title: First-phase insulin secretion has limited impact on postprandial glycemia in subjects with type 2 diabetes: correlations between hyperglycemic glucose clamp and meal test.
abstract: BACKGROUND
  Lack of first-phase insulin (INS) secretion is regarded as causative for high postprandial glucose excursions in subjects with type 2 diabetes. We aimed to determine the impact of early INS secretion on postprandial glycemia.
  
  
  METHODS
  Twenty subjects with type 2 diabetes (age 54 +/- 8 years, body mass index 28.7 +/- 2.7 kg/m(2) [mean +/- SD]) underwent a hyperglycemic glucose clamp and a meal test twice separated by a washout period of 4 weeks. Multiple regression analysis was used to identify determinants of postprandial glycemia.
  
  
  RESULTS
  During hyperglycemic glucose clamps eight subjects showed a preserved first-phase INS secretion (P1+), whereas 12 subjects showed none (P1-). Both subject groups differed in fasting blood glucose (BG) (116 +/- 7 vs. 147 +/- 31 mg/dL, P = 0.011) and glycosylated hemoglobin (6.0 +/- 0.4 vs. 6.7 +/- 0.8, P = 0.041). Total INS secretory response during glucose clamps was higher in P1+ than P1- (INS-area under the concentration vs. time curve [AUC](0-120 min) 6.7 +/- 2.7 vs. 3.2 +/- 2.1 mU.min/mL; P = 0.006). During meal tests, however, INS-AUC(0-120 min) was similar between P1+ and P1-, whereas early INS secretion was still different (INS-AUC(0-60 min) 3.9 +/- 1.8 vs. 2.1 +/- 1.0 mU.min/mL; P = 0.031). Despite higher INS-AUC(0-60 min) in P1+, early postprandial BG was comparable between groups (BG-AUC(0-60 min) 1.5 +/- 0.5 vs. 1.6 +/- 0.6 g.min/dL; difference not significant). Multiple regression analyses showed no impact of first-phase INS secretion on postprandial glycemia, either in P1+ or in P1-. Nevertheless, in P1-, but not in P1+, postprandial glycemia was negatively correlated with INS sensitivity (R(2) = 0.83, P < 0.001).
  
  
  CONCLUSIONS
  This study, correlating results of hyperglycemic glucose clamps with meal tests, shows that a preserved first-phase INS secretion has only a limited impact on postprandial glucose excursions in a group of subjects in early-stage type 2 diabetes.
authors.affiliation: Profil Institut für Stoffwechselforschung GmbH, 41460 Neuss, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Rave
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Sidharta
authors.forename: Jasper
authors.initials: J
authors.lastname: Dingemanse
authors.forename: Lutz
authors.initials: L
authors.lastname: Heinemann
authors.forename: Kerstin
authors.initials: K
authors.lastname: Roggen
mesh_terms: D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism*; D015331:Cohort Studies; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D015309:Glucose Clamp Technique / Q000379:methods*; D005951:Glucose Tolerance Test / Q000592:standards*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period
chemical_list: D001786:Blood Glucose; D007328:Insulin