Gene Expression Profile of Human Skeletal Muscle and Adipose Tissue of Chinese Han Patients with Type 2 Diabetes Mellitus

Objective To study the differential patterns of gene expression in skeletal muscle and adipose tissue between type 2 diabetes mellitus （T2DM） patients and healthy subjects using DNA microarray analysis, Methods T2DM patiens were divided into female group, young male group and old male group. DNA microarray analysis and quantitative real-time PCR were carried out to anaIyze the relation between gene expressions and T2DM. Results The mRNA expression of 298, 578, and 350 genes was changed in the skeletal muscle of diabetes mellitus patients compared with control subjects. The 1320, 1143, and 2847 genes were modified in adipose tissue of the three groups. Among the genes surveyed, the change of 25 and 39 gene transcripts in skeletal muscle and adipose tissue was ≥2 folds, These differentially expressed genes were classified into 15 categories according to their functions. Conclusion New genes are found and T2DM can be prevented or cured.

Correlation between the Polymorphism of PPARγ-2 gene and the Susceptibility of Type 2 Diabetes Mellitus in Guangxi Bama Mini-pigs

[ Objective] The research aimed to discuss the relationship between the polymorphism of PPARy.2 gene and the susceptibility of type 2 diabetes mellitus （T2DM） in Guangxi Bama mini-pigs. [ Method] 24 Guangxi Bama mini-pigs were fed with high-fat and high-sucrose diet, and partial sequences of exon 2 of PPARy-2 gene were amplified by using PCR method. In addition, the contents of fasting blood glucose and insulin （INS） in Guangxi Bama mini-pigs were determined, and the glucose tolerance test （GTT） was also carried out. [ Result] There was one SNP site （19813A/G） Jn partial sequence of exon 2 of the cloned PPAFly-2 gene, and AA （7 pigs） and AG （17 pigs） genotype were detected. The contents of fasting insulin and 60-min blood glucose in GTT in AG-genotype Guangxi Bama mini-pigs were significantly higher than those of AA genotype （ P 〈0.05）, while the incidence of T2DM in AG-genotype Guangxi Bama mini-pigs （71.4%） was obviously higher than that of AA gen- otype （5.9%）. [ Conclusion] The polymorphism of 19813A/G in exon 2 of PPARy-2 gene was related with the susceptibility of T2DM in Guangxi Bama mini-pigs.

Silkworm Extract Ameliorates Type 2 Diabetes Mellitus and Protects Pancreaticβ-cell Functions in Rats

Objective The aim of the present study was to investigate the hypoglycemic effects of silkworm extract(SE)on experimental type 2 diabetes mellitus(T2DM)rats.Methods SE was prepared by dissolving freeze-dried silkworm powder in 70%(v/v)aqueous ethanol.T2DM rats were induced by feeding them a high fat diet and an intraperitoneal injection of streptozotocin(STZ).The blood glucose,free fatty acid(FFA),malondialdehyde(MDA),tumor necrosis factor alpha(TNF-α)and superoxide dismutase(SOD)levels were detected by enzyme-linked immunosorbent assay(ELISA).The quality of SE was controlled by high performance liquid chromatography(HPLC;Agilent 1260,Agilent,USA).Hematoxylin-eosin(HE)staining was performed for histological evaluation.Antibody expression was assessed via immunohistochemistry(IHC)staining.Results SE could improve insulin resistance and islet cell function by reducing FFA,MDA and TNF-αlevels and increasing SOD level.In addition,pancreatic HE staining analysis revealed that SE has a protective effect on isletβ-cells.Conclusions The present study indicates that SE has hypoglycemic as well as pancreatic protective effects in T2DM model rats.

