Pathogenesis of type 2 diabetes risk in black Africans: a South African perspective

Goedecke, Julia H.; Olsson, Tommy

doi:10.1111/joim.13083

Cited by 30 publications

(33 citation statements)

References 84 publications

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“…Our results in the IRAS Family Study and MILES suggest this may not be the case in African Americans, Hispanics, or non-Hispanic Whites. This is noteworthy given that numerous studies have found that insulin clearance is decreased in individuals of African descent, compared to other racial groups, and is a driver of hyperinsulinemia [ 23 , 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Defining the Relative Role of Insulin Clearance in Early Dysglycemia in Relation to Insulin Sensitivity and Insulin Secretion: The Microbiome and Insulin Longitudinal Evaluation Study (MILES)

et al. 2021

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Insulin resistance and insufficient insulin secretion are well-recognized contributors to type 2 diabetes. A potential role of reduced insulin clearance has been suggested, but few studies have investigated the contribution of insulin clearance while simultaneously examining decreased insulin sensitivity and secretion. The goal of this study was to conduct such an investigation in a cohort of 353 non-Hispanic White and African American individuals recruited in the Microbiome and Insulin Longitudinal Evaluation Study (MILES). Participants underwent oral glucose tolerance tests from which insulin sensitivity, insulin secretion, insulin clearance, and disposition index were calculated. Regression models examined the individual and joint contributions of these traits to early dysglycemia (prediabetes or newly diagnosed diabetes). In separate models, reduced insulin sensitivity, reduced disposition index, and reduced insulin clearance were associated with dysglycemia. In a joint model, only insulin resistance and reduced insulin secretion were associated with dysglycemia. Models with insulin sensitivity, disposition index, or three insulin traits had the highest discriminative value for dysglycemia (area under the receiver operating characteristics curve of 0.82 to 0.89). These results suggest that in the race groups studied, insulin resistance and compromised insulin secretion are the main independent underlying defects leading to early dysglycemia.

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Section: Discussionmentioning

confidence: 99%

Defining the Relative Role of Insulin Clearance in Early Dysglycemia in Relation to Insulin Sensitivity and Insulin Secretion: The Microbiome and Insulin Longitudinal Evaluation Study (MILES)

et al. 2021

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“…It is possible that in AA, IMAT may play a larger role in insulin resistance. In addition to higher levels of IMAT, it has been hypothesized that the increased risk of insulin resistance observed in AA may also be a consequence of higher insulin secretion, decreased hepatic insulin clearance and increased mitochondrial efficiency/oxidative stress 37,38 . It is possible that in AA children and adults, these unique metabolic/endocrine phenotypes have a larger influence on the pathogenesis of insulin resistance compared to other racial/ethnic groups.…”

Section: Discussionmentioning

confidence: 99%

Genetic risk score prediction of leg fat and insulin sensitivity differs by race/ethnicity in early pubertal children

et al. 2021

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Summary Background In the United States, the underlying reasons for racial/ethnic disparities in type 2 diabetes risk remain unclear. However, differences in genetic risk for insulin resistance and peripheral adipose tissue distribution may be contributing factors. Objective To investigate racial/ethnic differences in associations of genetic risk for insulin resistance with leg fat and insulin sensitivity in a cohort of American children. Methods Participants were healthy European–American (n = 83), African–American (n = 79) and Hispanic–American (n = 74) children aged 7–12 years. Genetic risk scores were derived from published variants associated with insulin resistance phenotypes in European adults. Body composition was assessed using dual‐energy X‐ray absorptiometry. Insulin sensitivity was determined from the frequently sampled intravenous glucose tolerance test and minimal modelling. Statistical models were adjusted for age, sex, pubertal stage and body composition. Results In the combined cohort, risk score was inversely associated with insulin sensitivity (p = 0.033) but not leg fat (p = 0.170). Within Hispanic Americans, risk score was inversely associated with insulin sensitivity (p = 0.027) and leg fat (p = 0.005), while associations were non‐significant in European and African Americans (p > 0.200). Conclusions The higher type 2 diabetes risk observed among Hispanic Americans may have a genetic basis related to an inability to store lipid in peripheral adipose tissue.

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“…Notably, most of the reported cross-sectional studies that have explored the associations between cortisol and cardiometabolic risk factors were conducted in non-Africans ( 3 , 4 , 5 , 6 ). Africans have a different metabolic phenotype to that of their European counterparts ( 11 , 12 ). Some studies have shown that in urban settings Africans have a higher prevalence of obesity and insulin resistance, yet have less visceral adipose tissue (VAT) than Europeans ( 13 , 14 , 15 ).…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoids associate with cardiometabolic risk factors in black South Africans

Dlamini

Lombard

Micklesfield

et al. 2021

Endocrine Connections

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Circulating glucocorticoids are associated with the metabolic syndrome and related cardiometabolic risk factors in non-Africans. This study investigated these associations in Africans, whose metabolic phenotype reportedly differs from Europeans. Measures of adiposity, blood pressure, glycaemia, insulin resistance, and lipid profile, were measured in 316 African men and 788 African women living in Soweto, Johannesburg. The 2009 harmonized criteria were used to define the metabolic syndrome. Serum glucocorticoids were measured using liquid chromatography-mass spectrometry. Cortisol was associated with greater odds of presenting with the metabolic syndrome (odds ratio (95% confidence interval, 95%CI) =1.50 [1.04, 2.17] and higher systolic (beta coefficient, β (95%CI) =0.04 [0.01, 0.08]) and diastolic (0.05 [0.02, 0.09]) blood pressure, but higher HDL (0.10 [0.02, 0.19]) and lower LDL (-0.14 [-0.24, -0.03]) cholesterol concentrations, in the combined sample of men and women. In contrast, corticosterone was only associated with higher insulin sensitivity (Matsuda index; 0.22 [0.03, 0.41]), but this was not independent of BMI. Sex-specific associations were observed, such that both cortisol and corticosterone were associated with higher fasting glucose (standardized β (95%CI): 0.24 [0.12, 0.36] for cortisol; and 0.12 [0.01, 0.23] for corticosterone) and HbA1c (0.13 [0.01, 0.25] for cortisol; and 0.12 [0.01, 0.24] for corticosterone) in men only, but lower HbA1c (0.10 [ -0.20, -0.01] for cortisol; and -0.09 [-0.18, -0.03] for corticosterone) in women only. Our study reports for the first time that associations between circulating glucocorticoid concentrations and key cardiometabolic risk factors exhibit both glucocorticoid- and sex-specificity in Africans.

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Pathogenesis of type 2 diabetes risk in black Africans: a South African perspective

Cited by 30 publications

References 84 publications

Defining the Relative Role of Insulin Clearance in Early Dysglycemia in Relation to Insulin Sensitivity and Insulin Secretion: The Microbiome and Insulin Longitudinal Evaluation Study (MILES)

Defining the Relative Role of Insulin Clearance in Early Dysglycemia in Relation to Insulin Sensitivity and Insulin Secretion: The Microbiome and Insulin Longitudinal Evaluation Study (MILES)

Genetic risk score prediction of leg fat and insulin sensitivity differs by race/ethnicity in early pubertal children

Glucocorticoids associate with cardiometabolic risk factors in black South Africans

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