Comparative efficacy and safety of Gla-300 versus IDegAsp in insulin-naïve people with type 2 diabetes mellitus uncontrolled on oral anti-diabetics.

AIM: To compare the efficacy and safety of insulin glargine-300 once daily (Gla-300) with insulin degludec/aspart (IDegAsp) once daily in patients with type 2 diabetes (T2D) inadequately controlled on oral anti-diabetic drugs (OADs). MATERIALS AND METHODS: A systematic literature review of randomized controlled trials was followed by an indirect treatment comparison of studies involving insulin naïve adults, inadequately controlled [glycated haemoglobin (HbA1c) ≥7.0%] on OADs, who received Gla-300 or IDegAsp once daily. Outcomes of interest were change in HbA1c, blood glucose, weight and insulin dose, as well as incidence and event rate of hypoglycaemia and other adverse events. RESULTS: Four trials with broadly similar baseline patient characteristics were included in the meta-analyses and indirect treatment comparison. At 24-28 weeks, the indirect comparison of Gla-300 to IDegAsp once daily estimated no statistically significant difference for change in HbA1c (%) from baseline [mean difference of 0.10% (95% CI: -0.20, 0.39; p = .52)]; a statistically significant mean difference of -1.31 kg (95% CI: -1.97, -0.65; p < .05) for change in body weight from baseline; statistically significant odds ratios of 0.62 (95% CI: 0.41, 0.93; p < .05) for incidence of any hypoglycaemia; and 0.47 (95% CI: 0.25, 0.87; p < .05) for incidence of anytime confirmed hypoglycaemia (plasma glucose <3.0-3.1 mmol/L). No significant differences were observed for insulin dose and adverse events. CONCLUSION: In insulin-naïve patients with T2D inadequately controlled on OADs, commencing Gla-300 shows a comparable HbA1c reduction, but with significantly less weight gain and a lower incidence of any and confirmed hypoglycaemia compared with commencing IDegAsp.

Henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.

AIM: To evaluate the efficacy and safety of henagliflozin in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin. MATERIAL AND METHODS: This multicentre phase 3 trial included a 24-week randomized, double-blind, placebo-controlled period, followed by a 28-week extension period. Patients with a glycated haemoglobin (HbA1c) level of 7.0% (53 mmol/mol) to 10.5% (91 mmol/mol) were randomized and treated with once-daily placebo (n = 161), henagliflozin 5 mg (n = 162), or henagliflozin 10 mg (n = 160). After 24 weeks, patients on placebo were switched to 5 mg or 10 mg henagliflozin for the additional 28-week treatment, and patients on henagliflozin during 24-week treatment period maintained this initial therapy. The primary endpoint was change in HbA1c from baseline to Week 24. RESULTS: At Week 24, the least squares mean HbA1c changes versus placebo from baseline were - 0.76% (-8.3 mmol/mol) and - 0.80% (-8.7 mmol/mol) for henagliflozin 5 and 10 mg, respectively (all P < 0.0001). Compared with the placebo group, both doses of henagliflozin lowered fasting plasma glucose, 2-hour postprandial plasma glucose, body weight and blood pressure, and increased the proportions of patients achieving HbA1c <7.0% (53 mmol/mol) at Week 24. The trends in these improvements were sustained over an additional 28 weeks. Slightly higher proportions of ketosis and presence of urine ketone bodies were observed in patients treated with henagliflozin compared to placebo at Week 24. No diabetic ketoacidosis or episodes of severe hypoglycaemia were reported. CONCLUSIONS: Henagliflozin 5 mg or 10 mg as add-on therapy to metformin provided a new therapeutic option for the treatment of T2DM patients who have inadequate glycaemic control with metformin alone, and was generally well tolerated.

Thyroid dysfunction following radiofrequency ablation for benign thyroid nodules: more likely to occur within one-week and in high-risk population.

