The relationship between obese protein and noninsulin-dependent diabetes mellitus

To explore the role of obese protein (OP), the product of the obese gene, in the development of non-insulin-dependent diabetes mellitus (NIDDM). Metbods: Plasma obese protein level was measured by radioimmunoassay in 21 normal subjects, 24 adult obese patients and 20 patients with NIDDM. Results: The levels of the plasma obese protein in NIDDM patients (81. 0±17. 5 pg/ml) were very significantly lower than those in normal subjects (194. 3±17. 7 pg/ml) and obese patients (109.1±16. 4 pg/ml ) (P<0.01). The levels of the plasma obese protein in non-obese NIDDM patients were very significantly lower than those in non-obese normal subjects (P<0.01), and the levels of the plasma obese protein in obese NIDDM patients were very significantly lower than those in obese patients (P<0. 01). The leve1s of the plasma obese protein in NIDDM patients were significantly correlated with polyphagia (P<0.05), but not correlated with the body weight indexes after strict dieting, and the plasma levels of cholesterol, triglyceride, fasting glucose, hemoglobiti A, and the insulin levels during glucose tolerance test (P>0.05). Couclusion: Low plasma level of obese protein is one of the important factors contributing to obesity,and plasma obese protein may be closely related to the generation of NIDDM.

Non-Diabetic Renal Disease in Patients with Type 2 Diabetes Mellitus with Proteinuria

Background: Diabetes mellitus (DM) is the leading cause of end stage renal disease (ESRD) worldwide. Although DM with proteinuria is the ultimate result of diabetic nephropathy (DN), a wide spectrum of non-diabetic renal diseases (NDRD) can occur in such patients. Objective: To observe the frequency and histological pattern of NDRD in diabetic patients with proteinuria and to explore their association with clinical and laboratory parameters. Methods: This cross-sectional study was conducted in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from April 2016 to September 2017. In this study a total of 38 cases of DM with proteinuria (>1 gm/24-hour) were selected purposively. Renal biopsy was done in all patients. Based on histological findings they were categorized into two groups;Group 1 with NDRD and Group II with DN. Their clinical and laboratory parameters were analyzed and compared. Results: Among the total study subjects, 21 (55.3%) were male and 17 (44.7%) were female, mean (±SD) age 43.45 ± 9.99 years in the NDRD group and 41.57 ± 9.50 years in the DN group. Thirty one cases (81.6%) out of thirty eight had NDRD and seven (18.4%) cases had isolated DN;therefore more than two third cases had NDRD. Duration of DM was found to be significantly shorter (p = 0.004) in the NDRD group. Diabetic retinopathy was present in 12.9% cases in NDRD group vs. 57.1% cases in DN group (p = 0.025). Frequency of microscopic hematuria was significantly higher (90.3%) in NDRD patients (p = 0.002). Conclusion: The frequency of NDRD in type 2 diabetic patients other than diabetic nephropathy is relatively high. Membrano proliferative glomeru-lonephritis and membranous nephropathy are more common in NDRD. Absence of diabetic retinopathy, presence of hematuria and shorter duration of DM are markers associated with NDRD in type 2 DM, which are important indicators for renal biopsy in diabetic patients with proteinuria.

SGLT-2 inhibitors in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus: A systematic review

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.

Xenotransplantation of embryonic pig pancreas for treatment of diabetes mellitus in non-human primates

Transplantation therapy for diabetes in humans is limited by the low availability of human donor whole pancreas or islets. Outcomes are complicated by immunosuppressive drug toxicity. Xenotransplantation is a strategy to overcome supply problems. Implantation of tissue obtained early during embryogenesis is a way to reduce transplant immunogenicity. Pig insulin is biologically active in humans. In that regard the pig is an appropriate xenogeneic organ donor. Insulin-producing cells originating from embryonic pig pancreas obtained very early following pancreatic primordium formation [embryonic day 28 (E28)] engraft long-term in rhesus macaques. Endocrine cells originating from embryonic pig pancreas transplanted in host mesentery migrate to mesenteric lymph nodes, engraft, differentiate and improve glucose tolerance in rhesus macaques without the need for immune suppression. Transplantation of embryonic pig pancreas is a novel approach towards beta cell replacement therapy that could be applicable to humans.

