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Objective: To establish an accurate and robust calculation model for predicting hemoglobin A1c (HbA1c) for people with type 2 diabetes (T2D) by using the fewest discrete blood glucose values according to an irregular data set and propose an appropriate cost-effective and scientific scheme for routine blood glucose monitoring. Methods: By using two data sets obtained from 2017 to 2022, which involved 2432 people with T2D, ∼420,000 irregular blood glucose values, and 10,000 HbA1c values, multiple blood glucose monitoring schemes were designed and compared to find the optimal one. The data were structured and then fitted using a regularized extreme learning machine, and the results were evaluated on the basis of indicators such as mean absolute error (MAE), root mean square error, and the relevance analysis (R) value; the optimal scheme for routine blood glucose monitoring was determined by combining the accuracy and the cost and was compared with previous studies in terms of accuracy and stability. Results: Data fitting results for the chosen scheme: R = 0.8029 ( P  < 0.001), MAE = 0.3181% (95% confidence interval, 0.2666-0.3695%). Within the last 4 weeks before the prediction of HbA1c, a minimum of only seven fasting and seven postprandial blood glucose values are needed, of which are one fasting and one postprandial blood glucose values per 4 days. Compared with previous studies, the prediction model shows better accuracy and stability ( P  < 0.05), especially under the great glucose fluctuation group. Conclusion: A minimized calculation model for accurately and robustly predicting HbA1c using discrete self-monitoring of blood glucose data within 4 weeks for people with T2D has been established and provides a new reference for the design of a scheme for blood glucose monitoring. The diabetes care clinic of Peking University First Hospital (Registration Number: ChiCTR2300068139).

Diabetic gastroparesis (DGP) is a common complication of type 2 diabetes mellitus (T2DM). Alpinia officinarum Hance (AOH) is one of the most commonly used both as a food and folk medicines, which is rich in diarylheptanoids and flavonoids. The gastroprotection and hypoglycemic effect make AOH has great potential in developing of anti-DGP complementary medicine. However, the molecular mechanisms of AOH that act against DGP are yet to be elucidated. In this study, we evaluated the therapeutic effects, the potential molecular mechanism, and the changes of gut microbiota of AOH in DGP. The 5 components of the AOH were analyzed, and the potential signaling pathway of AOH improving DGP was predicted by molecular docking. Subsequently, DGP rat model was constructed using high-fat-irregular-diet, AOH intervention significantly reduced blood glucose levels, increased gastrointestinal propulsion rate, and improved gastric histological morphology in DGP rats. Meanwhile, AOH has been shown to regulate the SCF/c-kit signaling pathway and rebalance the gut microbiota, which may be closely related to its role in improving DGP. Taken together, AOH may play a protective role on DGP through multiple mechanisms, which might pave the road for development and utilization of AOH., Competing Interests: Declaration of Competing Interest The research was conducted in the absence of any commercial or financial relationships. All authors have no competing interests to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: DN is a common complication of diabetes. However, diabetes combined with renal injury may involve DN or NDKD, with different treatment schemes. The purpose of our study was to determine the independent risk factors of DN and establish a risk score model to help differentiate DN and NDKD, providing a reference for clinical treatment., Methods: A total of 678 T2D patients who had undergone renal biopsy in four affiliated hospitals of Peking University were consecutively enrolled. Patients were assigned to the DN group and NDKD group according to histopathological results. Seventy percent of patients from PKUFH were randomly assigned to the training group, and the remaining 30% were assigned to the internal validation group. Patients from the other three centers were assigned to the external validation group. We used univariate and multivariate logistic regression analyses to identify independent risk factors of DN in the training group and conducted multivariate logistic regression analysis with these independent risk factors in the training group to find regression coefficients " β " to establish a risk score model. Finally, we conducted internal and external validation of the model with ROC curves., Results: Diabetic retinopathy, diabetes duration ≥ 5 years, eGFR < 30 ml/min/1.73 m 2 , 24 h UTP ≥ 3 g, and no hematuria were independent risk factors ( P < 0.05), and each factor scored 2, 1, 1, 1, and 1. We assigned the patients to a low-risk group (0-1 points), a medium-risk group (2-3 points), and a high-risk group (4-6 points), representing unlikely DN, possibly DN, and a high probability of DN, respectively. The AUCs were 0.860, 0.924, and 0.855 for the training, internal validation, and external validation groups, respectively., Conclusion: The risk score model could help differentiate DN and NDKD in a noninvasive manner, reduce the number of renal biopsies, and provide a reference for clinical treatment., Competing Interests: All authors declare that they have no conflicts of interest relevant to this article., (Copyright © 2023 Yuetong Zhao et al.)

