Enhanced glucagon-like peptide-1 (GLP-1) response to oral glucose in glucose-intolerant HIV-infected patients on antiretroviral therapy.
OBJECTIVE
We investigated whether the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are major regulators of glucose tolerance through the stimulation of insulin secretion, contribute to impaired glucose tolerance (IGT) among HIV-infected patients on highly active antiretroviral therapy (HAART).


METHODS
Eighteen HIV-infected male patients (six lipodystrophic and 12 nonlipodystrophic) with normal glucose tolerance (NGT) were compared with 10 HIV-infected male patients (eight lipodystrophic and two nonlipodystrophic) with IGT. Plasma concentrations of GLP-1 and GIP were determined frequently during a 3-h, 75-g glucose tolerance test. Insulin secretion rates (ISRs) were calculated by deconvolution of C-peptide concentrations.


RESULTS
The incremental area under the curve (incrAUC) for GLP-1 was increased by 250% in IGT patients compared with NGT patients (1455+/-422 vs. 409+/-254 pmol/L/180 min, respectively; P<0.05), whereas the incrAUC for GIP did not differ between the study groups (7689+/-1097 vs. 8041+/-998 pmol/L/180 min, respectively; not significant). In pooled study groups, the GIP incrAUC correlated positively with the ISR incrAUC without adjustment (r=0.38, P<0.05) and following adjustment for glucose incrAUC (r=0.49, P<0.01).


CONCLUSIONS
Our data suggest: (1) that glucose-intolerant, HIV-infected male patients may display enhanced GLP-1 responses to oral glucose compared with normal glucose-tolerant HIV-infected male patients, which may represent a compensatory mechanism rather than explain the IGT; (2) that the GIP response may be associated with ISR independently of plasma glucose in nondiabetic HIV-infected males on HAART.
Andersen
O
O
Department of Infectious Diseases, Hvidovre University Hospital, Copenhagen, Denmark. oandersen@dadlnet.dk
Haugaard
S B
SB
Holst
J J
JJ
Deacon
C F
CF
Iversen
J
J
Andersen
U B
UB
Nielsen
J O
JO
Madsbad
S
S
D000328:Adult; D000704:Analysis of Variance; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D002096:C-Peptide / Q000032:analysis; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005934:Glucagon / Q000097:blood*; D052216:Glucagon-Like Peptide 1; D005947:Glucose; D018149:Glucose Intolerance / Q000097:blood / Q000821:virology*; D005951:Glucose Tolerance Test; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood / Q000188:drug therapy; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000097:blood*; D011498:Protein Precursors / Q000097:blood*
D000998:Antiviral Agents; D001786:Blood Glucose; D002096:C-Peptide; D010446:Peptide Fragments; D011498:Protein Precursors; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose