Underestimated risk of secondary complications in pathogenic and glucose-elevating GCK variant carriers with type 2 diabetes

Here are the Underestimated risk of secondary complications in pathogenic and glucose-elevating GCK variant carriers with type 2 diabetes journals presenting the latest research across various disciplines. From social sciences to technology, each article is expected to provide valuable insights to our readers.

Underestimated risk of secondary complications in hemodialysis, underestimated risk of secondary complications in pathogenic priming, underestimated risk of secondary complications after spinal cord, underestimated risk of secondary complications of osteoporosis, underestimated risk of secondary complications in cataract, underestimated risk of secondary complications in pathogenic escherichia, underestimated risk of secondary complications in childbirth, underestimated risk of secondary cataract.

Underestimated risk of secondary complications in pathogenic and glucose-elevating GCK variant carriers with type 2 diabetes

Background: Natural HbA1c levels in GCK Maturity-onset diabetes of the young (GCK-MODY) patients often sit above the diagnostic threshold for type 2 diabetes (T2D). Treatments to lower HbA1c levels show reduced effectiveness in these individuals, yet in case studies to date, GCK-MODY patients often evade secondary T2D complications. Given these deviations, genetic screening of GCK may be clinically useful, but population studies are needed to more broadly understand T2D-related complications in GCK variant carriers.

Methods: To identify GCK variant carriers at the population level, we used both ACMG/AMP variant interpretation for GCK-MODY pathogenicity and a state-of-the-art variant interpretation strategy based on functional and statistical evidence to predict glucose elevations. Presence of pathogenic and glucose-elevating GCK variants was assessed in two cohorts (n~535,000). We identified 442 individuals with GCK variants pre dicted to increase glucose (~1/1200), with 150 (34%) of these individuals harboring variants reaching a pathogenic interpretation.

Results: In a retrospective analysis, we show that in addition to elevated HbA1c, pathogenic variant carriers are 10x as likely, and all other glucose-elevating GCK variant carriers are 3x as likely, to receive a T2D diagnosis compared to non-GCK carriers. Surprisingly, carriers of pathogenic and glucose-elevating GCK variants with T2D develop T2D-related complications at rates more than double that of individuals without T2D, comparable to non-GCK individuals with T2D. Conclusions: This population-level assessment shows secondary complications in individuals with pathogenic and glucose-elevating GCK variants and T2D and suggests that genotyping for these variants should be considered in a precision medicine approach for T2D treatment and prevention. © The Author(s) 2024.

Authors : Schiabor Barrett K.M.; Telis N.; McEwen L.M.; Burrows E.K.; Khuder B.; Judge D.P.; Pawloski P.A.; Grzymski J.J.; Washington N.L.; Bolze A.; Cirulli E.T.

Source : Springer Nature