A Study of Factors Related to the Incidence of Cataract in Patients with Non-Insulin Dependent Diabetes Mellitus

Purpose: To investigate the factors related to the development of cataract in patientswith non-insulin dependent diabetes mellitus(NIDDM).Methods: 792 NIDDM patients received ophthalmologic examinations including visualacuity, external status of the eyes, slit lamp microscopy and ophthalmoscopy. Glucose,urea nitrogen (BUN), creatinine (Cr), urine acid (UA), N-acetyl-β2-D-glucosaminidase(NAG), β2-microglobulin(β2-MG) and serum albumin in blood were quantitativelytested. Glucose, pH value, protein, cells, cast and ketobodies in urine were assayed.Diagnosis of cataract was based on lens opacities classification system Ⅱ. Any patientmeeting "NⅡ", "CⅡ" or "PⅡ" level was diagnosed as cataract.Results: The incidence of cataract in this group of NIDDM was 62.37 % (494/792),which significantly related to the duration of the disease course, but not to the sex of thepatient. The occurrence rate of cataract in patients suffering from NIDDM of less thanfive years duration, from five to ten years, and more than ten years was 49.67 % (228/459), 71.84 % (125/174), and 88.68 % (141/159), respectively. The occurrence ofcataract in patients diagnosed of the disease from five to ten years and more than tenyears was much higher than that of those with the course of the disease less than fiveyears( P ＜ 0.05 and P ＜ 0. 001, respectively) . Rising concentrations of blood ureanitrogen, creatinine, glycosylated hemoglobin HbA1c(G-HbA1c), N-acetyl-β2-D-glucosaminidase(NAG) and β2-microglobulin(β2-MG) indicated malfunction of thekidneys, and the rate of cataract occurrence in these patients was higher.Conclusion: This study indicates that prolongation of the duration of non-insulindependent diabetes mellitus, renal dysfunction, as well as poor blood glucose control,may accelerate the development of cataract.

Impact of Diabetes Mellitus on the Treatment Outcomes of Chemotherapy in Women with Breast Cancer——A Population-Based Prospective Cohort Study

There are few population-based data in investigating the impact of diabetes on chemotherapy adverse effects and treatment outcomes of non-metastatic breast cancer. The purpose of this study is to evaluate whether diabetes affects the patterns of use in chemotherapy, toxic effects of chemotherapy, and treatment outcomes for non-metastatic breast cancer in Taiwan. The study results can provide physicians for making a decision whether or not to use chemotherapy based on the individual patients＇ condition.

Prevalence of Diabetes Mellitus among Adult Residents of Tinda Rural Community, Nigeria

Aim: Diabetes mellitus (DM) is an emerging disease of public health concern in Nigeria. There has been growing speculation about rural dwellers not being susceptible to this ailment due to their lifestyle. However, this could be attributed to the paucity of data obtained from rural communities. This community-based survey was conducted to provide recent data about the prevalence of DM in a rural community in Northern Nigeria. Subject and Methods: Purposive sampling was used to recruit 78 participants from about 200 adults within the community in September 2019. Consent was obtained to retrieve their blood glucose results and socio-demographic data from an out-patient clinic. Data were entered and analyzed using SPSS version 20. Results: Over half (55%) of the respondents were male, while majority (88%) were involved in agrarian professions. Majority (69%) of the respondents were between 18 to 35 years, while around 10% were over 50 years. The respondents had an average blood glucose level of 5.20 ± 0.62 mmol/L, with 6.50 mmol/L as the maximum reading. The prevalence of DM was 0.0%, majority (68%) had normal glucose level, while the remainder had pre-diabetes glucose levels. There were no statistically significant associations between the respondents’ blood glucose level and any of their socio-demographic characteristics. However, the oldest respondents, male respondents, and traders had the highest blood glucose levels in their respective categories. Conclusion: The absence of a healthcare center in the community was of concern, as this would impede efforts to monitor the prevalence of non-communicable disease like DM. It is recommended that health interventions to discourage the rural dwellers from embracing adverse urban lifestyles associated with DM should be prioritized.

