Diabetic nephropathy(DN)is the leading cause of end-stage renal disease and is also associated with increased risk for cardiovascular events.Until recently,strict glycemic control and blockade of the renin-angiotensin...Diabetic nephropathy(DN)is the leading cause of end-stage renal disease and is also associated with increased risk for cardiovascular events.Until recently,strict glycemic control and blockade of the renin-angiotensin system(RAS)constituted the mainstay of treatment of DN.However,randomized controlled trials showed that sodium-glucose cotransporter 2 inhibitors further reduce the progression of DN.Therefore,these agents are recommended in all patients with DN regardless of DN stage and HbA1c levels.Moreover,additional blockade of the RAS with finerenone,a selective non-steroidal mineralocorticoid receptor antagonist,was also shown to prevent both the decline of renal function and cardiovascular events in this population.Finally,promising preliminary findings suggest that glucagon-like peptide 1 receptor agonists might also exert reno-and cardioprotective effects in patients with DN.Hopefully,this knowledge will improve the outcomes of this high-risk group of patients.展开更多
AIM: To assess whether ischemic stroke severity and outcome is more adverse in patients with type 2 diabetes mellitus(T2DM). METHODS: Consecutive patients hospitalized for acute ischemic stroke between September 2010 ...AIM: To assess whether ischemic stroke severity and outcome is more adverse in patients with type 2 diabetes mellitus(T2DM). METHODS: Consecutive patients hospitalized for acute ischemic stroke between September 2010 and June 2013 were studied prospectively(n = 482; 40.2% males, age 78.8 ± 6.7 years). T2 DM was defined as self-reported T2 DM or antidiabetic treatment. Stroke severity was evaluated with the National Institutes of Health Stroke Scale(NIHSS) score at admission. The outcome was assessed with the modified Rankin scale(m RS) score at discharge and with in-hospital mortality. Adverse outcome was defined as m RS score at discharge ≥ 2 or in-hospital death. The length of hospitalization was also recorded.RESULTS: T2 DM was present in 32.2% of the study population. Patients with T2 DM had a larger waist circumference, higher serum triglyceride and glucose levels and lower serum high-density lipoprotein cholesterol levels as well as higher prevalence of hypertension, coronary heart disease and congestive heart failure than patients without T2 DM. On the other hand, diabetic patients had lower low-density lipoprotein cholesterol levels and reported smaller consumption of alcohol than non-diabetic patients. At admission, the NIHSS score did not differ between patients with and without T2DM(8.7 ± 8.8 and 8.6 ± 9.2, respectively; P = NS). At discharge, the m RS score also did not differ between the two groups(2.7 ± 2.1 and 2.7 ± 2.2 in patients with and without T2 DM, respectively; P = NS). Rates of adverse outcome were also similar in patients with and without T2DM(62.3% and 58.5%, respectively; P = NS). However, when we adjusted for the differences between patients with T2 DM and those without T2 DM in cardiovascular risk factors, T2 DM was independently associated with adverse outcome [relative risk(RR) = 2.39; 95%CI: 1.21-4.72, P = 0.012]. Inhospital mortality rates did not differ between patients with T2 DM and those without T2DM(9.0% and 9.8%, respectively; P = NS). In multivariate analysis adjusting for the difference in cardiovascular risk factors between the two groups, T2 DM was again not associated with in-hospital death. CONCLUSION: T2 DM does not appear to affect ischemic stroke severity but is independently associated with a worse functional outcome at discharge.展开更多
The development of effective nucleos(t)ide analogs(NAs)against hepatitis B virus(HBV)has improved the outcome of patients with chronic hepatitis B(CHB).This review updates issues related to the management of CHB patie...The development of effective nucleos(t)ide analogs(NAs)against hepatitis B virus(HBV)has improved the outcome of patients with chronic hepatitis B(CHB).This review updates issues related to the management of CHB patients included in special populations.Entecavir(ETV)and tenofovir(TDF)represent the currently recommended first-line NAs in patients with HBV decompensated cirrhosis.The combination of HBV immunoglobulin(usually for a finite duration)and NA is considered the standard of care for prophylaxis against HBV recurrence after liver transplantation.TDF is the best choice for hemodialysis patients and in patients with chronic kidney disease with nucleoside resistance.ETV and telbivudine are the preferred options in na?ve renal transplant recipients and with low viremia levels,respectively.All hepatitis B surface antigen(HBs Ag)-positive candidates should be treated with NAs before renal transplantation to achieve undetectable HBV DNA at the time of transplantation.Conventional interferon or NAs can also be used in children,on the basis of well-established therapeutic indication.Pregnant women at high risk of perinatal transmission could be treated with lamivudine,telbivudine or TDF in the last trimester of pregnancy.HBs Ag-positive patients under immunosuppression should receive NA preemptively(regardless of HBV DNA levels)up to 12 mo after its cessation.In HBs Ag negative,anti-HBc positive patients under immunosuppression,further studies are needed to form a final conclusion;however,it seems that anti-HBV prophylaxis is justified in such patients with hematological diseases and/or for those receiving rituximab-containing regimens,regardless of their antiHBs or serum HBV DNA status.展开更多
Nonalcoholic fatty liver disease(NAFLD) is the commonest chronic liver disease and its prevalence is increasing driven by the pandemic of obesity and type 2 diabetes mellitus. NAFLD can progress to cirrhosis and is as...Nonalcoholic fatty liver disease(NAFLD) is the commonest chronic liver disease and its prevalence is increasing driven by the pandemic of obesity and type 2 diabetes mellitus. NAFLD can progress to cirrhosis and is associated with increased risk for cardiovascular disease and hepatocellular cancer. Diet and exercise are limited by suboptimal long-term adherence in patients with NAFLD. On the other hand, current pharmacological treatment of NAFLD has limited efficacy and unfavorable safety profile. In this context, obeticholic acid(OCA), a selective agonist of the farnesoid X receptors, might represent a useful option in these patients. Preclinical studies suggest that OCA improves hepatic steatosis, inflammation and fibrosis. A proof-of-concept study and the randomized, placebo-controlled Farnesoid X Receptor Ligand Obeticholic Acid in non-alcoholic steatohepatitis Treatment(FLINT) trial also showed improvements in liver histology in patients with NAFLD who received OCA. Weight loss and reduction in blood pressure were also observed. However, the effects of OCA on insulin resistance are conflicting and the lipid profile is adversely affected by this agent. In addition, pruritus is frequently observed during treatment with OCA and might lead to treatment discontinuation. However, given the limitations of existing treatments for NAFLD, OCA might represent a useful therapeutic option in selected patients with NAFLD.展开更多
