A SNP in G6PC2 predicts insulin secretion in type 1 diabetes.


We investigated whether single nucleotide polymorphisms in genes related to glucose metabolism correlate with insulin secretion in type 1 diabetes patients. A cohort of 49 type 1 diabetes patients underwent serial mixed meal tolerance tests to assess insulin secretion. Patients were genotyped for SNPs related to glucose metabolism: CDKAL1 rs7754840, G6PC2 rs560887, HHEX rs1111875, KCNJ11 rs5215. Recently diagnosed patients (<100 days) homozygous for the G allele of G6PC2 had higher area under the curve C-peptide on mixed meal tolerance tests compared to non-homozygous patients (344.8 ± 203.2 vs. 167.9 ± 131.5, p = 0.04). Other SNPs did not correlate with insulin secretion in the new onset period. In a longitudinal survival analysis, homozygosity for the minor allele (A) in G6PC2 predicted more rapid loss of insulin secretion over time. A SNP in the beta cell gene G6PC2 may correlate with preserved insulin secretion in type 1 diabetes.


Sanda, Srinath; Wei, Shan; Rue, Tessa; Shilling, Heather; Greenbaum, Carla;


  • Cyclin-Dependent Kinase 5/ genetics
  • Diabetes Mellitus, Type 1/ genetics
  • Diabetes Mellitus, Type 1/ metabolism
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Glucose-6-Phosphatase/ genetics
  • Homeodomain Proteins/ genetics
  • Homozygote
  • Humans
  • Insulin/ secretion
  • Male
  • Polymorphism, Single Nucleotide
  • Potassium Channels, Inwardly Rectifying/ genetics
  • Predictive Value of Tests
  • Transcription Factors/ genetics

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