Exploring the determinants of ethnic differences in insulin clearance between men of Black African and White European ethnicity

Ladwa, Meera; Bello, Oluwatoyosi; Hakim, Olah; Boselli, Maria Linda; Shojaee‐Moradie, Fariba; Umpleby, A. Margot; Peacock, Janet L.; Amiel, Stephanie A.; Bonadonna, Riccardo C.; Goff, Louise

doi:10.1007/s00592-021-01809-4

Cited by 5 publications

References 47 publications

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Total adiponectin in indigenous Melanesians on Kitava

Carrera‐Bastos,

Fontes‐Villalba,

Ahrén

et al. 2024

American J Hum Biol

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ObjectivesExperimental and small human studies have indicated that high total adiponectin levels have beneficial cardiometabolic effects. In contrast, however, high total adiponectin levels are also associated with higher all‐cause and cardiovascular mortality in thoroughly adjusted epidemiological studies. To gain further insight into these seemingly contradictory results, we report results on total adiponectin from the indigenous Melanesian population of Kitava, Trobriand Islands, Papua New Guinea, where an apparent absence of cardiometabolic disease has been previously reported.MethodsFasting levels of serum total adiponectin were measured cross‐sectionally in ≥40‐year‐old Kitavans (n = 102) and Swedish controls matched for age and sex (n = 108). Multivariable linear regression was used for the analysis of associations with total adiponectin when controlled for group, sex, smoking, hypertension and/or type 2 diabetes, age, and body mass index.ResultsTotal adiponectin was lower for Kitavans compared to Swedish controls (Median [Mdn] 4.6 μg/mL, range 1.0–206 μg/mL and Mdn 9.7 μg/mL, range 3.1–104 μg/mL, respectively, r = .64, p < .001). Lower total adiponectin was associated with Kitavan group, male sex (only in Swedish controls), smoking (only in Kitavans and Swedish controls combined), younger age (not in Swedish controls), higher BMI, lower total, low‐density lipoprotein, high‐density lipoprotein (HDL) (only in Kitavans and Swedish controls combined), and non‐HDL cholesterol, and higher anti‐PC IgG (only in Kitavans and Swedish controls combined).ConclusionTotal adiponectin in Kitavans was significantly lower than in Swedish controls.

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Total adiponectin in indigenous Melanesians on Kitava

Carrera‐Bastos,

Fontes‐Villalba,

Ahrén

et al. 2024

American J Hum Biol

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Insulin clearance at randomisation and in response to treatment in youth with type 2 diabetes: a secondary analysis of the TODAY randomised clinical trial

Nadeau,

Arslanian,

Bacha

et al. 2024

Diabetologia

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Cross-sectional, interventional, and causal investigation of insulin sensitivity using plasma proteomics in diverse populations

Kho,

Wary,

Zanetti

et al. 2024

Preprint

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Background: We previously reported significant correlations between a direct measure of insulin sensitivity (IS) and blood levels of proteins measured using the Proximity Extension Assay (PEA) in two European cohorts. However, protein correlations with IS within non-European populations, in response to short-term interventions that improve IS, and any causal associations with IS have not yet been established. Methods: We measured 1,470 proteins using the PEA in the plasma of 1,015 research participants at Stanford University who underwent one or more direct measures of IS. Association analyses were carried out with multivariable linear regression within and across Stanford subgroups and within each of the two European cohorts. Association statistics were also meta-analyzed after transformation and harmonization of the two direct measures of IS. Lastly, we performed genome-wide association studies of IS and used genetic instruments of plasma proteins from the UK Biobank to identify candidate causal proteins for IS through Mendelian Randomization (MR) analysis. Results: In age and sex adjusted model, 810 proteins were associated with baseline IS among 652 self-reported European participants in the Stanford cohort at a false discovery rate (FDR) < 0.05. Effect sizes for these proteins were highly correlated with those observed in 122 South Asian, 92 East Asian, 85 Hispanic, and 52 Black/African American persons (r= 0.68 to 0.83, all P<=4.3x10^-113). Meta-analysis of the full Stanford cohort with the two European cohorts (N=2,945) yielded 247 significant protein associations (FDR < 0.05), with 75 remaining significant after further adjustment for body mass index. In a subset of Stanford participants undergoing insulin sensitizing interventions (N=53 taking thiazolidinediones, N=66 with weight loss), 79.6% of protein level changes were directionally consistent with the respective baseline association (observed/expected p=6.7x10^-16). MR analyses identified eight candidate causal proteins for IS, among which were SELE and ASGR1, proteins with established drug targets currently under investigation. Conclusion: Plasma proteins measured using the PEA provide a robust signature for IS across diverse populations and after short-term insulin sensitizing interventions highlighting their potential value as universal biomarkers of insulin resistance. A small subset of markers provided insights into potential causal molecular mechanisms and therapeutic targets.

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Exploring the determinants of ethnic differences in insulin clearance between men of Black African and White European ethnicity

Cited by 5 publications

References 47 publications

Total adiponectin in indigenous Melanesians on Kitava

Total adiponectin in indigenous Melanesians on Kitava

Insulin clearance at randomisation and in response to treatment in youth with type 2 diabetes: a secondary analysis of the TODAY randomised clinical trial

Cross-sectional, interventional, and causal investigation of insulin sensitivity using plasma proteomics in diverse populations

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