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.

Preliminary observational study of metabonomics in patients with early and late-onset type 2 diabetes mellitus based on UPLC-Q-TOF/MS.

Non-targeted metabonomic techniques were used to explore changes in metabolic profiles of patients with early onset and late onset T2DM. Newly diagnosed early onset T2DM (EarT2DM) and late onset T2DM (LatT2DM) patients were recruited, and the matched age, sex, and low-risk population of diabetes mellitus were selected as the control group. 117 adults were recruited in the study, including 21 in EarT2DM group with 25 in corresponding control group (heaCG1), and 48 in LatT2DM group with 23 in corresponding control group (heaCG2). There were 15 relatively distinctive metabolic variants in EarT2DM group and 10 distinctive metabolic variants in LatT2DM group. The same changing pathways mainly involved protein, aminoacyl-tRNA biosynthesis, fatty acid biosynthesis, taurine metabolism, arginine biosynthesis, lysosome and mTOR signaling pathway. The independent disturbed pathways in EarT2DM included branched chain amino acids, alanine, aspartate and glutamate metabolism. The independent disturbed pathways in LatT2DM involved linoleic acid metabolism, biosynthesis of unsaturated fatty acids, arginine, proline metabolism and FoxO signaling pathway. T2DM patients at different diagnosed ages may have different metabolite profiles. These metabolic differences need to be further verified.

Key enzyme in charge of ketone reabsorption of renal tubular SMCT1 may be a new target in diabetic kidney disease.

OBJECTIVE: A ketogenic diet or mildly increased ketone body levels are beneficial for diabetic kidney disease (DKD) patients. Our previous study has found that sodium-coupled monocarboxylate transporter 1 (SMCT1), a key enzyme in charge of ketone reabsorption, possesses beneficial effects on the function of renal tubular epithelial cells (TECs) in energy crisis. Our present study is to investigate whether SMCT1 is important in maintaining the physiological function of renal tubular and plays a role in DKD. METHODS: We tested the expression of SMCT1 in kidney tissues from DKD patients receiving kidney biopsy as well as diabetes mice. We compared the difference of ß-hydroxybutyrate (ß-HB) levels in serum, urine and kidney tissues between diabetic mice and control. Using recombinant adeno-associated viral vector containing SMCT1 (encoded by Slc5a8 gene), we tested the effect of SMCT1 upregulation on microalbuminuria as well as its effects on mitochondrial energy metabolism in diabetic mice. Then we investigated the role of SMCT1 and its ß-HB reabsorption function in maintaining the physiological function of renal tubular using renal tubule-specific Slc5a8 gene knockout mice. Transcriptomes and proteomics analysis were used to explore the underlying mechanism. RESULTS: SMCT1 downregulation was found in DKD patients as well as in diabetic mice. Moreover, diabetic mice had a decreased renal ß-HB level compared with control, and SMCT1 upregulation could improve microalbuminuria and mitochondrial energy metabolism. In renal tubule-specific Slc5a8 gene knockout mice, microalbuminuria occurred early at 24 weeks of age, accompanied by ATP shortage and metabolic reprogramming in the kidney; however, supplementation with ß-HB precursor substance 1,3-butanediol in food alleviated kidney damage as well as energy metabolic reprogramming. CONCLUSIONS: Decreased SMCT1 expression and its ketone reabsorption function play an important role in the occurrence of DKD. SMCT1 may be a new promising target in treating DKD.

A J-shaped relationship between ketones and the risk of diabetic kidney disease in patients with type 2 diabetes: New insights from a cross-sectional study.

