Dataset Information

Estimated glucose disposal rate as a candidate biomarker for thrombotic biomarkers in T1D: a pooled analysis.

ABSTRACT:

Purpose

To determine the utility of estimated glucose disposal rate (eGDR) as a candidate biomarker for thrombotic biomarkers in patients with type 1 diabetes (T1D).

Methods

We reanalysed baseline pretreatment data in a subset of patients with T1D from two previous RCTs, consisting of a panel of thrombotic markers, including fibrinogen, tissue factor (TF) activity, and plasminogen-activator inhibitor (PAI)-1, and TNFα, and clinical factors (age, T1D duration, HbA1c, insulin requirements, BMI, blood pressure, and eGDR). We employed univariate linear regression models to investigate associations between clinical parameters and eGDR with thrombotic biomarkers.

Results

Thirty-two patients were included [mean ± SD age 31 ± 7 years, HbA1c of 58 ± 9 mmol/mol (7.5 ± 0.8%), eGDR 7.73 ± 2.61]. eGDR negatively associated with fibrinogen (P < 0.001), PAI-1 concentrations (P = 0.005), and TF activity (P = 0.020), but not TNFα levels (P = 0.881). We identified 2 clusters of patients displaying significantly different characteristics; 56% (n = 18) were categorised as 'higher-risk', eliciting significantly higher fibrinogen (+ 1514 ± 594 μg/mL; P < 0.001), TF activity (+ 59.23 ± 9.42 pmol/mL; P < 0.001), and PAI-1 (+ 8.48 ± 1.58 pmol/dL; P < 0.001), HbA1c concentrations (+ 14.20 ± 1.04 mmol/mol; P < 0.001), age (+ 7 ± 3 years; P < 0.001), duration of diabetes (15 ± 2 years; P < 0.001), BMI (+ 7.66 ± 2.61 kg/m²; P < 0.001), and lower mean eGDR (- 3.98 ± 1.07; P < 0.001).

Conclusions

Compared to BMI and insulin requirements, classical surrogates of insulin resistance, eGDR is a suitable and superior thrombotic risk indicator in T1D.

Trial registration

ISRCTN4081115; registered 27 June 2017.

SUBMITTER: O'Mahoney LL

PROVIDER: S-EPMC8502148 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Estimated glucose disposal rate as a candidate biomarker for thrombotic biomarkers in T1D: a pooled analysis.

O'Mahoney L L LL Kietsiriroje N N Pearson S S West D J DJ Holmes M M Ajjan R A RA Campbell M D MD

Journal of endocrinological investigation 20210317 11

<h4>Purpose</h4>To determine the utility of estimated glucose disposal rate (eGDR) as a candidate biomarker for thrombotic biomarkers in patients with type 1 diabetes (T1D).<h4>Methods</h4>We reanalysed baseline pretreatment data in a subset of patients with T1D from two previous RCTs, consisting of a panel of thrombotic markers, including fibrinogen, tissue factor (TF) activity, and plasminogen-activator inhibitor (PAI)-1, and TNFα, and clinical factors (age, T1D duration, HbA1c, insulin requir ...[more]

PMID: 33730349

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Project description:BackgroundEstimated glucose disposal rate (eGDR), a simple and noninvasive measure of insulin resistance, has been proven to be an independent risk factor for first-time stroke and all-cause mortality. In this study, we aimed to investigate the associations between eGDR and the stroke outcome in patients with first-time acute ischemic stroke (AIS).MethodsWe included first-time AIS patients with available data on eGDR in the China National Stroke Registry III (CNSR-III), and divided the subjects into lower eGDR group (eGDR ≤ 6 mg/kg/min) and higher eGDR group (eGDR > 6 mg/kg/min). The primary outcome was excellent functional outcome (modified Rankin Scale score 0-1) at 3 months. Secondary outcomes included stroke recurrence and favorable functional outcome (modified Rankin Scale score 0-2) at 3 months, and functional outcome and combined vascular event at one year. Univariate and multivariate analyses were performed to evaluate the association between eGDR and outcomes.ResultsA total of 6,271 patients with AIS were included in this study. The median values of eGDR in lower and higher eGDR group were 5.0 mg/kg/min (interquartile range, 4.2-5.6) and 7.6 mg/kg/min (interquartile range, 6.8-9.6), respectively. Patients with higher eGDR were significantly associated with higher incidence of excellent functional outcome (adjusted odds ratio, 1.24; 95% confidence interval, 1.06-1.45; P < 0.01) at 3 months and favorable (adjusted odds ratio, 1.55; 95% confidence interval, 1.24-1.93; P < 0.01) and excellent (adjusted odds ratio, 1.28; 95% confidence interval, 1.08-1.51; P < 0.01) functional outcome at one year. However, there was no significant difference in stroke recurrence between these two groups at 3 months (adjusted odds ratio, 0.81; 95% confidence interval, 0.61-1.06; P = 0.12) and one year (adjusted odds ratio, 0.91; 95% confidence interval, 0.73-1.14; P = 0.41).ConclusioneGDR is a predictor of functional outcome in patients with AIS, independent of traditional cardiovascular predictors.

