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Hyperproinsulinaemia in normoglycaemic lipodystrophic HIV‐infected patients
Author(s) -
Haugaard S. B.,
Andersen O.,
Hales C. N.,
Halsall I.,
Rosenfalck A. M.,
Iversen J.,
Madsbad S.
Publication year - 2006
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2006.01640.x
Subject(s) - human immunodeficiency virus (hiv) , lipodystrophy , medicine , virology , antiretroviral therapy , viral load
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 (NAÏVE)] 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 NAÏVE. 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 β‐cell dysfunction in those patients with insulin resistance and low DI.