Chronic hepatitis B (CHB) is a major risk factor for hepatocellular carcinoma (HCC). The prevention of HCC is of paramount importance in patients with CHB, particularly in those with cirrhosis. Antiviral treatment can...Chronic hepatitis B (CHB) is a major risk factor for hepatocellular carcinoma (HCC). The prevention of HCC is of paramount importance in patients with CHB, particularly in those with cirrhosis. Antiviral treatment can potentially reduce the risk for HCC since it suppresses viral replication, induces HBeAg seroconversion and improves liver histology. However, most evidence supporting a protective effect of antiviral treatment originates from non-randomized or retrospective studies and is limited to conventional interferon and lamivudine. There is a paucity of data on the effects of pegylated interferon and "newer" oral agents (telbivudine, tenofovir, entecavir) on HCC risk. However, it should be emphasized that the existing randomized control studies in patients with CHB were relatively short-term and not designed to assess the effects of antiviral treatment on HCC risk. Since viral load directly correlates with HCC risk, it is reasonable to hypothesize that the reduction in viral load with antiviral treatment will also lower the risk of HCC. This benefit might become more readily apparent with the newer agents used in the management of CHB which are more effective and have a more favorable resistance profile.展开更多
Nonalcoholic fatty liver disease(NAFLD) is the commonest chronic liver disease and includes simple steatosis and nonalcoholic steatohepatitis(NASH). Since NASH progresses to cirrhosis more frequently and increases liv...Nonalcoholic fatty liver disease(NAFLD) is the commonest chronic liver disease and includes simple steatosis and nonalcoholic steatohepatitis(NASH). Since NASH progresses to cirrhosis more frequently and increases liver-related and cardiovascular disease risk substantially more than simple steatosis, there is a great need to differentiate the two entities. Liver biopsy is the gold standard for the diagnosis of NAFLD but its disadvantages, including the risk of complications and sampling bias, stress the need for developing alternative diagnostic methods. Accordingly, several non-invasive markers have been evaluated for the diagnosis of simple steatosis and NASH, including both serological indices and imaging methods. The present review summarizes the current knowledge on the role of these markers in the diagnosis of NAFLD. Current data suggest that ultrasound and the fibrosis-4 score are probably the most appealing methods for detecting steatosis and for distinguishing NASH from simple steatosis, respectively, because of their low cost and relatively high accuracy. However, currently available methods, both serologic and imaging, cannot obviate the need for liver biopsy for diagnosing NASH due to their substantial false positive and false negative rates. Therefore, the current role of these methods is probably limited in patients who are unwilling or have contraindications for undergoing biopsy.展开更多
Nonalcoholic fatty liver disease(NAFLD) is the commonest chronic liver disease in high-income countries and is associated with increased morbidity and mortality. Macrophages appear to play an important role in the dev...Nonalcoholic fatty liver disease(NAFLD) is the commonest chronic liver disease in high-income countries and is associated with increased morbidity and mortality. Macrophages appear to play an important role in the development and progression of hepatic fibrosis in patients with NAFLD. Accordingly, modulation of macrophage trafficking might represent an attractive therapeutic strategy in this population. Cenicriviroc is an oral inhibitor of the chemokine ligand 2/C-C chemokine receptor 2 pathway, which plays an important role in the hepatic recruitment of the macrophages. Preclinical studies and a phase 2b study in humans suggest that this agent might hold promise in the management of NAFLD.展开更多
Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in developed countries and is associated not only with increased risk for liver disease-related complications but also with higher cardi...Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in developed countries and is associated not only with increased risk for liver disease-related complications but also with higher cardiovascular morbidity. Accordingly, lipid-lowering agents are frequently considered in these patients to reduce cardiovascular risk. However, there have been concerns regarding the safety of these agents in patients with chronic liver diseases. In the present review, we discuss the safety of lipid-lowering agents in patients with NAFLD as well as their effects on both cardiovascular and liver disease in this population. Accumulating data suggest that statins are safe in patients with NAFLD and that they reduce the increased cardiovascular morbidity of this population. However, it is still unclear whether statins are also useful as a treatment for NAFLD per se, since there are very limited and conflicting data on their effects on liver histology. There is also very scarce evidence regarding the safety and efficacy of other lipid-lowering agents in patients with NAFLD. Randomized controlled studies are needed to evaluate the role of lipid-lowering agents and particularly statins for the prevention of both cardiovascular and liver disease-related complications in this high-risk population.展开更多
Diabetic retinopathy affects a substantial proportion of patients with diabetes mellitus(DM) and is the leading cause of blindness in working-aged adults. Even though the incidence of diabetic retinopathy has declined...Diabetic retinopathy affects a substantial proportion of patients with diabetes mellitus(DM) and is the leading cause of blindness in working-aged adults. Even though the incidence of diabetic retinopathy has declined in the last decades, its prevalence increased and is expected to rise further as a result of the increasing incidence of type 2 DM(T2DM) and the longer life expectancy of patients with DM. The pathogenesis of diabetic retinopathy is multifactorial. Some observational studies suggested an association between dyslipidemia and the development and progression of retinopathy in patients with DM but others did not confirm this association. Regarding lipid-lowering agents, studies that evaluated the role of statins in the management of these patients are mostly small and yielded discrepant results. Large randomized studies with statins in patients with T2DM showed no benefit of these agents on diabetic retinopathy but were not designed to address this effect. In contrast, both preclinical data and two large randomized controlled studies, the FIELD and the ACCORD trial, showed that fenofibrate delays the progression of diabetic retinopathy. Even though the mechanisms underpinning this favorable effect are not entirely clear, these findings suggest that fenofibrate might represent a useful tool for the management of diabetic retinopathy.展开更多
