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BACKGROUND: Patients with type 2 diabetes often face early tubular injury, necessitating effective treatment strategies. This study aimed to evaluate the impact of the SGLT2 inhibitor empagliflozin on early tubular injury biomarkers in type 2 diabetes patients with normoalbuminuria. METHODS: A randomized controlled clinical study comprising 54 patients selected based on specific criteria was conducted. Patients were divided into an intervention group (empagliflozin, n = 27) and a control group (n = 27) and treated for 6 weeks. Tubular injury biomarkers KIM-1 and NGAL were assessed pre- and post-treatment. RESULTS: Both groups demonstrated comparable baseline characteristics. Post-treatment, fasting and postprandial blood glucose levels decreased similarly in both groups. The intervention group exhibited better improvements in total cholesterol, low-density lipoprotein, and blood uric acid levels. Renal function indicators, including UACR and eGFR, showed greater enhancements in the intervention group. Significant reductions in KIM-1 and NGAL were observed in the intervention group. CONCLUSION: Treatment with empagliflozin in type 2 diabetes patients with normoalbuminuria led to a notable decrease in tubular injury biomarkers KIM-1 and NGAL. These findings highlight the potential of SGLT2 inhibitors in early tubular protection, offering a new therapeutic approach.

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AIMS: To observe the alterations in functional magnetic resonance imaging parameters in normoalbuminuric type 2 diabetic patients undergoing SGLT2 inhibitor empagliflozin treatment and investigate the early tubular protective effects of the inhibitor. METHODS: This study was performed in normoalbuminuric type 2 diabetes mellitus patients (UACR < 30 mg/g, eGFR ≥ 60 ml/min/1.73 m2). The patients were divided into the intervention group (empagliflozin) and the control group (27 cases each). The intervention group was treated with 10 mg/day empagliflozin tablets orally, while the control group had adjustments to their basic treatment stage. The patients were treated for 6 weeks. RESULTS: The baseline clinical data of the two groups were comparable (P˃0.05). The intervention group exhibited better improvements in blood lipid profiles and more significant reductions in blood uric acid levels compared to the control group (P < 0.05). The two groups had No significant difference in blood pressure changes (P˃0.05). Notably, the intervention group demonstrated a greater reduction in UACR and a more substantial decline in eGFR than the control group (P < 0.05). Regarding functional magnetic resonance imaging parameters, the MD value of the renal medulla region in the intervention group increased after treatment, while the MR2* value of the renal medulla region decreased (P < 0.05). CONCLUSIONS: SGLT2 inhibitor empagliflozin can reduce UACR and eGFR levels in early type 2 diabetic patients with normal proteinuria. Moreover, empagliflozin therapy led to an increase in the MD value and a decrease in the MR2* value of the renal medulla, evidencing the early tubular protective effects of this therapy.

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Objective: Both functional magnetic resonance imaging and renal tubular injury markers have been proved to be able to detect early renal damage in normoalbuminuric diabetic patients. This study mainly explored the functional magnetic resonance imaging parameters and renal tubular injury markers in the early evaluation of type 2 diabetes. Methods: A case observation study was established, and 62 patients with early-stage low-risk type 2 diabetes mellitus with normoalbuminuric (UACR<30 mg/g, eGFR≥60 ml/min/1.73 m2) were included for analysis. Urine kidney damage was determined by ELISA. Kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) assessment of renal tubular injury, and use of intravoxel incoherent motion magnetic resonance Imaging (intravoxel incoherent motion, IVIM) and blood oxygen level dependent magnetic resonance imaging (blood oxygen level dependent, BOLD) to evaluate renal cortex, medulla blood perfusion, water molecule diffusion, oxygenation level and other functional information, using linear correlation to analyze the correlation between functional magnetic resonance imaging parameters and markers of renal tubular injury. Results: The correlation analysis between IVIM parameters and renal tubular injury markers showed that KIM-1 was inversely correlated with the MD value of the renal medulla region parameter (r = -0.24, P = .03), and was closely related to the other IVIM cortex and medulla. There was no correlation between qualitative parameters (P > .05), and no correlation between NGAL and all parameters of IVIM (P > .05). The correlation analysis between BOLD parameters and renal tubular injury markers showed that KIM-1 was positively correlated with renal medulla region parameter MR2* value (r = 0.26, P = .04) and MCR value (r = 0.28, P = .03), respectively. There was also a positive correlation between NGAL and renal medulla region parameter MR2* value (r = 0.24, P = .04). Conclusion: In the early low-risk type 2 diabetic patients with normoalbuminuria, the more obvious the renal medullary water molecule diffusion disorder, the higher the renal tubular injury marker KIM-1, and the more severe renal medullary hypoxia, the renal tubular injury. The higher the markers KIM-1 and NGAL are, it is proved that the hypoxia and water diffusion disorder in the early renal medulla are related to renal tubular damage.

