Several studies have indicated that inflammatory markers were associated with the risk of mild cognitive impairment (MCI) in type 2 diabetes (T2D). Serum folate was related to MCI as well as inflammation. However, no studies have investigated the association between inflammatory markers and MCI taking account of serum folate level in T2D patients. This study aimed to conduct a case-control study to evaluate the association between inflammatory markers and MCI taking account of serum folate level in Chinese patients with T2D. This study consisted of 126 T2D patients (63 cases with MCI and 63 controls without MCI). Clinical parameters, serum folate, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) were measured. Spearman correlation analysis and logistic regression analysis were used to analyze the association between the inflammatory markers and the risk of MCI in T2D patients. There were higher serum hs-CRP, IL-6 and TNF-α in T2D cases with MCI compared with the controls. Serum folate was negatively correlated with hs-CRP, TNF-α, and IL-6 (P < 0.05). In multivariate analysis, there were significant associations between serum IL-6 or hs-CRP and MCI after adjusting for the confounding variables, however, the association between hs-CRP and MCI disappeared after further adjusting for serum folate. Further subgroup analysis revealed that the significant association between hs-CRP and MCI only existed in the low folate subgroup (< 7.0 μg/L; OR = 3.34, 95% CI: 1.05–10.64), not in the high folate subgroup (≥7.0 μg/L; OR = 2.16, 95% CI: 0.68–6.88) after adjusting for the confounding variables. Serum IL-6 and hs-CRP were associated with the risk of MCI in Chinese patients with T2D. Serum folate might modify the association between serum hs-CRP and MCI in T2D patients.

Background: Treatment with the alpha-glucosidase inhibitor (AGI) acarbose is associated with a significant reduction the risk of cardiovascular events. However, the underlying mechanisms of this effect are unclear. AGIs were recently suggested to participate in stimulating glucagon-like peptide 1 (GLP-1) secretion. We therefore examined the effects of a 24-week treatment of acarbose on endogenous GLP-1, nitric oxide (NO) levels, nitric oxide synthase (NOS) activity, and carotid intima-media thickness (CIMT) in newly diagnosed patients with type 2 diabetes (T2D). Methods: Blood was drawn from 24 subjects (14 male, 10 female, age: 50.7 ± 7.36 years, BMI: 26.64 ± 3.38 kg/m², GHbA1c: 7.00 ± 0.74%) with drug-naïve T2D at 0 and 120 min following a standard mixed meal for the measurements of active GLP-1, NO and NOS. The CIMT was measured prior to and following 24 weeks of acarbose monotherapy (mean dose: 268 mg daily). Results: Following 24 weeks of acarbose treatment, both fasting and postprandial plasma GLP-1 levels were increased. In patients with increased postprandial GLP-1 levels, serum NO levels and NOS activities were also significantly increased and were positively related to GLP-1 levels. Although the CIMT was not significantly altered following treatment with acarbose, a decreased CIMT was negatively correlated with increased GLP-1 levels. Conclusions: Twenty-four weeks of acarbose monotherapy in newly diagnosed patients with T2D is associated with significantly increased levels of both fasting and postprandial GLP-1 as well as significantly increased NO levels and NOS activity for those patients in whom postprandial GLP-1 levels were increased. Therefore, the benefits of acarbose on cardiovascular risk may be related to its stimulation of GLP-1 secretion.

Non-proliferative diabetic retinopathy is the early stage of diabetic retinopathy. Automatic detection of non-proliferative diabetic retinopathy is significant for clinical diagnosis, early screening and course progression of patients. This paper introduces the design and implementation of an automatic system for screening non-proliferative diabetic retinopathy based on color fundus images. Firstly, the fundus structures, including blood vessels, optic disc and macula, are extracted and located, respectively. In particular, a new optic disc localization method using parabolic fitting is proposed based on the physiological structure characteristics of optic disc and blood vessels. Then, early lesions, such as microaneurysms, hemorrhages and hard exudates, are detected based on their respective characteristics. An equivalent optical model simulating human eyes is designed based on the anatomical structure of retina. Main structures and early lesions are reconstructed in the 3D space for better visualization. Finally, the severity of each image is evaluated based on the international criteria of diabetic retinopathy. The system has been tested on public databases and images from hospitals. Experimental results demonstrate that the proposed system achieves high accuracy for main structures and early lesions detection. The results of severity classification for non-proliferative diabetic retinopathy are also accurate and suitable. Our system can assist ophthalmologists for clinical diagnosis, automatic screening and course progression of patients.