Project description:BackgroundFrailty is a common geriatric syndrome associated with many adverse health outcomes. Identifying the risk factors of frailty is crucial and the insulin resistance (IR) is considered as a potential target. The estimated glucose disposal rate (eGDR) is a simple and reliable surrogate marker of IR. Associations of eGDR with frailty have not been explored. This study aimed to investigate the associations of eGDR with frailty progression.MethodsWe used data from two prospective cohorts of the China Health and Retirement Longitudinal Study (CHARLS) and Health and Retirement Study (HRS). The eGDR was calculated as follows: eGDR (mg/kg/min) = 21.158 - (0.09×waist circumference) - (3.407×hypertension) - (0.551×glycosylated hemoglobin A1c) [waist circumference (cm), hypertension (yes = 1/no = 0), and glycosylated hemoglobin A1c (%)]. Participants were divided into three categories by tertiles of eGDR. Frailty index (FI) was calculated every two years and used to assess the degree of frailty which ranged from 0 to 100. Frailty progression was assessed by repeated measurements of FI during follow-up. Linear mixed-effect models were used to analyze the associations of eGDR with frailty progression.Results8872 participants from CHARLS (mean age: 58.9 years, female: 53.3%) and 5864 participants from HRS (mean age: 67.0 years, female: 59.0%) were included. The median follow-up periods were 7.0 years in the CHARLS and 12.8 years in the HRS, respectively. Compared to participants with lower tertile (T1) of eGDR, those with upper tertile (T3) of eGDR showed decelerated FI progression (CHARLS, β: -0.294, 95%CI -0.390 to -0.198, P < 0.001; HRS, β: -0.378, 95%CI -0.474 to -0.281, P < 0.001). Continuous eGDR was also associated with FI progression for significant deceleration in FI progression with per 1 SD increase in eGDR (CHARLS, β: -0.142, 95%CI -0.181 to -0.103, P < 0.001; HRS, β: -0.170, 95%CI -0.209 to -0.130, P < 0.001). These associations were still observed after excluding baseline frail participants. Furthermore, the associations of eGDR with FI progression were consistent among participants with and without diabetes.ConclusionRegardless of diabetes or not, a higher level of eGDR was associated with the decelerated frailty progression. Our findings highlight the role of eGDR in frailty progression and recommend taking effective interventions to improve eGDR for preventing frailty progression.

Project description:BackgroundInsulin resistance (IR) is a central pathophysiological factor in metabolic syndrome (MetS) and an essential driver of cardiovascular disease (CVD) and mortality. The estimated glucose disposal rate (eGDR) is a reliable marker of IR and has been associated with CVD prognosis. This study aims to examine the relationship between eGDR, MetS, and their predictive roles in clinical outcomes.MethodsData from the NHANES (2001-2018) were utilized, with a cross-sectional design applied to evaluate the association between eGDR and MetS prevalence, and a cohort design employed for mortality follow-up. Weighted logistic regression models were used to examine the association between eGDR and MetS. Weighted Cox proportional hazard models were applied to assess the link between eGDR and both all-cause and CVD mortality. To examine the non-linear associations between the eGDR, MetS, and mortality outcomes, restricted cubic spline (RCS) analysis was applied. Additionally, the predictive performance of eGDR, and other IR indices (TyG, HOMA-IR), for mortality was assessed using the C-statistic.ResultsA robust negative association between eGDR and MetS prevalence was found, following full covariate adjustment (p < 0.001). The core findings were consistent across subgroups (all p < 0.001). Cox regression analysis indicated that in individuals with MetS, each standard deviation (SD) increment in eGDR was associated with an 11% and 18% decrement in the risk of all-cause and CVD mortality, respectively. RCS analysis displayed a non-linear association between eGDR and MetS prevalence, while a linear association between eGDR and mortality. The C-statistic showed that eGDR, compared to the TyG index and HOMA-IR, significantly improved predictive power for all-cause mortality (p = 0.007).ConclusioneGDR is strongly associated with MetS and predicts all-cause and CVD mortality in individuals with MetS. Compared to TyG and HOMA-IR, eGDR offers superior predictive value for all-cause mortality, highlighting its potential as a useful tool in clinical risk assessment.