Aim: To evaluate the efficacy of iGlarLixi in the Asian Pacific (AP) population with type 2 diabetes (T2D) using derived time-in-ranges calculated from seven-point self-measured blood glucose., Methods: Two phase III trials were analysed. LixiLan-O-AP was performed in insulin-naive T2D patients (n = 878) randomized to iGlarLixi, glargine 100 units/mL (iGlar) or lixisenatide (Lixi). LixiLan-L-CN was performed in insulin-treated T2D patients (n = 426) randomized to iGlarLixi or iGlar. Changes in derived time-in-ranges from baseline to end-of-treatment (EOT) and estimated treatment differences (ETDs) were analysed. The proportions of patients achieving 70% or higher derived time-in-range (dTIR), 5% or higher dTIR improvement, and the composite triple target (≥ 70% dTIR, < 4% derived time-below-the-range [dTBR] and < 25% derived time-above-the-range [dTAR]) were calculated., Results: The changes from baseline to EOT in dTIR with iGlarLixi were greater versus iGlar (ETD 1 : 11.45% [95% CI, 7.66% to 15.24%]) or Lixi (ETD 2 : 20.54% [95% CI, 15.74% to 25.33%]) in LixiLan-O-AP, and versus iGlar (ETD: 16.59% [95% CI, 12.09% to 21.08%]) in LixiLan-L-CN. In LixiLan-O-AP, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT with iGlarLixi were 77.5% and 77.8%, respectively, higher than with iGlar (61.1% and 75.3%) or Lixi (47.0% and 53.0%). In LixiLan-L-CN, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT were 71.4% and 59.8% with iGlarLixi, greater than with iGlar (45.4% and 39.5%). More patients achieved the triple target with iGlarLixi compared with iGlar or Lixi., Conclusion: iGlarLixi achieved greater improvements in dTIR parameters versus iGlar or Lixi in insulin-naïve and insulin-experienced AP people with T2D., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objective: The study aimed to investigate the attitudes of people with diabetes mellitus (DM) on COVID-19 vaccination and its influence on the glycemic control., Methods: Data were collected from a consecutive series of adults (age > 18 years) with type 2 diabetes under regular follow-ups in the Integrated Care Diabetes Outpatient Clinic of Peking University First Hospital from December 1 st to December 31 st 2021. An online interview questionnaire was conducted, and demographic data including age, sex category, history of drug allergy, history of hypertension, the duration of diabetes, reasons for vaccine hesitancy (VH) and adverse reactions after each injection of vaccines was collected. Glucose levels were collected from medical records., Results: Thirty-nine (22.9%) subjects experienced VH and 131 (77.1%) people living with diabetes received inactivated vaccine against COVID-19. Hesitant individuals had a higher proportion of female gender (vaccinated group vs. VH group, 62/131 vs. 26/39, p = 0.044), higher baseline glycosylated hemoglobin A 1c (HbA 1c ) (vaccinated group vs. VH group, 6.56 ± 0.95% vs. 7.54 ± 2.01%, p < 0.001) and elevated baseline postprandial blood glucose (PBG) (vaccinated group vs. VH group, 8.32 ± 1.97 mmol/L vs. 9.44 ± 2.94 mmol/L, p = 0.015). Subjects of male gender (p = 0.025) and history of hypertension (p = 0.021) were likely to get vaccinated, while higher HbA1c was negatively associated with an elevated propensity to receive anti-COVID-19 vaccine (p = 0.003). Most common reasons for hesitating to receive COVID-19 vaccination were worrying about the possibility of leading to other diseases (30.8%), followed by fearing of glucose variation (17.9%). Systemic adverse reactions were reported in 30.5% individuals after the first injection of inactivated vaccines, and resolved within 3 days in medium. Fasting blood glucose (FBG) decreased significantly after the third injection compared with FBG after the second dose (second vs. third, 6.78 ± 1.24 mmol/L vs. 6.41 ± 1.30 mmol/L, p = 0.027). HbA 1c reduced significantly from 6.56% before vaccination to 6.35% after the second injection (p = 0.012)., Conclusions: Our study demonstrated that vaccine hesitancy was lower among male subjects and people with hypertension, while vaccine confidence was reduced in people with poor glycemic control. HbA 1c level was lower along with vaccination., (© 2022. The Author(s).)