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. NAFLD is considerably more frequent in patients with type 2 diabetes mellitus (T2DM) than in the general populat...Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. NAFLD is considerably more frequent in patients with type 2 diabetes mellitus (T2DM) than in the general population and is also more severe histologically in this group. Sodium-glucose co-transporter-2 (SGLT2) inhibitors, the newest class of antidiabetic agents, appear to represent a promising option for the management of NAFLD in patients with T2DM. In a number of studies, treatment with SGLT2 inhibitors resulted in a reduction in hepatic steatosis and in transaminase levels. However, existing studies are small, their follow-up period was short and none evaluated the effects of SGLT2 inhibitors on liver histology. Accordingly, larger studies are needed to verify these preliminary results and define the role of SGLT2 inhibitors in the treatment of NAFLD in patients with T2DM.展开更多
Clopidogrel is a widely used antiplatelet agent for the secondary prevention of cardiovascular events in patients with stable coronary heart disease, acute coronary syndromes and ischemic stroke. Even though clopidogr...Clopidogrel is a widely used antiplatelet agent for the secondary prevention of cardiovascular events in patients with stable coronary heart disease, acute coronary syndromes and ischemic stroke. Even though clopidogrel is safer than aspirin in terms of risk for gastrointestinal(GI) bleeding, the elderly, and patients with a history of prior GI bleeding, with Helicobacter pylori infection or those who are also treated with aspirin, anticoagulants, corticosteroids or nonsteroidal antiinflammatory drugs are at high risk for GI complications when treated with clopidogrel. Accordingly, proton pump inhibitors are frequently administered in combination with clopidogrel to reduce the risk for GI bleeding. Nevertheless, pharmacodynamic studies suggest that omeprazole might attenuate the antiplatelet effect of clopidogrel. However, in observational studies, this interaction does not appear to translate into increased cardiovascular risk in patients treated with this combination. Moreover, in the only randomized, double-blind study that assessed the cardiovascular implications of combining clopidogrel and omeprazole, patients treated with clopidogrel/omeprazole combination had reduced risk for GI events and similar risk for cardiovascular events than patients treated with clopidogrel and placebo. However, the premature interruption of the study and the lack of power analysis in terms of the cardiovascular endpoint do not allow definite conclusions regarding the cardiovascular safety of clopidogrel/omeprazole combination. Other proton pump inhibitors do not appear to interact with clopidogrel. Nevertheless, given the limitations of existing observational and interventional studies, the decision to administer proton pump inhibitors to patients treated with clopidogrel should be individualized based on the patient's bleeding and cardiovascular risk.展开更多
Diabetes mellitus(DM) is a major risk factor for cardiovascular events, including ischemic stroke. Moreover, ischemic stroke appears to be more severe in these patients and to be associated with less favorable outcome...Diabetes mellitus(DM) is a major risk factor for cardiovascular events, including ischemic stroke. Moreover, ischemic stroke appears to be more severe in these patients and to be associated with less favorable outcomes. However, strict glycemic control does not appear to reduce the risk of ischemic stroke. On the other hand, newer glucose-lowering agents(glucagon-like peptide 1 receptor agonists and sodiumglucose cotransporter 2 inhibitors) reduced the risk of cardiovascular events in recent randomized, placebocontrolled trials. Semaglutide also reduced the risk of ischemic stroke. These benefits are independent of glucose lowering and might be due to the favorable effects of these agents on body weight and blood pressure. Pioglitazone also reduced the risk of recurrent stroke in patients with insulin resistance or type 2 DM but the unfavorable safety profile limits its use. In contrast, sulfonylureas and dipeptidyl peptidase 4 inhibitors have a neutral effect on cardiovascular morbidity and might be less attractive options in this high-risk population.展开更多
Herbal medicine products represent a common therapeutic approach in the East and are gaining increasing popularity in Western countries. They are unjustifiably considered to be side-effect free; on the contrary, sever...Herbal medicine products represent a common therapeutic approach in the East and are gaining increasing popularity in Western countries. They are unjustifiably considered to be side-effect free; on the contrary, severe toxicity, including catastrophic hepatic injury has been reported in association with their use. Vigilance isrequired from both physicians and the general public. Physicians should always suspect herbal medicines when evaluating a patient with unexplained liver injury. Regulation standards for herbal products need to be reconsidered, so that the efficacy and safety of these products have been clearly demonstrated before they enter the markets.展开更多
Pulmonary embolism(PE)is an important public health problem.In August2019,the European Society of Cardiology in collaboration with the European Respiratory Society released new guidelines for the diagnosis and managem...Pulmonary embolism(PE)is an important public health problem.In August2019,the European Society of Cardiology in collaboration with the European Respiratory Society released new guidelines for the diagnosis and management of PE.We discuss the basic changes between these recent guidelines and the previous guidelines that were published in 2014.Regarding diagnosis,the new guidelines propose the use of an age-adjusted cut-off level of D-dimers instead of a fixed cut-off value.A D-dimer test adapted to clinical possibility should also be considered instead of fixed cut-off level of D-dimer.Detailed recommendations for the diagnosis of PE during pregnancy are also provided.Regarding risk stratification,assessment of PE-related early mortality risk is recommended.Moreover,the importance of right ventricular dysfunction is emphasized in lowrisk patients.For further risk stratification of the severity of PE in patients without hemodynamic instability,use of validated scores that combine clinical,imaging and laboratory PE-related prognostic factors might also be considered.Regarding treatment,the possibility of early discharge is mentioned in patients without severe comorbidities,who are not of high risk for sudden death and in whom proper medical management at home and proper medical follow up can be ensured.The new guidelines also suggest that pro-brain natriuretic peptide levels,right ventricular function and the presence of thrombus in the right heart could be useful for guiding the decision of early discharge.Overall,these new guidelines introduce several key changes and knowledge and adherence to them will improve the outcome of patients with PE.展开更多
