AIM： To examine the risk of renal events in patients with biopsy-proven diabetic nephropathy （DN） and its possible associated factors.METHODS： Clinical and histological data of 60 pa-tients diagnosed with diabetic...AIM： To examine the risk of renal events in patients with biopsy-proven diabetic nephropathy （DN） and its possible associated factors.METHODS： Clinical and histological data of 60 pa-tients diagnosed with diabetic nephropathy were retro-spectively collected. Patients with evidence or suspicion of other nephropathies were excluded from the study. The fnal event was defned as renal replacement ther-apy （RRT） initiation or progression of chronic kidney disease （CKD）, according to the KDIGO 2012 defnition of a decrease in CKD category and a decrease in GFR of 25% or more. RESULTS： A total of 45 patients with a follow-up of at least 3 mo were included. Most of the patients presented type 2 DM, with a mean age of 58.3 years old. The time of evolution of DM was 9.6 ± 7.8 years, al-though in 13 patients, it was less than 5 years. A total of 62% of patients reached the fnal event in a mean period of 3.4 years （95%CI： 2.1-4.7）, with 21 of them requiring dialysis. The factors that were indepen-dently associated with renal survival were estimated glomerular fltration rate （eGFR） at the time of biopsy, cardiovascular disease （CVD） history and HbA1c less than 7%. Therefore, for each 10 mL/min per 1.73 m2 reduction in eGFR, we obtained a DN progression risk of HR = 2 （1.3-3.0） （P = 0.001）; patients with CVD were at greater risk for DN progression （HR = 2.8, 1.1-7.1, P = 0.032）, and CKD patients with HbA1c 〈 7% demonstrated greater renal risk than patients with HbA1c ≥ 7%, with an HR of 2.9 （1.0-8.4） （P = 0.054）.CONCLUSION： A past history of CVD is a risk fac-tor for DN progression. Levels of HbA1c less than 7% could favor an eGFR decrease in these patients.展开更多
1 Introduction Erectile dysfunction （ED） and coronary artery disease （CAD） are closely linked, as both conditions share the same cardiovascular risk factors. Indeed, these risk factors can determine endothelial d...1 Introduction Erectile dysfunction （ED） and coronary artery disease （CAD） are closely linked, as both conditions share the same cardiovascular risk factors. Indeed, these risk factors can determine endothelial dysfunction that represents the common underlying mechanism of both ED and CAD. The prevalence of ED is about three-fold higher among diabetic patients than in the general population and a higher prevalence of CAD has been observed in people with diabetes when compared to non-diabetic subjects.Some studies showed that ED can be a powerful marker of silent CAD and a strong predictor of cardiovascular events in apparently uncomplicated type 2 diabetic patients Therefore ED is now considered as a sentinel symptom of silent CAD, as ED often precedes the onset of myocardial ischemia itself by many years.展开更多
Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and af...Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.展开更多
The prevalence of obesity and related conditions like non-alcoholic fatty liver disease(NAFLD) is increasing worldwide and therapeutic options are limited.Alternative treatment options are therefore intensively sought...The prevalence of obesity and related conditions like non-alcoholic fatty liver disease(NAFLD) is increasing worldwide and therapeutic options are limited.Alternative treatment options are therefore intensively sought after.An interesting candidate is the natural polyphenol resveratrol(RSV) that activates adenosinmonophosphate-activated protein kinase(AMPK) and silent information regulation-2 homolog 1(SIRT1).In addition,RSV has known anti-oxidant and anti-inflammatory effects.Here,we review the current evidence for RSVmediated effects on NAFLD and address the different aspects of NAFLD and non-alcoholic steatohepatitis(NASH) pathogenesis with respect to free fatty acid(FFA) flux from adipose tissue,hepatic de novo lipogenesis,inadequate FFA β-oxidation and additional intra- and extrahepatic inflammatory and oxidant hits.We review the in vivo evidence from animal studies and clinical trials.The abundance of animal studies reports a decrease in hepatic triglyceride accumulation,liver weight and a general improvement in histological fatty liver changes,along with a reduction in circulating insulin,glucose and lipid levels.Some studies document AMPK or SIRT1 activation,and modulation of relevant markers of hepatic lipogenesis,inflammation and oxidation status.However,AMPK/SIRT1-independent actions are also likely.Clinical trials are scarce and have primarily been performed with a focus on overweight/obese participants without a focus on NAFLD/NASH and histological liver changes.Future clinical studies with appropriate design are needed to clarify the true impact of RSV treatment in NAFLD/NASH patients.展开更多
