BOTH INSULIN RESISTANCE AND INSULIN SECRETION ARE INVOLVED IN THE PRE-DIABETES OF ACROMEGALY

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. Aim. To assess the relative role of IR and insulin secretion in the pre-diabetes of acromegaly. Methods. 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. Results. There were 51 subjects with pre-diabetes and 75 subjects with normal glucose tolerance (NOT). 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 OH serum level in pre-diabetes group (r =0.22, p=0.12) but correlated significantly in NOT group (r= 0.5, p<0.001). In contrast, the pre-diabetes group had a lower HOMA-B% index than NOT group (165.4 +/- 15.7 vs 228.5 +/- 29, p<0.001). HOMA-B% did not correlate with nadir OH in both groups. Unadjusted ICI 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 NOT groups regarding age, duration of acromegaly and sex. Conclusions. Our data suggest that reduced basal and stimulated insulin secretion express the failure of beta-cells adaptation to increased OH-induced-insulin resistance and is the pathogenic mechanism of pre-diabetes in acromegaly.