Metabolic landscape of human alveolar type II epithelial cells undergoing epithelial-mesenchymal transition induced directly by silica exposure.

Epithelial-mesenchymal transition (EMT) plays an irreplaceable role in the development of silicosis. However, molecular mechanisms of EMT induced by silica exposure still remain to be addressed. Herein, metabolic profiles of human alveolar type II epithelial cells (A549 cells) exposed directly to silica were characterized using non-targeted metabolomic approaches. A total of 84 differential metabolites (DMs) were identified in silica-treated A549 cells undergoing EMT, which were mainly enriched in metabolisms of amino acids (e.g., glutamate, alanine, aspartate), purine metabolism, glycolysis, etc. The number of DMs identified in the A549 cells obviously increased with the elevated exposure concentration of silica. Remarkably, glutamine catabolism was significantly promoted in the silica-treated A549 cells, and the levels of related metabolites (e.g., succinate) and enzymes (e.g., α-ketoglutarate (α-KG) dehydrogenase) were substantially up-regulated, with a preference to α-KG pathway. Supplementation of glutamine into the cell culture could substantially enhance the expression levels of both EMT-related markers and Snail (zinc finger transcription factor). Our results suggest that the EMT of human alveolar epithelial cells directly induced by silica can be essential to the development of silicosis.

Basal Hyperglycemia Contributes More Than Fifty Percent to Time in Range in Pregnant Women with Type 1 Diabetes.

AIMS: To evaluate the relative contribution of basal hyperglycemia (BHG) and postprandial hyperglycemia (PHG) to the time in range (TIR) categories and adverse pregnancy outcomes in pregnant women with type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: This observational study included 112 pregnancies with T1DM from the CARNATION study who wore continuous glucose monitoring (CGM) devices during pregnancy. The data from CGM were analyzed for TIR (range, 3.5-7.8 mmol/L), areas under the curve (AUC) of PHG, AUC of BHG, basal and postprandial hyperglycemia contribution rates. The contribution rates of BHG and PHG to the different levels of TIR(＜60%, 60-78%, ≥78%) and adverse pregnancy outcomes were analyzed. RESULTS: The participants' average age was 28.8±3.9 years with a diabetes duration of 8.4±6.2 years. All women experienced a mean TIR of 75.6±19.0% and a mean HbA1c of 6.2±1.1% during pregnancy. The BHG contribution accounted for 74.9(36.8, 100)%, 69.2(13.4, 100)%, and 66.5(10.0, 100)% (P＜0.001) and PHG accounted for 25.1(0, 63.2)% and 30.8(0, 86.6)% and 33.5(0, 90.0)% (P＜0.001) when participants experienced the TIR＜60%, 60-78%, ≥78%, respectively. Participants with higher BHG contribution rates tended to have more adverse pregnancy outcomes. CONCLUSIONS: Basal hyperglycemia was the major contributor to TIR during pregnancy. Along with controlling the postprandial hyperglycemia, pregnant women with T1DM who did not reach the target of TIR may benefit more from the optimization of insulin regimens focusing on reducing basal glucose.

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.

Effect of artificial pancreas system use on glycaemic control among pregnant women with type 1 diabetes mellitus: A meta-analysis of randomized controlled trials.

AIM: To assess the efficacy of artificial pancreas systems (APS) use among pregnant women with type 1 diabetes mellitus (T1DM) by conducting a meta-analysis. METHODS: We searched five databases, including EMBASE, Web of Science, PubMed, Cochrane Library and SCOPUS, for literature on APS use among pregnant women with T1DM before October 9, 2023. The primary endpoint was 24-hour time in range (TIR; 3.5-7.8 mmol/L). Secondary endpoints included glycaemic metrics for 24-hour (mean blood glucose [MBG], time above range [TAR], time below range [TBR]), and overnight TIR and TBR. RESULTS: We identified four randomized controlled trials involving 164 participants; one study with 16 participants focused on overnight APS use, and the other three focused on 24-hour APS use. Compared with standard care, APS exhibited a favourable effect on 24-hour TIR (standard mean difference [SMD] = 0.53, 95% confidence interval [CI] 0.25, 0.80, P < 0.001), overnight TIR (SMD = 0.67, 95% CI 0.39, 0.95, P < 0.001), and overnight TBR (<3.5 mmol/L; SMD = -0.49, 95% CI -0.77, -0.21 P < 0.001), while there was no significant difference in 24-hour TAR, 24-hour TBR, or MBG between the two groups. We further conducted subgroup analyses after removing the trial focused on overnight APS use and showed that 24-hour APS use reduced not only the 24-hour TIR (SMD = 0.41, 95% CI 0.12, 0.71; P = 0.007) but also the 24-hour TBR (<2.8 mmol/L; SMD = -0.77, 95% CI -1.32, -0.23, P = 0.006). CONCLUSION: Our findings suggest that APS might improve 24-hour TIR and overnight glycaemic control, and 24-hour APS use also significantly reduced 24-hour TBR (2.8 mmol/L) among pregnant women with T1DM.

