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
Lack of conclusive beneficial effects of strict glycemic control on macrovascular complications has been very frustrating for clinicians involved in care of patients with diabetes mellitus (DM). Highly publicized cont...Lack of conclusive beneficial effects of strict glycemic control on macrovascular complications has been very frustrating for clinicians involved in care of patients with diabetes mellitus (DM). Highly publicized controversy surrounding cardiovascular (CV) safety of rosiglitazone resulted in major changes in United States Food and Drug Administration policy in 2008 regarding approval process of new antidiabetic medications, which has resulted in revolutionary data from several large CV outcome trials over the last few years. All drugs in glucagon-like peptide-1 receptor agonist (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT-2) inhibitor classes have shown to be CV safe with heterogeneous results on CV efficacy. Given twofold higher CV disease mortality in patients with DM than without DM, GLP-1 RAs and SGLT-2-inhibitors are important additions to clinician’s armamentarium and should be second line-therapy particularly in patients with T2DM and established atherosclerotic CV disease or high risks for CV disease. Abundance of data and heterogeneity in CV outcome trials results can make it difficult for clinicians, particularly primary care physicians, to stay updated with all the recent evidence. The scope of this comprehensive review will focus on all major CV outcome studies evaluating CV safety and efficacy of GLP-1 RAs and SGLT-2 inhibitors.展开更多
Osteoporosis has become a serious health problem throughout the world which is associated with an increased risk of bone fractures and mortality among the people of middle to old ages.Diabetes is also a major health p...Osteoporosis has become a serious health problem throughout the world which is associated with an increased risk of bone fractures and mortality among the people of middle to old ages.Diabetes is also a major health problem among the people of all age ranges and the sufferers due to this abnormality increasing day by day.The aim of this review is to summarize the possible mechanisms through which diabetes may induce osteoporosis.Diabetes mellitus generally exerts its effect on different parts of the body including bone cells specially the osteoblast and osteoclast,muscles,retina of the eyes,adipose tissue,endocrine system specially parathyroid hormone(PTH) and estrogen,cytokines,nervous system and digestive system.Diabetes negatively regulates osteoblast differentiation and function while positively regulates osteoclast differentiation and function through the regulation of different intermediate factors and thereby decreases bone formation while increases bone resorption.Some factors such as diabetic neuropathy,reactive oxygen species,Vitamin D,PTH have their effects on muscle cells.Diabetes decreases the muscle strength through regulating these factors in various ways and ultimately increases the risk of fall that may cause bone fractures.展开更多
The study by Cao et al aimed to identify early second-trimester biomarkers that could predict gestational diabetes mellitus(GDM)development using advanced proteomic techniques,such as Isobaric tags for relative and ab...The study by Cao et al aimed to identify early second-trimester biomarkers that could predict gestational diabetes mellitus(GDM)development using advanced proteomic techniques,such as Isobaric tags for relative and absolute quantitation isobaric tags for relative and absolute quantitation and liquid chromatography-mass spectrometry liquid chromatography-mass spectrometry.Their analysis revealed 47 differentially expressed proteins in the GDM group,with retinol-binding protein 4 and angiopoietin-like 8 showing significantly elevated serum levels compared to controls.Although these findings are promising,the study is limited by its small sample size(n=4 per group)and lacks essential details on the reproducibility and reliability of the protein quantification methods used.Furthermore,the absence of experimental validation weakens the interpretation of the protein-protein interaction network identified through bioinformatics analysis.The study's focus on second-trimester biomarkers raises concerns about whether this is a sufficiently early period to implement preventive interventions for GDM.Predicting GDM risk during the first trimester or pre-conceptional period may offer more clinical relevance.Despite its limitations,the study presents valuable insights into potential GDM biomarkers,but larger,well-validated studies are needed to establish their predictive utility and generalizability.展开更多
Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close rel...Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.展开更多
Cardiac autonomic neuropathy(CAN)is an often overlooked and common complication of diabetes mellitus.CAN is associated with increased cardiovascular morbidity and mortality.The pathogenesis of CAN is complex and invol...Cardiac autonomic neuropathy(CAN)is an often overlooked and common complication of diabetes mellitus.CAN is associated with increased cardiovascular morbidity and mortality.The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death.In addition,autoimmune and genetic factors are involved in the development of CAN.CAN might be subclinical for several years until the patient develops resting tachycardia,exercise intolerance,postural hypotension,cardiac dysfunction and diabetic cardiomyopathy.During its sub-clinical phase,heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic.Newer imaging techniques(such as scintigraphy)have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system.One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN;however,the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN,and also proposed screening for CAN in patients with diabetes mellitus.A major challenge,however,is the lack of specific treatment to slow the progression or prevent the development of CAN.Lifestyle changes,improved metabolic control might prevent or slow the progression of CAN.Reversal will require combination of these treatments with new targeted therapeutic approaches.The aim of this article is to review the latest evidence regarding the epidemiology,pathogenesis,manifestations,diagnosis and treatment for CAN.展开更多
Free fatty acids are known to play a key role in promoting loss of insulin sensitivity in type 2 diabetes mellitus but the underlying mechanism is still unclear.It has been postulated that an increase in the intracell...Free fatty acids are known to play a key role in promoting loss of insulin sensitivity in type 2 diabetes mellitus but the underlying mechanism is still unclear.It has been postulated that an increase in the intracellular concentration of fatty acid metabolites activates a serine kinase cascade,which leads to defects in insu-lin signaling downstream to the insulin receptor.In addition,the complex network of adipokines released from adipose tissue modulates the response of tissues to insulin.Among the many molecules involved in the intracellular processing of the signal provided by insulin,the insulin receptor substrate-2,the protein kinase B and the forkhead transcription factor Foxo 1a are of particular interest,as recent data has provided strong evidence that dysfunction of these proteins results in insulin resistance in vivo.Recently,studies have revealed that phosphoinositidedependent kinase 1-independent phosphorylation of protein kinase Cε causes a reduction in insulin receptor gene expression.Additionally,it has been suggested that mitochondrial dysfunction triggers activation of several serine kinases,and weakens insulin signal transduction.Thus,in this review,the current developments in understanding the pathophysiological processes of insulin resistance in type 2 diabetes have been summarized.In addition,this study provides potential new targets for the treatment and prevention of type 2 diabetes.展开更多
