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Predictive role of serum C-peptide in new-onset renal dysfunction in type 2 diabetes: a longitudinal observational study.
Sun, D, Hu, Y, Ma, Y, Wang, H
Frontiers in endocrinology. 2023;:1227260
Abstract
BACKGROUND Our previous cross-sectional study has demonstrated the independently non-linear relationship between fasting C-peptide with renal dysfunction odds in patients with type 2 diabetes (T2D) in China. This longitudinal observational study aims to explore the role of serum C-peptide in risk prediction of new-onset renal dysfunction, then construct a predictive model based on serum C-peptide and other clinical parameters. METHODS The patients with T2D and normal renal function at baseline were recruited in this study. The LASSO algorithm was performed to filter potential predictors from the baseline variables. Logistic regression (LR) was performed to construct the predictive model for new-onset renal dysfunction risk. Power analysis was performed to assess the statistical power of the model. RESULTS During a 2-year follow-up period, 21.08% (35/166) of subjects with T2D and normal renal function at baseline progressed to renal dysfunction. Six predictors were determined using LASSO regression, including baseline albumin-to-creatinine ratio, glycated hemoglobin, hypertension, retinol-binding protein-to-creatinine ratio, quartiles of fasting C-peptide, and quartiles of fasting C-peptide to 2h postprandial C-peptide ratio. These 6 predictors were incorporated to develop model for renal dysfunction risk prediction using LR. Finally, the LR model achieved a high efficiency, with an AUC of 0.83 (0.76 - 0.91), an accuracy of 75.80%, a sensitivity of 88.60%, and a specificity of 70.80%. According to the power analysis, the statistical power of the LR model was found to be 0.81, which was at a relatively high level. Finally, a nomogram was developed to make the model more available for individualized prediction in clinical practice. CONCLUSION Our results indicated that the baseline level of serum C-peptide had the potential role in the risk prediction of new-onset renal dysfunction. The LR model demonstrated high efficiency and had the potential to guide individualized risk assessments for renal dysfunction in clinical practice.
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2.
Low-Carbohydrate and Low-Fat Diet with Metabolic-Dysfunction-Associated Fatty Liver Disease.
Hu, C, Huang, R, Li, R, Ning, N, He, Y, Zhang, J, Wang, Y, Ma, Y, Jin, L
Nutrients. 2023;(22)
Abstract
BACKGROUND This observational cross-sectional study was designed to explore the effects of a low-carbohydrate diet (LCD) and a low-fat diet (LFD) on metabolic-dysfunction-associated fatty liver disease (MAFLD). METHODS This study involved 3961 adults. The associations between LCD/LFD scores and MAFLD were evaluated utilizing a multivariable logistic regression model. Additionally, a leave-one-out model was applied to assess the effect of isocaloric substitution of specific macronutrients. RESULTS Participants within the highest tertile of healthy LCD scores (0.63; 95% confidence interval [CI], 0.45-0.89) or with a healthy LFD score (0.64; 95%CI, 0.48-0.86) faced a lower MAFLD risk. Furthermore, compared with tertile 1, individuals with unhealthy LFD scores in terile 2 or tertile 3 had 49% (95%CI, 1.17-1.90) and 77% (95%CI, 1.19-2.63) higher risk levels for MAFLD, respectively. CONCLUSIONS Healthy LCD and healthy LFD are protective against MAFLD, while unhealthy LFD can increase the risk of MAFLD. Both the quantity and quality of macronutrients might have significant influences on MAFLD.
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Non-linear association of fasting C-peptide and uric acid levels with renal dysfunction based on restricted cubic spline in patients with type 2 diabetes: A real-world study.