BACKGROUND: Radiofrequency ablation (RFA) has been recommended as the treatment for benign thyroid nodules (BTNs) by some guidelines. However, detailed follow-up instructions for thyroid function about the timing and affected populations after RFA are lacked due to insufficient researches. This 12-month prospective study aimed to evaluate the incidence and risk factors of thyroid dysfunction at different time points after RFA, especially within 1 week that previous studies didn't concern. METHODS: Seventy-five euthyroid patients who underwent RFA for symptomatic BTNs were enrolled (ChiCTR-INR-16007884). The incidence of thyroid dysfunction within 1 week, at 1, 6, and 12 months after RFA was evaluated. The risk factors for different types of thyroid dysfunction in the different terms were further analyzed. RESULTS: Within 1 week after RFA, the incidence of thyroid dysfunction was as high as 36.00% unexpectedly, and only overt thyrotoxicosis and subclinical thyrotoxicosis occurred, which were significantly associated with the low-normal baseline thyrotropin (TSH) level (p = 0.001) and high ablation volume ratio (p = 0.008). From 1 to 12 months (the long term), the incidence dropped significantly and remained low (8.00-12.00%); and thyroid dysfunction presented as overt thyrotoxicosis, subclinical thyrotoxicosis, and subclinical hypothyroidism. The long-term thyrotoxicosis group had more cases with diabetes and lower baseline TSH levels. The long-term subclinical hypothyroidism group had more cases with positive thyroid peroxidase antibodies, higher baseline TSH levels, and higher ablation volume ratios. CONCLUSIONS: After the RFA of BTNs, thyroid dysfunction was more likely to occur within 1 week and in populations with risk factors.

Liraglutide, Sitagliptin, and Insulin Glargine Added to Metformin: The Effect on Body Weight and Intrahepatic Lipid in Patients With Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease.

To investigate the effect of antidiabetic agents on nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM), 75 patients with T2DM and NAFLD under inadequate glycemic control by metformin were randomized (1:1:1) to receive add-on liraglutide, sitagliptin, or insulin glargine in this 26-week trial. The primary endpoint was the change in intrahepatic lipid (IHL) from baseline to week 26 as quantified by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF). Secondary endpoints included changes in abdominal adiposity (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT]), glycated hemoglobin, and body weight from baseline to week 26. We analysed data from intent-to-treat population. MRI-PDFF, VAT, and weight decreased significantly with liraglutide (15.4% ± 5.6% to 12.5% ± 6.4%, P < 0.001; 171.4 ± 27.8 to 150.5 ± 30.8, P = 0.003; 86.6 ± 12.9 kg to 82.9 ± 11.1 kg, P = 0.005, respectively) and sitagliptin (15.5% ± 5.6% to 11.7% ± 5.0%, P = 0.001; 153.4 ± 31.5 to 139.8 ± 27.3, P = 0.027; 88.2 ± 13.6 kg to 86.5 ± 13.2 kg, P = 0.005, respectively). No significant change in MRI-PDFF, VAT, or body weight was observed with insulin glargine. SAT decreased significantly in the liraglutide group (239.9 ± 69.0 to 211.3 ± 76.1; P = 0.020) but not in the sitagliptin and insulin glargine groups. Changes from baseline in MRI-PDFF, VAT, and body weight were significantly greater with liraglutide than insulin glargine but did not differ significantly between liraglutide and sitagliptin. Conclusion: Combined with metformin, both liraglutide and sitagliptin, but not insulin glargine, reduced body weight, IHL, and VAT in addition to improving glycemic control in patients with T2DM and NAFLD.

The effects of caveolin1 on ß cell proliferation.

Our study aims to access the influence of caveolin1 (CAV1) on ß cell expression profiles. We knocked down the expression of CAV1 in both NIT-1 cells and islets isolated from C57BL/6J mice using an RNA interference technique, which was realized by the transfer of an shRNA vector targeting CAV1 mRNA into NIT-1 cells or islets through latent virus infection. First, we identified the change in gene expression profiles in islets, in which the CAV1 expression level was down-regulated, as ascertained by mouse gene expression microarray, and the results showed that pathways related to ß cell proliferation and pancreatic secretion functions were significantly influenced. The results of MTT demonstrated that the knockdown of CAV1 expression in NIT-1 cells promoted proliferation. The protein array results showed that pro-apoptotic cytokines were down-regulated in the NIT-1 cell line with CAV1 knockdown. These findings suggest that CAV1 might be involved in apoptosis and proliferation regulation in ß cells, and therefore could be a potential target for the development of novel therapies for diabetes mellitus.

