A novel refined classification system for type 2 diabetes in adults: A Chinese retrospective cohort study.

AIMS: We propose a simple type 2 diabetes mellitus (T2DM) classification method based on fasting C-peptide (FCP) levels and examined its feasibility and validity. METHODS: Adult T2DM patients first diagnosed in our tertiary care centre from January 2009 to January 2020 were included. Patients were followed until January 2021; their clinical characteristics, chronic complications, treatment regimen, and glycaemic control were compared. RESULTS: In total, 5644 T2DM patients were included. Three subgroups were established based on FCP levels: subtype T1 (FCP ≤ 1.0 µg/L), 1423 patients (25.21%); subtype T2 (FCP 1.0-2.5 µg/L), 2914 patients (51.63%); and subtype T3 (FCP ≥ 2.5 µg/L), 1307 patients (23.16%). T1 was characterised by older age, lower body mass indices, higher initial glycosylated haemoglobin (HbA1c) levels, and the lowest homoeostatic model assessment 2 estimates of ß-cell function (HOMA2-ß) and HOMA2-insulin resistance at baseline. The T3 group's clinical characteristics were opposite to those of T1. T3 patients showed higher incidence rates and risks of diabetic kidney disease, diabetic peripheral vascular disease, and non-alcoholic fatty liver, while the risks of diabetic retinopathy and diabetic peripheral neuropathy were highest in T1. Insulin, glycosidase inhibitors, and thiazolidinedione were the most frequently used drugs, but the use of metformin, dipeptidyl peptidase-4 inhibitor, and insulin secretagogue drugs was slightly lower in T1. T1 maintained higher HbA1c levels throughout follow-up. Overall HbA1c fluctuations were more significant in T3 than in T1 and T2. CONCLUSIONS: The new adult T2DM classification is simple and clear and will help classify different T2DM clinical characteristics and guide treatment plans.

Effect of Hedan Tablets on Body Weight and Insulin Resistance in Patients with Metabolic Syndrome.

INTRODUCTION: Apart from their recognized lipid-lowering effect, Hedan tablets, a mixture of Chinese herbal medicines, have demonstrated a certain weight-loss effect in clinical practice. The aim of this randomized, double-blind, placebo-controlled study was to verify the effect of Hedan tablets on body weight (BW) and insulin resistance (IR) in patients with metabolic syndrome (MetS). METHODS: A total of 62 eligible patients with MetS were divided into two groups: the treatment group (Hedan tablets at 4.38 g/day tid) and the control group (placebo treatment). Both groups attended follow-ups at 8, 16, and 24 weeks during the process. The parameters of the assessment include lipid level, BW, triglyceride (TG) to high-density lipoprotein cholesterol (HDLc) ratio (TG/HDLc), homeostasis model assessment for IR (HOMA-IR) index, and adiponectin. RESULTS: Patients in the treatment group showed a significant decrease in BW compared to those in the control group (-4.47 vs. 0.06 kg) after 8 weeks of treatment. A significant decrease in body mass index (BMI) was also observed in the treatment group after 16 weeks of treatment (-1.79 vs. -0.03 kg/m2). In the treatment group, 20 out of 31 (64.5%) patients lost 5-10% BW and 4 out of 31 (12.9%) patients lost over 10% BW after 24 weeks of treatment. Although there were no significant changes in the patients' HOMA-IR, the treatment group showed a significant reduction in TG/HDLc (-0.98 vs. -0.19) after 8 weeks of treatment and a significant increase in adiponectin (6.87 vs. -0.43) after 16 weeks of treatment. DISCUSSION/CONCLUSION: The Hedan tablets significantly improve BW, BMI, TG/HDLc, and adiponectin in patients with MetS. Thus, Hedan tablets may be used as an adjunct to existing MetS management methods.

Applying the China-PAR Risk Algorithm to Assess 10-year Atherosclerotic Cardiovascular Disease Risk in Populations Receiving Routine Physical Examinations in Eastern China.

