Association of a SLC30A8 Genetic Variant with Monotherapy of Repaglinide and Rosiglitazone Effect in Newly Diagnosed Type 2 Diabetes Patients in China

Objective To investigate a potential relationship between Solute carrier family 30 （zinc transporter） member 8 （SLC3OAS） rs13266634 variant and efficacy of rosiglitazone or repaglinide in treating newly diagnosed Chinese type 2 diabetes patients. Methods A total of 209 diabetic patients without any antihyperglycemic history were recruited and treated with repaglinide or rosiglitazone randomly for 48 weeks （104 and 105 patients, respectively）. Anthropometric measurements and clinical laboratory tests were carried out before and after the treatment. An non-synonymous variant rs13266634 was genotyped by matrix-assisted laser desorption ionization-time of flight mass spectroscopy. Results Ninety-one patients in repaglinide group and ninety-three patients in rosiglitazone group completed the study. 6 value of homeostasis model assessment of beta cell function （HOMA-B） and 6 value of fasting proinsulin levels were statistically significant between three genotype groups （P=0.0149 and 0.0246, respectively） after rosiglitazone treatment. However, no genotype association was observed in the repaglinide or rosiglitazone group with other parameters. Conclusion The SLC3OA8 variant was associated with the efficacy of insulin sensitizer monotherapy on insulin secretion in patients with newly diagnosed type 2 diabetes mellitus in Shanghai, China.

Cigarette Smoking Increases Risk for Incident Metabolic Syndrome in Chinese Men—Shanghai Diabetes Study

Objective To determine whether smoking increases the risk for developing metabolic syndrome （MetS） in Chinese men.Methods A total of 693 men with no MetS at baseline were followed for 2.9‐5.5 years.Subjects were divided into nonsmokers,ex‐smokers,and current smokers according to baseline smoking status.Results After adjusting for age,education level,alcohol intake,fasting plasma insulin,HOMA‐IR index,and BMI at baseline and weight change,current smokers were dose‐dependently associated with increased risk for developing new MetS compared with nonsmokers.The odds ratio （OR） was 2.131 （95% CI,1.264,3.592;P0.01） for the NCEPIII definition or 3.083 （95% CI,1.807,5.295;P0.01） for the JCDCG definition of MetS.Ex‐smokers who had quit for ≥13 years significantly decreased the risk for developing new MetS defined by the JCDCG definition.Compared with nonsmokers,current smokers were significantly associated with increased incidence of hypertriglyceridemia and low HDL‐C.Conclusion Smoking is a risk factor for developing MetS in Chinese men after adjusting for age,education level,alcohol intake,fasting plasma insulin,HOMA‐IR,BMI,and weight change.This could be due to an increased incidence of dyslipidemia.Smoking cessation for 13 years decreased the risk for developing MetS defined by the JCDCG definition.

Consensus on rapid screening for prodromal Alzheimer's disease in China

Alzheimer's disease(AD)is a common cause of dementia,characterised by cerebral amyloid-βdeposition,pathological tau and neurodegeneration.The prodromal stage of AD(pAD)refers to patients with mild cognitive impairment(MCl)and evidence of AD's pathology.At this stage,disease-modifying interventions should be used to prevent the progression to dementia.Given the inherent heterogeneity of MCl,more specific biomarkers are needed to elucidate the underlying AD's pathology.Although the uses of cerebrospinal fluid and positron emission tomography are widely accepted methods for detecting AD's pathology,their clinical applications are limited by their high costs and invasiveness,particularly in low-income areas in China.Therefore,to improve the early detection of Alzheimer's disease(AD)pathology through cost-effective screening methods,a panel of 45neurologists,psychiatrists andgerontologistswas invited to establish a formal consensus on the screening of pAD in China.The supportive evidence and grades of recommendations are based on a systematic literature review andfocus group discussion.National meetings were held to allow participants to review,vote and provide their expert opinions to reach a consensus.A majority(two-thirds)decision was used for questions for which consensus could not be reached.Recommended screening methods are presented in this publication,including neuropsychological assessment,peripheral biomarkers and brain imaging.In addition,a general workflow for Screening pAD in China is established,which will help clinicians identify individuals at high risk and determine therapeutic targets.