[Glucose characteristics in normal glucose tolerance subjects with metabolic syndrome].

OBJECTIVE: To explore the characteristics of glycemic variability in normal glucose tolerance (NGT) subjects with metabolic syndrome (MetS). METHODS: A total of 40 NGT subjects diagnosed by oral glucose tolerance test (OGTT) were divided into two groups of metabolic syndrome (MetS) or without MetS (Non-MetS) according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) criteria. Fasting blood glucose (FBG), OGTT 2 h blood glucose (2 h BG), hemoglobin A1c (HbA1c) and glycemic variability were assessed. Glycemic variability was assessed by calculating standard deviation of MBG (SDBG), mean amplitude of glycemic excursions (MAGE), largest amplitude of glycemic excursions (LAGE) and means of daily differences (MODD) from the 72 h data of continuous glucose monitoring system (CGMS) in real life. The time of diurnal glycemic variability was also calculated. RESULTS: No significant inter-group difference existed in FBG, 2 h BG or HbA1c. Glycemic variability was higher in MetS than that in Non-MetS group. But only MAGE (2.12±0.92 vs 1.50±0.68 mmol/L, P=0.02) showed significant inter-group difference. Logistic regression analysis revealed that MAGE was significantly correlated with MetS (OR=2.74, 95% CI: 1.08-6.97, P=0.03) and independently from FBG, PBG, HbA1c and other glycemic variability indices. CONCLUSIONS: Glycemic variability increases in NGT subjects with MetS. And MAGE may better describe the population's glucose metabolism.

Glycated haemoglobin A1c for diagnosing diabetes in Chinese subjects over 50 years old: a community-based cross-sectional study.

OBJECTIVE: Little is known about using glycated haemoglobin A1c (HbA1c) to diagnose diabetes in Chinese subjects over 50 years old. This study aims to evaluate HbA1c in diagnosing diabetes and identify the optimal threshold to be used in Chinese community subjects aged over 50 years. METHODS: A community-based cross-sectional survey was conducted from October 2010 to January 2011 in Shipai community of Guangzhou, Guangdong, China. A total of 1494 subjects (72·8%) aged over 50 years were investigated. Fasting plasma glucose (FPG1st ) and HbA1c were assayed in each participant. Diabetic candidates with FPG1st ≥ 5·6 mmol/l or HbA1c ≥ 39 mmol/mol (5·7%) were informed to undergo a 75-g oral glucose tolerance test (OGTT). Diagnosis of diabetes was made by 1999 World Health Organization criteria. Sensitivity and specificity of HbA1 c for diagnosing diabetes were calculated by receiver operating characteristics (ROC) curve. RESULTS: Among 1494 subjects, 161 subjects (10·8%) with previously diagnosed diabetes and 21 with missing data were excluded. Among the remaining 1312 subjects (87·8%), 861 subjects (65·6%) with either FPG1st ≥ 5·6 mmol/l or HbA1c ≥ 39 mmol/mol (5·7%) were invited to perform OGTT. Finally, 453 subjects (52·6%) performed OGTT (FPG2nd and 2-h plasma glucose were measured) and 54 subjects (11·9%) were identified as being diabetes. The area under ROC curve was 0·916 (0·887-0·940) for HbA1c and 0·972 (0·953-0·985) for FPG2nd in diagnosing diabetes (P = 0·045). An HbA1c threshold of 48 mmol/mol (6·5%) yielded the highest combination of sensitivity (75·9%) and specificity (95·5%) for diagnosing diabetes. CONCLUSION: An HbA1 c threshold of 48 mmol/mol (6·5%) was highly specific and had a good sensitivity for diagnosing diabetes among Chinese subjects aged over 50 years with FPG ≥ 5·6 mmol/l or HbA1c ≥ 39 mmol/mol (5·7%). This threshold may be suitable for diagnosing diabetes in Chinese subjects over 50 years old.

Caveolin-1 deficiency alleviates palmitate-induced intracellular lipid accumulation and inflammation in pancreatic ß cells.

