scholarly journals The Usefulness of Serum Biomarkers in the Early Stages of Diabetic Retinopathy: Results of the EUROCONDOR Clinical Trial

2020 ◽  
Vol 9 (4) ◽  
pp. 1233 ◽  
Author(s):  
Cristina Hernández ◽  
Massimo Porta ◽  
Francesco Bandello ◽  
Jakob Grauslund ◽  
Simon P. Harding ◽  
...  

The main aim of this study was to evaluate the ability of serum biomarkers to predict the worsening of retinal neurodysfunction in subjects with type 2 diabetes. For this purpose, we measured selected molecules (N-epsilon-carboxy methyl lysine (CML), laminin P1 (Lam-P1), and asymmetric dimethylarginine (ADMA)) in the serum of 341 participants of the EUROCONDOR study at baseline, 24, and 48 weeks. Retinal neurodysfunction was assessed by measuring implicit time (IT) using multifocal electroretinography, and structural changes were examined by spectral domain–optical coherence tomography. The values of IT at baseline were directly correlated with baseline serum concentrations of CML (r = 0.135, p = 0.013). Furthermore, in the placebo group, increase in CML concentration throughout follow-up correlated with the IT (r = 0.20; p = 0.03). Baseline serum levels of CML also correlated with macular retinal thickness (RT) (r = 0.231; p < 0.001). Baseline Lam-P1 levels correlated with the increase of the RT at the end of follow-up in the placebo group (r = 0.22; p = 0.016). We provide evidence that CML may be a biomarker of both retinal neurodysfunction and RT, whereas Lam-P1 was associated with RT only. Therefore, circulating levels of these molecules could provide a complementary tool for monitoring the early changes of diabetic retinopathy (DR).

2014 ◽  
Vol 84 (1-2) ◽  
pp. 27-34 ◽  
Author(s):  
Nasser M. Al-Daghri ◽  
Khalid M. Alkharfy ◽  
Nasiruddin Khan ◽  
Hanan A. Alfawaz ◽  
Abdulrahman S. Al-Ajlan ◽  
...  

The aim of our study was to evaluate the effects of vitamin D supplementation on circulating levels of magnesium and selenium in patients with type 2 diabetes mellitus (T2DM). A total of 126 adult Saudi patients (55 men and 71 women, mean age 53.6 ± 10.7 years) with controlled T2DM were randomly recruited for the study. All subjects were given vitamin D3 tablets (2000 IU/day) for six months. Follow-up mean concentrations of serum 25-hydroxyvitamin D [25-(OH) vitamin D] significantly increased in both men (34.1 ± 12.4 to 57.8 ± 17.0 nmol/L) and women (35.7 ± 13.5 to 60.1 ± 18.5 nmol/L, p < 0.001), while levels of parathyroid hormone (PTH) decreased significantly in both men (1.6 ± 0.17 to 0.96 ± 0.10 pmol/L, p = 0.003) and women (1.6 ± 0.17 to 1.0 ± 0.14 pmol/L, p = 0.02). In addition, there was a significant increase in serum levels of selenium and magnesium in men and women (p-values < 0.001 and 0.04, respectively) after follow-up. In women, a significant correlation was observed between delta change (variables at six months-variable at baseline) of serum magnesium versus high-density lipoprotein (HDL)-cholesterol (r = 0.36, p = 0.006) and fasting glucose (r = - 0.33, p = 0.01). In men, there was a significant correlation between serum selenium and triglycerides (r = 0.32, p = 0.04). Vitamin D supplementation improves serum concentrations of magnesium and selenium in a gender-dependent manner, which in turn could affect several cardiometabolic parameters such as glucose and lipids.


2021 ◽  
Author(s):  
Lynette J. Oost ◽  
Amber A.W.A. van der Heijden ◽  
Emma A. Vermeulen ◽  
Caro Bos ◽  
Petra J.M. Elders ◽  
...  

