title: TCF7L2 and therapeutic response to sulfonylureas in patients with type 2 diabetes.
abstract: BACKGROUND
  Variants in the TCF7L2 have been shown to be associated with an increased risk for type 2 diabetes (T2D). Since the association with diabetes could be explained by effects on insulin secretion, we investigated whether patients with diabetes risk alleles at rs7903146 might have an altered hypoglycaemic response to sulfonylureas (SUs).
  
  
  METHODS
  We recruited 189 patients with T2D being treated with SUs and determined the rs7903146 diabetes risk genotype. We used a logistic regression with secondary SU failure defined as an A1C ≥7.0% after 6 months of SU treatment.
  
  
  RESULTS
  In univariate regression analyses, TCF7L2 genotype was the only predictor of SU treatment failure. The rs7903146 T allele was significantly more frequent in the group of patients who failed to respond to SU (36%) than in the control group (26%) [P = 0.046; odds ratio (OR): 1.57 (1.01-2.45) in an additive mode of inheritance].
  
  
  CONCLUSIONS
  Our data suggest that patients with diabetes risk alleles in TCF7L2 have an altered hypoglycaemic response to SUs resulting in earlier secondary failure.
authors.affiliation: Interdisciplinary Centre for Clinical Research, University of Leipzig, Leipzig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Holstein
authors.forename: Michael
authors.initials: M
authors.lastname: Hahn
authors.forename: Antje
authors.initials: A
authors.lastname: Körner
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D000078790:Insulin Secretion; D008297:Male; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D058118:Transcription Factor 7-Like 2 Protein