Predictors of and barriers to follow-up uptake: analysis of factors and perceived barriers among high-risk individuals with diabetes after screening in China.

OBJECTIVE: The objective of this study was to identify variables that predict adherence to follow-up visits among people who are positive for diabetes during screening and to investigate barriers to follow-up. STUDY DESIGN: A retrospective cohort study linking individual-level registry data was performed. METHODS: First, we compared the characteristics of attenders and non-attenders. Second, we investigated perceived barriers using a questionnaire in a random sample of people who failed to attend the follow-up visit. RESULTS: A total of 27,806 (16.4%) patients attended the follow-up visits. Multiple logistic regression analysis revealed that individuals aged ≥75 years were more likely to attend follow-up than were those aged 35-45 years (odds ratio [OR]: 1.97 [95% confidence interval {CI}: 1.82-2.15]), male (OR: 1.15 [95% CI: 1.12-1.18]), obese (OR: 1.36 [95% CI: 1.29-1.43]), had positive family history of diabetes (OR: 1.37 [95% CI: 1.30-1.45]), hypertension (OR: 1.05 [95% CI: 1.01-1.09]), high glucose levels (OR: 1.10 [95% CI: 1.09-1.11]), and high diabetes risk scores (OR: 1.02 [95% CI: 1.02-1.03]) facilitated follow-up. However, overweight (OR: 0.95 [95% CI: 0.92-0.99]) and central obesity (OR: 0.86 [95% CI: 0.83-0.90]) predicted no follow-up. Among nonattenders, diabetes beliefs, time restrictions and distance from home to hospitals were the top three barriers hindering follow-up visits. CONCLUSIONS: Specific individual-level characteristics predicted adherence to follow-up visits, and some personal and sociocultural barriers hindered follow-up visits.

Plasma-derived exosomal miRNA profiles associated with type 1 diabetes.

AIMS: Recently, exosomal miRNAs have been shown to play important roles in multiple diseases, including type 1 diabetes (T1D). To assess the biomarker potential of exosomal miRNAs for T1D, we measured the expression profiles of plasma-derived exosomal miRNAs in T1D and explored their potential functions by bioinformatic analysis. MATERIALS AND METHODS: In the discovery phase, exosome samples were isolated from plasma by size exclusion chromatography from 10 T1D patients and 10 sex- (p = 0.36), age- (p = 0.97), and body mass index-matched (p = 0.47) healthy control subjects. Exosomal miRNA expression profiles were measured using the Illumina NovaSeq 6000 platform. With verification by quantitative real-time PCR (qRT-PCR), we used multiple bioinformatics approaches to explore the potential biological functions of the identified differentially expressed miRNAs. The diagnostic signature of exosomal miRNAs was evaluated by least absolute shrinkage and selection operator (LASSO) regression and evaluated based on the area under the receiver operating characteristic curve (AUC). RESULTS: In total, 43 differentially expressed miRNAs, among which 34 were upregulated and 9 were downregulated, were identified in T1D. After correcting for multiple testing using false discovery rate, 11 identified exosomal miRNAs still showed statistical significance. Among the 5 selected miRNAs, 3 miRNAs (miR-103a-3p, miR-144-5p and miR-454-3p) were successfully validated by qRT-PCR. The biological analysis-enriched terms included protein autophosphorylation and the Hedgehog signalling pathway. The highest AUC of exosomal miRNA was 0.889 under the LASSO model. The expression levels of 5 selected exosomal miRNAs were correlated with multiple clinical characteristics such as fasting C-peptide and postprandial C-peptide. CONCLUSIONS: Our results indicated that plasma-derived exosomal miRNAs could serve as promising diagnostic biomarkers of T1D.

Using point-of-care HbA1c to facilitate the identification of diabetes and abnormal glucose regulation in primary healthcare settings.

Background: Glycated hemoglobin A1c (HbA1c) is a critical index for the diagnosis and glycemic control evaluation of diabetes. However, a standardized method for HbA1c measurement is unaffordable and unavailable among the Chinese population in low-resource rural settings. Point-of-care (POC) HbA1c testing is convenient and inexpensive, but its performance remains to be elucidated. Objective: To investigate the value of POC HbA1c for identifying diabetes and abnormal glucose regulation (AGR) in the resource-limited Chinese population. Methods: Participants were recruited from 6 Township Health Centers in Hunan Province. Samples for POC HbA1c, venous HbA1c, fasting plasma glucose, and 2 h-plasma glucose were obtained after physical examination. The oral glucose tolerance test was performed as the gold standard for diagnosis. The diagnostic capacities of the POC HbA1c measurement in predicting undiagnosed diabetes and AGR were evaluated. Results: Among 388 participants, 274 (70.6%) normoglycemic controls, 63 (16.2%) prediabetes patients, and 51 (13.1%) diabetes patients were identified with oral glucose tolerance test (OGTT). Meanwhile, among 97 participants who underwent two HbA1c detection methods simultaneously, a positive correlation was found between POC HbA1c and standardized HbA1c (r = 0.75, P < 0.001). No notable systematic difference was observed from the Bland-Altman Plots. The POC HbA1c cutoff values were 5.95 and 5.25%, which efficiently identified diabetes (AUC 0.92) and AGR (AUC 0.89), respectively. Conclusions: The alternative POC HbA1c test efficiently discriminated AGR and diabetes from normoglycemia, especially among the Chinese population in primary healthcare settings.