AIM:To evaluate metabolic control and health-related quality of life(HRQOL)in a type 1 diabetes mellitus(T1DM)population.METHODS:As part of a prospective cohort study,283T1DM patients treated with various insulin trea...AIM:To evaluate metabolic control and health-related quality of life(HRQOL)in a type 1 diabetes mellitus(T1DM)population.METHODS:As part of a prospective cohort study,283T1DM patients treated with various insulin treatment modalities including multiple daily injections(MDI)and continuous subcutaneous insulin infusion(CSII)were examined annually.HRQOL was measured using the SF-36 and EuroQol questionnaires.Data regarding HRQOL,glycaemic and metabolic control from baseline and follow-up measures in 2002 and 2010 were analysed.Linear mixed models were used to calculate estimated values and differences between the three moments in time and the three treatment modalities.RESULTS:Significant changes[meanΔ(95%CI)]in body mass index[2.4 kg/m2(1.0,3.8)],systolic blood pressure[-6.4 mmHg(-11.4,-1.3)]and EuroQol-VAS[-7.3(-11.4,-3.3)]were observed over time.In 2010,168 patients were lost to follow-up.Regarding mode of therapy,52 patients remained on MDI,28 remained on CSII,and 33 patients switched from MDI to CSII during follow-up.Among patients on MDI,HRQOL decreased significantly over time:mental component summary[-9.8(-16.3,-3.2)],physical component summary[-8.6(-15.3,-1.8)]and EuroQol-VAS[-8.1(-14.0,-2.3)],P<0.05 for all.For patients using CSII,the EuroQol-VAS decreased[-9.6(-17.5,-1.7)].None of the changes over time in HRQOL differed significantly with the changes over time within the other treatment groups.CONCLUSION:No differences with respect to metabolic and HRQOL parameters between the various insulin treatment modalities were observed after 15 years of follow-up in T1DM patients.展开更多
AIM: To investigate the antihyperglycemic, antihyperlipidemic and antioxidant functions of a polyherbal formulation, "Diabegon", in human subjects with type 2 diabetes mellitus.METHODS: A total of 33 human s...AIM: To investigate the antihyperglycemic, antihyperlipidemic and antioxidant functions of a polyherbal formulation, "Diabegon", in human subjects with type 2 diabetes mellitus.METHODS: A total of 33 human subjects with type 2 diabetes mellitus were recruited for the study and all anthropological and biochemical parameters were recorded at the time of registration. The subjects were given hot water extract obtained from 10 gm of "Diabegon" powder, "Diabegon kwath", on an empty stomach everyday in the morning under personal supervision for 6 mo. The therapeutic functions of the "Diabegon kwath" was assessed by monitoring the blood glucoselevels at monthly intervals and glycosylated hemoglobin, lipid profile and biomarkers of oxidative stress, liver and kidney function markers at three monthly intervals in the study subjects. RESULTS: Daily administration of hot water extract of "Diabegon" regularly for 6 mo resulted in significant reductions of blood glucose and glycosylated hemoglobin levels. There was also a significant increase in high density lipoprotein cholesterol levels with concomitant decreases in total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density lipoprotein. A significant improvement in glycosuria and proteinuria was also observed. Also, the subjects exhibited a significant improvement in enzymatic and nonenzymatic biochemical markers of oxidative stress. The kidney and liver functions remained normal and in fact improved in many subjects.CONCLUSION: The study which is first of its kind, advocates "Diabegon kwath" as a safe and effective Ayurvedic therapy for the treatment of human type 2 diabetes mellitus and further placebo controlled trial may substantiate the therapeutic efficacy of the formulation.展开更多
Human sodium-glucose cotransporter 2 (hSGLT2) is a membrane protein responsible for glucose reabsorption from the glomerular filtrate in the proximal tubule. Inhibition of hSGLT2 has been regarded as a brand new thera...Human sodium-glucose cotransporter 2 (hSGLT2) is a membrane protein responsible for glucose reabsorption from the glomerular filtrate in the proximal tubule. Inhibition of hSGLT2 has been regarded as a brand new therapeutic approach for the treatment of type 2 diabetes mellitus (T2DM) due to its non-insulin related characteristics with less side effects. Current commercially available hSGLT2 inhibitors are all C-glycoside inhibitors. Previous studies have reported that N-glycoside inhibitors have better potential to serve as new drugs due to their good metabolic stability. In addition, non-glycoside inhibitors have been shown to exhibit the capability to overcome the existing problems of current glycoside inhibitors, including low tissue permeability, poor stability and short serum half-time. Here, we aimed to discover novel N-glycoside and non-glycoside hSGLT2 inhibitors by a combination of several computational approaches. A ligand-based pharmacophore model was generated, well validated and subsequently utilized as a 3D query to identify novel hSGLT2 inhibitors from National Cancer Institute (NCI) and Traditional Chinese Medicine (TCM) databases. Finally, one N-glycoside (NSC679207) and one non-glycoside (TCM_Piperenol_A) hSGLT2 inhibitors were successfully identified, which were proven to exhibit excellent binding affinities, pharmacokinetic properties and less toxicity than the commercially available hSGLT2 inhibitor, canagliflozin, via molecular docking, ADMET prediction, molecular dynamics (MD) simulations and binding free energy calculations. All together, our results strongly suggest that these two compounds have great potential to serve as novel hSGLT2 inhibitors for the treatment of T2DM and their efficacies may be further examined by a series of in vitro and/or in vivo bioassays.展开更多
In this editorial,we have commented on the article that has been published in the recent issue of World Journal of Clinical Cases.The authors have described a case of unilateral thyroid cyst and have opined that the a...In this editorial,we have commented on the article that has been published in the recent issue of World Journal of Clinical Cases.The authors have described a case of unilateral thyroid cyst and have opined that the acute onset of infection may be linked to diabetes mellitus(DM).We have focused on the role of nutrition in the association between DM and infection.Patients with DM are at a high risk of infection,which could also be attributed to nutrition-related factors.Nutritional interventions for patients with diabetes are mainly based on a low-calorie diet,which can be achieved by adhering to a low-carbohydrate diet.However,dietary fiber supplementation is recommended to maintain the diversity of the gut microbiota.Furthermore,high-quality protein can prevent the increased risk of infection due to malnutrition.Supplementation of vitamins C,vitamins A,vitamins D,and folic acid improves blood sugar control and facilitates immune regulation.Mineral deficiencies augment the risk of infection,but the relationship with diabetes is mostly U-shaped and a good intake should be maintained.展开更多
The accumulation of fat in the pancreatic gland has been referred to using various synonyms,such as pancreatic lipomatosis,fatty replacement,fatty infiltration,fatty pancreas,lipomatous pseudohypertrophy,non-alcoholic...The accumulation of fat in the pancreatic gland has been referred to using various synonyms,such as pancreatic lipomatosis,fatty replacement,fatty infiltration,fatty pancreas,lipomatous pseudohypertrophy,non-alcoholic fatty pancreatic disease and pancreatic steatosis We believe that pancreatic steatosis is the best description of fat accumulation in the pancreatic gland without fat replacement,and this term also describes the possibility that the fat accumulation is a reversible process.A review of the existing literature was carried out,and it was found that there was notable evidence from both the pathological and the imaging point of view that pancreatic steatosis is an increasing problem due to the increasing incidence of obesity.The conclusion was that pancreatic steatosis was easily detectable using modern imaging techniques,such as ultrasonography,endoscopic ultrasonography,computed tomography and magnetic resonance imaging.Pancreatic steatosis was not due to the presence of diabetes mellitus but was highly associated with the metabolic syndrome.The possible presence of steatopancreatitis should be better evaluated,especially regarding the inflammatory cascade,and additional studies are needed which are capable of assessing whether non-alcoholic steatopancreatitis really exists as does non-alcoholic steatohepatitis.Finally,the presence of exocrine pancreatic function should be extensively evaluated in patients with pancreatic steatosis.展开更多