Efficacy and safety of Android artificial pancreas system use at home among adults with type 1 diabetes mellitus in China: protocol of a 26-week, free-living, randomised, open-label, two-arm, two-phase, crossover trial.

INTRODUCTION: Do-it-yourself artificial pancreas system (DIY APS) is built using commercially available insulin pump, continuous glucose monitoring (CGM) and an open-source algorithm. Compared with commercial products, DIY systems are affordable, allow personalised settings and provide updated algorithms, making them a more promising therapy for most patients with type 1 diabetes mellitus (T1DM). Many small and self-reported observational studies have found that their real-world use was associated with potential metabolic and psychological benefits. However, rigorous-designed studies are urgently needed to confirm its efficacy and safety. METHODS AND ANALYSIS: In this 26-week randomised, open-label, two-arm, two-phase, crossover trial, participants aged 18-75 years, with T1DM and glycated haemoglobin (HbA1c) 7-11%, will use AndroidAPS during one 12-week period and sensor-augmented pump during another 12-week period. This study will recruit at least 24 randomised participants. AndroidAPS consists of three components: (1) real-time CGM; (2) insulin pump; (3) AndroidAPS algorithm implemented in Android smartphone. The primary endpoint is time in range (3.9-10.0 mmol/L) derived from CGM. The main secondary endpoints include percentage of sensor glucose values below, within and above target range; mean sensor glucose value; measures of glycaemic variability and centralised HbA1c. Safety endpoints mainly include the frequency of hypoglycaemia events, diabetic ketoacidosis and other serious adverse events. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University. There will be verbal and written information regarding the trial given to each participant. The study will be disseminated through peer-reviewed publications and conference presentations. OVERALL STATUS: Recruiting. STUDY START: 11 February 2023. PRIMARY COMPLETION: 31 July 2024. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05726461).

Selective venous sampling in primary hyperparathyroidism caused by ectopic parathyroid gland: a case report and literature review.

BACKGROUND: As an invasive technique, selective venous sampling (SVS) is considered a useful method to identify a lesion's location to increase the success rate of secondary surgery in patients with primary hyperparathyroidism (pHPT) caused by ectopic parathyroid adenomas. CASE PRESENTATION: We present a case of post-surgical persistent hypercalcemia and elevated parathyroid hormone (PTH) levels in a 44-year-old woman with previously undetected parathyroid adenoma. An SVS was then performed for further localization of the adenoma, as other non-invasive methods showed negative results. After SVS, an ectopic adenoma was suspected in the sheath of the left carotid artery, previously considered as a schwannoma, and was pathologically confirmed after the second operation. Postoperatively, the patient's symptoms disappeared and serum levels of PTH and calcium normalized. CONCLUSIONS: SVS can provide precise diagnosis and accurate positioning before re-operation in patients with pHPT.

A pregnancy-specific Glucose management indicator derived from continuous glucose monitoring in pregnant women with type 1 diabetes.

