Occurrence of ochratoxin A in Sichuan bacon from different geographical regions and characterization and biocontrol of ochratoxigenic Aspergillus westerdijkiae strain 21G2-1A.

Sichuan bacon represents the most prevalent dry-cured meat product across Southwest China, but it is vulnerable to fungal spoilage. In the present study, a total of 47 Sichuan bacons were obtained from different regions of the Sichuan Province and analyzed for the presence of ochratoxin A (OTA), yielding a positive rate of 23.4 % (11/47). All the observed OTA concentrations exceeded the maximum admissible dose in meat products (1 µg/kg) established by some EU countries, with the highest OTA concentration being 250.75 µg/kg, which raises a food safety concern and reveals the need for a standardized scientific processing protocol. Then, an OTA-producing fungus named 21G2-1A was isolated from positive samples and found to be Aspergillus westerdijkiae. Further characterization suggested a positive correlation between fungal growth and OTA production. The optimal temperature for the former was 25 °C, while it was 20 °C for the latter. Although the A. westerdijkiae strain 21G2-1A demonstrated greater mycelium growth in the presence of NaCl, OTA production was significantly dismissed when the salinity was greater than 5 %. Four lactic acid bacteria (LAB) were screened out as antagonists against the ochratoxigenic fungus. In vitro evaluation of the antagonists revealed that live cells inhibited fungal growth, and adsorption also contributed to OTA removal at different levels. This study sheds some light on OTA control in Sichuan bacon through a biological approach.

Estimating the effect of lipid-lowering agents on novel subtypes of adult-onset diabetes.

AIMS: The aims of the present study were to assess the effects of lipid-lowering drugs [HMG-CoA reductase inhibitors, proprotein convertase subtilisin/kexin type 9 inhibitors, and Niemann-Pick C1-Like 1 (NPC1L1) inhibitors] on novel subtypes of adult-onset diabetes through a Mendelian randomisation study. MATERIALS AND METHODS: We first inferred causal associations between lipid-related traits [including high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoproteins A-I, and apolipoproteins B] and novel subtypes of adult-onset diabetes. The expression quantitative trait loci of drug target genes for three classes of lipid-lowering drugs, as well as genetic variants within or nearby drug target genes associated with LDL-C, were then utilised as proxies for the exposure of lipid-lowering drugs. Mendelian randomisation analysis was performed using summary data from genome-wide association studies of LDL-C, severe autoimmune diabetes, severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes. RESULTS: There was an association between HMGCR-mediated LDL-C and the risk of SIRD [odds ratio (OR) = 0.305, 95% confidence interval (CI) = 0.129-0.723; p = 0.007], and there was an association of PCSK9-mediated LDL-C with the risk of SIDD (OR = 0.253, 95% CI = 0.120-0.532; p < 0.001) and MOD (OR = 0.345, 95% CI = 0.171-0.696; p = 0.003). Moreover, NPC1L1-mediated LDL-C (OR = 0.109, 95% CI = 0.019-0.613; p = 0.012) and the increased expression of NPC1L1 gene in blood (OR = 0.727, 95% CI = 0.541-0.977; p = 0.034) both showed a significant association with SIRD. These results were further confirmed by sensitivity analyses. CONCLUSIONS: In summary, the different lipid-lowering medications have a specific effect on the increased risk of different novel subtypes of adult-onset diabetes.

Energy-dependent photoion angular distributions in two-body Coulomb explosions of molecules.

We experimentally study two-body Coulomb explosions of CO2, O2, and CH3Cl molecules in intense femtosecond laser pulses. We observe an obvious variation in the ionic angular distribution of the fragments with respect to the kinetic energy releases (KERs). Using a classical model based on ab initio potential energy curves, we find that the dependence of the ionic angular distribution on the KER is relevant to the fact that the accurate potential energy deviates significantly from the value determined by applying the Coulomb interaction approximation at a relatively small internuclear distance of the molecule. We show that the KER-dependent ionic angular distribution provides an effective way to determine the critical internuclear distance at which the Coulomb interaction approximation holds or breaks down without relying on the knowledge of the accurate potential energy curves.

Distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study.

