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

• Published in: Journal of endocrinological investigation Vol. 44; no. 11; pp. 2417 - 2426
• Main Authors: O’Mahoney, L. L., Kietsiriroje, N., Pearson, S., West, D. J., Holmes, M., Ajjan, R. A., Campbell, M. D.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.11.2021; Springer Nature B.V
• Subjects: Adult; Age; Biomarkers; Biomarkers - analysis; Biomarkers - blood; Blood Coagulation - physiology; Blood Glucose - analysis; Blood Glucose - metabolism; Blood pressure; Body Mass Index; Cluster Analysis; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - metabolism; Endocrinology; Female; Fibrinogen; Fibrinogen - analysis; Glycated Hemoglobin A - analysis; Glycated Hemoglobin A - metabolism; Humans; Insulin; Insulin - therapeutic use; Insulin Resistance; Internal Medicine; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Original; Original Article; Patients; Plasminogen Activator Inhibitor 1 - blood; Plasminogen activator inhibitors; Platelet Aggregation - physiology; Regression analysis; Risk Assessment; Thromboplastin - analysis; Thrombosis - blood; Thrombosis - diagnosis; Thrombosis - etiology; Tissue factor; Tumor necrosis factor-α; Cluster analysis; Type 1 diabetes; Thrombosis; eGDR
• ISSN: 1720-8386; 0391-4097; 1720-8386
• DOI: 10.1007/s40618-021-01550-3

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/m 2 ; 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.