AIM: To investigate the association between circulating ß-hydroxybutyric acid (ßOHB) and diabetic kidney disease (DKD) risk in patients with type 2 diabetes (T2D). MATERIALS AND METHODS: A total of 1388 patients with T2D were recruited. Participants were divided into high and normal ßOHB groups. Participants in the normal ßOHB group were divided into four subgroups according to ßOHB quartile (Q). The relationships of ßOHB with DKD and DKD subtype were analysed using chi-square and binary logistic regression. Restricted cubic splines were used to explore the non-linear correlation between ßOHB concentration and DKD risk in the total population. RESULTS: A higher prevalence of DKD was detected in the high compared with the normal ßOHB group (43.3% vs. 33.3%, P = .041). Participants in the Q4 group (ßOHB, 0.12-0.30 mM) had the lowest prevalence of DKD (P = .001). In the binary logistic regression model, the multivariable-adjusted odds ratios (ORs) (95% confidence intervals [CIs]) for DKD risk were 2.30 (1.62-3.26) for Q1, 1.80 (1.23-2.62) for Q2 and 1.63 (1.10-2.41) for Q3 relative to Q4 (P < .001). Restricted cubic spline analyses suggested a J-shaped association of circulating ßOHB concentration with DKD risk. DKD risk was lowest at a serum ßOHB concentration of 0.183 mM (OR, 0.63; 95% CI, 0.52-0.77). CONCLUSIONS: A J-shaped relationship between circulating ketone level and DKD risk in patients with T2D was determined. Circulating ßOHB in the range of 0.12-0.30 mM was associated with a lower risk of DKD. Further studies are warranted to verify the causality and to elucidate the underlying mechanisms.

Identifying optimal ranges of weight gain at the end of the second trimester result from a population-based cohort study.

OBJECTIVE: To identify the optimal weight gain at the end of the second trimester. DESIGN: This was a population-based cohort study from the antenatal care system in Tianjin, China. We calculated gestational weight gain (GWG) based on the weight measured in the first trimester and the end of the second trimester. Restricted cubic spline analysis was performed to model the possible non-linear relationships between GWG and adverse outcomes. The optimal GWG was defined as the value of the lowest risk. Non-inferiority margins and the shape of the spline curves identified the recommended ranges in Chinese-specific BMI categories. SETTING: Tianjin Maternal and Child Health Cohort. PARTICIPANTS: Singleton pregnant women aged 18-45 years. RESULTS: In total, 69 859 pregnant women were included. Adverse outcome (including stillbirth, preterm birth, hypertensive disorders of pregnancy, gestational diabetes mellitus, small and large for gestational age) was significantly associated with GWG at the end of the second trimester. The risk score was non-linearly correlated with GWG in the underweight, normal weight and overweight groups. GWG at the end of the second trimester should not be < 7 kg in underweight group. For most normal-weight women, a GWG of about 8 kg is optimal. Pregnant women who are overweight should not have a GWG of more than 9 kg. We advised women with overweight and obesity to keep positive growth of GWG (> 0 kg) in the first and second trimesters. CONCLUSIONS: According to the comprehensive adverse maternal and infant outcomes, we recommend the optimal GWG at the end of the second trimester. This study may provide a considerable reference for weight management.

Urine Immunoglobin G Greater Than 2.45 mg/L Has a Correlation with the Onset and Progression of Diabetic Kidney Disease: A Retrospective Cohort Study.

AIM: To further assess the correlation between urine immunoglobin G (IgG) greater than 2.45 mg/L and the onset and progression of diabetic kidney disease (DKD). METHODS: One thousand and thirty-five patients with type 2 diabetes mellitus (T2DM) were divided into two groups based on the baseline levels of 24 h urinary albumin excretion (24 h UAE): one group with 24 h UAE < 30 mg/24 h and one with 24 h UAE ≥ 30 mg/24 h. The groups were subdivided using baseline levels of urine IgG (≤2.45 mg/L and >2.45 mg/L; hereafter, the Low and High groups, respectively). We used logistic regression to assess the risk of urine IgG and it exceeding 2.45 mg/L. Kaplan-Meier curves were used to compare the onset and progression time of DKD. The receiver operating characteristic curve was used to test the predictive value of urine IgG exceeding 2.45 mg/L. RESULTS: Urine IgG was an independent risk factor for the onset and progression of DKD. The rate and risk of DKD onset and progression at the end of follow-up increased significantly in the High group. The onset and progression time of DKD was earlier in the High group. Urine IgG exceeding 2.45 mg/L has a certain predictive value for DKD onset. CONCLUSIONS: Urine IgG exceeding 2.45 mg/L has a correlation with the onset and progression of DKD, and it also has a certain predictive value for DKD onset.

Establishment and validation of the cut-off values of estimated glomerular filtration rate and urinary albumin-to-creatinine ratio for diabetic kidney disease: A multi-center, prospective cohort study.