OBJECTIVE: To assess the 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk score among adults in eastern China using the China-PAR equation which formulated primarily for the Chinese population. METHODS: Data from 72,129 individuals from 35-74 years old who received routine physical examinations in eastern China were analyzed in this study. The 10-year risk scores were calculated using the China-PAR equation. The chi-square test and logistic regression were then performed to evaluate the association between the selected risk factors and overall CVD risk. RESULTS: The mean 10-year ASCVD risk scores were 3.82% ± 3.76% in men and 1.30% ± 1.65% in women based on the China-PAR equation. Overall, 20% of men and 3.5% of women were intermediate-risk, and 7.3% of men and 0.3% of women were high-risk. Waist to hip ratio (WHR) [OR = 1.16 (CI 95% = 1.06-1.26)], waist to height ratio (WHtR) [OR = 1.16 (CI 95% = 1.05-1.28)], non-high-density lipoprotein cholesterol (non-HDL-C) [OR = 1.23 (CI 95% = 1.09-1.39)], and total cholesterol (TC)/HDL-C [OR = 1.68 (CI 95% = 1.46-1.94)] were more strongly associated with CVD risk than body-mass index (BMI), waist circumference (WC), and TC alone. CONCLUSION: Male-specific prevention and treatment strategies for ASCVD are needed in eastern China. In addition, WHR, WHtR, non-HDL-C, and TC/HDL-C which not included in the the China-PAR equation were also independently associated with 10-year ASCVD risk score categories.

Roux-en-Y gastric bypass decreases endotoxemia and inflammatory stress in association with improvements in gut permeability in obese diabetic rats.

BACKGROUND: Postoperative modulation of the gut microbiome has been suggested to contribute to the metabolic benefits after metabolic surgery, but the mechanisms underlying these metabolic benefits remain unknown. Previously, we reported that Roux-en-Y gastric bypass (RYGB) surgery in Zucker diabetic fatty (ZDF) rats increased the abundance of Proteobacteria and Gammaproteobacteria. However, theoretically, these Gram-negative bacteria may elevate lipopolysaccharide (LPS) levels. Therefore, in this study we further investigated the potential mechanisms by which RYGB improves glucose homeostasis, endotoxemia, and inflammatory stress in ZDF rats. METHODS: Rats were divided into three groups: (a) an RYGB group (RY); (b) a sham-operated group pair-fed with the RY group; and (c) a sham-operated group fed ad libitum. Changes in LPS, cytokine levels, intestinal permeability (evaluated using the fluorescein isothiocyanate-dextran method), and intestinal epithelial tight junction proteins zona occludins (ZO)-1, occludin, and claudin-1 were assessed 10 weeks postoperatively. RESULTS: Rats that underwent RYGB exhibited sustained weight loss and reduced glucose, as well as lower cytokine and LPS concentrations, than rats in the control groups. In the colonic epithelium, ZO1 and claudin-1 (Cldn1) mRNA levels were higher in the RY than control groups. Intestinal permeability declined in the RY group and was positively correlated with LPS levels and negatively correlated with ZO-1, occludin, and claudin-1 expression. CONCLUSIONS: The results demonstrate that RYGB can reduce the extent of endotoxemia and inflammation, which is associated with improved tight junction integrity and intestinal barrier strength. These effects may explain why a low level of inflammation is maintained after RYGB and the postoperative increase in Gram-negative bacteria.

The effect of metabolic surgery on nonobese patients (BMI<30 kg/m2) with type 2 diabetes: a systematic review.

BACKGROUND: The influence of metabolic surgery on the glucose and lipid profiles of nonobese body mass index<30 kg/m2 patients with type 2 diabetes, particularly the effect ≥1 year, remains unknown. METHODS: PubMed and Ovid Embase were used. SETTING: University hospitals. RESULTS: In total, 21 studies including 921 patients were examined in this systematic review, the results of which revealed decrease in body mass index, waist circumference, fasting plasma glucose, glycosylated hemoglobin A1C, fasting C-peptide, fasting insulin, homeostasis model of assessment for insulin resistance index, triglycerides, total cholesterol, and low-density lipoprotein cholesterol. An increase in high-density lipoprotein cholesterol was also observed. The diabetes remission rates ranged from 13.3% to 90.2% according to 20 studies. The incidence of gastrointestinal bleeding ranged from 1% to 10% according to 9 studies. Four studies reported anemia after Roux-en-Y gastric bypass or one-anastomosis gastric bypass, with the incidence ranging from 8% to 33%. CONCLUSIONS: Nonobese patients can achieve improvements in weight-related indices and glucose and lipid profiles in the short and medium term after metabolic surgery; however, the complications of metabolic surgery warrant further attention.

