Identifying Early Signs of Foot Complications in Childhood-onset Type 2 Diabetes Mellitus - PROJECT SUMMARY Non-traumatic lower extremity amputation is on the rise in young adults (18-44 years old), which is likely due to the 95% increase in childhood-onset type 2 diabetes (T2D) in the United States. Forefoot and midfoot deformities are common diabetic foot complications that initiate the cascade of events leading to increased dynamic pressure, a precursor of ulceration, leading to amputation. In adult-onset T2D, we found that bone mineral density and motion are significantly related to deformity and plantar pressure. However, we do not know if people with childhood-onset T2D present with forefoot or midfoot deformity pathways to ulceration and amputation. We suspect that childhood-onset T2D will primarily follow a midfoot deformity pathway because of the increased presence of midfoot deformity in children with T2D, likely a result of early and severe onset of obesity. Thus, this application will address the gap of knowledge by investigating the deformity pathway in childhood-onset T2D. K99 Phase: Aim 1.1. Determine the effects of T2D, obesity, bone mineral density, and motion on foot deformity and plantar pressure in adults (18-45 years old, N=36), which will provide the foundation for understanding the foot deformity and plantar pressure in adults with childhood-onset T2D. Aim 1.2. Test feasibility and methodological application of imaging measures for the R00 phase in children with T2D and obesity (age 14- <18 years old, N=5), which will assist in adapting methods to pediatrics and provide pilot data for the R00 phase. R00 Phase: Aim 2.1. Determine the effects of T2D, obesity, bone mineral density, and motion on foot deformity and plantar pressure in children (14-<18 years old, N=54), which will provide the first-ever dataset of foot-specific bone mineral density, motion, and deformity in children. Aim 2.2. Explore candidate contributing factors to foot deformity in children (age 14-<18 years old; R00 N=54, K99 N=5, total N=59), which will identify contributors to foot deformity, informing interventional targets for amputation prevention. In both K99 and R00 phases, we will use unsupervised machine learning algorithms to understand the relationships between all variables and participants. Then, we will use multivariable regression models to test specific hypothesized relationships. The K99 project will provide me with multi-disciplinary training in (1) foot specific-imaging, (2) childhood-onset T2D, (3) statistical modeling, (4) writing and managing NIH R01 grants, and (5) improving science communication, teaching, and mentoring skills. My long-term goal is to become a leading clinical researcher investigating diabetic foot complications in childhood-onset T2D over the lifespan and preventing ulceration and amputation impacted by early-onset diabetic foot complications. This K99/R00 award will provide the foundational knowledge required to support future NIH R01 grants investigating longitudinal and interventional trials and prevent foot deformity to reduce the risks of amputation in individuals with childhood-onset T2D.