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 >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 <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 <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.

Beta-Hydroxybutyric Acid Inhibits Renal Tubular Reabsorption via the AKT/DAB2/Megalin Signalling Pathway.

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 (ß2-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, ß2-MG, RBP, NAG, or GAL was higher in the DK group too. After controlling ketosis, urinary microalbumin, TF, IgG, ß2-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.

Hyperinsulinemia impairs the metabolic switch to ketone body utilization in proximal renal tubular epithelial cells under energy crisis via the inhibition of the SIRT3/SMCT1 pathway.

Objective: To investigate the effects and mechanism of hyperinsulinemia on the metabolic switch to ß-hydroxybutyrate (BHB) absorption and utilization under a starvation or hypoxic environment in proximal tubular epithelial cells. Methods: A high-fat diet-induced hyperinsulinemia model in ZDF rats was used to test the expression of key enzymes/proteins of ketone body metabolism in the kidney. Notably, 12-week-old renal tubule SMCT1 specific knockout mice (SMCT1 flox/floxCre+) and control mice (SMCT1 flox/floxCre-) were used to confirm the roles of SMCT1 in kidney protection under starvation. The changes of key enzymes/proteins of energy metabolism, mitochondrial function, and albumin endocytosis in HK2 cells under low glucose/hypoxic environments with or without 50 ng/mL insulin were studied. Silent information regulation 2 homolog 3 (SIRT3) was overexpressed to evaluate the effect of hyperinsulinemia on the metabolic switch to BHB absorption and utilization through the SIRT3/SMCT1 pathway in HK2 cells. Results: In ZDF rats, the expression of HMGCS2 increased, the SMCT1 expression decreased, while SCOT remained unchanged. In renal tubule SMCT1 gene-specific knockout mice, starvation for 48 h induced an increase in the levels of urine retinol-binding protein, N-acetyl-ß-glucosaminidase, and transferrin, which reflected tubular damages. In HK2 cells under an environment of starvation and hypoxia, the levels of key enzymes related to fatty acid oxidation and ketone body metabolism were increased, whereas glucose glycolysis did not change. The addition of 2 mmol/l BHB improved ATP production, mitochondrial biosynthesis, and endocytic albumin function, while cell apoptosis was reduced in HK2 cells. The addition of 50 ng/ml insulin resulted in the decreased expression of SMCT1 along with an impaired mitochondrial function, decreased ATP production, and increased apoptosis. The overexpression of SIRT3 or SMCT1 reversed these alterations induced by a high level of insulin both in low-glucose and hypoxic environments. Conclusions: The increased absorption and utilization of BHB is part of the metabolic flexibility of renal tubular epithelial cells under starvation and hypoxic environments, which exhibits a protective effect on renal tubular epithelial cells by improving the mitochondrial function and cell survival. Moreover, hyperinsulinemia inhibits the absorption of BHB through the inhibition of the SIRT3/SMCT1 pathway.

Sex-specific mediating effect of gestational weight gain between pre-pregnancy body mass index and gestational diabetes mellitus.

BACKGROUND: Inappropriate weight gain may increase the risk of gestational diabetes mellitus (GDM). However, the relationship between pre-pregnancy body mass index (BMI), weight gain, and GDM has not been precisely quantified. This study aimed to explore whether gestational weight gain played a mediating role between pre-pregnancy BMI and GDM and whether the mediating effect was sex specific. METHODS: This study established a population-based observational cohort to assess weight gain in pregnant women. Mediation analyses were performed to quantify whether weight gain mediated the association between pre-pregnancy BMI and GDM. RESULTS: A total of 67,777 pregnant women were included in the final analysis, among whom 6751 (10.0%) were diagnosed with GDM. We verified that both pre-pregnancy BMI and weight gain were associated with GDM, and that BMI negatively contributed to weight gain. We also found that weight gain had a significant mediating effect on the relationship between pre-pregnancy BMI and GDM (Za × Zb confidence intervals [CIs] 0.00234-0.00618). Furthermore, the effect was sex-specific, in that it was only significant in overweight women carrying female fetuses (Za × Zb CIs 0.00422-0.01977), but not male fetuses (Za × Zb CIs -0.00085 to 0.01236). CONCLUSIONS: Weight gain during pregnancy had a fetal sex-specific mediating effect between pre-pregnancy BMI and GDM.

