Beta-cell dysfunction and low insulin clearance in insulin-resistant human immunodeficiency virus (HIV)-infected patients with lipodystrophy.
OBJECTIVE
To obtain a better understanding of the physiological aspects of glucose homeostasis in human immunodeficiency virus (HIV)-infected patients with lipodystrophy, we evaluated separately beta-cell function and insulin sensitivity after an oral glucose load.


METHODS
Beta-cell function was investigated during an oral glucose tolerance test (OGTT) (75 g, 180 min) in 16 lipodystrophic HIV-infected patients and in 15 age- and weight-matched nonlipodystrophic HIV-infected patients. All participants were sedentary Caucasian males, who were on highly active antiretroviral therapy with no history of diabetes mellitus or impaired glucose tolerance. Prehepatic insulin secretion rates were estimated by deconvolution of C-peptide concentrations. A composite measure of insulin sensitivity was derived from the OGTT.


RESULTS
Beta-cell secretory capacity (i.e. the rate of change in insulin secretion per unit change in glucose concentration) was similar in lipodystrophic and nonlipodystrophic patients (6.2 +/- 1.0 mU kg(-1) min(-1) mg(-1) dl vs. 5.4 +/- 0.4, P > 0.4), but insulin sensitivity was reduced by 61% in lipodystrophic patients (P < 0.004). The disposition index (insulin capacity multiplied with insulin sensitivity) and insulin clearance rate were reduced in lipodystrophic patients (-55%, P < 0.003 and -31%, P < 0.004). Insulin clearance rate correlated strongly with insulin sensitivity (r = 0.82, P < 0.001). More lipodystrophic than nonlipodystrophic patients exhibited impaired glucose tolerance and diabetes mellitus (63%vs. 20%, P < 0.05).


CONCLUSIONS
Our data support the concept that impaired glucose tolerance in lipodystrophic HIV-infected patients relates to a failure of the beta-cells to fully compensate for decrements in insulin sensitivity despite simultaneous reduction in insulin clearance.
Haugaard
Steen B
SB
Clinical Research Unit, Hvidovre University Hospital, University of Copenhagen, Denmark. sbhau@dadlnet.dk
Andersen
Ove
O
Vølund
Aage
A
Hansen
Birgitte R
BR
Iversen
Johan
J
Andersen
Ulrik B
UB
Nielsen
Jens Ole
JO
Madsbad
Sten
S
D000328:Adult; D000886:Anthropometry / Q000379:methods; D019380:Anti-HIV Agents / Q000008:administration & dosage; D023241:Antiretroviral Therapy, Highly Active; D001786:Blood Glucose / Q000378:metabolism; D004334:Drug Administration Schedule; D005951:Glucose Tolerance Test; D015658:HIV Infections / Q000188:drug therapy; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged
D019380:Anti-HIV Agents; D001786:Blood Glucose; D007328:Insulin