Association Studies of 3 Candidate Genes with Type 2 Diabetes Mellitus in a Chinese Population

Objectives To explore the relationship between the polymorphisms of the selected short tandem repeats (STRs) of the candidate genes and type 2 diabetes mellitus (DM) in a Chinese population,the role of genetic and environmental factors in the development of type 2 diabetes. Methods STRs including D11S916 of uncoupling protein 3 (UCP3) gene,binucleotide repeat (CA)n within intron 6 [HSLi6(CA)] of hormone-sensitive lipase(HSL)gene and D20S501 of protein tyrosine phosphatase-1B (PTP-1B)gene polymorphisms were detected, by poiymerase chain reaction(PCR) ,poly-acrylamide gel electrophoresis and silver staining in 106 patients with type 2 DM and 102 control subjects. Results The allele distribution of UCP3 and HSL gene differed significantly between patients with type 2 diabetes and control subjects (X2 = 26. 12,P<0. 005; X2 = 10. 33,P<0. 005,respectively). For UCP3 and HSL gene,the frequencies of alleles A6,A7,A8 and allele B9 were much higher in diabetic patients than in control subjects (0. 090 vs 0. 020,P<0. 005; 0. 109 vs 0. 015,P <0. 005; 0. 033 vs 0. 000,P<0. 05; 0. 033 vs 0. 005,P<0. 05,respectively),while the frequencies of allele A1 and allele B5 were lower in diabetic patients than in control subjects (0. 090 vs 0. 206,P<0. 005; 0. 057 vs 0. 118,P<0. 05,respectively). At D20S501 locus,The allele distribution of PTP-1B gene had no significant difference in two groups (X2 = 3. 77, P>0. 05). Multi-variate logistic regression analysis showed positive correlation between alleles A6,A7 of UCP3 gene,systolic blood pressure, apolipoprotein B, lipoprotein (a) and type 2 diabetes. Conclusion Our data show that D11S916 of UCP3 gene and HSLi6(CA) of HSL gene polymorphisms are associated with type 2 diabetes in Chinese suggesting that UCP3 and HSL might represent susceptibility genes for type 2 diabetes. D20S501 of PTP-IB gem polymorphism is not associated with type 2 diabetes in Chinese. Alleles A6, A7 of UCP3 gene, systolic blood pressure, apolipoprotein B,Upoprotein (a) may play some role in the development of type 2 diabetes.

Hepatic glycogenosis: An underdiagnosed complication of diabetes mellitus?

Hepatic glycogenosis(HG) is characterized by excessive glycogen accumulation in hepatocytes and represents a hepatic complication of diabetes that particularly occurs in patients with longstanding poorly controlled type 1 diabetes(T1D). HG has been reported to be a very rare disease, although it is believed to be extremely underdiagnosed because it is not possible to distinguish it from non-alcoholic fatty liver disease(NAFLD) unless a liver biopsy is performed. In contrast to HG, NAFLD is characterized by liver fat accumulation and is the more likely diagnosis for patients with type 2 diabetes and metabolic syndrome. The pathogenesis of HG involves the concomitant presence of insulin and excess glucose, which increases glycogen storage in the liver. HG is characterized by a transient elevation in liver transaminases and hepatomegaly. Differentiating between these two conditions is of the utmost importance because HG is a benign disease that is potentially reversible by improving glycemic control, whereas NAFLD can progress to cirrhosis. Therefore, HG should be suspected when liver dysfunction occurs in patients with poorly controlled T1 D. The aim of this article is to review the epidemiology, clinical characteristics, pathogenesis and histology of HG.

Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR

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.