Chen, L, Hu, Y, Ma, Y, Wang, H
Frontiers in endocrinology. 2023;:1157123
Abstract
BACKGROUND Previous studies had showed divergent findings on the associations of C-peptide and/or uric acid (UA) with renal dysfunction odds in patients with type 2 diabetes mellitus (T2DM). We hypothesized that there were non-linear relationships between C-peptide, UA and renal dysfunction odds. This study aimed to further investigate the relationships of different stratification of C-peptide and UA with renal dysfunction in patients with T2DM. METHOD We conducted a cross-sectional real-world observational study of 411 patients with T2DM. The levels of fasting C-peptide, 2h postprandial C-peptide, the ratio of fasting C-peptide to 2h postprandial C-peptide (C0/C2 ratio), UA and other characteristics were recorded. Restricted cubic spline (RCS) curves was performed to evaluated the associations of stratified C-peptide and UA with renal dysfunction odds. RESULTS Fasting C-peptide, C0/C2 ratio and UA were independently and significantly associated with renal dysfunction in patients with T2DM as assessed by multivariate analyses (p < 0.05). In especial, non-linear relationships with threshold effects were observed among fasting C-peptide, UA and renal dysfunction according to RCS analyses. Compared with patients with 0.28 ≤ fasting C-peptide ≤ 0.56 nmol/L, patients with fasting C-peptide < 0.28 nmol/L (OR = 1.38, p = 0.246) or fasting C-peptide > 0.56 nmol/L (OR = 1.85, p = 0.021) had relatively higher renal dysfunction odds after adjusting for confounding factors. Similarly, compared with patients with 276 ≤ UA ≤ 409 μmol/L, patients with UA < 276 μmol/L (OR = 1.32, p = 0.262) or UA > 409 μmol/L (OR = 6.24, p < 0.001) had relatively higher odds of renal dysfunction. CONCLUSION The renal dysfunction odds in patients with T2DM was non-linearly associated with the levels of serum fasting C-peptide and UA. Fasting C-peptide and UA might have the potential role in odds stratification of renal dysfunction.
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Effects of Hypovitaminosis D on Preoperative Pain Threshold and Perioperative Opioid Use in Colorectal Cancer Surgery: A Cohort Study.
Xia, J, Li, D, Yu, G, Xu, B, Gao, X, Wang, H, Ma, Y, Li, X, Xiong, Y
Pain physician. 2022;(7):E1009-E1019
Abstract
BACKGROUND Postoperative pain after colorectal cancer surgery has a significant impact on postoperative physical and mental health. Vitamin D deficiency has been correlated with both acute pain states, including postoperative and post-traumatic pain, and several chronic pain diseases. The effects of hypovitaminosis D on preoperative pain threshold and perioperative opioid use in colorectal cancer surgery still need to be studied. OBJECTIVES To find the relationship between hypovitaminosis D on pain threshold, perioperative opioid use, and postoperative complications in colorectal cancer surgery. STUDY DESIGN A total of 112 patients, who were enrolled in this prospective, observational trial, were divided into 2 groups based on their preoperative serum 25-hydroxyvitamin D (25 [OH] D3) levels: (1) group D: vitamin D-deficient group (< 20 ng/mL); and (2) group S: vitamin D-sufficient group (>= 20 ng/mL). METHODS Primary outcomes were pain threshold indexes, perioperative dosages of opioid use, and postoperative pain. Secondary outcomes were other postoperative complications. RESULTS Preoperative serum level of vitamin D was 14.94 ± 3.10 ng/mL in group D and 24.20 ± 4.80 ng/mL in group S. Significant differences were showed in the 3 indexes of pain threshold and analgesic consumption between the 2 groups (P < 0.05). A low 25 (OH) D3 level was associated with a higher opioid dose of sufentanil. There was an association between 25 (OH) D3 and pain enduring threshold (PET), beta coefficient beta = 0.532, 95% confidential interval (0.440, 0.623), P < 0.001. The history of diabetes mellitus (DM) and vitamin C and vitamin D levels may be risk factors of surgical site infections (SSI), and the binary logistics regression model is statistically significant, chi-squared = 35.028, P < 0.001. LIMITATIONS There is room for further expansion in the sample size. Our study lacked objective indicators to measure pain threshold. Intestinal recovery time and total hospital stay were not included in the final analysis. In the follow-up study, the vitamin D supplementation group should be set and the specific site of colorectal cancer surgery also needs to be divided more carefully. CONCLUSIONS On the basis of the study results, hypovitaminosis D is associated with increased perioperative opioid consumption in colorectal cancer surgery. Sensory perception and pain threshold of patients with insufficient 25 (OH) D3 concentration were more sensitive, and PET was lower. History of DM, vitamin D, and vitamin C may be factors related with SSI. Future studies are needed to investigate their relationship further and discover if postoperative pain and pain threshold can benefit from vitamin D supplementation in these patients.