Aims: To evaluate the efficacy and safety of iGlarLixi compared with iGlar in Chinese adults with type 2 diabetes advancing therapy from basal insulin ± oral antihyperglycaemic drugs., Materials and Methods: LixiLan-L-CN (NCT03798080) was a 30-week randomized, active-controlled, open-label, parallel-group, multicentre study. Participants were randomized 1:1 to iGlarLixi or iGlar. The primary objective was to show the superiority of iGlarLixi over iGlar in glycated haemoglobin (HbA1c) change from baseline to Week 30., Results: In total, 426 participants were randomized to iGlarLixi (n = 212) or iGlar (n = 214). Mean age was 58 years, 67% had a body mass index ≥24 kg/m 2 , corresponding to overweight/obesity, and the mean diabetes duration was 12.3 years. From mean baseline HbA1c of 8.1% in both groups, greater decreases were seen with iGlarLixi versus iGlar [least squares mean difference: -0.7 (95% confidence interval: -0.9, -0.6)%; p < .0001] to final HbA1c of 6.7% and 7.4%, respectively. HbA1c <7.0% achievement was greater with iGlarLixi (63.3%) versus iGlar (29.9%; p < .0001). Mean body weight decreased with iGlarLixi and increased with iGlar [least squares mean difference: -0.9 (95% confidence interval: -1.4, -0.5) kg; p = .0001]. Hypoglycaemia incidence was similar between groups. Few gastrointestinal adverse events occurred (rated mild/moderate) with a slightly higher incidence with iGlarLixi than iGlar., Conclusions: iGlarLixi provided better glycaemic control and facilitated more participants to reach glycaemic targets alongside beneficial effects on body weight, no additional risk of hypoglycaemia, and few gastrointestinal AEs, supporting iGlarLixi use as an efficacious and well tolerated therapy option in Chinese people with long-standing T2D advancing therapy from basal insulin., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Oxidative stress interferes with blood glucose homeostasis, leading to insulin resistance (IR) and hyperglycemia, which eventually induce type 2 diabetes (T2DM). Fermented noni ( Morinda citrifolia L.) fruit juice (FNJ) is a traditional folk medicine in Polynesia as well as a functional food supplement with a variety of health benefits. In this study, the efficacy and mechanism of FNJ in improving oxidative stress and IR were investigated under the synergistic effect of Nrf2/ARE pathway and gut flora in vivo and in vitro . In vitro , insulin resistant HepG2 cells were established with 50 mM high glucose, and 25 μM rosiglitazone (ROSI) was used as a positive control. In vivo , male C57BLKS mice in the CON group were fed a normal diet and C57BLKS/J-db/db (db/db) mice were treated with 10 mg kg -1 d -1 ROSI and 6.5 and 13 mL kg -1 d -1 FNJ for 8 weeks, respectively. The results showed that 3-5% FNJ markedly improved IR by increasing glucose uptake and consumption and ameliorated oxidative stress via up-regulating the expression of related antioxidant enzymes such as SOD and GPx and attenuating ROS and MDA in IR-HepG2 cells. In vivo , db/db mice exhibited hyperglycemia, hyperinsulinemia, and oxidative stress, whereas FNJ significantly inverted those conditions. Moreover, FNJ supplementation notably increased the gut microbiota diversity of T2DM mice and remodeled the gut microbial composition to suppress microbial disorder. Specifically, FNJ increased the ratio of F/B and lowered the Proteobacteria abundance at the phylum level. The db/db mice were enriched in Enterobacteriaceae, Klebsiella, and Klebsiella-pneumonia, while FNJ feeding significantly up-regulated Rikenellaceae. In addition, western blotting and qPCR experiments showed that FNJ promoted the expression of Nrf2, HO-1, IRS1, PI3K, AKT, and GLUT4 and reduced the JNK level both in vivo and vitro . These results confirmed that FNJ had a protective effect on oxidative stress and IR by activating Nrf2/ARE signaling pathway and regulating gut flora in db/db mice and IR-HepG2 cells.

