The effects of economic status on metabolic control in type 2 diabetes mellitus at 10 metabolic management centers in China.

OBJECTIVE: This study investigated the association of economic status with metabolic index control in type 2 diabetes mellitus (T2DM) patients. METHODS: In total, 37 454 T2DM patients from 10 National Metabolic Management Centers in China were recruited and categorized into two groups: a high-gross domestic product (GDP) group (n = 23 993) and a low-GDP group (n = 13 461). Sociodemographic characteristics, medical histories, and lifestyle factors were recorded. Logistic regression and interaction analysis were performed to evaluate the association of economic status and healthy lifestyle with metabolic control. RESULTS: Compared to the low-GDP group, there were fewer patients with glycated hemoglobin (HbA1c) levels ≥7% in the high-GDP group. Fewer patients with a high GDP had an abnormal metabolic state (HbA1c ≥ 7%, blood pressure [BP] ≥130/80 mm Hg, total cholesterol [TCH] ≥4.5 mmol/L or body mass index [BMI] ≥24 kg/m2 ). The risks of developing HbA1c ≥ 7% (odds ratios [OR] = 0.545 [95% CI: 0.515-0.577], p < .001), BP ≥ 130/80 mm Hg (OR = 0.808 [95% CI: 0.770-0.849], p < .001), BMI ≥ 24 kg/m2 (OR = 0.840 [95% CI: 0.799-0.884], p < .001), and an abnormal metabolic state (OR = 0.533 [95% CI: 0.444-0.636], p < .001) were significantly lower in the high-GDP group even after adjustment for confounding factors. Younger participants; those with a family history of diabetes, normal weight, and a physical activity level up to standard; and those who did not drink alcohol in the high-GDP group were predisposed to better glycemic levels. CONCLUSIONS: T2DM patients in economically developed regions had better metabolic control, especially glycemic control. A healthy lifestyle had an additive effect on achieving glycemic goals, even among high-GDP patients.

Association of visceral fat area or BMI with arterial stiffness in ideal cardiovascular health metrics among T2DM patients.

BACKGROUND: "Obesity paradox" occurs in type 2 diabetes mellitus (T2DM) patients when body mass index (BMI) is applied to define obesity. We examined the association of visceral fat area (VFA) as an obesity measurement with arterial stiffness in seven ideal cardiovascular health metrics (ICVHMs). METHODS: A total of 29 048 patients were included in the analysis from June 2017 to April 2021 in 10 sites of National Metabolic Management Centers. ICVHMs were modified from the recommendations of the American Heart Association. Brachial-ankle pulse wave velocity (BaPWV) ≥ 1400 cm/s was employed to evaluate increased arterial stiffness. Multivariate regression models were used to compare the different effects of BMI and VFA on arterial stiffness. RESULTS: Lower VFA was more strongly associated with low BaPWV than lower BMI when other ICVHMs were included (adjusted odds ratio [OR], 0.85 [95% confidence interval [CI], 0.80-0.90] vs OR 1.08 [95% CI, 1.00-1.17]). Multivariable-adjusted ORs for arterial stiffness were highest in patients with the VAT area VFA in the range of 150-200 cm2 (adjusted OR, 1.26 [95% CI 1.12-1.41]). Compared with participants with VAT VFA < 100 cm2 , among participants with higher VAT VFA, the OR for arterial stiffness decreased gradually from 1.89 (95% CI, 1.73-2.07) in patients who had ≤1 ICVHM to 0.39 (95% CI, 0.25-0.62) in patients who had ≥5 ICVHMs. CONCLUSION: In patients with T2DM, using VAT for anthropometric measures of obesity, VFA was more relevant to cardiovascular risk than BMI in the seven ICVHMs. For anthropometric measures of obesity in the ICVHMs to describe cardiovascular risk VFA would be more optimal than BMI.

Fotagliptin monotherapy with alogliptin as an active comparator in patients with uncontrolled type 2 diabetes mellitus: a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. TRIAL REGISTRATION: ClinicalTrail.gov NCT05782192.

[Establishment and Evaluation of a Nomogram Prediction Model for the Risks of Nontraumatic Fracture in Older Adults with Type 2 Diabetes Mellitus].

