Thyroid hormone levels tied to maturation of implanted PECs in T1D patients

Thyroid hormones play a significant role in pancreatic endoderm cell (PEC) therapy in patients with type 1 diabetes (T1D), according to a study, noting that a thyroid hormone adjuvant therapy may be helpful in improving cell outcomes in some recipients of PEC.

“Macroencapsulated PECs can reverse diabetes in rodents, and preclinical studies revealed that thyroid hormones in vitro and in vivo bias PECs to differentiate into insulin-producing cells,” the researchers said.

An ongoing trial demonstrated the safety of implanting microencapsulated PECs into T1D patients but provided mixed results. “Though most patients developed meal responsive C-peptide, levels were heterogeneous and explanted grafts had variable numbers of surviving cells with variable distribution of endocrine cells,” the researchers said.

In the current study, circulating triiodothyronine and thyroxine levels were measured in T1D patients treated at one of the seven sites of the ongoing clinical trial. Then, the researchers determined if thyroid hormone levels correlated with the C-peptide or glucagon levels and cell fate of implanted PECs.

Triiodothyronine and thyroxine levels both showed a significant correlation with the proportion of cells that adopted an insulin-producing fate with a mature phenotype.

On the other hand, an inverse association was seen between thyroid hormone levels and circulating glucagon levels after implantation. This indicated that thyroid hormones “lead PECs to favour an insulin-producing fate over a glucagon-producing fate,” the researchers said.

“In mice, hyperthyroidism led to more rapid maturation of PECs into insulin-producing cells similar in phenotype to PECs in euthyroid mice,” they added.