Effects of recent, short-term hyperglycemia on responses to hypoglycemia in humans. Relevance to the pathogenesis of hypoglycemia unawareness and hyperglycemia-induced insulin resistance.
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 approximately 13.5 mmol/l) or euglycemia (PG approximately 5 mmol/l) between 1600 and 2200 the previous day (glucose and insulin infused on both occasions), as well as after nocturnal hyperglycemia (PG approximately 13.5 mmol/l) or euglycemia between 2300 and 0500. The IDDM patients were studied after 15 h of euglycemia or hyperglycemia (approximately 17 mmol/l) but identical hyperinsulinemia (approximately 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 mumol.kg-1.min-1, IDDM patients 33 +/- 3.1 vs. 42.5 +/- 3.9 mumol.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.(ABSTRACT TRUNCATED AT 250 WORDS)
Fanelli
C
C
Dipartimento di Medicina Interna e Scienze Endocrine e Metaboliche, Università di Perugia, Italy.
Pampanelli
S
S
Calderone
S
S
Lepore
M
M
Annibale
B
B
Compagnucci
P
P
Brunetti
P
P
Bolli
G B
GB
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007003:Hypoglycemia / Q000150:complications / Q000209:etiology / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin