01) the Program for Backbone College Teachers issued by the Ministry of Education of China.
文摘To confirm the existence of hepatic stem cells (HSCs), fetal liver cells isolated from mice on embryonic day 13 (ED13) were long-term cultured in vitro. Growth of the cells was observed intensively and characteristics were iden-tified by immunocytochemistry. The results showed that some of the cells grew as colonies, in which some cells ex-pressed AFP, CD34 and Albumin. Then the cells were trans-planted intravenously into irradiated syngeneic mice. At day 12 a number of small hyperplasia nodules were seen in the apparently enlarged spleens of recipient mice. Moreover, some nodules were positive for AFP and CD34 and consisted of various types of cells, suggesting the very existence of he-patic stem cells in the mouse fetal liver.
