title: Beta-cell dysfunction and low insulin clearance in insulin-resistant human immunodeficiency virus (HIV)-infected patients with lipodystrophy.
abstract: 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.
authors.affiliation: Clinical Research Unit, Hvidovre University Hospital, University of Copenhagen, Denmark. sbhau@dadlnet.dk
authors.forename: Steen B
authors.initials: SB
authors.lastname: Haugaard
authors.forename: Ove
authors.initials: O
authors.lastname: Andersen
authors.forename: Aage
authors.initials: A
authors.lastname: Vølund
authors.forename: Birgitte R
authors.initials: BR
authors.lastname: Hansen
authors.forename: Johan
authors.initials: J
authors.lastname: Iversen
authors.forename: Ulrik B
authors.initials: UB
authors.lastname: Andersen
authors.forename: Jens Ole
authors.initials: JO
authors.lastname: Nielsen
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
mesh_terms: 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
chemical_list: D019380:Anti-HIV Agents; D001786:Blood Glucose; D007328:Insulin