The Antidepressant Effects of GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis.

AIM/HYPOTHESIS: Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may exert positive effects in patients with depression. Our aim was to conduct a systematic review and meta-analysis to examine the antidepressant effects of GLP-1RAs. METHODS: Randomized controlled trials and prospective cohort studies investigating the effects of GLP-1RAs versus placebo or other antidiabetic therapies on depressive symptoms were searched for using multiple electronic sources (CENTRAL, PubMed, EMBASE, PsycINFO, World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, China Network Knowledge Infrastructure, China Biomedical Database, Wan Fang data, and Chinese Scientific Journals Database) from inception to February 16, 2023. We utilized a random effects model to analyze standardized mean differences for the change in depression rating scales comparing GLP-1RA treated groups with control treated groups. RESULTS: The meta-analysis comprising 2,071 participants included 5 randomized controlled trials and 1 prospective cohort study. The meta-analysis indicated that the change from baseline in depression rating scale scores decreased significantly when patients received treatment with GLP-1RAs compared to control treatments (SMD = -0.12, 95% CI [-0.21, -0.03], pSMD <0.01, I2 = 0%, pQ = 0.52). The subgroup analysis showed that the effects of GLP-1RAs on depressive symptoms were consistent in patients with Type 2 diabetes mellitus (SMD = -0.12, 95% CI [-0.21, -0.03], pSMD <0.01, I2 = 2%, pQ = 0.40). CONCLUSIONS: Adults treated with GLP-1RAs showed significant reductions in the depression rating scale scores compared to those treated with control substances. Our findings suggest that GLP-1RAs may be a potential treatment for alleviating depressive symptoms in humans.

Prevalence of very high cardiovascular disease risk in patients with type 2 diabetes mellitus: A population-based cross-sectional screening study.

AIM: The 2019 ESC/EASD guidelines categorize cardiovascular disease risk (CVD) in patients with diabetes mellitus (DM). Assessing CVD risk is necessary to identify individuals at very high risk of CVD, enabling tailored and precise intervention for this high-risk population. This study aims to evaluate the severity of a very high risk for CVD stratification among patients with type 2 DM (T2DM) across different regions in China. METHODS: We conducted a cross-sectional screening study from 1 January 2020 to 30 December 2022. Disease duration, body mass index (BMI), targeted organ damage, such as atherosclerotic heart disease, proteinuria, impaired renal function, left ventricular hypertrophy, retinopathy and known CVD risk factors, were collected from diabetic patients by professionally trained physicians. The risk of CV in patients with DM was categorized into two groups: very high risk and others, according to the 2019 ESC/EASD guidelines. RESULTS: In total, 1 870 720 participants from 1669 hospitals in 30 provinces of China, excluding Tibet, Taiwan, Hong Kong and Macao, were enrolled from 2020 to 2022, among whom 67.50% of patients with T2DM were at very high risk for CVD. The proportions of very high-risk T2DM were higher in Northeast China (75.82%), Central China (73.65%) and Southwest China (72.66%), while the lowest prevalence of very high-risk T2DM was found in Southern China (60.15%). The multivariate binary logistic regression analyses suggested that the category of very high risk for CVD is associated with age [odds ratio (OR) = 1.04; 95% confidence interval (CI): 1.04-1.04; p < .0001], BMI (OR = 1.07; 95% CI: 1.07-1.07; p < .0001), duration of DM (OR = 1.05; 95% CI: 1.05-1.05; p < .0001), hypertension (OR = 3.75; 95% CI: 3.72-3.78; p < .0001), dyslipidaemia (OR = 5.22; 95% CI: 5.18-5.27; p < .0001) and smoking (OR = 2.92; 95% CI: 2.89-2.95; p < .0001). CONCLUSIONS: This study represented the largest observational study of CVD risk assessment in patients with T2DM in China. The CVD risk situation of patients with diabetes in China is critical, and comprehensive control and management of CVD risk factors, such as hypertension, BMI and dyslipidaemia, in patients with DM need to be strengthened in patients with T2DM in China.