Role of Fibroblast Growth Factor 19 in Maintaining Nutrient Homeostasis and Disease

Fibroblast growth factor 19 （FGF19） is a kind of gut-derived postprandial hormone. As an atypical member of the FGF family, FGF19 functions as an endocrine hormone except regulating cell growth and differentiation. FGF19 plays a key role in coordination of liver bile acid biosynthesis and gallbladder motility, and acts as a regulator of metabolic homeostasis, including strengthening insulin sensitivity, decreasing triglyceride concentration and reducing body weight.

Correlation between Waist Circumference and Carotid Intima-Media Thickness in Women from Shanghai, China

Objective To evaluate whether waist circumference （WC） 〉85 cm is related to asymptomatic preclinical atherosclerosis in women from Shanghai, China. Methods A total of 2365 females aged 〉20 years recruited from 4 communities underwent physical examination and carotid artery scanning. Their carotid intima-media thickness （C-iMT） was measured. Results The C-IMT was significantly higher in overweight or obese women with their BMI 〉25.0 kg/m2 {P〈O.01） and in those with their WC _〉85 cm than in those with their WC 〈85 cm （P〈O.01）. Spearman and partial correlation analysis showed that the C-IMT was significantly correlated with WC which was independent of menopausal status. The C-IMT significantly increased with the increasing WC and reached to a platform in about 85 cm. An increment tendency was found in the subgroup with its WC 〈 85 cm （P〈O.01） while no significant tendency was found in the subgroup with its WC_〉85 cm （P=0.07）. Multiple stepwise regression analysis showed that the WC was an independent risk factor for C-IMT. In logistic regression model, the odd ratio of WC _〉80 cm, _〉80 cm and 〈85 cm and 〉85 cm for evaluating the risk of C-IMT elevation was 2.632, 2.501, and 1.878, respectively. Conclusion WC is significantly correlated with C-IMT in women from Shanghai, China, and WC_〉85 cm may be used in identifying the risk of subclinical carotid atherosclerosis.

Data Resource Profile:A Protocol of China National Diabetic Chronic Complications Study

Diabetes affects approximately 10.5%of adults worldwide,and its chronic complications lead to severely disabling sequelae and premature death,thus placing a heavy healthcare burden on both patients affected and society[1].China has experienced a dramatic increase in diabetes prevalence from 0.67%in 1980[2]to 12.8%in 2018[3]and has approximately one-quarter of people with diabetes worldwide[1].It is therefore essential to understand the epidemiologic characteristics of the chronic complications and co-morbidities of diabetes,and the current status of diabetes management to guide planning for appropriate diabetes care and intervention for these complications and co-morbidities at the national level[4-7].

Relationship between Waist Circumference and Elevation of Carotid Intima-media Thickness in Newly-diagnosed Diabetic Patients

Objective Waist circumference, as a brief indicator of visceral obesity, is associated with multi-metabolic disorders and cardiovascular diseases. The present study was aimed to find out the relationship between waist circumference and carotid intima media thickness （C-IMT）, as well as the best waist circumference cutoff for identifying C-IMT elevation in Chinese male patients with newly-diagnosed diabetes. Methods Five hundred and seventy-eight patients from Department of Endocrinology and Metabolism in Shanghai Sixth People＇s Hospital affiliated to Shanghai Jiao Tong University were enrolled. Both physical examination （for measurement of waist circumference） and carotid ultrasonography （for measurement of C-IMT） were performed. Results After grouping according to the quartiles of C-IMT, the waist circumference increased across all its quartiles. The waist circumference in 3rd and 4th quartiles （90.7_＋9.8 cm and 90.8＋9.6 cm） was significant higher than in 1st and 2nd quartiles （P〈0.05）. When subjects were divided into 4 groups according to waist circumference, the C-IMT of subjects with waist circumference 90-95 cm was significant higher than that of subjects with waist circumference 85-90 cm and less than 85 cm respectively （P〈0.05）. Both spearman and partial correlation analysis showed that C-IMT was positively correlated with waist circumference （P〈0.01）. C-IMT was found significantly elevated with the increase of waist circumference. Multiple stepwise regression analysis showed that waist circumference was one of the independent risk factors of C-IMT. After an average of 2.23_＋0.85 years follow up, there was a significant elevation of C-IMT in the group with baseline waist circumference over 90 cm P〈0.05）, while no significant difference was detected in the group with baseline waist circumference less than 90 cm （P=0.27）. Logistic regression showed that baseline waist circumference over 90 cm was associated with a relative risk to C-IMT elevation of 1.132 （95% CI 1.043-1.431, P〈0.05）. Conclusion Among newly-diagnosed diabetic male patients, waist circumference over 90 cm not only reflects sub-clinical atherosclerosis in early stage, but also predicts the progression of atherosclerosis.

