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Statins as a risk factor for diabetic retinopathy: a Mendelian randomization and cross-sectional observational study.
Chen, C, Zhang, H, Lan, Y, Yan, W, Liu, S, Chen, Y, Xie, T, Ning, J, Yan, X, Shang, L, et al
Journal of translational medicine. 2024;(1):298
Abstract
BACKGROUND Diabetic retinopathy (DR) is the foremost cause of vision loss among the global working-age population, and statins are among the most frequently prescribed drugs for lipid management in patients with DR. The exact relationship between statins and DR has not been determined. This study sought to validate the causal association between statins usage and diabetic retinopathy. METHODS The summary-data-based Mendelian randomization (SMR) method and inverse-variance-weighted Mendelian randomization (IVW-MR) were used to identify the causal relationship between statins and DR via the use of expression quantitative trait loci (eQTL) data for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) (31,684 blood samples), low density lipoprotein cholesterol-related GWAS data (sample size: 440,546), and DR-related GWAS data (14,584 cases and 176,010 controls). Additionally, a cross-sectional observational study based on the data from the National Health and Nutrition Examination Survey (NHANES) was conducted to supplement the association between DR and statins (sample size: 106,911). The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) was employed to evaluate the results. RESULTS Based on the results of the MR analysis, HMGCR inhibitors were causally connected with a noticeably greater incidence of DR (IVW: OR = 0.54, 95% CI [0.42, 0.69], p = 0.000002; SMR: OR = 0.66, 95% CI [0.52, 0.84], p = 0.00073). Subgroup analysis revealed that the results were not affected by the severity of DR. The sensitivity analysis revealed the stability and reliability of the MR analysis results. The results from the cross-sectional study based on NHANES also support the association between not taking statins and a decreased risk of DR (OR = 0.54, 95% CI [0.37, 0.79], p = 0.001). CONCLUSIONS This study revealed that a significant increase in DR risk was causally related to statins use, providing novel insights into the role of statins in DR. However, further investigations are needed to verify these findings.
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Parathyroidectomy and Cinacalcet Use in Medicare-Insured Kidney Transplant Recipients.
Wang, AX, Liu, S, Montez-Rath, ME, Chertow, GM, Lenihan, CR
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2023;(3):270-280.e1
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Abstract
RATIONALE & OBJECTIVE Posttransplant hyperparathyroidism is common, and treatment practices are poorly characterized. The goal of this study was to examine the incidence, associations, and outcomes of posttransplant parathyroidectomy and calcimimetic use in a cohort of Medicare-insured US kidney transplant recipients. STUDY DESIGN Retrospective observational cohort study. SETTING & PARTICIPANTS We used the US Renal Data System to extract demographic, clinical, and prescription data from Medicare Parts A, B, and D-insured patients who received their first kidney transplant in 2007-2013. We excluded patients with pretransplant parathyroidectomy. PREDICTORS Calendar year of transplantation and pretransplant patient characteristics. OUTCOME (1) Incidence of and secular trends in parathyroidectomy and cinacalcet use in the 3 years after transplant; (2) 90-day outcomes after posttransplant parathyroidectomy and cinacalcet initiation. ANALYTICAL APPROACH Temporal trends and pretransplant correlates of parathyroidectomy and cinacalcet use were assessed using proportional hazards models and multivariable Poisson regression, respectively. RESULTS The inclusion criteria were met by 30,127 patients, of whom 10,707 used cinacalcet before transplant, 551 underwent posttransplant parathyroidectomy, and 5,413 filled≥1 prescription for cinacalcet. The rate of posttransplant parathyroidectomy was stable over time. By contrast, cinacalcet use increased during the period studied. Long dialysis vintage and pretransplant cinacalcet use were strongly associated with posttransplant parathyroidectomy and cinacalcet use. Roughly 1 in 4 patients were hospitalized within 90 days of posttransplant parathyroidectomy, with hypocalcemia-related diagnoses being the most common complication. Parathyroidectomy (vs cinacalcet initiation) was not associated with an increase in acute kidney injury. LIMITATIONS We lacked access to laboratory data to help assess the severity of secondary/tertiary hyperparathyroidism. The cohort was limited to Medicare beneficiaries. CONCLUSIONS Almost one-fifth of our study cohort was treated with parathyroidectomy and/or cinacalcet. Further studies are needed to establish the optimal treatment for posttransplant hyperparathyroidism.
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Early changes to retinal structure in patients with diabetic retinopathy as determined by ultrawide swept-source optical coherence tomography-angiography.
