OBJECTIVE: The role of lower hemoglobin A1c (HbA1c) variability in the effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on acute kidney injury (AKI) remains unclear. We compared AKI risk between SGLT2i and dipeptidyl peptidase 4 inhibitors (DPP4i) initiators. Additionally, we aimed to explore the extent to which SGLT2i\'s influence on AKI risk is mediated by reducing long-term HbA1c variability.
METHODS: Using 2018-2022 year data in Yinzhou Regional Health Care Database, we included adult, type 2 diabetes patients who were new users of SGLT2i or DPP4i. The effect of SGLT2i versus DPP4i on AKI, HbA1c variability, and AKI through HbA1c variability was compared using inverse probability of treatment weighted Cox proportional hazards models, median regression models, and causal mediation analysis.
RESULTS: With a median follow-up of 1.76 years, 19 717 adults (for SGLT2i, n = 6008; for DPP4i, n = 13 709) with type 2 diabetes were included. The adjusted hazard ratio for SGLT2i versus DPP4i was 0.79 (95% confidence interval [CI] 0.64-0.98) for AKI. The adjusted differences in median HbA1c variability score (HVS) and HbA1c reduction were -16.67% (95% CI: -27.71% to -5.62%) and -1.98% (95% CI: -14.34% to 10.38%), respectively. Furthermore, lower AKI risk associated with SGLT2i was moderately mediated (22.77%) through HVS. The results remained consistent across various subgroups and sensitivity analyses.
CONCLUSIONS: Compared to DPP4i, lower AKI risk associated with SGLT2i is moderately mediated through HbA1c variability. These findings enhance our understanding of the effect of SGLT2i on AKI and underscore the importance of considering HbA1c variability in diabetes treatment and management.

BACKGROUND: This study aims to evaluate the effects of sodium-glucose cotransporter 1 inhibitors (SGLT1i) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) on neurodegenerative disorders and to investigate the role of hemoglobin A1c (HbA1c) levels.
METHODS: Utilizing drug target Mendelian randomization, we employed single nucleotide polymorphisms (SNPs) proximal to the SLC5A1 and SLC5A2 genes to analyze the influence of SGLT1i and SGLT2i on Alzheimer\'s disease (AD), Parkinson\'s disease (PD), multiple sclerosis (MS), frontotemporal dementia (FTD), Lewy body dementia (LBD), and amyotrophic lateral sclerosis (ALS), with type 2 diabetes (T2D) as a positive control. An additional analysis examined the impact of HbA1c levels on the same disorders.
RESULTS: SGLT1i exhibited a significant association with decreased risk for ALS and MS. Conversely, SGLT2i were linked to an increased risk of AD, PD, and MS. Elevated HbA1c levels, independent of SGLT1 and SGLT2 effects, were associated with an increased risk of PD. Sensitivity analyses supported the robustness of these findings.
CONCLUSIONS: Our study suggests that SGLT1i may confer protection against ALS and MS, whereas SGLT2i could elevate the risk of AD, PD, and MS. Additionally, elevated HbA1c levels emerged as a risk factor for PD. These findings underscore the importance of personalized approaches in the utilization of SGLT inhibitors, considering their varying impacts on the risks of neurodegenerative diseases.

BACKGROUND: Cognitive dysfunction is the main manifestation of central neuropathy. Although cognitive impairments tend to be overlooked in patients with diabetes mellitus (DM), there is a growing body of evidence linking DM to cognitive dysfunction. Hyperglycemia is closely related to neurological abnormalities, while often disregarded in clinical practice. Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM (T2DM).
OBJECTIVE: To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c (HbA1c) levels.
METHODS: A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital. The participants were divided into four groups according to their HbA1c levels using the interquartile method, namely Q1 (< 7.875%), Q2 (7.875%-9.050%), Q3 (9.050%-11.200%) and Q4 (≥ 11.200%). Clinical data were collected and measured, including age, height, weight, neck/waist/hip circumferences, blood pressure, comorbidities, duration of DM, and biochemical indicators. Meanwhile, neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy.
RESULTS: The HbA1c level was significantly associated with urinary microalbumin (mALB), triglyceride, low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-β), N-acetylaspartate/creatine (NAA/Cr), and NAA/choline (NAA/Cho). Spearman correlation analysis showed that mALB, LDL-C, HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c (P < 0.05), whereas HOMA-β was negatively correlated with the HbA1c level (P < 0.05). Ordered multiple logistic regression analysis showed that NAA/Cho [Odds ratio (OR): 1.608, 95% confidence interval (95%CI): 1.004-2.578, P < 0.05], LDL-C (OR: 1.627, 95%CI: 1.119-2.370, P < 0.05), and HOMA-IR (OR: 1.107, 95%CI: 1.031-1.188, P < 0.01) were independent predictors of poor glycemic control.
CONCLUSIONS: The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control, which may be the basis for the changes in cognitive function in diabetic patients.