OBJECTIVE: Glucose management indicator (GMI) is a core metric derived from continuous glucose monitoring (CGM) and is widely used to evaluate glucose control in patients with diabetes. No study has explored the pregnancy-specific GMI. This study aimed to derive a best-fitting model to calculate GMI from mean blood glucose (MBG) obtained from CGM among pregnant women with type 1 diabetes mellitus (T1DM). METHODS: A total of 272 CGM data and corresponding laboratory HbA1c from 98 pregnant women with T1DM in the CARNATION study were analysed in this study. Continuous glucose monitoring data were collected to calculate MBG, time-in-range (TIR), and glycaemic variability parameters. The relationships between the MBG and HbA1c during pregnancy and postpartum were explored. Mix-effect regression analysis with polynomial terms and cross-validation method was conducted to investigate the best-fitting model to calculate GMI from MBG obtained by CGM. RESULTS: The pregnant women had a mean age of 28.9 ± 3.8 years, with a diabetes duration of 8.8 ± 6.2 years and a mean body mass index (BMI) of 21.1 ± 2.5 kg/m2 . The HbA1c levels were 6.1 ± 1.0% and 6.4 ± 1.0% during pregnancy and at postpartum (p = 0.024). The MBG levels were lower during pregnancy than those at postpartum (6.5 ± 1.1 mmol/L vs. 7.1 ± 1.5 mmol/L, p = 0.008). After adjusting the confounders of haemoglobin (Hb), BMI, trimesters, disease duration, mean amplitude of glycaemic excursions and CV%, we developed a pregnancy-specific GMI-MBG equation: GMI for pregnancy (%) = 0.84-0.28* [Trimester] + 0.08 * [ BMI in kg/m2 ] + 0.01 * [Hb in g/mL] + 0.50 * [MBG in mmol/L]. CONCLUSIONS: We derived a pregnancy-specific GMI equation, which should be recommended for antenatal clinical care. CLINICAL TRIAL REGISTRY NUMBER: ChiCTR1900025955.

Relations Between Body Fat Mass and Insulin Resistance in Non-Obese Patients with Idiopathic Hypogonadotropic Hypogonadism and Normal Glucose Tolerance.

The purpose of this study was to investigate the relationship between body fat mass and insulin resistance in non-obese patients with idiopathic hypogonadotropic hypogonadism (IHH) and normal glucose tolerance. A total of 42 patients with IHH and normal glucose tolerance, and BMI lower than 28 kg/m2 were recruited. Patients were required to have a normal glucose tolerance test for inclusion in the study. Ten Healthy subjects were recruited as control group. Laboratory studies included fasting insulin, testosterone, and lipids. Waist circumference (WC), weight, and body fat mass were measured, and waist-to-hip ratio (WHR), body mass index (BMI), HOMA-IR, and logHOMA-B were calculated. Data were compared between groups, and linear regression was used to determine relations. Blood pressure, fasting glucose, BMI, WHR, and lipids were similar between the groups. Fasting insulin levels (15.61±7.66 mIU/l vs. 7.60±3.84 mIU/l), logHOMA-B (2.39±0.29 vs. 2.03±0.21), HOMA-IR (3.38±1.71 vs. 1.64±0.91), and body fat mass (30.49±9.46% vs. 21.11±4.31%) were significantly greater in the IHH group compared with those in control group (all p<0.05). Multivariable linear regression showed that in IHH patients body fat mass was an independent predictor of fasting insulin level (ß=0.71, p<0.01), logHOMA-B (ß=0.02, p<0.05), and HOMA-IR (ß=0.14, p<0.05). Body fat mass is an independent predictor of insulin resistance in non-obese IHH patients with normal glucose tolerance.

Beta-2-Microglobulin is an Independent Risk Factor for Asymptomatic Carotid Atherosclerosis in Patients with Primary Aldosteronism.

