title: Angiotensin-converting enzyme insertion/deletion polymorphism and severe hypoglycemia complicating type 2 diabetes: the Fremantle Diabetes Study.
abstract: OBJECTIVE
  The aim of this study was to determine whether the angiotensin-converting enzyme (ACE) gene I/D polymorphisms independently predict severe hypoglycemia in community-dwelling type 2 patients.
  
  
  METHODS
  Six hundred and two patients who were ACE genotyped at baseline and assessed in 1998 were followed up to the end of June 2006. Severe hypoglycemia was defined as that requiring documented health service use as the primary diagnosis. Cox proportional hazards modeling was used to determine the predictors of first episode and zero-inflated negative binomial regression modeling identified predictors of frequency.
  
  
  RESULTS
  Forty-nine patients (8.1%) experienced 63 episodes of severe hypoglycemia. After adjusting for previously identified significant independent predictors of time to first episode, both ACE DD genotype and ACE inhibitor therapy, but not their interaction, added to the model [hazard ratio (95% confidence interval): 2.34 (1.29-4.26), P = 0.006, and 1.77 (0.99-3.13), P = 0.052, respectively]. Similarly, after adjusting for previously identified risk factors for multiple episodes of severe hypoglycemia, ACE DD genotype was independently associated with increased risk [incidence relative risk (95% confidence interval): 1.80 (1.00-3.24), P = 0.050].
  
  
  CONCLUSIONS
  ACE DD genotype was associated with an approximately 2-fold increased risk of the first episode of severe hypoglycemia and its subsequent frequency in well-characterized patients with type 2 diabetes. Consistent with previous case-control studies, ACE inhibitor therapy was a weak predictor of severe hypoglycemia. ACE I/D genotyping might provide useful adjunctive prognostic information when intensive glycemic control measures are contemplated.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, PO Box 480, Fremantle, Western Australia 6959, Australia. tdavis@meddent.uwa.edu.au
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Davis
authors.forename: Simon G A
authors.initials: SG
authors.lastname: Brown
authors.forename: Ian G
authors.initials: IG
authors.lastname: Jacobs
authors.forename: Max
authors.initials: M
authors.lastname: Bulsara
authors.forename: John
authors.initials: J
authors.lastname: Beilby
authors.forename: David G
authors.initials: DG
authors.lastname: Bruce
authors.forename: Timothy M E
authors.initials: TM
authors.lastname: Davis
mesh_terms: D000368:Aged; D001315:Australia; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007003:Hypoglycemia / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D054643:INDEL Mutation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000502:physiology; D011379:Prognosis; D012720:Severity of Illness Index
chemical_list: D007703:Peptidyl-Dipeptidase A