AIN To study the relationship of Imp2 and DR3genes with type Ⅰ diabetes mellitus.NETHODS Imp2 genotypes and DR3 wereidentified in 68 patients with type Ⅰ diabetesmellitus(Ⅰ-DM)and 71 healthy controls.Then,Ⅰ-DM pat...AIN To study the relationship of Imp2 and DR3genes with type Ⅰ diabetes mellitus.NETHODS Imp2 genotypes and DR3 wereidentified in 68 patients with type Ⅰ diabetesmellitus(Ⅰ-DM)and 71 healthy controls.Then,Ⅰ-DM patients and controls were respectivelyallocated into DR3-positive and DR3-negativegroups.The frequencies of Imp2 and DR3 genein random subjects,and Imp2 genotypes in DR3-matched subjects were compared between Ⅰ-DMpatients and controls.At the same time,Ⅰ-DMpatients were divided into 3 groups based on theonset age of diabetics:group A≤14 years,group B 15-30 years and group C≥31 years.RESULTS The frequency of DR3 in Ⅰ-DMpatients was significantly higher than that incontrols(47% vs 21%,P【0.005),and it wassignificantly higher in group A than that in groupB+C(70% vs 36%,x^2=7.07,P【0.01).Therewas a significant difference among groups withdifferent onset age of diabetics(x^2=8.19,rp=0.33,P【0.05).In random subjects,thefrequency of Imp2.R/R in Ⅰ-DM patients waslower(43% vs 61%,P【0.05)and Imp2.R/Hhigher(53% vs 28%,P【0.05)than that incontrols,and there was no significant differenceamong groups with different onset age ofdiabetics.In DR3-positive subjects,thefrequency of Imp2.R/R in Ⅰ-DM patients waslower(47% vs 87%,P【0.05)and Imp2-R/H higher(47% vs 13%,P【0.05)than that incontrols.In DR3-negative subjects,thefrequency of Imp2.R/H in Ⅰ-DM patients washigher than that in controls(58% vs 32%,P【0.01),but the frequency of Imp2-R/R and Imp2H/H was not significantly different betweenthese two groups.CONCLUSION DR3 gene may be one of thesusceptible genes of Ⅰ-DM,and significantlyrelated to the onset age of diabetics,and thepersons with DR3 may have an younger onsetage of diabeteS.The Imp2-R/R may be theprotective genotype of Ⅰ-DM,and Imp2-R/H thesusceptible genotype.These were not affectedby DR3 gene.Imp-2 genotypes were not relatedwith the onset age of diabetics.展开更多
Neuropathy is a common complication of diabetes mellitus(DM) with a wide clinical spectrum that encompasses generalized to focal and multifocal forms. Entrapment neuropathies(EN), which are focal forms, are so frequen...Neuropathy is a common complication of diabetes mellitus(DM) with a wide clinical spectrum that encompasses generalized to focal and multifocal forms. Entrapment neuropathies(EN), which are focal forms, are so frequent at any stage of the diabetic disease, that they may be considered a neurophysiological hallmarkof peripheral nerve involvement in DM. Indeed, EN may be the earliest neurophysiological abnormalities in DM,particularly in the upper limbs, even in the absence of a generalized polyneuropathy, or it may be superimposed on a generalized diabetic neuropathy. This remarkable frequency of EN in diabetes is underlain by a peculiar pathophysiological background. Due to the metabolic alterations consequent to abnormal glucose metabolism,the peripheral nerves show both functional impairment and structural changes, even in the preclinical stage,making them more prone to entrapment in anatomically constrained channels. This review discusses the most common and relevant EN encountered in diabetic patient in their epidemiological, pathophysiological and diagnostic features.展开更多
Diabetes has become a growing concern in Japan, both medically and financially. The medical cost of diabetes was estimated at 1215 billion yen for fiscal year 2011. We analyzed the length of stay (LOS) in a hospital f...Diabetes has become a growing concern in Japan, both medically and financially. The medical cost of diabetes was estimated at 1215 billion yen for fiscal year 2011. We analyzed the length of stay (LOS) in a hospital for type 2 diabetes mellitus patients who participated in educational programs to determine factors affecting LOS. Data on 991 patients obtained from 28 Red Cross hospitals in 2008 were used. For the analysis, we used the Box-Cox transformation model and Hausman test. The results revealed that patients aged 75 years and above and those with comorbidities and complications were prone to longer LOS. The analysis also revealed significant differences in LOS across the hospitals, even after controlling for patient characteristics. Finally, we applied the least squares method to determine the effects of hospital and regional factors and revealed that patients’ LOS was affected by the region’s average LOS. Regional corporations and networks appeared to be important in improving educational programs.展开更多
Background: The organs in the body function in coherent organ networks. These organ networks are commonly known as physiological systems. Blood Glucose, Blood Pressure and pH exhibit the characteristics of neurally re...Background: The organs in the body function in coherent organ networks. These organ networks are commonly known as physiological systems. Blood Glucose, Blood Pressure and pH exhibit the characteristics of neurally regulated Physiological Systems. Any medical condition, such as diabetes, has origins which are due to systemic dysfunction. This influences the genetic expression of proteins and the rate at which such expressed proteins subsequently react. Increased levels of acidity influence the levels of available minerals, protein conformation, and hence the rate at which expressed proteins such as insulin and leptin react or function. This is particularly significant in diabetes etiology where a deficiency of insulin and insulin-“resistance” are significant features of type 1 and type 2 diabetes. Proteins such as Insulin absorb and emit light. Moreover, the spectrum and intensity of the bioluminescence emitted from glycated proteins (which are more significantly bioluminescent) influence colour perception. Accordingly, changes to the diabetic’s colour perception can be used as the basis of a cognitive screening technique which is able to quantify the influence of genotype and phenotype. This may have significant advantages over current biomarker techniques which are not able to satisfactorily determine the earliest onset of?diabetes or distinguish between the symptomatic and presymptomatic onset of diabetes. Such methodology, based upon the properties of proteins, i.e. effectively, the rate at which proteins are expressed and the rate at which such expressed proteins subsequently react, allows the clinician to quantify genotype and phenotype and may contribute to a greater understanding of the processes responsible for what are commonly known as type 1 and type 2 diabetes. The aim of this article is to highlight the limitations of the current techniques used to diagnose diabetes and to highlight, at least from the theoretical perspective, the significance of the autonomic nervous system and physiological systems;in particular, how changes to colour perception are related to the function and/or stability of the autonomic nervous system;and how such phenomena can be used diagnostically. This article discusses this method—a mathematical model of the autonomic nervous system and physiological systems—which has been incorporated into the prototype technology Virtual Scanning;and in conclusion, illustrates how Diabetes appears to be a problem of acidity and consequently of mineral deficiency. It outlines how genotype and phenotype are both significant factors in the regulation of Blood Glucose, i.e. type 1 diabetes is predominantly genetic and is associated with hypoglycaemia whilst type 2 diabetes is due to environmental or phenotypic cause and is associated with hyperglycaemia. Both can occur simultaneously and hence explain why someone with type 2 diabetes may be prescribed insulin, i.e. in order to quantify the extent of a pathology such as diabetes mellitus and/or any other common pathology, it appears necessary to quantify the influence of genotype (genetic capacity) and phenotype (physiological demand). Accordingly the categorisation of diabetes as type 1 and type 2 may be misleading.