The rising rates of obesity in youth have concurrently led to an increase in the rates of type 2 diabetes mellitus (T2DM) in this age group. However, there are limited data on the efficacy of different antidiabetic ag...The rising rates of obesity in youth have concurrently led to an increase in the rates of type 2 diabetes mellitus (T2DM) in this age group. However, there are limited data on the efficacy of different antidiabetic agents in youth. In this context, the Treatment Options for Type 2 Diabetes in Adolescents and Youth trial recently reported that the majority of obese children and adolescents 10-17-years old with newly diagnosed T2DM (T2DM duration less than 2 years) could not achieve HbA1c levels < 8% for more than 1 year with metformin monotherapy, metformin plus rosiglitazone combination, or metformin and lifestyle changes. These findings suggest that, in the majority of youth with T2DM, tight long-term glycemic control with oral agents is an elusive goal and that most patients will require treatment with insulin within a few years of diagnosis to achieve HbA1c targets and reduce the risk of macro- and microvascular complications. Therefore, reducing the incidence of T2DM by preventing pediatric obesity through the implementation of lifestyle changes in the community should be the primary objective of healthcare systems.展开更多
Heart failure(HF)is a major complication of diabetes mellitus(DM).Patients with DM have considerably higher risk for HF than non-diabetic subjects and HF is also more severe in the former.Given the rising prevalence o...Heart failure(HF)is a major complication of diabetes mellitus(DM).Patients with DM have considerably higher risk for HF than non-diabetic subjects and HF is also more severe in the former.Given the rising prevalence of DM,the management of HF in diabetic patients has become the focus of increased attention.In this context,the findings of several randomized,placebo-controlled trials that evaluated the effects of sodium-glucose co-transporter-2 inhibitors on the risk of hospitalization for HF in patients with type 2 DM represent a paradigm shift in the management of HF.These agents consistently reduced the risk of hospitalization for HF both in patients with and in those without HF.These benefits appear to be partly independent from glucose-lowering and have also been reported in patients without DM.However,there are more limited data regarding the benefit of sodium-glucose co-transporter-2 inhibitors in patients with HF and preserved left ventricular ejection fraction,which is the commonest type of HF in diabetic patients.展开更多
Diabetes mellitus(DM)is an independent risk factor for admission to intensive care unit and death in patients with coronavirus disease 2019(COVID-19).On the other hand,medications used in the management of COVID-19 ar...Diabetes mellitus(DM)is an independent risk factor for admission to intensive care unit and death in patients with coronavirus disease 2019(COVID-19).On the other hand,medications used in the management of COVID-19 are potentially associated with increases in blood glucose levels and a higher incidence of infections.Accordingly,care of patients with DM and acute COVID-19 requires careful consideration of both diseases.Hyperglycemia and hypoglycemia are associated with adverse outcomes and therefore frequent measurement of blood glucose levels and a basal-bolus insulin regimen are required in most patients.Regarding the management of COVID-19,dexamethasone increases blood glucose levels and might also increase the risk for infections.On the other hand,limited data suggest that antiviral and immunomodulatory agents used in COVID-19 are not strongly associated with higher incidence of infections in this population.As knowledge evolves in this field,optimization of the management of both DM and COVID-19 will hopefully improve the outcome of these patients。展开更多
Nonalcoholic fatty liver disease(NAFLD) is the commonest liver disease in Western countries.Treatment of NAFLD is currently based on lifestyle measures and no effective pharmacologic treatment is available so far.Emer...Nonalcoholic fatty liver disease(NAFLD) is the commonest liver disease in Western countries.Treatment of NAFLD is currently based on lifestyle measures and no effective pharmacologic treatment is available so far.Emerging evidence,mainly from animal studies,suggests that the renin-angiotensin-aldosterone system may be of major importance in the pathogenesis of NAFLD and indicates that angiotensin-converting enzyme inhibitors(ACE-I) and angiotensin receptor blockers(ARBs) as a potentially useful therapeutic approach.However,data from human studies are limited and contradictory.In addition,there are few randomized controlled trials(RCTs) on the effects of ACE-I or ARB in patients with NAFLD and most data are from retrospective studies,pilot prospective studies and post hoc analyses of clinical trials.Accordingly,more and larger RCTs are needed to directly assess the effectiveness of ACE-I and ARBs in NAFLD.展开更多
The possible relationship between diabetes mellitus (DM) and colorectal cancer (CRC), concerning pathophysiological and molecular mechanisms is highlighted in this review. The most recent and complete articles and dev...The possible relationship between diabetes mellitus (DM) and colorectal cancer (CRC), concerning pathophysiological and molecular mechanisms is highlighted in this review. The most recent and complete articles and developments in this particular field were thoroughly reviewed. Common risk factors, such as obesity, sedentary lifestyle, and Western diet between DM and CRC, led to the theory that DM might be a causal agent for CRC development. Various studies have connected type 2 DM and CRC, either proximal or distal, in both sexes. Additionally, chronic insulin treatment has been linked with increased colorectal tumor risk among type 2 diabetic patients. Interestingly, elevated hemoglobin A1c has been proven to be an independent predictor of aggressive clinical behavior in CRC patients. These mechanisms include the insulin-like growth factor-hyperinsulinemia theory and the participation of oncogenic intracellular signaling pathways. Furthermore, it has been proposed that Cox-2 inhibitors might have a role in decreasing the incidence of CRC. Finally, the use of statins to reduce the risk for colon cancer in patients with diabetes has remained controversial. Diabetic patients over 50 should receive counseling regarding their elevated risk for CRC, and screening colonoscopy should be recommended before initiating insulin therapy. However, there are no current guidelines, and this strategy is not yet applicable to some countries, as the corresponding risk would not allow screening colonoscopy to be adopted. There is strong evidence to indicate that DM is a causal agent for CRC development. This conclusion provides new impetus for re-evaluating CRC screening worldwide.展开更多
