Endocrine Abstracts

In acromegalic patients growth hormone (GH) excess induces insulin resistance but whether this is sufficient, in the face of normal insulin secretion, for pre-diabetes (impaired fasting glucose (IFG) and impaired glucose tolerance (IGT)) to occur is a matter of debate.

Aim: To assess the relative role of insulin resistance and insulin secretion in the pre-diabetes of acromegaly.

Methods: One hundred and twenty-four patients with acromegaly (78 women, 46 men, mean age 50±11 years) addmited to our department were included in the study. Plasma glucose, GH and insulin levels were measured basal and 30, 60 and 120 min during a 75 g oral glucose tolerance test (OGTT). Insulin resistance was assessed by HOMA-IR index (fasting plasma glucose (FPG) (mg/dl)*fasting plasma insulin (FPI) (mU/l)/22.5*18). Basal and stimulated insulin secretion was assessed using HOMA-B% index (FPI (mU/l)*20)/(FPG (mg/dl)/18–3.5)) and insulinogenic index (IGI) (Δ insulin(30′–0′) (mU/l)*100/glucose(30′) (mg/dl) respectively. The local Ethic Committee approved the study.

Results: According to ADA criteria, there were 49 subjects with pre-diabetes (30 IFG, 11 IGT and 8 combined glucose intolerance). Seventy-five subjects had normal glucose tolerance (NGT). There were no significant differences between pre-diabetes group and NGT group regarding age (53±13 vs 48.7±11 years, P=NS), sex (53 vs 69.3% women, P=NS) and nadir GH in OGTT (18±17 vs 12.3±17 ng/ml, P=NS). The pre-diabetes group had a significantly higher HOMA-IR index (4.6±3.1 vs 2.6±2.1, P<0.001) and lower HOMA-B% index (159±108 vs 236±257, P=0.02) than NGT group. IGI did not differ between the two groups (39±48 vs 48±43, P=NS) but IGI/HOMA-IR was signifficantly lower in pre-diabetes group (9.7±8 vs 24.5±26, P<0.001). Nadir serum GH correlated with HOMA-IR index (r=0.35, P<0.001) but not with HOMA-B% or IGI.

Conclusions: Our data suggest that reduced basal and stimulated insulin secretion, reflecting the failure of β-cells adaptation to increased, GH-induced insulin resistance, leads to pre-diabetes in acromegaly.