Can Fetuin-A Be a Marker for Insulin Resistance and Poor Glycemic Control in Children with Type 1 Diabetes Mellitus?

Abstract

Objective:Metabolic impairment in type 1 diabetes mellitus (T1DM) with poor glycemic control causes insulin resistance, non-alcoholic fatty liver disease (NAFLD), atherosclerosis, and increased carotid intima-media thickness (CIMT). Fetuin-A has a protective effect in cardiovascular disorders and is increased in hepatosteatosis. We aimed to investigate the reliability of fetuin-A levels in early detection of diabetic complications in children with T1DM and to identify a cut-off value that may show poor metabolic control.Methods:The study included 80 patients who had T1DM for at least 5 years and who had no chronic complications or an auto-immune disorder. Blood samples were drawn to measure hemoglobin A1c (HbA1c), biochemical parameters, and fetuin-A levels. Anthropometric parameters were also measured. Percent body fat was calculated. Hepatosteatosis and CIMT were assessed by sonography. Results:Mean age of the patients was 13.5 years. Grade 1 hepatosteatosis was detected in 10%. Patients were stratified into 2 groups based on presence of NAFLD. Fetuin-A level was increased in patients with NAFLD. We identified a fetuin-A cut-off value (514.28 ng/mL; sensitivity: 47.34; specificity: 96.72) that may predict NAFLD. HbA1c and total cholesterol levels were found to be higher in patients with fetuin-A levels above higher the cut-off value.Conclusion:Fetuin-A is a reliable parameter in the prediction of complications and poor glycemic control in patients with T1DM.

Relationship of Serum Fetuin A with Metabolic and Clinical Parameters in German Children and Adolescents with Type 1 Diabetes

“…In contrast to the previous results, we could not reproduce the positive correlation of fetuin A with BMI/BMI SDS [41-43], similar to most former studies in healthy, obese, or T2D adults [13, 53, 54]. …”

“…Three previous studies from Egypt, Greece, and Turkey have meanwhile investigated fetuin A in children and adolescents with T1D [41-43]; however, their cohorts were smaller than ours, they had shorter follow-up, and they did not focus on comorbidities. In contrast to the previous results, we could not reproduce the positive correlation of fetuin A with BMI/BMI SDS [41-43], similar to most former studies in healthy, obese, or T2D adults [13, 53, 54].…”

“…However, previous data on fetuin A and atherosclerosis in non-T1D cohorts are inconsistent: both low and high fetuin A concentrations were associated with cardiovascular disease and mortality risk [21-23]. Some authors suggested that fetuin A plays a protective role against vascular calcification and atherosclerosis [23, 59, 60], while others found that higher fetuin A levels are associated with arterial stiffness, increased intima media thickness [41, 43, 61, 62], and an increased risk of peripheral arterial disease, myocardial infarction, and ischemic stroke [20, 63, 64]. Comorbidity and late complication rates were low and not related to fetuin A levels, e.g., we did not observe any case with diabetic retinopathy in our cohort, which may be either due to the fact that the number of patients was too low, that patients were too young to observe late complications, or that fetuin A is not a reliable marker for increased complications in young T1D patients.…”

“…The most recent study from Turkey in 80 T1D patients [43] showed a positive correlation of fetuin A with HbA1c, intima media thickness of the carotid arteries, aminotransferases, and body fat content; however, the authors detected a 10% NAFLD rate, which is higher than what we expect in our population [37]. In accordance with two of the abovementioned studies, fetuin A was not positively correlated with HbA1c in our T1D cohort, while positive associations have been described in gestational diabetes, T2D, or the metabolic syndrome [13, 14, 55].…”

“…Previous pediatric studies have determined fetuin A levels in healthy children [39, 40] as well as in obese children with and without T2D and NAFLD [2, 4, 13], and only three smaller studies have investigated fetuin A in children with T1D, with partially conflicting results [41-43]. …”