Lipotoxicity-induced pancreatic ß cell damage is a strong predictor of type 2 diabetes mellitus (T2DM). Our previous work showed that Caveolin-1 (Cav-1) depletion decreased ß-cell apoptosis and improved ß-cell viability. Further microarray analysis indicated significant changes in the expression of genes related to fatty acid metabolism and inflammation. The objective of this study was to explore the role of Cav-1 in intracellular lipid accumulation and inflammation in ß cells under lipotoxic conditions. Here, we established a ß-cell-specific Cav-1 knockout (ß-Cav-1 KO) mouse model and a CAV-1 depleted ß cell line (NIT-1). We found that Cav-1 silencing significantly reduced palmitate (PA)-induced intracellular triglyceride (TG) accumulation and decreased proinflammatory factor expression in both the mouse and cell models. Further mechanistic investigation revealed that amelioration of lipid metabolism was achieved through the downregulation of lipogenic markers (SREBP-1c, FAS and ACC) and upregulation of a fatty acid oxidation marker (CPT-1). Meanwhile, decrease of inflammatory cytokines (IL-6, TNF-α, and IL-1ß) secretion was found with the involvement of the IKKß/NF-κB signaling pathways. Our findings suggest that Cav-1 is of considerable importance in regulating lipotoxicity-induced ß-cell intracellular lipid accumulation and inflammation.

Comparison of changes in adipokine and inflammatory cytokine levels in patients with newly diagnosed type 2 diabetes treated with exenatide, insulin, or pioglitazone: A post-hoc study of the CONFIDENCE trial.

Background: Adipokines and inflammatory cytokines (ADICs) play important roles in type 2 diabetes mellitus (T2DM). This study aimed to compare the changes of ADIC levels (ΔADICs) in patients with newly diagnosed T2DM treated with different antihyperglycemic agents, and further investigate the impact of these changes on metabolic indices, ß-cell function and insulin resistance (IR). Methods: Four hundred and sixteen patients with newly diagnosed T2DM from 25 centers in China randomly received 48-week intervention with exenatide, insulin or pioglitazone. Anthropometric and laboratory data, indices of ß-cell function and IR, and levels of AIDCs, including interleukin-1 beta (IL-1ß), interferon-gamma (IFN-γ), leptin, and fibroblast growth factor 21 (FGF21) were detected at baseline and the end of the study. Results: In total, 281 participants (68 % male, age: 50.3 ± 9.4 years) completed the study. After 48- week treatment, IL-1ß and IFN-γ were significantly decreased with exenatide treatment (P < 0.001 and P = 0.001, respectively), but increased with insulin (P = 0.009 and P = 0.026, respectively). However, pioglitazone treatment had no impact on ADICs. No significant change in leptin or FGF21 was detected with any of the treatments. After adjustment for baseline values and changes of body weight, waist and HbA1c, the between-group differences were found in ΔIL-1ß (exenatide vs. insulin: P = 0.048; and exenatide vs. pioglitazone: P = 0.003, respectively) and ΔIFN-γ (exenatide vs. insulin: P = 0.049; and exenatide vs. pioglitazone: P < 0.001, respectively). Multiple linear regression analysis indicated that Δweight was associated with ΔIL-1ß (ß = 0.753; 95 % CI, 0.137-1.369; P = 0.017). After adjusting for treatment effects, Δweight was also be correlated with ΔFGF21 (ß = 1.097; 95%CI, 0.250-1.944; P = 0.012); furthermore, ΔHOMA-IR was correlated with Δleptin (ß = 0.078; 95%CI, 0.008-0.147; P = 0.029) as well. However, ΔHOMA-IR was not significantly associated with ΔIL-1ß after adjusting for treatment effects (P = 0.513). Conclusion: Exenatide treatment led to significant changes of inflammatory cytokines levels (IL-1ß and IFN-γ), but not adipokines (leptin and FGF21), in newly diagnosed T2DM patients. The exenatide-mediated improvement in weight and IR may be associated with a decrease in inflammatory cytokine levels.