Zeng, Y, Liu, M, Li, M, Wei, D, Mao, M, Liu, X, Chen, S, Liu, Y, Chen, B, Yang, L, et al
Frontiers in endocrinology. 2023;:1143535
Abstract
PURPOSE To investigate retinal vascular changes in patients with diabetic retinopathy (DR) using the newly developed ultrawide rapid scanning swept-source optical coherence tomography angiography (SS-OCTA) device. METHODS This cross-sectional, observational study enrolled 24 patients (47 eyes) with DR, 45 patients (87 eyes) with diabetes mellitus (DM) without DR, and 36 control subjects (71 eyes). All subjects underwent 24 × 20 mm SS-OCTA examination. Vascular density (VD) and the thickness of the central macula (CM; 1 mm diameter) and temporal fan-shaped areas of 1-3 mm (T3), 3-6 mm (T6), 6-11 mm (T11), 11-16 mm (T16), and 16-21 mm (T21) were compared among groups. The VD and the thicknesses of the superficial vascular complex (SVC) and deep vascular complex (DVC) were analyzed separately. The predictive values of VD and thickness changes in DM and DR patients were evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS The average VDs of the SVC in the CM and the T3, T6, T11, T16, and T21 areas were significantly lower in the DR than in the control group, whereas only the average VD of the SVC in the T21 area was significantly lower in the DM group. The average VD of the DVC in the CM was significantly increased in the DR group, whereas the average VDs of the DVC in the CM and T21 area were significantly decreased in the DM group. Evaluation of the DR group showed significant increases in the thicknesses of SVC-nourishing segments in the CM and T3, T6, and T11 areas and significant increases in the thicknesses of DVC-nourishing segments in the CM and T3 and T6 areas. In contrast, none of these parameters showed significant changes in the DM group. ROC curve analysis showed that the average VD of the SVC in the CM, T3, and T21 had better ability to predict DR, with areas under the ROC curves (AUCs) of 0.8608, 0.8505, and 0.8353, respectively. The average VD of the DVC in the CM was also predictive of DR, with an AUC of 0.8407. CONCLUSIONS The newly developed ultrawide SS-OCTA device was better able to reveal early peripheral retinal vascular changes than traditional devices.
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The Portfolio Diet and Incident Type 2 Diabetes: Findings From the Women's Health Initiative Prospective Cohort Study.
Glenn, AJ, Li, J, Lo, K, Jenkins, DJA, Boucher, BA, Hanley, AJ, Kendall, CWC, Shadyab, AH, Tinker, LF, Chessler, SD, et al
Diabetes care. 2023;(1):28-37
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OBJECTIVE A plant-based dietary pattern, the Portfolio Diet, has been shown to lower LDL cholesterol and other cardiovascular disease risk factors. However, no study has evaluated the association of this diet with incident type 2 diabetes. RESEARCH DESIGN AND METHODS This analysis included 145,299 postmenopausal women free of diabetes at baseline in the Women's Health Initiative (WHI) Clinical Trials and Observational Study from 1993 to 2021. Adherence to the diet was assessed with a score based on six components (high in plant protein [soy and pulses], nuts, viscous fiber, plant sterols, and monounsaturated fat and low in saturated fat and cholesterol) determined from a validated food-frequency questionnaire. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs of the association of the Portfolio Diet, alongside the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets, with incident type 2 diabetes, with adjustment for potential confounders. RESULTS Over a mean follow-up of 16.0 years, 13,943 cases of incident type 2 diabetes were identified. In comparisons of the highest with the lowest quintiles of adherence, the HRs for risk of incident type 2 diabetes were 0.77 (95% CI 0.72, 0.82) for the Portfolio Diet, 0.69 (0.64, 0.73) for the DASH diet, and 0.78 (0.74, 0.83) for the Mediterranean diet. These findings were attenuated by 10% after additional adjustment for BMI. CONCLUSIONS Greater adherence to the plant-predominant Portfolio, DASH, and Mediterranean diets was prospectively associated with lower risk of type 2 diabetes in postmenopausal women.
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Investigating linear and nonlinear associations of LDL cholesterol with incident chronic kidney disease, atherosclerotic cardiovascular disease and all-cause mortality: A prospective and Mendelian randomization study.