Retagliptin as add-on therapy to metformin in Chinese 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 retagliptin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin. MATERIALS AND METHODS: This multicentre, phase 3 trial consisted of a 16-week, randomized, double-blind, placebo-controlled period, where patients with HbA1c levels between 7.5% and 11.0% were randomized to receive either once-daily (QD) retagliptin 100 mg (n = 87) or placebo (n = 87), both as an add-on to metformin. The primary endpoint was the change in HbA1c from baseline to week 16. RESULTS: At week 16, the least squares mean change in HbA1c from baseline, compared with placebo, was -0.82% (95% CI, -1.05% to -0.58%) for the retagliptin 100 mg QD group (P < .0001) per treatment policy estimand. Significantly higher proportions of patients in the retagliptin 100 mg QD group achieved HbA1c levels of less than 6.5% (11.5%) and less than 7.0% (26.4%) compared with those receiving placebo (0% and 4.6%; P = .0016 and P < .0001, respectively) at week 16. Retagliptin 100 mg QD also lowered fasting plasma glucose and 2-hour postprandial plasma glucose levels. The incidence of adverse events (AEs) during the treatment period was similar between the two groups. However, slightly higher proportions of increased lipase and increased amylase in the retagliptin 100 mg QD group were observed. No patients discontinued treatment permanently because of AEs, and no episodes of severe hypoglycaemia were reported. CONCLUSIONS: Retagliptin 100 mg QD as an add-on therapy to metformin offers a new therapeutic option for treating Chinese patients with T2D inadequately controlled by metformin alone, and is generally well tolerated.

A multicentre, prospective, non-interventional study evaluating the safety of dapagliflozin in patients with type 2 diabetes in routine clinical practice in China (DONATE).

BACKGROUND: There are few large-scale studies evaluating the safety of the sodium-glucose cotransporter-2 inhibitor, dapagliflozin, in Chinese patients with type 2 diabetes. DONATE, a multicentre, single-arm, prospective, non-interventional study, is the first real-world study evaluating the safety of dapagliflozin in Chinese patients with type 2 diabetes in routine clinical practice. METHODS: Between August 2017 and July 2020, patients with type 2 diabetes who had initiated dapagliflozin therapy and received ≥1 dose were prospectively recruited from 88 hospitals in China. Patients were subsequently followed up for 24 weeks; if patients discontinued dapagliflozin they were followed up for an additional 7 days after treatment discontinuation. The primary outcome was the proportion of patients with adverse events and serious adverse events, particularly key adverse events of special interest (AESI) including urinary tract infection, genital tract infection (typical symptoms with or without microbiological diagnosis) and hypoglycaemia (typical symptoms with or without blood glucose ≤3.9 mmol/L, or blood glucose ≤3.9 mmol/L without symptoms). Exploratory outcomes included the absolute change in metabolic parameters and the proportion of patients with other AESI including volume depletion, abnormal blood electrolytes, polyuria, renal impairment, diabetic ketoacidosis, hepatic impairment and haematuria. RESULTS: A total of 3000 patients were enrolled, of whom 2990 (99.7%) were included in the safety analysis set. Mean (SD) age was 52.6 (12.0) years, and 65.8% of patients were male. Mean (SD) duration of type 2 diabetes at enrolment was 8.4 (7.1) years. Mean (SD) treatment duration of dapagliflozin was 209.1 (157.6) days. Adverse events were reported in 35.4% (n = 1059) of patients during the 24-week follow-up period. Overall, 9.0% (n = 268) were related to treatment and 6.2% (n = 186) were serious. Urinary tract infection, genital tract infection and hypoglycaemia were reported in 2.3% (n = 70), 1.3% (n = 39) and 1.1% (n = 32) of patients, respectively. The proportion of patients with other AESI was also low: polyuria (0.7%; n = 21), volume depletion (0.3%; n = 9), renal impairment (0.3%; n = 8), hepatic impairment (0.2%; n = 7), haematuria (0.2%; n = 6) and diabetic ketoacidosis (0.1%; n = 2). CONCLUSIONS: This study demonstrated that once-daily dapagliflozin was well tolerated in Chinese patients with type 2 diabetes and the overall safety profile of dapagliflozin in clinical practice in China was consistent with that reported in clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03156985. Registered on 16 May, 2017.

