PMID- 32501612 OWN - NLM STAT- MEDLINE DCOM- 20210802 LR - 20221207 IS - 1399-5448 (Electronic) IS - 1399-543X (Print) IS - 1399-543X (Linking) VI - 21 IP - 6 DP - 2020 Sep TI - Circulating adhesion molecules and associations with HbA1c, hypertension, nephropathy, and retinopathy in the Treatment Options for type 2 Diabetes in Adolescent and Youth study. PG - 923-931 LID - 10.1111/pedi.13062 [doi] AB - BACKGROUND: 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. METHODS: 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. RESULTS: 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). E-selectin 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 E-selectin was 15.5% higher in participants with microalbuminuria (both P < .01). There was no significant association of adhesion molecule levels with retinopathy. CONCLUSION: 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. CI - (c) 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Tryggestad, Jeanie B AU - Tryggestad JB AD - Department of Diabetes and Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. FAU - Shah, Rachana D AU - Shah RD AD - Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. FAU - Braffett, Barbara H AU - Braffett BH AUID- ORCID: 0000-0002-2184-9754 AD - The Biostatistics Center, George Washington University, Rockville, Maryland, USA. FAU - Bacha, Fida AU - Bacha F AD - Department of Diabetes and Endocrinology, Baylor College of Medicine, Houston, Texas, USA. FAU - Gidding, Samuel S AU - Gidding SS AD - FH Foundation, Pasadena, California, USA. FAU - Gubitosi-Klug, Rose A AU - Gubitosi-Klug RA AUID- ORCID: 0000-0002-7376-6870 AD - Department of Pediatric Endocrinology, Diabetes and Metabolism, Case Western Reserve University, Cleveland, Ohio, USA. FAU - Shah, Amy S AU - Shah AS AD - Division of Endocrinology, Cincinnati Children's Hospital and the University of Cincinnati, Cincinnati, Ohio, USA. FAU - Urbina, Elaine M AU - Urbina EM AD - Division of Endocrinology, Cincinnati Children's Hospital and the University of Cincinnati, Cincinnati, Ohio, USA. FAU - Levitt Katz, Lorraine E AU - Levitt Katz LE AD - Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. CN - TODAY Study Group LA - eng GR - U01 DK061254/DK/NIDDK NIH HHS/United States GR - U01 DK061242/DK/NIDDK NIH HHS/United States GR - U01 DK061212/DK/NIDDK NIH HHS/United States GR - U01 DK061230/DK/NIDDK NIH HHS/United States GR - U01 DK061239/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200702 PL - Denmark TA - Pediatr Diabetes JT - Pediatric diabetes JID - 100939345 RN - 0 (Cell Adhesion Molecules) RN - 0 (Glycated Hemoglobin A) RN - 05V02F2KDG (Rosiglitazone) RN - 9100L32L2N (Metformin) SB - IM MH - Adolescent MH - Age of Onset MH - Cell Adhesion Molecules/*blood MH - Child MH - Combined Modality Therapy MH - Diabetes Mellitus, Type 2/*blood/*complications/epidemiology/therapy MH - Diabetic Angiopathies/blood/epidemiology/etiology/therapy MH - Diabetic Nephropathies/blood/complications/epidemiology/therapy MH - Diabetic Retinopathy/blood/complications/epidemiology/therapy MH - Drug Therapy, Combination MH - Female MH - Follow-Up Studies MH - Glycated Hemoglobin/analysis/*metabolism MH - Humans MH - Hypertension/*blood/complications/epidemiology/therapy MH - Male MH - Metformin/administration & dosage MH - Risk Reduction Behavior MH - Rosiglitazone/administration & dosage PMC - PMC7877547 MID - NIHMS1649118 OTO - NOTNLM OT - HbA1c OT - adhesion molecules OT - microvascular complications OT - type 2 diabetes COIS- CONFLICT OF INTEREST The authors declare no potential conflict of interest. EDAT- 2020/06/06 06:00 MHDA- 2021/08/03 06:00 PMCR- 2021/02/11 CRDT- 2020/06/06 06:00 PHST- 2020/03/06 00:00 [received] PHST- 2020/04/30 00:00 [revised] PHST- 2020/05/28 00:00 [accepted] PHST- 2020/06/06 06:00 [pubmed] PHST- 2021/08/03 06:00 [medline] PHST- 2020/06/06 06:00 [entrez] PHST- 2021/02/11 00:00 [pmc-release] AID - 10.1111/pedi.13062 [doi] PST - ppublish SO - Pediatr Diabetes. 2020 Sep;21(6):923-931. doi: 10.1111/pedi.13062. Epub 2020 Jul 2.