Modulation of the gut microbiome: a systematic review of the effect of bariatric surgery.

OBJECTIVE: Bariatric surgery is recommended for patients with obesity and type 2 diabetes. Recent evidence suggested a strong connection between gut microbiota and bariatric surgery. DESIGN: Systematic review. METHODS: The PubMed and OVID EMBASE were used, and articles concerning bariatric surgery and gut microbiota were screened. The main outcome measures were alterations of gut microbiota after bariatric surgery and correlations between gut microbiota and host metabolism. We applied the system of evidence level to evaluate the alteration of microbiota. Modulation of short-chain fatty acid and gut genetic content was also investigated. RESULTS: Totally 12 animal experiments and 9 clinical studies were included. Based on strong evidence, 4 phyla (Bacteroidetes, Fusobacteria, Verrucomicrobia and Proteobacteria) increased after surgery; within the phylum Firmicutes, Lactobacillales and Enterococcus increased; and within the phylum Proteobacteria, Gammaproteobacteria, Enterobacteriales Enterobacteriaceae and several genera and species increased. Decreased microbial groups were Firmicutes, Clostridiales, Clostridiaceae, Blautia and Dorea. However, the change in microbial diversity is still under debate. Faecalibacterium prausnitzii, Lactobacillus and Coprococcus comes are implicated in many of the outcomes, including body composition and glucose homeostasis. CONCLUSIONS: There is strong evidence to support a considerable alteration of the gut microbiome after bariatric surgery. Deeper investigations are required to confirm the mechanisms that link the gut microbiome and metabolic alterations in human metabolism.

Effects of bariatric surgery on glycemic and lipid metabolism, surgical complication and quality of life in adolescents with obesity: a systematic review and meta-analysis.

BACKGROUND: Obesity in adolescents is associated with numerous health risks and co-morbidities, including type 2 diabetes and dyslipidemia. Bariatric surgery on adolescents induces weight loss, but little is known about metabolic effects of these operations. OBJECTIVE: To explore weight loss and metabolic effects of bariatric surgery on young people. SETTING: A systematic review and meta-analysis. University Hospital, China. METHODS: PubMed and EMBASE were searched for relevant studies up to July 2017. The related studies in adolescents after operation were included. RESULTS: A total of 49 studies with 3007 patients were included. The average preoperative age ranged from 13.9 to 19.9 years. Roux-en-Y gastric bypass (n = 1216), laparoscopic adjustable gastric banding (n = 1028), and laparoscopic sleeve gastrectomy (n = 665) were the most common bariatric surgeries performed. At the longest follow-up (range, 12-120 mo), bariatric surgery led to an overall 16.43 kg/m2 (95% confidence interval [CI]: 14.84-18.01) and 31% (95% CI: 28%-34%) reduction in body mass index. There were significant improvements in glycemic and lipid profiles including glycosylated hemoglobin A1C, fasting blood insulin, fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, postoperatively at 12 months. The remission rate of dyslipidemia was 55% (95% CI: 34%-76%), 70% (95% CI: 55%-82%), and 95% (95% CI: 80%-100%) at 1, 3, and>5 years after surgery. Roux-en-Y gastric bypass produced better improvements than other surgical procedures. CONCLUSION: Bariatric surgery in adolescents may achieve significant weight loss, and glycemic and lipid control. Further well-designed studies with longer follow-up are warranted to provide more reliable evidence.

Berberine protects against diet-induced obesity through regulating metabolic endotoxemia and gut hormone levels.

