Finding the Cause for Post-Transplant Diabetes Mellitus After Allogeneic Hematopoietic Cell Transplant

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.

Inclusion Criteria for Patients:

- Patients undergoing matched related donor (MRD) allogeneic hematopoietic stem cell
transplantation (HCT).

Exclusion Criteria for Patients:

- Patients who have not received an allogeneic HCT

- 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

- Unrelated donor, umbilical cord blood, mismatched, or haploidentical transplants

- Patients receiving T cell depletion or thymoglobulin as part of their transplant

- 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

Additional exclusion criteria (Arms 1 and 2Aim 1 only):

-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

DONORS Inclusion Criteria for Donors (Arm 1 and Arm 2) Donors undergoing stem cell
collection for match related allogeneic stem cell transplant

Exclusion Criteria for Donors (Arms 1 and 2):

- 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