Related Experiment Video
Updated: Aug 9, 2026

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
Insulin resistance in HIV protease inhibitor-associated diabetes
K E Yarasheski1, P Tebas, C Sigmund
1Division of Endocrinology, Diabetes, and Metabolism, Washington University Medical School, St. Louis, Missouri 63110, USA. key@imgate.wustl.edu
Background:
Fasting hyperglycemia has been associated with HIV protease inhibitor (PI) therapy.
Objective:
To determine whether absolute insulin deficiency or insulin resistance with relative insulin deficiency and an elevated body mass index (BMI) contribute to HIV PI-associated diabetes.
Design:
Cross-sectional evaluation.
Patients:
8 healthy seronegative men, 10 nondiabetic HIV-positive patients naive to PI, 15 nondiabetic HIV-positive patients receiving PI (BMI = 26 kg/m2), 6 nondiabetic HIV-positive patients receiving PI (BMI = 31 kg/m2), and 8 HIV-positive patients with diabetes receiving PI (BMI = 34 kg/m2). All patients on PI received indinavir.
Measurements:
Fasting concentrations of glucoregulatory hormones. Direct effects of indinavir (20 microM) on rat pancreatic beta-cell function in vitro.
Results:
In hyperglycemic HIV-positive subjects, circulating concentrations of insulin, C-peptide, proinsulin, glucagon, and the proinsulin/insulin ratio were increased when compared with those of the other 4 groups (p < .05). Morning fasting serum cortisol concentrations were not different among the 5 groups. Glutamic acid decarboxylase (GAD) antibody titers were uncommon in all groups. High BMI was not always associated with diabetes. In vitro, indinavir did not inhibit proinsulin to insulin conversion or impair glucose-induced secretion of insulin and C-peptide from rat beta-cells.
Conclusions:
The pathogenesis of HIV PI-associated diabetes involves peripheral insulin resistance with insulin deficiency relative to hyperglucagonemia and a high BMI. Pancreatic beta-cell function was not impaired by indinavir. HIV PI-associated diabetes mirrors that of non-insulin-dependent diabetes mellitus and impaired insulin action in the periphery.
Related Concept Videos
Diabetes Mellitus: Overview and Type I Subtype
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
Oral Hypoglycemic Agents: Biguanides and Glitazones
Dipeptidyl Peptidase 4 Inhibitors
Type I Diabetes II: Pathophysiology
Type II Diabetes II: Pathophysiology
Inhibitors of Virion Maturation and Assembly