Type 2 diabetes mellitus (T2DM) is a leading cause of blindness, non-traumatic amputation and end-stage renal disease as well as a major cardiovascular risk factor. Tight glycemic control reduces the incidence of micr...Type 2 diabetes mellitus (T2DM) is a leading cause of blindness, non-traumatic amputation and end-stage renal disease as well as a major cardiovascular risk factor. Tight glycemic control reduces the incidence of microvascular complications of T2DM whereas its effects on macrovascular complication are more controversial. However, glycemic targets are achieved by a minority of diabetic patients despite the availability of several antidiabetic agents. In the present commentary, we discuss the findings of two recent randomized studies that compared bariatric surgery with medical treatment in patients with uncontrolled T2DM. Both studies showed that bariatric surgery results in remission of T2DM in the majority of patients. However, both studies were limited to relatively young patients without comorbidities, had relatively short follow-up and did not assess the effects of surgery on T2DM complications. Moreover, the perioperative complications of bariatric surgery and its limited availability in some areas are additional barriers to the wider implementation of this therapeutic approach. On the other hand, the elucidation of the mechanisms underpinning the resolution of T2DM following bariatric surgery might resultin the development of novel, more effective pharmacotherapies for this common disease.展开更多
文摘Diabetic nephropathy(DN)is the leading cause of end-stage renal disease and is also associated with increased risk for cardiovascular events.Until recently,strict glycemic control and blockade of the renin-angiotensin system(RAS)constituted the mainstay of treatment of DN.However,randomized controlled trials showed that sodium-glucose cotransporter 2 inhibitors further reduce the progression of DN.Therefore,these agents are recommended in all patients with DN regardless of DN stage and HbA1c levels.Moreover,additional blockade of the RAS with finerenone,a selective non-steroidal mineralocorticoid receptor antagonist,was also shown to prevent both the decline of renal function and cardiovascular events in this population.Finally,promising preliminary findings suggest that glucagon-like peptide 1 receptor agonists might also exert reno-and cardioprotective effects in patients with DN.Hopefully,this knowledge will improve the outcomes of this high-risk group of patients.
文摘AIM: To assess whether ischemic stroke severity and outcome is more adverse in patients with type 2 diabetes mellitus(T2DM). METHODS: Consecutive patients hospitalized for acute ischemic stroke between September 2010 and June 2013 were studied prospectively(n = 482; 40.2% males, age 78.8 ± 6.7 years). T2 DM was defined as self-reported T2 DM or antidiabetic treatment. Stroke severity was evaluated with the National Institutes of Health Stroke Scale(NIHSS) score at admission. The outcome was assessed with the modified Rankin scale(m RS) score at discharge and with in-hospital mortality. Adverse outcome was defined as m RS score at discharge ≥ 2 or in-hospital death. The length of hospitalization was also recorded.RESULTS: T2 DM was present in 32.2% of the study population. Patients with T2 DM had a larger waist circumference, higher serum triglyceride and glucose levels and lower serum high-density lipoprotein cholesterol levels as well as higher prevalence of hypertension, coronary heart disease and congestive heart failure than patients without T2 DM. On the other hand, diabetic patients had lower low-density lipoprotein cholesterol levels and reported smaller consumption of alcohol than non-diabetic patients. At admission, the NIHSS score did not differ between patients with and without T2DM(8.7 ± 8.8 and 8.6 ± 9.2, respectively; P = NS). At discharge, the m RS score also did not differ between the two groups(2.7 ± 2.1 and 2.7 ± 2.2 in patients with and without T2 DM, respectively; P = NS). Rates of adverse outcome were also similar in patients with and without T2DM(62.3% and 58.5%, respectively; P = NS). However, when we adjusted for the differences between patients with T2 DM and those without T2 DM in cardiovascular risk factors, T2 DM was independently associated with adverse outcome [relative risk(RR) = 2.39; 95%CI: 1.21-4.72, P = 0.012]. Inhospital mortality rates did not differ between patients with T2 DM and those without T2DM(9.0% and 9.8%, respectively; P = NS). In multivariate analysis adjusting for the difference in cardiovascular risk factors between the two groups, T2 DM was again not associated with in-hospital death. CONCLUSION: T2 DM does not appear to affect ischemic stroke severity but is independently associated with a worse functional outcome at discharge.
文摘The development of effective nucleos(t)ide analogs(NAs)against hepatitis B virus(HBV)has improved the outcome of patients with chronic hepatitis B(CHB).This review updates issues related to the management of CHB patients included in special populations.Entecavir(ETV)and tenofovir(TDF)represent the currently recommended first-line NAs in patients with HBV decompensated cirrhosis.The combination of HBV immunoglobulin(usually for a finite duration)and NA is considered the standard of care for prophylaxis against HBV recurrence after liver transplantation.TDF is the best choice for hemodialysis patients and in patients with chronic kidney disease with nucleoside resistance.ETV and telbivudine are the preferred options in na?ve renal transplant recipients and with low viremia levels,respectively.All hepatitis B surface antigen(HBs Ag)-positive candidates should be treated with NAs before renal transplantation to achieve undetectable HBV DNA at the time of transplantation.Conventional interferon or NAs can also be used in children,on the basis of well-established therapeutic indication.Pregnant women at high risk of perinatal transmission could be treated with lamivudine,telbivudine or TDF in the last trimester of pregnancy.HBs Ag-positive patients under immunosuppression should receive NA preemptively(regardless of HBV DNA levels)up to 12 mo after its cessation.In HBs Ag negative,anti-HBc positive patients under immunosuppression,further studies are needed to form a final conclusion;however,it seems that anti-HBV prophylaxis is justified in such patients with hematological diseases and/or for those receiving rituximab-containing regimens,regardless of their antiHBs or serum HBV DNA status.