The Impact of Cigarette Smoking on Metabolic Syndrome

Metabolic syndrome （MetS） is a constellation of interconnected cardiometabolic disorders, including obesity, hyperglycemia, dyslipidemia, and elevated blood pressure. MetS is a precursor to type 2 diabetes mellitus （T2DM） and cardiovascular disease （CVD）; it increases the risk of T2DM by 3-4 times[11 and the risk of CVD by 1.4-fold[21, and is more prevalent in obese individuals. As the obesity rates increase, the prevalence of MetS in the population is increased. In 2006, the global prevalence of MetS in adults was estimated to be 20%-25%TM, and in China, in 2007-2008, using the criteria of the Chinese Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults （JCDCG）, it reached 21.9% among the adult population aged 〉20 vears old[4].

The thickness and volume of the choroid,outer retinal layers and retinal pigment epithelium layer changes in patients with diabetic retinopathy

AIM: To evaluate the thickness and volume changes of the choroidal, outer retinal layers(ORL) and retinal pigment epithelium(RPE) in patients with diabetic retinopathy(DR) using optical coherence tomography(OCT) and correlate them with visual acuity.METHODS: We carried out a retrospective observational case series. Consecutive DR patients were recruited for color fundus photography and OCT assessment. The RPE, ORL and choroidal thickness were measured. The correlation with the best-corrected visual acuity(BCVA) was also investigated.RESULTS: The study included 128 eyes, comprising 45 eyes of 25 diabetic macular edema(DME) patients, 34 eyes of 20 DR without DME(non-DME) patients, and 49 eyes of 25 age-matched normal individuals. The choroidal thickness in DR patients were decreased statistically significantly compared with the control group(P<0.05). The mean macular ORL thickness in DME(73.02±15.34 μm) and non-DME groups(76.35±7.32 μm) were decreased statistically significantly compared with the control group(80.20±5.85 μm; P=0.006, P=0.013, respectively). In both the non-DME and DME groups, the RPE thickness were decreased compared with the control group(P<0.05), except in the macular and central ring. The BCVA were significant interactions with the total inner retinal volume and macular RPE thickness in the DME group(r=0.115, P<0.001, r=-0.013, P=0.017, respectively).CONCLUSION: The choroid, ORL and RPE thickness are significantly decreased in DR patients compared with controls in different segments.

Peripapillary vessel density and retinal nerve fiber layer thickness changes in early diabetes retinopathy

·AIM:To perform a quantitative analysis of the peripapillary vessel density(VD)and retinal nerve fiber layer(RNFL)thickness changes in patients with early stage of diabetic retinopathy(DR).·METHODS:In this case-control study,swept-source optical coherence tomography angiography(SS-OCTA)imaging was used to examine diabetic and age-matched healthy subjects.The optic disc HD 6×6 mm^(2) blood flow imaging scan mode was selected.Automatic software was used to measure the peripapillary VD,capillary vessel density(CVD),and RNLF in an optic nerve head(ONH)filed based on the Garway-Heath map.In addition,the correlation between peripapillary VD,CVD,and RNFL was further investigated.·RESULTS:The cohort consisted of 32 healthy individuals and 72 patients with diabetes(34 eyes with no DR and 38 eyes with mild-moderate NPDR).Peripapillary VD decreased in the mild-moderate NPDR group compared to the control group in most regions(P<0.05).Peripapillary CVD and RNFL thickness were significantly lower in the mild-moderate NPDR group in the superior temporal(ST)quadrants(P=0.018.P=0.030).In the correlation analysis of each region,the RNFL thickness in the NS region was positively correlated with the peripapillary VD and CVD(r=0.233,P=0.05;r=0.288.P=0.015).In the TI region,the RNFL thickness was positively correlated with the peripapillary CVD(r=0.237,P=0.047).·CONCLUSION:The measurement based on the ONH topographic map may be helpful in detecting functional and structural impairments in DR.The peripapillary VD,CVD and RNFL decrease in early DR,and the RNFL thickness altered in association with the CVD or/and VD in some regions.