Wang, Z, Xiao, Y, Lu, J, Zou, C, Huang, W, Zhang, J, Liu, S, Han, L, Jiao, F, Tian, D, et al
Atherosclerosis. 2023;:117394
Abstract
BACKGROUND AND AIMS Observational studies suggest potential nonlinear associations of low-density lipoprotein cholesterol (LDL-C) with cardio-renal diseases and mortality, but the causal nature of these associations is unclear. We aimed to determine the shape of causal relationships of LDL-C with incident chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality, and to evaluate the absolute risk of adverse outcomes contributed by LDL-C itself. METHODS Observational analysis and one-sample Mendelian randomization (MR) with linear and nonlinear assumptions were performed using the UK Biobank of >0.3 million participants with no reported prescription of lipid-lowering drugs. Two-sample MR on summary-level data from the Global Lipid Genetics Consortium (N = 296,680) and the CKDGen (N = 625,219) was employed to replicate the relationship for kidney traits. The 10-year probabilities of the outcomes was estimated by integrating the MR and Cox models. RESULTS Observationally, participants with low LDL-C were significantly associated with a decreased risk of ASCVD, but an increased risk of CKD and all-cause mortality. Univariable MR showed an inverse total effect of LDL-C on incident CKD (HR [95% CI]:0.84 [0.73-0.96]; p = 0.011), a positive effect on ASCVD (1.41 [1.29-1.53]; p<0.001), and no significant causal effect on all-cause mortality. Multivariable MR, controlling for high-density lipoprotein cholesterol (HDL-C) and triglycerides, identified a positive direct effect on ASCVD (1.32 [1.18-1.47]; p<0.001), but not on CKD and all-cause mortality. These results indicated that genetically predicted low LDL-C had an inverse indirect effect on CKD mediated by HDL-C and triglycerides, which was validated by a two-sample MR analysis using summary-level data from the Global Lipid Genetics Consortium (N = 296,680) and the CKDGen consortium (N = 625,219). Suggestive evidence of a nonlinear causal association between LDL-C and CKD was found. The 10-year probability curve showed that LDL-C concentrations below 3.5 mmol/L were associated with an increased risk of CKD. CONCLUSIONS In the general population, lower LDL-C was causally associated with lower risk of ASCVD, but appeared to have a trade-off for an increased risk of CKD, with not much effect on all-cause mortality. LDL-C concentration below 3.5 mmol/L may increase the risk of CKD.
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Differences in Metabolomic Profiles Between Black and White Women and Risk of Coronary Heart Disease: an Observational Study of Women From Four US Cohorts.
Hu, J, Yao, J, Deng, S, Balasubramanian, R, Jiménez, MC, Li, J, Guo, X, Cruz, DE, Gao, Y, Huang, T, et al
Circulation research. 2022;(7):601-615
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Abstract
BACKGROUND Racial differences in metabolomic profiles may reflect underlying differences in social determinants of health by self-reported race and may be related to racial disparities in coronary heart disease (CHD) among women in the United States. However, the magnitude of differences in metabolomic profiles between Black and White women in the United States has not been well-described. It also remains unknown whether such differences are related to differences in CHD risk. METHODS Plasma metabolomic profiles were analyzed using liquid chromatography-tandem mass spectrometry in the WHI-OS (Women's Health Initiative-Observational Study; 138 Black and 696 White women), WHI-HT trials (WHI-Hormone Therapy; 156 Black and 1138 White women), MESA (Multi-Ethnic Study of Atherosclerosis; 114 Black and 219 White women), JHS (Jackson Heart Study; 1465 Black women with 107 incident CHD cases), and NHS (Nurses' Health Study; 2506 White women with 136 incident CHD cases). First, linear regression models were used to estimate associations between self-reported race and 472 metabolites in WHI-OS (discovery); findings were replicated in WHI-HT and validated in MESA. Second, we used elastic net regression to construct a racial difference metabolomic pattern (RDMP) representing differences in the metabolomic patterns between Black and White women in the WHI-OS; the RDMP was validated in the WHI-HT and MESA. Third, using conditional logistic regressions in the WHI (717 CHD cases and 719 matched controls), we examined associations of metabolites with large differences in levels by race and the RDMP with risk of CHD, and the results were replicated in Black women from the JHS and White women from the NHS. RESULTS Of the 472 tested metabolites, levels of 259 (54.9%) metabolites, mostly lipid metabolites and amino acids, significantly differed between Black and White women in both WHI-OS and WHI-HT after adjusting for baseline characteristics, socioeconomic status, lifestyle factors, baseline health conditions, and medication use (false discovery rate <0.05); similar trends were observed in MESA. The RDMP, composed of 152 metabolites, was identified in the WHI-OS and showed significantly different distributions between Black and White women in the WHI-HT and MESA. Higher RDMP quartiles were associated with an increased risk of incident CHD (odds ratio=1.51 [0.97-2.37] for the highest quartile comparing to the lowest; Ptrend=0.02), independent of self-reported race and known CHD risk factors. In race-stratified analyses, the RDMP-CHD associations were more pronounced in White women. Similar patterns were observed in Black women from the JHS and White women from the NHS. CONCLUSIONS Metabolomic profiles significantly and substantially differ between Black and White women and may be associated with CHD risk and racial disparities in US women.