Effect of smartphone apps on glycemic control in young patients with type 1 diabetes: A meta-analysis.

Objectives: Achieving glycemic control is a great challenge for young patients with type 1 diabetes (T1D), especially during the transition from childhood to adulthood. As various smartphone apps have been developed to improve glycemic control in T1D, we performed a meta-analysis of randomized controlled trials to assess the effect of smartphone apps on glycemic control in young patients with T1D. Methods: We systematically searched PubMed, Embase, and the Cochrane Library for randomized controlled trials comparing combined usual care and smartphone app treatment to usual care alone. This meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The primary outcomes were the weighted difference in means (WMD) of HbA1c change from baseline and the person-years incidence of mild hypoglycemia or severe hypoglycemia between intervention and control groups. We assessed pooled data by use of a random-effects model. Results: Of 1,190 identified studies, nine were eligible and included in our analysis (N = 748 participants). Relative to the control, using smartphone apps yielded a non-significant reduction in glycated hemoglobin (HbA1c) (WMD = -0.26, 95% CI: -0.56 to 0.05; p = 0.10) and no increased frequency of mild hypoglycemia (WMD = 1.87, 95% CI: -1.52 to 5.27; p = 0.49) or severe hypoglycemia (WMD = -0.04, 95% CI: -0.35 to 0.27; p = 0.80). In further subgroup analysis, compared with the recording-style app group, the auxiliary-style app group exhibited a significant reduction in HbA1c (WMD = -0.83, 95% CI: -1.10 to -0.56, p < 0.001). Conclusion: The current pooled data analysis did not reveal a significant reduction in HbA1c in young patients with T1D undergoing treatment with smartphone apps and usual care in combination. However, auxiliary-style apps with insulin or carbo calculators were beneficial in reducing HbA1c.

Primary care providers' knowledge, attitudes, and practices related to prediabetes in China: A cross-sectional study.

Background: The management of prediabetes has great clinical significance, and primary care providers (PCPs) play important roles in the management and prevention of diabetes in China. Nevertheless, little is known about PCPs' knowledge, attitudes, and practices (KAP) regarding prediabetes. This cross-sectional study aimed to assess the KAP regarding prediabetes among PCPs in the Central China region. Methods: This cross-sectional study was conducted using self-administered KAP questionnaires among PCPs from Central China region. Results: In total, 720 PCPs completed the survey. Most physicians (85.8%) claimed to be aware of the adverse effects of prediabetes and reported positive attitudes toward prediabetes prevention, but the PCPs' knowledge of prediabetes and management practices showed substantial gaps. The prediabetes knowledge level and practice subscale scores of the PCPs were only 54.7% and 32.6%, respectively, of the corresponding optimal scores. Female PCPs showed higher prediabetes knowledge level scores (p = 0.04) and better practice scores (p = 0.038). Knowledge and attitude scores were inversely correlated with participants' age and duration of practice (p < 0.001). The PCPs who served in township hospitals had significantly higher knowledge and attitude scores than those who served in village clinics (p < 0.001). Furthermore, knowledge and practice scores increased with increasing professional titles. Recent continuing medical education (CME) attendance had a significant positive influence on knowledge of prediabetes (p = 0.029), but more than four-fifths of the surveyed PCPs did not participate in diabetes-related CME in the past year. Conclusions: Substantial gaps were observed in PCPs' knowledge and practices regarding prediabetes in the Central China region. CME programmes were under-utilized by PCPs. Structured programmes are required to improve PCPs' prediabetes-related knowledge and practices in China.

Case Report: Subacute thyroiditis after receiving inactivated SARS-CoV-2 vaccine (BBIBP-CorV).

Background: Subacute thyroiditis, an inflammatory disease, has been reported caused by vaccines in rare cases. In the context of the coronavirus disease 19 pandemic, various SARS-CoV-2 vaccines have been developed and may be potential triggers for subacute thyroiditis. Case presentation: We report a case of subacute thyroiditis 3 days after receiving the second dose of inactivated SARS-CoV-2 vaccine (BBIBP-CorV). The patient did not report a previous history of thyroid disease, upper respiratory tract infection, or COVID-19. Physical examination, laboratory testing, ultrasonography, and radioactive iodine uptake were consistent with subacute thyroiditis. During follow-up, the patient recovered from symptoms and signs, and imaging changes except for hypothyroidism, requiring an ongoing thyroxine replacement. Conclusions: Inactivated SARS-CoV-2 vaccine may be a causal trigger leading to subacute thyroiditis. Clinicians should be aware of subacute thyroiditis as a possible thyroid-related side effect of an inactivated SARS-CoV-2 vaccine.