Effects of treatment with Glucagon-like peptide-1 receptor agonist on prediabetes with overweight/obesity: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the effects of Glucagon-like peptide-1 receptor agonist (GLP-1RA) on prediabetes with overweight/obesity. METHODS: A search of PubMed, Embase, Cochrane Library, and Web of Science databases was performed to identify randomised controlled trials (up to 4 July 2022) which evaluated the effect of GLP-1RA on prediabetes with overweight/obesity. RESULTS: Eight hundred and nine articles were retrieved (80 from PubMed, 481 from Embase, 137 from Cochrane library, and 111 from Web of Science) and a total of 5 articles were included in this meta-analysis. More individuals in GLP-1RAs group regressed from prediabetes to normoglycemia than individuals in the placebo group (OR = 4.56, 95% CI:3.58, 5.80, P = 0.004); fewer individuals in GLP-1RAs group were diagnosed with diabetes than those in the placebo group (OR = 0.31, 95% CI:0.12,0.81, P = 0.017). Results from five studies showed that GLP-1RAs significantly reduced fasting glucose (mean difference = -0.41 mmol/L, 95% CI: -0.58, -0.25, P < 0.00001), with an acceptable heterogeneity (I2  = 42%). CONCLUSIONS: The present meta-analysis suggested that GLP-1RA significantly improves glucose metabolism, reduces systolic blood pressure and body weight in prediabetes with overweight/obesity. It could also prevent the development of diabetes and reverse abnormal glucose metabolism.

Safety and effectiveness of dulaglutide in Chinese adults with type 2 diabetes mellitus in a real-world setting: A prospective, observational post-marketing study.

AIM: To our knowledge, this is the first real-world study to investigate the safety and effectiveness of a glucagon-like peptide-1 receptor agonist in Chinese patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This prospective, observational, post-marketing study conducted at 46 hospitals in China included adults with T2DM prescribed dulaglutide in routine clinical practice. The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs) and serious AEs in patients who received ≥1 dose of dulaglutide, for up to 24 weeks. Exploratory endpoints included changes in patient-reported glycated haemoglobin (HbA1c) and body weight. Post hoc analyses and multivariate regression were also performed. RESULTS: From 20 January 2020 to 24 November 2021, 3291 patients received dulaglutide and entered the safety analysis. TEAEs were reported in 1333 (40.5%) patients; the most commonly reported were nausea (n = 193, 5.9%), diarrhoea (n = 183, 5.6%) and decreased appetite (n = 179, 5.4%). serious AEs were reported in 160 (4.9%) patients. TEAEs led to treatment discontinuation in 212 (6.4%) patients. The mean absolute change in HbA1c from baseline to week 24 was -1.65% (p < .001). Greater reductions in HbA1c at week 24 were observed in patients with T2DM duration ≤5 years (p = .002), baseline HbA1c ≥8.5% (p < .001), and without atherosclerotic cardiovascular disease (p = .002). The mean absolute change in body weight from baseline at week 24 was -2.62 kg (p < .001). CONCLUSION: Dulaglutide showed a safety profile consistent with previous reports and significantly reduced HbA1c in a real-world setting. These findings support the clinical use of dulaglutide and inform the individualized treatment of patients with T2DM in China.

Efficacy and safety of basal-first titration order in individuals with type 2 diabetes receiving short-term intensive insulin therapy: An exploratory analysis of BEYOND V.