Systemic inflammation, which can be induced by metabolic endotoxemia, and corresponding high­fat diet­mediated metabolic disorders are associated with gut microbiota. In the present study reverse transcription-polymerase chain reaction, immunofluorescence, pyrosequencing, ELISA and Oil Red O staining were performed to assess whether berberine can protect against diet-induced obesity, through modulating the gut microbiota and consequently improving metabolic endotoxemia and gastrointestinal hormone levels. Alterations in the gut microbiota induced by berberine resulted in a significant reduction in bacterial lipopolysaccharide levels in portal plasma. Levels of inflammatory and oxidative stress markers, as well as the mRNA expression levels of macrophage infiltration markers in visceral adipose tissue, were also reduced by berberine. Inhibition of the inflammatory response was associated with a reduction in intestinal permeability and an increase in the expression of tight junction proteins. In addition, berberine was reported to restore aberrant levels of gut hormones in the portal plasma, such as glucagon­like peptide­1 and ­2, peptide YY, glucose­dependent insulinotropic polypeptide and pancreatic polypeptide. The present findings indicated that berberine, through modulating gut microbiota, restored the gut barrier, reduced metabolic endotoxemia and systemic inflammation, and improved gut peptide levels in high­fat diet­fed rats. The present study suggests that berberine may be an effective therapeutic strategy for the treatment of obesity and insulin resistance.

Gut microbiota after Roux-en-Y gastric bypass and sleeve gastrectomy in a diabetic rat model: Increased diversity and associations of discriminant genera with metabolic changes.

Recent work with gut microbiota after bariatric surgery is limited, and the results have not been in agreement. Given the role of the gut microbiota in regulating host metabolism, we explored the effect of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on the modifications of gut microbiota with regard to the potential influence of food intake and/or weight loss and examined their links with host metabolism. Zucker diabetic fatty rats were divided into the following groups: RYGB; sham-operated with pair-fed as RYGB; sham-operated fed ad libitum; and SG. The metabolic effects and gut microbiota profile were analyzed 10 weeks postoperatively. Associations between discriminating genera and metabolic markers after RYGB were explored. The 2 procedures induced similar glucose improvement and increased flora diversity after 10 weeks compared with sham-operated groups. RYGB induced a marked higher relative abundance of Proteobacteria/Gammaproteobacteria and Betaproteobacteria and increased emergence of Fusobacteria and Clostridium, whereas SG resulted in more abundant Actinobacteria compared with other groups. Most of the 12 discriminant genera correlated with changes in metabolic phenotype, but only 28.6% of these correlations were independent of weight, and 4 discriminant genera still negatively correlated with serum insulin level independent of food intake and weight loss after RYGB. These data demonstrate that RYGB and SG surgery produced similar diversity but different microbiota compositions changes in Zucker diabetic fatty rats. These findings stimulate deeper explorations of functions of the discriminate microbiota and the mechanisms linking postsurgical modulation of gut microbiota and improvements in insulin resistance.

Depletion of NAD pool contributes to impairment of endothelial progenitor cell mobilization in diabetes.

OBJECTIVE: The impaired mobilization of endothelial progenitor cells (EPCs) from bone marrow (BM) critically contributes to the diabetes-associated vascular complications. Here, we investigated the relationship between the nicotinamide phosphoribosyltransferase (NAMPT)-controlled nicotinamide adenine dinucleotide (NAD) metabolism and the impaired mobilization of BM-derived EPCs in diabetic condition. METHODS: The NAMPT-NAD pool in BM and BM-derived EPCs in wild-type (WT) and diabetic db/db mice was determined. Nicotinamide, a natural substrate for NAD biosynthesis, was administrated for 2weeks in db/db mice to examine the influence of enhancing NAD pool on BM and blood EPCs number. The modulations of stromal cell-derived factor-1α (SDF-1α) and endothelial nitric oxide synthase (eNOS) protein in BM were measured using immunoblotting. The EPCs intracellular NAMPT level and NAD concentration, as well as the blood EPCs number, were compared between 9 healthy people and 16 patients with type 2 diabetes mellitus (T2DM). The T2DM patients were treated with nicotinamide for two weeks and then the blood EPCs number was determined. Moreover, the association between blood EPCs numbers and EPCs intracellular NAD(+)/NAMPT protein levels in 21 healthy individuals was determined. RESULTS: We found that NAD concentration and NAMPT expression in BM and BM-derived EPCs of db/db mice were significantly lower than those in WT mice BM. Enhancing NAD pool not only increased the EPCs intracellular NAD concentration and blood EPCs number, but also improved post-ischemic wound healing and blood reperfusion in db/db mice with hind-limb ischemia model. Enhancing NAD pool rescued the impaired modulations of stromal cell-derived factor-1α (SDF-1α) and endothelial nitric oxide synthase (eNOS) protein levels in db/db mice BM upon hind-limb ischemia. In addition, enhancing NAD pool significantly inhibited PARP and caspase-3 activates in db/db mice BM. The intracellular NAMPT-NAD pool was positively associated with blood EPCs number in healthy individuals. At last, we found that the EPC intracellular NAMPT and NAD(+) levels were reduced in T2DM patients and enhancing NAD pool elevated the circulating blood EPCs number in T2DM patients. CONCLUSION: Our results indicate that the depletion of NAD pool may contribute to the impairment of EPCs mobilization in diabetic condition, and imply the potential therapeutic value of nicotinamide in the prevention and treatment for cardiovascular complications of diabetes.