Project description:Background and aimsInsulin resistance contributes to the development of type 2 diabetes (T2D) and is also a cardiovascular risk factor. The aim of this study was to investigate the potential association between insulin resistance measured by estimated glucose disposal rate (eGDR) and risk of stroke and mortality thereof in people with T2D.Materials and methodsNationwide population based observational cohort study that included all T2D patients from the Swedish national diabetes registry between 2004 and 2016 with full data on eGDR and categorised as following: < 4, 4-6, 6-8, and ≥ 8 mg/kg/min. We calculated crude incidence rates and 95% confidence intervals (CIs) and used multiple Cox regression to estimate hazard ratios (HRs) to assess the association between the risk of stroke and death, according to the eGDR categories in which the lowest category < 4 (i.e., highest grade of insulin resistance), served as a reference. The relative importance attributed of each factor in the eGDR formula was measured by the R2 (± SE) values calculating the explainable log-likelihoods in the Cox regression.ResultsA total of 104 697 T2D individuals, 44.5% women, mean age of 63 years, were included. During a median follow up-time of 5.6 years, 4201 strokes occurred (4.0%). After multivariate adjustment the HRs (95% CI) for stroke in patients with eGDR categories between 4-6, 6-8 and > 8 were: 0.77 (0.69-0.87), 0.68 (0.58-0.80) and 0.60 (0.48-0.76), compared to the reference < 4. Corresponding numbers for the risk of death were: 0.82 (0.70-0.94), 0.75 (0.64-0.88) and 0.68 (0.53-0.89). The attributed relative risk R2 (± SE) for each variable in the eGDR formula and stroke was for: hypertension (0.045 ± 0.0024), HbA1c (0.013 ± 0.0014), and waist (0.006 ± 0.0009), respectively.ConclusionA low eGDR (a measure of insulin resistance) is associated with an increased risk of stroke and death in individuals with T2D. The relative attributed risk was most important for hypertension.

Project description:BackgroundEstimated glucose disposal rate (eGDR) is considered as a reliable alternative indicator of insulin resistance. However, the relationship between eGDR levels and mortality among individuals with cardiometabolic syndrome (CMS), as well as within different glucose metabolic states in this population, remains unclear.MethodsWe conducted a cohort study on 9928 CMS participants from the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018. The relationship between eGDR levels and mortality in the CMS population was evaluated using multivariable Cox proportional hazards regression models and restricted cubic splines (RCS). Finally, stratified analysis was performed to determine the relationship between eGDR levels and mortality in different subgroups.ResultsCox regression analysis showed a significant correlation between eGDR levels and both all-cause and cause-specific mortality in the entire CMS population (all p < 0.05). RCS analysis revealed a non-linear relationship between eGDR levels and both all-cause (p for overall < 0.001, p for non-linear < 0.001) and diabetes specific mortality (p for overall < 0.001, p for non-linear = 0.004) in CMS population, while a linear relationship with cardiovascular specific mortality (p for overall < 0.001, p for non-linear = 0.091). In participants with baseline diabetes mellitus (DM), eGDR levels were significantly correlated with all-cause mortality, cardiovascular specific mortality, and diabetes specific mortality (all p < 0.05). In CMS participants with baseline pre-diabetes mellitus (Pre-DM), eGDR levels were significantly correlated with cardiovascular-specific and diabetes-specific mortality (all p < 0.05). In CMS participants with baseline normal glucose regulation (NGR), eGDR levels were only significantly related to diabetes specific mortality (p < 0.05).ConclusionThere is a significant correlation between eGDR levels and both all-cause and cause-specific mortality in the entire CMS population. Furthermore, the protective effect of high eGDR levels on mortality persists across various glucose metabolic states.

Project description:BackgroundEstimated glucose disposal rate (eGDR) is a novel, clinically available, and cost-effective surrogate of insulin resistance. The current study aimed to assess the association between eGDR and prevalent heart failure (HF), and further evaluate the value of eGDR in detecting prevalent HF in a general population.Methods25,450 subjects from the National Health and Nutrition Examination Survey 1999-2018 were included. HF was recorded according to the subjects' reports. Logistic regression was employed to analyze the association between eGDR and HF, the results were summarized as Per standard deviation (SD) change. Then, subgroup analysis tested whether the main result from logistic regression was robust in several conventional subpopulations. Finally, receiver-operating characteristic curve (ROC) and reclassification analysis were utilized to evaluate the potential value of eGDR in improving the detection of prevalent HF.ResultsThe prevalence of reported HF was 2.96% (753 subjects). After adjusting demographic, laboratory, anthropometric, and medical history data, each SD increment of eGDR could result in a 43.3% (P < 0.001) risk reduction for prevalent HF. In the quartile analysis, the top quartile had a 31.1% (P < 0.001) risk of prevalent HF compared to the bottom quartile in the full model. Smooth curve fitting demonstrated that the association was linear in the whole range of eGDR (P for non-linearity = 0.313). Subgroup analysis revealed that the association was robust in age, sex, race, diabetes, and hypertension subgroups (All P for interaction > 0.05). Additionally, ROC analysis displayed a significant improvement in the detection of prevalent HF (0.869 vs. 0.873, P = 0.008); reclassification analysis also confirmed the improvement from eGDR (All P < 0.001).ConclusionOur study indicates that eGDR, a costless surrogate of insulin resistance, may have a linear and robust association with the prevalent HF. Furthermore, our findings implicate the potential value of eGDR in refining the detection of prevalent HF in the general population.

Dataset Information

Estimated glucose disposal rate as a candidate biomarker for thrombotic biomarkers in T1D: a pooled analysis.

Purpose

Methods

Results

Conclusions

Trial registration

Publications

Estimated glucose disposal rate as a candidate biomarker for thrombotic biomarkers in T1D: a pooled analysis.

Similar Datasets

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