Predicting population: development and validation of a new predictive nomogram for evaluating medication nonadherence risk in a type 2 diabetes.

Background: Diabetes mellitus is a growing global health challenge and affects patients of all ages. Treatment aims to keep blood glucose levels close to normal and to prevent or delay complications. However, adherence to antidiabetic medicines is often unsatisfactory. Purpose: Here, we established and internally validated a medication nonadherence risk nomogram for use in Chinese type 2 diabetes mellitus (T2DM) patients. Methods: This cross-sectional study was carried out from July-December 2020 on randomly selected T2DM patients visiting a diabetes clinic and included 753 participants. Adherence was analyzed based on an eight-item Morisky Medication Adherence Scale (MMAS-8). Other data, including patient demographics, treatment, complications, and comorbidities, were also collected on questionnaires. Optimization of feature selection to develop the medication nonadherence risk model was achieved using the least absolute shrinkage and selection operator regression model (LASSO). A prediction model comprising features selected from LASSO model was designed by applying multivariable logistic regression analysis. The decision curve analysis, calibration plot, and C-index were utilized to assess the performance of the model in terms of discrimination, calibration, and clinical usefulness. Bootstrapping validation was applied for internal validation. Results: The prediction nomogram comprised several factors including sex, marital status, education level, employment, distance, self-monitoringofbloodglucose, disease duration, and dosing frequency of daily hypoglycemics (pills, insulin, or glucagon-like peptide-1). The model exhibited good calibration and good discrimination (C-index = 0.79, 95% CI [0.75-0.83]). In the validation samples, a high C-index (0.75) was achieved. Results of the decision curve analysis revealed that the nonadherence nomogram could be applied in clinical practice in cases where the intervention is decided at a nonadherence possibility threshold of 12%. Conclusion: The number of patients who adhere to anti-diabetes therapy was small. Being single male, having no formal education, employed, far from hospital, long disease duration, and taking antidiabetics twice or thrice daily, had significant negative correlation with medication adherence. Thus, strategies for improving adherence are urgently needed.

Reductions in Intestinal Taurine-Conjugated Bile Acids and Short-Chain Fatty Acid-Producing Bacteria Might be Novel Mechanisms of Type 2 Diabetes Mellitus in Otsuka Long-Evans Tokushima Fatty Rats.

BACKGROUND: The pathogenesis of spontaneously diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats, among the best models for human type 2 diabetes mellitus (T2DM), remains poorly defined. Therefore, we investigated the dynamic changes in taurine-conjugated bile acids (T-BAs) and intestinal microbiota during T2DM development in OLETF rats. METHODS: OLETF rats and corresponding diabetes-resistant Long Evans Tokushima Otsuka (LETO) rats were fed a normal baseline diet. The progress of T2DM was divided into four phases, including normal glycemia-normal insulinemia (baseline), normal glycemia-hyperinsulinemia, impaired glucose tolerance, and DM. Body weight, liver function, blood lipids, fasting plasma glucose, fasting plasma insulin, fasting plasma glucagon-like peptide (GLP)-1 and GLP-2, serum and fecal T-BAs, and gut microbiota were analyzed during the entire course of T2DM development. RESULTS: There were reductions in fecal T-BAs and short-chain fatty acids (SCFAs)-producing bacteria including Phascolarctobacterium and Lactobacillus in OLETF rats compared with those in LETO rats at baseline, and low levels of fecal T-BAs and SCFAs-producing bacteria were maintained throughout the whole course of the development of T2DM among OLETF rats compared with those in corresponding age-matched LETO rats. Fecal taurine-conjugated chenodeoxycholic acid correlated positively with Phascolarctobacterium. Fecal taurine-conjugated deoxycholic acid correlated positively with Lactobacillus and fasting plasma GLP-1 and inversely with fasting plasma glucose. CONCLUSION: The fecal BAs profiles and microbiota structure among OLETF rats were different from those of LETO rats during the entire course of T2DM development, indicating that reductions in intestinal T-BAs and specific SCFA-producing bacteria may be potential mechanisms of T2DM in OLETF rats.