Background: Patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) present intestinal disturbances. Recent epidemiological data have showed that, worldwide, over half of newly diagnosed T1D patients were adults. However, the gut microbial alterations in adult-onset T1D are unclear. We aimed to identify the signatures of gut microbiota and metabolites in patients with adult-onset T1D systematically, comparing with T2D patients and healthy controls (HCs). Methods: This study enrolled 218 subjects from February 2019 to April 2022 (discovery cohort: 36 HCs, 51 patients with adult-onset T1D and 56 patients with T2D; validation cohort: 28 HCs, 27 patients with adult-onset T1D and 20 patients with T2D). Gut microbial profiles of the study subjects were investigated by metagenomic sequencing, and their faecal and serum metabolites were measured with targeted metabolomics. The study was registered on ClinicalTrials.gov (NCT05252728). Findings: Patients with adult-onset T1D had significant differences in the composition of bacteria and their metabolites, characterized by notable depletion of short-chain fatty acid-producing bacteria, especially Eubacterium rectale. This was associated with a severe loss of phenolic acids and their derivatives, including gallic acid (associated with glucose metabolism) and 3,4-dihydroxyhydrocinnamic acid (linked with glucose metabolism and pancreatic beta cell autoimmunity). A predictive model based on six bacteria and six metabolites simultaneously discriminated adult-onset T1D from T2D and HCs with high accuracy. Interestingly, bacterial-viral or bacterial-fungal trans-kingdom relationships, especially positive correlations between bacteriophages and beneficial bacteria, were significantly reduced in adult-onset T1D compared to HCs. Interpretation: Adult-onset T1D patients exhibit unique changes in host-microbiota-metabolite interactions. Gut microbiota and metabolite-based algorithms could be used as additional tools for differential diagnosis of different types of diabetes and beyond. Funding: National Key Research and Development Program of China, the National Natural Science Foundation of China.

The Prevalence of Metabolically Unhealthy Normal Weight and Its Influence on the Risk of Diabetes.

CONTEXT: Diabetes is a major health problem and metabolically unhealthy is an important risk factor. OBJECTIVE: To conduct the first nationally representative study on epidemiological data of metabolically unhealthy normal weight (MUNW) focused only on nondiabetic subjects and determine the predictive effect on diabetes in China. METHODS: A longitudinal study was conducted using data from the Rich Healthcare Group in China. Metabolic status was determined by the revised National Cholesterol Education Program Adult Treatment Panel III criteria, and individuals with 2 or more criteria were categorized as MUNW and diagnosed with metabolic syndrome (MetS) if they met 3 or more. RESULTS: Of a total of 63 830 nondiabetic normal-weight individuals, 8935 (14.0%) were classified as MUNW and 1916 (3.00%) were diagnosed with MetS. After adjusting for potential confounders, individuals with MUNW had a greater diabetes risk (4.234, 95% CI 3.089-5.803) than those without MUNW during an average of 3.10 years of follow-up. Also, the multivariable-adjusted hazard ratios for developing diabetes were 3.069 (95% CI 1.790-5.263), 7.990 (95% CI 4.668-13.677), and 11.950 (95% CI 6.618-21.579) for participants with 1, 2, and 3 or more components, respectively, compared with those without any components. Further analyses suggested that the number of MetS components present is associated with the risk of diabetes, especially in metabolically unhealthy normal-weight young male adults. Multivariable-adjusted hazard ratios (95% CI) for incident diabetes among individuals with 1, 2, and at least 3 components were 4.45 (1.45-13.72), 9.82 (3.05-31.64), and 15.13 (3.70-61.84) for participants aged ≤44 years, and 3.55 (1.81-6.97), 8.52 (4.34-16.73), and 13.69 (6.51-28.77) for male participants, respectively. CONCLUSIONS: The prevalence of MUNW is 14% in Chinese normal-weight nondiabetic individuals, and active intervention is necessary for this category of people. The presence of MUNW significantly increases the risk of diabetes, and the risk of diabetes is associated with the number of MetS components present in the patient.

Emerging trends and focus on the link between gut microbiota and type 1 diabetes: A bibliometric and visualization analysis.