Diabetic peripheral neuropathy (DPN), peripheral artery disease (PAD), and foot deformity are the most common causes of diabetic foot, which can considerably worsen the patient's quality of life. In this study, we aimed to investigate the prevalence and risk factors associated with DPN, PAD, and foot deformity among patients with diabetes living in Beijing, China. In total, 3,898 diabetes patients from 11 hospitals in Beijing were evaluated using questionnaires and physical examinations, and 3,758 patients were included in the analysis. We compared the demographic, clinical, biological characteristics, and comorbidities of patients with and without DPN, PAD, or foot deformity, and used binary logistic regression analysis to identify potential factors associated with these outcomes. Overall, 882 patients (23.5%) had DPN, 437 patients (11.6%) had PAD, and 1,117 patients (29.7%) had foot deformities, including callus. The risk factors for DPN included: age ≥40 years, a ≥10+year duration of diabetes, a body mass index of <18.5 kg/m 2 or ≥24 kg/m 2 , a systolic blood pressure (SBP) of ≥140 mm Hg, a hemoglobin A 1c (HbA 1c ) level of ≥7%, chronic kidney disease, and cerebrovascular disease. The risk factors for PAD included: a 15+ year diabetes duration, a body mass index of <18.5 kg/m 2 , a SBP of ≥140 mm Hg, a HbA 1c level of ≥7%, chronic kidney disease, coronary heart disease, and cerebrovascular disease. The risk factors for skeletal foot deformities included: women, age ≥40 years, a SBP ≥140 mm Hg, and hyperlipidemia. The risk factors for callus formation included: women, a SBP ≥140 mm Hg, and hyperlipidemia. In conclusion, the prevalence of foot deformities was higher than DPN and PAD in patients with diabetes. Managing the risk factors for DPN, PAD, and foot deformity is important for reducing the risk of diabetic foot., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Yuan, Liu, Yuan, Sun, Zhang, Qi, Li, Zhang, Wen and Guo.)

Aims: To explore the associations between polymorphisms in SIRT1 and coronary heart disease (CHD) risk in Chinese Han patients with type 2 diabetes (T2D)., Methods: This case-controlled study enrolled 492 patients with T2D: 297 with CHD and 195 without CHD. Five SIRT1 haplotype-tagging single-nucleotide polymorphisms (rs3818291, rs12242965, rs3818292, rs4746720, and rs16924934) were selected from Chinese Han data in the GRCh37.p13 phase 3 database and genotyped by polymerase chain reaction-restriction fraction length polymorphism or sequencing., Results: The rs16924934 G allele was associated with a higher risk of CHD than the A allele (odds ratio (OR) = 1.429; 95% confidence interval (CI) = 1.003-2.037; P = 0.048). Using an additive inheritance model, the rs3818291 G/A genotype was associated with a higher CHD risk than the G/G genotype (OR' = 1.683; 95%CI = 1.033-2.743; P ' = 0.037 after adjustment for CHD risk factors). Smokers carrying G/A or A/A rs3818291 genotypes had a 3-fold higher CHD risk than those carrying GG (adjusted OR' = 3.035; P ' = 0.011) and a 2.6-fold higher CHD risk than nonsmokers carrying GG (adjusted OR' = 2.604; P ' = 0.033)., Conclusions: Genetic polymorphisms of SIRT1 are associated with the risk of CHD in a Chinese Han population with T2D., Competing Interests: The authors declares that they have no conflicts of interest., (Copyright © 2022 Yuxin Wang et al.)

