New Study from UPMC Children’s Multidisciplinary Team Finds Potential Biomarker of Early Complications from Type 1 Diabetes

A new study led by members of the Muzumdar Laboratory in the Division of Pediatric Endocrinology at UPMC Children’s, along with colleagues from the Divisions of Pediatric Endocrinology, Pulmonary Medicine and Nephrology, has new findings published in the journal Frontiers in Endocrinology that point to a possible new biomarker that can be indicative of early complications of type 1 diabetes (T1D) in pediatric patients.

Research assistant professor Zhenwei Gong, PhD, from the Muzumdar Laboratory, was the study's lead author. Jacqueline Ho, MD, MS, Division Chief of Pediatric Nephrology, and an expert in the study of microRNA in kidney disease,Ingrid Libman, MD, PhD, Director of the Diabetes Program, as well as Erick Forno, MD, MPH, ATSF, director of the Pediatric Asthma Center at UPMC Children's, contributed to the research.

“A study like this shows the multidisciplinary power at work at UPMC Children’s and the Department of Pediatrics at the University of Pittsburgh,” says Radhika Muzumdar, MD, chief of Pediatric Endocrinology at UPMC Children’s.

The clinical importance of the study’s findings is related to the limitations around current lab tests in detecting the early signals of diabetic nephropathy, a complication of T1D that contributes to the significant morbidity and mortality associated with the disease. The use of albuminuria levels as a marker can be suboptimal in early stages of the disease; therefore, a more definitive marker of early or subclinical DN would be greatly helpful in improving patient care and long-term outcomes.

“This study is also an example of the unique collaboration that we foster in our institution, going from bedside to bench and back to bedside,” says Dr. Libman.

Dr. Gong and colleagues' study found that serum klotho (KL) and a specific microRNA – miR-192 – were significantly altered in a cohort of 79 pediatric patients with T1D, such that levels of klotho decreased and miR-192 increased with diabetes duration and severity.

The research is also notable for the novel finding that miR-192 is directly responsible for the regulation of KL.

In addition to changes in serum levels of potential biomarkers, the findings also are supportive of miR-192 and KL influencing processes including inflammation, cellular oxidative stress, and senescence, all of which, to varying degrees, are implicated in complications arising from T1D.

“We believe that, with our current level of evidence, further studies are warranted to look deeper into KL and miR-192 as early biomarkers or potential therapeutic targets to address diabetic nephropathy,” says Dr. Gong.

Read the full study using the link below.

Reference

Gong Z, Banchs PAP, Liu Y, Fu H, Arena VC, Forno E, Libman I, Ho J, Muzumdar R. Serum a-KL, a Potential Early Marker of Diabetes Complications in Youth With T1D, Is Regulated by miRNA 192. Front Endocrinol (Lausanne). 2022 Aug 5; 13: 937093.