'Vidangadi Lauha' for obese type 2 diabetes mellitus patients - An open-label randomized controlled clinical trial.

BACKGROUND: Type 2 diabetes mellitus in obese persons is becoming alarming due to the increasing prevalence of its microvascular and macrovascular complications. Multi-targeted treatment can be considered better than single-targeted treatment because of the multiple pathways involved in the pathogenesis of diabetes and its complications. OBJECTIVE: The study aimed to evaluate the efficacy of 'Vidangadi Lauha' (VL) (an Ayurveda formulation) compared with Metformin for obese type II diabetes mellitus. METHODOLOGY: This is an open-label randomized controlled clinical study.Participants were divided into two groups. The trial Group received VL 5 gm BID, and the control group received tablet metformin (MT) 500 mg BID for three months. RESULTS: VL showed reduction in HbA1c from 8.048(0.95) to 7.14(0.73), (CI, 0.7810 to 1.035; p < 0.0001) while MT showed reduction in HbA1C from 8.3(0.99) to7.18(0.67), (CI, 0.9220 to 1.305; p < 0.0001). VL showed improvement in the Quality of life instrument for the Indian Diabetes questionnaire(QOLID) score from 113.87(11.36) to 136.47(8.703) (CI, -25.68 to -19.52; p < 0.0001) as compared to MT 128.57(7.9) to 102.32(7.9), (CI, 23.19 to 29.39; p < 0.0001) VL showed reduction in bowel symptom questionnaire 30.275(8.077) to 13.2(1.265), (CI, 14.60-19.51; p < 0.0001) as compared to MT from 23.85(7.530) to 38.25(6.332), (CI, -15.99 to -12.80; p < 0.0001). CONCLUSION: Both treatments were equally effective in reducing blood sugar fasting (F), post-meal (PM) glycated hemoglobin (HbA1C), and body mass index (BMI). VL is more effective than MT in reducing Ayurvedic symptoms, waist-hip ratio, cholesterol, quality of life, and bowel symptom questionnaire score.

Liraglutide combined with metformin treatment for obese people with type 2 diabetes mellitus: a systematic review and meta-analysis.

AIM: To assess clinical efficacy and safety of liraglutide combined with metformin (LMT) in obese patients with type 2 diabetes (ODP) by conducting a meta-analysis of randomized controlled trials (RCTs). METHODS: PubMed, EMBASE, Cochrane Library, CNKI, CNKI, and VIP databases were systematically searched for randomized controlled trials (RCTs) through January 1, 2015 to investigate the effectiveness of liraglutide combined with metformin treatment (LMT) in obesity patients with type 2 diabetes (ODP). Meta-analysis (using generic inverse variance random effects model) was performed when there were two or more studies reporting on the same evaluation indicators. Review Manager V.5.3 was used to perform the meta-analysis. RESULTS: A total of 1289 participants from 15 RCTs were selected for the final meta-analysis. A synthesis of current evidence of LMT for treating ODP was provided in this protocol. CONCLUSION: This review will offer insights for future research and provide reference for LMT treatment for ODP.

Long-term pharmacokinetic and pharmacological evaluations of a novel indole-benzazepinone derivative on obese Type 2 diabetes mellitus.

Background: Owing to the chronic nature of Type 2 diabetes mellitus, antidiabetic drugs must have long-lasting efficacy. Compound 1 has a good inhibitory effect on acute hyperglycemia, but its long-term hypoglycemic effect has not been evaluated. Results: Preliminary prediction and in vitro experimental pharmacokinetic results support the use of compound 1 for long-term in vivo experiments. Long-term experiments demonstrated that compound 1 significantly reduces blood glucose, improves the oral glucose tolerance of obese mice and has a positive effect on body weight, free fatty acid, hepatocyte steatosis and inflammatory cell infiltration. Conclusion: These findings lay a good foundation for the further exploration and development of novel glycogen phosphorylase inhibitors.

Therapy to Obese Type 2 Diabetes Mellitus: How Far Will We Go Down the Wrong Road?