AIMS: To present the results of an exploratory analysis of the BEYOND V study in which Chinese individuals with uncontrolled type 2 diabetes (T2D) received short-term intensive insulin therapy (SIIT) during study run-in (prior to randomization) using a basal-first insulin titration method. MATERIALS AND METHODS: This was exclusively an exploratory analysis of the 7- to 10-day run-in period of BEYOND V. Participants were hospitalized and had oral therapies withdrawn (except metformin). They received SIIT with once-daily insulin glargine and three-times-daily premeal insulin glulisine, titrated daily from a total starting dose of 0.4 to 0.5 units/kg/d, first adjusting insulin glargine to achieve fasting blood glucose (FBG) of 4.4 to 6.1 mmol/L (79 to 119 mg/dL), then insulin glulisine to achieve pre-meal blood glucose of 4.4 to 6.1 mmol/L. Key outcomes were the proportions of participants achieving FBG and 2-hour postprandial blood glucose (PBG) targets. RESULTS: Overall, 397 entered the run-in (mean 54.2 years, 235 males [59.2%]). At the end of SIIT, 374/396 participants (94.4%) had both FBG <7.0 mmol/L (<126 mg/dL) and 2-hour PBG <10 mmol/L (<180 mg/dL) and 282/396 (71.2%) had both FBG <6.1 mmol/L (<100 mg/dL) and 2-hour PBG <10 mmol/L. The mean first time taken to achieve FBG <7 mmol/L, 2-hour PBG <10 mmol/L, and both, was 4.35, 3.88, and 5.04 days, respectively. Hypoglycaemia occurred in 99 participants (24.9%). There was no severe hypoglycaemia. CONCLUSIONS: Titrating basal insulin first is an effective and safe method of SIIT in individuals with T2D, rapidly achieving target glucose levels with a relatively low rate of hypoglycaemia.

Paternal sleep deprivation induces metabolic perturbations in male offspring via altered LRP5 DNA methylation of pancreatic islets.

Diabetes and metabolic perturbation are global health challenges. Sleep insufficiency may trigger metabolic dysregulation leading to diabetes. However, the intergenerational transmission of this environmental information is not clearly understood. The research objective was to determine the possible effect of paternal sleep deprivation on the metabolic phenotype of the offspring and to investigate the underlying mechanism of epigenetic inheritance. Male offspring of sleep-deprived fathers exhibit glucose intolerance, insulin resistance, and impaired insulin secretion. In these SD-F1 offspring, a reduction in beta cell mass and proliferation of beta cells were observed. Mechanistically, in pancreatic islets of SD-F1 offspring, we identified alterations in DNA methylation at the promoter region of the LRP5 (LDL receptor related protein 5) gene, a coreceptor of Wnt signaling, resulting in downregulation of downstream effectors cyclin D1, cyclin D2, and Ctnnb1. Restoration of Lrp5 in the pancreas of SD-F1 male mice could improve impaired glucose tolerance and expression of cyclin D1, cyclin D2, and Ctnnb1. This study might significantly contribute to our understanding of the effects of sleeplessness on health and metabolic disease risk from the perspective of the heritable epigenome.

The effect of statin adherence on patients with type 2 diabetes after percutaneous coronary intervention for acute coronary syndrome.

PURPOSE: To investigate the effect of long-term statin adherence among patients with type 2 diabetes mellitus (T2DM) after percutaneous coronary intervention (PCI) for acute coronary syndrome. MAIN OUTCOME MEASURES: All-cause readmission after initial PCI intervention was defined as the main outcome of the study. Readmission for revascularization, cerebrovascular disease, and so on among the study population was analyzed as secondary outcomes. METHODS: A total of 11,172 patients with T2DM who underwent PCI for ACS were selected from the Beijing Basic Medical Insurance Database for urban employees between January 1, 2014, and December 31, 2018. Patients' long-term adherence to statin utilization was investigated during a 3-year follow-up period through survival analysis after adjusting for covariates, including outpatient medications for secondary prevention of coronary heart disease and other complications. RESULTS: Among patients, 29.7% showed a high level of adherence in terms of statin utilization after 3 years of follow-up. High statin utilization adherence was associated with a reduction in all-cause hospitalization rates compared to those with low levels of adherence (62.72% vs. 68.18%; HR, 0.85 [95% CI, 0.80-0.90], P < 0.0001). For secondary outcomes, a high level of statin adherence showed a protective effect as well: readmission rate for revascularization (49.56% vs. 53.96%, HR, 0.87 [95% CI, 0.82-0.93], P < 0.0001), readmission rate for cerebrovascular disease (6.78% vs. 10.17%, HR, 0.65 [95% CI, 0.55-0.76], P < 0.0001), and diabetes-related readmissionrate (11.05% vs. 14.81%, HR, 0.69 [95% CI, 0.61-0.79], P < 0.0001). CONCLUSION: In Beijing, long-term statin adherence among patients with T2DM after PCI is still not high, and the incidence of all-cause readmission, revascularization and cerebrovascular disease may be reduced through improving statin adherence.