Case-control analysis of the <i>ERAP1</i>polymorphism rs30187 in Italian type 1 diabetes mellitus patients

Autoimmune diseases are a heterogeneous group of disorders affecting different organs and tissues whose incidence are increasing worldwide. New tools, such as genome-wide association studies, have provided evidence for new susceptibility loci and candidate genes in the disease process including common susceptibility genes involved in the immunological synapse and T cell activation. Close linkages have been found in a number of diseases, including ankylosing spondylitis, multiple sclerosis, Crohn’s disease and insulin-dependent diabetes mellitus (Type 1 diabetes mellitus). The evidence for some associations with Type 1 diabetes was previously found in the region containing 5q15/ERAP1 (endoplasmic reticulum aminopeptidase 1) (rs30187, ARTS1). Our aim was to conduct the first casecontrol study to test the association between the rs30187 polymorphism of ERAP1 and the development of Type 1 diabetes mellitus in patients selected from continental Italy. All control subjects were matched for the sex, age, ethnic origin and geographical area. Genotyping of the rs30187 polymorphism of ERAP1 was carried out by the allelic discrimination assay on DNA extracted from whole blood. We did not observe a statistically significant prevalence of the rs30187 polymorphism of ERAP1 in our cohort of patients than in controls suggesting a minor contribution of this gene to the pathogenesis of Type 1 diabetes mellitus in Italian patients.

Spouses of patients with diabetes mellitus type 2 at increased risk of high blood glucose levels

Introduction: Diabetes mellitus type 2 is a growing threat in developing countries already burdened with high levels of infectious disease. Screening the general population has debatable advantages. This study aims to determine whether spouses of patients with diabetes mellitus have higher random blood glucose (RBG) levels as well as the benefit of RBG testing as a targetted screening tool. Methodology: The survey employed a cross-sectional comparative study of spouses’ of diabetics and non-diabetics attending the general out-patient department of the LagosStateUniversityTeaching Hospital (LASUTH), Ikeja. A modified WHO STEPS Surveillance Instrument and a one-touch Glucometer were used to collect data. Blood pressures and BMI were measured and correlated to blood glucose levels. Results: Prevalence of high RBG was found to be 7% among spouses of diabetics and 3.3% among spouses of non-diabetic patients. Mean RBG was 5.57 mmol/L and 7.7 mmol/L within the age group 40 - 49 years and 50 - 59 years respectively among spouses of diabetic patients compared to 5.4 mmol/L and 5.5 mmol/L within the same age group among the spouses non-diabetics. Spouses of patients with diabetes mellitus had higher systolic and diastolic blood pressures and BMI compared to spouses of non-diabetics. Conclusion: Being male, married to a diabetic patient, lower educational levels and higher body mass index are significantly associated with higher random blood glucose in the spouses of diabetic patients. Random blood glucose measurements are an effective screening tool and spouses of diabetic patients can benefit from targeted screening in controlled clinical settings.

Research Progress on Non-Drug Treatment for Blood Glucose Control of Type 2 Diabetes Mellitus

Type 2 diabetes mellitus （T2DM） is one of the common endocrinology diseases that greatly affects the health care sector and economy. Application of hypoglycemic drugs has its own drawbacks and the use of non-drug therapy on treating T2DM has drawn much attention recently. This paper reviewed the research development of the non-pharmacological interventions on T2DM in recent years, including dietary therapy, exercise therapy, psychotherapy, acupuncture and moxibustion therapies and so on. The authors mentioned the problems in the research of non-drug treatment for blood glucose control of T2DM and put forward new ideas for the research in the future. Further well-designed trials with large sample size and long-term follow-up are needed to confirm current conclusions.

The mutation of insulin receptor substrate-1 gene in Chinese patients with non insulin dependent diabetes mellitus