Retinal Neuropathy in IGT Stage of OLETF Rats: Another Characteristic Change of Diabetic Retinopathy.

AIMS: We investigated the changes of retinal structure in normal glucose tolerance (NGT), impaired glucose tolerance (IGT), diabetes mellitus (DM), and diabetic kidney disease (DKD) stages in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: We assigned OLETF rats to four groups based on their OGTT results and 24 h urinary microalbumin (24 h UMA) levels: NGT, IGT, DM, and DKD groups. We observed the structural and the corresponding pathological changes and quantified the expression of HIF-1α, iNOS, NF-κB, VEGF, ICAM-1, and occludin in the retina. RESULTS: Significant damage to the retinal structure, especially in retinal ganglion cells (RGCs), was observed in the IGT stage. The expression of HIF-1α, iNOS, NF-κB, VEGF, and ICAM-1 was significantly upregulated, while that of occludin was downregulated. CONCLUSION: Significant retinal neuropathy occurs in the IGT stage. Inflammation and hypoxia may damage the blood retina barrier (BRB), leading to diabetic retinopathy.

Pathological Hyperinsulinemia and Hyperglycemia in the Impaired Glucose Tolerance Stage Mediate Endothelial Dysfunction Through miR-21, PTEN/AKT/eNOS, and MARK/ET-1 Pathways.

Background: Impaired glucose tolerance (IGT) is an important prediabetic stage characterized by elevated concentrations of glucose and insulin in the blood. The pathological hyperglycemia and hyperinsulinemia in IGT may regulate the expression of microRNA-21 (miR-21) and affect the downstream insulin signaling pathways, leading to endothelial cell dysfunction and early renal damage. Methods: The individual and combined effects of insulin and glucose were investigated using human glomerular endothelial cells (HGECs). The expression levels of miR-21, and PTEN/AKT/eNOS and MAPK/ET-1 pathway proteins in the treated cells were measured. The levels of nitric oxide (NO) and endothelin-1 (ET-1) secreted by the cells were also measured. The role of miR-21 in mediating the regulatory effects of insulin and glucose was assessed by overexpression/inhibition of this miRNA using mimics/inhibitor. Results: High (>16.7 mmol/L) concentration of glucose upregulated the expression of miR-21, leading to the activation and inhibition of the PTEN/AKT/eNOS and MAPK/ET-1 pathways, and upregulation of NO and downregulation of ET-1 secretion, respectively. High (>25 ng/mL) concentration of insulin downregulated the expression of miR-21, and lead to the activation of the MAPK/ET-1 and inhibition of the PTEN/AKT/eNOS pathway, thereby upregulating the expression of ET-1 and downregulating the secretion of NO. MiR-21 was observed to play a key role by directly controlling the activation of the insulin signaling pathways when the cells were cotreated with different concentrations of insulin and glucose. The expression of miR-21 was found to be dependent on the relative concentration of insulin and glucose. Under simulated conditions of the IGT stage (8.3 mmol/L glucose + 50 ng/mL insulin), the inhibitory effect of high insulin concentration on miR-21 expression in the cells attenuated the activation by high glucose concentration, resulting in the downregulation of miR-21, upregulation of ET-1 and downregulation of NO secretion. Conclusion: Taken together, these results indicate that high insulin and glucose concentrations regulate the secretory function of glomerular endothelial cells in opposite ways by regulating the expression of miRNA-21. Pathological concentrations of insulin and glucose in the IGT stage may lead to a decrease in miR-21 expression, thereby disordering the secretion of vasoactive factors, resulting in renal tubule ischemia.

Different Appearance of Chest CT Images of T2DM and NDM Patients with COVID-19 Pneumonia Based on an Artificial Intelligent Quantitative Method.