AIM: To identify the association between serum beta-2-microglobulin (B2M) or cystatin C (CysC) and asymptomatic carotid atherosclerosis in patients with primary aldosteronism (PA). METHODS: In this cross-sectional study, 265 subjects were enrolled, including 83 patients with PA, 91 with essential hypertension (EH), and 91 normotensive (NT) controls. B2M, CysC, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were measured, and the aldosterone-to-renin ratio (ARR) was calculated. Carotid intima-media thickness (cIMT), increased cIMT, and presence of carotid plaque or carotid stenosis ＜50% in the carotid artery were measured via ultrasonography to evaluate the degree of asymptomatic carotid atherosclerosis. RESULTS: CIMT increased in the NT, EH, and PA groups (0.60 (0.50, 0.80) mm vs. 0.80 (0.60, 1.00) mm vs. 0.90 (0.70, 1.10) mm, P＜0.01), so as the prevalence of increased cIMT and presence of carotid plaque (both P＜0.05). The B2M and CysC levels exhibited the same trend (B2M: 1.60±0.34 mg/L, 1.80±0.41 mg/L, 1.98±0.64 mg/L, P＜0.05; CysC: 0.76±0.12 mg/L, 0.88±0.17 mg/L, 0.94±0.23 mg/L, P＜0.05). B2M, CysC, PAC, and ARR were all positively associated with cIMT (all P＜0.01) in the PA group. After adjusting for potential confounders, B2M, PAC, but not CysC or ARR were independently associated with increased cIMT and presence of carotid plaque and carotid stenosis ＜50%, respectively. The receiver operating characteristic (ROC) curve analysis revealed that B2M and PAC demonstrated significant predictive ability for increased cIMT and presence of carotid plaque and carotid stenosis ＜50%. CONCLUSION: B2M is an independent risk factor for asymptomatic carotid atherosclerosis in patients with PA.

Mid-upper arm circumference as a simple tool for identifying central obesity and insulin resistance in type 2 diabetes.

BACKGROUND: Our research aimed to explore the correlation between mid-upper arm circumference (MUAC) and central obesity and insulin resistance (IR) in Chinese subjects with type 2 diabetes. MATERIALS: A total of 103 participants (60 men) were recruited in our study. MUAC was measured around the mid-arm between the shoulder and elbow. Waist circumference (WC) was obtained as central obesity parameter, and the IR parameter of Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) was calculated. The subjects were divided into three groups according to the tertiles cut-points of MUAC level. RESULTS: Body mass index (BMI), WC, the percentages of central obesity and HOMA-IR were significantly higher in the groups with higher MUAC than those in the group with lower MUAC (all P < 0.05). Pearson analysis showed that MUAC was correlated with BMI, WC, waist-to-hip ratio (WHR), logHOMA-IR, low density lipoprotein cholesterol (LDL-C), uric acid (UA) and high density lipoprotein cholesterol (HDL-C) in all subjects. Multivariate linear regression analysis revealed that MUAC was independently associated with logHOMA-IR (ß = 0.036, P<0.001) after adjusting for age, gender, WHR, UA, TG, LDL-C and HDL-C. Binary logistic regression analysis revealed that MUAC was an independent predictor of central obesity (OR: 2.129, 95%CI: 1.311-3.457, P = 0.002). Furthermore, MUAC≥30.9cm for male and ≥30.0cm for female were the optimal cutoff values for identifying central obesity. CONCLUSIONS: Our study indicated that among Chinese subjects with type 2 diabetes, MUAC is a simple and effective tool for the determination of central obesity and IR. Additionally, the larger MUAC is proved to be more associated with metabolic risk factors of higher UA and LDL-C and lowever HDL-C.

Effects of Metformin Added to Insulin in Adolescents with Type 1 Diabetes: An Exploratory Crossover Randomized Trial.

BACKGROUND: To comprehensively assess the effects of metformin added to insulin on metabolic control, insulin sensitivity, and cardiovascular autonomic function in adolescents with type 1 diabetes. MATERIALS AND METHODS: This was an exploratory, crossover, randomized trial conducted in adolescents with type 1 diabetes aged 12-18 years old. Participants were randomly received metformin (≤1000 mg/d) added to insulin for 24 weeks followed by insulin monotherapy for a subsequent 24 weeks or vice versa. Blood pressure, body mass index, insulin dose, estimated insulin sensitivity, glycated hemoglobin A1c (HbA1c), and lipid profiles were measured, with a 72-hour continuous glucose monitoring and 24-hour Holter monitoring performed at baseline, 24, and 50 weeks for the assessments of glucose variability and heart rate variability. RESULTS: Seventeen patients with mean ± SD age 14.4 ± 2.3 years, body mass index 18.17 ± 1.81 kg/m2, median (IQR) diabetes duration 4.50 (3.58, 6.92) years, and HbA1c 9.0% (8.5%, 9.4%) were enrolled. The between-group difference in HbA1c of 0.28% (95% CI -0.39 to 0.95%) was not significant (P = 0.40). Changes in body mass index, insulin dose, blood pressure, lipid profiles, and estimated insulin sensitivity were similar for metformin add-on vs. insulin monotherapy. Glucose variability also did not differ. Compared with insulin monotherapy, metformin add-on significantly increased multiple heart rate variability parameters. CONCLUSIONS: Metformin added to insulin did not improve metabolic control or glucose variability in lean/normal-weight adolescents with type 1 diabetes. However, metformin added to insulin significantly increased heart rate variability, suggesting that metformin might improve cardiovascular autonomic function in this population.

