Inappropriate suppression of glucagon during OGTT but not during isoglycaemic i.v. glucose infusion contributes to the reduced incretin effect in type 2 diabetes mellitus
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Inappropriate suppression of glucagon during OGTT but not during isoglycaemic i.v. glucose infusion contributes to the reduced incretin effect in type 2 diabetes mellitus. / Knop, F K; Vilsbøll, T; Madsbad, S; Holst, Jens Juul; Krarup, T.
I: Diabetologia, Bind 50, Nr. 4, 04.2007, s. 797-805.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Inappropriate suppression of glucagon during OGTT but not during isoglycaemic i.v. glucose infusion contributes to the reduced incretin effect in type 2 diabetes mellitus
AU - Knop, F K
AU - Vilsbøll, T
AU - Madsbad, S
AU - Holst, Jens Juul
AU - Krarup, T
PY - 2007/4
Y1 - 2007/4
N2 - AIMS/HYPOTHESIS: We investigated glucagon responses during OGTT and isoglycaemic i.v. glucose infusion, respectively, to further elucidate the mechanisms behind the glucose intolerance in patients with type 2 diabetes.MATERIALS AND METHODS: Ten patients (eight men) with type 2 diabetes (age: 64 [51-80] years; BMI: 23 [21-26] kg/m(2); HbA(1c): 6.9 [6.2-8.7]%, values mean [range]) and ten control subjects matched for sex, age and BMI were studied. Blood was sampled on two separate days following a 4-h 50-g OGTT and an isoglycaemic i.v. glucose infusion, respectively.RESULTS: Isoglycaemia during the 2 days was obtained in both groups. In the control subjects no difference in glucagon suppression during the first 45 min of OGTT and isoglycaemic i.v. glucose infusion (-36 +/- 12 vs -64 +/- 23 mmol/l x 45 min; p = NS) was observed, whereas in the group of patients with type 2 diabetes significant glucagon suppression only occurred following isoglycaemic i.v. glucose infusion (-63 +/- 21 vs 10 +/- 16 mmol/l x 45 min; p = 0.002). The incretin effect was significantly reduced in patients with type 2 diabetes compared with control subjects, but no significant differences in the secretion of glucagon-like peptide-1 or glucose-dependent insulinotropic polypeptide between the two groups during OGTT or isoglycaemic i.v. glucose infusion, respectively, could explain this.CONCLUSIONS/INTERPRETATION: Attenuated and delayed glucagon suppression in patients with type 2 diabetes occurs after oral ingestion of glucose, while isoglycaemic i.v. administration of glucose results in normal suppression of glucagon. We suggest that this phenomenon contributes both to the glucose intolerance and to the reduced incretin effect observed in patients with type 2 diabetes.
AB - AIMS/HYPOTHESIS: We investigated glucagon responses during OGTT and isoglycaemic i.v. glucose infusion, respectively, to further elucidate the mechanisms behind the glucose intolerance in patients with type 2 diabetes.MATERIALS AND METHODS: Ten patients (eight men) with type 2 diabetes (age: 64 [51-80] years; BMI: 23 [21-26] kg/m(2); HbA(1c): 6.9 [6.2-8.7]%, values mean [range]) and ten control subjects matched for sex, age and BMI were studied. Blood was sampled on two separate days following a 4-h 50-g OGTT and an isoglycaemic i.v. glucose infusion, respectively.RESULTS: Isoglycaemia during the 2 days was obtained in both groups. In the control subjects no difference in glucagon suppression during the first 45 min of OGTT and isoglycaemic i.v. glucose infusion (-36 +/- 12 vs -64 +/- 23 mmol/l x 45 min; p = NS) was observed, whereas in the group of patients with type 2 diabetes significant glucagon suppression only occurred following isoglycaemic i.v. glucose infusion (-63 +/- 21 vs 10 +/- 16 mmol/l x 45 min; p = 0.002). The incretin effect was significantly reduced in patients with type 2 diabetes compared with control subjects, but no significant differences in the secretion of glucagon-like peptide-1 or glucose-dependent insulinotropic polypeptide between the two groups during OGTT or isoglycaemic i.v. glucose infusion, respectively, could explain this.CONCLUSIONS/INTERPRETATION: Attenuated and delayed glucagon suppression in patients with type 2 diabetes occurs after oral ingestion of glucose, while isoglycaemic i.v. administration of glucose results in normal suppression of glucagon. We suggest that this phenomenon contributes both to the glucose intolerance and to the reduced incretin effect observed in patients with type 2 diabetes.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Case-Control Studies
KW - Diabetes Mellitus, Type 2
KW - Female
KW - Glucagon
KW - Glucagon-Like Peptide 1
KW - Glucose
KW - Glucose Tolerance Test
KW - Humans
KW - Insulin
KW - Male
KW - Middle Aged
KW - Time Factors
U2 - 10.1007/s00125-006-0566-z
DO - 10.1007/s00125-006-0566-z
M3 - Journal article
C2 - 17225124
VL - 50
SP - 797
EP - 805
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 4
ER -
ID: 132050399