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a common comorbidity with type 2 diabetes.The existing therapeutic options for NAFLD are not adequate.Hypocaloric diet and exercise is the cornerstone of therapy i...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a common comorbidity with type 2 diabetes.The existing therapeutic options for NAFLD are not adequate.Hypocaloric diet and exercise is the cornerstone of therapy in NAFLD.Pioglitazone is the only drug recommended in diabetes patients with biopsy proven non-alcoholic steatohepatitis.The frequent coexistence of NAFLD and type 2 diabetes with their combined adverse health consequences and inadequate therapeutic options makes it necessary to search for newer alternatives.AIM To assess the effect of sodium glucose cotransporter-2(SGLT-2)inhibitors on liver enzymes in type 2 diabetes patients with NAFLD.METHODS We searched PubMed/MEDLINE,Cochrane library,Google scholar,and Clinicaltrials.gov for the relevant articles to be included in this systematic review.Human studies done in type 2 diabetes patients with NAFLD treated with SGLT-2 inhibitors for at least 12 wk were included.Data from eight studies(four randomised controlled trials and four observational studies)were extracted and a narrative synthesis was done.A total of 214 patients were treated with SGLT-2 inhibitors in these studies(94 in randomised controlled trials and 120 in observational studies).RESULTS The primary outcome measure was change in serum alanine aminotransferase level.Out of eight studies,seven studies showed a significant decrease in serum alanine aminotransferase level.Most of the studies revealed reduction in serum level of other liver enzymes like aspartate aminotransferase and gamma glutamyl transferase.Five studies that reported a change in hepatic fat exhibited a significant reduction in hepatic fat content in those treated with SGLT-2 inhibitors.Likewise,among the three studies that evaluated a change in indices of hepatic fibrosis,two studies revealed a significant improvement in liver fibrosis.Moreover,there was an improvement in obesity,insulin resistance,glycaemia,and lipid parameters in those subjects taking SGLT-2 inhibitors.The studies disclosed that about 17%(30/176)of the subjects taking SGLT-2 inhibitors developed adverse events and more than 40%(10/23)of them had genitourinary tract infections.CONCLUSION Based on low to moderate quality of evidence,SGLT-2 inhibitors improve the serum level of liver enzymes,decrease liver fat,and fibrosis with additional beneficial effects on various metabolic parameters in type 2 diabetes patients with NAFLD.展开更多
AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar...AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar rats with streptozotocin(65 mg/kg) and verified using an oral glucose tolerance test. After anesthesia, the left coronary artery was occluded for 40 min followed by 80 min reperfusion. Blood glucose level was measured during surgery. Rats were randomized into six groups as follows:(1) control rats;(2) insulin(0.1 U/kg) treated rats prior to ischemia;(3) insulin(0.1 U/kg) treated rats at reperfusion;(4) GLP-1 a(140 mg/kg) treated rats prior to ischemia;(5) GLP-1 a(140 mg/kg) treated rats at reperfusion; and(6) rats treated with GLP-1 a(140 mg/kg) prior to ischemia plus insulin(0.1 U/kg) at reperfusion. Myocardial area at risk and infarct size was measured planimetrically using Evans blue and triphenyltetrazolium chloride staining, respectively.RESULTS There was no significant difference in the myocardial area at risk among groups. Insulin treatment before ischemia resulted in a significant increase in infarct size(34.7% ± 3.4% vs 18.6% ± 3.1% in the control rats, P < 0.05). Post-ischemic administration of insulin or GLP-1 a had no effect on infarct size. However, pre-ischemic administration of GLP-1 a reduced infarct size to 12% ± 2.2%(P < 0.05). The maximal infarct size reduction was observed in the group treated with GLP-1 a prior to ischemia and insulin at reperfusion(8% ± 1.6%, P < 0.05 vs the control and GLP-1 a alone treated groups).CONCLUSION GLP-1 a pre-administration results in myocardial infarct size reduction in rats with T2 DM. These effects are maximal in rats treated with GLP-1 a pre-ischemia plus insulin at reperfusion.展开更多
AIM: To study the eradication rate of Helicobacter pylori (Hp) in a group of type 2 diabetes and compared it with an age and sex matched non-diabetic group.METHODS: 40 diabetic patients (21 females, 19 males;56±7...AIM: To study the eradication rate of Helicobacter pylori (Hp) in a group of type 2 diabetes and compared it with an age and sex matched non-diabetic group.METHODS: 40 diabetic patients (21 females, 19 males;56±7 years) and 40 non-diabetic dyspeptic patients (20females, 20 males; 54±9 years) were evaluated. Diabetic patients with dyspeptic complaints were referred for upper gastrointestinal endoscopies; 2 corpus and 2 antral gastric biopsy specimens were performed on each patient. Patients with positive Hp results on histopathological examination comprised the study group. Non-diabetic dyspeptic patients seen at the Gastroenterology Outpatient Clinic and with the same biopsy and treatment protocol formed the control group.A triple therapy with amoxycillin (1 g b.i.d), clarithromycin (500 mg b.i.d) and omeprazole (20 mg b.i.d.) was given to both groups for 10 days. Cure was defined as the absence of Hp infection assessed by corpus and antrum biopsies in control upper gastrointestinal endoscopies performed 6weeks after completing the antimicrobial therapy.RESULTS: The eradication rate was 50 % in the diabetic group versus 85 % in the non-diabetic control group (P<0.001).CONCLUSION: Type 2 diabetic patients showed a significantly lower eradication rate than controls which may be due to changes in microvasculature of the stomach and to frequent antibiotic usage because of recurrent bacterial infections with the development of resistant strains.展开更多
To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases ri...To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases risk of macrovascular and microvascular complications. At present there are different treatments, both oral and injectable, available for the treatment of type 2 diabetes mellitus(T2DM). Treatment algorithms designed to reduce the development or progression of the complications of diabetes emphasizes the need for good glycaemic control. The aim of this review is to perform an update on the benefits and limitations of different drugs, both current and future, for the treatment of T2 DM. Initial intervention should focus on lifestyle changes. Moreover, changes in lifestyle have proven to be beneficial, but for many patients is a complication keep long term. Physicians should be familiar with the different types of existing drugs for the treatment of diabetes and select the most effective, safe and better tolerated by patients. Metformin remains the first choice of treatment for most patients. Other alternative or second-line treatment options should be individualized depending on the characteristics of each patient. This article reviews the treatments available for patients with T2 DM, with an emphasis on agents introduced within the last decade.展开更多
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.