Effect of the Gut Microbiota on Obesity and Its Underlying Mechanisms: an Update

Obesity has become one of the most prevalent health issues of our time. According to a 2012 WHO report, around 3.4 million adults die each year as a result of being overweight or obese. Humans are in fact superorganisms composed of both human and microbial cells with 2 sets of genes, those encoded in our own genome and those encoded in our microbiota. All these cells and genes have the potential to influence our health.

Relationship of serum vitamin D levels with diabetic microvascular complications in patients with type 2 diabetes mellitus

Background:Vitamin D deficiency has been reported to be associated with diabetic microvascular complications,but previous studies have only focused on the relationship between vitamin D and specific complications.Therefore,we aimed to explore the relationship between vitamin D level and diabetic microvascular complications in general,including diabetic retinopathy(DR),diabetic nephropathy(DN),and diabetic peripheral neuropathy(DPN).Methods:This was a cross-sectional study of 815 patients with type 2 diabetes mellitus(T2DM).Clinical information and laboratory results were collected from the medical records.The relationship between vitamin D and the three diabetic microvascular complications was investigated.Results:The serum 25-hydroxyvitamin D(25[OH]D)level of patients with DPN and/or DN was significantly lower than that of T2DM patients without any microvascular complications(P<0.01).Univariate analysis showed that the 25(OH)D level was related to DPN and DN,but not DR.After adjustment,the 25(OH)D level was confirmed to be an independent protective factor for DPN(odds ratio[OR]:0.968,P=0.004)and DN(OR:0.962,P=0.006).The prevalence of DPN and DN increased significantly as the serum 25(OH)D levels decreased.Furthermore,patients with both DPN and DN had the lowest concentration of serum 25(OH)D(P<0.001),and the prevalence of macroalbuminuria increased more abruptly than that of microalbuminuria across the 25(OH)D tertiles.Among the patients with vitamin D insufficiency,those with DPN presented more comorbid macroalbuminuria than those without DPN(15.32%vs.4.91%;P=0.001).Conclusions:Vitamin D deficiency is independently associated with higher risk of DPN and DN,but not DR,in T2DM patients.Further,it may be a potential predictor for both the occurrence and severity of DPN and DN.

Targeted gene panel provides advantages over whole-exome sequencing for diagnosing obesity and diabetes mellitus

A small fraction of patients diagnosed with obesity or diabetes mellitus has an underlying monogenic cause.Here,we constructed a targeted gene panel consisting of 83 genes reported to be causative for monogenic obesity or diabetes.We performed this panel in 481 patients to detect causative variants and compared these results with whole-exome sequencing(WES)data available for 146 of these patients.The coverage of targeted gene panel sequencing was significantly higher than that of WES.The diagnostic yield in patients sequenced by the panel was 32.9%with subsequent WES leading to three additional diagnoses with two novel genes.In total,178 variants in 83 genes were detected in 146 patients by targeted sequencing.Three of the 178 variants were missed by WES,although the WES-only approach had a similar diagnostic yield.For the 335 samples only receiving targeted sequencing,the diagnostic yield was 32.2%.In conclusion,taking into account the lower costs,shorter turnaround time,and higher quality of data,targeted sequencing is a more effective screening method for monogenic obesity and diabetes compared to WES.Therefore,this approach could be routinely established and used as a first-tier test in clinical practice for specific patients.

Effectiveness of quality of care for patients with type 2 diabetes in China:findings from the Shanghai Integration Model(SIM)

This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai,China.A total of 173235 patients with type 2 diabetes in 2017 were included in the analysis.Profiles of risk factors and intermediate outcomes were determined.The patients had a mean age of 66.43±8.12(standard deviation(SD))years and a mean diabetes duration of 7.95±5.53(SD)years.The percentage of patients who achieved the target level for HbA_(1c)(<7.0%)was 48.6%.Patients who achieved the target levels for blood pressure(BP)<130/80 mmHg and low-density lipoprotein-cholesterol(LDL-c)<2.6 mmol/L reached 17.5%and 34.0%,respectively.A total of 3.8%achieved all three target levels,and the value increased to 6.8%with an adaptation of the BP target level(<140/90 mmHg)for those over 65 years.Multivariable analysis identified the factors associated with a great likelihood of achieving all three target levels:male,young age,short diabetes duration,low body mass index,macrovascular complications,no microvascular complications,prescribed with lipid-lowering medication,and no prescription of antihypertensive medication.In conclusion,nearly 50%and one-third of the patients with diabetes met the target levels for HbA_(1c)and LDL-c,respectively,with a low percentage achieving the BP target level.The percentage of patients who achieved all three target levels needs significant improvement.

