Racial/Ethnic Differences in Insulin Resistance and Beta Cell Function: Relationship to Racial Disparities in Type 2 Diabetes among African Americans versus Caucasians
- 375 Downloads
Both biological and sociocultural factors have been implicated in the well-documented racial disparity in incidence and prevalence of type 2 diabetes (T2D) between African Americans (AA) and non-Hispanic whites (NHW). This review examines the extent to which biological differences in glucose metabolism, specifically insulin resistance and beta cell function (BCF), contribute to this disparity. The majority of available data suggests that AA are more insulin resistant and have upregulated BCF compared to NHW. Increasing evidence implicates high insulin secretion as a cause rather than consequence of T2D; therefore, upregulated BCF in AA may specifically confer increased risk of T2D in this cohort. Racial disparities in the metabolic characteristics of T2D have direct implications for the treatment and health consequences of this disease; therefore, future research is needed to determine whether strategies to reduce insulin secretion in AA may prevent or delay T2D and lessen racial health disparities.
KeywordsInsulin sensitivity Beta cell function Disposition index Glucose metabolism
Nawfal Istfan reports grants from the American Diabetes Association.
Compliance with Ethics Guidelines
Conflict of Interest
Brooke R. Hasson and Nawfal Istfan declare that they have no conflict of interest.
Caroline Apovian reports grants and personal fees from Orexigen Therapeutics, Inc., personal fees from Johnson & Johnson, personal fees from Nutrisystem, Inc., grants and personal fees from GI Dynamics, Inc., personal fees from EnteroMedics, Inc., personal fees from Zafgen Inc., personal fees from Arena Pharmaceuticals, personal fees from Merck & Co., Inc., grants and personal fees from Sanofi-Aventis US LLC, grants and personal fees from Amylin Pharmaceuticals, grants from The Dr. Robert C. and Veronica Atkins Foundation, grants from Aspire Bariatrics, Inc., grants and personal fees from Takeda Pharmaceuticals, and grants from Pfizer, Inc.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 1.Prevention CfDCa (2011) National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. In: Atlanta GUSDoHaHS, Centers for Disease Control and Prevention, 2011 (ed).Google Scholar
- 7.Harris MI, Hadden WC, Knowler WC, Bennett PH. Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in U.S. population aged 20–74 yr. Diabetes. 1987;36:523–34.Google Scholar
- 23.Lettre G, Palmer CD, Young T, Ejebe KG, Allayee H, Benjamin EJ, et al. Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project. PLoS Genet. 2011;7:e1001300. doi: 10.1371/journal.pgen.1001300.CrossRefPubMedCentralPubMedGoogle Scholar
- 24.Cheng CY, Reich D, Haiman CA, Tandon A, Patterson N, Selvin E, et al. African ancestry and its correlation to type 2 diabetes in African Americans: a genetic admixture analysis in three U.S. population cohorts. PLoS One. 2012;7:e32840. doi: 10.1371/journal.pone.0032840.CrossRefPubMedCentralPubMedGoogle Scholar
- 29.•Bacha F, Gungor N, Lee S, Arslanian SA. Type 2 diabetes in youth: are there racial differences in beta-cell responsiveness relative to insulin sensitivity? Pediatr Diabetes. 2012;13:259–65. doi: 10.1111/j.1399-5448.2011.00820.x. This paper shows that, similar to non-diabetic youth, AA adolescents with T2D compared with their NHW counterparts have an upregulated beta-cell function relative to insulin sensitivity. CrossRefPubMedCentralPubMedGoogle Scholar
- 32.Ellis AC, Alvarez JA, Granger WM, Ovalle F, Gower BA. Ethnic differences in glucose disposal, hepatic insulin sensitivity, and endogenous glucose production among African American and European American women. Metabolism. 2012;61:634–40. doi: 10.1016/j.metabol.2011.09.011.CrossRefPubMedCentralPubMedGoogle Scholar
- 33.•Kodama K, Tojjar D, Yamada S, Toda K, Patel CJ, Butte AJ. Ethnic differences in the relationship between insulin sensitivity and insulin response: a systematic review and meta-analysis. Diabetes Care. 2013;36:1789–96. doi: 10.2337/dc12-1235. This paper suggest that the genetic background of Africans Americans makes them more and differentially susceptible to diabetes than Caucasians. A meta-analysis the different natural courses of diabetes onset is presented for AA and NHW.CrossRefPubMedCentralPubMedGoogle Scholar