文摘Nonalcoholic fatty liver disease(NAFLD) is the commonest chronic liver disease and its prevalence is increasing driven by the pandemic of obesity and type 2 diabetes mellitus. NAFLD can progress to cirrhosis and is associated with increased risk for cardiovascular disease and hepatocellular cancer. Diet and exercise are limited by suboptimal long-term adherence in patients with NAFLD. On the other hand, current pharmacological treatment of NAFLD has limited efficacy and unfavorable safety profile. In this context, obeticholic acid(OCA), a selective agonist of the farnesoid X receptors, might represent a useful option in these patients. Preclinical studies suggest that OCA improves hepatic steatosis, inflammation and fibrosis. A proof-of-concept study and the randomized, placebo-controlled Farnesoid X Receptor Ligand Obeticholic Acid in non-alcoholic steatohepatitis Treatment(FLINT) trial also showed improvements in liver histology in patients with NAFLD who received OCA. Weight loss and reduction in blood pressure were also observed. However, the effects of OCA on insulin resistance are conflicting and the lipid profile is adversely affected by this agent. In addition, pruritus is frequently observed during treatment with OCA and might lead to treatment discontinuation. However, given the limitations of existing treatments for NAFLD, OCA might represent a useful therapeutic option in selected patients with NAFLD.
文摘Chronic hepatitis B (CHB) is a major risk factor for hepatocellular carcinoma (HCC). The prevention of HCC is of paramount importance in patients with CHB, particularly in those with cirrhosis. Antiviral treatment can potentially reduce the risk for HCC since it suppresses viral replication, induces HBeAg seroconversion and improves liver histology. However, most evidence supporting a protective effect of antiviral treatment originates from non-randomized or retrospective studies and is limited to conventional interferon and lamivudine. There is a paucity of data on the effects of pegylated interferon and "newer" oral agents (telbivudine, tenofovir, entecavir) on HCC risk. However, it should be emphasized that the existing randomized control studies in patients with CHB were relatively short-term and not designed to assess the effects of antiviral treatment on HCC risk. Since viral load directly correlates with HCC risk, it is reasonable to hypothesize that the reduction in viral load with antiviral treatment will also lower the risk of HCC. This benefit might become more readily apparent with the newer agents used in the management of CHB which are more effective and have a more favorable resistance profile.
文摘Nonalcoholic fatty liver disease(NAFLD) is the commonest chronic liver disease and includes simple steatosis and nonalcoholic steatohepatitis(NASH). Since NASH progresses to cirrhosis more frequently and increases liver-related and cardiovascular disease risk substantially more than simple steatosis, there is a great need to differentiate the two entities. Liver biopsy is the gold standard for the diagnosis of NAFLD but its disadvantages, including the risk of complications and sampling bias, stress the need for developing alternative diagnostic methods. Accordingly, several non-invasive markers have been evaluated for the diagnosis of simple steatosis and NASH, including both serological indices and imaging methods. The present review summarizes the current knowledge on the role of these markers in the diagnosis of NAFLD. Current data suggest that ultrasound and the fibrosis-4 score are probably the most appealing methods for detecting steatosis and for distinguishing NASH from simple steatosis, respectively, because of their low cost and relatively high accuracy. However, currently available methods, both serologic and imaging, cannot obviate the need for liver biopsy for diagnosing NASH due to their substantial false positive and false negative rates. Therefore, the current role of these methods is probably limited in patients who are unwilling or have contraindications for undergoing biopsy.
文摘Nonalcoholic fatty liver disease(NAFLD) is the commonest chronic liver disease in high-income countries and is associated with increased morbidity and mortality. Macrophages appear to play an important role in the development and progression of hepatic fibrosis in patients with NAFLD. Accordingly, modulation of macrophage trafficking might represent an attractive therapeutic strategy in this population. Cenicriviroc is an oral inhibitor of the chemokine ligand 2/C-C chemokine receptor 2 pathway, which plays an important role in the hepatic recruitment of the macrophages. Preclinical studies and a phase 2b study in humans suggest that this agent might hold promise in the management of NAFLD.
文摘Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in developed countries and is associated not only with increased risk for liver disease-related complications but also with higher cardiovascular morbidity. Accordingly, lipid-lowering agents are frequently considered in these patients to reduce cardiovascular risk. However, there have been concerns regarding the safety of these agents in patients with chronic liver diseases. In the present review, we discuss the safety of lipid-lowering agents in patients with NAFLD as well as their effects on both cardiovascular and liver disease in this population. Accumulating data suggest that statins are safe in patients with NAFLD and that they reduce the increased cardiovascular morbidity of this population. However, it is still unclear whether statins are also useful as a treatment for NAFLD per se, since there are very limited and conflicting data on their effects on liver histology. There is also very scarce evidence regarding the safety and efficacy of other lipid-lowering agents in patients with NAFLD. Randomized controlled studies are needed to evaluate the role of lipid-lowering agents and particularly statins for the prevention of both cardiovascular and liver disease-related complications in this high-risk population.