<p><b>Objective</b></p> <p>We investigated whether serum magnesium (Mg<sup>2+</sup>) was prospectively associated with macro- or microvascular complications and mediated by glycemic control (Hemoglobin A<sub>1c</sub> (HbA<sub>1c</sub>)), in T2D.</p> <p> </p> <p><b>Research Design and Methods</b></p> <p>We analyzed in 4,348 participants the association of serum Mg<sup>2+</sup> with macrovascular disease and mortality (acute myocardial infarction (AMI), coronary heart disease (CHD), heart failure (HF), cerebrovascular accident (CVA), peripheral arterial disease (PAD)), atrial fibrillation (AF) and microvascular complications (chronic kidney disease (CKD), diabetic retinopathy and diabetic foot) using Cox regression, adjusted for confounders. Mediation analysis was performed to assess whether HbA<sub>1c</sub> mediated these associations.</p> <p> </p> <p><b>Results</b></p> <p>The average baseline serum Mg<sup>2+</sup> concentration was 0.80 ± 0.08 mmol/L. Serum Mg<sup>2+</sup> was during 6.1 years of follow-up inversely associated with major macrovascular 0.87 (95% CI: 0.76; 1.00), HF 0.76 (95% CI: 0.62; 0.93) and AF 0.59 (95% CI: 0.49; 0.72). Serum Mg<sup>2+</sup> was not associated with AMI, CHD, CVA and PAD. Serum Mg<sup>2+</sup> was during 5.1 years of follow-up inversely associated with<sup> </sup>overall microvascular events 0.85 (95% CI: 0.78; 0.91), 0.89 (95% CI: 0.82; 0.96) for CKD, 0.77 (95% CI: 0.61; 0.98) for diabetic retinopathy and 0.85 (95% CI: 0.78; 0.92) for diabetic foot. HbA<sub>1c</sub> mediated the associations of serum Mg<sup>2+ </sup>with HF, overall microvascular events, diabetic retinopathy and diabetic foot.</p> <p> </p> <p><b>Conclusions</b></p> <p>Serum Mg<sup>2+</sup> concentration is inversely associated with the risk to develop HF, AF and with the occurrence of CKD, diabetic retinopathy and foot complications, in T2D. Glycemic control partially mediated the association of serum Mg<sup>2+</sup> with HF and microvascular complications. </p>


2020 ◽  
Vol 8 (1) ◽  
pp. e001325 ◽  
Author(s):  
Ramachandran Rajalakshmi ◽  
Coimbatore Subramanian Shanthi Rani ◽  
Ulagamathesan Venkatesan ◽  
Ranjit Unnikrishnan ◽  
Ranjit Mohan Anjana ◽  
...  

IntroductionPrevious epidemiological studies have reported on the prevalence of diabetic kidney disease (DKD) and diabetic retinopathy (DR) from India. The aim of this study is to evaluate the effect of DKD on the development of new-onset DR and sight-threatening diabetic retinopathy (STDR) in Asian Indians with type 2 diabetes (T2D).Research design and methodsThe study was done on anonymized electronic medical record data of people with T2D who had undergone screening for DR and renal work-up as part of routine follow-up at a tertiary care diabetes center in Chennai, South India. The baseline data retrieved included clinical and biochemical parameters including renal profiles (serum creatinine, estimated glomerular filtration rate (eGFR) and albuminuria). Grading of DR was performed using the modified Early Treatment Diabetic Retinopathy Study grading system. STDR was defined as the presence of proliferative diabetic retinopathy (PDR) and/or diabetic macular edema. DKD was defined by the presence of albuminuria (≥30 µg/mg) and/or reduction in eGFR (<60 mL/min/1.73 m2). Cox regression analysis was used to evaluate the hazard ratio (HR) for DR and STDR.ResultsData of 19 909 individuals with T2D (mean age 59.6±10.2 years, mean duration of diabetes 11.1±12.1 years, 66.1% male) were analyzed. At baseline, DR was present in 7818 individuals (39.3%), of whom 2249 (11.3%) had STDR. During the mean follow-up period of 3.9±1.9 years, 2140 (17.7%) developed new-onset DR and 980 individuals with non-proliferative DR (NPDR) at baseline progressed to STDR. Higher serum creatinine (HR 1.5, 95% CI 1.3 to 1.7; p<0.0001), eGFR <30 mL/min/1.73 m2 (HR 4.9, 95% CI 2.9 to 8.2; p<0.0001) and presence of macroalbuminuria >300 µg/mg (HR 3.0, 95% CI 2.4 to 3.8; p<0.0001) at baseline were associated with increased risk of progression to STDR.ConclusionsDKD at baseline is a risk factor for progression to STDR. Physicians should promptly refer their patients with DKD to ophthalmologists for timely detection and management of STDR.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
I Mueller ◽  
U Uwe Kuehl ◽  
T Thomas Vogl ◽  
A Alexander Krannich ◽  
S Sophie Van Linthout ◽  
...  