UNASSIGNED: Most glycated hemoglobin A1c (HbA1c) analytical reagents used were obtained from the analyzer\'s manufacturer. However, clinical laboratories need more choices for HbA1c analytical reagents to overcome the limitations of dedicated reagents for special analyzers. We developed new mobile phase buffers as HbA1c diagnostic reagents and evaluated their analytical performance for the HbA1c assay.
UNASSIGNED: Different mobile phase buffers used as HbA1c diagnostic reagents were prepared using different concentrations of sodium salts. According to the Clinical and Laboratory Standards Institute (CLSI) recommendation guidelines, the analytical performances of the newly developed mobile phase buffers were evaluated on an ARKRAY HA-8160 Analyzer. Both quality controls and clinical blood samples were used in these experiments. To assess the quality of the newly developed mobile phase buffers, precision, accuracy, linearity, carryover, interference, bias, correlation with commercial reagents, and stability were analyzed.
UNASSIGNED: The CVs of intra-assay precision and interassay precision of quality control and clinical.There were fewer than 1.00 % blood sample assays using the newly developed mobile phase buffer. The RDs of accuracy were less than 1.00 %. Linearity: R2 = 0.9998 in the concentration range of 4.40%-17.30 %. Carryover: 0.00 %. Reagent comparison revealed that the Pearson regression equation was Y = 0.9884x+0.05692 (R2 = 0.9977), and the Bland-Altman mean difference was -0.02650 % (CI: -0.2121 %-0.1591 %) between the two analytical reagents. Stability was also acceptable within 12 months. This mobile phase buffer showed good anti-interference ability.
UNASSIGNED: The newly developed mobile phase buffers demonstrated good analytical performance and were suitable for clinical HbA1c assays on an ARKRAY HA-8160 Analyzer.

UNASSIGNED: This study aimed to explore the stable longitudinal patient-centered self-protective factors of glycosylated hemoglobin (HbA1c) in adolescents with type 1 diabetes mellitus (T1DM).
UNASSIGNED: We used both cross-sectional and longitudinal datasets at the Diabetes Education Center and National Endocrine and Metabolism Centre of a university hospital in China from April 2020 to July 2022. Participants were assessed using the Adolescent Diabetic Behavior Rating Scale (DBRS), Diabetes Strengths and Resilience Measure for Adolescents (DSTAR-Teen). HbA1c and other clinical variables were obtained from the medical record at the same time. 266 adolescents (131 male, age 14.1±3.9 years) completed the cross-sectional assessments and 131 (62 male, age 14.6±3.3 years) participated in a follow-up at a 1-year visit interval.
UNASSIGNED: Logistic regression analysis of cross-sectional data of 266 cases showed that there were significant positive effects between pump treatment (β=0.090, OR 2.460, P=0.005), DBRS scores (β=2.593, OR 13.366, P=0.002) and the meeting of standard HbA1c (<7.5%, 58 mmol/mol). Disease duration (β=-0.071, OR 0.932, P=0.033) was negatively correlated with it. The longitudinal multivariate generalized estimation equation model showed that DBRS scores (β=3.165, OR 23.681, P=0.009) and DSTAR-Teen scores (β=0.050, OR 1.051, P=0.012) had a positive influence on the meeting of standard HbA1c over one year time of 131 cases.
UNASSIGNED: Self-care and resilience had higher cross-temporal stability in influencing glycemic control over time. To reach a better glycemic control and improve long-term health outcomes, attention should be paid to the detection and enhancement of these patient-centered promoters.

