No Two Ways About It: Reconceptualizing Type 2 Diabetes

Drawing on years of prior research, a new paper published recently in The Journal of Clinical Endocrinology & Metabolism makes the case for a wider classification of a complex disease such as type 2 diabetes. A new series of subsets would take into account race, age at onset, and a host of other contributing factors.

Type 2 diabetes, often called the “silent pandemic” is a complex disease with complex etiologies. Recently, researchers have called for approaches to management that better differentiate the “types” of type 2 diabetes, a move widely supported.

However, exacerbating the complexity of the disease and of its treatment are the long-established health disparities in disease progression, risk for comorbidities, outcomes, and response to treatment that occur across race and ethnicity, for which social determinants of health are largely responsible.

Published in January in The Journal of Clinical Endocrinology & Metabolism, “Association of Diabetes Subgroups with Race/Ethnicity, Risk Factor Burden and Complications: The MASALA and MESA Studies,” Michael P. Bancks, PhD, MPH, of the Wake Forest School of Medicine in Winston-Salem, NC, and team take up the monumental task of “[unraveling] the heterogeneity” of type 2 diabetes. Bancks explains that this study draws on prior research over the last three years that stratified patients into subgroups comprising various differences in patient clinical characteristics and risk for complications. Those studies, though eye-opening, focused largely on White populations, whereas Bancks and team’s new study reaches much farther in terms of population sampling.

The team sought to answer, can the phenotypic data and clustering approaches previously used, for example, by Ahlqvist E, Storm P, Käräjämäki A, et al. among Scandinavians be applied in the U.S. to multiple ethnic groups — South Asians, Hispanics, African Americans, non-Hispanic Whites, and Chinese Americans? Secondly, can such subgrouping predict outcomes? “Our goal here was to make this important area of research applicable to a broader, racially, and ethnically diverse population,” Bancks says.

One Size Doesn’t Fit All

From two prospective community-based cohort studies, the Mediators of Atherosclerosis in South Asians Living in America (MASALA) and the Multi-Ethnic Study of Atherosclerosis (MESA), the team comprising researchers from centers across the U.S., zeroed in on five diabetes subgroups among 1,293 South Asian, Hispanic, African American, non-Hispanic White, and Chinese American participants:

• Older age at diabetes onset (43%)
• Severe hyperglycemia (26%)
• Severe obesity (20%)
• Younger age at onset (1%)
• Requiring insulin medication use (9%)

Their suspicion from the outset was that the five clinical subgroups would comprise different ethnicities, and risk for complications would also vary.

“Across the diabetes subgroups, distribution of race/ethnicity was different. For example, among the older onset subgroup, there was not the same distribution of individuals from a particular ethnicity, and, on the flip side, individuals from a particular ethnicity were not equally allocated to each of the five subgroups,” Bancks explains. “Because of what we know about social determinants of health that lead to disparities in diabetes health outcomes, we hypothesized that the subgroups would be associated with race/ethnicity and that it would not be uniform across subgroups or race/ethnicity.” The most common subgroup was older onset for four of the five ethnicities. For South Asians, severe hyperglycemia was most likely.

“Categorizing finer classifications of diabetes subgroups has really gained a lot of momentum in the field, and a lot of people are doing great work in this area because it’s an important issue. But we also want to make sure that how we are preventing diabetes complications is equitable. We were able to characterize these five subgroups that differ in their risk for complications, so really we’re seeing that that not all type 2 diabetes is the same.”  – Michael P. Bancks, PhD, MPH, Wake Forest School of Medicine, Winston-Salem, N.C.

Data collection in MASALA and MESA occurred at in-person clinic visits that included completing health questionnaires, blood draws, and cardiac computed tomography (CT) scans to measure coronary artery calcium. Bancks and team compared intra- and inter-subgroup differences by race/ethnicity and sex as well as sociodemographic factors, health behaviors, and cardiovascular and renal complications risk factors.

In addition to confirming their first hunch that the subgroups would differ by race ethnicity, importantly, they also found that these subgroups differ in their development of diabetes complications, as they thought would be the case. “One of the major take-home messages we found is that the risk or the probability that people develop a certain complication isn’t the same across diabetes subgroups,” Bancks says. “There are subgroups who have a greater risk for developing cardiovascular and renal complications.” The older age at diabetes onset subgroup was least as risk for those complications.

Expanding the Taxonomy

These findings have big clinical implications: “If we observe that certain diabetes subgroups are at greater risk for certain complications, we need to really try to help those subgroups avoid complications. And if who fits a certain diabetes subgroup is not equal across race and ethnicity due to many various factors, we really need to not allow certain groups of individuals to get left behind,” Bancks says.

On the clinician–patient level, this might translate into stratifying patients — determining which subgroup they best align with — to both head off the complications that diabetes subgroup is most prospectively associated with and to tailor treatment. “What strategies can they implement there in the clinic with their patient to prevent subclinical complications, or for those already manifest, what can they do to prevent them from progressing further and ultimately becoming a major clinical event such as a heart attack?” Bancks asks.

“Because of what we know about social determinants of health that lead to disparities in diabetes health outcomes, we hypothesized that the subgroups would be associated with race/ethnicity and that it would not be uniform across subgroups or race/ethnicity.” – Michael P. Bancks, PhD, MPH, Wake Forest School of Medicine, Winston-Salem, N.C.

There are research implications as well. In the coming years, it will be critical to understand what leads individuals to develop the characteristics that would align them with a certain diabetes subgroup. “There is likely an interplay between genetic, behavioral, social, and environmental characteristics and factors that usher people down the path toward a particular diabetes subgroup.” Bancks says.

“Categorizing finer classifications of diabetes subgroups has really gained a lot of momentum in the field, and a lot of people are doing great work in this area because it’s an important issue,” Bancks says. “But we also want to make sure that how we are preventing diabetes complications is equitable. We were able to characterize these five subgroups that differ in their risk for complications, so really we’re seeing that that not all type 2 diabetes is the same.”

Moreover, we can begin using these more nuanced classifications to better inform how public health interventions, clinicians, and healthcare institutions manage diabetes in individuals of different race/ethnicities.

Horvath is a freelance writer based in Baltimore, Md. She wrote about the ENDO 2021 Presidential Plenary sessions in the January and March issues.

You can download the entire May 2021 issue here.