A single episode of recent hypoglycemia increases, whereas long-term hyperglycemia decreases, the glycemic thresholds of responses of counterregulatory hormone and symptoms to subsequent hypoglycemia in humans. To assess whether short-term, antecedent hyperglycemia exerts effects opposite to those observed after acute hypoglycemia, seven normal, nondiabetic subjects and eight insulin-dependent diabetes mellitus (IDDM) patients were studied during hyperinsulinemic-hypoglycemic clamp (sequential, 90-min plateaus of plasma glucose [PG] of 4.3, 3.7, 3.0, and 2.4 mmol/l). Nondiabetic subjects were studied the morning after either 6-h clamped hyperglycemia (PG ∼ 13.5 mmol/l) or euglycemia (PG ∼5 mmol/l) between 1600 and 2200 the previous day (glucose and insulin infused on both occasions), as well as after nocturnal hyperglycemia (PG ∼ 13.5 mmol/l) or euglycemia between 2300 and 0500. The IDDM patients were studied after 15 h of euglycemia or hyperglycemia (∼ 17 mmol/l) but identical hyperinsulinemia (∼ 225 pmol/l) between 1600 and 0700. Neither PG thresholds of counterregulatory hormone, symptoms, onset of cognitive dysfunction to hypoglycemia, nor maximal responses were affected by antecedent, short-term hyperglycemia in normal nondiabetic subjects and IDDM patients (NS). However, the rate of glucose infusion required to maintain hypoglycemic plateaus during hypoglycemia was lower after hyperglycemia (nondiabetic subjects 31.2 ± 3.4 vs. 36.7 ± 4 ³mol · kg−1·min−1, IDDM patients 33 ± 3.1 vs. 42.5 ± 3.9 ³mol · kg−1 · min−1; P < 0.05) indicating greater insulin resistance induced by antecedent hyperglycemia. In conclusion, in contrast to acute hypoglycemia and long-term hyperglycemia, recent, short-term hyperglycemia does not affect physiological responses to hypoglycemia. However, recent, short-term hyperglycemia induces insulin resistance that contributes to glucose counterregulation. This is relevant to IDDM patients who have deficient glucagon and adrenaline responses to hypoglycemia.

This content is only available via PDF.