Endocrine Abstracts

Beta-cell function of HIV-infected patients on highly active antiretroviral therapy (HAART), who display lipodystrophy, may be impaired. An early defect in beta-cell function may be characterized by an increased secretion of 32–33 split proinsulin (SP) and intact proinsulin (IP).

To address this issue the secretion pattern of SP and IP of 16 HIV-infected men with lipodystrophy (LIPO) and 15 HIV-infected men without lipodystrophy (NONLIPO) were studied during an oral glucose tolerance test (OGTT). All patients received HAART. Insulin secretion rates were determined by deconvolution of plasma C-peptide concentrations.

More LIPO than NONLIPO patients displayed diabetes mellitus and impaired glucose tolerance than a normal glucose tolerance (LIPO 2/8/6 vs NONLIPO 1/2/12, P=0.05). LIPO had increased fasting SP, IP, ratio of SP/IP, area under the curve (AUC) of SP and IP during early phase of the OGTT (0, 10, 20 minutes), and AUC-SP and AUC-IP during the late phase of the OGTT (45, 75, 105 minutes), respectively, compared to NONLIPO (Ps<0.05). LIPO exhibited significantly increased fasting SP/IP ratio, fasting SP/insulin ratio and ratios of total proinsulin to C-peptide during the OGTT. LIPO displayed increased incremental secretion of IP during the first 10 minutes of the OGTT (P<0.05), despite the fact that the incremental insulin secretion during this period did not differ between LIPO and NONLIPO.

These data suggest that HIV-infected patients with lipodystrophy display major perturbations of proinsulin secretion in the fasting state and during an OGTT, which is compatible with the notion of a beta-cell dysfunction of such patients.