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Prediction of the Short-Term Risk of New-Onset Renal Dysfunction in Patients with Type 2 Diabetes: A Longitudinal Observational Study.
Xu, J, Shan, X, Xu, Y, Ma, Y, Wang, H
Journal of immunology research. 2022;:6289261
Abstract
BACKGROUND Studies in the past decade have reported many novel biomarkers for predicting the new-onset or progression risk of renal dysfunction in patients with type 2 diabetes (T2D) based on the genomic, metabolomic, and proteomic technologies. These novel predictive markers, however, are difficult to be widely used in clinical practice over the short term due to their high technology content, instability, and high cost. This study was aimed at evaluating the associations of clinical features and six traditional renal markers with the short-term risk of new-onset renal dysfunction in patients with T2D. METHODS This study involved 213 participants with T2D and normal renal function at baseline. The baseline levels of the albumin-to-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), alpha-1-microglobulin-to-creatinine ratio (A1MCR), neutrophil gelatinase-associated lipocalin-to-creatinine ratio, transferrin-to-creatinine ratio (UTRF/Cr), and retinol-binding protein-to-creatinine ratio (URBP/Cr) were analyzed. Multivariate logistic models were established and validated. RESULTS During the two-year follow-up period, 23.01% participants progressed to renal dysfunction. The basal levels of ACR, A1MCR, UTRF/Cr, and URBP/Cr were the independent risk factors of new-onset renal dysfunction (P < 0.05). Several logistic models incorporating clinical characteristics and these renal markers were constructed for predicting the short-term risk of new-onset renal dysfunction. Comparatively, the model including age, glycated hemoglobin (HbA1c), hypertension, ACR, A1MCR, UTRF/Cr, and URBP/Cr levels at baseline had the highest potential (C - index = 0.785, P < 0.001). This model was validated using the K-fold cross-validation method; the accuracy was 0.815 ± 0.013 in training sets and 0.784 ± 0.019 in validation sets, indicating a good consistency for predicting the new-onset renal dysfunction risk. Finally, a nomogram based on this model was constructed to provide a quantitative tool to assess the individualized risk of short-term new-onset renal dysfunction. CONCLUSION The model incorporating these markers and clinical features may have a high potential to predict the short-term risk of new-onset renal dysfunction.
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Linear and nonlinear analyses of the association between low-density lipoprotein cholesterol and diabetes: The spurious U-curve in observational study.
Ma, Y, Zhou, Z, Li, X, Ding, K, Xiao, H, Wu, Y, Wu, T, Chen, D
Frontiers in endocrinology. 2022;:1009095
Abstract
OBJECTIVE Hyperlipidemia is traditionally considered a risk factor for diabetes. The effect of low-density lipoprotein cholesterol (LDL-C) is counterintuitive to diabetes. We sought to investigate the relationship between LDL-C and diabetes for better lipid management. METHODS We tested the shape of association between LDL-C and diabetes and created polygenic risk scores of LDL-C and generated linear Mendelian randomization (MR) estimates for the effect of LDL-C and diabetes. We evaluated for nonlinearity in the observational and genetic relationship between LDL-C and diabetes. RESULTS Traditional observational analysis suggested a complex non-linear association between LDL-C and diabetes while nonlinear MR analyses found no evidence for a non-linear association. Under the assumption of linear association, we found a consistently protective effect of LDL-C against diabetes among the females without lipid-lowering drugs use. The ORs were 0.84 (95% CI, 0.72-0.97, P=0.0168) in an observational analysis which was more prominent in MR analysis and suggested increasing the overall distribution of LDL-C in females led to an overall decrease in the risk of diabetes (P=0.0258). CONCLUSIONS We verified the liner protective effect of LDL-C against diabetes among the females without lipid-lowering drug use. Non-linear associations between LDL-C against diabetes in observational analysis are not causal.
