Glucose-stimulated prehepatic insulin secretion is associated with circulating alanine, triglyceride, glucagon, lactate and TNF-alpha in patients with HIV-lipodystrophy.
OBJECTIVE
We examined whether insulin-resistant lipodystrophic HIV-infected patients with known high fasting prehepatic insulin secretion rates (FISRs) displayed alterations in first-phase prehepatic insulin response to intravenous glucose (ISREG0-10 min).


METHODS
Eighteen normoglycaemic lipodystrophic HIV-infected (LIPO) patients and 25 normoglycaemic nonlipodystrophic HIV-infected patients (controls) were included in the study. The prehepatic insulin secretion rate was estimated by deconvolution of C-peptide concentrations, and insulin sensitivity (SIRd) was estimated by the glucose clamp technique. The disposition index (Di=ISREG0-10 min x SIRd) was calculated to estimate the beta-cell response relative to insulin sensitivity.


RESULTS
FISR was increased by 69% (P<0.001), whereas median Di was decreased by 75% (P<0.01), primarily as a result of a reduction of SI(Rd) by 60% (P<0.001) in LIPO patients compared with controls. Three LIPO groups were identified arbitrarily according to their FISR and ISREG0-10 min values relative to those of controls. Four LIPO patients displayed high FISR [+3 standard deviations (SD), P<0.001], high ISREG0-10 min (+3 SD, P<0.001) and low SIRd (P<0.01), suggesting an intact B-cell capacity to compensate insulin resistance; six LIPO patients exhibited high FISR (+3SD, P<0.001), low ISREG0-10min (-1 SD, P=0.01), and low SIRd (P<0.01), suggesting depletion of readily releasable insulin stores; the remaining eight LIPO patients and controls displayed identical FISR and ISREG0-10 min. Increased concentrations of the nonglucose insulin secretagogues triglyceride (+124%), alanine (+35%) and glucagon (+88%), and also lactate (+96%) and tumour necrosis factor (TNF)-alpha (+62%) were observed in the 10 LIPO patients with aberrations in FISR and ISREG0-10 min compared with the remaining HIV-infected patients (all P<0.05).


CONCLUSIONS
Plasma triglyceride, alanine, glucagon, lactate and TNF-alpha may be associated with alterations in the first-phase prehepatic insulin secretion response to intravenous glucose in normoglycaemic lipodystrophic HIV-infected patients.
Department of Infectious Diseases, Hvidovre University Hospital, Hvidovre, Copenhagen, Denmark. sbhau@dadlnet.dk
S B
SB
Haugaard
O
O
Andersen
S B
SB
Pedersen
F
F
Dela
C F
CF
Deacon
J J
JJ
Holst
J
J
Iversen
S
S
Madsbad
D000328:Adult; D000409:Alanine / Q000097:blood; D002096:C-Peptide / Q000032:analysis; D016022:Case-Control Studies; D005934:Glucagon / Q000097:blood; D005947:Glucose; D015309:Glucose Clamp Technique; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007773:Lactates / Q000097:blood; D008297:Male; D008875:Middle Aged; D013268:Stimulation, Chemical; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D002096:C-Peptide; D007328:Insulin; D007773:Lactates; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D005934:Glucagon; D005947:Glucose; D000409:Alanine