Objective: To analyze the risk factors for nontraumatic fractures in older adults with type 2 diabetes mellitus, to establish a nomogram prediction model, and to evaluate the model. Methods: The clinical data of 278 older adults with type 2 diabetes mellitus were collected as the modeling group, and the clinical data of 109 older adults with type 2 diabetes mellitus were collected as the validation group. In both groups, patients were divided into a fracture subgroup and a non-fracture subgroup according to whether there were nontraumatic fractures after patients developed type 2 diabetes mellitus. Multivariate logistic regression was done to identify factors influencing the risks of non-traumatic fracture in older patients with type 2 diabetes mellitus. R software was used to construct a nomogram prediction model, and then the accuracy and clinical validity of the nomogram (area under the ROC curve, H-L fit curve, and calibration curve) were evaluated. Results: In the modeling group, the incidence of nontraumatic fractures in older adults with type 2 diabetes mellitus was 24.46% (68/278). The two subgroups showed significant differences in age, diabetic peripheral neuropathy, smoking history, drinking history, serum triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glycated hemoglobin (HbA1c), and hypertension history ( P<0.05). Age, diabetic peripheral neuropathy, HbA1c and history of hypertension were independent risk factors for nontraumatic fractures in older patients with type 2 diabetes mellitus ( P<0.05). A nomogram prediction model was constructed accordingly and the internal verification results of the prediction model were as follows: the area under the ROC curve was 0.774 (0.680-0.869), the slope of the calibration curve was close to 1, and the H-L fit curve was χ 2=12.643, P=0.125. External validation was conducted with the patients in the validation group. The results showed that the area under the ROC curve was 0.780 (0.670-0.890). The prediction probability of the calibration curve was close to the actual probability, suggesting that the model had good discrimination and accuracy. Conclusion: Age, diabetic peripheral neuropathy, HbA1c, and hypertension history are independent risk factors for nontraumatic fractures in older adults with type 2 diabetes mellitus, and the prediction model established consequently has high accuracy and discrimination. Medical workers can take preventive measures based on individual patient factors to reduce the possibility of nontraumatic fractures in older adults with type 2 diabetes mellitus.

Kidney disease parameters, metabolic goal achievement, and arterial stiffness risk in Chinese adult people with type 2 diabetes.

BACKGROUND: To investigate the arterial stiffness (AS) risk within urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) categories and the joint effect between kidney disease parameters and metabolic goal achievement on AS risk in adult people with type 2 diabetes (T2D). METHODS: A total of 27 439 Chinese participants with T2D from 10 National Metabolic Management Centers (MMC) were categorized into four albuminuria/decreased eGFR groups. The criteria for decreased eGFR and AS were eGFR <90 ml/min/1.73 m2 and brachial-ankle pulse wave velocity value >the 75th percentile (1770.0 cm/s). Three metabolic goals were defined as glycated hemoglobin <7%, BP <130/80 mmHg, andlow-density lipoprotein cholesterol <2.6 mmol/L. RESULTS: After full adjustment, odds ratios (ORs) for AS were highest for albuminuria and decreased eGFR (2.23 [1.98-2.52]) and were higher for albuminuria and normal eGFR (1.52 [1.39-1.67]) than for those with nonalbuminuria and decreased eGFR (1.17 [1.04-1.32]). Both UACR and eGFR in the subgroup or overall population independently correlated with AS risk. The achievement of ≥2 metabolic goals counteracted the association between albuminuria and AS risk (OR: 0.93; 95% CI: 0.80-1.07; p = .311). When the metabolic goals added up to ≥2 for patients with decreased eGFR, they showed significantly lower AS risk (OR: 0.65; 95% CI: 0.56-0.74; p < .001). CONCLUSIONS: Both higher UACR and lower eGFR are determinants of AS risk, with UACR more strongly related to AS than eGFR in adults with T2D. The correlation between albuminuria/decreased eGFR and AS was modified by the achievement of multiple metabolic elements.

Follow-up frequency and clinical outcomes in patients with type 2 diabetes: A prospective analysis based on multicenter real-world data.