UNASSIGNED: Hyperglycemia in individuals with diabetes is associated with chronic kidney disease (CKD); however, little is known about its association with those without diabetes. Our goal was to investigate the association between glycemic indicators and CKD in individuals without diabetes.
UNASSIGNED: This cross-sectional study included 9610 participants without diabetes who participated in the Health and Nutrition Examination Survey between 2005 and 2016. Exposures included postprandial glucose dip (PGD), fasting blood glucose (FBG), oral glucose tolerance test two-hour blood glucose (OGTT-2HBG), and glycated hemoglobin (HbA1C) levels. Moreover, CKD was defined as an estimated glomerular filtration rate below 60 mL/min per 1.73 m2 or a urinary albumin-creatinine ratio of ≥ 30 mg/g. Two multivariate models were constructed. Interaction effects were also explored.
UNASSIGNED: The mean age of the participants was 46.0 years, with 50.3 % being females. The prevalence of CKD was 12.6 %. In the final multivariable models, the odds ratios (ORs) for CKD were 1.51 (95 % confidence interval [CI]: 1.22,1.88, p < 0.001) for participants in the highest quartile of PGD,1.46 (95 %CI: 1.13,1.87, p = 0.004) for OGTT-2HBG, and 1.33 (95 %CI: 1.04,1.70, p = 0.020) for HbA1C, when compared with the quartile 1. No significant association was observed between FBG levels and CKD in the final model. Additionally, interactions were observed between PGD and body mass index, as well as between PGD and alcohol consumption in relation to CKD.
UNASSIGNED: The study identified that high levels of PGD, OGTT-2HBG, and HBA1C were significantly associated with a high prevalence of CKD in individuals without diabetes.

This systematic review was aimed to evaluate the effect of non-surgical periodontal therapy (NSPT) on hemoglobin A1c (HbA1c) in periodontitis patients without diabetes mellitus (DM).
The present systematic review and meta-analysis were performed through searching the following electronic databases: EMBASE, MEDLINE, Web of Science, Cochrane Library and Open GREY. Interventional studies of periodontitis patients without DM were investigated. HbA1c changes in these patients before and after NSPT were analyzed. Subgroup analysis and sensitivity analysis were employed to identify sources of heterogeneity.
Three reviewers independently selected the eligible studies by screening the titles and abstract. Then, a full-text analysis was performed. The reasons for excluding studies were recorded. Any disagreements were settled by discussion with a fourth reviewer. All the four reviewers extracted and crosschecked the data, and disagreements were resolved by discussion. There are 21 case-series studies (self-controlled studies) and 1 non-randomized interventional studies (NRIs) were included.
For periodontitis patients without DM, a total of 469 individuals from 22 studies were enrolled. The pooled analysis demonstrated that it was significantly changed in HbA1c levels at 3-month follow-up (0.16 with 95 % CI 0.04, 0.27; P = 0.008), and 6-month follow-up (0.17 % with 95 % CI 0.08, 0.27; P < 0.001) compared with baseline. Smoking, gender, experience of periodontal therapy and HbA1c value at baseline could be the sources of heterogeneity.
NSPT is potentially beneficial for the management of HbA1c in periodontitis patients with high risks of DM. However, high-quality randomized controlled trials are still necessary to confirm these conclusions.
The systemic review evaluated the effect of NSPT on HbA1c in periodontitis patients without DM. The analysis may be beneficial to the management and control of the high risks of DM in periodontitis patients.

OBJECTIVE: Some studies show that high circulating cystatin C (CysC) may predict cardiovascular events and death after ischemic stroke onset. However, the association between serum CysC and outcome in ischemic stroke patients remains contradictory. We sought to assess the association between a specific stroke subgroup, brainstem infarction (BSI) and serum CysC.
METHODS: A total of 324 acute BSI patients were included in the study. Serum CysC was used to calculate estimated glomerular filtration rate (eGFRCysC) at baseline. Modified Rankin scale score ((mRS) ≥3) six months after acute BSI indicates poor functional outcome. Patients were categorized into two groups according to mRS and eGFRCysC. Logistic regression analyses were performed to determine independent risk factors.
RESULTS: Lower eGFRCysC was associated with hemoglobin A1c (HbA1c). This risk remained statistically significant after controlling for age, hypertension, initial National Institutes of Health Stroke Scale (NIHSS) score, HbA1c, fibrinogen and homocysteine. The serum eGFRCysC levels were significantly lower in the poor functional outcome group than the good functional outcome group (P<0.001). Multivariate logistic regression analyses showed that eGFRCysC level was significantly lower in the poor outcome group after adjusting for age, previous infarctions, initial NIHSS score, and HbA1c.
CONCLUSIONS: Lower eGFRCysC levels were strongly associated with poor functional outcome of acute BSI patients with a higher HbA1c level. Lower eGFRCysC may be a more helpful serologic biomarker for the prediction of prognosis in BSI.