Objective: To conduct the first thorough bibliometric analysis to evaluate and quantify global research regarding to the gut microbiota and type 1 diabetes (T1D). Methods: A literature search for research studies on gut microbiota and T1D was conducted using the Web of Science Core Collection (WoSCC) database on 24 September 2022. VOSviewer software and the packages Bibliometrix R and ggplot used in RStudio were applied to perform the bibliometric and visualization analysis. Results: A total of 639 publications was extracted using the terms "gut microbiota" and "type 1 diabetes" (and their synonyms in MeSH). Ultimately, 324 articles were included in the bibliometric analysis. The United States and European countries are the main contributors to this field, and the top 10 most influential institutions are all based in the United States, Finland and Denmark. The three most influential researchers in this field are Li Wen, Jorma Ilonen and Mikael Knip. Historical direct citation analysis showed the evolution of the most cited papers in the field of T1D and gut microbiota. Clustering analysis defined seven clusters, covering the current main topics in both basic and clinical research on T1D and gut microbiota. The most commonly found high-frequency keywords in the period from 2018 to 2021 were "metagenomics," "neutrophils" and "machine learning." Conclusion: The application of multi-omics and machine learning approaches will be a necessary future step for better understanding gut microbiota in T1D. Finally, the future outlook for customized therapy toward reshaping gut microbiota of T1D patients remains promising.

Serum Metabolomics Reveals a Potential Benefit of Methionine in Type 1 Diabetes Patients with Poor Glycemic Control and High Glycemic Variability.

Glycemic variability (GV) in some patients with type 1 diabetes (T1D) remains heterogeneous despite comparable clinical indicators, and whether other factors are involved is yet unknown. Metabolites in the serum indicate a broad effect of GV on cellular metabolism and therefore are more likely to indicate metabolic dysregulation associated with T1D. To compare the metabolomic profiles between high GV (GV-H, coefficient of variation (CV) of glucose ≥ 36%) and low GV (GV-L, CV < 36%) groups and to identify potential GV biomarkers, metabolomics profiling was carried out on serum samples from 17 patients with high GV, 16 matched (for age, sex, body mass index (BMI), diabetes duration, insulin dose, glycated hemoglobin (HbA1c), fasting, and 2 h postprandial C-peptide) patients with low GV (exploratory set), and another 21 (GV-H/GV-L: 11/10) matched patients (validation set). Subsequently, 25 metabolites were significantly enriched in seven Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between the GV-H and GV-L groups in the exploratory set. Only the differences in spermidine, L-methionine, and trehalose remained significant after validation. The area under the curve of these three metabolites combined in distinguishing GV-H from GV-L was 0.952 and 0.918 in the exploratory and validation sets, respectively. L-methionine was significantly inversely related to HbA1c and glucose CV, while spermidine was significantly positively associated with glucose CV. Differences in trehalose were not as reliable as those in spermidine and L-methionine because of the relatively low amounts of trehalose and the inconsistent fold change sizes in the exploratory and validation sets. Our findings suggest that metabolomic disturbances may impact the GV of T1D. Additional in vitro and in vivo mechanistic studies are required to elucidate the relationship between spermidine and L-methionine levels and GV in T1D patients with different geographical and nutritional backgrounds.

Assessing the medical resources in COVID-19 based on evolutionary game.

COVID-19 has brought a great challenge to the medical system. A key scientific question is how to make a balance between home quarantine and staying in the hospital. To this end, we propose a game-based susceptible-exposed-asymptomatic -symptomatic- hospitalized-recovery-dead model to reveal such a situation. In this new framework, time-varying cure rate and mortality are employed and a parameter m is introduced to regulate the probability that individuals are willing to go to the hospital. Through extensive simulations, we find that (1) for low transmission rates (ß < 0.2), the high value of m (the willingness to stay in the hospital) indicates the full use of medical resources, and thus the pandemic can be easily contained; (2) for high transmission rates (ß > 0.2), large values of m lead to breakdown of the healthcare system, which will further increase the cumulative number of confirmed cases and death cases. Finally, we conduct the empirical analysis using the data from Japan and other typical countries to illustrate the proposed model and to test how our model explains reality.

Characterization of immune checkpoint inhibitor-associated fulminant type 1 diabetes associated with autoantibody status and ethnic origin.

