Counterregulatory Hormone and Symptom Responses to Insulin-Induced Hypoglycemia in the Postprandial State in Humans

Abstract

Plasma counterregulatory hormones and symptoms were measured during hypoglycemia in the postprandial and in the fasting state in humans to establish differences in physiological responses. We studied 8 nondiabetic subjects and 10 subjects with type 1 diabetes on two different occasions during clamped insulin-induced hypoglycemia (2.4 mmol/l) in the sitting position. On one occasion, subjects ate a standard mixed meal, and on the other they remained fasting. In response to postprandial as compared with fasting hypoglycemia, nondiabetic subjects exhibited lower total symptom scores (6.6 ± 0.4 vs. 11.5 ± 0.8, P = 0.001), which was due to less hunger (1.1 ± 0.1 vs. 4.2 ± 0.2), lower suppression of plasma C-peptide (0.23 ± 0.1 vs. 0.08 ± 0.07 nmol/l, P = 0.032), and greater responses of plasma glucagon (248 ± 29 vs. 163 ± 25 ng · l−1 · min−1, P = 0.018), plasma adrenaline (4.5 ± 0.6 vs. 3.1 ± 0.4 nmol · l−1 · min−1, P = 0.037), norepinephrine (3.8 ± 0.3 vs. 3.2 ± 0.2 nmol · l−1 · min−1, P = 0.037), and pancreatic polypeptide (217 ± 12 vs. 159 ± 22 pmol · l−1 · min−1, P = 0.08). Except for plasma C-peptide, responses in diabetic subjects were similarly affected. Notably, in diabetic subjects responses of glucagon, which were absent in the fasting state, nearly normalized after a meal. In conclusion, in the postprandial compared with the fasting hypoglycemic state, total symptoms are less, but counterregulatory hormones are greater and responses of glucagon nearly normalize in type 1 diabetic subjects.