Application and prospect of artificial intellingence in diabetes care

Diabetes is one of the fastest-growing non-communicable diseases,becoming an important public health concern worldwide as well as in China.Currently,China has the largest population living with diabetes.Artificial intelligence(AI)is a fast-growingfield and its applications to diabetes could enable the delivery of better management services for people with diabetes.This perspective summarized the latestfindings of digital tech-nologies and AI use in the following areas of diabetes care,mainly including screening and risk predictions of diabetes and diabetic complications,precise monitoring and inter-vention combined with new technologies,and mobile health application in self-management support for people with diabetes.Challenges to promote further use of AI in diabetes care included data standardization and integra-tion,performance of AI-based medical devices,motivation of patients,and sensitivity to privacy.In summary,although the AI applications in clinical practice is still at an early stage,we are moving toward a new paradigm for diabetes care with the rapid development and emerging application of AI.

Bile acid signaling in the regulation of whole body metabolic and immunological homeostasis

Bile acids(BAs)play a crucial role in nutrient absorption and act as key regulators of lipid and glucose metabolism and immune homeostasis.Through the enterohepatic circulation,BAs are synthesized,metabolized,and reabsorbed,with a portion entering the vascular circulation and distributing systemically.This allows BAs to interact with receptors in all major organs,leading to organ-organ interactions that regulate both local and global metabolic processes,as well as the immune system.This review focuses on the whole-body effects of BA-mediated metabolic and immunological regulation,including in the brain,heart,liver,intestine,eyes,skin,adipose tissue,and muscle.Targeting BA synthesis and receptor signaling is a promising strategy for the development of novel therapies for various diseases throughout the body.

Desulfovibrio vulgaris,a potent acetic acid-producing bacterium,increased by Astragalus polysaccharides to attenuate nonalcoholic fatty liver disease in mice

OBJECTIVE Although the underlying mechanism is largely unknown,gut dysbiosis has emerged as a central initiator of obesity-related diseases including nonalcoholic fatty liver disease(NAFLD),type 2 diabetes and metabolic syndrome.The emerging evidence support the use of prebiotics like herb-derived polysaccharides for treating NAFLD by modulating gut microbiome.So,our study focused on the microbiota-dependent anti-NAFLD effect and the exact mechanisms of Astragalus polysaccharides(APS)extracted from Astragalus mongholicus Bunge in high-fat diet(HFD)fed mice.METHODS Co-housing experiment was used to assess the microbiota dependent anti-NAFLD effect of APS.Then,targeted metabolomics and metagenomics were adopted for determining short-chain fatty acids(SCFAs)and bacteria that were specifically enriched by APS.Further in vitro experiment was carried out to test the capacity of SCFAs-producing of identified bacterium.Finally,the anti-NAFLD efficacy of identified bacterium was tested in HFD fed mice.RESULTS Our results first demonstrated the anti-NAFLD effect of APS in HFD fed mice and the contribution of gut microbiota.Moreover,our results indicated that SCFAs,predominantly acetic acid were elevated in APS-supplemented mice and ex vivo experiment.Metagenomics revealed that D.vulgaris from Desulfovibrio genus was not only enriched by APS,but also a potent generator of acetic acid,which showed significant anti-NAFLD effects in HFD fed mice.In addition,D.vulgaris modulated the hepatic gene expression pattern of lipids metabolism,particularly suppressed hepatic fatty acid synthase(FASN)and CD36 protein expression.CONCLUSION APS enriched D.vulgaris is effective on attenuating hepatic steatosis possibly through producing acetic acid,and modulation on hepatic lipids metabolism in mice.Further studies are warranted to explore the long-term impacts of D.vulgaris on host metabolism and the underlying mechanism.