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Ultra-widefield color fundus photography combined with high-speed ultra-widefield swept-source optical coherence tomography angiography for non-invasive detection of lesions in diabetic retinopathy.
Li, J, Wei, D, Mao, M, Li, M, Liu, S, Li, F, Chen, L, Liu, M, Leng, H, Wang, Y, et al
Frontiers in public health. 2022;:1047608
Abstract
PURPOSE To compare the detection rate of diabetic retinopathy (DR) lesions and the agreement of DR severity grading using the ultra-widefield color fundus photography (UWF CFP) combined with high-speed ultra-widefield swept-source optical coherence tomography angiography (UWF SS-OCTA) or fluorescein angiography (FFA). METHODS This prospective, observational study recruited diabetic patients who had already taken the FFA examination from November 2021 to June 2022. These patients had either no DR or any stage of DR. All participants were imaged with a 200° UWF CFP and UWF SS-OCTA using a 24 × 20 mm scan model. Images were independently evaluated for the presence or absence of DR lesions including microaneurysms (MAs), intraretinal hemorrhage (IRH), non-perfusion areas (NPAs), intraretinal microvascular abnormalities (IRMAs), venous beading (VB), neovascularization elsewhere (NVE), neovascularization of the optic disc (NVD), and vitreous or preretinal hemorrhage (VH/PRH). Agreement of DR severity grading based on UWF CFP plus UWF SS-OCTA and UWF CFP plus FFA was compared. All statistical analyses were performed using SPSS V.26.0. RESULTS One hundred and fifty-three eyes of 86 participants were enrolled in the study. The combination of UWF CFP with UWF SS-OCTA showed a similar detection rate compared with UWF CFP plus FFA for all the characteristic DR lesions (p>0.05), except NPAs (p = 0.039). Good agreement was shown for the identification of VB (κ = 0.635), and very good agreement for rest of the DR lesions between the two combination methods (κ-value ranged from 0.858 to 0.974). When comparing the grading of DR severity, very good agreement was achieved between UWF CFP plus UWF SS-OCTA and UWF CFP plusr FFA (κ = 0.869). CONCLUSION UWF CFP plus UWF SS-OCTA had a very good agreement in detecting DR lesions and determining the severity of DR compared with UWF CFP plus FFA. This modality has the potential to be used as a fast, reliable, and non-invasive method for DR screening and monitoring in the future.
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HOMA-IR as a risk factor of gestational diabetes mellitus and a novel simple surrogate index in early pregnancy.
Song, S, Zhang, Y, Qiao, X, Duo, Y, Xu, J, Peng, Z, Zhang, J, Chen, Y, Nie, X, Sun, Q, et al
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2022;(3):694-701
Abstract
OBJECTIVE To assess the association between insulin resistance and gestational diabetes mellitus (GDM) in early pregnancy and find a simple surrogate index of the homeostasis model assessment of insulin resistance (HOMA-IR). METHODS A total of 700 pregnant women were included in this prospective, double-center, observational cohort study. The glucose and lipid metabolic characterization was performed at 6-12 weeks of pregnancy. All participants underwent a 75-g oral glucose tolerance test at 24-28 weeks of pregnancy. Linear regression analysis was applied to find a novel surrogate index of HOMA-IR. Binary logistic analysis was applied to estimate possible associations of different indices with GDM and insulin resistance. RESULTS GDM was diagnosed in 145 of 700 women with singleton pregnancies (20.7%). HOMA-IR was higher in the GDM group than in the normal glucose tolerance (NGT) group and was an individual risk factor for GDM (adjusted risk ratio RR 1.371, 95% confidence interval [CI] 1.129-1.665, P < 0.001). TyHGB index as the surrogate index of HOMA-IR was represented as TG/HDL-C + 0.7*FBG (mmol/L) +0.1*preBMI (kg/m2 )(where TG/HDL-C is triglyceride/high-density lipoprotein cholesterol; FBG is fasting blood glucose, and preBMI is the pre-pregnancy body mass index [calculated as weight in kilograms divided by the square of height in meters]). The cut-off point of the TyHGB index was 6.0 (area under the curve 0.827, 95% CI 0.794-0.861, P < 0.001) for mild insulin resistance. CONCLUSION Increased HOMA-IR in early pregnancy was a risk factor of GDM. TyHGB index could be a surrogate index of HOMA-IR and had a predictive value for GDM.
