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Aim: People of Black African ancestry, who are known to be at disproportionately high risk of type 2 diabetes (T2D), typically exhibit lower hepatic insulin clearance compared with White Europeans. However, the mechanisms underlying this metabolic characteristic are poorly understood. We explored whether low insulin clearance in Black African (BA) men could be explained by insulin resistance, subclinical inflammation or adiponectin concentrations. Methods: BA and White European (WE) men, categorised as either normal glucose tolerant (NGT) or with T2D, were recruited to undergo the following: a mixed meal tolerance test with C-peptide modelling to determine endogenous insulin clearance; fasting serum adiponectin and cytokine profiles; a hyperinsulinaemic–euglycaemic clamp to measure whole-body insulin sensitivity; and magnetic resonance imaging to quantify visceral adipose tissue. Results: Forty BA (20 NGT and 20 T2D) and 41 WE (23 NGT and 18 T2D) men were studied. BA men had significantly lower insulin clearance (P = 0.011) and lower plasma adiponectin (P = 0.031) compared with WE men. In multiple regression analysis, ethnicity, insulin sensitivity and plasma adiponectin were independent predictors of insulin clearance, while age, visceral adiposity and tumour necrosis factor alpha (TNF-α) did not significantly contribute to the variation. Conclusion: These data suggest that adiponectin may play a direct role in the upregulation of insulin clearance beyond its insulin-sensitising properties. [ABSTRACT FROM AUTHOR]

Aim: To investigate relationships between insulin clearance, insulin secretion, hepatic fat accumulation and insulin sensitivity in black African (BA) and white European (WE) men. Methods: Twenty‐three BA and twenty‐three WE men with normal glucose tolerance, matched for age and body mass index, underwent a hyperglycaemic clamp to measure insulin secretion and clearance, hyperinsulinaemic‐euglycaemic clamp with stable glucose isotope infusion to measure whole‐body and hepatic‐specific insulin sensitivity, and magnetic resonance imaging to quantify intrahepatic lipid (IHL). Results: BA men had higher glucose‐stimulated peripheral insulin levels (48.1 [35.5, 65.2] × 103 vs. 29.9 [23.3, 38.4] × 103 pmol L−1 × min, P =.017) and lower endogeneous insulin clearance (771.6 [227.8] vs. 1381 [534.3] mL m−2 body surface area min −1, P <.001) compared with WE men. There were no ethnic differences in beta‐cell insulin secretion or beta‐cell responsivity to glucose, even after adjustment for prevailing insulin sensitivity. In WE men, endogenous insulin clearance was correlated with whole‐body insulin sensitivity (r = 0.691, P =.001) and inversely correlated with IHL (r = −0.674, P =.001). These associations were not found in BA men. Conclusions: While normally glucose‐tolerant BA men have similar insulin secretory responses to their WE counterparts, they have markedly lower insulin clearance, which does not appear to be explained by either insulin resistance or hepatic fat accumulation. Low insulin clearance may be the primary mechanism of hyperinsulinaemia in populations of African origin. [ABSTRACT FROM AUTHOR]

Objectives: In men of black west African (BAM) and white European (WEM) ethnicity, we aimed to (1) compare adipose tissue, peripheral and hepatic insulin sensitivity and (2) investigate associations between ectopic fat and insulin sensitivity by ethnicity. Design and methods: In overweight BAM (n = 21) and WEM (n = 23) with normal glucose tolerance, we performed a two-step hyperinsulinaemic-euglycaemic clamp with infusion of [6,6 ²H2]-glucose and [²H5]-glycerol to measure whole body, peripheral, hepatic and adipose tissue insulin sensitivity (lipolysis). Visceral adipose tissue (VAT), intrahepatic lipids (IHL) and intramyocellular (IMCL) lipids were measured using MRI and spectroscopy. Associations between insulin sensitivity and ectopic fat were assessed using Pearson's correlation coefficient by ethnicity and regression analysis. Results: There were no ethnic differences in whole body or tissue-specific insulin sensitivity (all P > 0.05). Suppression of lipolysis was inversely associated with VAT and IHL in WEM but not BAM (VAT: WEM r = -0.68, P < 0.01; BAM r = 0.07, P = 0.79. IHL: WEM r = -0.52, P = 0.01; BAM r = -0.12, P = 0.63). IMCL was inversely associated with skeletal muscle insulin sensitivity in WEM but not BAM (WEM r = -0.56, P < 0.01; BAM r = -0.09, P = 0.75) and IHL was inversely associated with hepatic insulin sensitivity in WEM but not BAM (WEM r = -0.53, P = 0.02; BAM r = -0.13, P = 0.62). Conclusions: Ectopic fat deposition may play a lesser role in reducing insulin sensitivity in men of black African ethnicity and may not be driven by lipolysis. Resistance to storing VAT, IHL and IMCL may enable men of black African ethnicity to maintain comparable insulin sensitivity to white Europeans. [ABSTRACT FROM AUTHOR]

Intrahepatic lipid (IHL) is linked with reduced hepatic insulin sensitivity and insulin clearance. Despite their high risk for type 2 diabetes (T2D), there have been limited investigations of these relationships in black populations. We investigated these relationships in 18 white European (WE) and 18 black West African (BWA) men with T2D <5 years. They underwent magnetic resonance imaging to quantify IHL, a hyperinsulinemic euglycaemic clamp with [6,6 2H2] glucose infusion to assess hepatic insulin sensitivity and a hyperglycaemic clamp to assess insulin clearance. BWA men had lower IHL than WE men (3.7 [5.3] vs 6.6 [10.6]%, P = 0.03). IHL was inversely associated with basal hepatic insulin sensitivity in WE but not BWA men (BWA: r = −0.01, P = 0.96; WE: r = −0.72, P = 0.006) with a significant interaction by ethnicity (Pinteraction = 0.05); however, IHL was not associated with % suppression of endogenous glucose production by insulin in either ethnicity. IHL showed a trend to an association with insulin clearance in BWA only (BWA: r = −0.42, P = 0.09; WE: r = −0.14, P = 0.58). The lack of association between IHL and hepatic insulin sensitivity in BWA men indicates IHL may play a lesser detrimental role in T2D in BWA men. [ABSTRACT FROM AUTHOR]