文摘AIM： To examine the risk of renal events in patients with biopsy-proven diabetic nephropathy （DN） and its possible associated factors.METHODS： Clinical and histological data of 60 pa-tients diagnosed with diabetic nephropathy were retro-spectively collected. Patients with evidence or suspicion of other nephropathies were excluded from the study. The fnal event was defned as renal replacement ther-apy （RRT） initiation or progression of chronic kidney disease （CKD）, according to the KDIGO 2012 defnition of a decrease in CKD category and a decrease in GFR of 25% or more. RESULTS： A total of 45 patients with a follow-up of at least 3 mo were included. Most of the patients presented type 2 DM, with a mean age of 58.3 years old. The time of evolution of DM was 9.6 ± 7.8 years, al-though in 13 patients, it was less than 5 years. A total of 62% of patients reached the fnal event in a mean period of 3.4 years （95%CI： 2.1-4.7）, with 21 of them requiring dialysis. The factors that were indepen-dently associated with renal survival were estimated glomerular fltration rate （eGFR） at the time of biopsy, cardiovascular disease （CVD） history and HbA1c less than 7%. Therefore, for each 10 mL/min per 1.73 m2 reduction in eGFR, we obtained a DN progression risk of HR = 2 （1.3-3.0） （P = 0.001）; patients with CVD were at greater risk for DN progression （HR = 2.8, 1.1-7.1, P = 0.032）, and CKD patients with HbA1c 〈 7% demonstrated greater renal risk than patients with HbA1c ≥ 7%, with an HR of 2.9 （1.0-8.4） （P = 0.054）.CONCLUSION： A past history of CVD is a risk fac-tor for DN progression. Levels of HbA1c less than 7% could favor an eGFR decrease in these patients.
文摘1 Introduction Erectile dysfunction （ED） and coronary artery disease （CAD） are closely linked, as both conditions share the same cardiovascular risk factors. Indeed, these risk factors can determine endothelial dysfunction that represents the common underlying mechanism of both ED and CAD. The prevalence of ED is about three-fold higher among diabetic patients than in the general population and a higher prevalence of CAD has been observed in people with diabetes when compared to non-diabetic subjects.Some studies showed that ED can be a powerful marker of silent CAD and a strong predictor of cardiovascular events in apparently uncomplicated type 2 diabetic patients Therefore ED is now considered as a sentinel symptom of silent CAD, as ED often precedes the onset of myocardial ischemia itself by many years.
基金supported by American Diabetes Association,American Heart Association,NIH NIEHS,NIH NIA,NIH NINDS,and NIH ARRA
文摘Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.
基金Supported by Aarhus University and the Danish Council for Independent Research,Medical Sciences,No.11-107912The Danish Strategic Research Council has supported the LIRMOI study on RSV effects in NAFLD and metabolic diseases,No.10-093499+5 种基金The NOVO Nordisk Foundation has supported Grnbk H by a research grantsupported by the Robert WStorr Bequest to the Sydney MedicalFoundation,University of Sydneya National Health and Medical Research Council of Australia (NHMRC) Program Grant No.1053206Project grants 632630 and 1049857
文摘The prevalence of obesity and related conditions like non-alcoholic fatty liver disease(NAFLD) is increasing worldwide and therapeutic options are limited.Alternative treatment options are therefore intensively sought after.An interesting candidate is the natural polyphenol resveratrol(RSV) that activates adenosinmonophosphate-activated protein kinase(AMPK) and silent information regulation-2 homolog 1(SIRT1).In addition,RSV has known anti-oxidant and anti-inflammatory effects.Here,we review the current evidence for RSVmediated effects on NAFLD and address the different aspects of NAFLD and non-alcoholic steatohepatitis(NASH) pathogenesis with respect to free fatty acid(FFA) flux from adipose tissue,hepatic de novo lipogenesis,inadequate FFA β-oxidation and additional intra- and extrahepatic inflammatory and oxidant hits.We review the in vivo evidence from animal studies and clinical trials.The abundance of animal studies reports a decrease in hepatic triglyceride accumulation,liver weight and a general improvement in histological fatty liver changes,along with a reduction in circulating insulin,glucose and lipid levels.Some studies document AMPK or SIRT1 activation,and modulation of relevant markers of hepatic lipogenesis,inflammation and oxidation status.However,AMPK/SIRT1-independent actions are also likely.Clinical trials are scarce and have primarily been performed with a focus on overweight/obese participants without a focus on NAFLD/NASH and histological liver changes.Future clinical studies with appropriate design are needed to clarify the true impact of RSV treatment in NAFLD/NASH patients.