Abstract Background The alarmin S100A8/A9 has been shown to be of importance in several inflammatory cardiovascular disorders. We recently demonstrated the pivotal role of cardiac S100A8/A9 in human and experimental Coxsackievirus B3 (CVB3)-induced myocarditis (MC). Purpose We aimed to evaluate whether serum S100A8/A9 levels are a marker in patients with a recent onset of MC Methods Serum S100A8/A9, hsCRP, and NT pro-BNP levels were analyzed in patients with a recent onset of MC (≤30 days (d), n=29; ejection fraction (EF): 44.3%±13%), dilated cardiomyopathy patients with inflammation (DCMi: n=112; EF: 28.8%±12%) or without inflammation (DCM: n=58; EF: 26.7%±9%), and controls (co: n=25; EF: 68.5%±5%). Blood samples and endomyocardial biopsies (EMB) were collected at time point (T1). In a subgroup, S100A8/A9 serum levels and EMB were available at T1 (n=10) and follow-up (T2, n=10, mean follow-up 8 months). Results MC ≤30 d patients showed a 4.5-fold (p<0.0001), 19.3-fold (p<0.0001), and 4.0-fold (p<0.0001) increase in S100A8/A9, hsCRP, NT pro-BNP levels vs co, respectively. S100A8/A9 levels correlated with the disease activity, displayed by EMB counts of inflammatory cells (CD3: r=0.464, p=0.0128, XY pairs=28, LFA-1: r=0.551, p=0.002, XY pairs=28, Mac-1: r=0.418, p=0.026, XY pairs=28), and the EF (r=0.545, p=0.0027, XY pairs=28). MC ≤30 d patients showed an association between serum S100A8/A9 levels and EMB S100A8 (r=0.482, p=0.060, XY pairs=16), S100A9 (r=0.441, p=0.088, XY pairs=16), nucleotide-binding oligomerization domain containing-protein 2 (NOD2, r=0.55, p=0.035, XY=15), and Nod-like receptor family, pyrin domain-containing 3 protein (NLRP3, r=0.52, p=0.048, XY=15) mRNA levels. Also EMB S100A8 and S100A9 mRNA levels showed a significant correlation with EMB NOD2 and NLRP3 mRNA expression. Serum S100A8/A9 levels were increased by 3.0-fold (p<0.0001) and 1.8-fold (p=0.0005) in DCMi (n=112), and DCM (n=58) patients vs co, respectively. However, the S100A8/A9 levels of DCMi and DCM patients were 1.5-fold (p=0.07) and 2.5-fold (p<0.0001) lower vs MC ≤30 d patients. ROC analyses of S100A8/A9 in MC ≤30 d provided a cut-off of 583 ng/ml with a specificity=92%, sensitivity=86.2%, a PPV=92.6%, a NPV=85.2%, and an AUC=0.934 vs co, which was superior to hsCRP (cut-off=5 mg/l): specificity=95.8%, sensitivity=58.6%, a PPV=94.4%, a NPV=65.7%, AUC=0.885. In the subgroup, S100A8/A9 levels decreased after heart failure medication (T1: 2454±1931 ng/ml vs T2: 934.4±552 ng/ml; p=0.002), reflected by a decrease of EMB inflammatory cells. Baseline serum S100A8/A9 levels predicted the change in EMB CD3 and Mac-1. Conclusions These results support an additional value for S100A8/A9 serum levels as a potential diagnostic biomarker and as a tool to monitor the course of the disease. We provide first evidence that S100A8/A9 is connected to the NOD2-NLRP3 pathway in these patients. Acknowledgement/Funding Novartis


Cardiology ◽  
2019 ◽  
Vol 142 (1) ◽  
pp. 7-13
Author(s):  
Gabriele Di Gesaro ◽  
Giuseppa Caccamo ◽  
Diego Bellavia ◽  
Calogero Falletta ◽  
Chiara Minà ◽  
...  

