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Title: Circulating adhesion molecules and associations with HbA1c, hypertension, nephropathy, and retinopathy in the treatment options for type 2 diabetes in adolescent and youth study

item TRYGGESTAD, JEANIE - University Of Oklahoma Health Sciences Center
item SHAH, RACHANA - Children'S Hospital - Philadelphia, Pennsylvania
item BRAFFETT, BARBARA - George Washington University
item BACHA, FIDA - Children'S Nutrition Research Center (CNRC)
item GIDDING, SAMUEL - Familial Hypercholesterolemia Foundation
item GUBITOSI-KLUG, ROSE - Case Western Reserve University (CWRU)
item SHAH, AMY - University Of Cincinnati
item URBINA, ELAINE - University Of Cincinnati
item LEVITT KATZ, LORRAINE - Children'S Hospital - Philadelphia, Pennsylvania

Submitted to: Pediatric Diabetes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/28/2020
Publication Date: 6/5/2020
Citation: Tryggestad, J.B., Shah, R.D., Braffett, B.H., Bacha, F., Gidding, S.S., Gubitosi-Klug, R.A., Shah, A.S., Urbina, E.M., Levitt Katz, L.E. 2020. Circulating adhesion molecules and associations with HbA1c, hypertension, nephropathy, and retinopathy in the treatment options for type 2 Diabetes in adolescent and youth study. Pediatric Diabetes.

Interpretive Summary: Early stages of injury to the wall of the blood vessels are facilitated by substances called adhesion molecules that allow the inflammatory cells to interact with the vessel wall. This leads to plaque formation or atherosclerosis. Children and adolescents with type 2 diabetes may be at risk for these early changes in the vessels. Investigators evaluated 515 youth who participated in the "Treatment Options for Type 2 Diabetes in Adolescents and Youth" or TODAY study. They studied whether adhesion molecules increase overtime and how they may relate to blood sugar control and different treatments used to treat diabetes in children. They found that over 1 to 3 years, there were significant changes in these substances. This was not related to a specific treatment, but was related to increase in sugar levels and blood pressure. Some of these inflammatory substances were associated with early kidney damage. They concluded that these molecules rise with worse diabetes control in youth, and are related to blood pressure and early kidney disease which are markers of early injury to the blood vessels. This emphasizes the importance of blood sugar control and blood pressure treatment in youth with obesity and diabetes.

Technical Abstract: The Treatment Options for type 2 Diabetes in Adolescent and Youth study, a randomized clinical trial of three treatments for type 2 diabetes (T2DM) in youth, demonstrated treatment failure (defined as sustained HbA1c >/-8%, or inability to wean insulin after 3 months after acute metabolic decomposition) in over half of the participants. Given that binding of mononuclear cells to vascular endothelium, initiated by cellular adhesion molecules and chemokines, is an early step in vascular injury, we sought to evaluate (a) changes in cellular adhesion molecule levels during the trial; (b) effect of diabetes treatment; and (c) association of markers with HbA1c, hypertension, hypercholesterolemia, nephropathy, and retinopathy. Participants (n = 515 of 699) that had baseline assessment of adhesion molecules (monocyte chemoattractant protein-1 [MCP-1], vascular cell adhesion marker [VCAM], intercellular adhesion marker [ICAM], and E-Selectin) and at least one other assessment, measured at month 12, 24, or 36, were included. Over 1 to 3 years, significant increases in MCP-1 and decreases in VCAM(both P < .0001) concentrations were found; however, no significant interactions were identified with treatment group for any molecule. For every 1% increase in HbA1c, ICAM increased by 1.8%, VCAM by 1.5%, and E-selectin by 6.8% (all P < .0001). Eselectin increased by 3.7% and 4.2% for every 10 mm Hg increase in systolic and diastolic blood pressure, respectively (both P < .0001). ICAM was 10.2% higher and Eselectin was 15.5% higher in participants with microalbuminuria (both P < .01). There was no significant association of adhesion molecule levels with retinopathy. Concentrations of cellular adhesion molecules rise with increasing HbA1c in youth with T2DM, and are associated with blood pressure and microalbuminuria, markers of vascular injury.