PMID- 16125528
OWN - NLM
STAT- MEDLINE
DCOM- 20051101
LR  - 20111117
IS  - 0026-0495 (Print)
IS  - 0026-0495 (Linking)
VI  - 54
IP  - 9
DP  - 2005 Sep
TI  - Impact of glucagon response on postprandial hyperglycemia in men with impaired 
      glucose tolerance and type 2 diabetes mellitus.
PG  - 1168-73
AB  - Glucagon is the physiological antagonist of insulin. Postprandial (pp) 
      hyperglycemia in impaired glucose tolerance (IGT) and in type 2 diabetes mellitus 
      (T2DM) may also depend on irregularities in glucagon secretion. This study 
      investigated the glucagon excursion after a lipid-glucose-protein tolerance test 
      in subjects with different stages of glucose intolerance. We also analyzed the 
      relationship between pp glucagon secretion and hyperglycemias. A total of 64 men 
      (27 healthy subjects with normal glucose tolerance [NGT], 15 with IGT, and 22 
      with T2DM) were examined. Plasma glucose (PG), insulin, proinsulin, free fatty 
      acids, and triglycerides were measured in the fasting state and at 30 minutes and 
      2, 3, 4, and 6 hours after the intake of the test meal, which contained 126 g 
      carbohydrates, 92 g fat, and 17 g protein. Postprandial concentrations of 
      metabolic parameters were calculated as area under the curve (AUC). Glucagon was 
      measured in the fasting state and at 30 minutes and 2 and 4 hours pp. Early 
      glucagon increment was defined as glucagon at 30 minutes minus fasting glucagon. 
      The insulin response was quantified as insulin increment divided by PG increment 
      in the corresponding time. Insulin resistance was calculated using lomeostasis 
      model assessment (HOMA). Fasting glucagon was significantly increased in IGT vs 
      NGT (P<.05), and early glucagon increment was significantly higher in T2DM vs NGT 
      and IGT (P<.05). The 2-hour glucagon concentration after the load (AUC) was 
      increased in IGT and T2DM vs NGT (P<.05). Early glucagon increment and the 2-hour 
      AUC of glucagon were strongly correlated to pp glycemia (r=0.494 and P=.001, and 
      r=0.439 and P=.003, respectively). An inverse correlation was observed between 
      early glucagon increment and insulin response at 30 minutes and 2 hours after the 
      meal load (r=-0.287 and P=.026, and r=-0.435 and P=.001, respectively). The 
      2-hour AUC of glucagon was significantly associated with insulin resistance 
      (r=0.354, P=.020). Multivariate analysis revealed 2-hour insulin response and 
      early glucagon increment as significant independent determinants of the AUC of PG 
      in IGT (R=0.787). In T2DM, 2-hour insulin response, insulin resistance, and early 
      glucagon increment were significant determinants of the AUC of PG (R=0.867). Our 
      study suggests an important role for the irregularities in glucagon response in 
      the pp glucose excursion after a standardized oral mixed meal in IGT and in T2DM. 
      According to our data, a bihormonal imbalance starts before diabetes is 
      diagnosed. Prospective studies are needed to evaluate the impact of glucagon on 
      the progression of glucose intolerance and the possible effects of medicinal 
      suppression of glucagon increment to prevent the progression of glucose 
      tolerance.
FAU - Henkel, Elena
AU  - Henkel E
AD  - Centre for Clinical Studies-Metabolism and Endocrinology, Science and Technology 
      Transfer, Technical University, D-01307 Dresden, Germany. henkel@gwtonline-zks.de
FAU - Menschikowski, Mario
AU  - Menschikowski M
FAU - Koehler, Carsta
AU  - Koehler C
FAU - Leonhardt, Wolfgang
AU  - Leonhardt W
FAU - Hanefeld, Markolf
AU  - Hanefeld M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Blood Glucose)
RN  - 0 (Dietary Fats)
RN  - 0 (Dietary Proteins)
RN  - 0 (Insulin)
RN  - 9007-92-5 (Glucagon)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Blood Glucose
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Dietary Fats/administration & dosage
MH  - Dietary Proteins/administration & dosage
MH  - Fasting
MH  - Glucagon/*blood
MH  - Glucose Intolerance/*metabolism
MH  - Glucose Tolerance Test
MH  - Humans
MH  - Hyperglycemia/*metabolism
MH  - Insulin/blood
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Postprandial Period/*physiology
EDAT- 2005/08/30 09:00
MHDA- 2005/11/03 09:00
CRDT- 2005/08/30 09:00
PHST- 2004/11/22 00:00 [received]
PHST- 2005/02/16 00:00 [revised]
PHST- 2005/03/01 00:00 [accepted]
PHST- 2005/08/30 09:00 [pubmed]
PHST- 2005/11/03 09:00 [medline]
PHST- 2005/08/30 09:00 [entrez]
AID - S0026-0495(05)00147-2 [pii]
AID - 10.1016/j.metabol.2005.03.024 [doi]
PST - ppublish
SO  - Metabolism. 2005 Sep;54(9):1168-73. doi: 10.1016/j.metabol.2005.03.024.