Type 2 & other diabetes

Targeted proteomics identifies potential biomarkers of dysglycaemia, beta cell function and insulin sensitivity in Black African men and women

DiabetologiaPublished Cross-sectional study

Authors' conclusion

We validated 34 proteins that were associated with type 2 diabetes, of which 11 were associated with measures of type 2 diabetes pathophysiology such as peripheral insulin sensitivity and beta cell function. This study highlights biomarkers that are similar between cohorts of different ancestry, with different lifestyles and sociodemographic profiles. The African-specific biomarkers identified require validation in African cohorts to identify risk markers and increase our understanding of the pathophysiology of type 2 diabetes in African populations.

Study context

Population
Black South African men and women, Middle-Aged Soweto Cohort (MASC); validation in Swedish EpiHealth cohort (normal glucose tolerance (NGT), n=1706; impaired fasting glucose, n=550; T2D, n=210)MASC · Black South African men 380 · women 375
Participants
546 / 116 / 93
Exposure
NGT vs impaired glucose metabolism (IGM) vs T2D
  • NGTn = 546reference
  • IGMn = 116
  • T2Dn = 93
Outcome
Circulating proteins associated with dysglycaemia (IGM or T2D), among 184 pre-selected protein biomarkers
Methodological detailstargeted proteomics, external validation cohort
  • Targeted proteomics
  • External validation cohort

Main finding

As reported in the abstract

Proteins associated with dysglycaemia

Proteins associated with dysglycaemia in MASC

73

Validated in EpiHealth cohort

34

Validated proteins associated with measures of insulin dynamics (most with HOMA-IR)

11

Observational data: associations, not effects.

Further findings

IGFBP2 and HOMA-IR, by sex

Women: coefficient
−0.35 (95% CI −0.44, −0.25)
Men: coefficient
−0.09 (95% CI −0.15, −0.03)
  • Sex-specific analysis

TIMP4 and insulin secretion and beta cell function, women only

Insulin secretion: coefficient
0.05 (95% CI 0.001, 0.11; p for interaction=0.025)
Beta cell function: coefficient
0.06 (95% CI 0.02, 0.09; p for interaction=0.013)
  • Not mediated by adiposity

IGFBP2 and OGTT insulin sensitivity, men

Coefficient
0.38 (95% CI 0.27, 0.49; p for interaction=0.004)

Mediation by fat mass index of IGFBP2 associations, men

Insulin sensitivity: total effect mediated
40.7% (95% CI 37.0, 43.6)
HOMA-IR: total effect mediated
39.1% (95% CI 31.1, 43.5)
  • A posteriori analysis

Original publication

Targeted proteomics identifies potential biomarkers of dysglycaemia, beta cell function and insulin sensitivity in Black African men and women. Diabetologia. Published 17 September 2022. doi:10.1007/s00125-022-05788-1

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