Association between the SUMO4 M55V Polymorphism and Susceptibility to Type 2 Diabetes Mellitus:A Meta-analysis

Objective The aim of this study is to determine whether the SUMO4 M55V polymorphism is associated with susceptibility to type 2 diabetes mellitus （T2DM）. Methods A meta-analysis was performed to detect the potential association of the SUMO4 M55V polymorphism and susceptibility to T2DM under dominant, recessive, co-dominant （homogeneous and heterogeneous）, and additive models. Results A total of eight articles including 10 case-control studies, with a total of 2932 cases and 2679 controls, were included in this meta-analysis. The significant association between the SUMO4 M55V polymorphism and susceptibility to T2DM was observed in the dominant model （GG ＋ GA versus AA： OR = 1.21, 95% CI = 1.05-1.40, P = 0.009）, recessive model （GG versus GA ＋ AA： OR = 1.29, 95% CI = 1.07-1.356, P = 0.010）, homozygous model （GG versus AA： OR = 1.41, 95% CI = 1.06-1.56, P = 0.001）, and additive model （G versus A： OR = 1.18, 95% CI = 1.08-1.29, P = 0.001）, and marginally significant in the heterozygous model （GA versus AA： OR = 1.16, 95% CI = 0.98-1.36, P = 0.080）. In subgroup analyses, significant associations were observed in the Chinese population under four genetic models excluding the heterozygous model, whereas no statistically significant associations were observed in the Japanese population under each of the five genetic models. Conclusion The meta-analysis demonstrated that the G allele of the SUMO4 M55V polymorphism could be a susceptible risk locus to T2DM, mainly in the Chinese population, while the association in other ethnic population needs to be further validated in studies with relatively large samples.

Initiation of Basal Insulin in Patients with Uncontrolled Type 2 Diabetes Mellitus

Type 2 diabetes mellitus is a growing health problem, characterized by insulin resistance progressing to beta cell dysfunction and insulin deficiency, most of these patients will need intensification of treatment and initiation of insulin to delay or prevent diabetic complications. Glycemic control is the most important aspect of management, and in reducing morbidity and mortality of the diseases. Control of plasma glucose in patients with diabetes can be assessed by HbA1c, FPG, PPG, but still HbA1c% remains the gold standard for assessment of glycemic control and follow up of diabetic patients. The aim of this study is to assess HbA1c% in patients on oral anti-diabetic drugs, with poor glycemic control before and after adding basal insulin, with titration of the dose of insulin depending on fasting blood sugar. 82 patients with uncontrolled type 2 diabetes (43.9% male, 56.1% female), with HbA1c more than 9%, on two types of oral diabetic medication or more, were started on basal insulin (glargine, lantus) and followed for three to six months. Overall 82 patients with type 2 diabetes mellitus were included in the study. The mean age of the study population was 58.4 years, the mean duration of the disease range was 13.4 years. All patients with HbA1c more than 9%, without organ failure, were included in the study. The mean HbA1c overall had decreased from mean of 11.15% before starting basal insulin to the mean of 8.43% within 3 to 6 month, after initiating basal insulin, this difference was significant at p < 0.001. There was no adverse effect on this medication in any of the study group. The addition of basal insulin to oral anti-diabetic medication in uncontrolled insulin-naïve type 2 diabetic patients resulted in significant improvement of glycemic control, with improved HbA1c level, without adverse effects.

Surfactin alleviated hyperglycaemia in mice with type 2 diabetes induced by a high-fat diet and streptozotocin