COVID-19 is a kind of pneumonia with new coronavirus infection, and the risk of death in COVID-19 patients with diabetes is four times higher than that in healthy people. It is unclear whether there is a difference in chest CT images between type 2 diabetes mellitus (T2DM) and non-diabetes mellitus (NDM) COVID-19 patients. The aim of this study was to investigate the differences in chest CT images between T2DM and NDM patients with COVID-19 based on a quantitative method of artificial intelligence. A total of 62 patients with COVID-19 pneumonia were retrospectively enrolled and divided into group A (T2DM COVID-19 pneumonia group, n = 15) and group B (NDM COVID-19 pneumonia group, n = 47). The clinical and laboratory examination information of the two groups was collected. Quantitative features (volume of consolidation shadows and ground glass shadows, proportion of consolidation shadow (or ground glass shadow) to lobe volume, total volume, total proportion, and number) of chest spiral CT images were extracted using Dr. Wise @Pneumonia software. The results showed that among the 26 CT image features, the total volume and proportion of bilateral pulmonary consolidation shadow in group A were larger than those in group B (P=0.031 and 0.019, respectively); there was no significant difference in the total volume and proportion of bilateral pulmonary ground glass density shadow between the two groups (P > 0.05). In group A, the blood glucose level was correlated with the volume of consolidation shadow and the proportion of consolidation shadow to right middle lobe volume, and higher than those patients in group B. In conclusion, the inflammatory exudation in the lung of COVID-19 patients with diabetes is more serious than that of patients without diabetes based on the quantitative method of artificial intelligence. Moreover, the blood glucose level is positively correlated with pulmonary inflammatory exudation in COVID-19 patients.

Vildagliptin Attenuates Myocardial Dysfunction and Restores Autophagy via miR-21/SPRY1/ERK in Diabetic Mice Heart.

Aim: Vildagliptin (vild) improves diastolic dysfunction and is associated with a lower relative risk of major adverse cardiovascular events in younger patients. The present study aimed to evaluate whether vild prevents the development of diabetic cardiomyopathy in type 2 diabetic mice and identify its underlying mechanisms. Methods: Type 2 diabetic mouse model was generated using wild-type (WT) (C57BL/6J) and miR-21 knockout mice by treatment with HFD/STZ. Cardiomyocyte-specific miR-21 overexpression was achieved using adeno-associated virus 9. Echocardiography was used to evaluate cardiac function in mice. Morphology, autophagy, and proteins levels in related pathway were analyzed. qRT-PCR was used to detect miR-21. Rat cardiac myoblast cell line (H9c2) cells were transfected with miR-21 mimics and inhibitor to explore the related mechanisms of miR-21 in diabetic cardiomyopathy. Results: Vild restored autophagy and alleviated fibrosis, thereby enhancing cardiac function in DM mice. In addition, miR-21 levels were increased under high glucose conditions. miR-21 knockout DM mice with miR-21 knockout had reduced cardiac hypertrophy and cardiac dysfunction compared to WT DM mice. Overexpression of miR-21 aggravated fibrosis, reduced autophagy, and attenuated the protective effect of vild on cardiac function. In high-glucose-treated H9c2 cells, the downstream effectors of sprouty homolog 1 (SPRY1) including extracellular signal-regulated kinases (ERK) and mammalian target of rapamycin showed significant changes following transfection with miR-21 mimics or inhibitor. Conclusion: The results of our study indicate that vild prevents DCM by restoring autophagy through the miR-21/SPRY1/ERK/mTOR pathway. Therefore, miR-21 is a target in the development of DCM, and vild demonstrates significant potential for clinical application in prevention of DCM.

Composite cardiovascular risk and BMI affected comparative profiles of BIAsp 30 + metformin vs BIAsp 30 monotherapy: a MERIT post-hoc analysis.

We assessed whether comparative efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) plus metformin versus BIAsp 30 monotherapy differed for patients with type 2 diabetes mellitus (T2DM) inadequately controlled with oral antidiabetic drugs with different cardiovascular risk scores and different body mass indexes (BMI) by performing a post hoc analysis of the randomized controlled MERIT study. In the MERIT study, eligible patients were randomized 1:1 to receive BIAsp 30 plus metformin or BIAsp 30 for 16 weeks. Patients in the 2 treatment groups were classified into "low" and "high" risk subgroups based on their GloboRisk scores and into "BMI ≤ 26 kg/m2"and "BMI > 26 kg/m2" subgroups. Primary efficacy endpoint was between-treatments comparison of HbA1c changes from baseline for these 2 sets of subgroups. Between-treatments comparisons of secondary efficacy and safety endpoints were also performed. We found that BIAsp 30 plus metformin led to significantly higher percentage of high-risk patients achieving HbA1c target < 7% than BIAsp 30 monotherapy, with an overall comparable safety profile for high-risk patients. Meanwhile, for patients with BMI ≤ 26 kg/m2, compared with BIAsp 30 monotherapy, BIAsp 30 plus metformin led to significantly higher percentages of patients achieving HbA1c target (47.83% vs 28.17%, P = 0.0165) and composite target of HbA1c < 7% without hypoglycemia or weight gain (20.29% vs 6.85%, P = 0.0187) and have a slightly better safety profile. In conclusion, for T2DM patients at high CV risk or with BMI ≤ 26 kg/m2, BIAsp 30 plus metformin was preferable to BIAsp 30 monotherapy.