Traditional glucose-lowering chemical agents, including various types of insulin and insulin secretagogues, insulin sensitizers, gliptins, etc., are based on diabetic pathogenesis of insulin resistance (IR) and islet insufficiency. Numerous evidence-based medical studies have shown that these traditional hypoglycemic chemical agents do not provide cardiovascular benefit to patients with type 2 diabetes mellitus (T2DM) and may even increase the risk of all-cause mortality. Based on research evidence published to date, these studies show that overload of energy could increase the incidence and prevalence of T2DM, and reduction in the heat load can significantly reduce the incidence of T2DM. Therefore, the essence of T2DM is heat overload, meaning heat overload is the etiology of obese T2DM. At the same time, results of numerous studies show that heat overloading is the cause of IR. IR and islet dysfunction are protective factors in intervening with heat overload. These drugs, which are based on the mechanisms of IR and islet insufficiency, increase caloric reserve and cause or worsen obesity, which is equivalent to exacerbating the basic etiology and the cardiovascular risk factor of T2DM. Thus, a reasonable strategy for prevention and treatment of obese T2DM appears to promote the negative balance of calories and the elimination of caloric reserves. Chinese herbal medicines can promote negative balance of heat in many aspects, which can bring new hope for prevention and treatment of T2DM.

Impact of low-carbohydrate diet intervention on weight rebound in obese type 2 diabetes mellitus patients who underwent metabolic surgery / 中华内分泌外科杂志

Objective To observe the improvement of weight rebound in obese type 2 diabetes mellitus patients who underwent metabolic surgery after low-carbohydrate diet intervention.Methods 38 patients with obese type 2 diabetes mellitus who had underwent metabolic surgery in Changhai Hospital from Jan.2010 to Nov.2015,were randomly divided into two groups and intervened by low carbohydrate (LC) diet or diabetes mellitus (DM) diet.The blood glucose and body weight of the two groups were compared and analyzed.Results There was no statistical difference in fasting blood glucose,HbA1c,fasting C-peptide,body weight,waistline and BMI value(t=0.34,S=1.00-32.5,P＞0.05)in diabetes mellitus diet intervention group;while there was significant statistical difference in fasting blood glucose,body weight,waistline and BMI (t=2.38,S=17-24.5,P＜0.05)in low-carbo hydrate diet intervention group.There was significant differences in body weight difference (Z=2.31,P＜0.05),BMI difference(Z=2.36,P＜0.05),and weight rebound rate(P＜0.05) between the two groups,with the low carbohydrate diet intervention group displaying advantages.Conclusions Low carbohydrate diet intervention can improve fasting blood glucose,obesity indexes in obese type 2 diabetes mellitus patients who underwent metabolic surgery.Compared with diabetes mellitus diet intervention,low carbohydrate diet intervention can more greatly improve weight,weight rebound rate,rebound scale and have more advantages for maintaining the operation effects.

Expression of MicroRNA-448 and SIRT1 and Prognosis of Obese Type 2 Diabetic Mellitus Patients After Laparoscopic Bariatric Surgery.

BACKGROUND/AIMS: This study sought to investigate the expression and prognostic value of peripheral blood microRNA-448 (miR-448) and its target gene SIRT1 after laparoscopic bariatric surgery in obese type 2 diabetic mellitus (T2DM) patients. METHODS: Obese T2DM patients were selected and treated with laparoscopic bariatric surgery. Enzyme-linked immunosorbent assay (ELISA) was used to measure SIRT1 protein expression. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to determine the mRNA expression of the related gene. Endothelial progenitor cells (EPCs) were grouped into blank, negative control (NC), miR-448 mimic, miR-448 inhibitor, siRNA-SIRT1 and miR-448 inhibitor + siRNA-SIRT1 groups. Transwell assays and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were applied to determine cell invasion and cell viability. A tube formation assay and an adherence test were utilized to assess the angiogenic and adhesive capacities of the cells. RESULTS: In peripheral blood, the expression of miR-448 was reduced, whereas the mRNA and protein expression of SIRT1 was increased after surgery compared to before surgery. miR-448 expression was lower and mRNA and protein expression of SIRT1 was higher in the effective group than in the ineffective group after surgery. SIRT1 is a target gene of miR-448. miR-448 can suppress viability and invasion, and it reflects the angiogenic and adhesive capacity of EPCs and the protein expression of relative genes in EPCs through targeting SIRT1. CONCLUSION: The results demonstrated that miR-448 and its target gene SIRT1 can serve as prognostic indicators for obese T2DM patients after laparoscopic bariatric surgery.