[Primary culturing and effects of insulin glargine on proliferation, differentiation of human preadipocytes from subcutaneous and omental adipose tissue].

OBJECTIVE: To compare the morphological and functional differences of human primary preadipocytes from different fat depots and explore the effects of insulin glargine on their proliferation and differentiation. METHODS: Primary preadipocytes isolated from human subcutaneous and omental adipose tissue by collagenase I were passaged in vitro.Inverted phase contrast microscope was used to observe the morphological differences of two kinds of preadipocytes. Then two kinds of preadipocytes were cultured or induced to differentiation with different doses of insulin glargine. The methyl thiazolyl tetrazolium (MTT) assay was used to detect their proliferative differences.Reverse transcription-polymerase chain reaction (RT-PCR) was used to observe the effects of insulin on adipogenic gene expression. RESULTS: (1) Both preadipocytes could be successfully cultured from adipose tissue and amplified in vitro.Subcutaneous preadipocytes were more slender and proliferated more quickly while omental preadipocytes were polygonal and aged easily.(2) MTT results showed that insulin glargine could inhibit the proliferation of omental preadipocytes in a dose-dependent fashion. After 72 h incubation, compared with negative control, the absorbance (A) value of 1000 nmol/L insulin glargine group decreased greatly (0.144 ± 0.021 vs 0.267 ± 0.040, P < 0.01). But it had no effect on subcutaneous preadipocytes (0.305 ± 0.045 vs 0.350 ± 0.037, P > 0.05). (3) Insulin at 500 nmol/L was a suitable concentration for inducing differentiation.RT-PCR analysis showed that, for subcutaneous adipocytes, adipogenic genes such as peroxisome proliferator-activated receptor gamma (PPARγ) (F = 31.31, P < 0.01) and CCAAT enhancer binding protein α (C/EBPα) (F = 9.86, P < 0.05) had the highest mRNA expression while preadipocytes gene Pref-1 had the lowest expression at this concentration. But insulin dose had no obvious effect on PPARγ or C/EBPα mRNA (P > 0.05) for omental adipocytes. CONCLUSION: Insulin glargine could inhibit the proliferation of omental preadipocytes, and enhance the differentiation of subcutaneous and omental preadipocytes.

Adrenal Hemorrhage in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome: A Case Report and Literature Review.

Antiphospholipid syndrome (APS) is an autoimmune disorder while adrenal hemorrhage could be its rare complication. Herein, we report the case of a 32-year-old unmarried woman with a history of systemic lupus erythematosus (SLE) who was hospitalized after complaints of upper abdominal pain, limb weakness, and loss of appetite for 2 weeks. Laboratory examination revealed hyponatremia, low plasma cortisol levels, increased adrenocorticotropic hormone levels, and a positive anticardiolipin antibody status. Furthermore, computed tomography (CT) revealed the presence of bilateral adrenal masses. Ultimately, based on dynamic changes in CT images, these masses were diagnosed as adrenal hemorrhage owing to APS. A computer-assisted literature search was conducted to identify cases of primary adrenal insufficiency associated with APS and/or SLE. The clinical features, laboratory examination, treatments, and outcomes of these cases were summarized. Our findings emphasize the importance of screening for adrenal insufficiency in patients with SLE or APS who present with abdominal complaints, asthenia, and hyponatremia. It is also recommended to test for APS all patients with adrenal hemorrhage.

Malonylation of Acetyl-CoA carboxylase 1 promotes hepatic steatosis and is attenuated by ketogenic diet in NAFLD.

Protein post-translational modifications (PTMs) participate in important bioactive regulatory processes and therefore can help elucidate the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Here, we investigate the involvement of PTMs in ketogenic diet (KD)-improved fatty liver by multi-omics and reveal a core target of lysine malonylation, acetyl-coenzyme A (CoA) carboxylase 1 (ACC1). ACC1 protein levels and Lys1523 malonylation are significantly decreased by KD. A malonylation-mimic mutant of ACC1 increases its enzyme activity and stability to promote hepatic steatosis, whereas the malonylation-null mutant upregulates the ubiquitination degradation of ACC1. A customized Lys1523ACC1 malonylation antibody confirms the increased malonylation of ACC1 in the NAFLD samples. Overall, the lysine malonylation of ACC1 is attenuated by KD in NAFLD and plays an important role in promoting hepatic steatosis. Malonylation is critical for ACC1 activity and stability, highlighting the anti-malonylation effect of ACC1 as a potential strategy for treating NAFLD.