文摘Diabetic retinopathy affects a substantial proportion of patients with diabetes mellitus(DM) and is the leading cause of blindness in working-aged adults. Even though the incidence of diabetic retinopathy has declined in the last decades, its prevalence increased and is expected to rise further as a result of the increasing incidence of type 2 DM(T2DM) and the longer life expectancy of patients with DM. The pathogenesis of diabetic retinopathy is multifactorial. Some observational studies suggested an association between dyslipidemia and the development and progression of retinopathy in patients with DM but others did not confirm this association. Regarding lipid-lowering agents, studies that evaluated the role of statins in the management of these patients are mostly small and yielded discrepant results. Large randomized studies with statins in patients with T2DM showed no benefit of these agents on diabetic retinopathy but were not designed to address this effect. In contrast, both preclinical data and two large randomized controlled studies, the FIELD and the ACCORD trial, showed that fenofibrate delays the progression of diabetic retinopathy. Even though the mechanisms underpinning this favorable effect are not entirely clear, these findings suggest that fenofibrate might represent a useful tool for the management of diabetic retinopathy.
文摘Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. NAFLD is considerably more frequent in patients with type 2 diabetes mellitus (T2DM) than in the general population and is also more severe histologically in this group. Sodium-glucose co-transporter-2 (SGLT2) inhibitors, the newest class of antidiabetic agents, appear to represent a promising option for the management of NAFLD in patients with T2DM. In a number of studies, treatment with SGLT2 inhibitors resulted in a reduction in hepatic steatosis and in transaminase levels. However, existing studies are small, their follow-up period was short and none evaluated the effects of SGLT2 inhibitors on liver histology. Accordingly, larger studies are needed to verify these preliminary results and define the role of SGLT2 inhibitors in the treatment of NAFLD in patients with T2DM.
文摘Clopidogrel is a widely used antiplatelet agent for the secondary prevention of cardiovascular events in patients with stable coronary heart disease, acute coronary syndromes and ischemic stroke. Even though clopidogrel is safer than aspirin in terms of risk for gastrointestinal(GI) bleeding, the elderly, and patients with a history of prior GI bleeding, with Helicobacter pylori infection or those who are also treated with aspirin, anticoagulants, corticosteroids or nonsteroidal antiinflammatory drugs are at high risk for GI complications when treated with clopidogrel. Accordingly, proton pump inhibitors are frequently administered in combination with clopidogrel to reduce the risk for GI bleeding. Nevertheless, pharmacodynamic studies suggest that omeprazole might attenuate the antiplatelet effect of clopidogrel. However, in observational studies, this interaction does not appear to translate into increased cardiovascular risk in patients treated with this combination. Moreover, in the only randomized, double-blind study that assessed the cardiovascular implications of combining clopidogrel and omeprazole, patients treated with clopidogrel/omeprazole combination had reduced risk for GI events and similar risk for cardiovascular events than patients treated with clopidogrel and placebo. However, the premature interruption of the study and the lack of power analysis in terms of the cardiovascular endpoint do not allow definite conclusions regarding the cardiovascular safety of clopidogrel/omeprazole combination. Other proton pump inhibitors do not appear to interact with clopidogrel. Nevertheless, given the limitations of existing observational and interventional studies, the decision to administer proton pump inhibitors to patients treated with clopidogrel should be individualized based on the patient's bleeding and cardiovascular risk.
文摘Diabetes mellitus(DM) is a major risk factor for cardiovascular events, including ischemic stroke. Moreover, ischemic stroke appears to be more severe in these patients and to be associated with less favorable outcomes. However, strict glycemic control does not appear to reduce the risk of ischemic stroke. On the other hand, newer glucose-lowering agents(glucagon-like peptide 1 receptor agonists and sodiumglucose cotransporter 2 inhibitors) reduced the risk of cardiovascular events in recent randomized, placebocontrolled trials. Semaglutide also reduced the risk of ischemic stroke. These benefits are independent of glucose lowering and might be due to the favorable effects of these agents on body weight and blood pressure. Pioglitazone also reduced the risk of recurrent stroke in patients with insulin resistance or type 2 DM but the unfavorable safety profile limits its use. In contrast, sulfonylureas and dipeptidyl peptidase 4 inhibitors have a neutral effect on cardiovascular morbidity and might be less attractive options in this high-risk population.
文摘Herbal medicine products represent a common therapeutic approach in the East and are gaining increasing popularity in Western countries. They are unjustifiably considered to be side-effect free; on the contrary, severe toxicity, including catastrophic hepatic injury has been reported in association with their use. Vigilance isrequired from both physicians and the general public. Physicians should always suspect herbal medicines when evaluating a patient with unexplained liver injury. Regulation standards for herbal products need to be reconsidered, so that the efficacy and safety of these products have been clearly demonstrated before they enter the markets.
文摘Pulmonary embolism(PE)is an important public health problem.In August2019,the European Society of Cardiology in collaboration with the European Respiratory Society released new guidelines for the diagnosis and management of PE.We discuss the basic changes between these recent guidelines and the previous guidelines that were published in 2014.Regarding diagnosis,the new guidelines propose the use of an age-adjusted cut-off level of D-dimers instead of a fixed cut-off value.A D-dimer test adapted to clinical possibility should also be considered instead of fixed cut-off level of D-dimer.Detailed recommendations for the diagnosis of PE during pregnancy are also provided.Regarding risk stratification,assessment of PE-related early mortality risk is recommended.Moreover,the importance of right ventricular dysfunction is emphasized in lowrisk patients.For further risk stratification of the severity of PE in patients without hemodynamic instability,use of validated scores that combine clinical,imaging and laboratory PE-related prognostic factors might also be considered.Regarding treatment,the possibility of early discharge is mentioned in patients without severe comorbidities,who are not of high risk for sudden death and in whom proper medical management at home and proper medical follow up can be ensured.The new guidelines also suggest that pro-brain natriuretic peptide levels,right ventricular function and the presence of thrombus in the right heart could be useful for guiding the decision of early discharge.Overall,these new guidelines introduce several key changes and knowledge and adherence to them will improve the outcome of patients with PE.