Regulation of plasma lipid homeostasis by hepatic lipoprotein lipase in adult mice.

LPL is a pivotal rate-limiting enzyme to catalyze the hydrolysis of TG in circulation, and plays a critical role in regulating lipid metabolism. However, little attention has been paid to LPL in the adult liver due to its relatively low expression. Here we show that endogenous hepatic LPL plays an important physiological role in plasma lipid homeostasis in adult mice. We generated a mouse model with the Lpl gene specifically ablated in hepatocytes with the Cre/LoxP approach, and found that specific deletion of hepatic Lpl resulted in a significant decrease in plasma LPL contents and activity. As a result, the postprandial TG clearance was markedly impaired, and plasma TG and cholesterol levels were significantly elevated. However, deficiency of hepatic Lpl did not change the liver TG and cholesterol contents or glucose homeostasis. Taken together, our study reveals that hepatic LPL is involved in the regulation of plasma LPL activity and lipid homeostasis.

Expression of Phosphorylated AMP-Activated Protein Kinase Predicts Response to Transarterial Chemoembolization in Postoperative Cases of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in the world. Transcatheter arterial chemoembolization (TACE) was commonly used for HCC patients postoperatively. However, the survival benefits of adjuvant TACE were controversial due to the extensive heterogeneity of HCC. Hence, there is a critical need to explore potential biomarkers that can predict the clinical response to TACE. The AMP-activated protein kinase (AMPK) is a highly conserved heterotrimeric serine/threonine kinase that plays a central role in linking metabolism and cancer development. In this study, we aimed at evaluating the association of pAMPKα (Thr172) status with clinical outcomes in HCC patients treated with or without postoperative adjuvant TACE.pAMPKα (Thr172) expression was assessed using immunohistochemical analysis in a cohort of 378 Chinese HCC patients who had undergone tumor resection. Kaplan-Meier analysis and multivariate Cox proportional hazards models were used to study the impact on clinical outcomes.High pAMPKα (Thr172) expression was associated with improved disease-free and overall survival and was an independent prognostic factor for overall survival by multivariate analysis. Furthermore, low pAMPKα (Thr172) expression level was correlated with high percentage of OV6 tumor-initiating cells (T-ICs) in HCC specimens.To our knowledge, it can be demonstrated for the first time that pAMPKα (Thr172) status is associated with response to postoperative adjuvant TACE. High pAMPKα (Thr172) level in HCC may serve as a positive predictor of survival in HCC patients undergoing TACE.

Long-Term outcomes and experience of laparoscopic adjustable gastric banding: one center's results in China.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB), as one major bariatric surgery for treatment of obesity, results in ineffective long-term weight loss and a high reoperation rate. The objective of this study was to evaluate the long-term effects of LAGB on the weight loss outcomes and reoperation rates of obese patients with different body mass index (BMI) levels in China. METHODS: A retrospective study was performed to review the follow-up data of obese patients who underwent LAGB at Shanghai Changhai Hospital between November 2003 and May 2013. The main outcomes included weight loss, percentage excess weight loss (%EWL), reoperation rate, and reasons for reoperation. RESULTS: A total of 254 LAGB procedures were performed in our hospital. By the end of May 2013, 145 Chinese patients (57.8%) were followed up, 99 patients with BMI ≥ 35 kg/m(2) (high BMI group) and 46 patients with BMI < 35 kg/m(2) (low BMI group). In the high BMI group, the mean %EWL was > 25% within 5 years postoperatively, but it decreased to less than 25% after 5 years. However, in the low BMI group, the mean %EWL at each time point was over 50%. The reoperation rate was 33.1%; it was 17.4% in the low BMI group and 34.3% in the high BMI group. CONCLUSION: LAGB is more effective with a lower reoperation rate for obese patients with a BMI < 35 kg/m(2) compared to BMI ≥ 35 kg/m(2) in our population.