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Role of hsa‑miR‑105 during the pathogenesis of paclitaxel resistance and its clinical implication in ovarian cancer.
Li, M, Zhang, S, Ma, Y, Yang, Y, An, R
Oncology reports. 2021;(5)
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Abstract
More than 70% of patients with epithelial ovarian cancer (EOC), one of the leading cause of gynecological cancer‑related deaths worldwide, are diagnosed at an advanced stage of the disease. Currently, the mainstay for treatment of advanced EOC is tumor debulking surgery followed by combined platinum‑ and paclitaxel (PTX)‑based chemotherapy. However, most patients eventually develop chemoresistance, which remains a major obstacle to successful treatment. Herein, by using clinical specimens and experimentally induced cell models, we found that the expression levels of hsa‑miR‑105 were significantly decreased in PTX‑resistant EOC tissues and cell lines. Follow‑up functional experiments demonstrated that repression of hsa‑miR‑105 conferred resistance to paclitaxel in EOC cells, whereas restoration of hsa‑miR‑105 expression in situ via intratumoral injection of hsa‑miR‑105 micrON™ agomir potentiated in vivo sensitivity to PTX and thereafter significantly inhibited tumor growth in a PTX‑challenged xenograft model. Mechanistically, hsa‑miR‑105 exerted its tumor suppressor function by directly inhibiting the zinc and ring finger 2 (ZNRF2) signaling pathway. Importantly, aberrant expression of hsa‑miR‑105 in both tumor and circulating samples predicted a poor post‑chemotherapy prognosis in EOC patients. These findings collectively suggest that hsa‑miR‑105 may act as a potent tumor suppressor miRNA during the progression of EOC, likely affecting cell proliferation, invasiveness and chemosensitivity to PTX, and functioning at least in part via inhibition of ZNRF2 signaling. The stability and availability and ease in measurement of circulating hsa‑miR‑105 make it a valuable diagnostic/prognostic biomarker candidate for chemotherapy of EOC.
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Quantifying the pattern of retinal vascular orientation in diabetic retinopathy using optical coherence tomography angiography.
Ma, Y, Ohr, MP, Pan, X, Roberts, CJ
Scientific reports. 2021;(1):15826
Abstract
Quantitative imaging using optical coherence tomography angiography (OCTA) could provide objective tools for the detection and characterization of diabetic retinopathy (DR). In this study, an operator combining the second derivative and Gaussian multiscale convolution is applied to identify the retinal orientation at each pixel in the OCTA image. We quantified the pattern of retinal vascular orientation and developed three novel quantitative metrics including vessel preferred orientation, vessel anisotropy, and vessel area. Each of eight 45º sectors of the circular disk centered at the macular region was defined as the region of interest. Significant sectoral differences were observed in the preferred orientation (p < 0.0001) and vessel area (p < 0.0001) in the 34 healthy subjects, whereas vessel anisotropy did not demonstrate a significant difference among the eight sectors (p = 0.054). Differential retinal microvascular orientation patterns were observed between healthy controls (n = 34) and the DR subjects (n = 7). The vessel area characterized from the vascular orientation pattern was shown to be strongly correlated with the traditionally reported vessel density (Pearson R > 0.97, p < 0.0001). With three metrics calculated from the vascular orientation pattern simultaneously and sectorally, our quantitative assessment for retinal microvasculature provides more information than vessel density alone and thereby may enhance the detection of DR. These preliminary results suggest the feasibility and advantage of our vessel orientation-based quantitative approach using OCTA to characterize DR-associated changes in retinal microvasculature.
