January - March 2010, Volume 6, Issue 1

Niculescu DA, Purice M, Lichiardopol R, Coculescu M

Both insulin resistance and insulin secretion are involved in the pre-diabetes of acromegaly

Acta Endo (Buc) 2010, 6 (1): 35-42
doi: 10.4183/aeb.2010.35

In acromegalic patients growth hormone (GH) excess induces insulin resistance (IR) but whether this is sufficient for pre-diabetes to occur is a matter of debate.\r\nAim. To assess the relative role of IR and insulin secretion in the pre-diabetes of acromegaly.\r\nMethods. 126 patients with acromegaly (79 women, 47 men) were included. Plasma glucose, GH and insulin levels were measured basal and 30, 60 and 120 minutes during a 75 g oral glucose tolerance test (OGTT). Basal and stimulated IR was assessed by homeostasis model assessment (HOMA), insulin resistance index (HOMA-IR) and insulin sensitivity index (ISI) derived from OGTT (OGTTISI) respectively. Basal and stimulated insulin secretion was assessed using HOMA-B% index and insulinogenic index (IGI), respectively. The local Ethic Committee approved the study.\r\nResults. There were 51 subjects with pre-diabetes and 75 subjects with normal glucose tolerance (NGT). Pre-diabetes group had a significantly higher HOMA-IR index (4.8?3.3 vs 2.5?1.6, p<0.001) and nadir GH in OGTT (9.4 (4.3, 22.2) vs. 4.8 (2.2, 14.5) ng/mL, p=0.02) than NGT group. HOMA-IR did not correlate with nadir GH serum level in pre-diabetes group (r =0.22, p=0.12) but correlated significantly in NGT group (r= 0.5, p<0.001). In contrast, the pre-diabetes group had a lower HOMA-B% index than NGT group (165.4?15.7 vs 228.5?29, p<0.001). HOMA-B% did not correlate with nadir GH in both groups. Unadjusted IGI did not differ between the two groups (0.40?0.07 vs. 0.48?0.05, p=0.34) but became statistically significant after adjusting for both basal IR (HOMA-IR) (0.31?0.06 vs. 0.54?0.05, p=0.01) and stimulated IR (OGTTISI) (0.30?0.06 vs. 0.54?0.05, p=0.005). There were no significant differences between pre-diabetes and NGT groups regarding age, duration of acromegaly and sex.\r\nConclusions. Our data suggest that reduced basal and stimulated insulin secretion express the failure of &#946;-cells adaptation to increased GH-induced-insulin resistance and is the pathogenic mechanism of pre-diabetes in acromegaly.

Keywords: acromegaly, insulin resistance, insulin secretion, pre-diabetes

Correspondence: M. Coculescu, &#8220;Carol Davila&#8221; University - Dpt. of Endocrinology, &#8220;C.I. Parhon&#8221; National Institute of Endocrinology, 34-36 Aviatorilor Bvd, Bucharest 011863, Romania\r\nE - mail: m.coculescu@uni-davila.ro, Fax: +4021 3198718