Nicholas J. Wareham, FMedSci, FRCP, FFPHM, MBBS, MSc, PhD, this year’s recipient of the Kelly West Award for Outstanding Achievement in Epidemiology, discussed how specifying and quantifying the relationship between risk factors and type 2 diabetes can help translate epidemiological observations into preventive action during his award lecture Sunday, June 27.

Dr. Wareham’s lecture, Risk Factors and Type 2 Diabetes, can be viewed by registered meeting attendees at ADA2021.org through September 29, 2021. If you haven’t registered for the Virtual 81st Scientific Sessions, register today to access all of the valuable meeting content.

“Beyond the establishment that a particular factor is a risk factor for diabetes, the accumulation of a much greater understanding about the details of the relationship between those risk factors and diabetes, and the generation of that understanding, has clinical and public health utility,” said Dr. Wareham, Director of the Medical Research Council Epidemiology Unit, Co-director of the Institute of Metabolic Science, and Professor of Epidemiology, University of Cambridge, United Kingdom.

As an early-career scientist, Dr. Wareham developed a strong interest in diabetes screening and was fascinated by then-emerging details of the links between risk factors and type 2 diabetes.

“I was struck by how the field had evolved from understanding in the late 1970s, which was essentially qualitative and aimed at what was an accepted list of risk factors for diabetes such as obesity—and rather pejoratively indolence—and those (risk factors) that were suspected but not proven,” he said.

Initial observations of an association between physical activity and future risk of type 2 diabetes came from research such as the Nurses’ Health Study, in which participants were asked how many times a week they engaged in physical activity that was sufficiently rigorous to produce a sweat.

“There was an overall 33% difference in risk between those responding that they did such activity at least once weekly compared to those who did not, with evidence of dose-response,” Dr. Wareham said. “There was evidence of confounding by obesity, but in the BMI-adjusted results, there was still an overall significant association, albeit one that was attenuated towards the null.”

Although the Nurses’ Health Study and other studies were important in providing evidence that physical inactivity is a risk factor for diabetes, Dr. Wareham said that multiple questions were left unanswered, most notably how to convert such observations into preventive messages.

“It remained unclear how much physical activity was enough for metabolic health. This uncertainty arises because it’s unclear what the physical activity question, as used in the Nurses’ Health Study, is actually assessing,” he said.

Moving forward into the 1990s and early 2000s, advances in genetics research provided a new understanding of risk factors on a population scale. However, researchers were still not able to determine ways to develop individualized prevention approaches, suggesting that new approaches needed to be considered, Dr. Wareham said. In order to consider whether risk factors are the same in all populations, it is imperative to integrate population and molecular science and move from within-population investigation to the study of between-population differences, he explained.

“The largest differences in risk are between populations. One approach to this would be to meta-analyze reported data from different population studies,” Dr. Wareham continued. “However, there is a major challenge of harmonization, since even within the narrow range of studies included, there is massive variation in what aspects of physical activity have been assessed and how it’s been parameterized.”

Putting all studies on a common quantitative scale is possible, he said, but it’s extremely challenging and requires refined approaches to risk-factor harmonization.

In an effort to bring harmonized data together internationally, Dr. Wareham discussed the establishment of InterConnect, a global initiative designed to facilitate the coordination of population research on the interaction between genetic and environmental factors in the etiology of obesity and diabetes.

“The InterConnect project is a federated approach to meta-analysis where the analysis goes to the data rather than vice versa,” he said. “It’s also imperative that we accelerate progress in using epidemiological data to develop sustainable solutions, which is why we have established a group [GDAR: Global Diet and Activity Research] to investigate population-level interventions in low- and middle-income countries.”