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Prognostic impact of estimated remnant-like particle cholesterol in patients with differing glycometabolic status: an observational cohort study from China.
Zhao, Q, Zhang, TY, Cheng, YJ, Ma, Y, Xu, YK, Yang, JQ, Zhou, YJ
Lipids in health and disease. 2020;(1):179
Abstract
BACKGROUND It is uncertain whether estimated remnant-like particle cholesterol (RLP-C) could predict residual risk in patients with different glycometabolic status. This study aimed to evaluate the relationship between estimated RLP-C and adverse prognosis in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) treated with percutaneous coronary intervention (PCI) and to identify the potential impact of glycometabolism on the predictive value of estimated RLP-C. METHODS The study assessed 2419 participants with NSTE-ACS undergoing PCI at Beijing Anzhen Hospital from January to December 2015. Estimated RLP-C was calculated as follows: total cholesterol (TC) minus low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). The adverse events included all-cause death, non-fatal myocardial infarction (MI), and ischemia-driven revascularization. RESULTS Estimated RLP-C was prominently associated with adverse prognosis in the total population [hazard ratio (HR) 1.291 per 1-SD increase, 95% confidence interval (CI) 1.119-1.490, P < 0.001], independent of confounding risk factors. However, subgroup analysis showed that increasing estimated RLP-C was related to a higher risk of adverse events in the diabetic population only [HR 1.385 per 1-SD increase, 95% CI 1.183-1.620, P < 0.001]. Estimated RLP-C failed to be a significant determinant of adverse prognosis in non-diabetic and pre-diabetic subgroups. The addition of estimated RLP-C to a baseline model including traditional risk factors enhanced the predictive performance both in total and diabetic populations. CONCLUSIONS High estimated RLP-C level is a significant predictor for recurrent adverse events in patients with diabetes and NSTE-ACS treated with PCI.
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Association between serum irisin concentrations and sarcopenia in patients with liver cirrhosis: a cross-sectional study.
Zhao, M, Zhou, X, Yuan, C, Li, R, Ma, Y, Tang, X
Scientific reports. 2020;(1):16093
Abstract
Sarcopenia is an independent predictor of mortality in patients with liver cirrhosis. However, evidence has emerged that skeletal muscles mediate their protective effect against sarcopenia by secreting myokines. Therefore, we investigated whether irisin was associated with sarcopenia in patients with liver cirrhosis. This was an observational cross-sectional study of data collected from 187 cirrhotic patients. Sarcopenia was defined by computed tomography (CT) scans using specific cutoffs of the 3rd lumbar vertebra skeletal muscle index (L3 SMI). Morning irisin levels were obtained in all patients. Of the 187 patients, sarcopenia was noted in 73 (39%). Irisin concentrations were lower in sarcopenic patients (32.40 pg/ml [interquartile range (IQR): 18.70, 121.26], p < 0.001) than in nonsarcopenic patients. There was a weak correlation between L3 SMI and irisin levels (r = 0.516, p < 0.001). Multivariable regression analysis including L3 SMI, body mass index (BMI), very-low-density lipoprotein (VLDL)-cholesterol, aspartate aminotransferase (AST), adiponectin, and irisin levels showed that L3 SMI (odds ratio [OR] = 0.915, p = 0.023), adiponectin levels (OR = 1.074, p = 0.014), irisin levels (OR = 0.993, p < 0.001) and BMI (OR = 0.456, p = 0.004) were independently associated with sarcopenia. Irisin levels are associated with sarcopenia in patients with liver cirrhosis. This paper addresses a gap in the literature and facilitates the future transition into clinical treatment.