Research Database
A multi-‘omics approach to identifying youth at high risk of early-onset type 2 diabetes
Wei Perng, PhD
Institution:
Colorado School of Public Health
Grant Number:
7-22-ICTSPM-08
Type of Grant:
Translational
Diabetes Type:
Pre-diabetes/insulin resistance
Focus:
Project Date:
-
Project Status:
active

Research Description

Type 2 diabetes (T2D) is on the rise among young people worldwide. Although the occurrence of early-onset T2D is undoubtedly related to the childhood obesity epidemic, little else is known about the pathophysiological processes that culminate in T2D, which prevents us from implementing effective interventions. We posit that identifying targets for preventive intervention requires studying and following initially healthy youth to identify unfavorable changes in glucose and insulin biomarkers until development of dysglycemia (impaired glucose tolerance, impaired fasting glucose, or T2D), which occurs more frequently in early adulthood than in earlier life stages. Here, we capitalize on Exploring Perinatal Outcomes among CHildren (EPOCH), a small but well-characterized cohort of healthy youth, originally recruited to study the effects of overnutrition in utero on metabolic risk across childhood (age 10 y, n=604) and adolescence (age 16 y, n=417). We now propose a 3rd research visit in young adulthood (age ~26 y; target n=350) to study how changes in metabolism and BMI lead to development of dysglycemia by young adulthood. Additionally, we leverage deep phenotyping data to characterize novel biomarkers and build prediction models that identify youth who should be the focus of T2D precision prevention efforts. The work we propose is not only highly significant, but also time sensitive: as EPOCH participants enter adulthood, cases of dysglycemia are directly relevant to the etiology of early-onset T2D, as there is still minimal confounding by reproductive history and age-related declines in beta cell function.

Research Profile

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?

This research project seeks to accelerate efforts to prevent early-onset type 2 diabetes through characterization of high-risk glucose-insulin homeostasis and body mass index trajectories from childhood through young adulthood, and development of multi-'omics prediction algorithms.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

While this project focuses on prevention of type 2 diabetes, research findings will also help someone with diabetes through identification of adverse changes to glucose-insulin homeostasis that should be avoided, if possible; and identification of modifiable risk factors to optimize glycemic control. Additionally, as this project leverages rich data on metabolic disease risk factors from gestation through young adulthood, findings will inform primordial prevention of diabetes for future generations.

Why important for you, personally, to become involved in diabetes research? What role will this award play?

I am invested in diabetes prevention research because my mother had gestational diabetes while pregnant with my brother, who, as a young adult, has a predisposition towards weight gain and a high HbA1c, presumably due in part to in utero exposure to maternal diabetes. Additionally, both of my parents are prediabetic, further bolstering my motivation to identify determinants of pre-clinical disease progression. This award directly supports my research program on use of 'omics technologies within a lifecourse framework to advance precision prevention of early-onset metabolic diseases.

In what direction do you see the future of diabetes research going?

I envision that my efforts in diabetes research will advance preclinical insights on use of metabolomics to harness metabolic heterogeneity and improve individualized risk prediction for early-onset type 2 diabetes. Additionally, I have initiated non-traditional collaborations to improve scalability of 'omics technologies and accessibility of care to ensure that advancements in precision medicine will close rather than widen gaps in health disparities between the most advantaged and most disadvantaged segments of the population.