Effects of the ABCC8 R1420H loss-of-function variant on beta-cell function, diabetes incidence, and retinopathy
Authors' conclusion
The ABCC8 R1420H variant is associated with increased risks of diabetes and of retinopathy, which may be partially explained by higher glycemia levels and worse beta-cell function.
Study context
- Population
- American Indians previously genotyped for R1420H with available phenotypic data; beta-cell function analysed in those without diabetes aged ≥5 years; median follow-up 13.5 years (IQR 4.5–26.8)254 variant carriers
- Participants
- 7,675 participants
- Exposure
- ABCC8 R1420H variant carriers vs non-carriers
- Carriersn = 254
- Outcome
- Beta-cell function (insulin secretion vs insulin sensitivity)
Methodological detailscross-sectional analyses of diabetes complications, hierarchical logistic regression, standard major axis regression
- Cross-sectional analyses of diabetes complications
- Hierarchical logistic regression
- Standard major axis regression
Main finding
As reported in the abstract
- Worse beta-cell function in carriers, in children and adults
- Insulin sensitivity: no difference (p=0.50)
- Carriers vs Non-carriers: P = 0.0004
Observational data: associations, not effects.
Further findings
Insulin sensitivity
- No difference in insulin sensitivity, carriers vs non-carriers
- P = 0.50
T2D incidence
- At any BMI and age before 35 years, carriers had higher T2D incidence
Prevalence of increased albuminuria (albumin-to-creatinine ratio (ACR) ≥30 mg/g)
- Variant not associated with prevalence of increased albuminuria, OR
- 0.87 (0.66 to 1.16) (95% CI)
Prevalence of severe albuminuria (ACR ≥300 mg/g)
- Variant not associated with prevalence of severe albuminuria, OR
- 0.96 (0.55 to 1.68) (95% CI)
Prevalence of reduced eGFR (<60 mL/min/1.73 m²)
- Variant not associated with prevalence of reduced eGFR, OR
- 0.44 (0.18 to 1.06) (95% CI)
Retinopathy prevalence
- Variant significantly associated with higher retinopathy prevalence, OR
- 1.74 (1.19 to 2.53) (95% CI)
- Association only partially mediated by glycemia, duration of diabetes, retinopathy risk factors or insulin use
- <11%
- Retinopathy prevalence in carriers higher regardless of diabetes presence
Original publication
Effects of the ABCC8 R1420H loss-of-function variant on beta-cell function, diabetes incidence, and retinopathy. BMJ Open Diabetes Res Care. Published 12 December 2023. doi:10.
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