Interdisciplinary

Ilya Nemenman, PhD

PROFESSOR, EMORY COLLEGE OF ARTS AND SCIENCES, PHYSICS / BIOLOGY

Priyathama Vellanki,MD

ASSOCIATE PROFESSOR, EMORY UNIVERSITY SCHOOL OF MEDICINE, MEDICINE

Modeling ketosis-prone diabetes remission via diverse mechanisms of glucotoxicity

Type 2 diabetes (T2D) is one of the most common chronic diseases worldwide. It is characterized by a runaway increase of blood glucose levels due to glucose being toxic to pancreatic beta-cells, decreasing their ability to secrete insulin, which, in turn, is needed for glucose disposal. Remission is rare, and treatment with multiple medications is typically required. However, T2D is a heterogeneous disease, and a subtype called “ketosis-prone diabetes” (KPD) has been identified, which especially affects patients of African origin. Unlike other types of T2D, KPD emerges suddenly, and intensive insulin therapy often leads to KPD remission in weeks or months. Mechanisms of this remission are poorly understood. We hypothesize that KPD is caused by a distinct form of glucose toxicity, which is acute and reversible. The faster rate of this toxicity can account for the rapid onset of KPD, and its reversibility allows for the remission. In this proposal we will create and clinically validate—using newly collected patient data—the first mathematical model of the onset and remission of KPD, enabling us to predict diverse diabetes remission outcomes following insulin treatment.