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Neurological and Psychological Characteristics of Young Nitrous Oxide Abusers and Its Underlying Causes During the COVID-19 Lockdown.
Wu, G, Wang, S, Wang, T, Han, J, Yu, A, Feng, C, Wang, Y, Liu, S
Frontiers in public health. 2022;:854977
Abstract
BACKGROUND The COVID-19 pandemic has a serious impact on the mental health of the public due to its economic and social impact. And psychological effects have led to drug and alcohol abuse. After the city lifted the lockdown, we consecutively encountered several young nitrous oxide abusers admitted to hospital for neurological treatment. PURPOSE To inform physician decisions and social intervention, this observational study aimed at investigating the neurological and psychological characteristics of nitrous oxide abusers and its underlying causes during the COVID-19 lockdown. METHODS The nitrous oxide abusers who sought neurological treatment at our hospital between May 2020 and June 2020 were enrolled. Clinical data including socio-demographic, physical examination, laboratory examination, electromyography and neuroimaging were collected. Their motivations for inhaling nitrous oxide, knowledge about the nitrous oxide abuse and the accompanying of family were investigated face to face. Psychological status was assessed by the Symptom Checklist 90 (SCL-90) psychological evaluation. RESULTS Six nitrous oxide abusers were enrolled and the age was 22 ± 4.3. Clinical presentations included varying degrees of limb numbness and an ataxic gait. Laboratory examination revealed that all the patients did not have pernicious anemia, 4 patients had decreased vitamin B12 while 3 patients exhibited elevated homocysteine levels. MR of the spinal cord revealed that 4 patients had abnormal signals in the cervical spinal cord of high symmetry with splayed or inverted V sign after T2WI. Electromyogram (EMG) test showed 5 patients had peripheral nerve damage. The SCL-90 psychological evaluation results indicated that all patients had severe anxiety, depression and psychosis and they had severer psychological problems than ordinary citizens. Their motives for inhaling nitrous oxide are to relieve boredom, curiosity and buddy pressure. Their family spent <1 day per week to stay with them during city lockdown. CONCLUSION The enrolled patients caused by abuse of nitrous oxide presented with symptoms of subacute combined with spinal degeneration. They had more serious psychological problems related to the COVID-19 pandemic. These cases make us value the psychological problems of young people under the outbreak and take multi-layered measures from families, schools (companies), hospitals, and governments to address it.
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Correlation Between Gut Microbiota and Testosterone in Male Patients With Type 2 Diabetes Mellitus.
Liu, S, Cao, R, Liu, L, Lv, Y, Qi, X, Yuan, Z, Fan, X, Yu, C, Guan, Q
Frontiers in endocrinology. 2022;:836485
Abstract
OBJECTIVE This study aimed at investigating the association between testosterone levels and gut microbiota in male patients with type 2 diabetes mellitus (T2DM) and providing a new strategy to elucidate the pathological mechanism of testosterone deficiency in T2DM patients. METHODS In an observational study including 46 T2DM male patients, the peripheral venous blood and fecal samples of all subjects were collected. The V3-V4 regions of bacterial 16S rDNA were amplified and sequenced. Alpha and beta diversities were calculated by QIIME software. The possible association between gut microbial community and clinical indicators was assessed using the Spearman correlation coefficient. The association between the relative abundance of bacteria and testosterone levels was discovered using linear regression analysis in R language. RESULTS There was no substantial difference in alpha and beta diversity. Blautia and Lachnospirales were significantly much higher in the testosterone deficiency group. Linear regression analysis showed that the abundance of Firmicutes at the phylum level and Lachnospirales at the order level were negatively correlated with testosterone level. After correcting for C-reactive protein (CRP) and homeostatic model assessment of insulin resistance (HOMA-IR), the relative abundance of Lachnospirales still had a significant negative correlation with testosterone level. Meanwhile, at the genus level, Lachnoclostridium, Blautia, and Bergeyella had a statistically significant negative association with testosterone level, respectively. Blautia was positively associated with FPG and total cholesterol level. Streptococcus was found positively associated with insulin, connecting peptide, and index of homeostatic model assessment of insulin resistance. CONCLUSION T2DM patients with testosterone deficiency have different gut microbiota compositions compared with T2DM patients alone. Low serum testosterone patients tend to have an increased abundance of opportunistic pathogens, which may be related to the occurrence and development of testosterone deficiency.