Type 2 diabetes mellitus(T2DM)is associated with liver dysfunction and intestinal dysbiosis.Bioactive peptides(BAPs)have been reported to ameliorate T2DM by preventing oxidative damage to the liver.Bacillus amyloliquefaciens fmb50 produces the lipopeptide surfactin with a wide range of biological activities.The effects of surfactin on T2DM,on the other hand,have not been studied.In the present study,80 mg/kg body weight surfactin supplementation lowered fasting blood glucose(FBG)levels by 21.05%and insulin resistance(IR)by 18.18%compared with those in the T2DM group,reduced inflammation,and increased antioxidant activity in mice with T2DM induced by a high-fat diet(HFD)and streptozotocin(STZ).According to further research,surfactin administration reduced Firmicutes-to-Bacteroidetes ratios while increasing Bifi dobacterium abundance by 20 times and the level of the tight junction protein Occludin by 18.38%and ZO-1 by 66.60%.Furthermore,surfactin also improved hepatic glucose metabolism by activating the adenosine monophosphate-activated protein kinase(AMPK)signalling pathway,increasing glycogen synthesis and glucose transporter 2(GLUT2)protein expression while reducing glucose-6-phosphatase(G6Pase)protein expression.In addition,the increased Bifi dobacterium abundance indirectly reduced the liver burden of the metabolic products indole,cresol and amine produced by saprophytic bacteria.All of these findings revealed that surfactin not only ameliorated HFD/STZ-induced gut dysbiosis and preserved intestinal barrier integrity but also enhanced hepatic glucose metabolism and detoxifi cation function in T2DM mice.The gut microbiota appeared to be important in controlling glucose metabolism,IR,fat accumulation,inflammation and antioxidation,according to Spearman’s correlation coeffi cients.All data indicated that surfactin alleviated hyperglycaemia in mice with T2DM induced by HFD/STZ.

Expert Consensus on Clinical Management of T2DM Combined with Obesity Reversal Treatment in China(2023 Edition)

With lifestyle changes,the incidence of type 2 diabetes(T2DM)and obesity has significantly increased,becoming major chronic diseases that seriously threaten the health of China’s residents.Both domestic and international guidelines and consensus exist regarding the diagnosis and management of this disease.In recent years,T2DM treatment has focused more on new tactics that lean towards a patient-centered comprehensive management approach,replacing the traditional glucose-centered approach.Additionally,an increasing amount of evidence in medicine suggests that the reversal of diabetes is possible.However,there is currently no expert consensus on the clinical management of T2DM combined with obesity reversal treatment.Therefore,experts and scholars in China with extensive experience in T2DM combined with obesity reversal treatment have been invited to develop this consensus.The content includes early identification and diagnosis of T2DM combined with obesity,definition and mechanisms of diabetes reversal,disease assessment and grading,staging of diabetes and goals of reversal,the 2+N reversal strategy,inpatient system treatment combined with comprehensive outpatient management(including weight control,precise nutrition,scientific exercise,glucose-lowering medication,psychological intervention,rehabilitation therapy,and remote follow-up through online platforms),and evaluation of post-reversal efficacy.The aim is to further improve the level of T2DM combined with obesity reversal diagnosis,treatment,and management in China,and to implement the Healthy China strategy.

Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

Solute carriers(SLCs) constitute the largest superfamily of membrane transporter proteins.These transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and ions.They actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake(e.g., SLC2A4/GLUT4), glucose reabsorption(e.g., SLC5A2/SGLT2), thermogenesis(e.g., SLC25A7/UCP-1), and ATP production(e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus(T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone(SLCO1B1/OATP1B1) and metformin(SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

A comparative study of pancreas transplantation between type 1 and 2 diabetes mellitus

Background:Pancreas transplantation remains the best long-term treatment option to achieve physiological euglycemia and insulin independence in patients with labile diabetes mellitus(DM).It is widely accepted as an optimal procedure for type 1 DM(T1DM),but its application in type 2 DM(T2DM)is not unanimously acknowledged.Methods:In total,146 diabetes patients undergoing pancreas transplantation were included in this study.Clinical data and outcomes were compared between the T1DM and T2DM groups.Results:Majority(93%)of the pancreas transplantations in T2DM were for uremic recipients.Complications occurred in 106(73%)patients,including 70(48%)with early complications before discharge and 79(54%)with late complications during follow-up period.Overall,rejection of pancreas graft occurred in 37(25%)patients.Total rejection rate in T2DM recipients was significantly lower than that in T1DM.The short-and long-term outcomes for endocrine function in terms of fasting blood sugar and hemoglobin A1c levels and graft survival rates are comparable between the T2DM and T1DM groups.Conclusions:T2DM is not inferior to T1DM after pancreas transplantation in terms of surgical risks,immunological and endocrine outcomes,and graft survival rates.Therefore,pancreas transplantation could be an effective option to treat selected uremic T2DM patients without significant insulin resistance.

