Complete loss of SLC30A8 in humans improves glucose metabolism and beta cell function
Authors' conclusion
The corrected insulin response, disposition index and insulin sensitivity index in LoF heterozygotes and homozygotes indicated higher glucose-stimulated insulin secretion with preserved beta cell function that was independent of BMI. These data suggest that therapeutic inhibition of SLC30A8, up to and including complete knockout, may treat type 2 diabetes safely and effectively.
Study context
- Population
- Participants of the Pakistan Genome Resource (PGR) biobankPGR biobank
- Participants
- 145,037 participants
- Comparison
- SLC30A8 loss-of-function (LoF) heterozygotes and homozygotes vs non-carriers
- LoF homozygotesn = 18
- LoF heterozygotesn = 1,024
- Outcome
- T2D risk
Methodological detailsbiobank whole-exome and whole-genome sequencing, recall-by-genotype OGTTs
- Biobank whole-exome and whole-genome sequencing
- Recall-by-genotype OGTTs
Main finding
As reported in the abstract
Each group vs non-carriersEstimate (95% CI)P value
LoF carriers
OR (additive) 0.62(0.53–0.72)
P = 1.1×10-9LoF homozygotes
OR (recessive) 0.34(0.12–0.93)
P = 0.04Further findings
OGTT glucose and insulin (recall-by-genotype)
- Gene dose-dependent reduction in glucose levels, coupled with elevated insulin
Original publication
Complete loss of SLC30A8 in humans improves glucose metabolism and beta cell function. Diabetologia. Published 29 September 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →