Amy Sanghavi Shah, MD, MS, Associate Professor

Investigators at Cincinnati Children’s Hospital along with others aim to understand the association between youth-onset diabetes and cardiovascular health. Work performed as part of a multicenter collaboration called the SEARCH for Diabetes in Youth Study, found young adults in their early twenties with youth onset diabetes are at risk for future heart failure. Researchers studied young adults with type 1 diabetes and type 2 diabetes diagnosed in childhood. Participants with type 2 diabetes had thicker heart and worse diastolic function, but the prevalence of cardiac dysfunction was high in both groups (57.7% in type 2 diabetes vs 47.2% in type 1 diabetes, p<0.05). Risk factors associated with worse diastolic function included weight, blood pressure, glucose control and heart rate. Diastolic function is important because it may predict a special kind of heart failure: heart failure with preserved ejection fraction (HFpEF) for which there are currently no effective treatments. These data suggest young adults with diabetes may be at increased risk for HFpEF, but improvements in weight, blood pressure, glucose control and heart rate may lower this risk. This work received funding from the NIH and CDC and is a collaboration between investigators in the Division of Endocrinology (Shah and Lawrence Dolan, MD) and the Division of Cardiology (Elaine Urbina, MD, MS) at Cincinnati Children’s along with three other sites in the U.S. (Seattle, Colorado, and South Carolina).

Amy Sanghavi Shah, MD, Associate Professor

Researchers at Cincinnati Children’s (Shah in the Division of Endocrinology and Michael Helmrath, MD, in the Center for Bariatric Research and Innovation) along with investigators at Denver Children’s Hospital recently launched a study in adolescents that will provide a head-to-head comparison of the most popular type of bariatric surgery from vertical sleeve gastrectomy to advanced medical management. The need for such research is critical. Type 2 diabetes in youth is different than adult onset: it is more aggressive and progresses faster and youth develop more severe comorbidities. As a result, we need a better understanding of effective treatments. This work funded by the National Institutes of Health, will enroll 90 patients between the ages of 13 and 19 across two sites. One group will undergo vertical sleeve gastrectomy, approved for adolescents with obesity. The control group will receive advanced medical therapy targeting at lowering hemoglobin A1c to less than 6.5% in order to prevent diabetes related complications. In addition, the study aims to understand the mechanisms underlying metabolic bariatric surgery in youth. The idea is that understanding how surgery works could guide the development of non-surgical treatments to target these same pathways.

Philippe Backeljauw, MD, Professor of Pediatrics

Aggrecan is a proteoglycan found in articular and growth plate cartilage. Aggrecan deficiency, due to heterozygous mutations in the ACAN gene, causes dominantly inherited short stature, often with advanced skeletal maturation, and may result in premature growth cessation. Affected individuals may also develop osteochondritis dissecans, early-onset osteoarthritis and degenerative disc disease. Previously, no specific therapy was available to improve these patients’ growth potential. Backeljauw and colleagues investigated the effects of one year of therapy with recombinant human growth hormone (rhGH) on linear growth in prepubertal children with aggrecan deficiency. Treatment with rhGH in a small cohort of patients with short stature due to aggrecan deficiency improved linear growth. All (six) patients completing a full year of treatment demonstrated a favorable response, characterized by a median delta height SD of +0.6. These children qualified for an additional two years of treatment as part of our study’s extension trial, with identification and enrollment of additional patients. The study reported no significant adverse events. Longer treatment will demonstrate if the initial growth response is sustainable and leads to improved adult height.