title: Treatment with protease inhibitors associated with peripheral insulin resistance and impaired oral glucose tolerance in HIV-1-infected patients.
abstract: BACKGROUND
  The use of protease inhibitors in the treatment of HIV-1 infection is associated with the new onset of diabetes mellitus, hyperlipidaemia and lipodystrophy. It is unclear whether these findings are coincidental or whether they reflect a causative effect of protease inhibitors.
  
  
  OBJECTIVE
  To evaluate the effect of treatment with protease inhibitors on insulin sensitivity, oral glucose tolerance and serum lipids in HIV-infected patients in order to determine whether treatment with protease inhibitors can cause peripheral insulin resistance.
  
  
  METHODS
  Cross-sectional controlled study in HIV-infected patients treated with protease inhibitors to assess insulin sensitivity, oral glucose tolerance and changes in serum lipids.
  
  
  METHODS
  Sixty-seven patients treated with protease inhibitors, 13 therapy-naive patients and 18 HIV-negative control subjects were tested for insulin sensitivity (intravenous insulin tolerance test). In a subgroup of 24 treated patients, oral glucose tolerance was determined. Serum lipids prior to and under treatment with protease inhibitors were compared.
  
  
  RESULTS
  Patients on protease inhibitors had a significantly decreased insulin sensitivity when compared with therapy-naive patients (median, 75 and 156 micromol/l/min, respectively; P < 0.001). All treated patients with impaired (n=4) or diabetic (n=9) oral glucose tolerance, and four out of 11 patients with normal glucose tolerance showed peripheral insulin resistance; all therapy-naive patients had normal insulin sensitivity. Treatment with protease inhibitors led to a significant increase in total triglycerides and cholesterol in the 67 treated patients (median increase, 113 and 37 mg/ml, respectively).
  
  
  CONCLUSIONS
  Treatment with protease inhibitors is associated with peripheral insulin resistance, leading to impaired or diabetic oral glucose tolerance in some of the patients, and with hyperlipidaemia. Overall, there is a large variation in the severity and clinical presentation of protease inhibitor-associated metabolic side-effects.
authors.affiliation: Infektionsambulanz, Medizinische Poliklinik, Ludwig-Maximilians Universität München, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Walli
authors.forename: O
authors.initials: O
authors.lastname: Herfort
authors.forename: G M
authors.initials: GM
authors.lastname: Michl
authors.forename: T
authors.initials: T
authors.lastname: Demant
authors.forename: H
authors.initials: H
authors.lastname: Jäger
authors.forename: C
authors.initials: C
authors.lastname: Dieterle
authors.forename: J R
authors.initials: JR
authors.lastname: Bogner
authors.forename: R
authors.initials: R
authors.lastname: Landgraf
authors.forename: F D
authors.initials: FD
authors.lastname: Goebel
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D002784:Cholesterol / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D015497:HIV-1; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D014280:Triglycerides; D002784:Cholesterol