Objective: Fulminant type 1 diabetes may uniquely occur as a fatal adverse event during immune checkpoint inhibitor (ICI) therapy. We investigated the clinical and immunological characteristics of ICI-associated fulminant type 1 diabetes (IFD). Research design and methods: We enrolled 80 patients with IFD (77 cases from the literature), 56 patients with ICI-associated type 1 diabetes (IT1D) (55 cases from the literature), 45 patients with traditional fulminant type 1 diabetes (TFD), and 43 patients with acute-onset type 1 diabetes for comprehensive analysis including islet autoantibodies and subgroup analysis based on ethnic origin. Results: Patients with IFD accounted for 58.8% (80/136) of patients with ICI-related diabetes. IFD had a more rapid onset than IT1D after ICI therapy (90.5 days vs. 120 days, p <0.05). The onset time and number of infusions after ICI therapy initiation were lower in the antibody-positive IFD group than that in the antibody-negative IFD group (both p <0.001). IFD had a more rapid onset and more serious among Caucasians than that among Asians (p <0.01, p <0.05, respectively), and the prevalence of islet autoantibody positivity in the Caucasian IFD were prominently higher than those in the Asian IFD (p <0.05). Onset age and plasma glucose levels were significantly higher in the IFD group than those in the TFD and acute-onset type 1 diabetes groups. HbA1c levels were slightly higher in patients with IFD than those with TFD. Conclusions: IFD is relatively common in Caucasian population where TFD is very rare or almost absent. IFD occurrence is significantly related to islet autoantibody status and ethnic origin.

The continuous spectrum of glycaemic variability changes with pancreatic islet function: A multicentre cross-sectional study in China.

AIMS: To investigate glycaemic variability (GV) patterns in patients with type 1 diabetes (T1D), type 2 diabetes (T2D), and latent autoimmune diabetes in adults (LADA). MATERIALS AND METHODS: A total of 842 subjects (510 T1D, 105 LADA, 227 T2D) were enrolled and underwent 1 week of continuous glucose monitoring (CGM). Clinical characteristics and CGM parameters were compared among T1D, LADA, and T2D. LADA patients were divided into two subgroups based on glutamic acid decarboxylase autoantibody titres (≥180 U/mL [LADA-1], <180 U/mL [LADA-2]) and compared. The C-peptide cut-offs for predicting a coefficient of variation (CV) of glucose ≥36% and a time in range (TIR) > 70% were determined using receiver operating characteristic analysis. RESULTS: Twenty-seven patients (9 T1D, 18 T2D) were excluded due to insufficient CGM data. Sex, diabetes duration and HbA1c were comparable among the three groups. Fasting and 2-h postprandial C-peptide (FCP, 2hCP) increased sequentially across T1D, LADA, and T2D. T1D and LADA patients had comparable TIR and GV, whereas those with T2D had much higher TIR and lower GV (p < 0.001). The GV of LADA-1 was close to that of T1D, while the GV of LADA-2 was close to that of T2D. CP exhibited the strongest negative correlation with GV. The cut-offs of FCP/2hCP for predicting a CV ≥ 36% and TIR >70% were 121.6/243.1 and 128.9/252.8 pmol/L, respectively. CONCLUSIONS: GV presented a continuous spectrum across T1D, LADA-1, LADA-2, and T2D. More frequent glucose monitoring is suggested for patients with impaired insulin secretion. CLINICAL TRAIL REGISTRATION: Chinese Clinical Trial Registration (ChiCTR) website approved by WHO; http://www.chictr.org.cn/ - ChiCTR2200065036.

Analysis of detrended fluctuation function derived from continuous glucose monitoring may assist in distinguishing latent autoimmune diabetes in adults from T2DM.