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OBJECTIVE: To explore the clinical outcomes and establish a predictive model of hypoglycemia during colonoscopy preparation for diabetic patients. METHODS: Three-hundred ninety-four patients with diabetes who received colonoscopy were retrospectively enrolled in this study and assigned to hypoglycemia or non-hypoglycemia groups. Information about clinical characteristics and outcomes during colonoscopy preparation was collected and compared between the two groups. Logistic regression analysis was applied to identify the risk factors of hypoglycemia. These risk factors were used to construct a hypoglycemia predictive model verified by the receiver operating characteristic (ROC) curve and Hosmer-Lemeshow goodness fit test. RESULTS: Among 394 participants, 66 (16.8%) underwent a total of 88 hypoglycemia attacks during the bowel preparation. Grade 1 hypoglycemia (≤3.9 mmol/L) comprised 90.9% (80/88) of all hypoglycemia attacks and grade 2 hypoglycemia accounted for 9.1% (8/88), signifying that grade 1 hypoglycemia is the most common type. No severe hypoglycemia was identified. The incidence of nocturnal hypoglycemia was 15.9%. Logistic regression analyses revealed that the main risk factors of hypoglycemia during colonoscopy preparation were postprandial C-peptide, serum triglyceride, gender, type of diabetes mellitus, and insulin injection frequencies. The area under the ROC curve of the hypoglycemia prediction model was 0.777 (95% CI: 0.720-0.833). CONCLUSION: Diabetic patients are prone to develop mild to moderate hypoglycemia during colonoscopy preparation. This study proposes a predictive model that could provide a reference for identifying patients with a high risk of hypoglycemia during colonoscopy preparation.

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OBJECTIVE: This study investigated the correlation of liver fat content (LFC) with metabolic characteristics and its association with chronic complications in type 2 diabetes mellitus (T2DM) patients. METHODS: Eighty-one prospectively enrolled T2DM patients were divided into non-alcoholic fatty liver disease (NAFLD) group and the non-NAFLD group according to the presence of NAFL complications. LFC was determined by MRI IDEAL-IQ Sequence, and patients were divided into 4 groups according to LFC by quartile method. Basic information, metabolic indexes, and occurrence of chronic complications in different groups were analyzed and compared. RESULTS: BMI, SBP, DBP, TG, ALT, AST, GGT, UA, HbA1c, FCP, 2 h CP, HOMA-IR, and HOMA-IS in the NAFLD group were significantly higher than the non-NAFLD group (P < 0.05). The incidences of chronic complications in the NAFLD group were higher than in the non-NAFLD group but not statistically significant (P > 0.05). BMI, SBP, DBP, TC, TG, ALT, AST, FCP, 2 h CP, HOMA-IR, and HOMA-IS showed significant differences between the patients with different LFC, and these indexes were significantly higher in patients with higher LFC than those with lower LFC (P < 0.05). Moreover, diabetes duration, TC, HOMA-IR, and LFC were the risk factors for ASCVD complications, while diabetes duration, TG, and LDL-C were risk factors for DN complications. Also, diabetes duration and SBP were risk factors for both DR and DPN complications in T2DM patients (P < 0.05). CONCLUSION: LFC is positively correlated with the severity of the systemic metabolic disorder and chronic complications in T2DM patients.