Two-dimensional ambipolar carriers of giant density at the diamond/cubic-BN(111) interfaces: toward complementary logic and quantum applications.

The extremely difficult ambipolar doping activation greatly hinders the outstanding performance of diamond for electronic devices. The main concern has been devoted to surface conduction by two-dimensional (2D) carriers. 2D hole gas (2DHG) in the diamond is induced by surface transfer doping dominated by the adsorbate's status and faces stability issues. Meanwhile, a feasible way to generate the other essential ambipolar carrier-2D electron gas (2DEG) is still lacking. We propose that the well-lattice-matched diamond/cBN(111) interfaces can spontaneously induce 2D ambipolar carriers with a giant density of 4.17 × 1014 cm-2, an order higher than other competitors. 2DEG and 2DHG can be separately achieved near the hetero-interfaces consisting of C-N and C-B bonds, respectively. Interestingly, the robust 2D charges are derived from a novel bulk-induced polarization-discontinuity at the interfaces, which can be attributed to an unexpected non-zero formal polarization of centrosymmetric cBN along the [111] direction. The existence of 2D ambipolar carriers at the diamond/cBN(111) interfaces has resolved the missing n-type conduction in diamond, thus opening up possibilities for complementary logic applications. Additionally, the high density of quantum-confined 2D ambipolar carriers provides an excellent platform for strongly correlated systems, which could lead to novel quantum information processing applications.

Scattering of arbitrarily incident Laguerre-Gaussian vortex electromagnetic beams by electrically large-scaled complex targets.

We implement an algorithm, termed parallel-processing physical optics, providing an efficient high-frequency approximation method to characterize the scattering of Laguerre-Gaussian (LG) vortex electromagnetic (EM) beams by electrically large-scaled complex targets. The incident beam is described by vector expressions in terms of electric and magnetic fields, and it is combined with rotation Euler angles to achieve an arbitrary incidence of the vortex beam. The validity and capability of the proposed method are illustrated numerically, and the effects of various beam parameters as well as target geometric models such as a blunt cone and Tomahawk-A missile on monostatic and bistatic radar cross section distributions are investigated. Results show that the scattering features of the vortex beam vary significantly with the parameters of the vortex beam and the target. These results are helpful to reveal the scattering mechanism of LG vortex EM beams and provide a reference for the application of vortex beams to detect electrically large-scaled targets.

Unveiling detection probability for multi-Gaussian correlated anomalous vortex modes in maritime atmospheric turbulence.

In this study, we employ the Rytov approximation to investigate the detection probability of orbital angular momentum (OAM) in multi-Gaussian correlated anomalous vortex (MGCAV) beams under non-Kolmogorov maritime atmospheric turbulence. Our results demonstrate that the OAM detection probability of a MGCAV beam is influenced by various factors, including beam parameters and the characteristics of maritime atmospheric turbulence. Specifically, an increase in propagation distance, beam order, and beam index, or a decrease in inner scale, spatial coherence width, and non-Kolmogorov parameter, leads to a decrease in the OAM detection probability. The phase characteristics of partially coherent vortex modes are affected by both atmospheric turbulence phase and initial random phase, resulting in reduced robustness compared to fully coherent vortex modes. Furthermore, a comparative analysis between Gaussian-Schell correlated anomalous vortex (GSCAV) beams and MGCAV beams reveals the superior resilience of GSCAV beams in mitigating the impact of maritime atmospheric turbulence. Moreover, specific combinations of beam order, topological charge, and beam waist, or the optimal beam width, yield maximum OAM detection probability or minimum scintillation. These findings provide valuable insights applicable to optical communication, particularly in scenarios above sea and ocean levels.

Association of carotid intima-media thickness with periodontitis may depend on glycemic control.