Background: We aimed to explore the performance of detrended fluctuation function (DFF) in distinguishing patients with latent autoimmune diabetes in adults (LADA) from type 2 diabetes mellitus (T2DM) with glucose data derived from continuous glucose monitoring. Methods: In total, 71 LADA and 152 T2DM patients were enrolled. Correlations between glucose parameters including time in range (TIR), mean glucose, standard deviation (SD), mean amplitude of glucose excursions (MAGE), coefficient of variation (CV), DFF and fasting and 2-hour postprandial C-peptide (FCP, 2hCP) were analyzed and compared. Receiver operating characteristics curve (ROC) analysis and 10-fold cross-validation were employed to explore and validate the performance of DFF in diabetes classification respectively. Results: Patients with LADA had a higher mean glucose, lower TIR, greater SD, MAGE and CV than those of T2DM (P<0.001). DFF achieved the strongest correlation with FCP (r = -0.705, P<0.001) as compared with TIR (r = 0.485, P<0.001), mean glucose (r = -0.337, P<0.001), SD (r = -0.645, P<0.001), MAGE (r = -0.663, P<0.001) and CV (r = -0.639, P<0.001). ROC analysis showed that DFF yielded the greatest area under the curve (AUC) of 0.862 (sensitivity: 71.2%, specificity: 84.9%) in differentiating LADA from T2DM as compared with TIR, mean glucose, SD, MAGE and CV (AUC: 0.722, 0.650, 0.800, 0.820 and 0.807, sensitivity: 71.8%, 47.9%, 63.6%, 72.7% and 78.8%, specificity: 67.8%, 83.6%, 80.9%, 80.3% and 72.4%, respectively). The kappa test indicated a good consistency between DFF and the actual diagnosis (kappa = 0.551, P<0.001). Ten-fold cross-validation showed a stable performance of DFF with a mean AUC of 0.863 (sensitivity: 78.8%, specificity: 77.8%) in 10 training sets and a mean AUC of 0.866 (sensitivity: 80.9%, specificity: 84.1%) in 10 test sets. Conclusions: A more violent glucose fluctuation pattern was marked in patients with LADA than T2DM. We first proposed the possible role of DFF in distinguishing patients with LADA from T2DM in our study population, which may assist in diabetes classification.

Metabolic syndrome associated with higher glycemic variability in type 1 diabetes: A multicenter cross-sectional study in china.

Aims: The comorbidity of metabolic syndrome (MetS) and type 1 diabetes mellitus (T1DM) is an obstacle to glucose control in patients with T1DM. We compared glycemic profiles using continuous glucose monitoring (CGM) systems in patients with T1DM with or without MetS. Methods: This was a multicenter cross-sectional study of patients with T1DM (N = 207) with or without MetS. CGM data were collected from study enrollment until discharge during a 1-week study session. We analyzed baseline HbA1c, average glucose, estimated HbA1c, time in range (TIR), time above range (TAR), time below range (TBR), coefficient of variation (CV), postprandial glucose excursions (PPGE) and other glycemic variability (GV) metrics. Logistic regression was developed to investigate the association between MetS and CGM metrics. Results: The results showed higher average baseline HbA1c levels, and a higher percentage of patients with baseline HbA1c levels ≥7.5%, in the T1DM with MetS group. Furthermore, MetS was associated with GV, which indicated a higher CV in patients with T1DM with MetS. However, our results showed that TAR, TIR, TBR and other GV metrics were comparable between the two groups. The T1DM with MetS group also had a higher proportion of patients with high CV (≥ 36%) than the group without MetS. In multivariable logistic regression analysis, the presence of MetS was a risk factor for high CV (≥ 36%) in our study participants. Conclusions: T1DM patients with MetS in our study had better ß-cell function. However, MetS was associated with worse glycemic control characterized by higher GV and HbA1c levels. Efforts should be expanded to improve treatment of MetS in patients with T1DM to achieve better glycemic control.

One-Stage Hydrothermal Growth and Characterization of Epitaxial LaMnO3 Films on SrTiO3 Substrate.

Epitaxial LaMnO3 thin films were grown on SrTiO3 substrate using a one-stage hydrothermal route from La(NO3)3, MnCl2 and KMnO4 in an aqueous solution of 10 M KOH at 340 °C. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) indicate full coverage of LaMnO3 on the substrate. X-ray diffraction in the symmetric ω/2θ mode suggests the film has an out-of-plane preferred orientation along the [001] direction of the substrate. The LaMnO3 epitaxial thin film growth mechanism is proposed based on the analysis of the atomic sharp interface formed between LaMnO3 and the SrTiO3 substrate, as seen by aberration-corrected scanning transmission electron microscopy (AC-STEM) imaging in combination with electronic energy loss spectroscopy (EELS). Compared with the conventional vapor deposition methods, the one-stage hydrothermal route opens up a new way to fabricate complex oxide epitaxial heterostructures.