Our study investigated the effectiveness of bacteria-killing nanotechnology Bio-Kil socks on bacterial burden reduction in diabetic patients and healthy individuals. Four strains of S. aureus and four strains of E. coli were cultured and dropped on Bio-Kil socks and control socks for 0 h, 8 h, and 48 h of incubation. Diluted samples were inoculated and bacterial counts were recorded. Additionally, 31 patients with type 2 diabetes and 31 healthy controls were assigned to wear one Bio-Kil sock on one foot and a control sock on the other for four hours, and then they were told to exchange socks from one foot to the other for four hours. The socks were sampled and diluted and then inoculated to record bacterial counts. Bacterial counts were reduced in Bio-Kil socks compared with control socks in all S. aureus strains after 0 h, 8 h, and 48 h of incubation. In E. coli strains, bacterial counts declined in Bio-Kil socks comparing with control socks in most of the experiments with ESBL-negative E. coli and ATCC35218 at 0 h and 48 h of incubation. In all participants, the mean bacterial counts significantly decreased in Bio-Kil socks in comparison with control socks both at 0 h and at 40 h of incubation ( p = 0.003 at 0 h and p = 0.006 at 40 h). Bio-Kil socks from diabetic patients showed significantly lessened bacterial count at 40 h of incubation ( p = 0.003). In healthy individuals, Bio-Kil socks reflected a significantly smaller mean bacterial count than control socks ( p = 0.016). Socks using Bio-Kil nanotechnology efficiently reduce bacterial counts in both diabetic patients and healthy individuals and might exert stronger efficacy in Gram-positive bacteria.

Background: Glucose-dependent insulinotropic polypeptide (GIP) is closely related to diabetes and obesity, both of which are confirmed to increase the risk of coronary artery disease (CAD). Our study aimed to investigate whether the polymorphisms in GIP genes could affect the risk of cardiovascular disease in type 2 diabetic patients in the Chinese Han population., Methods: We selected and genotyped two haplotype-tagging single nucleotide polymorphisms (tag-SNPs) (rs2291725 C>T, rs8078510 G>A) of GIP gene based on CHB data in HapMap Phase II database ( r 2 < 0.8). The case-control study of Chinese Han population involved 390 diabetic patients with CAD as positive group and 276 diabetic patients without CAD as control group. Allele and genotype frequencies were compared between the two groups., Results: In dominant inheritance model, the carriers of T/T or T/C had a lower risk of CAD (OR = 0.635, 95% CI = 0.463-0.872, p = 0.005), even after adjustment other CAD risk factors (gender, age, BMI, smoking status, dyslipidemia, hypertension history, and diabetic duration) (OR' = 0.769, 95% CI' = 0.626-0.945, p ' = 0.013). The allele A at rs8078510 was associated with decreased risk of CAD (OR = 0.732, p = 0.039). p = 0.018 in subgroup analysis, individuals with higher BMI (≥24 kg/m 2 ) had increased risk for CAD when carrying C/C at rs2291725 (OR' = 1.291, 95% CI' = 1.017-1.639, p ' = 0.036). In age < 55 men and age < 65 women, the carriers of allele C at rs2291725 had a higher risk of CAD than noncarriers (OR = 1.627, p = 0.015). Carriers of allele G in rs8078510 had higher susceptibility to CAD (OR = 2.049, 95% = CI 1.213-3.463, p = 0.007). p = 0.004; in addition, allele G in rs8078510 would bring higher CAD risk to the carriers who ever smoked (OR = 1.695, 95% CI = 1.080-2.660, p = 0.021)., Conclusion: The genetic variability of GIP gene is associated with CAD and it may play a role in the premature CAD in the Chinese Han population with type 2 diabetes.