文摘Lack of conclusive beneficial effects of strict glycemic control on macrovascular complications has been very frustrating for clinicians involved in care of patients with diabetes mellitus (DM). Highly publicized controversy surrounding cardiovascular (CV) safety of rosiglitazone resulted in major changes in United States Food and Drug Administration policy in 2008 regarding approval process of new antidiabetic medications, which has resulted in revolutionary data from several large CV outcome trials over the last few years. All drugs in glucagon-like peptide-1 receptor agonist (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT-2) inhibitor classes have shown to be CV safe with heterogeneous results on CV efficacy. Given twofold higher CV disease mortality in patients with DM than without DM, GLP-1 RAs and SGLT-2-inhibitors are important additions to clinician’s armamentarium and should be second line-therapy particularly in patients with T2DM and established atherosclerotic CV disease or high risks for CV disease. Abundance of data and heterogeneity in CV outcome trials results can make it difficult for clinicians, particularly primary care physicians, to stay updated with all the recent evidence. The scope of this comprehensive review will focus on all major CV outcome studies evaluating CV safety and efficacy of GLP-1 RAs and SGLT-2 inhibitors.
文摘Osteoporosis has become a serious health problem throughout the world which is associated with an increased risk of bone fractures and mortality among the people of middle to old ages.Diabetes is also a major health problem among the people of all age ranges and the sufferers due to this abnormality increasing day by day.The aim of this review is to summarize the possible mechanisms through which diabetes may induce osteoporosis.Diabetes mellitus generally exerts its effect on different parts of the body including bone cells specially the osteoblast and osteoclast,muscles,retina of the eyes,adipose tissue,endocrine system specially parathyroid hormone(PTH) and estrogen,cytokines,nervous system and digestive system.Diabetes negatively regulates osteoblast differentiation and function while positively regulates osteoclast differentiation and function through the regulation of different intermediate factors and thereby decreases bone formation while increases bone resorption.Some factors such as diabetic neuropathy,reactive oxygen species,Vitamin D,PTH have their effects on muscle cells.Diabetes decreases the muscle strength through regulating these factors in various ways and ultimately increases the risk of fall that may cause bone fractures.
文摘The study by Cao et al aimed to identify early second-trimester biomarkers that could predict gestational diabetes mellitus(GDM)development using advanced proteomic techniques,such as Isobaric tags for relative and absolute quantitation isobaric tags for relative and absolute quantitation and liquid chromatography-mass spectrometry liquid chromatography-mass spectrometry.Their analysis revealed 47 differentially expressed proteins in the GDM group,with retinol-binding protein 4 and angiopoietin-like 8 showing significantly elevated serum levels compared to controls.Although these findings are promising,the study is limited by its small sample size(n=4 per group)and lacks essential details on the reproducibility and reliability of the protein quantification methods used.Furthermore,the absence of experimental validation weakens the interpretation of the protein-protein interaction network identified through bioinformatics analysis.The study's focus on second-trimester biomarkers raises concerns about whether this is a sufficiently early period to implement preventive interventions for GDM.Predicting GDM risk during the first trimester or pre-conceptional period may offer more clinical relevance.Despite its limitations,the study presents valuable insights into potential GDM biomarkers,but larger,well-validated studies are needed to establish their predictive utility and generalizability.
基金support from Region Stockholm,ALF-project(FoUI-960041)Open Access funding is provided by Karolinska Institute(both to IM)。
文摘Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.
文摘Cardiac autonomic neuropathy(CAN)is an often overlooked and common complication of diabetes mellitus.CAN is associated with increased cardiovascular morbidity and mortality.The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death.In addition,autoimmune and genetic factors are involved in the development of CAN.CAN might be subclinical for several years until the patient develops resting tachycardia,exercise intolerance,postural hypotension,cardiac dysfunction and diabetic cardiomyopathy.During its sub-clinical phase,heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic.Newer imaging techniques(such as scintigraphy)have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system.One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN;however,the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN,and also proposed screening for CAN in patients with diabetes mellitus.A major challenge,however,is the lack of specific treatment to slow the progression or prevent the development of CAN.Lifestyle changes,improved metabolic control might prevent or slow the progression of CAN.Reversal will require combination of these treatments with new targeted therapeutic approaches.The aim of this article is to review the latest evidence regarding the epidemiology,pathogenesis,manifestations,diagnosis and treatment for CAN.
文摘Free fatty acids are known to play a key role in promoting loss of insulin sensitivity in type 2 diabetes mellitus but the underlying mechanism is still unclear.It has been postulated that an increase in the intracellular concentration of fatty acid metabolites activates a serine kinase cascade,which leads to defects in insu-lin signaling downstream to the insulin receptor.In addition,the complex network of adipokines released from adipose tissue modulates the response of tissues to insulin.Among the many molecules involved in the intracellular processing of the signal provided by insulin,the insulin receptor substrate-2,the protein kinase B and the forkhead transcription factor Foxo 1a are of particular interest,as recent data has provided strong evidence that dysfunction of these proteins results in insulin resistance in vivo.Recently,studies have revealed that phosphoinositidedependent kinase 1-independent phosphorylation of protein kinase Cε causes a reduction in insulin receptor gene expression.Additionally,it has been suggested that mitochondrial dysfunction triggers activation of several serine kinases,and weakens insulin signal transduction.Thus,in this review,the current developments in understanding the pathophysiological processes of insulin resistance in type 2 diabetes have been summarized.In addition,this study provides potential new targets for the treatment and prevention of type 2 diabetes.