Thirty-two cases of type 2 diabetes mellitus of qi and yin deficiency treated with laser acupuncture

Objective To observe the clinical therapeutic effect of laser acupuncture on type 2 diabetes mellitus(T2DM)of qi and yin deficiency type.Methods Laser acupuncture was used to treat 32 patients of T2DM.Acupoint selection:Fèishū(肺俞BL13),Píshū(脾俞BL20),Shènshū(肾俞BL23),Wǎnxiàshū(胃脘下俞EX-B3),Sānyīnjiāo(三阴交SP6)and Zúsānlĭ足三里(ST36).It took 20 min in each treatment,five treatments a week.There were 2 days of interval in 2 weeks of treatment.Before and after treatment,the changes in fasting plasma glucose(FPG),postprandial 2 h glucose(2hPG),fasting insulin(FINS),glycosylated albumin(GA),insulin resistance index(HOMA-IR)and the symptom score of traditional Chinese medicine(TCM)were observed in the patients.The therapeutic effect was evaluated.Results Of 32 cases,8 cases were remarkably effective,18 cases effective and 6 cases failed.The total effective rate was 81.3%.At the end of treatment course,the level of every indicator after treatment was significantly lower than that before treatment(all P<0.01).Conclusion Laser acupuncture achieves the significant therapeutic effect on T2DM of qi and yin deficiency and this therapy deserves to be promoted in clinical application.

Structural Insight into the Design on Oleanolic Acid Derivatives as Potent Protein Tyrosine Phosphatase 1B Inhibitors

Oleanolic acid derivatives act as newer protein tyrosine phosphatase 1B （PTP-1B） inhibitors for type 2 diabetes mellitus （T2DM）. In order to understand the structural requirement of PTP-1B inhibitors, 52 oleanolic acid derivatives were divided into a training set （34 compounds） and a test set （18 compounds）. The highly reliable and predictive 3D-QSAR models were constructed by CoMFA, CoMSIA and topomer CoMFA methods, respectively. The results showed that the cross validated coefficient （q2） and non-cross-validated coefficient （R2） were 0.554 and 0.999 in the CoMFA model, 0.675 and 0.971 in the CoMSIA model, and 0.628 and 0.939 in the topomer CoMFA model, which suggests that three models are robust and have good exterior predictive capabilities. Furthermore, ten novel inhibitors with much higher inhibitory potency were designed. Our design strategy was that （i） the electronegative substituents （Cl, -CH2OH, OH and -CH2Cl） were introduced into the double bond of ring C, （ii） the hydrogen bond acceptor groups （C≡N and N atom）, electronegative groups （C≡N, N atom, -COOH and -COOCH3） and bulky substituents （C6H5N） were connected to the C-3 position, which would result in generating potent and selective PTP-1B inhibitors. We expect that the results in this paper have the potential to facilitate the process of design and to develop new potent PTP-1B inhibitors.

Targeting gut microbiota in type 2 diabetes mellitus:Potential roles of dietary flavonoids

Type 2 diabetes mellitus(T2DM)is a common endocrine and progressive metabolic disorder disease,which seriously threatens peoples’lives and health.Due to the high cost of clinical treatments and obvious side effects,looking for effective bioactive ingredients in the diet is an important strategy to prevent or even reduce the risk of diabetes.Epidemiological studies have suggested that dietary flavonoids have a potential antidiabetic effect,but the underlying mechanism remains unclear.Accumulating evidences indicates that gut microbiota has become an important target of dietary interventions.It plays essential roles in the digestion and absorption of flavonoids and affects the occurrence and progression of T2DM.This review systematically summarized the progress of dietary flavonoids targeting gut microbiota to ameliorate T2DM and analyzed possible molecular mechanisms.It suggests that flavonoids may prevent T2DM for healthy people and ameliorate health situations for T2DM patients.In addition,microbiota-based nutrition aims to provide personalized nutritional guidance to alter an individual’s microbiota and further improve response to dietary flavonoids,which will benefit to achieve a more effective diet for the prevention and management of T2DM.

