Comparative analysis of White and African American groups reveals unique lipid and inflammatory features of diabetes
Authors: Pacheco Sanchez Gabriela , Lopez Miranda , Velez Leandro M. , Tamburini Ian , Ujagar Naveena , Ayala Julio , Robles Gabriela De , Choi Hannah , Arriola John , Kapadia Rubina , Zonderman Alan B. , Evans Michele K. , Jang Cholsoon , Seldin Marcus M. , Nicholas Dequina A. 
Published: November 2024

ABSTRACTImportanceAfrican Americans have a higher prevalence of Type 2 Diabetes (T2D) compared to White groups. T2D is a health disparity clinically characterized by dysregulation of lipids and chronic inflammation. However, how the relationships among biological and sociological predictors of T2D drive this disparity remains to be addressed.ObjectiveTo determine characteristic plasma lipids and systemic inflammatory biomarkers contributing to diabetes presentation between White and African American groups.DesignWe performed a cross-sectional retrospective cohort study using pre-existing demographic and clinical data from two diverse studies: Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) and AllofUs. From HANDLS (N=40), we used information from wave 1 (2004). From AllofUs (N=17,339), we used data from the Registered Tier Dataset v7, available in the AllofUs researcher workbench.SettingHANDLS is a population-based cohort study involving 3720 participants in the Baltimore area supported by the Intramural Research Program of the National Institute on Aging. HANDLS is a longitudinal study designed to understand the sources of persistent health disparities in overall longevity and chronic disease in White and African American individuals. The AllofUs study is an NIH funded multicenter study consisting of patient-level data from 331,382 individuals from 35 hospitals in the United States aimed at sampling one million or more people living in the United States to provide a collection of broadly accessible data.ParticipantsThe HANDLS subcohort participants (N=40) were divided into four groups equally distributed by race, sex, and diabetes status. Groups were also matched by age, body mass index, and poverty status. The analysis pipeline consisted of evaluating the significance of the variables race and disease status using the 2-way ANOVA test and post-ANOVA comparisons using Fisher LSD test, reporting unadjusted p-values. Additionally, unsupervised (PCA) and supervised (OPLS-DA) clustering analysis was performed to determine putative biological drivers of variability and main immunological and metabolic features characterizing diabetes in White and African American groups from HANDLS. Major clinical findings were validated in a large cohort of White and African American groups with T2D in the AllofUS research study (N=17,339). AllofUs groups were of similar range in age and BMI as HANDLS. Furthermore, a linear regression model was built adjusting for age and BMI to determine differences in clinical findings between White and African American groups with T2D.Main Outcomes and MeasuresPrimary outcomes using a HANDLS subcohort (N=40) were clinical parameters related to diabetes, plasma lipids determined by lipidomics and measured by mass spectrometry, and cytokine profiling using a customized panel of 52 cytokines and growth factors measured by Luminex. Outcomes evaluated in the AllofUs study (N=17,339) were clinical: cholesterol to HDL ratio, triglycerides, fasting glucose, insulin, and hemoglobin A1C.ResultsIn the HANDLS subcohort, White individuals with diabetes had elevated cholesterol to HDL ratio (mean difference -1.869,p=0.0053), high-sensitivity C-reactive protein (mean difference -9.135,p=0.0040), and clusters of systemic triglycerides measured by lipidomics, compared to White individuals without diabetes. These clinical markers of dyslipidemia (cholesterol to HDL ratio and triglycerides) and inflammation (hs-CRP) were not significantly elevated in diabetes in African Americans from the HANDLS subcohort. These results persisted even when controlling for statin use. Diabetes in White individuals in the HANDLS cohort was characterized by a marked elevation in plasma lipids, while an inflammatory status characterized by Th17-cytokines was predominant in the African American group from the HANDLS subcohort. We validated the key findings of elevated triglycerides and cholesterol to HDL ratio in White individuals with T2D in a sample (N=17,339) of the AllofUs study.Conclusions and RelevanceOur results show that diabetes can manifest with healthy lipid profiles, particularly in these cohorts of African Americans. This study suggests that Th17-inflammation associated with diabetes is characteristic of African Americans, while a more classic inflammation is distinctive of White individuals from HANDLS cohort. Further, clinical markers of dyslipidemia seem to characterize diabetes presentation only in White groups, and not in African Americans.