Up-regulation of microRNA-203 inhibits myocardial fibrosis and oxidative stress in mice with diabetic cardiomyopathy through the inhibition of PI3K/Akt signaling pathway via PIK3CA.

Diabetic cardiomyopathy (DCM) refers to the myocardial dysfunction in the absence of coronary artery disease and hypertension. Recently, the role of microRNAs (miRs) in gene expression regulation has attracted much more attention. Studies have shown that the PI3K/Akt signaling pathway is involved in the growth, metabolism and apoptosis of myocardial cells. Therefore, this study aimed to explore the regulatory role of miR-203 in myocardial fibrosis in mice with DCM via involvement of the PI3K/Akt signaling pathway. Firstly, mouse model of diabetes mellitus (DM) was established and injected with agomir, antagomir or IGF-1 (PI3K/Akt signaling pathway activator) for investigating the role of miR-203 in PIK3CA and the PI3K/Akt signaling pathway. PIK3CA was identified as a target gene of miR-203, and overexpressed miR-203 inhibited the activation of PI3K/Akt signaling pathway. The obtained results indicated that up-regulation of miR-203 reduced myocardial hypertrophy, myocardial fibrosis, myocardial apoptosis, and levels of PIK3CA, PI3K, Akt, CoI I, CoI III, ANP, MDA and ROS in the myocardial tissues, by which DM-induced cardiac dysfunction and pathological changes could be ameliorated. Collectively, our present study highlighted that overexpression of miR-203 may function as a cardioprotective regulator in DCM by targeting PIK3CA via inactivation of PI3K/Akt signaling pathway.

Insulin requirement profiles and related factors of insulin pump therapy in patients with type 2 diabetes.

Continuous subcutaneous insulin infusion (CSII) is an effective therapy to control hyperglycemia in both patients with type 1 diabetes and type 2 diabetes. However, there is little data investigating the insulin dose setting during CSII therapy in type 2 diabetes to achieve optimal glycemic control and avoid the risk of hypoglycemia. Thus, this study is aimed to assess the dose characteristics of insulin requirement and explore the related clinical factors in patients with type 2 diabetes who were treated with CSII. A total of 327 patients (195 males) aged 52.9±12.5 years old were included in this study. Patients were treated with CSII to achieve the target fasting capillary blood glucose (4.4-7.0 mmol L-1) and 2-h postprandial capillary blood glucose (4.4-10.0 mmol L-1) by adjusting insulin infusion according to the seven-point capillary blood glucose profiles. Total daily insulin dose (TDD), total daily insulin dose per kilogram (TDD kg-1) and the ratio of total basal insulin dose (TBD) to TDD (%TBa) were calculated after patients achieved the glucose targets for at least 3 days via 1-2 weeks of CSII treatment. And insulin dose, insulin dosing patterns and the relevant clinical factors were analyzed. The mean ratio of basal/bolus insulin distribution of all patients was 40%:60%. Patients with central obesity needed more TDD (51.3±17.1 U versus 43.5±14.0 U, P<0.05) and TDD kg-1 (0.8±0.3 U kg-1 versus 0.7±0.2 U kg-1, P<0.05) than those without central obesity. Pearson's correlation analysis demonstrated that TDD was positively correlated with body mass index (BMI), waist circumference (WC), baseline fasting plasma glucose (FPG), fasting C-peptide level, 2 h-postprandial C-peptide level and time to achieve glycemic target (all P<0.05); TDD kg-1 was positively correlated with waist-to-hip ratio (WHR), baseline FPG, glycosylated hemoglobin A1c (HbA1c), fasting C-peptide level and time to achieve glycemic target, and negatively correlated with BMI (all P<0.05). Multiple linear regression analyses revealed that BMI (ß=1.796, P<0.01), WC (ß=0.709, P<0.01), baseline FPG (ß=1.459, P<0.01) and HbA1c (ß=0.930, P=0.021) were independently related to TDD. Gender (ß=-0.107, P=0.003), WC (ß=0.005, P=0.029), baseline FPG (ß=0.025, P<0.01) and HbA1c (ß=0.016, P=0.007) were independently associated with TDD kg-1. Gender (ß=-0.015, P=0.048) and disease duration (ß=0.134, P=0.029) were independently associated with %TBa. %TBa is around 40% in Chinese patients with type 2 diabetes treated with CSII when glycemic control is achieved. In addition to body weight or BMI, WC and glucose levels before CSII should be considered to set TDD. Patients with central obesity or poor glycemic control might need more TDD. Higher %TBa should be considered in female patients or patients with longer disease duration.

