Amide proton transfer weighted contrast has diagnostic capacity in detecting diabetic foot: an MRI-based case-control study.

Objective: To evaluate the role of foot muscle amide proton transfer weighted (APTw) contrast and tissue rest perfusion in quantifying diabetic foot (DF) infection and its correlation with blood parameters. Materials and methods: With approval from an ethical review board, this study included 40 diabetes mellitus (DM) patients with DF and 31 DM patients without DF or other lower extremity arterial disease. All subjects underwent MRI, which included foot sagittal APTw and coronal arterial spin labeling (ASL) imaging. The normalized MTRasym (3.5 ppm) and the ratio of blood flow (rBF) in rest status of the affected side lesions to the non-affected contralateral side were determined. The inter-group differences of these variables were evaluated. Furthermore, the association between normalized MTRasym (3.5 ppm), rBF, and blood parameters [fasting blood glucose (FBG), glycosylated hemoglobin content, C-reactive protein, neutrophil percentage, and white blood cell count] was explored. Using an ROC curve, the diagnostic capacity of normalized MTRasym (3.5 ppm), BF, and blood biochemical markers in differentiating with or without DF in DM was assessed. Results: In the DF group, MTRasym (3.5 ppm) and BF in lesion and normalized MTRasym (3.5 ppm) were higher than those in the control group (p < 0.05). In addition, correlations were identified between normalized MTRasym (3.5 ppm) and blood parameters, such as C-reactive protein, glycosylated hemoglobin content, FBG, neutrophil ratio, and white blood cell (p < 0.001). Meanwhile, association between BF in lesion and blood parameters, such as C-reactive protein, neutrophil percentage, and FBG (p < 0.01). AUC of normalized MTRasym (3.5 ppm) in identifying with/without DF in patients with DM is 0.986 (95% CI, 0.918-1.00) with the sensitivity of 97.22% and the specificity of 100%. Conclusion: Normalized MTRasym (3.5 ppm) and the BF in lesion may be treated as a safer and more convenient new indicator to evaluate the tissue infection without using a contrast agent, which may be useful in monitoring and preoperatively assessing DF patients with renal insufficiency.

Canagliflozin reverses Th1/Th2 imbalance and promotes podocyte autophagy in rats with membranous nephropathy.

Idiopathic membranous nephropathy is the main cause of chronic kidney disease (CKD). Studies have shown sodium-glucose co-transporter 2 (SGLT2) inhibitors significantly delay renal outcomes in patients with CKD, but the exact mechanism remains unknown. In this study, we investigated the mechanism by which the SGLT2 inhibitor canagliflozin attenuates podocyte injury by reversing the imbalance in Helper T cell 1 (Th1)/Helper T cell 2 (Th2) in peripheral blood of rats with membranous nephropathy (MN). MN rats were gavaged with canagliflozin (10 mg/kg/d) and losartan (10 mg/kg/d), respectively, for eight weeks. Compared with the MN group, the urinary ratio of total protein and the creatinine levels of the canagliflozin group decreased significantly. Canagliflozin improved the glomerulus pathological damage, increased the expression levels of podocyte marker proteins. The protective effect of canagliflozin on kidneys was more obvious than that of losartan. Treatment with canagliflozin increased the proportion of Th1 cells by 2.3 times, decreased the proportion of Th2 cells by 68.5%, and significantly restrained the synthesis of immunoglobulin G1 in B-cells and glomerulus subepithelial immune complex deposition. Co-culture of B-cells derived from MN rats with podocytes triggered the activation of phosphorylation of mTOR and ULK1 of podocytes, inhibited podocyte autophagy and resulted in podocyte injury. B-cells derived from canagliflozin treatment rats reversed these effects above. In conclusion, canagliflozin exerts a protective effect on kidneys by reversing the imbalance in Th1/Th2 cells in MN rats and restoring the autophagy of podocytes inhibited by the abnormal immunoglobulin G secretion from B-cells.

Effects of INSR genetic polymorphism on hippocampal volume and episodic memory in chinese type 2 diabetes.