文摘AIM:To evaluate metabolic control and health-related quality of life(HRQOL)in a type 1 diabetes mellitus(T1DM)population.METHODS:As part of a prospective cohort study,283T1DM patients treated with various insulin treatment modalities including multiple daily injections(MDI)and continuous subcutaneous insulin infusion(CSII)were examined annually.HRQOL was measured using the SF-36 and EuroQol questionnaires.Data regarding HRQOL,glycaemic and metabolic control from baseline and follow-up measures in 2002 and 2010 were analysed.Linear mixed models were used to calculate estimated values and differences between the three moments in time and the three treatment modalities.RESULTS:Significant changes[meanΔ(95%CI)]in body mass index[2.4 kg/m2(1.0,3.8)],systolic blood pressure[-6.4 mmHg(-11.4,-1.3)]and EuroQol-VAS[-7.3(-11.4,-3.3)]were observed over time.In 2010,168 patients were lost to follow-up.Regarding mode of therapy,52 patients remained on MDI,28 remained on CSII,and 33 patients switched from MDI to CSII during follow-up.Among patients on MDI,HRQOL decreased significantly over time:mental component summary[-9.8(-16.3,-3.2)],physical component summary[-8.6(-15.3,-1.8)]and EuroQol-VAS[-8.1(-14.0,-2.3)],P<0.05 for all.For patients using CSII,the EuroQol-VAS decreased[-9.6(-17.5,-1.7)].None of the changes over time in HRQOL differed significantly with the changes over time within the other treatment groups.CONCLUSION:No differences with respect to metabolic and HRQOL parameters between the various insulin treatment modalities were observed after 15 years of follow-up in T1DM patients.
基金Supported by AYUSH,New Delhi,India,No.F.NOZ.31014/02/2009/EMR-CCARSM/S Deendayal AushadhPvt.Ltd.Gwalior,India
文摘AIM: To investigate the antihyperglycemic, antihyperlipidemic and antioxidant functions of a polyherbal formulation, "Diabegon", in human subjects with type 2 diabetes mellitus.METHODS: A total of 33 human subjects with type 2 diabetes mellitus were recruited for the study and all anthropological and biochemical parameters were recorded at the time of registration. The subjects were given hot water extract obtained from 10 gm of "Diabegon" powder, "Diabegon kwath", on an empty stomach everyday in the morning under personal supervision for 6 mo. The therapeutic functions of the "Diabegon kwath" was assessed by monitoring the blood glucoselevels at monthly intervals and glycosylated hemoglobin, lipid profile and biomarkers of oxidative stress, liver and kidney function markers at three monthly intervals in the study subjects. RESULTS: Daily administration of hot water extract of "Diabegon" regularly for 6 mo resulted in significant reductions of blood glucose and glycosylated hemoglobin levels. There was also a significant increase in high density lipoprotein cholesterol levels with concomitant decreases in total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density lipoprotein. A significant improvement in glycosuria and proteinuria was also observed. Also, the subjects exhibited a significant improvement in enzymatic and nonenzymatic biochemical markers of oxidative stress. The kidney and liver functions remained normal and in fact improved in many subjects.CONCLUSION: The study which is first of its kind, advocates "Diabegon kwath" as a safe and effective Ayurvedic therapy for the treatment of human type 2 diabetes mellitus and further placebo controlled trial may substantiate the therapeutic efficacy of the formulation.
文摘Human sodium-glucose cotransporter 2 (hSGLT2) is a membrane protein responsible for glucose reabsorption from the glomerular filtrate in the proximal tubule. Inhibition of hSGLT2 has been regarded as a brand new therapeutic approach for the treatment of type 2 diabetes mellitus (T2DM) due to its non-insulin related characteristics with less side effects. Current commercially available hSGLT2 inhibitors are all C-glycoside inhibitors. Previous studies have reported that N-glycoside inhibitors have better potential to serve as new drugs due to their good metabolic stability. In addition, non-glycoside inhibitors have been shown to exhibit the capability to overcome the existing problems of current glycoside inhibitors, including low tissue permeability, poor stability and short serum half-time. Here, we aimed to discover novel N-glycoside and non-glycoside hSGLT2 inhibitors by a combination of several computational approaches. A ligand-based pharmacophore model was generated, well validated and subsequently utilized as a 3D query to identify novel hSGLT2 inhibitors from National Cancer Institute (NCI) and Traditional Chinese Medicine (TCM) databases. Finally, one N-glycoside (NSC679207) and one non-glycoside (TCM_Piperenol_A) hSGLT2 inhibitors were successfully identified, which were proven to exhibit excellent binding affinities, pharmacokinetic properties and less toxicity than the commercially available hSGLT2 inhibitor, canagliflozin, via molecular docking, ADMET prediction, molecular dynamics (MD) simulations and binding free energy calculations. All together, our results strongly suggest that these two compounds have great potential to serve as novel hSGLT2 inhibitors for the treatment of T2DM and their efficacies may be further examined by a series of in vitro and/or in vivo bioassays.
基金Supported by Scientific Research Foundation of Shanghai Municipal Health Commission of Changning District,No.20234Y038.
文摘In this editorial,we have commented on the article that has been published in the recent issue of World Journal of Clinical Cases.The authors have described a case of unilateral thyroid cyst and have opined that the acute onset of infection may be linked to diabetes mellitus(DM).We have focused on the role of nutrition in the association between DM and infection.Patients with DM are at a high risk of infection,which could also be attributed to nutrition-related factors.Nutritional interventions for patients with diabetes are mainly based on a low-calorie diet,which can be achieved by adhering to a low-carbohydrate diet.However,dietary fiber supplementation is recommended to maintain the diversity of the gut microbiota.Furthermore,high-quality protein can prevent the increased risk of infection due to malnutrition.Supplementation of vitamins C,vitamins A,vitamins D,and folic acid improves blood sugar control and facilitates immune regulation.Mineral deficiencies augment the risk of infection,but the relationship with diabetes is mostly U-shaped and a good intake should be maintained.
