PRIMARY OBJECTIVES:
I. To determine if changes in islet cell physiology are detectable before or after matched related donor (MRD) hematopoietic stem cell transplant (HCT) in patients developing new-onset post-transplant diabetes mellitus (PTDM).
1. To determine if a compensatory increase in glucose stimulated insulin secretion (GSIS) by β-cells precedes PTDM development in patients without diabetes undergoing MRD HCT.
2. To determine if excess glucagon secretion and impaired α-cell response to glucose or GLP-1 contributes to the hyperglycemia of PTDM.
II. To determine if the IL-33/ST2 axis promotes immune/islet cell dysregulation during PTDM.
OUTLINE:
Patients undergo 2 OGTTs and a standard hyperglycemic clamp procedure prior to HCT. Patients then undergo repeat OGTTs and a hyperglycemic clamp procedure once after HCT between days 80-100.
Recent or current history of diabetes mellitus, defined as:1) diabetes therapy within 6 months of enrollment, or 2) fasting blood glucose at "pre-admit" (screening) visit \>= 126 mg/dL
Pregnancy or breastfeeding
Umbilical cord blood transplants
Patients on established, chronic corticosteroid therapy (\> 10 mg /day of prednisone or prednisone equivalent) prior to transplant; established, chronic corticosteroid therapy is defined as daily dosing of \> 10 mg/day of prednisone or prednisone equivalent for at least 2 weeks prior to the start of conditioning/chemotherapy or plans to continue pre-transplant corticosteroids (\> 10 mg/day of prednisone or prednisone equivalent) indefinitely after transplantation
Inability to give informed consent
Any condition which, in the opinion of the investigator, might interfere with study objective
Any reason which, in the opinion of the investigator, adds additional risk to the patient
Diagnosis of diabetes by standard oral glucose tolerance testing prior to transplant (2-hour plasma glucose value ≥ 200 mg/dL) in either Arm 1 or 2 will exclude further testing as per Aim 1. Immunological / metabolic testing as per Aim 2 will still be allowed
Individuals not donating stem cells
Pregnancy or breastfeeding
Inability to give informed consent
Any condition which, in the opinion of the investigator, might interfere with study objective
Clareo Health | Finding the Cause for Post-Transplant Diabetes Mellitus After Allogeneic Hematopoietic Cell Transplant
