PROLACTIN AND BETA-ENDORPHIN RESPONSES TO HYPOGLYCEMIA ARE REDUCED INWELL-CONTROLLED INSULIN-DEPENDENT DIABETES-MELLITUS

Several pituitary hormones, including corticotropin (ACTH), growth hor mone (GH), prolactin, and B-endorphin (but not thyrotropin, follicle-s timulating hormone, dr luteinizing hormone), are released in response to hypoglycemia in normal subjects. In patients with insulin-dependent diabetes mellitus (IDDM), the degree of glycemic control is known to alter ACTH and GH responses to hypoglycemia. The current study was per formed to examine the effect of glycemic control on prolactin and B-en dorphin responses to hypoglycemia in subjects with IDDM. We performed 8-hour stepped hypoglycemic-hyperinsulinemic clamp studies (12 pmol/kg /min) during which plasma glucose was decreased from 5.0 mmol/L to 2.2 mmol/L in steps of 0.6 mmol/L every 30 minutes in 20 subjects with un complicated IDDM (12 males and eight females; age, 26 +/- 2 years; IDD M duration, 10 +/- 1 years; body mass index, 23.6 +/- 0.6 kg/m(2)) and 10 healthy subjects (five males and five females aged 30 +/- 1 years) . The 10 diabetic subjects in good glycemic control (mean hemoglobin A (1) [HbA(1)], 7.5% +/- 0.3%; normal range, 5.4% to 7.4%) were compared with the 10 poorly controlled patients (mean HbA(1), 12.6% +/- 0.5%; P <.001 v well-controlled diabetic group). During hypoglycemia, prolac tin levels in the well-controlled diabetic group did not change (7 +/- I mu g/L at plasma glucose 5.0 mmol/L to 9 +/- 2 mu g/L at plasma glu cose 2.2 mmol/L), whereas prolactin levers increased markedly in the p oorly controlled diabetic group (7 +/- 2 mu g/L to 44 +/- 17 mu g/L) a nd healthy volunteers (12 +/- 2 mu g/L to 60 +/- 19 mu g/L, P <.05 bet ween IDDM groups). The plasma glucose threshold required for stimulati on of prolactin secretion was 2.2 +/- 0.1 mmol/L in well-controlled ID DM, 3.0 +/- 0.4 mmol/L in poorly controlled IDDM, and 2.4 +/- 0.1 mmol /L in healthy subjects (P <.05 between IDDM groups). Responses in male s and females were similar. The increase in beta-endorphin levels was also attenuated in well-controlled IDDM patients (4 +/- 1 mu mol/L at plasma glucose 5.0 mmol/L to 11 +/- 4 pmol/L at plasma glucose 2.2 mmo l/L) versus poorly controlled IDDM patients (5 +/- 1 pmol/L to 26 +/- 7 pmol/L) and healthy subjects (8 +/- 1 pmol/L to 56 +/- 13 pmol/L). T he plasma glucose threshold required for stimulation of beta-endorphin release was again lower in well-controlled IDDM versus poorly control led IDDM patients (2.2 +/- 0.1 v 3.0 +/- 0.3 mmol/L) and healthy subje cts (2.5 +/- 0.4 mmol/L,P <.05 between IDDM groups). In conclusion, pr olactin and beta-endorphin responses to a standardized hypoglycemic st imulus (plasma glucose, 2.2 mmol/L) are reduced and plasma glucose lev els required to stimulate release of prolactin and beta-endorphin are lower in well-controlled IDDM compared with poorly controlled IDDM and healthy subjects. Thus, stress hormones not previously considered to have a primary role in plasma glucose recovery from hypoglycemia are a ffected by glycemic control, suggesting a more generalized alteration of hypothalamic-pituitary responses to hypoglycemia in IDDM patients w ith strict glycemic control. Copyright (C) 1996 by W.B. Saunders Compa ny