Metabolic Disorders Increase the Risk to Incident Cardiovascular Disease in Middle-aged and Elderly Chinese

Objective The association of metabolic syndrome （MetS） with cardiovascular diseases （CVD） has not been adequately explored in middle-aged and elderly Chinese. This study aimed to investigate MetS＇ prevalence and its impact on the CVD incidence in this specific population group. Methods A data set of a community-based prospective cohort study was analyzed. A total of 2300 subjects aged 40-94 years were followed up for the CVD events. MetS defined according to the JCDCG criteria was assessed at baseline, and the middle-aged and elderly groups were classified by the WHO definition. Results As compared with the middle-aged group, the prevalence of MetS increased by 0.6 times （34.6% vs. 21.3%） and the incidence density of CVD increased by 4.9 times in the elderly group （52.3/1000 person-year vs. 8.9/1000 person-year）. Furthermore, the multivariate Cox regression revealed that the risk to CVD incidence was independently related to increased waist circumference in the middle-aged group （HR=2.23, P〈0.01） and to elevated blood glucose in the elderly group （HR=1.39, P〈O.01）. Conclusion MetS was highly prevalent in middle-aged and elderly Chinese. MetS significantly increased the risk to OdD incidence in the elderly. All individuals with metabolic disorders should receive active clinical care to reduce the incidence of CVD.

Functional Metabolomics Reveals that Astragalus Polysaccharides Improve Lipids Metabolism through Microbial Metabolite 2-Hydroxybutyric Acid in Obese Mice

Polysaccharides are widely present in herbs with multiple activities,especially immunity regulation and metabolic benefits for metabolic disorders.However,the underlying mechanisms are not well under-stood.Functional metabolomics is increasingly used to investigate systemic effects on the host by iden-tifying metabolites with particular functions.This study explores the mechanisms underlying the metabolic benefits of Astragalus polysaccharides(APS)by adopting a functional metabolomics strategy.The effects of APS were determined in eight-week high-fat diet(HFD)-fed obese mice.Then,gas chromatography–time-of-flight mass spectrometry(GC–TOFMS)-based untargeted metabolomics was performed for an analysis of serum and liver tissues,and liquid chromatography–tandem mass spectrom-etry(LC–MS/MS)-based targeted metabolomics was performed.The potential functions of the metabo-lites were tested with in vitro and in vivo models of metabolic disorders.Our results first confirmed the metabolic benefits of APS in obese mice.Then,metabolomics analysis revealed that APS supplemen-tation reversed the HFD-induced metabolic changes,and identified 2-hydroxybutyric acid(2-HB)as a potential functional metabolite for APS activity that was significantly decreased by a HFD and reversed by APS.Further study indicated that 2-HB inhibited oleic acid(OA)-induced triglyceride(TG)accumula-tion.It was also found to stimulate the expression of proteins in lipid degradation in hepatocytes and TG lipolysis in 3T3-L1 cells.Moreover,it was found to reduce serum TG and regulate the proteins involved in lipid degradation in high-fat and high-sucrose(HFHS)-fed mice.In conclusion,our study demonstrates that the metabolic benefits of APS are at least partially due to 2-HB generation,which modulated lipid metabolism both in vitro and in vivo.Our results also highlight that functional metabolomics is practical for investigating the mechanism underlying the systemic benefits of plant polysaccharides.

Effects and mechanisms of berberine in diabetes treatment

Berberine from Rhizoma Coptidis is an oral hypoglycemic agent with anti-dyslipidemia and anti-obesity activities.Its metabolic activity of regulating blood glucose and lipids has been widely studied and evidenced in patients and various animal models.Berberine is known as an AMP-activated protein kinase(A MPK)activator.Its insulin-independent hypoglycemic effect is.related to inhibition of mitochondrial function,stimulation of glycolysis and activation of AMPK pathway.Additionally,berberine may also act as an x-glucosidase inhibitor.In the newly-diagnosed type 2 diabetic patients,berberine is able to lower blood insulin level via enhancing insulin sensitivity.However,in patients with poorβ-cell function,berberine may improve insulin secretion via resuscitating exhausted islets.Furthermore,berberine may have extra beneficial effects on diabetic cardiovascular complications due to its cholesterol-lowering,anti arrhythmias and nitric oxide(NO)inducing properties.The antioxidant and aldose reductase inhibitory activities of berberine may be useful in alleviating dia betic nephropathy.Although evidence from animal and human studies consistently supports the therapeutic activities of berberine,large-scale multicenter trials are still necessary to evaluate the efficacy of berberine on diabetes and its related complications.