Dominant PDX1 deficiency causes highly penetrant diabetes at different ages, associated with obesity and exocrine pancreatic deficiency: Lessons for precision medicine
Authors' conclusion
This study reveals diverse clinical presentations among the carriers of a P/LP PDX1 variant, highlighting strong variations in diabetes onset, and unexpectedly high prevalence of obesity and pancreatic development abnormalities. Clinical data suggest that DPP4i and GLP1-RA may be the best effective treatments to manage both glucose and weight controls, opening new avenue in precision diabetic medicine.
Study context
- Population
- Carriers of heterozygous P/LP PDX1 variants: a family with a novel variant, and documented carriers from Human Gene Mutation Database (HGMD), RaDiO study and T2DKP (87 K participants)
- Outcome
- Phenotypes of P/LP PDX1 variant carriers
Methodological detailsfamily-based, database analysis (HGMD, RaDiO, T2DKP)
- Family-based
- Database analysis (HGMD, RaDiO, T2DKP)
Main finding
As reported in the abstract
Family: p.G232S variant identified in relatives
4
HGMD carriers with diabetes (onset from eight days of life to 67 years)
79 %
HGMD carriers with pancreatic insufficiency
63 %
HGMD carriers with obesity
40 %
Observational data: associations, not effects.
Further findings
T2D risk
- P/LP PDX1 variants increased risk of T2D, confirmed in T2DKP
Treatment
- DPP-4i and GLP-1 RA enabled good glucose control without hypoglycaemia, and weight management
Original publication
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