Cystatin C Is an Important Biomarker for Cardiovascular Autonomic Dysfunction in Chinese Type 2 Diabetic Patients.

BACKGROUND: Cardiovascular autonomic dysfunction is closely related to increased mortality in patients with diabetes. Previous studies have proved that cystatin C (CysC) is an important predictor of both peripheral neuropathy and cardiovascular events. However, whether CysC is also associated with cardiovascular autonomic dysfunction remains unclear. Therefore, the aim of this study was to investigate the relationship between CysC and cardiovascular autonomic dysfunction in type 2 diabetic patients without renal dysfunction. METHODS: A total of 161 type 2 diabetic patients with normal serum creatinine (less than 133 µmol/l) and estimated glomerular filtration rate (eGFR) higher than 60 ml/min per 1.73 m2 were recruited in our study. Cardiovascular autonomic dysfunction was determined by heart rate variability (HRV) measured by a 24-hour Holter monitor. Serum CysC was tested by particle-enhanced turbidimetric immunoassay, and subjects were divided into three groups based on the tertiles of CysC. Pearson correlation analysis was used to evaluate the association between different indexes, and the association of CysC with HRV indexes was assessed by multivariate linear regression analysis. RESULTS: The HRV parameters were lower in the group with the highest CysC concentration than in the groups with lower levels of CysC (P < 0.05). Pearson correlation analysis showed a negative relationship between CysC and the HRV parameters, including SDNN (r = -0.31, P < 0.001), SDANN (r = -0.25, P = 0.002), and logLF (r = -0.18, P = 0.023). Furthermore, multivariate linear regression analysis revealed that CysC was independently correlated with SDNN (ß = -24.11, P = 0.015) and SDANN (ß = -19.88, P = 0.047) after adjusting for the confounding factors of gender, age, blood pressure, body mass index, eGFR, and hemoglobin A1c. CONCLUSIONS: Serum CysC levels are associated with cardiovascular autonomic dysfunction; furthermore, CysC may be a reliable and convenient biomarker for detecting cardiovascular autonomic dysfunction.

Effect of baseline body mass index on glycemic control and weight change with exenatide monotherapy in Chinese drug-naïve type 2 diabetic patients.

BACKGROUND: The weight-reducing effect of exenatide has been proved, but too much weight loss in normal-weight patients may concern physicians. This study evaluated the effects of exenatide monotherapy on glycemic control and weight change in normal-weight, overweight, and obese patients with newly diagnosed type 2 diabetes (T2D). METHODS: In this multicenter prospective study, 29 normal-weight, 54 overweight, and 27 obese newly diagnosed and drug-naïve patients with T2D were treated with exenatide for 48 weeks. The primary efficacy endpoint was the effect of baseline body mass index (BMI) on glycemic control, measured as the change in HbA1c from baseline to Week 48 compared among different BMI groups. Other endpoints included comparisons of the effects of exenatide on fasting plasma glucose (FPG), postprandial plasma glucose (PPG), body weight, and other metabolic indices. RESULTS: After 48-week treatment, the estimated mean changes in HbA1c in normal-weight, overweight, and obese patients were -1.9%, -1.8%, and -1.5%, respectively (P = 0.290 among groups after adjustment for baseline values). There were similar declines in FPG and 0.5- and 2-hour PPG among groups. There were non-significant trends from normal-weight to overweight to obese patients for increased weight reduction (decreases of 2.2, 3.9, and 4.0 kg, respectively; P = 0.104) and changes in waist circumference (decreases of 2.2, 3.2, and 5.6 cm, respectively; P = 0.078). CONCLUSIONS: Baseline BMI had no effect on glycemic control, weight change, or other metabolic indices with exenatide monotherapy. Normal-weight patients with T2D would benefit from exenatide as much as overweight or obese patients on glucose control, without increased risk of excess weight loss.

