Insulin resistance and insulin secretion in non-diabetic acromegalic patients

Insulin resistance (IR) can be induced by high amounts of growth hormone (GH).

To set up, in acromegaly without diabetes mellitus, a correlation between the disease activity in GH-secreting adenoma (AA) - assessed by minimum GH serum level during an oral glucose tolerance test (OGTT) - and severity of insulin resistance (IR), assessed by HOMA-IR index.

75 out of 88 consecutive patients with acromegaly hospitalized in our department were included in this study. 13 patients proved to have diabetes mellitus and were excluded. Serum glucose, GH and insulin levels were measured by immunoradiometricassay basal and at 30, 60 and 120 minutes after a 75 g OGTT in 88 patients with active or cured acromegaly. IR was assessed using HOMA-IR index (Homa-IR=basal serum glucose (mg/dl) x basal serum insulin (mU/L)/22.5 x 18). A value over 2.5 was considered indicating IR.

Out of 75 patients without diabetes mellitus, 36 subjects (48%) were presenting with IR (34 with active disease, 2 cured). We found a significant positive correlation (r=0.56, p<0.001) between AA and HOMA-IR. The GH minimal level corresponding to the intersection of the exponential regression curve with the HOMA-IR level of 2.5 was 8.8 ng/mL, a cut-off point indicating IR with 82% specificity and 78% sensitivity. The odds ratio for developing IR becomes significant at a minimum GH level during OGTT of 2 ng/mL (odds ratio 7.6, 95% confidence interval 2-29).

The severity of IR revealed by acromegaly correlates with GH production. A GH serum level higher than 2 ng/mL during OGTT indicates an increased risk for developing IR. This cut-off level of GH can be used as one of criteria of cured disease, regarding the lack of metabolic effects.