BACKGROUND: There is evidence indicating that atherosclerosis is associated with periodontitis, especially in those with diabetes. The purpose of the present study was to determine whether glycemic control influences such association. METHODS: Cross-sectional data on 214 patients diagnosed with type 2 diabetes mellitus were obtained including results of basic laboratory tests, a periodontal examination, and carotid measurements. The association of periodontal parameters and carotid intima-media thickness (cIMT) or carotid plaque (CP) was evaluated in subgroups. RESULTS: Mean cIMT was significantly correlated with mean PLI, mean BI or number of PD ≥4 mm in the whole sample and the group with poor glycemic control. In the group with good glycemic control, however, only the number of PD ≥4 mm was associated with mean cIMT. A multiple logistic regression analysis also revealed that each 1 increase in mean PLI, mean BI or number of PD ≥4 mm was correlated with an increased cIMT in the whole sample. CONCLUSIONS: In addition to confirming the relationship between periodontitis and atherosclerosis, our study found a stronger association in groups with poor glycemic control compared to those with good glycemic control, suggesting that blood glucose modifies the association between periodontitis and arterial injury.

Assessment of the impact of shift work on thyroid disorders: a systematic review and meta-analysis.

PURPOSE: Shift work including night work is a common work pattern worldwide and researchers have no consensus on the impact of shift work on thyroid disorders. We aimed to conduct a meta-analysis to summarize the evidence from published studies to ascertain the impact of shift work on thyroid disorders. METHODS: Studies on the link between shift work and thyroid disorders published in Pubmed, Embase, Medline, and Cochrane databases by September 2021 were searched. Newcastle-Ottawa scale was used to assess the quality of included studies. The Mantel-Haenszel statistical method and the inverse-variance statistical method were used to evaluate the pooled results of dichotomous and continuous variables, respectively. Study heterogeneity analysis was performed using I2 statistics. Sensitivity analysis was conducted by omitting one study each time and re-calculating the pooled results of the remaining studies. RESULTS: Seven eligible studies were included in the systematic review and meta-analysis. The results showed that shift work would lead to an increase in TSH (SMD: 0.30; 95%CI: 0.05-0.55; P = 0.02; I2 = 64%) and FT4 (SMD: 0.21; 95%CI: 0.02-0.40; P = 0.03; I2 = 0%). However, shift work had no clear effect on the risk of positive thyroid autoantibodies (OR: 1.26; 95%CI: 0.62-2.55; P = 0.52; I2 = 63%). CONCLUSION: Shift work may be associated with abnormal TSH and FT4 levels. Thyroid health is affected in shift workers and it is advisable to remind patients to get good sleep the night before testing thyroid function.

Biomechanical Evaluation of Rigid Interspinous Process Fixation Combined With Lumbar Interbody Fusion Using Hybrid Testing Protocol.

Rigid interspinous process fixation (RIPF) has been recently discussed as an alternative to pedicle screw fixation (PSF) for reducing trauma in lumbar interbody fusion (LIF) surgery. This study aimed to investigate biomechanics of the lumbar spine with RIPF, and also to compare biomechanical differences between two postoperative stages (before and after bony fusion). Based on an intact finite-element model of lumbosacral spine, the models of single-level LIF with RIPF or conventional PSF were developed and were computed for biomechanical responses to the moments of four physiological motions using hybrid testing protocol. It was found that compared with PSF, range of motion (ROM), intradiscal pressure (IDP), and facet joint forces (FJF) at adjacent segments of the surgical level for RIPF were decreased by up to 8.4%, 2.3%, and 16.8%, respectively, but ROM and endplate stress at the surgical segment were increased by up to 285.3% and 174.3%, respectively. The results of comparison between lumbar spine with RIPF before and after bony fusion showed that ROM and endplate stress at the surgical segment were decreased by up to 62.6% and 40.4%, respectively, when achieved to bony fusion. These findings suggest that lumbar spine with RIPF as compared to PSF has potential to decrease the risk of adjacent segment degeneration but might have lower stability of surgical segment and an increased risk of cage subsidence; When achieved bony fusion, it might be helpful for the lumbar spine with RIPF in increasing stability of surgical segment and reducing failure of bone contact with cage.

