Mapping Diabetes: Pregnancy to Puberty Research

What can life course research uncover about diabetes, and how can this approach enhance our understanding of prevention strategies for chronic diseases?

The U.S. government reports that more than 5,000 people are diagnosed with diabetes every day. An additional 1 out of every 3 people have prediabetes, and about 90% of those people don’t even know it. This chronic disease, in which the body can’t regulate blood sugar, can also cause blindness, kidney failure, heart attack, stroke, and lower limb amputation — and disease prevalence is rapidly on the rise.

Dana Dabelea, MD, PhD, has committed her career to studying diabetes from every angle. She knows it’s not enough to just study the disease in isolation — it’s about going deeper to understand why diabetes happens in the first place and what factors and exposures play a role. With that understanding, her goal is to work toward prevention.

Nearly a decade ago, Dr. Dabelea noticed a gap in diabetes research across the University of Colorado Anschutz Medical Campus, with different pockets of work happening side-by-side but not under one unified umbrella. That’s when she founded the Lifecourse Epidemiology of Adiposity & Diabetes (LEAD) Center to bridge that gap and focus on research across the lifespan — a novel approach at the time. This holistic, multifaceted approach enables the team at the LEAD Center to set their sights on not just understanding this chronic illness but pursuing a path to prevention. She decided to not just study one aspect of diabetes across age groups, but to expand her work to all the different exposures that can impact disease onset.

“It’s not only our molecular structure, our epigenetics, our genetic background, but it’s also the above-the-skin environment — the familial environments, the community environments, the structural factors, including social determinants of health and structural racism,” Dr. Dabelea says. “Unless you look at the totality of this environment, we will not understand pathogenesis of disease; we will not understand how to promote health by preventing disease.”

Preventing diabetes before birth

To fully understand all the elements of disease prevention for diabetes, Dr. Dabelea knew she needed to go back to the start of life and zoom out to analyze risk factors through a prebirth cohort. In 2009, the LEAD Center launched a longitudinal research study — the Healthy Start study — to look at the metabolic and behavioral factors during pregnancy and early life that contribute to the development of obesity and related health problems, such as insulin resistance and inflammatory markers.

Funded by the National Institutes of Health, the study enrolled more than 1,400 pregnant women to start collecting data, and the team has continued to follow the children for nearly 15 years. The researchers started by exploring how women’s experiences during pregnancy, such as diet and physical activity, along with environment, could affect their child’s growth throughout infancy and childhood. Now, the team is following that same cohort of children through a critical phase of development — puberty — where exposure to risk factors can be more impactful.

“We’ve never studied such a large cohort as they transition through puberty in terms of metabolic health and obesity development, especially in a group of healthy kids who we have so much information on before they transition to that phase,” Dr. Dabelea says. “Puberty is a sensitive period when a lot of chronic childhood diseases develop, such as Type 2 diabetes, insulin resistance, and obesity.”

Countless findings have been uncovered through this research already, such as the importance of supplementing vitamin D for pregnant patients to reduce the risk of elevated blood pressure in their children. The data also revealed how exposure to tobacco smoke during pregnancy can lead to impaired neurocognitive development in early childhood that impacts academic achievement later in life. And the team published research about how pregnant patients can lower their risk of abnormal blood glucose levels, a key risk factor for developing gestational diabetes, through physical activity, diet quality and mental health care.

Dr. Dabelea hopes the Healthy Start study can continue through the next phases of life for this cohort — transitioning to becoming independent adults and even continuing into the future when they might decide to have kids of their own. The Healthy Start study also contributes to a larger NIH consortium called ECHO, Environmental Influences and Child Health Outcomes, with dozens of other prebirth cohorts looking to analyze all aspects of child health through longer studies.

Prioritizing health equity in diabetes research

Another priority area for the LEAD Center is community-based participatory research for populations that are typically not represented in studies. “If all our knowledge comes from white kids, I think we’re increasing disparities, not contributing to decreases,” Dr. Dabelea says. “Our campus is great for recruiting, because it has hospitals, but people who touch the hospitals have health insurance. So, while I tap into this population for some of our studies, a lot of our studies are outside campus and the traditional medical campus setting.”

Dr. Dabelea has worked closely for many years with the Navajo Nation, a community that has one of the highest rates of Type 2 diabetes in the country. These collaborations have been ongoing for 20 years, with community members actively involved in developing protocols and implementing studies.

Right now, the team is wrapping up a diabetes intervention program that focuses on lifestyle interventions with American Indian children ages 7 to 10. They used a formal group curriculum with 12 different lessons about meal planning, physical activity and stress, along with motivational interviewing sessions with families to identify roadblocks and equip them with a toolbox of local resources. Dr. Dabelea and the team are analyzing the data to see if these interventions played a role in reducing obesity and preventing dysglycemia, or abnormality in blood sugar levels.

“As the risk factors to chronic diseases develop over the life course, disparities develop over the life course as well,” Dr. Dabelea says. “That’s why it’s important that in these multicenter studies that we all do, we always include populations who are clinically underserved from socioeconomic perspectives and who do not participate typically in observational studies or clinical trials.”