Research of mechanisms of liraglutide inducing expression of fibroblast growth factor 21 in white adipose tissues of obese type 2 diabetic rats / 中国药理学通报

Aim To investigate the effect of liraglutide on expression of fibroblast growth factor 21 in white ad-ipose tissues and its mechanisms. Methods Male SD rats were subjected to a standard control diet or high-fat diet ( HFD) for 12 weeks, then the HFD group was in-jected introperitoneally with 30 mg · kg-1 streptozoto-cin to induce type 2 diabetes mellitus model. Half number of rats of type 2 diabetes mellitus were injected with liraglutide ( DM +LRG, 0. 4 mg · kg-1 · d-1 , two times one day ) for another 6 weeks. Serum bio-chemical indices and FGF21 levels were detected. The pathological changes in epididymal adipose tissues were detected by HE staining. The mRNA and protein ex-pression and phosphorylation of FGF21 , peroxisome proliferator-activated receptor γ ( PPARγ) , fibroblast growth factor receptor 3 (FGFR3),β-Klotho, liver ki-nase B1(LKB1), AMP-activated kinase (AMPK), a-cetyl-CoA carboxylase ( ACC ) and phosphorylation of signaling molecules in MAPK pathway were assessed by RT-PCR, immunohistochemistry and Western blot re-spectively. Results Body mass and serum lipid, ALT and AST levels increased in DM group, while FGF21 level decreased, and the volume of adipose cells in ep-ididymal adipose tissues was expanded. Expressions of FGF21, PPARγ, p-FGFR3, β-Klotho, p-LKB1, p-AMPK, p-ACC were down-regulated, while p-ERK, p-JNK and p-p38 expression were all increased. These indices were reverted by liraglutide treatment. Conclu-sion Liraglutide has significant lipid-lowering effect, which maybe related with increased FGF21 expression, activating AMPK pathway and inhibiting MAPK path-way.

The effect of combination of gliclazide and sitagliptin on the treatment of poorly obese obese patients with type 2 diabetes mellitus / 中国生化药物杂志

Objective To investigate the effect of psychological intervention combined with gliclazide and sitagliptin on the treatment of poorly obese obese patients with type 2 diabetes mellitus. Methods 96 obese patients with type 2 diabetes mellitus who had poor control of blood glucose after insulin treatment were randomly divided into control group and experimental group,48 cases in each groups. Gliclazide and sitagliptin (FBG), glycosylated hemoglobin (HbA1c), 2h postprandial blood glucose (2hPG), fasting insulin (FIns) were measured before and after 15 weeks of treatment in the control group. situation. Results FBG, HbA1c, 2hPG and FIns were significantly lower in the experimental group than in the control group (P<0.05). Conclusion The combination of gliclazide and sitagliptin on the treatment of poorly obese type 2 diabetes mellitus with insulin treatment can significantly reduce the blood glucose level of patients and promote it.

Effect of gliclazide and sitagliptin on insulin control in poorly controlled obese patients with type 2 diabetes mellitus / 中国生化药物杂志

Objective To explore the effect of gliclazide and Sig Leo Dean on insulin treatment for poor glycemic control in obese patients with type 2 diabetes mellitus. Methods 80 cases of insulin treatment for poor glycemic control in obese patients with type 2 diabetes mellitus treated in our hospital from March 2015 to January 2017 were randomly divided into two groups,with 40 cases in each group.The control group was treated with gliclazide The observation group was treated with Sig Leo Dean.The therapeutic effects of the two groups were observed and compared. Results 2 hours postprandial blood glucose levels improved in the observation group was better than that of the control group, the body weight, blood pressure, fasting blood glucose of two groups were improved, and there were no significant difference between the two groups; The incidence rate of adverse reactions was 2.5% in the observation group, 10% in the control group, the difference was not statistically significant (P<0.05). Conclusion Analysis of gliclazide and Sig Leo Dean on insulin treatment for poor glycemic control in obese patients with type 2 diabetes mellitus curative effect, Sig Leo Dean for the glycaemic improvement effect is higher, reduce the incidence of adverse reactions, so more medication safety, it is worthy of clinical promotion Application.