Preoperative use of furosemide may increase the incidence of acute kidney injury after coronary artery bypass grafting: a propensity score-matched study.

OBJECTIVES: Furosemide is usually administered before the Coronary artery bypass grafting (CABG) to improve water-sodium retention. However, no final conclusions are available on the postoperative renal outcome of furosemide. We evaluated the effect of preoperative furosemide on acute kidney injury (AKI) after CABG. METHODS: We recorded the use of furosemide 14 days before surgery in all patients who underwent CABG from 2016 to 2017. Patients were divided into furosemide (F) group and non-furosemide (NF) group according to preoperative use of furosemide. A 1:1 propensity score matching was performed. Multivariate analyses were conducted to determine risk factors for AKI after CABG. RESULTS: Overall, 974 patients were included in the study, of which 82 cases were complicated with postoperative AKI. The incidence of AKI was significantly increased in F group than NF group (28.9% vs. 7.4%, p = 0.000). After adjusting for risk factors, the incidence of AKI in the F group was 5.34 times more than the NF group (95% confidence interval [CI] 2.45-11.64; p = 0.000). The incidence of AKI increased significantly when the cumulative dosage of furosemide exceeded 110 mg (odds ratio [OR] 6.23; 95% CI 2.07-18.74, p = 0.001) and 250 mg (OR 8.31; 95% CI 2.87-24.02, p = 0.000). After the propensity-matching group analysis, same results were obtained. CONCLUSIONS: The incidence of AKI after CABG was related to the use of preoperative furosemide, and it increased exponentially with the increase of cumulative dose of furosemide. This provides guidance for the dose of preoperative furosemide.

Application of non-mydriatic fundus examination and artificial intelligence to promote the screening of diabetic retinopathy in the endocrine clinic: an observational study of T2DM patients in Tianjin, China.

BACKGROUND: We aimed to determine the role of non-mydriatic fundus examination and artificial intelligence (AI) in screening diabetic retinopathy (DR) in patients with diabetes in the Metabolic Disease Management Center (MMC) in Tianjin, China. METHODS: Adult patients with type 2 diabetes mellitus who were first treated by MMC in Tianjin First Central Hospital and Tianjin 4th Center Hospital were divided into two groups according to the time that MMC was equipped with the non-mydriatic ophthalmoscope and AI system and could complete fundus examination independently (the former was the control group, the latter was the observation group). The observation indices were as follows: the incidence of DR, the fundus screening rate of the two groups, and fundus screening of diabetic patients with different course of disease. RESULTS: A total of 5039 patients were enrolled in this study. The incidence rate of DR was 18.6%, 29.8%, and 49.6% in patients with diabetes duration of ⩽1 year, 1-5 years, and >5 years, respectively. The screening rate of fundus in the observation group was significantly higher compared with the control group (81.3% versus 28.4%, χ 2 = 1430.918, p < 0.001). The DR screening rate of the observation group was also significantly higher compared with the control group in patients with diabetes duration of ⩽1 year (77.3% versus 20.6%; χ 2 = 797.534, p < 0.001), 1-5 years (82.5% versus 31.0%; χ 2 = 197.124, p < 0.001) and ⩾5 years (86.9% versus 37.1%; χ2 = 475.609, p < 0.001). CONCLUSIONS: In the case of limited medical resources, MMC can carry out one-stop examination, treatment, and management of DR through non-mydratic fundus examination and AI assistance, thus incorporating the DR screening process into the endocrine clinic, so as to facilitate early diagnosis.