Inflammation and Incident Diabetes: The Role of Race and Ethnicity.

With the increasing global prevalence of type 2 diabetes (T2D), identification of risk factors is critical for developing intervention and prevention strategies. Numerous studies have effectively characterized many of these risk factors, which include insulin resistance, hyperlipidemia, obesity, physical inactivity, and dietary patterns, among others. With extended exposure to these risk factors, chronic inflammation has been strongly suggested as an important cause of insulin resistance and pancreatic beta cell dysfunction. In addition, reviews from the National Health and Nutrition Examination Survey and other epidemiologic studies have reported further differences in the levels of inflammatory cytokines by racial and ethnic cohorts in the United States, which may be related to incident diabetes in these different groups (1).

In this issue of the Journal of Clinical Endocrinology and Metabolism, Peper and coauthors from the University of Vermont and the University of Alabama at Birmingham longitudinally assessed whether the proinflammatory marker C-reactive protein (CRP) mediated racial differences in diabetes incidence in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. This report recruited 30 239 US Black and White adults nationwide, oversampling Black adults and those living in the “Stroke Belt,” an area of the United States with increased stroke mortality (2). Of the 11 073 participants without baseline diabetes (33% Black, 67% White), incident diabetes was 12.5%. Compared to White participants, Black participants with higher CRP at baseline had significantly higher risk of incident diabetes and higher risk of diabetes at CRP < 3 mg/L but not at CRP ≥ 3mg/L. Interestingly, CRP mediated 10% of the racial difference in incident diabetes among Black women but not among men.

This article tackled a crucial question on the potential differences in diabetes incidence between Black and White populations. While Blacks face disproportionately greater T2D prevalence and mortality than Whites, contributing factors to this difference remain understudied. Peper et al noted several observations: First, elevated CRP was a risk factor for diabetes regardless of race, which confirmed the findings of many studies regarding the role of the inflammatory response in T2D development (3, 4). Second, the difference in excess diabetes burden among Blacks also existed at low CRP levels, suggesting that inflammation alone was unlikely to be the main driver of the observed racial differences and further emphasizing the possible role of other non-inflammatory risk factors in the pathogenesis of T2D. Lastly, the excess diabetes burden mediated by sex could be related to a further association between T2D and risk factors for elevated CRP, ranging from visceral adiposity to smoking, alcohol use, physical inactivity, and stress and depression.

The article, however, has its important limitations. For one, the diagnosis of diabetes was limited to fasting glucose ≥ 126 mg/dL, nonfasting random glucose ≥ 200 mg/dL, or self-reported use of insulin or oral diabetes medications. Although this approach was similar to that of other observational studies (5, 6), the diagnosis of diabetes could have been strengthened with the use of hemoglobin A1c, confirmatory review of medical records, or consideration of signs and symptoms of hyperglycemia in those with elevated random glucose levels. Additionally, the exclusive use of CRP, a nonspecific inflammatory marker, does not propose more definite insights into particular pathways predisposing to diabetes development. This limitation could have been addressed with a more robust assessment of other inflammatory markers such as fibrinogen, plasminogen activator inhibitor-1, and the various cytokines.

Nevertheless, Peper et al raise vital questions in our continuing quest to elucidate how inflammatory mechanisms in T2D development are impacted by complex multilevel factors tied to race and ethnicity. Population-based studies have demonstrated that Blacks and Latinx are among the ethnic groups possessing the highest mean CRP levels (7). Previously, these differences have been often attributed to potential genetic differences in the various ethnic groups. However, given that the exponential increase in T2D incidence is a relatively recent phenomenon, the observed elevated levels of inflammatory cytokines are most likely due to differences in environmental factors and social context experienced by the different minority cohorts. Many of these factors that have been shown to increase inflammation are similar to those being experienced at a disproportionately greater degree by minority subjects, including pollution and less access to education, healthy food sources, and safe living facilities.

Furthermore, health-related disparities arising from structural racism in the healthcare system can create biased outcomes independent of genetic differences. For example, recent data on cultural competency measures among different ethnic groups with diabetes have shown that while Blacks and Latinx placed the greatest importance on sharing cultures with their providers, they were less likely to encounter providers who shared or understood their cultures (8). Given the tremendous diversity of ethnic and racial groups in the country, it is important to develop studies that characterize differences in both individual and environmental risk factors for chronic metabolic diseases such as T2D. A participatory-based approach should be encouraged to integrate key members of the study population in study design, planning, and analysis. These additional and essential steps can provide culturally sensitive and structured research cohorts that may prove indispensable in advancing our understanding of the differences in the risk factors surrounding the complex causes of T2D.