文摘The rising rates of obesity in youth have concurrently led to an increase in the rates of type 2 diabetes mellitus (T2DM) in this age group. However, there are limited data on the efficacy of different antidiabetic agents in youth. In this context, the Treatment Options for Type 2 Diabetes in Adolescents and Youth trial recently reported that the majority of obese children and adolescents 10-17-years old with newly diagnosed T2DM (T2DM duration less than 2 years) could not achieve HbA1c levels < 8% for more than 1 year with metformin monotherapy, metformin plus rosiglitazone combination, or metformin and lifestyle changes. These findings suggest that, in the majority of youth with T2DM, tight long-term glycemic control with oral agents is an elusive goal and that most patients will require treatment with insulin within a few years of diagnosis to achieve HbA1c targets and reduce the risk of macro- and microvascular complications. Therefore, reducing the incidence of T2DM by preventing pediatric obesity through the implementation of lifestyle changes in the community should be the primary objective of healthcare systems.
文摘Heart failure(HF)is a major complication of diabetes mellitus(DM).Patients with DM have considerably higher risk for HF than non-diabetic subjects and HF is also more severe in the former.Given the rising prevalence of DM,the management of HF in diabetic patients has become the focus of increased attention.In this context,the findings of several randomized,placebo-controlled trials that evaluated the effects of sodium-glucose co-transporter-2 inhibitors on the risk of hospitalization for HF in patients with type 2 DM represent a paradigm shift in the management of HF.These agents consistently reduced the risk of hospitalization for HF both in patients with and in those without HF.These benefits appear to be partly independent from glucose-lowering and have also been reported in patients without DM.However,there are more limited data regarding the benefit of sodium-glucose co-transporter-2 inhibitors in patients with HF and preserved left ventricular ejection fraction,which is the commonest type of HF in diabetic patients.
文摘Diabetes mellitus(DM)is an independent risk factor for admission to intensive care unit and death in patients with coronavirus disease 2019(COVID-19).On the other hand,medications used in the management of COVID-19 are potentially associated with increases in blood glucose levels and a higher incidence of infections.Accordingly,care of patients with DM and acute COVID-19 requires careful consideration of both diseases.Hyperglycemia and hypoglycemia are associated with adverse outcomes and therefore frequent measurement of blood glucose levels and a basal-bolus insulin regimen are required in most patients.Regarding the management of COVID-19,dexamethasone increases blood glucose levels and might also increase the risk for infections.On the other hand,limited data suggest that antiviral and immunomodulatory agents used in COVID-19 are not strongly associated with higher incidence of infections in this population.As knowledge evolves in this field,optimization of the management of both DM and COVID-19 will hopefully improve the outcome of these patients。
文摘Nonalcoholic fatty liver disease(NAFLD) is the commonest liver disease in Western countries.Treatment of NAFLD is currently based on lifestyle measures and no effective pharmacologic treatment is available so far.Emerging evidence,mainly from animal studies,suggests that the renin-angiotensin-aldosterone system may be of major importance in the pathogenesis of NAFLD and indicates that angiotensin-converting enzyme inhibitors(ACE-I) and angiotensin receptor blockers(ARBs) as a potentially useful therapeutic approach.However,data from human studies are limited and contradictory.In addition,there are few randomized controlled trials(RCTs) on the effects of ACE-I or ARB in patients with NAFLD and most data are from retrospective studies,pilot prospective studies and post hoc analyses of clinical trials.Accordingly,more and larger RCTs are needed to directly assess the effectiveness of ACE-I and ARBs in NAFLD.
文摘The possible relationship between diabetes mellitus (DM) and colorectal cancer (CRC), concerning pathophysiological and molecular mechanisms is highlighted in this review. The most recent and complete articles and developments in this particular field were thoroughly reviewed. Common risk factors, such as obesity, sedentary lifestyle, and Western diet between DM and CRC, led to the theory that DM might be a causal agent for CRC development. Various studies have connected type 2 DM and CRC, either proximal or distal, in both sexes. Additionally, chronic insulin treatment has been linked with increased colorectal tumor risk among type 2 diabetic patients. Interestingly, elevated hemoglobin A1c has been proven to be an independent predictor of aggressive clinical behavior in CRC patients. These mechanisms include the insulin-like growth factor-hyperinsulinemia theory and the participation of oncogenic intracellular signaling pathways. Furthermore, it has been proposed that Cox-2 inhibitors might have a role in decreasing the incidence of CRC. Finally, the use of statins to reduce the risk for colon cancer in patients with diabetes has remained controversial. Diabetic patients over 50 should receive counseling regarding their elevated risk for CRC, and screening colonoscopy should be recommended before initiating insulin therapy. However, there are no current guidelines, and this strategy is not yet applicable to some countries, as the corresponding risk would not allow screening colonoscopy to be adopted. There is strong evidence to indicate that DM is a causal agent for CRC development. This conclusion provides new impetus for re-evaluating CRC screening worldwide.
文摘Type 2 diabetes mellitus (T2DM) is a leading cause of blindness, non-traumatic amputation and end-stage renal disease as well as a major cardiovascular risk factor. Tight glycemic control reduces the incidence of microvascular complications of T2DM whereas its effects on macrovascular complication are more controversial. However, glycemic targets are achieved by a minority of diabetic patients despite the availability of several antidiabetic agents. In the present commentary, we discuss the findings of two recent randomized studies that compared bariatric surgery with medical treatment in patients with uncontrolled T2DM. Both studies showed that bariatric surgery results in remission of T2DM in the majority of patients. However, both studies were limited to relatively young patients without comorbidities, had relatively short follow-up and did not assess the effects of surgery on T2DM complications. Moreover, the perioperative complications of bariatric surgery and its limited availability in some areas are additional barriers to the wider implementation of this therapeutic approach. On the other hand, the elucidation of the mechanisms underpinning the resolution of T2DM following bariatric surgery might resultin the development of novel, more effective pharmacotherapies for this common disease.