Corrigendum: Effect of the Chinese New Year public holiday on the glycemic control of T1DM with intensive insulin therapy.

[This corrects the article DOI: 10.3389/fendo.2022.915482.].

Effect of the Chinese New Year Public Holiday on the Glycemic Control of T1DM With Intensive Insulin Therapy.

Aims: There is limited evidence that evaluates the glycemic control of type 1 diabetes mellitus (T1DM) during the Chinese New Year public holiday in China. The Chinese New Year public holiday represents various challenges to glycemic control, especially in T1DM patients, in China. We aimed to assess the effect of the Chinese New Year public holiday on several glucose metrics using flash glucose monitoring (FGM) in patients with T1DM. Methods: Complete FGM data for 1 week before, 1 week during and 1 week after the Chinese New Year public holiday were available for 71 T1DM patients treated with multiple daily insulin injection (MDI) therapy (n = 51) or continuous subcutaneous insulin infusion (CSII) treatment (n = 20). The mean age of the study participants was 13 (9, 30) years. Of note, 59.2% of the patients (n = 42) were adults, and 40.8% of the patients (n = 29) were minors. The interval between each two adjacent periods was one week. The indicators of mean glucose, glucose variability and time in different glycemic ranges were analyzed. Results: The Chinese New Year public holiday was associated with an increase in mean blood glucose (8.4 ± 1.7 vs. 9.2 ± 2.5; P < 0.001) and time above range (TAR) (27.9% ± 16.6% vs. 35.0% ± 22.3%; P< 0.001) but a decrease in time in range (TIR) (65.1% ± 15.5% vs. 58.0% ± 19.0%; P < 0.001) and coefficient of variation (CV) (65.1% ± 15.5% vs. 58.0% ± 19.0%; P < 0.001). There was no significant difference in time below range (TBR). The glycemic control deteriorated during the Chinese New Year public holiday in our study population regardless of age. Interestingly, in the CSII group, none of the metrics of glucose control significantly changed during the Chinese New Year public holiday. Conclusions: These results suggested that less self-management may worsen glycemic control in the short term, indicating a need for more refined management algorithms during the Chinese New Year public holiday for T1DM patients.

Full experimental determination of tunneling time with attosecond-scale streaking method.

Tunneling is one of the most fundamental and ubiquitous processes in the quantum world. The question of how long a particle takes to tunnel through a potential barrier has sparked a long-standing debate since the early days of quantum mechanics. Here, we propose and demonstrate a novel scheme to accurately determine the tunneling time of an electron. In this scheme, a weak laser field is used to streak the tunneling current produced by a strong elliptically polarized laser field in an attoclock configuration, allowing us to retrieve the tunneling ionization time relative to the field maximum with a precision of a few attoseconds. This overcomes the difficulties in previous attoclock measurements wherein the Coulomb effect on the photoelectron momentum distribution has to be removed with theoretical models and it requires accurate information of the driving laser fields. We demonstrate that the tunneling time of an electron from an atom is close to zero within our experimental accuracy. Our study represents a straightforward approach toward attosecond time-resolved imaging of electron motion in atoms and molecules.

Host gene effects on gut microbiota in type 1 diabetes.

Type 1 diabetes (T1D) is an organ-specific autoimmune disease characterized by progressive pancreatic ß-cell loss. Both a predisposing genetic background, that may encompass mutations in several genes, as well as exposure to environmental factors can affect the progression of autoimmune responses to multiple pancreatic islet autoantigens. Many genetic variants that increase the risk of T1D are found in immunity genes involved in sensing and responding to microorganisms. Although increasing evidence indicates that the gut microbiome composition may promote or prevent T1D development, little is known about the link between gut microbiota and T1D susceptibility genes in patients with T1D. Recent studies in the inbred non-obese diabetic (NOD) mouse, a widely used model of T1D, have suggested that many genetic loci can influence gut microbiome composition to modulate islet autoimmunity. This review summarizes evidence that examines the effect of host genes on gut microbiota diversity and function during T1D development. Knowledge of the host gene-gut microbiota interactions at play during T1D progression may help us identify new diagnostic and prognostic tools and help also design effective strategies for disease treatment.

