Hyperproinsulinaemia in Normoglycaemic Lipodystrophic Hiv-infected Patients.
From: Department of Endocrinology and Internal Medicine, Hvidovre University Hospital, Copenhagen, Denmark. sbhau@dadlnet.dk
European journal of clinical investigation
- Publish Date: Jun 2006
- ISSN: 0014-2972
- Volume: 36
- Issue: 6
- Pages: 436-45
- Medium: Print
- Language: English
- Citation (JAMA): Haugaard S B, Andersen O, Hales C N, et al. Hyperproinsulinaemia in Normoglycaemic Lipodystrophic Hiv-infected Patients.. Eur. J. Clin. Invest. Jun 2006;36:436-45
Abstract
BACKGROUND: We aimed to investigate whether the insulin precursors, intact (IP) and 32-33 split proinsulin (SP), which are elevated in states of insulin resistance and predict type 2 diabetes, would be elevated in human immunodeficiency virus (HIV)-infected patients with lipodystrophy (LIPO). MATERIALS AND METHODS: Forty-three normoglycaemic HIV-infected patients [18 LIPO and 18 without lipodystrophy (NONLIPO) receiving antiretroviral drugs, and seven patients naïve to antiretroviral drugs (NAIVE)] were examined. Insulin precursors were measured during fasting, during an intravenous glucose tolerance test and during a hyperinsulinaemic-euglycaemic clamp, respectively. Insulin secretion rates (ISR) were determined by deconvolution of C-peptide concentrations. Disposition index (DI) was calculated as insulin sensitivity (Si(RD)) multiplied by the first-phase insulin response to intravenous glucose. RESULTS: LIPO exhibited increased fasting IP and SP (P < 0.05), a higher proportion of elevated fasting IP (3.1 pmol L(-1), 66% vs. 33% and 28%, P < 0.05) and SP (7.2 pmol L(-1), 50%, 11% and 0%, P < 0.01), reduced Si(RD) (> 50%, P < 0.001) and increased ISR (P < 0.001) compared with NONLIPO and NAIVE. Fasting SP and IP correlated positively with ISR (P < 0.001) and inversely and hyperbolically with Si(RD) (P < 0.001). Fasting SP/insulin ratio correlated inversely with Si(RD) (P < 0.05). Incremental IP + SP/insulin ratio after an intravenous glucose bolus correlated inversely with DI (P < 0.01), but did not differ between study groups. CONCLUSIONS: Proinsulin appeared to be increased in HIV-lipodystrophy, but no more than caused by the increased ISR. Nevertheless, the inverse correlations between SP/insulin ratio versus Si(RD) and incremental total proinsulin/insulin ratio versus DI may argue for a subtle beta-cell dysfunction in those patients with insulin resistance and low DI.
Mesh Headings (Keywords): Adult, Antiretroviral Therapy, Highly Active, Blood Glucose, Body Composition, C-Peptide, Fasting, Glucose Tolerance Test, HIV Infections, HIV-1, HIV-Associated Lipodystrophy Syndrome, Humans, Hyperlipidemias, Insulin, Insulin Resistance, Male, Middle Aged, Proinsulin
Check for Full Text / PubMed Unique Identifier (PMID): 16684128
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