文摘The accumulation of fat in the pancreatic gland has been referred to using various synonyms,such as pancreatic lipomatosis,fatty replacement,fatty infiltration,fatty pancreas,lipomatous pseudohypertrophy,non-alcoholic fatty pancreatic disease and pancreatic steatosis We believe that pancreatic steatosis is the best description of fat accumulation in the pancreatic gland without fat replacement,and this term also describes the possibility that the fat accumulation is a reversible process.A review of the existing literature was carried out,and it was found that there was notable evidence from both the pathological and the imaging point of view that pancreatic steatosis is an increasing problem due to the increasing incidence of obesity.The conclusion was that pancreatic steatosis was easily detectable using modern imaging techniques,such as ultrasonography,endoscopic ultrasonography,computed tomography and magnetic resonance imaging.Pancreatic steatosis was not due to the presence of diabetes mellitus but was highly associated with the metabolic syndrome.The possible presence of steatopancreatitis should be better evaluated,especially regarding the inflammatory cascade,and additional studies are needed which are capable of assessing whether non-alcoholic steatopancreatitis really exists as does non-alcoholic steatohepatitis.Finally,the presence of exocrine pancreatic function should be extensively evaluated in patients with pancreatic steatosis.
文摘AIN To study the relationship of Imp2 and DR3genes with type Ⅰ diabetes mellitus.NETHODS Imp2 genotypes and DR3 wereidentified in 68 patients with type Ⅰ diabetesmellitus(Ⅰ-DM)and 71 healthy controls.Then,Ⅰ-DM patients and controls were respectivelyallocated into DR3-positive and DR3-negativegroups.The frequencies of Imp2 and DR3 genein random subjects,and Imp2 genotypes in DR3-matched subjects were compared between Ⅰ-DMpatients and controls.At the same time,Ⅰ-DMpatients were divided into 3 groups based on theonset age of diabetics:group A≤14 years,group B 15-30 years and group C≥31 years.RESULTS The frequency of DR3 in Ⅰ-DMpatients was significantly higher than that incontrols(47% vs 21%,P【0.005),and it wassignificantly higher in group A than that in groupB+C(70% vs 36%,x^2=7.07,P【0.01).Therewas a significant difference among groups withdifferent onset age of diabetics(x^2=8.19,rp=0.33,P【0.05).In random subjects,thefrequency of Imp2.R/R in Ⅰ-DM patients waslower(43% vs 61%,P【0.05)and Imp2.R/Hhigher(53% vs 28%,P【0.05)than that incontrols,and there was no significant differenceamong groups with different onset age ofdiabetics.In DR3-positive subjects,thefrequency of Imp2.R/R in Ⅰ-DM patients waslower(47% vs 87%,P【0.05)and Imp2-R/H higher(47% vs 13%,P【0.05)than that incontrols.In DR3-negative subjects,thefrequency of Imp2.R/H in Ⅰ-DM patients washigher than that in controls(58% vs 32%,P【0.01),but the frequency of Imp2-R/R and Imp2H/H was not significantly different betweenthese two groups.CONCLUSION DR3 gene may be one of thesusceptible genes of Ⅰ-DM,and significantlyrelated to the onset age of diabetics,and thepersons with DR3 may have an younger onsetage of diabeteS.The Imp2-R/R may be theprotective genotype of Ⅰ-DM,and Imp2-R/H thesusceptible genotype.These were not affectedby DR3 gene.Imp-2 genotypes were not relatedwith the onset age of diabetics.
文摘Neuropathy is a common complication of diabetes mellitus(DM) with a wide clinical spectrum that encompasses generalized to focal and multifocal forms. Entrapment neuropathies(EN), which are focal forms, are so frequent at any stage of the diabetic disease, that they may be considered a neurophysiological hallmarkof peripheral nerve involvement in DM. Indeed, EN may be the earliest neurophysiological abnormalities in DM,particularly in the upper limbs, even in the absence of a generalized polyneuropathy, or it may be superimposed on a generalized diabetic neuropathy. This remarkable frequency of EN in diabetes is underlain by a peculiar pathophysiological background. Due to the metabolic alterations consequent to abnormal glucose metabolism,the peripheral nerves show both functional impairment and structural changes, even in the preclinical stage,making them more prone to entrapment in anatomically constrained channels. This review discusses the most common and relevant EN encountered in diabetic patient in their epidemiological, pathophysiological and diagnostic features.
文摘Diabetes has become a growing concern in Japan, both medically and financially. The medical cost of diabetes was estimated at 1215 billion yen for fiscal year 2011. We analyzed the length of stay (LOS) in a hospital for type 2 diabetes mellitus patients who participated in educational programs to determine factors affecting LOS. Data on 991 patients obtained from 28 Red Cross hospitals in 2008 were used. For the analysis, we used the Box-Cox transformation model and Hausman test. The results revealed that patients aged 75 years and above and those with comorbidities and complications were prone to longer LOS. The analysis also revealed significant differences in LOS across the hospitals, even after controlling for patient characteristics. Finally, we applied the least squares method to determine the effects of hospital and regional factors and revealed that patients’ LOS was affected by the region’s average LOS. Regional corporations and networks appeared to be important in improving educational programs.
