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.

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.

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.

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.

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.