Activation of Sirtuin 1 Attenuates High Glucose-Induced Neuronal Apoptosis by Deacetylating p53.

Diabetes mellitus (DM) has been proven to be a key risk factor for cognitive impairment. Previous studies have implicated hippocampal neuronal apoptosis in diabetes-related cognitive impairment. However, the underlying mechanism remains unknown. Sirtuin 1 (SIRT1) is a protein deacetylase depended on nicotinamide adenine dinucleotide. Furthermore, it is indispensable in normal learning and memory. Whether SIRT1 is taken part in diabetes-induced neuronal apoptosis and thus involve in the development of diabetic cognitive impairment is still not clear. To address this issue, we examined the possible role of SIRT1 in hippocampal neuronal apoptosis in streptozotocin-induced diabetic mice. Furthermore, the possible mechanism was investigated in high glucose-induced SH-SY5Y cells. We found that downregulation of the activity and expression of SIRT1 was associated with increased hippocampal neuronal apoptosis in mice. In vitro, cell apoptosis induced by high glucose which was accompanied by a downregulation of SIRT1 and an increased acetylation of p53. On the contrary, activation of SIRT1 using its agonist resveratrol ameliorated cell apoptosis via deacetylating p53. Our data suggest that high concentration of glucose can induce neuronal apoptosis through downregulation of SIRT1 and increased acetylation of p53, which likely contribute to the development of cognitive impairment in diabetes.

High glucose up-regulates Semaphorin 3A expression via the mTOR signaling pathway in keratinocytes: A potential mechanism and therapeutic target for diabetic small fiber neuropathy.

Small fiber neuropathy (SFN) is a common complication in diabetes, and is characterized by decreased intraepidermal nerve fiber density (IENFD). Semaphorin 3A (Sema3A), which is produced by keratinocytes, has a chemorepulsive effect on intraepidermal nerve fibers. mTOR signaling can mediate local protein synthesis that is critical for growth of axons and dendrites. Therefore, this study aimed to investigate whether Sema3A is up-regulated in diabetic keratinocytes via the mTOR-mediated p70 S6K and 4E-BP1 signaling pathways, and furthermore whether it is involved in the pathogenesis of diabetic SFN. IENFD, expression of Sema3A, and mTOR signaling, were evaluated in the skin of diabetic patients with SFN as well as control subjects. Sema3A and mTOR signaling were also assessed in HaCaT cells which had been treated with high glucose (HG) or recombinant Sema3A (rSema3A) in the presence or absence of rapamycin. Small fiber dysfunction was evaluated by examining IENFD and using behavioral tests in control and streptozotocin-induced diabetic rats treated with or without rapamycin. We found that higher Sema3A expression and over-activation of mTOR signaling, was accompanied by reduced IENFD in the skin of diabetic patients compared with control subjects. The expression of Sema3A, and mTOR signaling were up-regulated in HaCaT cells incubated with HG or rSema3A, and this could be attenuated by rapamycin. Hyperalgesia, reduced IENFD, and up-regulated Sema3A and mTOR signaling were also detected in diabetic rats. These effects were ameliorated by rapamycin treatment. Our data indicate that HG up-regulates Sema3A expression by activating mTOR signaling in diabetic keratinocytes. This pathway may therefore play a critical role in diabetic SFN.

High glucose induces formation of tau hyperphosphorylation via Cav-1-mTOR pathway: A potential molecular mechanism for diabetes-induced cognitive dysfunction.

The abnormally hyperphosphorylated tau is thought to be implicated in diabetes-associated cognitive deficits. The role of mammalian target of rapamycin (mTOR) / S6 kinase (S6K) signalling in the formation of tau hyperphosphorylation has been previously studied. Caveolin-1 (Cav-1), the essential structure protein of caveolae, promotes neuronal survival and growth, and inhibits glucose metabolism. In this study, we aimed to investigate the role of Cav-1 in the formation of tau hyperphosphorylation under chronic hyperglycemic condition (HGC). Diabetic rats were induced by streptozotocin (STZ). Primary hippocampal neurons with or without molecular intervention such as the transient over-expression or knock-down were subjected to HGC. The obtained experimental samples were analyzed by real time quantitative RT-PCR, Western blot, immunofluorescence or immunohistochemisty. We found: 1) that a chronic HGC directly decreases Cav-1 expression, increases tau phosphorylation and activates mTOR/S6K signalling in the brain neurons of diabetic rats, 2) that overexpression of Cav-1 attenuates tau hyperphosphorylation induced by chronic HGC in primary hippocampal neurons, whereas down-regulation of Cav-1 using Cav-1 siRNA dramatically worsens tau hyperphosphorylation via mTOR/S6K signalling pathway, and 3) that the down-regulation of Cav-1 induced by HGC is independent of mTOR signalling. Our results suggest that tau hyperphosphorylation and the sustained over-activated mTOR signalling under hyperglycemia may be due to the suppression of Cav-1. Therefore, Cav-1 is a potential therapeutic target for diabetes-induced cognitive dysfunction.