New-Onset Post-Transplant Diabetes Mellitus after Allogeneic Hematopoietic Cell Transplant Is Initiated by Insulin Resistance, Not Immunosuppressive Medications.

Autor: Engelhardt BG; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: brian.engelhardt@vanderbilt.edu., Savani U; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Jung DK; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Powers AC; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Medicine, VA Tennessee Valley Healthcare, Nashville, Tennessee., Jagasia M; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Chen H; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee., Winnick JJ; Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio., Tamboli RA; Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee., Crowe JE Jr; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee., Abumrad NN; Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
Jazyk: angličtina
Zdroj: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [Biol Blood Marrow Transplant] 2019 Jun; Vol. 25 (6), pp. 1225-1231. Date of Electronic Publication: 2019 Feb 07.
DOI: 10.1016/j.bbmt.2019.02.001
Abstrakt: New-onset post-transplant diabetes mellitus (PTDM) occurs frequently after allogeneic hematopoietic cell transplant (HCT). Although calcineurin inhibitors and corticosteroids are assumed to be the cause for hyperglycemia, patients developing PTDM have elevated fasting C-peptide levels before HCT and before immunosuppressive medications. To determine if PTDM results from established insulin resistance present before transplant, we performed oral glucose tolerance tests (OGTTs) and measured whole body, peripheral, and hepatic insulin sensitivity with euglycemic hyperinsulinemic clamps before and 90 days after HLA-identical sibling donor HCT in 20 patients without pretransplant diabetes. HCT recipients were prospectively followed for the development of new-onset PTDM defined as a weekly fasting blood glucose ≥ 126 mg/dL or random blood glucose ≥ 200 mg/dL. During the first 100 days all patients received calcineurin inhibitors, and 11 individuals (55%) were prospectively diagnosed with new-onset PTDM. PTDM diagnosis preceded corticosteroid treatment. During the pretransplant OGTT, elevated fasting (87 mg/dL versus 101 mg/dL; P = .005) but not 2-hour postprandial glucose levels predicted PTDM diagnosis (P = .648). In response to insulin infusion during the euglycemic hyperinsulinemic clamp, patients developing PTDM had lower whole body glucose utilization (P = .047) and decreased peripheral/skeletal muscle uptake (P = .031) before and after transplant, respectively, when compared with non-PTDM patients. Hepatic insulin sensitivity did not differ. Survival was decreased in PTDM patients (2-year estimate, 55% versus 100%; P = .039). Insulin resistance before HCT is a risk factor for PTDM independent of immunosuppression. Fasting pretransplant glucose levels identified PTDM susceptibility, and peripheral insulin resistance could be targeted for prevention and treatment of PTDM after HCT.
(Copyright © 2019 American Society for Blood and Marrow Transplantation. All rights reserved.)
Databáze: MEDLINE
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