Thyroid stimulating hormone aggravates diabetic retinopathy through the mitochondrial apoptotic pathway.

Diabetic retinopathy (DR) is a common complication of diabetes mellitus. High glucose-induced mitochondrial apoptosis is involved in the loss of retinal pericytes (PCs), which is considered to be a predominant pathologic change of diabetic retinopathy (DR). A high thyroid stimulating hormone (TSH) serum level is associated with an increased prevalence of DR in diabetic patients. Here, we investigated whether TSH regulated glucose-induced PCs loss through TSH-receptor (TSHR)-dependent mitochondrial apoptosis. First, the serum TSH level was found to be an independent risk factor for DR in Type 2 diabetic study participants (odds ratio = 2.294; 95% confidence interval: 1.925-2.733; p ≤ 0.001). Second, human PCs were treated with different concentrations of glucose, with or without bovine TSH (b-TSH). Glucose induced mitochondrial apoptosis through various mechanisms, including through regulating the expression of apoptosis-related proteins and inducing mitochondrial dysfunction, which could be deteriorated by costimulation of glucose and b-TSH. Additionally, we detected functional TSHR in PCs; blocking TSHR significantly restricted TSH-induced apoptosis. Thus, the presence of functional TSHR in human retinal PCs may facilitate the effect of high TSH on high glucose-induced PCs loss through TSHR-dependent mitochondrial apoptosis.

Scattering of partially coherent vortex beam by rough surface in atmospheric turbulence.

A double-passage propagation model of partially coherent Laguerre-Gaussian (LG) vortex beams with orbital angular momentum (OAM) modes in turbulent atmosphere after scattering from Gaussian rough surfaces was formulated. Rough surface scattering had a weak effect on the spreading of a vortex beam in turbulent atmosphere. However, it severely influenced the phase on this beam, rapidly reducing the original OAM mode's relative intensity. The OAM spectrum information is more useful than the intensity information for rough surface object remote sensing. Additionally, by comparing the scattering intensity in monostatic and bistatic systems, the enhanced backscatter of vortex beams from Gaussian rough surfaces was verified.

Time-Restricted Feeding Restored Insulin-Growth Hormone Balance and Improved Substrate and Energy Metabolism in MC4RKO Obese Mice.

BACKGROUND: Dysregulation of metabolic regulatory hormones often occurs during the progress of obesity. Key regulatory hormone insulin-growth hormone (GH) balance has recently been proposed to maintain metabolism profiles. Time-restricted feeding (TRF) is an effective strategy against obesity without detailed research on pulsatile GH releasing patterns. METHODS: TRF was performed in an over-eating melanocortin 4 receptor-knockout (MC4RKO) obese mouse model using normal food. Body weight and food intake were measured. Series of blood samples were collected for 6-h pulsatile GH profile, glucose tolerance test, and insulin tolerance test at 5, 8, and 9 weeks of TRF, respectively. Indirect calorimetric recordings were performed by the Phenomaster system at 6 weeks for 1 week, and body composition was measured by nuclear magnetic resonance spectroscopy (NMR). Substrate- and energy metabolism-related gene expressions were measured in terminal liver and subcutaneous white adipose tissues. RESULTS: TRF increased pulsatile GH secretion in dark phase and suppressed hyperinsulinemia in MC4RKO obese mice to reach a reduced insulin/GH ratio. This was accompanied by the improvement in insulin sensitivity, metabolic flexibility, glucose tolerance, and decreased glucose fluctuation, together with appropriate modification of gene expression involved in substrate metabolism and adipose tissue browning. NMR measurement showed that TRF decreased fat mass but increased lean mass. Indirect calorimeter recording indicated that TRF decreased the respiratory exchange ratio (RER) reflecting consumption of more fatty acid in energy production in light phase and increased the oxygen consumption during activities in dark phase. CONCLUSIONS: TRF effectively decreases hyperinsulinemia and restores pulsatile GH secretion in the overeating obese mice with significant improvement in substrate and energy metabolism and body composition without reducing total caloric intake.

Rotating Day and Night Disturb Growth Hormone Secretion Profiles, Body Energy Metabolism, and Insulin Levels in Mice.