OBJECTIVE: To identify the relationship between mutation in the insulin receptor substrate-1 (IRS-1) gene and the incidence of non-insulin-dependent diabetes mellitus (NIDDM) in the Chinese population. METHODS: Samples were obtained from 68 Chinese patients with NIDDM and 68 control subjects. The +1700-(+)4437 bp fragment of the IRS-1 gene was screened by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. All SSCP variations were submitted to DNA sequence analysis. RESULTS: Two amino acid variations [GGG-->AGG (G971 R) and CCT-->TCT (P1079 S)] and 3 silent mutations [GAT-->GAC(D422D), CCA-->CCC(P737 P) and GCA-->GCG (A804 A)] were identified, among which the CCA-->CCC(P737 P) and CCT-->TCT(P1079S) have not been previously reported. All five variations were found in Chinese patients with NIDDM, while GCA-->GCG(A804A) was the only one found in control subjects. The overall incidence of the five variations in Chinese patients with NIDDM were much higher than that in control subjects (38.2% vs 7.4%, chi 2 = 18.42, P GCG (A804A), and its frequency was significantly higher in Chinese patients with NIDDM than in controls (26.5% vs 7.4%, chi 2 = 8.84, P 0.05). CONCLUSION: These results indicate that there may be a relation between these nucleotide variations of IRS-1 gene and Chinese patients with NIDDM.

Clinical Study on Jiang Tang San（降糖散）in Treating Non－Insulin Dependent Diabetes Mellitus Patiente

The therapeutic effect of Jiang Tang San (JTS) on 30 cases with non-insulin dependent dia-betes mellitus (NIDDM) , was observed, whose fasting blood glucose ranged trom 11. 1 mmol/L to 13. 8mmol/L. The results suggested that JTS has significant effect on NIDDM patients in lowering blood glucose,blood lipid and blood pressure levels. Clinical symptoms and blood glucose improved rapidly. JTS promotedthe elevation of serum insulin level 1 hour after meal. The total effective rate of lowering blood glucosereached 86. 7% . The results showed JTS is better than berberine on lowering blood glucose ( P< 0. 01 ) andwhen patients failed to respond to other hypoglycemics or on recurrence JTS was still effective. There wereno marked side-effects during the course of treatment.

Therapeutic Effect of Berberine on 60 Patients with Non－Insulin Dependent Diabetes Mellitus and Experimental Research

The effects of berberine on 60 cases with noninsulin dependent diabetes mellitus and ex-perimental research results were observed in this study. The results suggest berberine has significant ef-fects on noninsulin dependent diabetes mellitus patients and experimental diabetes in animals in the re-duction of blood glucose levels. The clinical symptoms basically disappeared and the level of serum insulinrose. The total effective rate was up to 90 percent and there were no signiticant side-effects. It was foundthat berberine has an effect on the recovery of pancreas islet cells, through pathological examination onthe animal subjects.

Effects of Supplemented Taohe Chengqi Decoction (桃核承气汤) in Treating Insulin Resistance in Rats with Non-Insulin Dependent Diabetes Mellitus

Objective: To investigate the effect of supplemented Taohe Chengqi Decoction (桃核承气汤,STHCQD) in treating non-insulin dependent diabetes mellitus (NIDDM). Methods: The model of rats withNIDDM was formed with injection of streptozotocin and fed on high calorie diet to study the effects of STHCQDon the release of insulin sensitivity. Results: (l ) Fasting serum glucose, serum insulin, intake of food and waterwere significantly decreased (P < 0. 05 -- 0. 01 ) in STHCQD-treated diabetic rats as compared with untreated diabetic rats, while the insulin sensitivity was significantly increased (P < 0. 05 ). (2) The liver cell membranesfrom STHCQD-treated diabetic rats released the quantity of insulin receptor which inhibited adenylate cyclaseactivity, but this effect was blunted in untreated diabetic rats (P < 0. 05). (3) A significantly increased glucoseoxidation in adipocyte of STHCQD-treated diabetic rats was found as compared with those of untreated diabeticrats (P< 0. 05). Conclusions: STHCQD therapy Increased sensitivity and responsiveness of target cells to insulin, i. e. it might decrease insulin resistance at receptor sites and POst--receptor sites in rats with NIDDM, butcould not.reverse the insulin resistance.