Aims: We investigated the association between ubiquitin-conjugating enzyme E2Z (UBE2Z) gene SNP rs46522 and the risk of CAD in a Chinese Han population with type 2 diabetes and explored a possible interactive effect with environmental risk factors of CAD., Methods: 665 patients with T2D were enrolled; 390 were CAD patients and 275 were non-CAD patients. Genotype analysis of rs46522 (T>C) was performed using PCR-RFLP., Results: The SNP rs47522 was associated with the risk of CAD supposing recessive inheritance model (TT versus CC+CT, OR' = 1.277, 95%CI' 1.039-1.570, p ' = 0.020) and codominant model (TT versus CT, OR' = 1.673, 95%CI' 1.088-2.570, p ' = 0.019) after adjustment for confounders of CAD. A synergistic effect of rs46522 and BMI was discovered ( β = 0.012, p for interreaction  = 0.028). In subgroup analysis, minor allele T was significantly associated with CAD in overweight and obesity subgroup ( p = 0.034), and the association was also proved in recessive model (OR = 1.537, 95%CI 1.075-2.196, p = 0.018). Smokers with genotype TT had threefold risk of CAD in comparison to nonsmokers with genotype TC or CC ( p < 0.001)., Conclusions: The SNP rs46522 in UBE2Z gene is associated with the risk of CAD in the individuals of Chinese Han descent with type 2 diabetes and is of synergistic effect with BMI.

Objective: This study aimed to investigate the role of MTP on lipid metabolism disorders in insulin-resistant rats and the potential mechanism through which metformin can improve lipid metabolism disorders., Methods: 30 OLETF rats served as research subjects and 18 LETO rats of the same strain served as the control group (LETO group). After the first oral glucose tolerance test (at 8-week-old), 6 rats were randomly killed from each group. The remaining 24 OLETF rats were randomly divided into untreated group (OLETF group) and treated group (OLETF/M group, cured with metformin). By the end of the 10th and 20th week of treatment, MTP in the liver was measured for all rats in the study., Results: All OLETF rats exhibited diabetic phenotypes at 18-week-old, with their triglyceride level higher than in LETO rats at the same age. In OLETF rats, MTP level in the liver was higher than in LETO rats at 18-week-old, and the difference was significant at 28-week-old [(13.79±1.47) vs. (8.20±1.14), p<0.05]. Treatment with metformin for 20weeks decreased triglyceride [(1.06±0.23) vs. (2.20±0.62) mmol/L, p<0.05] and total cholesterol [(1.90±0.19) vs. (2.36±0.14) mmol/L, p<0.05] in OLETF rats. Metformin also decreased MTP level in the liver [(7.65±1.31) vs. (13.79±1.47), p<0.01]., Conclusions: MTP may be associated with the lipid metabolism disorder in OLETF rats and metformin could improve lipid metabolism through reducing the expression of MTP., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Prediabetes is an early stage of β-cell dysfunction presenting as insulin resistance. Evidences suggest that endoplasmic reticulum (ER) stress is involved in the pathogenesis of type 2 diabetes mellitus and prediabetes. In a Chinese population with prediabetes, we investigated single nucleotide polymorphisms (SNPs) in the genes of PERK, JNK, XBP1, BIP and CHOP which encode molecular proteins involved in ER stress pathways., Methods: Nine SNPs at the PERK, JNK, XBP1, BIP and CHOP loci were genotyped by mass spectrometry in 1 448 unrelated individuals. By using a 75 g oral glucose tolerance test (OGTT), 828 subjects were diagnosed as prediabetes and 620 subjects aged 55 years and over as normal controls based on WHO diagnostic criteria (1999) for diabetes mellitus., Results: The allele C of SNP rs867529 at PERK locus was a risk factor for prediabetes, with the carriers of C allele genotype at a higher risk of prediabetes compared to non-carriers (OR = 1.279, 95% CI: 1.013-1.614, P = 0.039, after adjustment for age, sex and body mass index (BMI). The SNPs rs6750998 at PERK locus was associated with homeostasis model assessments of insulin resistance (HOMA-IR) (P = 0.019), and rs17037621 with BMI (P = 0.044). The allele G of SNP rs10986663 in BIP gene was associated with a decreased risk of prediabetes (OR = 0.699, 95% CI: 0.539-0.907, P = 0.007). The SNP rs2076431 in JNK gene was associated with fasting plasma glucose levels (P = 0.006) and waist-hip ratios (P = 0.019). The SNP rs2239815 in XBP1 gene was associated with 2-hour plasma glucose levels after 75 g oral glucose load (P = 0.048) in the observed population., Conclusion: Common variants at PERK and BIP loci contributed to the risk of prediabetes, and the genetic variations in JNK and XBP1 genes are associated with diabetes-related clinical parameters in this Chinese population.