Yue XD, et al. J Korean Med Sci. 2017 Apr;32(4):621-627. https://doi.org/10.3346/jkms.2017.32.4.621

Objective: We aimed to study the cut-off values of estimated glomerular filtration rate (eGFR) and the urinary albumin creatinine ratio (UACR) in the normal range for diabetic kidney disease (DKD).Methods: In this study, we conducted a retrospective, observational cohort study included 374 type 2 diabetic patients who had baseline eGFR ≥60 mL/min/1.73 m² and UACR <30 mg/g with up to 6 years of follow-up. The results were further validated in a multi-center, prospective cohort study.Results: In the development cohort, baseline eGFR (AUC: 0.90, cut-off value: 84.8 mL/min/1.73 m², sensitivity: 0.80, specificity: 0.85) or UACR (AUC: 0.74, cut-off value: 15.5mg/g, sensitivity: 0.69, specificity: 0.63) was the most effective single predictor for DKD. Moreover, compared with eGFR or UACR alone, the prediction model consisted of all of the independent risk factors did not improve the predictive performance (P &gt;0.05). The discrimination of eGFR at the cut-off value of 84.80 mL/min/1.73 m2 or UACR at 15.5mg/g with the largest Youden’s index was further confirmed in the validation cohort. The decrease rate of eGFR was faster in patients with UACR ≥15.5mg/g (P &lt;0.05). Furthermore, the decrease rate of eGFR or increase rate of UACR and the incidence and severity of cardiovascular disease (CVD) were higher in patients with eGFR ≤84.8 mL/min/1.73 m² or UACR ≥15.5mg/g (P &lt;0.05).Conclusions: In conclusion, eGFR ≤84.8mL/min/1.73 m² or UACR ≥15.5mg/g in the normal range may be an effective cut-off value for DKD and may increase the incidence and severity for CVD in type 2 diabetic patients.

Aim. Patients with diabetic ketosis often exhibit albuminuria. We previously found that acute hyperglycaemia can cause nephrotoxic injury. Here, we explored whether an excessive ketone body level causes kidney injury and the potential underlying mechanism. Methods. Fifty-six type 2 diabetes without ketosis (NDK group), 81 type 2 diabetes with ketosis (DK group), and 38 healthy controls (NC group) were enrolled. Clinical data were collected before and after controlling diabetic ketosis. Beta-hydroxybutyric acid (BOHB), an AKT activator, an AKT inhibitor, or plasmids encoding DAB2 were transformed into human renal proximal tubule epithelial cells (HK-2 cells). Results. The urinary albumin-to-creatinine ratio (ACR), transferrin (TF), immunoglobulin G (IgG), Beta2-microglobulin (β2-MG), retinol-binding protein (RBP), N-acetyl-beta-glucosaminidase (NAG), and Beta-galactosidase (GAL) were higher in the DK than NC and NDK groups. The proportion of patients with an increased urinary level of TF, IgG, β2-MG, RBP, NAG, or GAL was higher in the DK group too. After controlling ketosis, urinary microalbumin, TF, IgG, β2-MG, and RBP decreased significantly. In HK-2 cells, albumin endocytosis and megalin expression decreased with increasing BOHB concentration. Compared with BOHB treatment, BOHB with AKT activator significantly increased the DAB2, megalin levels and albumin endocytosis; the AKT inhibitor treatment exhibited the opposite effects. Compared with BOHB treatment, megalin expression and albumin endocytosis were significantly increased after BOHB with DAB2 overexpression treatment. Conclusions. Patients with diabetic ketosis may suffer from glomerular and tubular injuries that recover after ketosis control. High concentrations of BOHB downregulate megalin expression by inhibiting the AKT/DAB2/megalin signalling pathway and albumin endocytosis in proximal renal tubules.