Researchers Identify Endothelial Markers Correlated With Kidney Disfunction in T1D

Results of a prospective observational study indicated endothelial inflammatory disease occurs in the early stages of type 1 diabetes (T1D) in children.

Writing in the Journal of Clinical Medicine, researchers also noted correlations between selected markers of endothelial lesions, including plasminogen activator inhibitor 1 (PAI-1), selectin E (sE-SELECTIN), and estimated glomerular filtration rate (eGFR), suggesting they may function better than other markers of endothelial dysfunction as prognostic factors for kidney dysfunction in this population.

Diabetic neuropathy is one of the most serious complications of diabetes, resulting from metabolic disturbances and coexisting inflammation, authors explained.

Although albuminuria is considered one of the main markers of generalized vascular endothelium damage, “the increased concentrations of inflammation indices can already be found during the early period where changes occur in the kidneys, which occur long before glomerulosclerosis and which may disappear after the metabolic balance of the disease is regained,” they added. Other factors can also impact the progression of vascular changes.

In an effort to determine if biomarkers of inflammation and endothelial dysfunction are associated with T1D prognosis, researchers conducted a series of tests among 66 patients and analyzed effects of T1D duration and other disease characteristics on the extent of endothelial damage.

A total of 36 boys and 30 girls with T1D treated at a single center were included in the study, while 21 healthy children made up the control group (10 boys, 11 girls).

Investigators collected data on anthropometric measurements and analyzed patients’ blood and urine samples for sVCAM-1, sICAM-1, sE-SELECTIN, PAI-1, ADMA and RAGE. “We used the serum from patients to determine the biochemical substances produced by the endothelium…because their concentrations increase rapidly in states of cellular stress,” researchers said.

Analyses revealed:

• In those with T1D, significantly higher concentrations of all of the assayed markers were observed compared with healthy controls (P < .001)
• All of the evaluated markers positively correlated with the disease duration, age, and body mass index of the patients
• Only PAI-1 and sE-SELECTIN were characteristic of linear correlations with eGFR
• Taking into account the degree of diabetes metabolic control, the highest concentrations of the studied endothelial damage markers were observed in children with the lowest glycated hemoglobin (A1C) values, ie, between 6.5% and 8.9%, while the lowest ones were observed in the children with the worst glycemic control (A1C ≥ 14%)
• sE-SELECTIN had the highest R2 = 0.09 and had a regression coefficient of −0.75, SE = 0.28, and intercept = 209.28 (P =.0088)
• sE-SELECTIN was proven to be an independent predictor (P= .033) of eGFR

Overall, it was possible to predict T1D based on each biomarker with 100% accuracy, authors wrote, while findings confirm “earlier reports that diabetes duration is an important risk factor for the development of chronic diabetes complications, which are characterized by chronic subclinical endothelial inflammation.”

Future studies are warranted to explore whether the evaluated markers are sensitive enough to assess vascular endothelial inflammation and can thus estimate the of the risk of vascular complications in patients with diabetes.

“When looking at this issue in the context of nephrological complications, attention should be given to the linear correlations between PAI-1 and eGFR as well as to those between sE-SELECTIN and eGFR, as such results may suggest a certain advantage of PAI-1 and sE-SELECTIN over the other endothelial dysfunction markers, especially regarding the identification of early changes in the kidneys,” researchers concluded.

Reference

Nocuń-Wasilewska K, Zwolińska D, Zubkiewicz-Kucharska A, and Polak-Jonkisz D. Evaluation of vascular endothelial function in children with type 1 diabetes mellitus. J Clin Med. Published online October 29, 2021. doi:10.3390/jcm10215065