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BACKGROUND: This work explored the effect of eKTANG, a new healthcare mode for diabetes patients, on diabetes management. METHODS: Allowing general utilization of medical service and health management based on Internet, eKTANG obtained the precise data like blood glucose and blood pressure examined by an intelligent glucometer, from which doctors and the nursing team will promptly analyze the data and return feedback to the patients. In our study, overall 204 patients receiving eKTANG management over 3 months in First Affiliated Hospital of Jinan University from May 2019 to Aug 2020 were enrolled as the research objects, with data collected from patient records. RESULTS: Through the biochemical test on relevant indexes of blood glucose, it was observed that FBG, PBG, HbA1c, TG, TC, LDL levels after management were lower than before whereas HDL expression after were lower than before. Contrasted with substandard group, standard group performed younger age, lower proportion of the married, decreased proportion of microvascular and macrovascular complications, longer course of disease, more frequent glucose monitoring, declined time of hyperglycemia and time of alarms, elevated time of euglycemia, increased proportion of diet control, more amount of exercise and higher compliance, as the number of patients choosing oral medicine in standard group was more than substandard group. The course of disease and time of hyperglycemia were risk factors of HbA1c standard reaching whereas frequency of glucose monitoring (≥1 time/week) and time of euglycemia were protective factors. CONCLUSION: eKTANG effectively improved diabetes management.

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BACKGROUND: This study aims to examine the cross-sectional association between serum total bilirubin (STB) and type 2 diabetes (T2D) risk in the general population, and whether obesity could moderate this association. METHODS: We used data from the 1999-2018 National Health and Nutrition Examination Surveys (NHANES), including a total of 38,641 US adult participants who were 18 years or older. The STB was classified as the low, moderate, and high groups according to tertiles. RESULTS: We found that participants with lower STB had a significantly higher risk of T2D than those with moderate (OR = 0.81; 95% CI 0.74, 0.89; P < 0.001) and high (OR = 0.65; 95% CI 0.59, 0.73; P < 0.001) STB. Also, a significant interaction between body mass index (BMI) and STB on T2D was observed (P < 0.001). Stratified analysis showed that low STB was associated with a 20% and 27% decrease of T2D risk for moderate and high STB groups in obese patients, however, these effect estimates were smaller in the population with lower BMI (< 30 kg/m2). Similar associations of STB with glycohemoglobin and insulin resistance were observed. CONCLUSION: This study suggests that STB is associated with an elevated risk of T2D. More importantly, we reported for the first time that BMI may moderate the association between bilirubin and T2D.

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To explore the relationship of glycemic variability with lower extremity arterial disease (LEAD) and diabetic peripheral neuropathy (DPN).Seventy-eight patients with type 2 diabetes were enrolled. All patients underwent 72-hour dynamic blood glucose monitoring and obtained mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), standard deviation of blood glucose (SD), largest amplitude of glycemic excursion (LAGE), mean blood glucose (MBG), T≥10.0 (percentage of time for blood glucose levels ≥10.0 mmol/L), T≤3.9 (percentage of time for blood glucose levels ≤3.9 mmol/L), and other glycemic variability parameters. In the meanwhile, in order to explore the correlation of glycemic variability parameters with ankle-brachial index (ABI), vibration perception threshold (VPT), and current perception threshold (CPT), all patients underwent quantitative diabetic foot screening, including ABI for quantitative assessment of lower extremity arterial lesions and VPT and CPT for quantitative assessment of peripheral neuropathy.Patients were divided into abnormal CPT group (n = 21) and normal CPT group (n = 57) according to the CPT values. Compared with the normal CPT group, abnormal CPT group showed significantly higher levels of HbA1c, longer duration of diabetes, and higher levels of T≤3.9 (P < .05). However, there was no significant difference of MAGE, SD, LAGE, MODD, and other glycemic variability parameters between abnormal CPT group and normal CPT group (P > .05). Pearson correlation analysis or Spearman correlation analysis showed that ABI negatively correlated with MBG, T≥10.0, SD, LAGE, and MAGE (P < .05), but no correlation of ABI with T≤3.9 and MODD (P > .05) was shown. VPT showed a positive correlation with T≥10.0 (P < .05), but no correlation with other glycemic variability parameters (P > .05). There was no correlation between the other CPT values and the glycemic variability parameters (P > .05), except that the left and right 250 Hz CPT values were positively correlated with T≤3.9 (P > .05).The higher the blood glucose levels, the severer the degree of LEAD and DPN lesions; the higher the incidence of hypoglycemia, the severer the degree of DPN lesions; the greater the fluctuation of blood glucose, the severer the degree of LEAD lesions. However, the glycemic variability was not significantly correlated with DPN.

