title: The effect of glibenclamide on insulin secretion at normal glucose concentrations.
abstract: OBJECTIVE
  The aim of this study was to investigate the incremental and proportional effect of a sulfonylurea on insulin secretion rates at low, elevated and high blood glucose, using parallel groups with ascending or descending glucose steps to minimise potential biases of a single stepped clamp order.
  
  
  METHODS
  Following 14 days on placebo or glibenclamide (2.5 mg) tablets twice daily, separated by 14 days washout, 19 type 2 diabetic patients had ascending or descending three-step hyperinsulinaemic glucose clamps at 4, 8 and 12 mmol/l. C-peptide secretion was estimated by two-compartment C-peptide deconvolution.
  
  
  RESULTS
  Patients in the ascending glucose steps group (n = 10) had mean (SD) age of 60.3 (6.5) years, BMI of 29.8 (4.9) kg/m(2) and fasting glucose on diet alone of 10.6 (2.9) mmol/l; while those in the descending glucose steps group (n = 9) had mean age of 58.2 (8.0) years, BMI of 30.5 (5.4) kg/m(2) and fasting glucose on diet alone of 9.8 (2.2) mmol/l. The geometric means (95% CI) of C-peptide secretion rates on placebo for glucose at 4.0, 8.0 and 12.0 mmol/l were 63 (46, 86), 143 (105, 195) and 205 (149, 281) pmol/min, respectively. On glibenclamide, this increased by 140 (99, 181), 126 (85, 167) and 158 (117, 199) pmol/min, respectively (p < 0.001 vs placebo). The absolute increment was significant (p < 0.001) and independent of clamp glucose concentration (p = 0.54). The proportional increase was greater at 4 mmol/l: 2.8-fold (2.4, 3.2), compared with 1.8-fold (1.5, 2.0) and 1.7-fold (1.4, 1.9) at 8 and 12 mmol/l, respectively (p < 0.001).
  
  
  CONCLUSIONS
  At low-normal glucose, glibenclamide exerted a disproportionate effect on insulin secretion. This study highlights the risks of hypoglycaemia when aiming for tight glucose control on this agent.
authors.affiliation: GMP Husby, Husby, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Riefflin
authors.forename: Usha
authors.initials: U
authors.lastname: Ayyagari
authors.forename: Susan E
authors.initials: SE
authors.lastname: Manley
authors.forename: Rury R
authors.initials: RR
authors.lastname: Holman
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Levy
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D015309:Glucose Clamp Technique; D005905:Glyburide / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D005905:Glyburide