Glycemic control among patients in China with type 2 diabetes mellitus receiving oral drugs or injectables.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) is increasing rapidly among Chinese adults, and limited data are available on T2DM management and the status of glycemic control in China. We assessed the efficacy of oral antidiabetes drugs (OADs), glucagon-like peptide-1 (GLP-1) receptor agonists, and insulin for treatment of T2DM across multiple regions in China. METHODS: This was a multicenter, cross-sectional survey of outpatients conducted in 606 hospitals across China. Data from all the patients were collected between April and June, 2011. RESULTS: A total of 238,639 patients were included in the survey. Eligible patients were treated with either OADs alone (n=157,212 [65.88%]), OADs plus insulin (n=80,973 [33.93%]), or OADs plus GLP-1 receptor agonists (n=454 [0.19%]). The OAD monotherapy, OAD + insulin, and OAD + GLP-1 receptor agonist groups had mean glycosylated hemoglobin (HbA1c) levels (±SD) of 7.67% (±1.58%), 8.21% (±1.91%), and 7.80% (±1.76%), respectively. Among those three groups, 34.63%, 26.21%, and 36.12% met the goal of HbA1c <7.0%, respectively. Mean HbA1c and achievement of A1c <7.0% was related to the duration of T2DM. CONCLUSIONS: Less than one third of the patients had achieved the goal of HbA1c <7.0%. Glycemic control decreased and insulin use increased with the duration of diabetes.

Protein tyrosine phosphatase 1B inhibits adipocyte differentiation and mediates TNFα action in obesity.

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of systemic glucose and insulin homeostasis; however, its exact role in adipocytes is poorly understood. This study was to elucidate the role of PTP1B in adipocyte differentiation and its implication in obesity. During differentiation of 3T3-L1 white preadipocytes, PTP1B decreased progressively with adipocyte maturation. Lentivirus-mediated PTP1B overexpression in preadipocytes delayed adipocyte differentiation, shown as lack of mature adipocytes, low level of lipid accumulation, and down-regulation of main markers (PPARγ2, SREBP-1c, FAS and LPL). In contrast, lentivirus-mediated PTP1B knockdown accelerated adipocyte differentiation, demonstrated as full of mature adipocytes, high level of lipid accumulation, and up-regulation of main markers. Dominant-negative inhibition on endogenous PTP1B by lentivirus-mediated overexpression of PTP1B double mutant in Tyr-46 and Asp-181 residues (LV-D/A-Y/F) also stimulated adipogenesis, more efficient than PTP1B knockdown. Diet-induced obesity mice exhibited an up-regulation of PTP1B and TNFα accompanied by a down-regulation of PPARγ2 in white adipose tissue. TNFα recombinant protein impeded PTP1B reduction and inhibited adipocyte differentiation in vitro; this inhibitory effect was prevented by LV-D/A-Y/F. Moreover, PTP1B inhibitor treatment improved adipogenesis and suppressed TNFα in adipose tissue of obese mice. All together, PTP1B negatively regulates adipocyte development and may mediate TNFα action to impair adipocyte differentiation in obesity. Our study provides novel evidence for the importance of PTP1B in obesity and for the potential application of PTP1B inhibitors.

[The safety and effectiveness of once daily detemir in patients with type 2 diabetes previously failing oral agents: the Chinese cohort from SOLVE(TM) observational study].