- 34.Haffner SM, D’Agostino R, Saad MF, Rewers M, Mykkanen L, Selby J, et al. Increased insulin resistance and insulin secretion in nondiabetic African-Americans and Hispanics compared with non-Hispanic whites. The insulin resistance atherosclerosis study. Diabetes. 1996;45:742–8.CrossRefPubMedGoogle Scholar
- 35.Lillioja S, Nyomba BL, Saad MF, Ferraro R, Castillo C, Bennett PH, et al. Exaggerated early insulin release and insulin resistance in a diabetes-prone population: a metabolic comparison of Pima Indians and Caucasians. J Clin Endocrinol Metab. 1991;73:866–76. doi: 10.1210/jcem-73-4-866.CrossRefPubMedGoogle Scholar
- 37.Hunt KJ, Resendez RG, Williams K, Haffner SM, Stern MP, Hazuda HP. All-cause and cardiovascular mortality among Mexican-American and non-Hispanic White older participants in the San Antonio Heart Study- evidence against the “Hispanic paradox”. Am J Epidemiol. 2003;158:1048–57.CrossRefPubMedGoogle Scholar
- 46.•Hasson RE, Adam TC, Davis JN, Watanabe RM, Goran MI. Compensatory responses to insulin resistance in obese African-American and Latina girls. Pediatr Obes. 2013;8:e68–73. doi: 10.1111/j.2047-6310.2013.00184.x. This paper suggests that compensatory mechanisms to insulin resistance do not appear to explain the ethnic differences in insulin responses to oral and intravenous glucose in obese African-American and Latina girls.CrossRefPubMedGoogle Scholar
- 47.Hannon TS, Bacha F, Lin Y, Arslanian SA. Hyperinsulinemia in African-American adolescents compared with their American white peers despite similar insulin sensitivity: a reflection of upregulated beta-cell function? Diabetes Care. 2008;31:1445–7. doi: 10.2337/dc08-0116.CrossRefPubMedCentralPubMedGoogle Scholar
- 49.•Chandler-Laney PC, Phadke RP, Granger WM, Fernandez JR, Munoz JA, Man CD, et al. Age-related changes in insulin sensitivity and beta-cell function among European-American and African-American women. Obesity (Silver Spring). 2011;19:528–35. doi: 10.1038/oby.2010.212. The data in this manuscript suggest that inherent ethnic differences in beta-cell function exist independently of adiposity and insulin sensitivity. CrossRefGoogle Scholar
- 51.•Chandler-Laney PC, Higgins PB, Granger W, Alvarez J, Casazza K, Fernandez JR, et al. Use of a simple liquid meal test to evaluate insulin sensitivity and beta-cell function in children. Pediatr Obes. 2014;9:102–10. doi: 10.1111/j.2047-6310.2013.00147.x. This paper describes how a liquid meal offers a valid and sensitive means of assessing insulin sensitivity and beta-cell responsivity in young children.CrossRefPubMedCentralPubMedGoogle Scholar
- 53.•Corkey BE. Banting lecture 2011: hyperinsulinemia: cause or consequence? Diabetes. 2012;61:4–13. doi: 10.2337/db11-1483. This paper summaries the scientific bases and mechanisms of how an increase in insulin secretion could play an important, yet poorly researched, role in the pathophysiology of diabetes.CrossRefPubMedCentralPubMedGoogle Scholar
- 56.•Yang X, Mei S, Gu H, Guo H, Zha L, Cai J, et al. Excess exposure to insulin (glargine) induces type 2 diabetes mellitus in mice on chow diet. J Endocrinol. 2014. doi: 10.1530/JOE-14-0117. This paper provides experimental support in normal mice consuming regular chow for the hypothesis that excess insulin can induce T2D.Google Scholar
- 68.Fried SK, Tittelbach T, Blumenthal J, Sreenivasan U, Robey L, Yi J, et al. Resistance to the antilipolytic effect of insulin in adipocytes of African-American compared to Caucasian postmenopausal women. J Lipid Res. 2010;51:1193–200. doi: 10.1194/jlr.P000935.CrossRefPubMedCentralPubMedGoogle Scholar
- 69.Smith LM, Yao-Borengasser A, Starks T, Tripputi M, Kern PA, Rasouli N. Insulin resistance in African-American and Caucasian women: differences in lipotoxicity, adipokines, and gene expression in adipose tissue and muscle. J Clin Endocrinol Metab. 2010;95:4441–8. doi: 10.1210/jc.2010-0017.CrossRefPubMedCentralPubMedGoogle Scholar
- 76.Velasquez-Mieyer PA, Cowan PA, Umpierrez GE, Lustig RH, Cashion AK, Burghen GA. Racial differences in glucagon-like peptide-1 (GLP-1) concentrations and insulin dynamics during oral glucose tolerance test in obese subjects. Int J Obes Relat Metab Disord. 2003;27:1359–64. doi: 10.1038/sj.ijo.0802415.CrossRefPubMedCentralPubMedGoogle Scholar
- 77.Velasquez-Mieyer PA, Umpierrez GE, Lustig RH, Cashion AK, Cowan PA, Christensen M, et al. Race affects insulin and GLP-1 secretion and response to a long-acting somatostatin analogue in obese adults. Int J Obes Relat Metab Disord. 2004;28:330–3. doi: 10.1038/sj.ijo.0802561.PubMedCentralPubMedGoogle Scholar