Heart failure (HF) with reduced ejection fraction (HFrEF) has a well-known epidemic relevance in western countries. It affects up to 1–2% of patients > 60 years and reaches a prevalence of 12% in octogenarian patients. The role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitive troponin I (hsTnI) in risk stratifying HFrEF patients has been established; at present, evidence is exclusively based on one-time assessments, and the prognostic usefulness of serial biochemical assessments in this population still remains to be determined. We prospectively recruited 226 patients with chronic HFrEF, who were all referred to the Outpatient Clinic of our institution from November 2011 through September 2014. Recruited patients underwent full clinical evaluation with complete history taking and physical examination as well as ECG, biochemical assessment, and standard 2D and Doppler flow echocardiography at the first visit, and then again at each visit during the follow-up, repeated every 6 months. During the follow-up period, cardiovascular (CV) death, which occurred in 16 patients, was not statistically correlated with gender (p = 0.088) or age (p = 0.1636); however, baseline serum levels of NT-proBNP, which were 3 times higher in deceased patients, were significantly related to this clinical event (p = 0.001). We found that NT-proBNP represents a strong and independent predictor of CV outcome; serum levels of hsTnI, which are significantly related to an increased risk of hospitalization, cannot properly predict the relative risk of CV mortality. Our study validates, eventually, the multimarker strategy, which reflects the complexity of the HF pathophysiology.


2005 ◽  
Vol 20 (4) ◽  
pp. 317-323 ◽  
Author(s):  
Tao-Hsin Tung ◽  
Shih-Jen Chen ◽  
Jorn-Hon Liu ◽  
Fenq-Lih Lee ◽  
An-Fei Li ◽  
...  

2015 ◽  
Vol 100 (4) ◽  
pp. 1368-1375 ◽  
Author(s):  
C. H. Lee ◽  
E. Y. L. Hui ◽  
Y. C. Woo ◽  
C. Y. Yeung ◽  
W. S. Chow ◽  
...  

Background: Elevated fibroblast growth factor 21 (FGF21) levels have been suggested, from cross-sectional studies, as an indicator of subclinical diabetic nephropathy. We investigated whether serum FGF21 was predictive of the development of diabetic nephropathy. Method: Baseline serum FGF21 levels were measured in 1136 Chinese type 2 diabetic subjects recruited from the Hong Kong West Diabetes Registry. The role of serum FGF21 in predicting decline in estimated glomerular filtration rate (eGFR) over a median follow-up of 4 years was analyzed using Cox regression analysis. Results: At baseline, serum FGF21 levels increased progressively with eGFR category (P for trend &lt;.001). Among 1071 subjects with baseline eGFR ≥ 30 mL/min/1.73 m2, serum FGF21 levels were significantly higher in those with eGFR decline during follow-up (n = 171) than those without decline (n = 900) (P &lt; .001). In multivariable Cox regression analysis, baseline serum FGF21 was independently associated with eGFR decline (hazard ratio, 1.21; 95% confidence interval [CI], 1.01–1.43; P = .036), even after adjustment for baseline eGFR. In a subgroup of 559 subjects with baseline eGFR ≥60 mL/min/1.73 m2 and normoalbuminuria, serum FGF21 level remained an independent predictor of eGFR decline (hazard ratio, 1.36; 95% CI, 1.06–1.76; P = .016). Integrated discrimination improvement (IDI) suggested that the inclusion of baseline serum FGF21 significantly improved the prediction of eGFR decline (IDI, 1%; 95% CI, 0.1–3.0; P = .013) in this subgroup, but not in the initial cohort involving all subjects. Conclusions: Elevated serum FGF21 levels may be a useful biomarker for predicting kidney disease progression, especially in the early stages of diabetic nephropathy.


2020 ◽  
Author(s):  
Jing Wang ◽  
Honghai Hu ◽  
Xiaowei Liu ◽  
Shenglong Zhao ◽  
Yuanyuan Zheng ◽  
...  

Abstract Background: Preeclampsia prediction improves maternal and fetal outcomes in pregnancy. We aimed to evaluate the preeclampsia prediction values of a series of serum biomarkers. Methods: Singleton pregnant women with preeclampsia-related clinical and/or laboratory presentations were recruited and had blood drawn at their first visits. The prospective cohort was further divided into preeclampsia-positive and preeclampsia-negative groups based on the follow-up results. The following markers were tested using the collected serum samples: soluble fms-like tyrosine kinase-1 ( sFlt-1); placental growth factor (PlGF); thrombomodulin (TM); tissue plasminogen activator inhibitor complex (tPAI-C); compliment factors C1q, B, and H; glycosylated fibronectin (GlyFn); pregnancy-associated plasma protein-A2 ( PAPP-A2); blood urea nitrogen (BUN); creatinine (Cre); uric acid (UA); and cystatin C (Cysc). Results: A total of 196 women with suspected preeclampsia were recruited with follow-up medical records. Twenty-five percent (n=49) of the recruited subjects developed preeclampsia before delivery, and 75% remained preeclampsia-negative (n=147). The serum levels of sFlt-1, BUN, Cre, UA, Cysc and PAPP-A2 were significantly elevated, and the PlGF level was significantly decreased in the preeclampsia-positive patients. In the receiver operating characteristics (ROC) analyses, the area under the curves were listed in the order of decreasing values: 0.73 (UA), 0.67 (sFlt-1/PlGF), 0.66 (Cysc), 0.65 (GlyFn/PlGF), 0.64 (PAPP-A2/PlGF), 0.63 (BUN), 0.63 (Cre), and 0.60 (PAPP-A2). With the cut-off values obtained from the ROC analyses, the positive predictive values of these serum markers were between 33.1% and 58.5%, and the negative predictive values were between 80.9% and 89.5%. Conclusions: Further studies are warranted to confirm the clinical utilities of the serum markers in preeclampsia prediction


