Yale Endocrinology Presents Studies on Type 2 Diabetes, Obesity and Breast Cancer – Yale School of Medicine

Silvio Inzucchi, MD, presented new data from the DELIVER trial at the European Association for the Study of Diabetes (EASD) in September, while Ania Jastreboff, MD, PhD, discussed the SURMOUNT-1 trial. Members of the Insogna and Wysolmerski labs presented at the American Society for Bone and Mineral Research Annual Meeting, also in September.
At a major symposium at the European Association for the Study of Diabetes (EASD) in Stockholm, Sweden, Silvio Inzucchi, MD, professor of medicine (endocrinology) presented new data from the DELIVER trial. DELIVER examined the effectiveness of the SGLT2 inhibitor dapagliflozin on clinical outcomes in over 6,000 patients with heart failure and mildly reduced or preserved ejection fraction. Inzucchi specifically reported on the outcomes by baseline subgroups defined by glycemic status. Dapagliflozin, originally developed as a glucose-lowering agent for type 2 diabetes, appeared equally effective in reducing the composite outcome of worsening heart failure and cardiovascular death in both those with diabetes, prediabetes, and normoglycemia, he said. “This, in combination with earlier findings from the DAPA-HF trial, which studied patients with heart failure and reduced ejection fraction, indicates that dapagliflozin improves heart failure outcomes across the spectra of both ejection fraction as well as glycemia,” Inzucchi reported.
Ania Jastreboff, MD, PhD, presented efficacy and safety data from the SURMOUNT1-1 trial at the EASD in September, with additional body composition and glycemic change data. Jastreboff was the site principal investigator at Yale and lead author for SURMOUNT-1, a study that demonstrated that people with obesity treated with the novel GIP/GLP-1 receptor agonist, tirzepatide, lost on average 52 pounds with the highest dose of the medication. Jastreboff also presented findings from the study at the 2022 American Diabetes Association Scientific Sessions in June, simultaneously published in New England Journal of Medicine.
Karl Insogna, MD, FACP, Ensign Professor of Medicine (endocrinology) and Director of the Yale Bone Center, traveled to Austin, Tx. in September for the American Society for Bone and Mineral Research (ASBMR) Annual Meeting where the following members of his lab, and the lab of John Wysolmerski, MD, professor of medicine (endocrinology) presented posters.
“Intracrine PTHrP Induces Secretory Differentiation and Tumor Development in Breast Cancer Model.”
Contributing authors: Kata Boras-Granic, Farzin M. Takyar, Pamela Dann, Julie R. Hens, Christina Marmol, Jongwon Lee, Martin E. Garcia Sola, Jungmin Choi, Lewis A. Chodosh, and John Wysolmerski.
Key Finding:
· PTHrP overexpression activates STAT5 and leads to increased proliferation and secretory differentiation of both normal mammary epithelial cells and mammary tumor cells, the result of an intracrine pathway rather than a function of secreted PTHrP. The greatest proportion of tumor cells with elevated PTHrP expression were found in triple negative breast cancers, where higher PTHrP mRNA levels correlated with an enrichment of STAT5-related gene expression.
“The Effects of Blood Storage on Parameters of Mineral Metabolism.”
Contributing authors: Christine A. Simpson, Evelyn Hsieh, Rebecca Sullivan, and Karl Insogna.
Key Finding:
· Depending on the method of collection and storage, samples that have been processed in a clinical laboratory may still be used to obtain accurate research results for the analytes we evaluated. These data will help in conducting resesarch studies in acute care settings where sample collection for purposes other than clinical management may not be possible.
“PTH does not change the expression of Adenylate-Uridylate-Rich Binding Element binding proteins as part of the mechanism by which it stabilizes Receptor Activator of NF Kappa B Ligand transcripts.”
Contributing author: Karl Insogna.
Key Findings:
· PTH increases RANKL mRNA expression in primary murine osteoblasts and UAMS cells
· PTH does not alter the expression of four known ARE-binding proteins
· Despite this latter finding, PTH treatment dramatically stabilizes RANKL mRNA in the absence of transcription
· This indicates that post-transcriptional mechanisms are responsible for PTH-dependent stabilization of RANKL transcripts
Yale’s Section of Endocrinology & Metabolism works to improve the health of individuals with endocrine and metabolic diseases by advancing scientific knowledge; applying new information to patient care; and training the next generation of physicians and scientists to become leaders in the field. To learn more about their work, visit Endocrinology & Metabolism.

source