Research Database
Genetic risk factors for adult-onset diabetes in populations of African Ancestry
Sarah A, PhD
Institution:
University of Pennsylvania
Grant Number:
1-19-VSN-02
Type of Grant:
Basic
Diabetes Type:
Both Type 1 and Type 2 Diabetes
Therapeutic Goal:
N/A
Project Date:
-
Project Status:
completed

Research Description

Risk for diabetes mellitus (DM) and cardiovascular disease is relatively high in African-descent populations. The goal of this project is to characterize genomic, immune, and metabolic biomarkers associated with DM in ethnically diverse Africans living indigenous lifestyles: Fulani herders, Bantu agriculturalists and Pygmy hunter-gatherers. Adult Fulani have high blood pressure values (40%) and/or high random blood glucose values and/or self-reported DM (5%) compared to Bantu (32% and 3%, respectively) and Pygmy (12% and 0%, respectively) populations in Cameroon. Fulani also have relative resistance to malaria, possibly due to a boosted inflammatory immune response. This project will test the hypothesis that risk for diabetes in African descent populations (with high levels of Bantu and Fulani ancestry) may be influenced by differences in inflammatory immune response due to adaptive mutations that protect against infectious disease in an African environment but may predispose towards risk for DM in a Western environment. Africans living indigenous lifestyles in rural Cameroon will be tested for biomarkers of Type 1 DM, Type 2 DM, Latent Autoimmune Diabetes in Adults and other ketosis-prone diabetes and genotyped to distinguish genetic variants associated with DM. Further, white blood cells from DM cases and controls will be stimulated by immune challenges to distinguish genetic variants influencing immune response. The proposed study has the potential to result in paradigm shifts in our understanding of the etiology and genetic risk factors for DM in populations of African ancestry which is critical for developing better diagnostics and therapeutics for DM in ethnically diverse populations.

Research Profile

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?

The focus of my research is to understand the mechanisms underlying differences in risk for diabetes across ethnically diverse populations in Africa who have different genetic ancestries and dietary habits. My research strategy integrates fieldwork in Africa, characterization of anthropometric variation and blood metabolites, dietary analysis and computational and gene function tests. We will develop innovative ways for adapting current methodologies to remote field conditions in Africa and implement new computational approaches for integration and analysis of diverse datasets. By studying variation in blood metabolites and risk for diabetes in African populations living indigenous lifestyles and comparing to urban African-American populations, this research has the potential to identify both genetic and environmental factors that influence risk for adult onset diabetes. It is hoped that identification of these factors may provide insights into both the etiology of type 2 diabetes in African descent populations and allow stratification of risk and improved guidelines for lifestyle and drug interventions to prevent or treat diabetes.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

The incidence of diabetes is increasing globally, from 415 million in 2015 to a projected 642 million in 2040. The highest rate of increase is in Africa, where the incidence of diabetes is predicted to more than double within the same period. The disproportionate increase in diabetes and cardiovascular disease risk amongst Africans has been influenced by westernization of dietary habits and sedentary lifestyles in a population that likely has a higher genetic risk. By understanding the contribution of genetics and lifestyle, my project could provide information on the causes for increased risk of diabetes in African-Americans and lead to more effective treatments.

Why important for you, personally, to become involved in diabetes research? What role will this award play?

Individuals of African ancestry in the U.S. have a high incidence of adult onset diabetes which is also on the rise in Africa. I am fundamentally motivated by my sincere concern that the scientific community needs to do more to alleviate health disparities. I have devoted my career to being an advocate for inclusion of minority populations in human genomics research. Given the high incidence of diabetes in African-Americans, I want to devote my future research towards studies that will help elucidate the causes of diabetes, and facilitate development of therapeutics, in ethnically diverse populations. This award will enable me to establish collaborations with interdisciplinary scientists and clinicians, both in the US and in Africa, to conduct research that could impact developing more effective treatment for patients with diabetes from globally diverse populations.

In what direction do you see the future of diabetes research going?

I see the future of diabetes research focusing on identifying individual risk factors for disease and development of personalized therapeutics. As we develop more cost effective genomic screening technologies, it will be possible to integrate genomic data with detailed information about cardio-metabolic traits obtained from wearable devices or electronic health records and with information about behavior and diet so that we can better understand the factors influencing risk of diabetes at an individual level. Inclusion of ethnically diverse individuals will be important for developing diagnostic markers and treatments that will be effective in global populations.