Abstract
PurposeTo determine the utility of estimated glucose disposal rate (eGDR) as a candidate biomarker for thrombotic biomarkers in patients with type 1 diabetes (T1D).MethodsWe 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.ResultsThirty-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).ConclusionsCompared to BMI and insulin requirements, classical surrogates of insulin resistance, eGDR is a suitable and superior thrombotic risk indicator in T1D.Trial registrationISRCTN4081115; registered 27 June 2017.
Highlights
Insulin resistance in type 1 diabetes (T1D) is an established risk factor for cardiovascular disease [1, 2], retinopathy [3], and premature mortality [4]
Identify which, clinical parameters may serve as candidate biomarkers for a thrombotic biomarker profile, we applied a Pearson correlation coefficient matrix across variables (Fig. 2). estimated glucose disposal rate (eGDR) was negatively correlated with fibrinogen (r = − 0.69; P < 0.001), plasminogen activator inhibitor-1 (PAI-1) concentrations (r = − 0.67; P = 0.005), and tissue factor (TF) activity (r = − 0.36; P = 0.020), but not TNFα levels (r = − 0.19; P = 0.881)
We examined, for the first time, the association between eGDR, a validated surrogate marker of insulin resistance, and thrombotic biomarkers in patients with T1D
Summary
Insulin resistance in type 1 diabetes (T1D) is an established risk factor for cardiovascular disease [1, 2], retinopathy [3], and premature mortality [4]. The pathological linkage between insulin resistance and increased vascular risk is largely in virtue of an enhanced prothrombotic milieu [5,6,7,8]. Journal of Endocrinological Investigation (2021) 44:2417–2426 plasminogen activator inhibitor-1 (PAI-1) [6] Both T1D [9] and insulin resistance are associated with a procoagulant plasma profile [10], whereby increased PA1-1 and fibrinogen and reduced tissue plasminogen activator promotes atherothrombosis [11]. As such, identifying and treating insulin resistance in people with T1D represents an important therapeutic goal in reducing thrombotic biomarkers and preventing the development of overt vascular complications. We applied an unsupervised, data-driven cluster analysis, to establish a novel classification for thrombosis in our cohort, based on shared commonalities between routine clinical parameters and thrombotic biomarkers
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