CHANGES OF NAILFOLD MICROCIRCULATION IN PATIENTS OF TYPE II DIABETES MELLITUS WITH DIABETIC RETINOPATHY

Objective. To study the changes of microcirculation in patients with diabetic retinopathy(DR). Methods. Examination were performed in 153 cases of type Ⅱ diabetes mellitus, among them, 72 cases were male, 81 cases were female, mean age 57.0±10.0 years, mean disease course 8.2±7.5 years. All cases were examined fundi by ophthalmologist, urinary albumin excretion rate (UAE) in 24 hours was measured by radioimmunoassay. Moreover, we examined the blood glucose, blood pressure, blood viscosity and observed the changes of naifold microcirculation. Results.It was found that there were more evident disturbance of microcirculation, markedly slowed velocity of blood flow(P<0.05), significantly increased aggregation of blood cells(P<0.05) and exudation around the loop(P<0.05) in the group with DR, compared with the group without DR. Conclusion. It was more evident disturbance of nailfold microcirculation in patients with diabetic retinopathy.

Non-alcoholic fatty liver disease and diabetes: From physiopathological interplay to diagnosis and treatment

Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in patients with diabetes mellitus and increasing evidence suggests that patients with type 2diabetes are at a particularly high risk for developing the progressive forms of NAFLD,non-alcoholic steatohepatitis and associated advanced liver fibrosis.Moreover,diabetes is an independent risk factor for NAFLD progression,and for hepatocellular carcinoma development and liver-related mortality in prospective studies.Notwithstanding,patients with NAFLD have an elevated prevalence of prediabetes.Recent studies have shown that NAFLD presence predicts the development of type2 diabetes.Diabetes and NAFLD have mutual pathogenetic mechanisms and it is possible that genetic and environmental factors interact with metabolic derangements to accelerate NAFLD progression in diabetic patients.The diagnosis of the more advanced stages of NAFLD in diabetic patients shares the same challenges as in non-diabetic patients and it includes imaging and serological methods,although histopathological evaluation is still considered the gold standard diagnostic method.An effective established treatment is not yet available for patients with steatohepatitis and fibrosis and randomized clinical trials including only diabetic patients are lacking.We sought to outline the published data including epidemiology,pathogenesis,diagnosis and treatment of NAFLD in diabetic patients,in order to better understand the interplay between these two prevalent diseases and identify the gaps that still need to be fulfilled in the management of NAFLD in patients with diabetes mellitus.

Mechanism of action of gypenosides on type 2 diabetes and non-alcoholic fatty liver disease in rats

AIM:To explore the mechanism of action of gypenosides(GPs)on type 2 diabetes mellitus and non-alcoholic fatty liver disease(T2DM-NAFLD)in rats.METHODS:Sixty rats were randomly divided into a healthy group,an untreated disease model group andGP-treatment groups.The study involved the evaluation of biochemical parameters,including serum aspartate transaminase(AST),alanine transferase(ALT),blood glucose(BG),triglycerides(TG)and total cholesterol(TC).Additionally,the protective effect of the treatments were confirmed histopathologically and the expression of TNF-αand NF-κB in the rat liver was analyzed using immunohistochemistry.The expression of proliferatoractivated receptor gamma(PPARγ)and cytochrome P450(CYP450)1A1 m RNA was determined by quantitative RTPCR.RESULTS:GP treatments at oral doses of 200,400,and800 mg/kg per day significantly decreased the levels of serum AST and ALT(P<0.05,P<0.01),especially at the dose of 800 mg/kg per day.To a similar extent,GP at800 mg/kg per day reduced the levels of BG(4.19±0.47,P<0.01),TG(80.08±10.05,P<0.01),TC(134.38±16.39,P<0.01)and serum insulin(42.01±5.04,P<0.01).The expression of TNF-αand NF-κB measured by immunohistochemistry was significantly reduced by GPs in a dose-dependent manner,and the expression of PPARγand CYP4501A1 m RNA,as measured using quantitative real-time PCR,were significantly down-regulated by GPs.Moreover,GPs decreased the infiltration of liver fats and reversed the histopathological changes in a dosedependent manner.CONCLUSION:This study suggests that GPs have a protective effect against T2DM-NAFLD by down-regulating the expression of TNF-αand NF-κB proteins,and PPARγand CYP4501A1 m RNAs.