Investigating potential protein markers of cardiovascular disease in children with type 1 diabetes mellitus

Abstract

Background: Type 1 diabetes mellitus (T1DM) is a metabolic disease characterized by dysglycaemia. Cardiovascular disease (CVD) is a major complication among T1DM patients and the leading cause of mortality later in life. Methods:The study subjects consisted of T1DM children with poor glycemic control (HbA1c > 7.5%) and healthy age and gender matched controls. Venous blood samples were collected and tested by utilizing a novel immunoassay panel with 96 protein biomarkers. Data were analyzed using non-linear regression analysis and the expression of biomarkers was compared between T1DM and healthy control groups using an unpaired student's t-test. Dynamic principal component analysis (PCA) was operated based on the differentially expressed proteins. Results: Ten T1DM children and 10 healthy controls were analyzed. Twelve CVD markers show significant differential expression between T1DM patients and healthy controls (p < 0.05). Dynamic PCA clustering based on differentially expressed proteins demonstrated an obvious clustering between the two populations. Conclusions: This preliminary study reveals the feasibility of utilizing a novel immunoassay panel to investigate potential biomarkers for predicting incipient CVD in children with T1DM. In future, longitudinal studies are required to track the relationships between measurements of the selected protein markers and the development of CVD in T1DM patients. K E Y W O R D S biomarkers, cardiovascular disease, paediatrics, type 1 diabetes mellitus Type 1 diabetes mellitus (T1DM) results in absolute insulin deficiency, polyuria, polydipsia, and weight loss [1]. Globally, the prevalence of T1DM is increasing [2], and is associated with a substantially heightened risk of microvascular and macrovascular complications such as neuropathy, nephropathy, retinopathy, cerebrovascular disease, and cardiovascular disease (CVD) [3]. Among T1DM patients, CVD is one of the major long-term complications and the main causes of mortality later in life [4]. Despite this, established biomarkers are limited in predicting T1DM related CVD. Glycated hemoglobin (HbA1c) was frequently used as a biomarker for risk assessment because levels can indicate average 3-month blood sugar levels [5-7]. However, the efficacy of intensive glycemic control still lacks consensus and the target HbA1c levels for T1DM patients varies significantly between organizations [5,8]. Other biomarkers such as lipid level, albumin, body mass index, inflammatory markers, blood pressure, or osteoprotegerin are affected by covariables such as obesity, retinopathy, or nephropathy, making them difficult to utilize as independent CVD predictors [7,9,10]. Early detection of disease progression is of importance in the prevention of the CVD complication in T1DM patients. In this

HbA1c levels and circulating inflammatory proteins at onset of type 1 diabetes in children and adolescents

“…Identifying risk factors (besides poor metabolic control) before complications from diabetes occur could also help doctors and nurses working with children and adolescents with type 1 diabetes to improve and personalise their treatment. Previous studies have suggested the association of circulating proteins as biomarkers of vascular disease in both adults and children with type 1 diabetes [9,10,30]. The current study observed increased sCD163 in patients with recent-onset type 1 diabetes with levels correlating to HbA1c.…”