BACKGROUND: To determine whether the follow-up frequency for type 2 diabetes mellitus (T2DM) patients in the National Metabolic Management Centers (MMCs) leads to different clinical outcomes. METHODS: A total of 19 908 T2DM patients with at least 6 months of facility-based follow-up were recruited in MMCs between June 2017 and April 2021 and divided into lower-frequency and higher-frequency follow-up (LFF and HFF) groups according to the median follow-up frequency of 2.0 (interquartile range 1.2) times per year. Metabolic parameters at baseline and at the last follow-up visit were analyzed. Multivariable linear regression models were performed to assess the relationship between follow-up frequency and between-group percentage changes, adjusting for the major covariables. Additional stratified analyses were conducted to evaluate the metabolic outcomes in the subgroups. RESULTS: The characteristics of the participants in the LFF and HFF groups were significantly different at baseline. Participants had significant improvements in multiple metabolic parameters after follow-up. Patients with HFF showed significantly greater decrease in percentage changes of fasting blood glucose (-4.95% ± 37.96% vs -2.21% ± 43.08%, P < .0001) and glycosylated hemoglobin (HbA1c) (-12.14% ± 19.78% vs -9.67% ± 20.29%, P < .0001) after adjustments compared to those with LFF. Furthermore, stratification analyses showed that significant between-group percentage changes of HbA1c were observed in those with younger age (<55 years) and higher HbA1c (>9%) at baseline (P for interaction <.001). CONCLUSIONS: HFF is associated with better metabolic outcomes. Participants, especially with younger age or worse HbA1c at baseline in the HFF group achieved better glycemic control than those in the LFF group.

Effects of basal and premixed insulin on glycemic control in type 2 diabetes patients based on multicenter prospective real-world data.

BACKGROUND: To investigate the different efficacies of glycemic control between basal and premixed insulin in participants with type 2 diabetes (T2DM) when non-insulin medications fail to reach treatment targets. METHODS: This was a prospective, large-scale, real-world study at 10 diabetes centers in China. Between June 2017 and June 2021, we enrolled 1104 T2DM participants initiated with either once-daily basal insulin or twice-daily premixed insulin when the glycosylated hemoglobin (HbA1c) control target was not met after at least two non-insulin agents were administered. A Cox proportional hazards regression model adjusting for multiple influencing factors was performed to compare the different effects of basal and premixed insulin on reaching the HbA1c control target. RESULTS: At baseline, basal insulin (57.3%) was prescribed more frequently than premixed insulin (42.7%). Patients with a higher body mass index (BMI) or higher HbA1c levels were more likely to receive premixed insulin than basal insulin (both p < 0.001). After a median follow-up of 12.0 months, compared to those with premixed insulin, the hazard ratio for reaching the HbA1c target to those with basal insulin was 1.10 (95% CI, 0.92-1.31; p = 0.29) after adjustment, and less weight gain was observed in those with basal insulin than with premixed insulin (percentage change of BMI from baseline -0.37[5.50]% vs 3.40[6.73]%, p < 0.0001). CONCLUSIONS: In this real-world study, once-daily basal insulin was more frequently prescribed and had similar glycemic control effects but less weight gain compared with twice-daily premixed insulin when used as initiation therapy for those in whom glycemic control with non-insulin medications failed.

Association of sedentary time and carotid atherosclerotic plaques in patients with type 2 diabetes.

BACKGROUND: Atherosclerosis is a common complication in patients with type 2 diabetes (T2DM). Multiple factors are involved in the development and progress of atherosclerosis. We evaluated the association of weekly sedentary time (WST) with carotid plaque formation. METHODS: After data cleaning, a total of 26 664 participants with T2DM from 10 National Metabolic Management Centers (MMCs) from June 2017 to April 2021 were enrolled. Self-reported lifestyle data including WST, sleeping time, smoking and drinking information, carotid artery ultrasound, and biochemical parameters were obtained. The independent association of carotid plaue with sedentary and other lifestyle behaviors was evaluated using multivariable logistic regression models, and odds ratio (OR) with 95% confidence interval (CI) were reported. Moreover, stratified analysis was conducted to demonstrate the influence of confounding factors. RESULTS: The mean (SD) age of the participants was 54.0 (11.6) years, and the median (interquartile range) WST was 35.0 (21.0, 42.0) h. Comparing with participants in the first tertile of WST, those in the second or third tertile of WST were younger and with a shorter duration of diabetes. There were positive associations between longer sedentary time and odds of artery plaque after adjustment, with corresponding ORs in the second and third tertile were 1.40 (95% CI: 1.31-1.50) and 1.67 (95% CI: 1.56-1.79), respectively. However, the effect of WST on plaque in patients aged 18-40 years old had no statistical significance; the p value in the third tertile was 0.163. CONCLUSIONS: In summary, higher WST appears to be associated with higher prevalence of carotid plaque in patients with T2DM, especially in aged populations.

