Incretin action maintains insulin secretion, but not hepatic insulin action, in people with impaired fasting glucose.
OBJECTIVE
To determine whether altered GLP-1 activity contributes to the abnormal endogenous glucose production (EGP) and insulin secretion characteristic of people with impaired fasting glucose (IFG).


METHODS
People with IFG (n=10) and normal glucose tolerance (NGT; n=13) underwent assessment of EGP (via [6,6-(2)H(2)]-glucose infusion). Parameters of whole body insulin action and secretion were estimated by IVGTT and OGTT. Measures of EGP and insulin secretion were made before and after sitagliptin administration.


RESULTS
EGP was not different at baseline (glucose R(a); 1.47+/-0.08 vs. 1.46+/-0.05mg/kg/min, IFG vs. NGT, p=0.93). However, when differences in circulating insulin were accounted for (EGPXSSPI; 20.2+/-2.1 vs. 14.4+/-1.0AU, vs. NGT, p=0.03) the hepatic insulin resistance index was significantly higher in IFG. Baseline insulin action (S(i); 2.3+/-0.1x10(-4)/microU/ml vs. 3.5+/-0.4x10(-4)/microU/ml, p=0.01, IFG vs. NGT) and secretion (DI; 587+/-81x10(-4)/min vs. 1171+/-226x10(-4)/min, p=0.04, IFG vs. NGT) were impaired in IFG when evaluated by the IVGTT, but not by OGTT (insulin sensitivity 4.52+/-1.08x10(-4)dl/kg/min vs. 6.73+/-1.16x10(-4)dl/kg/min, IFG vs. NGT, p=0.16; indices of basal (Phi(b)), static (Phi(s)), dynamic (Phi(d)), and total (Phi(t)) insulin secretion, p>0.07). Sitagliptin did not change EGP or insulin secretion in either group.


CONCLUSIONS
Incretin action maintained insulin secretion, but not hepatic insulin action, in people with IFG.
Perreault
Leigh
L
University of Colorado at Denver School of Medicine, Aurora, CO 80045, USA. leigh.perreault@ucdenver.edu
Man
Chiara Dalla
CD
Hunerdosse
Devon M
DM
Cobelli
Claudio
C
Bergman
Bryan C
BC
D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000502:physiology; D005947:Glucose / Q000737:chemistry / Q000493:pharmacokinetics; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy*; D054795:Incretins / Q000097:blood / Q000502:physiology*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
D001786:Blood Glucose; D002096:C-Peptide; D054873:Dipeptidyl-Peptidase IV Inhibitors; D054795:Incretins; D007328:Insulin; D011719:Pyrazines; D014230:Triazoles; D052216:Glucagon-Like Peptide 1; D005947:Glucose; D000068900:Sitagliptin Phosphate