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OBJECTIVE: Patients with diabetes mellitus, diabetic nephropathy (DN) and healthy donor were analyzed to test whether the early DN patients can be detected using both blood oxygenation level dependent (BOLD) and diffusion tensor imaging. METHODS: This study was approved by the Ethics Committee of our hospital. MR images were acquired on a 3.0-Tesla MR system (Discovery MR750, General Electric, Milwaukee, WI). 30 diabetic patients were divided into NAU (normal to mildly increased albuminuria, N = 15) and MAU (moderately increased albuminuria, N = 15) group based on the absence or presence of microalbuminuria. 15 controls with sex- and age-matched were enrolled in the study. Prior to MRI scan, all participants were instructed to collect their fresh morning urine samples for quantitative measurement of urinary microalbumin and urinary creatinine. Then, the estimations of serum creatinine, serum uric acid, HbAlc and fasting plasma glucose as well as fundus examinations were performed in all subjects. Then, the values of albumin-creatinine ratio (ACR) and estimated glomerular filtration rate were also calculated. All subjects underwent renal diffusion tensor imaging (DTI) and BOLD acquisition after fasting for 4 h. Regions of interest were placed in renal medulla and cortex for evaluating apparent diffusion coefficient (ADC), fractional anisotropy (FA) and R2* values by two experienced radiologists. The consistency between the two observations was estimated using intragroup correlation coefficients. To test differences in ADC, FA and R2* values across the three groups, the data were analyzed using separate one-way ANOVAs. Post-hoc pair wise comparisons were then performed using t-test. To investigate the clinical relevance of imaging parameters in both regions across the three groups, the correlations of values of the ACR/estimated glomerular filtration rate and of the ADC/FA/R2* were calculated. RESULTS: There was a high level of consistency of those ADC, FA and R2* values across the three groups on both renal cortex and medulla measured by the two doctors. The FA value of medulla in MAU group was lower than that in control (p < 0.01). The R2* value of medulla in the NAU group was higher than that in the control (p < 0.01), and the R2* value of medulla in the MAU group was lower than that in the control (p = 0.009) . Moreover, the current study revealed a decreasing trend in FA values of the renal medulla from the control group to NAU and MAU groups. Finally, a weak negatively correlation between medullary R2* and ACR was found in current study. CONCLUSION: Medullary R2* value might be a new more sensitive predictor of early DN. Meanwhile, BOLD imaging detected the medullary hypoxia at the simply diabetic stage, while DTI didn't identify the medullary directional diffusion changes at this stage. Based on our assumption mentioned above, it's presumable that BOLD imaging may be more sensitive for assessment of the early renal function changes than DTI. These imaging techniques are more accurate and practical than conventional tests. ADVANCES IN KNOWLEDGE: Non-invasive MRI was used to detect renal function changes at early DN stage.

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The retinol-binding protein 4 (RBP4) has been postulated to play a role in glucose homeostasis, insulin resistance, and diabetes mellitus in human and animal studies. The aim of the present study was to evaluate the role of RBP4 in Chinese patients with type 2 diabetes mellitus with and without diabetic retinopathy (DR). Plasma RBP4 concentrations were tested in 287 patients with type 2 diabetes. At baseline, demographic and clinical information including presence of DR and vision-threatening DR (VTDR) was collected. The relationship between RBP4 and DR (VTDR) was investigated using logistic regression. Patients with DR or VTDR had significantly higher plasma levels of RBP4 on admission (P<0.0001). Receiver operating characteristics (ROCs) to predict DR and VDTR demonstrated areas under the curve for RBP4 of 0.79 (95% confidence interval (CI): 0.73-0.85) and 0.90 (95% CI: 0.85-0.94), respectively, which were superior to other factors. For each 1 µg/ml increase in plasma level of RBP4, the unadjusted and adjusted risk of DR would be increased by 8% (with the odds ratio (OR) of 1.08 (95% CI: 1.05-1.13), P<0.001) and 5% (1.05 (1.02-1.11), P=0.001), respectively. It was 12% (with the OR of 1.12 (95% CI: 1.07-1.18), P<0.001) and 9% (1.09 (1.05-1.15), P<0.001) for VTDR. The present study shows that elevated plasma levels of RBP4 were associated with DR and VDTR in Chinese patients with type 2 diabetes, suggesting a possible role of RBP4 in the pathogenesis of DR complications. Lowering RBP4 could be a new strategy for treating type 2 diabetes with DR.

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