BACKGROUND: At present, the relationship between serum uric acid and blood glucose is controversial, and even opposite conclusions have been reached. We aimed to investigate the relationship between time in range and serum uric acid and estimate the influence of serum uric acid on blood glucose fluctuations in Chinese patients with type-2 diabetes mellitus (T2DM).
METHODS: A total of 458 hospitalized patients with T2DM were selected. According to the SUA level, patients were divided into four groups by quartile: Q1 (≤ 254.5 µmol/L), Q2 (254.5-306.0 µmol/L), Q3 (306.0-385.5 µmol/L) and Q4 (> 385.5 µmol/L). The differences in general data, TIR and other clinical indicators between the four groups were assessed. Multifactor regression was used to analyze the relationship between subgroups of SUA and TIR, TBR, TAR, MAGE, SD, ADRR, MODD and M value. Curve fitting was used to analyze the association between TIR and SUA and to identify the inflection point.
RESULTS: TIR showed an overall increasing trend with increasing SUA, while HbA1c, TAR, MAGE, SD, ADRR, MODD and M value showed an overall decreasing trend with increasing SUA. Multivariate regression analysis showed that, compared with Q1, there was no correlation between SUA and TIR, TAR, ADRR, SD, or MODD in all models of Q2. In the Q3 and Q4 groups, SUA was correlated with SD, MODD, and MAGE in all models. In the Q4 group, SUA was correlated with TIR, TAR, ADRR, and the M value in all models. When SUA > 306 µmol/L (Q3 and Q4), TIR and SUA have a curve-like relationship, and the inflection point of the fitted curve was SUA = 460 mmol/L. Before the inflection point, β was 0.1, indicating that when SUA increases by 10 mmol/L, the corresponding TIR increases by 1%. After the inflection point, there was no significant difference in the correlation between TIR and SUA (P > 0.05).
CONCLUSIONS: There is a close relationship between TIR and SUA in T2DM patients, it is speculated that SUA in a certain range had a positive protective effect on blood glucose control.

BACKGROUND: Previous studies have associated diabetes with reduced shoulder motion, increased pain, and higher postoperative retear risk after arthroscopic rotator cuff repair (ARCR). However, the impact of glycemic control, measured by hemoglobin A1c (HbA1c) levels, on retear and revision rates after ARCR in diabetic patients remains unclear.
METHODS: This systematic review was conducted using the PubMed, Cochrane Library, Web of Science, and Embase databases according to the preferred reporting conventions for systematic reviews and meta-analyses. Only studies that compared retears and revisions in ARCR patients with documented HbA1c levels between controlled and uncontrolled diabetes groups were included. Relevant data were extracted and analyzed using STATA software. The methodological index for nonrandomized studies was employed to assess the risk of bias in the selected studies. Additionally, heterogeneity tests and sensitivity analyses were conducted to evaluate potential heterogeneity within the samples, and publication bias was also detected.
RESULTS: Six studies (4395 patients), including five retrospective cohort studies and one case‒control study, were included. Four of these studies assessed retears involving 253 patients. Lower HbA1c levels, indicating better glycemic control, were significantly associated with reduced retear rates after ARCR in diabetic patients (P = 0.000; odds ratio = 0.242, 95 % confidence interval: 0.128-0.454; I2 = 25 %). For revision evaluations, two studies, with a total of 4142 patients, found no significant difference in rates between controlled and uncontrolled diabetes groups, and no publication bias was detected.
CONCLUSIONS: Following ARCR in diabetic patients, effective glycemic control significantly reduces retear rates without affecting revisions, and maintaining glycemic control in the postoperative period may contribute to rotator cuff healing.