Effect of modified gastric bypass on glycometabolism of non-obese type 2 diabetes mellitus in GK rats / 重庆医学

Objective To verify the feasibility and effectiveness of modified gastric bypass surgery in the treatment of non-obese type 2 diabetic mellitus(T2DM ) GK rats .Methods Forty male GK rats were randomly divided into four groups (n=10) ,the group A served as the modified gastric bypass ,group B as the Roux-en-Y gastric bypass ,group C as the sham operation and group D as the blank control group .Fasting blood glucose(FBG) ,glycosylated hemoglobin(HbA1c) and fasting serum insulin(FINS) in each group were detected at preoperative 1 week ,postoperative 1 ,2 ,4 ,8 ,12 weeks .Results The rat body mass at postoperative 1 week in the group A and B was significantly decreased compared with the group D ,and began to recover at postoperative 4 weeks , the rat body mass at the same time point had no statistical difference between the group A and B (P>0 .05) .FPG ,FINS and HbA1c at preoperative 1 week had no statistical difference among various groups (P>0 .05) .FPG and FINS at postoperative 1 week had no statistical difference among various groups (P>0 .05) .FPG and FINS at postoperative 2 ,4 ,8 ,12 weeks had no statistical difference between the group A and B(P>0 .05) ,which had no statistical difference between the group A with the group C and D (P>0 .05) . HbA1c at postoperative 4 weeks had no statistical difference among various groups (P>0 .05);which at postoperative 12 weeks had no statistical difference between the group A and B (P>0 .05) ,while which had no statistical difference between the group A with the group C and D(P>0 .05) .Conclusion The modified gastric bypass surgery has the improvement effect on glycometabolism of rat non-obese T2DM ,which is similar to that of Roux-en-Y gastric bypass surgery .

Transcriptomic alterations in the heart of non-obese type 2 diabetic Goto-Kakizaki rats.

BACKGROUND: There is a spectacular rise in the global prevalence of type 2 diabetes mellitus (T2DM) due to the worldwide obesity epidemic. However, a significant proportion of T2DM patients are non-obese and they also have an increased risk of cardiovascular diseases. As the Goto-Kakizaki (GK) rat is a well-known model of non-obese T2DM, the goal of this study was to investigate the effect of non-obese T2DM on cardiac alterations of the transcriptome in GK rats. METHODS: Fasting blood glucose, serum insulin and cholesterol levels were measured at 7, 11, and 15 weeks of age in male GK and control rats. Oral glucose tolerance test and pancreatic insulin level measurements were performed at 11 weeks of age. At week 15, total RNA was isolated from the myocardium and assayed by rat oligonucleotide microarray for 41,012 genes, and then expression of selected genes was confirmed by qRT-PCR. Gene ontology and protein-protein network analyses were performed to demonstrate potentially characteristic gene alterations and key genes in non-obese T2DM. RESULTS: Fasting blood glucose, serum insulin and cholesterol levels were significantly increased, glucose tolerance and insulin sensitivity were significantly impaired in GK rats as compared to controls. In hearts of GK rats, 204 genes showed significant up-regulation and 303 genes showed down-regulation as compared to controls according to microarray analysis. Genes with significantly altered expression in the heart due to non-obese T2DM includes functional clusters of metabolism (e.g. Cyp2e1, Akr1b10), signal transduction (e.g. Dpp4, Stat3), receptors and ion channels (e.g. Sln, Chrng), membrane and structural proteins (e.g. Tnni1, Mylk2, Col8a1, Adam33), cell growth and differentiation (e.g. Gpc3, Jund), immune response (e.g. C3, C4a), and others (e.g. Lrp8, Msln, Klkc1, Epn3). Gene ontology analysis revealed several significantly enriched functional inter-relationships between genes influenced by non-obese T2DM. Protein-protein interaction analysis demonstrated that Stat is a potential key gene influenced by non-obese T2DM. CONCLUSIONS: Non-obese T2DM alters cardiac gene expression profile. The altered genes may be involved in the development of cardiac pathologies and could be potential therapeutic targets in non-obese T2DM.