[Knockdown of long non-coding RNA actin filament-associated protein 1 antisense RNA1 (AFAP1-AS1) inhibits epithelial-mesenchymal transition, invasion and migration of TPC-1 papillary thyroid cancer cells].

Objective To detect the expression of long non-coding RNA (lncRNA) actin filament-related protein 1 antisense RNA1 (AFAP1-AS1) in papillary thyroid carcinoma tissue, and to investigate the effects of the knockdown of AFAP1-AS1 in TPC-1 papillary thyroid carcinoma cells on cell epithelial-mesenchymal transition (EMT) and related molecular mechanism in TPC-1 cells. Methods Real-time quantitative PCR was used to detect the expression of lncRNA AFAP1-AS1 in 60 cases of papillary thyroid carcinoma tissues. RNA interfering (RNAi) was used to knockdown AFAP1-AS1 in TPC-1 cells. TPC-1 cells were divided into AFAP1-AS1 knockdown (shAFAP1-AS1) group, negative control RNA (shNC) group and untransfected control group. The colony-formation assay, TranswellTM invasion and scratch healing assays were employed to detect the colony-forming ability, cell invasion ability and cell migration ability of TPC-1 cells, respectively. After knockdown of AFAP1-AS1, real-time quantitative PCR and Western blot analysis were used to detect the mRNA and protein levels of E-cadherin, vimentin, ß-catenin and snail2, respectively. Results Compared with the paracancerous tissue, the expression level of AFAP1-AS1 mRNA in the papillary thyroid carcinoma tissue significantly increased. Knockdown of AFAP1-AS1 significantly reduced the colony-forming ability, invasion and migration ability of TPC-1 cells. Compared with shNC group and control group, knockdown of AFAP1-AS1 significantly reduced the mRNA and protein expression of snail2, vimentin and ß-catenin. In contrast, the mRNA and protein expression of E-cadherin increased considerably. Conclusion The lncRNA AFAP1-AS1 is highly expressed in papillary thyroid carcinoma tissue. After knockdown of AFAP1-AS1 in TPC-1 cells, the colony-forming ability, invasion and migration ability of cancer cells are significantly down-regulated, which may be related to the inhibition of EMT.

Artificial intelligence-enabled screening for diabetic retinopathy: a real-world, multicenter and prospective study.

INTRODUCTION: Early screening for diabetic retinopathy (DR) with an efficient and scalable method is highly needed to reduce blindness, due to the growing epidemic of diabetes. The aim of the study was to validate an artificial intelligence-enabled DR screening and to investigate the prevalence of DR in adult patients with diabetes in China. RESEARCH DESIGN AND METHODS: The study was prospectively conducted at 155 diabetes centers in China. A non-mydriatic, macula-centered fundus photograph per eye was collected and graded through a deep learning (DL)-based, five-stage DR classification. Images from a randomly selected one-third of participants were used for the DL algorithm validation. RESULTS: In total, 47 269 patients (mean (SD) age, 54.29 (11.60) years) were enrolled. 15 805 randomly selected participants were reviewed by a panel of specialists for DL algorithm validation. The DR grading algorithms had a 83.3% (95% CI: 81.9% to 84.6%) sensitivity and a 92.5% (95% CI: 92.1% to 92.9%) specificity to detect referable DR. The five-stage DR classification performance (concordance: 83.0%) is comparable to the interobserver variability of specialists (concordance: 84.3%). The estimated prevalence in patients with diabetes detected by DL algorithm for any DR, referable DR and vision-threatening DR were 28.8% (95% CI: 28.4% to 29.3%), 24.4% (95% CI: 24.0% to 24.8%) and 10.8% (95% CI: 10.5% to 11.1%), respectively. The prevalence was higher in female, elderly, longer diabetes duration and higher glycated hemoglobin groups. CONCLUSION: This study performed, a nationwide, multicenter, DL-based DR screening and the results indicated the importance and feasibility of DR screening in clinical practice with this system deployed at diabetes centers. TRIAL REGISTRATION NUMBER: NCT04240652.