Combined non-alcoholic fatty liver disease and type 2 diabetes in severely obese patients-medium term effects of sleeve gastrectomy versus Roux-en-Y-gastric bypass on disease markers

Background:We aimed to evaluate the medium-term efficacy of sleeve gastrectomy(SG)vs.Roux-en-Y gastric bypass(RYGB)on remission of non-alcoholic fatty liver disease(NAFLD)in patients with type 2 diabetes mellitus(T2DM).Methods:We identified severely obese patients[body mass index(BMI)>35 kg/m^(2)]with NAFLD(as defined by the Longitudinal Assessment of Bariatric Surgery Study)and T2DM(as defined by the American Association of Clinical Endocrinologists and the American College of Endocrinology)who underwent SG or RYGB in a single university surgical centre.The cohorts were match-paired and data were analysed after at least 3 years of follow up.The key outcomes measured were:(I)the improvement of liver function tests and NAFLD markers;(II)glycemic control and insulin resistance.Results:Ninety-six patients were investigated;44(45.8%)were women.The mean pre-operative BMI was 45.2 kg/m2 in the SG and 42.0 kg/m^(2) in the RYGB group.SG and RYGB both significantly reduced serum liver enzyme concentrations.NAFLD markers resolved 2 years after SG in all patients.In contrast,only 78%and 80%of patients achieved remission of NAFLD 2 and 3 years after RYBG respectively.Both procedures resulted in comparable rates of remission of T2DM.Conclusions:Bariatric surgery with SG may be preferable to RYGB for obese patients with NAFLD and T2DM based on the rates of remission of markers of these co-morbidities.However,our results need to be confirmed in prospective trials.Understanding the metabolic effects of specific bariatric surgical procedures may facilitate the development of a personalised approach to weight-loss surgery.

Quantification of liver fat deposition in obese and diabetic patients:A pilot study on the correlation with myocardium and periapical fat content

Backgroud and aim:Non-alcoholic fatty liver disease(NAFLD)is a worldwide health problem,which associated with systemic health problems and causes a higher risk of all-cause mortality.The leading causes of death in NAFLD patients are cardiac complications followed by NAFLD-related liver complications.This study aimed to quantitatively measure the contents of liver and cardiac fat with varying degrees of NAFLD in an obese group and a type 2 diabetes mellitus(T2DM)group to explore differences and correlations.Materials and methods:This study included 170 patients who underwent echo asymmetry and least square estimation-iron quantification sequencing at 3.0 T magnetic resonance imaging.Fat fraction values were quantitatively measured in regions of interest of the liver,myocardium,and periapical adipose tissue.Results:In both the obese and T2DM groups,cardiac fat content was correlated with liver fat content using linear regression(P<0.01).For both the obese and T2DM groups,myocardial fat was higher in the T2DM group than that in the obese group(ventricular septum,3.33%±1.40%vs.2.51%±0.88%;the left ventricle,3.38%±1.43%vs.2.26%±0.87%).For the T2DM group,the different myocardial fat contents and myocardial enzymes were positively correlated with fatty liver severity by multiple comparisons of different degrees of NAFLD(P<0.05).Periapical fat was statistically significant only between mild fatty and normal liver(obese group,P<0.01;T2DM group,P¼0.01).Conclusion:T2DM patients with fatty liver had higher myocardial fat content than obese patients with fatty liver,and both had a linear relationship.Periapical fat is an index for liver fat deposition in patients.The myocardial fat contents in T2DM patients with an increase in the liver fat content,which would influence cardiac function,should be given more attention in clinic.