Author(s):  
Mitali Borooah ◽  
Shobhana Phukan

Background: Subclinical hypothyroidism (SCH) is defined as an asymptomatic condition characterized by normal serum levels of free thyroxine and elevated serum concentration of thyrotropin (>4.0µIU/ml). Association between diabetic retinopathy and SCH is unclear. Aim was to study the relationship between severity of diabetic retinopathy and SCH in patients of diabetic retinopathy with type 2 diabetes mellitus.Methods: 120 patients of diabetic retinopathy with known type 2 diabetes mellitus were taken and categorized them according to severity of diabetic retinopathy as per ETDRS classification. Serum thyrotropin (TSH) and free thyroxine (FT4) concentration were measured in all 120 patients. Patients with normal TSH and FT4 values are euthyroid patients and those with normal FT4 but TSH value >4µIU/ml are considered as having subclinical hypothyroidism. Severity of diabetic retinopathy is compared between the euthyroid and subclinical hypothyroid group.Results: Out of the 120 patients included in the study, 72 (60%) were male and 48 (40%) were female. 97 patients (80.83%) were Euthyroid and 23 patients (19.17%) had subclinical hypothyroidism. It was observed that prevalence of more severe form of diabetic retinopathy (severe NPDR and PDR) was higher in SCH group as compared to euthyroid group. Severity of diabetic retinopathy was compared with serum TSH level and it was seen that severity of diabetic retinopathy significantly increases with increase in serum TSH value.Conclusions: Patients with SCH had more severe form of diabetic retinopathy as compared to patients with euthyroidism. Severity of diabetic retinopathy significantly increases with increase in serum TSH value.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Jiang Huang ◽  
Yi Li ◽  
Yao Chen ◽  
Yuhong You ◽  
Tongtong Niu ◽  
...  

Purpose. To study retinal function defects in type 2 diabetic patients without clinically apparent retinopathy using a multifocal electroretinogram (mf-ERG). Methods. Seventy-six eyes of thirty-eight type 2 diabetes mellitus(DM) patients without clinically apparent retinopathy and sixty-four normal eyes of thirty-two healthy control (HC) participants were examined using mf-ERG. Results. Patients with type 2 DM without apparent diabetic retinopathy demonstrated an obvious implicit time delay of P1 in ring 1, ring 3, and ring 5 compared with healthy controls ( t = 5.184 , p ≤ 0.001 ; t = 8.077 , p ≤ 0.001 ; t = 2.000 , p = 0.047 , respectively). The implicit time (IT) in ring 4 of N1wave was significantly delayed in the DM group ( t = 2.327 , p = 0.021 ). Compared with the HC group, the implicit time of the P1 and N1 waves in the temporal retina zone was significantly prolonged ( t = 3.66 , p ≤ 0.001 ; t = 2.187 , p = 0.03 , respectively). And the amplitude of P1 in the temporal retina decreased in the DM group, which had a significantly statistical difference with the healthy controls ( t = − 6.963 , p ≤ 0.001 ). However, there were no differences in either the amplitude of the response or the implicit time of the nasal retina zone between DM and HC. The AUC of multiparameters of mf-ERG was higher in the diagnosis of DR patients. Conclusions. Patients with type 2 DM without clinically apparent retinopathy had a delayed implicit time of P1 wave in temporal regions of the postpole of the retina compared with HC subjects. It demonstrates that mf-ERG can detect the abnormal retinal change in the early stage of type2 DM patients without apparent diabetic retinopathy. Multiparameters of mf-ERG can improve the diagnostic efficacy of DR, and it may be a potential clinical biomarker for early diagnosis of DR.


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