Decreased ß-Cell Function is Associated with Cardiovascular Autonomic Neuropathy in Chinese Patients Newly Diagnosed with Type 2 Diabetes.

The influence of ß-cell function on cardiovascular autonomic neuropathy (CAN), an important diabetes-related complication, is still unclear. In this study, we aimed to investigate the association between residual ß-cell function and CAN in patients newly diagnosed with type 2 diabetes. We enrolled 90 newly-diagnosed type 2 diabetic patients and 37 participants with normal glucose tolerance as controls. The patients were divided into a CAN+ group (diabetic patients with CAN, n = 20) and a CAN- group (diabetic patients without CAN, n = 70) according to the standard Ewing battery of tests. Fasting and postprandial plasma glucose, insulin, and C-peptide were measured. Homeostasis model assessment-beta cells (HOMA-B) and HOMA-insulin resistance (IR) were calculated. The prevalence of CAN in this population was 22.2%. Compared with the CAN- group, the CAN+ group had significantly lower fasting plasma insulin (6.60 ± 4.39 vs 10.45 ± 7.82 µ/L, P = 0.029), fasting C-peptide (0.51 ± 0.20 vs 0.82 ± 0.51 nmol/L, P = 0.004), and HOMA-B (21.44 ± 17.06 vs 44.17 ± 38.49, P = 0.002). Fasting C-peptide was correlated with the Valsalva ratio (r = 0.24, P = 0.043) and the 30:15 test (r = 0.26, P = 0.023). Further analysis showed that fasting C-peptide (OR: 0.041, 95% CI 0.003-0.501, P = 0.012) and HOMA-B (OR: 0.965, 95% CI 0.934-0.996, P = 0.028) were independently associated with cardiovascular autonomic nerve function in this population. The patients with fasting C-peptide values < 0.67 nmol/L were more likely to have CAN than those with C-peptide levels ≥0.67 nmol/L (OR: 6.00, 95% CI 1.815-19.830, P = 0.003). A high prevalence of CAN was found in patients with newly-diagnosed type 2 diabetes. Decreased ß-cell function was closely associated with CAN in this population.

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.

Glycemic variability is an important risk factor for cardiovascular autonomic neuropathy in newly diagnosed type 2 diabetic patients.

BACKGROUND: The relationship between glycemic variability, another component of glycemic disorders as well as chronic sustained hyperglycemia, and cardiovascular autonomic neuropathy (CAN) has not been clarified. Our aim is to investigate the association between glycemic variability and CAN in newly diagnosed type 2 diabetic patients. METHODS: Ewing tests were performed in 90 newly diagnosed type 2 diabetic patients and 37 participants with normal glucose tolerance as control from May 1, 2009, through September 30, 2010. According to the scores from Ewing tests, diabetic patients were divided into two groups: without CAN (CAN-) and with CAN (CAN+). All participants underwent a 48-h to 72-h continuous glucose monitoring (CGM). Coefficient of variability of glycemia (%CV), mean amplitude of glycemic excursions (MAGE) and means of daily differences (MODD) were calculated with the CGM data. RESULTS: The prevalence of CAN in patients with newly diagnosed type 2 diabetes was 22.2%. An increasing trend of glycemic variability was found from control group, CAN- group to CAN+ group. MAGE in CAN+ group was significantly higher than that in CAN- group (5.27±1.99mmol/L vs. 4.04±1.39mmol/L, P=0.001). In the Logistic regression analysis, a significant relationship was shown between MAGE and CAN [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.01-2.73, P=0.018)]. The area under the receiver-operating characteristic curve for MAGE was superior to those for other dysglycemic indices in detecting CAN. CONCLUSIONS: Glycemic variability is associated with CAN in patients with newly diagnosed type 2 diabetes. Among the glycemic variability indices, MAGE is a significant indicator for detecting CAN.

[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.