AIMS: We aimed to investigate the effect of the type 2 diabetes-specific insulin/IGF signaling genetic variants on the hippocampal volume and their relationships with episodic memory in Chinese patients with type 2 diabetes. METHODS: Analysis of variance was used to evaluate the genotype-by-diagnosis interaction effect on hippocampal volume in Chinese participants (109 patients with type 2 diabetes, 116 healthy controls). Mediation analysis was performed to test whether the hippocampal volume would mediate the association between genotype and episodic memory in patients with type 2 diabetes. RESULTS: INSR (rs8101064) exhibited a significant genotype-by-diagnosis interaction effect on the bilateral hippocampal volumes (left, P = 0.020; right, P = 0.004, PFDR < 0.05). The T allele carriers exhibited smaller bilateral hippocampal volumes than the CC homozygotes in patients with type 2 diabetes (left, P = 0.004; right, P = 0.002). Mediation analysis revealed the significant mediation effect of the left hippocampal volume on the association between INSR (rs8101064) genetic polymorphism and the short- and long-term memory scores in patients with type 2 diabetes (short-term memory: 95% CI, -2.716, -0.266; long-term memory: 95% CI, -0.823, -0.103). CONCLUSIONS: Hyperglycemia exposure and INSR (rs8101064) genetic polymorphism had an interaction effect on the hippocampal volume, and the T allele of the INSR (rs8101064) may serve as a risk factor for the decreased hippocampal volume in Chinese patients with type 2 diabetes. The left hippocampal volume mediated the effect of INSR (rs8101064) genetic polymorphism on episodic memory in Chinese patients with type 2 diabetes, which provided a biological pathway for understanding how the INSR (rs8101064) genetic polymorphism affects episodic memory in type 2 diabetes.

Neurovascular coupling alterations in type 2 diabetes: a 5-year longitudinal MRI study.

INTRODUCTION: Respective alterations in resting-state brain neural activity and cerebral blood flow (CBF) in type 2 diabetes mellitus (T2DM) have been reported. However, their coupling alteration in T2DM remains largely unknown. RESEARCH DESIGN AND METHODS: Twenty-seven patients with T2DM aged 40-67 years and 36 well-matched healthy controls (HCs) underwent resting-state functional MRI (rs-fMRI) and arterial spin labeling (ASL) scans at two time points with a 5-year interval. Regional homogeneity (ReHo) and CBF were calculated from rs-fMRI and ASL, respectively. The standardized ReHo:CBF ratio (mReHo:mCBF ratio), the spontaneous neuronal activity per unit CBF supply, was compared between the two time points. Relationships between the mReHo:mCBF ratio and memory performance were analyzed. RESULTS: Over 5 years, decreased mReHo:mCBF ratios in patients with T2DM were mainly distributed in four regions, among which the left insula exhibited more severely decreased mReHo:mCBF ratio in patients with T2DM than in HCs, while the left postcentral gyrus, the right Rolandic operculum, and the right precentral gyrus showed no significant intergroup difference. Correlations between the mReHo:mCBF ratio and memory performance were also found in patients with T2DM. CONCLUSIONS: This study suggests that T2DM may accelerate neurovascular coupling impairment in specific brain regions (the left insula), contributing to memory decline. This study implies that the mReHo:mCBF ratio is a potential imaging marker for detecting neurovascular changes.

Enhanced Functional Coupling of Hippocampal Sub-regions in Congenitally and Late Blind Subjects.

The hippocampus has exhibited navigation-related changes in volume and activity after visual deprivation; however, the resting-state functional connectivity (rsFC) changes of the hippocampus in the blind remains unknown. In this study, we focused on sub-region-specific rsFC changes of the hippocampus and their association with the onset age of blindness. The rsFC patterns of the hippocampal sub-regions (head, body and tail) were compared among 20 congenitally blind (CB), 42 late blind (LB), and 50 sighted controls (SC). Compared with the SC, both the CB and the LB showed increased hippocampal rsFCs with the posterior cingulate cortex, angular gyrus, parieto-occpital sulcus, middle occipito-temporal conjunction, inferior temporal gyrus, orbital frontal cortex, and middle frontal gyrus. In the blind subjects, the hippocampal tail had more extensive rsFC changes than the anterior hippocampus (body and head). The CB and the LB had similar changes in hippocampal rsFC. These altered rsFCs of the hippocampal sub-regions were neither correlated with onset age in the LB nor the duration of blindness in CB or LB subjects. The increased coupling of the hippocampal intrinsic functional network may reflect enhanced loading of the hippocampal-related networks for non-visual memory processing. Furthermore, the similar changes of hippocampal rsFCs between the CB and the LB suggests an experience-dependent rather than a developmental-dependent plasticity of the hippocampal intrinsic functional network.