文摘Background: The organs in the body function in coherent organ networks. These organ networks are commonly known as physiological systems. Blood Glucose, Blood Pressure and pH exhibit the characteristics of neurally regulated Physiological Systems. Any medical condition, such as diabetes, has origins which are due to systemic dysfunction. This influences the genetic expression of proteins and the rate at which such expressed proteins subsequently react. Increased levels of acidity influence the levels of available minerals, protein conformation, and hence the rate at which expressed proteins such as insulin and leptin react or function. This is particularly significant in diabetes etiology where a deficiency of insulin and insulin-“resistance” are significant features of type 1 and type 2 diabetes. Proteins such as Insulin absorb and emit light. Moreover, the spectrum and intensity of the bioluminescence emitted from glycated proteins (which are more significantly bioluminescent) influence colour perception. Accordingly, changes to the diabetic’s colour perception can be used as the basis of a cognitive screening technique which is able to quantify the influence of genotype and phenotype. This may have significant advantages over current biomarker techniques which are not able to satisfactorily determine the earliest onset of?diabetes or distinguish between the symptomatic and presymptomatic onset of diabetes. Such methodology, based upon the properties of proteins, i.e. effectively, the rate at which proteins are expressed and the rate at which such expressed proteins subsequently react, allows the clinician to quantify genotype and phenotype and may contribute to a greater understanding of the processes responsible for what are commonly known as type 1 and type 2 diabetes. The aim of this article is to highlight the limitations of the current techniques used to diagnose diabetes and to highlight, at least from the theoretical perspective, the significance of the autonomic nervous system and physiological systems;in particular, how changes to colour perception are related to the function and/or stability of the autonomic nervous system;and how such phenomena can be used diagnostically. This article discusses this method—a mathematical model of the autonomic nervous system and physiological systems—which has been incorporated into the prototype technology Virtual Scanning;and in conclusion, illustrates how Diabetes appears to be a problem of acidity and consequently of mineral deficiency. It outlines how genotype and phenotype are both significant factors in the regulation of Blood Glucose, i.e. type 1 diabetes is predominantly genetic and is associated with hypoglycaemia whilst type 2 diabetes is due to environmental or phenotypic cause and is associated with hyperglycaemia. Both can occur simultaneously and hence explain why someone with type 2 diabetes may be prescribed insulin, i.e. in order to quantify the extent of a pathology such as diabetes mellitus and/or any other common pathology, it appears necessary to quantify the influence of genotype (genetic capacity) and phenotype (physiological demand). Accordingly the categorisation of diabetes as type 1 and type 2 may be misleading.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a common comorbidity with type 2 diabetes.The existing therapeutic options for NAFLD are not adequate.Hypocaloric diet and exercise is the cornerstone of therapy in NAFLD.Pioglitazone is the only drug recommended in diabetes patients with biopsy proven non-alcoholic steatohepatitis.The frequent coexistence of NAFLD and type 2 diabetes with their combined adverse health consequences and inadequate therapeutic options makes it necessary to search for newer alternatives.AIM To assess the effect of sodium glucose cotransporter-2(SGLT-2)inhibitors on liver enzymes in type 2 diabetes patients with NAFLD.METHODS We searched PubMed/MEDLINE,Cochrane library,Google scholar,and Clinicaltrials.gov for the relevant articles to be included in this systematic review.Human studies done in type 2 diabetes patients with NAFLD treated with SGLT-2 inhibitors for at least 12 wk were included.Data from eight studies(four randomised controlled trials and four observational studies)were extracted and a narrative synthesis was done.A total of 214 patients were treated with SGLT-2 inhibitors in these studies(94 in randomised controlled trials and 120 in observational studies).RESULTS The primary outcome measure was change in serum alanine aminotransferase level.Out of eight studies,seven studies showed a significant decrease in serum alanine aminotransferase level.Most of the studies revealed reduction in serum level of other liver enzymes like aspartate aminotransferase and gamma glutamyl transferase.Five studies that reported a change in hepatic fat exhibited a significant reduction in hepatic fat content in those treated with SGLT-2 inhibitors.Likewise,among the three studies that evaluated a change in indices of hepatic fibrosis,two studies revealed a significant improvement in liver fibrosis.Moreover,there was an improvement in obesity,insulin resistance,glycaemia,and lipid parameters in those subjects taking SGLT-2 inhibitors.The studies disclosed that about 17%(30/176)of the subjects taking SGLT-2 inhibitors developed adverse events and more than 40%(10/23)of them had genitourinary tract infections.CONCLUSION Based on low to moderate quality of evidence,SGLT-2 inhibitors improve the serum level of liver enzymes,decrease liver fat,and fibrosis with additional beneficial effects on various metabolic parameters in type 2 diabetes patients with NAFLD.
基金Supported by Russian Science Foundation,No.17-75-30052
文摘AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar rats with streptozotocin(65 mg/kg) and verified using an oral glucose tolerance test. After anesthesia, the left coronary artery was occluded for 40 min followed by 80 min reperfusion. Blood glucose level was measured during surgery. Rats were randomized into six groups as follows:(1) control rats;(2) insulin(0.1 U/kg) treated rats prior to ischemia;(3) insulin(0.1 U/kg) treated rats at reperfusion;(4) GLP-1 a(140 mg/kg) treated rats prior to ischemia;(5) GLP-1 a(140 mg/kg) treated rats at reperfusion; and(6) rats treated with GLP-1 a(140 mg/kg) prior to ischemia plus insulin(0.1 U/kg) at reperfusion. Myocardial area at risk and infarct size was measured planimetrically using Evans blue and triphenyltetrazolium chloride staining, respectively.RESULTS There was no significant difference in the myocardial area at risk among groups. Insulin treatment before ischemia resulted in a significant increase in infarct size(34.7% ± 3.4% vs 18.6% ± 3.1% in the control rats, P < 0.05). Post-ischemic administration of insulin or GLP-1 a had no effect on infarct size. However, pre-ischemic administration of GLP-1 a reduced infarct size to 12% ± 2.2%(P < 0.05). The maximal infarct size reduction was observed in the group treated with GLP-1 a prior to ischemia and insulin at reperfusion(8% ± 1.6%, P < 0.05 vs the control and GLP-1 a alone treated groups).CONCLUSION GLP-1 a pre-administration results in myocardial infarct size reduction in rats with T2 DM. These effects are maximal in rats treated with GLP-1 a pre-ischemia plus insulin at reperfusion.
文摘AIM: To study the eradication rate of Helicobacter pylori (Hp) in a group of type 2 diabetes and compared it with an age and sex matched non-diabetic group.METHODS: 40 diabetic patients (21 females, 19 males;56±7 years) and 40 non-diabetic dyspeptic patients (20females, 20 males; 54±9 years) were evaluated. Diabetic patients with dyspeptic complaints were referred for upper gastrointestinal endoscopies; 2 corpus and 2 antral gastric biopsy specimens were performed on each patient. Patients with positive Hp results on histopathological examination comprised the study group. Non-diabetic dyspeptic patients seen at the Gastroenterology Outpatient Clinic and with the same biopsy and treatment protocol formed the control group.A triple therapy with amoxycillin (1 g b.i.d), clarithromycin (500 mg b.i.d) and omeprazole (20 mg b.i.d.) was given to both groups for 10 days. Cure was defined as the absence of Hp infection assessed by corpus and antrum biopsies in control upper gastrointestinal endoscopies performed 6weeks after completing the antimicrobial therapy.RESULTS: The eradication rate was 50 % in the diabetic group versus 85 % in the non-diabetic control group (P<0.001).CONCLUSION: Type 2 diabetic patients showed a significantly lower eradication rate than controls which may be due to changes in microvasculature of the stomach and to frequent antibiotic usage because of recurrent bacterial infections with the development of resistant strains.
文摘To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases risk of macrovascular and microvascular complications. At present there are different treatments, both oral and injectable, available for the treatment of type 2 diabetes mellitus(T2DM). Treatment algorithms designed to reduce the development or progression of the complications of diabetes emphasizes the need for good glycaemic control. The aim of this review is to perform an update on the benefits and limitations of different drugs, both current and future, for the treatment of T2 DM. Initial intervention should focus on lifestyle changes. Moreover, changes in lifestyle have proven to be beneficial, but for many patients is a complication keep long term. Physicians should be familiar with the different types of existing drugs for the treatment of diabetes and select the most effective, safe and better tolerated by patients. Metformin remains the first choice of treatment for most patients. Other alternative or second-line treatment options should be individualized depending on the characteristics of each patient. This article reviews the treatments available for patients with T2 DM, with an emphasis on agents introduced within the last decade.