Effects of a combination of oral anti-diabetes drugs with basal insulin therapy on ß-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes.

BACKGROUND: Oral anti-diabetes drugs plus basal insulin (OAD + insulin) therapy in patients with newly diagnosed type 2 diabetes might improve ß-cell function and result in extended glycaemic remission. This randomised trial compared the effect on ß-cell function and diabetes remission rate between oral drug alone or with addition of basal insulin. METHODS: One hundred and twenty-nine patients, aged 35-50 years, were enrolled between June 2005 and June 2009. For initial correction of hyperglycaemia, patients with fasting plasma glucose ≥9.0 mmol/L and HbA(1c) ≥ 9.0%, were randomly assigned to therapy with oral drugs + insulin or oral drugs alone. Treatment was stopped after normoglycaemia was maintained for 3 months. Patients were then followed-up with diet and physical exercise. Blood glucose, HbA(1c) and insulin were measured prior to treatment and at 1-year follow-up. RESULTS: More patients achieved target glycaemic control in the oral drugs + insulin group [98.3% (58 of 59)] in less time [(10.4 ± 2.5) days] than those in the oral drug group [95.7% (67 of 70) and (12.4 ± 3.4) days]. At 1-year follow-up, more patients maintained target glycaemia without any drugs in the oral drug + insulin group than in the oral drug group [37.9% (22 of 58) vs 20.9% (14 of 67)]. Both treatments improved homeostasis model assessment-ß (HOMA-ß) and homeostasis model assessment-insulin resistance (HOMA-IR) significantly. They had similar effects on insulin resistance [lg(HOMA-IR): (0.50 ± 0.09) vs (0.48 ± 0.09), p = 0.23]. However, oral drugs + insulin could recover ß-cell function much more than OAD alone could [lg(HOMA-ß): (2.17 ± 0.14) vs (2.11 ± 0.13), p = 0.03]. CONCLUSION: In newly diagnosed type 2 diabetes, therapy with oral drugs + insulin has had favourable outcomes on recovery and maintenance of ß-cell function and protracted glycaemic remission compared with treatment with oral drugs alone.

[Depot-specific expression of caveolin-1 in human adipose tissue and their relationship with obesity and insulin resistance].

OBJECTIVE: To explore the depot-specific mRNA and protein expression of caveolin-1 (CAV-1) in human subcutaneous and omental adipose tissues and analyze their relationship with obesity and insulin resistance. METHODS: A total of 41 subjects with normal glucose regulation were recruited. Among them, there were 29 cases with normal body mass index (BMI) and 12 cases with BMI ≥ 24 kg/m(2). All were scheduled to undergone selective abdominal operations. The levels of fasting insulin (FINS) were measured by chemiluminescence enzyme-linked immunosorbent assay (ELISA) kit. Fasting plasma glucose (FPG) was tested by glucose oxidase and home model insulin resistance index (HOMA-IR) calculated. Real-time polymerase chain reaction (RT-PCR) and Western blotting were employed to assess the relative mRNA and protein expression of caveolin-1 in subcutaneous and omental adipose tissues. And the mRNA and protein expression of caveolin-1 from different fat depots were compared and their correlations with BMI and HOMA-IR analyzed. RESULTS: (1) FINS and HOMA-IR were significantly higher in the overweight and obesity group than those in the normal BMI group (FINS: (8.82 ± 3.79) mU/L vs (6.43 ± 4.38) mU/L, P < 0.05, HOMA-1R: 1.91 ± 0.85 vs 1.36 ± 0.72, P < 0.05). (2) The normal BMI group patients had the higher expression levels of caveolin-1 mRNA in omental adipose tissue than overweight counterparts (2.84 ± 0.86 vs 1.02 ± 0.36, P < 0.01). But the difference in subcutaneous adipose tissue was not significant (P > 0.05). (3) The caveolin-1 protein expression in omental adipose tissue of the normal BMI group was higher than that of overweight patients (1.68 ± 0.67 vs 0.73 ± 0.29, P < 0.05). And the difference between two groups was not significant (P > 0.05). (4)The expressions of caveolin-1 mRNA in omental adipose tissue were negatively correlated with BMI, waist circumstance, triglyceride and HOMA-IR (r = -0.441, -0.615, -0.539, -0.688, P < 0.05). No correlations were found between the expressions of caveolin-1 mRNA in subcutaneous adipose tissue with BMI, waist circumstance and HOMA-IR (P > 0.05). CONCLUSION: Differential depot-specific expressions of caveolin-1 are present in human subcutaneous and omental adipose tissues. A low expression of caveolin-1 in omental adipose tissue may contribute to the pathogenesis of obesity and insulin resistance.