BACKGROUND: Insulin and growth hormone (GH) - 2 vital metabolic regulatory hormones - regulate glucose, lipid, and energy metabolism. These 2 hormones determine substrate and energy metabolism under different living conditions. Shift of day and night affects the clock system and metabolism probably through altered insulin and GH secretion. METHODS: Five-week-old male mice were randomly assigned to a rotating light (RL) group (3-day normal light/dark cycle followed by 4-day reversed light/dark cycle per week) and normal light (NL) group. Body weight and food intake were recorded every week. Series of blood samples were collected for pulsatile GH analysis, glucose tolerance test, and insulin tolerance test at 9, 10, and 11 weeks from the start of intervention, respectively. Indirect calorimetric measurement was performed, and body composition was tested at 12 weeks. Expressions of energy and substrate metabolism-related genes were evaluated in pituitary and liver tissues at the end of 12-week intervention. RESULTS: The RL group had an increased number of GH pulsatile bursts and reduced GH mass/burst. RL also disturbed the GH secretion regularity and mode. It suppressed insulin secretion, which led to a disturbed insulin/GH balance. It was accompanied by the reduced metabolic flexibility and modified gene expression involved in energy balance and substrate metabolism. Indirect calorimeter recording revealed that RL decreased the respiratory exchange ratio (RER) and oxygen consumption at the dark phase, which resulted in an increase in fat mass and free fatty acid levels in circulation. CONCLUSION: RL disturbed pulsatile GH secretion and decreased insulin secretion in male mice with significant impairment in energy, substrate metabolism, and body composition.

Efficacy and safety of a basal insulin + 2-3 oral antihyperglycaemic drugs regimen versus a twice-daily premixed insulin + metformin regimen after short-term intensive insulin therapy in individuals with type 2 diabetes: The multicentre, open-label, randomized controlled BEYOND-V trial.

AIM: To compare the efficacy and safety of basal insulin glargine 100 units/ml (Gla) + 2-3 oral antihyperglycaemic drugs (OADs) with twice-daily premixed insulin aspart 70/30 (Asp30) + metformin (MET) after short-term intensive insulin therapy in adults with type 2 diabetes in China. MATERIALS AND METHODS: This open-label trial enrolled insulin-naïve adults with type 2 diabetes and an HbA1c of 7.5%-11.0% (58-97 mmol/mol) despite treatment with 2-3 OADs. All participants stopped previous OADs except MET, then received short-term intensive insulin therapy during the run-in period, when those with a fasting plasma glucose of less than 7.0 mmol/L and 2-hour postprandial glucose of less than 10.0 mmol/L were randomized to Gla + MET + a dipeptidyl peptidase-4 inhibitor or twice-daily Asp30 + MET. If HbA1c was more than 7.0% (>53 mmol/mol) at week 12, participants in the Gla group were added repaglinide or acarbose, at the physician's discretion, and participants in the Asp30 group continued to titrate insulin dose. The change in HbA1c from baseline to week 24 was assessed in the per protocol (PP) population (primary endpoint). RESULTS: There were 384 enrollees (192 each to Gla and Asp30); 367 were included in the PP analysis. The threshold for non-inferiority of Gla + OADs versus Asp30 + MET was met, with a least squares mean change from baseline in HbA1c of -1.72% and -1.70% (-42.2 and -42.1 mmol/mol), respectively (estimated difference -0.01%; 95% CI -0.20%, 0.17% [-0.1 mmol/mol; 95% CI -2.2, 1.9]). Achievement of HbA1c less than 7.0% (<53 mmol/mol) was comparable between the groups (60% vs. 57%). The proportion of participants with any (24% vs. 38%; P = .003), symptomatic (19% vs. 31%; P = .007) or confirmed hypoglycaemia (18% vs. 33%; P < .001) was lower in the Gla + OADs group. CONCLUSIONS: Compared with Asp30 + MET, Gla + 2-3 OADs showed similar efficacy but a lower hypoglycaemia risk in Chinese individuals with type 2 diabetes who had undergone short-term intensive insulin therapy.