Factors associated with glycemic variability in children with type 1 diabetes mellitus based on flash glucose monitoring system. / 基于扫描式葡萄糖监测系统的儿童1åž‹ç³–å°¿ç— æ‚£è€ è¡€ç³–æ³¢åŠ¨çš„å½±å“å› ç´ .

OBJECTIVES: Patients with classical type 1 diabetes mellitus (T1DM) require lifelong dependence on exogenous insulin therapy due to pancreatic beta-cell destruction and absolute insulin deficiency. T1DM accounts for about 90% of children with diabetes in China, with a rapid increase in incidence and a younger-age trend. Epidemiological studies have shown that the overall glycated haemoglobin (HbA1c) and compliance rate are low in Chinese children with T1DM. Optimal glucose control is the key for diabetes treatment, and maintaining blood glucose within the target range can prevent or delay chronic vascular complications in patients with T1DM. Therefore, this study aims to investigate the glycemic control of children with T1DM from Hunan and Henan Province with flash glucose monitoring system (FGMS), and to explore factors associated with glycemic variability. METHODS: A total of 215 children with T1DM under 14 years old were enrolled continuously in 16 hospitals from August 2017 to August 2020. All subjects wore a FGMS device to collect glucose data. Correlation of HbA1c, duration of diabetes, or glucose scan rates with glycemic variability was analyzed. Glucose variability was compared according to the duration of diabetes, HbA1c, glucose scan rates and insulin schema. RESULTS: HbA1c and duration of diabetes were positively correlated with mean blood glucose, standard deviation of glucose, mean amplitude of glucose excursions (MAGE), and coefficient of variation (CV) of glucose (all P<0.01). The glucose scan rates during FGMS wearing was significantly positively correlated with time in range (TIR) (P=0.001) and negatively correlated with MAGE and mean duration of hypoglycemia (all P<0.01). Children with duration ≤1 year had lower time below range (TBR) and MAGE when compared with those with duration >1 year (all P<0.05). TIR and TBR in patients with HbA1c ≤7.5% were higher (TIR: 65% vs 45%, TBR: 5% vs 4%, P<0.05), MAGE was lower (7.0 mmol/L vs 9.4 mmol/L, P<0.001) than those in HbA1c >7.5% group. Compared to the multiple daily insulin injections group, TIR was higher (60% vs 52%, P=0.006), MAGE was lower (P=0.006) in the continuous subcutaneous insulin infusion group. HbA1c was lower in the high scan rates (≥14 times/d) group (7.4% vs 8.0%, P=0.046), TIR was significantly higher (58% vs 47%, P<0.001), and MAGE was lower (P<0.001) than those in the low scan rate (<14 times/d) group. CONCLUSIONS: The overall glycemic control of T1DM patients under 14 years old in Hunan and Henan Province is under a high risk of hypoglycemia and great glycemic variability. Shorter duration of diabetes, targeted HbA1c, higher glucose scan rates, and CSII are associated with less glycemic variability.

Effects of SGLT2 inhibitors on haematocrit and haemoglobin levels and the associated cardiorenal benefits in T2DM patients: A meta-analysis.

To explore the effect and magnitude of effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on haematocrit and haemoglobin and the related cardiorenal benefits in patients with type 2 diabetes mellitus (T2DM), PubMed, Web of Science, CENTRAL and EMBASE were searched to identify eligible trials. Weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Seventy-eight studies were included in the meta-analysis. SGLT2 inhibitors significantly increased haematocrit and haemoglobin levels compared with control (total WMD 2.27% [95% CI 2.08, 2.47] and 6.20 g/L [95% CI 5.68, 6.73], respectively). Except for dapagliflozin (p = 0.000), no notable dose-dependent relationship was revealed for other SGLT2 inhibitors. The effect could be sustained or even slightly increased with long-term therapy (coef. =0.009, 95% CI [0.005, 0.013], p = 0.000). In subgroup analyses, haematocrit elevation increased with higher body mass index (BMI). A greater haematocrit elevation could be observed in white patients or when compared with active controls. In conclusion, SGLT2 inhibitors increased haematocrit and haemoglobin levels in T2DM patients. Changes in haematocrit and haemoglobin seem to be surrogate markers of improvement in renal metabolic stress, and important mediators involved in cardiorenal protection.