OBJECTIVE: Study of Once-daily LeVEmir(®) (SOLVE(TM)) was a 24-week international observational study to evaluate the safety and effectiveness of initiating once-daily insulin detemir (Levemir) as add-on therapy in patients with type 2 diabetes mellitus (T2DM) who failed treatment of oral anti-diabetic drugs (OAD). METHODS: The present study was derived from the data of Chinese cohort. A total of 3272 patients with T2DM failing OAD were enrolled in the study. Determir were prescribed to the patients by the decision of the physician. Clinical data were collected at baseline, week 12 and week 24 to evaluate the safety and effectiveness of detemir. RESULTS: The age of the patients was (56.2 ± 10.8) years with a diabetes duration of (7.1 ± 5.2) years. Their BMI was (25.3 ± 3.3) kg/m(2). No patient experienced any major or nocturnal hypoglycaemic event during the study. After 24 weeks of treatment, the glycosylated hemoglobin A1c (HbA1c) decreased from (8.33 ± 1.69)% to (7.16 ± 1.18)% with a mean change of -1.17%, the fasting plasma glucose decreased from (9.52 ± 2.59) mmol/L to (6.84 ± 1.42) mmol/L with a mean change of -2.7 mmol/L, and the 7-point blood glucose profile improved overall. Totally 49.1% of patients achieved HbA1c < 7%. The mean body weight decreased by 0.15 kg. CONCLUSIONS: Insulin detemir administered once daily as add-on therapy in patients with T2DM failing OAD regimen significantly reduces the risk of major hypoglycemia, improves glycemic control, increases the percentage of patients achieving treatment target with neutral effect on body weight.

Rosiglitazone protects against palmitate-induced pancreatic beta-cell death by activation of autophagy via 5'-AMP-activated protein kinase modulation.

Promoting beta-cell survival is crucial for the prevention of beta-cell failure in diabetes. Thiazolidinediones, a widely used drug to improve insulin sensitivity in clinical practice, is found to have a protective effect on islet beta-cell. To date, the mechanism underlying the protective role of thiazolidinedione on beta-cell survival remain largely unknown. Activation of autophagy was detected by transmission electron microscopy, western blot, and GFP-LC3 transfection. Cell viability was examined by WST-8. Cell apoptosis was demonstrated by DAPI and Annexin V/PI staining. Colony formation assay was used to detect long-term cell viability. We demonstrated that rosiglitazone-treated beta-cells were more resistant to palmitate-induced apoptosis. The conversion of LC3-I to LC3-II and accumulated autophagosomes were found to be upregulated in rosiglitazone-treated cells. Inhibition of autophagy augmented palmitate-induced apoptosis with rosiglitazone treatment, suggesting that autophagy plays an important role in the survival function of rosiglitazone on beta-cells. Furthermore, we showed that rosiglitazone could induce AMP-activated protein kinase (AMPK) phosphorylation and reduce p70S6 kinase phosphorylation. Inhibition of AMPK impaired autophagy activation and enhanced palmitate-induced apoptosis during rosiglitazone treatment. These findings reveal that rosiglitazone-induced autophagy contributes to its protective function on beta-cells during palmitate treatment.

Therapeutic effects of hydrogen saturated saline on rat diabetic model and insulin resistant model via reduction of oxidative stress.

BACKGROUND: Molecular hydrogen, as a novel antioxidant, has been proven effective in treating many diseases. This study aimed to evaluate the therapeutic effects of hydrogen saturated saline in treatment of a rat model of diabetes mellitus and a rat model of insulin resistant. METHODS: A rat diabetes mellitus model was established by feeding a high fat/high carbohydrate diet followed by injection of a small dose of streptozotocin, and an insulin resistant model was induced with a high glucose and high fat diet. Hydrogen saturated saline was administered to rats with both models conditions on a daily basis for eight weeks. A pioglitazone-treated group and normal saline-treated group served as positive and negative controls. The general condition, body weight, blood glucose, blood lipids, and serum insulin levels of rats were examined at the 8th week after treatment. The oxidative stress indices, including serum superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) were also evaluated after eight weeks of treatment using the commercial kits. RESULTS: Hydrogen saturated saline showed great efficiency in improving the insulin sensitivity and lowering blood glucose and lipids. Meanwhile, the therapeutic effects of hydrogen saturated saline were superior to those of pioglitazone. Hydrogen saturated saline markedly attenuated the MDA level and elevated the levels of antioxidants SOD and GSH. CONCLUSION: Hydrogen saturated saline may improve the insulin resistance and alleviate the symptoms of diabetes mellitus by reducing the oxidative stress and enhancing the anti-oxidant system.