[Characteristics of real-life glucose profiles monitored by continuous glucose monitoring system in persons with normal glucose tolerance].

OBJECTIVE: To decipher the characteristics of real-life glucose profiles in normal glucose tolerance (NGT) persons by continuous glucose monitoring system (CGMS). METHODS: Forty NGT subjects confirmed by oral glucose tolerance test (OGTT) completed a 3-day period of glucose monitoring via CGMS. RESULTS: The values of 24 h mean blood glucose (MBG), standard deviation of MBG (SDBG), mean amplitude of glycemic excursions (MAGE), largest amplitude of glycemic excursions (LAGE) and means of daily differences (MODD) were 6.0 ± 0.7, 0.9 ± 0.1, 1.9 ± 0.8, 2.9 ± 1.4 and 1.1 ± 0.1 mmol/L respectively. Two of them experienced asymptomatic hypoglycemia defined as glucose concentration < 2.8 mmol/L. And 72.5% (29/40) subjects reached glucose concentrations > 7.8 mmol/L for 5.2 ± 4.6 hours. In addition to higher glucose concentration (FPG: 5.0 ± 0.4 vs 4.8 ± 0.3 mmol/L, MBG: 6.4 ± 0.7 vs 5.7 ± 0.5 mmol/L), the subjects with glucose concentrations > 7.8 mmol/L showed more dramatic glucose excursion represented by higher SDBG (1.1 ± 0.3 vs 0.6 ± 0.2 mmol/L), MAGE (2.3 ± 1.1 vs 1.1 ± 0.3 mmol/L), LAGE (3.3 ± 1.2 vs 2.0 ± 1.0 mmol/L) and MODD (1.2 ± 0.4 vs 0.9 ± 0.3 mmol/L) versus those with glucose concentrations within 7.8 mmol/L. CONCLUSION: CGMS provides more detailed information of real-life glucose profiles in NGT subjects. And 72.5% NGT subjects in the present study spent a considerable amount of time at pre-diabetic or even diabetic glucose levels characterized by more predominant glucose excursion.

Dorzagliatin in drug-naïve patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial.

Improving glucose sensitivity remains an unmet medical need in treating type 2 diabetes (T2D). Dorzagliatin is a dual-acting, orally bioavailable glucokinase activator that enhances glucokinase activity in a glucose-dependent manner, improves glucose-stimulated insulin secretion and demonstrates effects on glycemic control in patients with T2D. We report the findings of a randomized, double-blind, placebo-controlled phase 3 clinical trial to evaluate the efficacy and safety of dorzagliatin in patients with T2D. Eligible drug-naïve patients with T2D (n = 463) were randomly assigned to the dorzagliatin or placebo group at a ratio of 2:1 for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin from baseline to week 24. Safety was assessed throughout the trial. At week 24, the least-squares mean change in glycated hemoglobin from baseline (95% confidence interval) was -1.07% (-1.19%, -0.95%) in the dorzagliatin group and -0.50% (-0.68%, -0.32%) in the placebo group (estimated treatment difference, -0.57%; 95% confidence interval: -0.79%, -0.36%; P < 0.001). The incidence of adverse events was similar between the two groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin group. In summary, dorzagliatin improved glycemic control in drug-naïve patients with T2D and showed a good tolerability and safety profile.

[Cross-sectional study of current situation of glycemic control with type 1 diabetes in Guangdong Province].

OBJECTIVE: To investigate the glycemic control and the related factors of type 1 diabetic patients in Guangdong Province. METHODS: Medical records and blood samples of type 1 diabetic patients were collected in 89 tertiary and secondary hospitals from all of the 21 cities in Guangdong Province. The clinical data were analyzed to explore the correlates of glycemic control. HbA1c levels, measured in Guangdong Diabetes Center, were used to assess glycemic control. RESULTS: 851 patients were enrolled from August 6, 2010 to May 25, 2011. There were 408 males and 443 females. The median (interquartile range) age was 29.6 years (20.3 - 41.3 years). The onset age of diabetes was 25.3 years (15.7 - 35.5 years). The disease duration was 3.3 years (1.0 - 7.3 years). The BMI was 19.9 kg/m(2) (17.9 - 21.8 kg/m(2)). HbA1c levels were 8.6% (6.9% - 11.0%) and only 234 (27.50%) patients reached the age-specific target levels. Correlates with poorer glycemic control were 13 - 19 years old (vs 7 - 12 and ≥ 20 years old), lower household income, not on dietary intervention, never accepting diabetic education and shorter diabetic duration. CONCLUSION: The majority of Guangdong type 1 diabetic patients did not achieve target values for glycemic control, indicating an urgent need for comprehensive management to improve glycemic control.

Caveolin-1 Is Essential for the Improvement of Insulin Sensitivity through AKT Activation during Glargine Treatment on Diabetic Mice.

Insulin treatment was confirmed to reduce insulin resistance, but the underlying mechanism remains unknown. Caveolin-1 (Cav-1) is a functional protein of the membrane lipid rafts, known as caveolae, and is widely expressed in mammalian adipose tissue. There is increasing evidence that show the involvement of Cav-1 in the AKT activation, which is responsible for insulin sensitivity. Our aim was to investigate the effect of Cav-1 depletion on insulin sensitivity and AKT activation in glargine-treated type 2 diabetic mice. Mice were exposed to a high-fat diet and subject to intraperitoneal injection of streptozotocin to induce diabetes. Next, glargine was administered to treat T2DM mice for 3 weeks (insulin group). The expression of Cav-1 was then silenced by injecting lentiviral-vectored short hairpin RNA (shRNA) through the tail vein of glargine-treated T2DM mice (CAV1-shRNA group), while scramble virus injection was used as a negative control (Ctrl-shRNA group). The results showed that glargine was able to upregulate the expression of PI3K and activate serine phosphorylation of AKT through the upregulation of Cav-1 expression in paraepididymal adipose tissue of the insulin group. However, glargine treatment could not activate AKT pathway in Cav-1 silenced diabetic mice. These results suggest that Cav-1 is essential for the activation of AKT and improving insulin sensitivity in type 2 diabetic mice during glargine treatment.

[The effects of early intensive therapy on islet beta cell function and long-term glycemia control in newly diagnosed type 2 diabetic patients with different fasting plasma glucose levels.].

OBJECTIVE: To investigate the effects of early intensive therapy on beta cell function and long-term glycemic control in newly diagnosed type 2 diabetic patients with different recruiting fasting plasma glucose (FPG) levels. METHODS: A total of 382 newly diagnosed type 2 diabetic patients with FPG 7.0 - 16.7 mmol/L were randomly assigned to therapy with insulin in the form of continuous subcutaneous insulin infusion (CSII) or multiple daily injection (MDI) or oral hypoglycemic agents (OHA, by using gliclazide and/or metformin) for initial rapid correction of hyperglycemia. The treatments were stopped after euglycemia had been maintained for 2 weeks. The patients were followed longitudinally on diet alone for 1 year. Intravenous glucose tolerances tests (IVGTTs) were performed and blood glucose, insulin and proinsulin were measured before and after therapy as well as at 1-year follow-up. Homeostasis model assessment (HOMA) of beta cell function and insulin resistance index (HOMA-beta and HOMA-IR) were calculated. All the patients were stratified on the recruiting FPG: stratum A (7.0 mmol/L