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.
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Original Articles|
May 01 1995
Effects of Recent, Short-Term Hyperglycemia on Responses to Hypoglycemia in Humans: Relevance to the Pathogenesis of Hypoglycemia Unawareness and Hyperglycemia-Induced Insulin Resistance
Carmine Fanelli;
Carmine Fanelli
Dipartimento di Medicina Interna e Scienze Endocrine e Metaboliche, Università di Perugia
Perugia, Italy
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Simone Pampanelli;
Simone Pampanelli
Dipartimento di Medicina Interna e Scienze Endocrine e Metaboliche, Università di Perugia
Perugia, Italy
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Stella Calderone;
Stella Calderone
Dipartimento di Medicina Interna e Scienze Endocrine e Metaboliche, Università di Perugia
Perugia, Italy
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Mauro Lepore;
Mauro Lepore
Dipartimento di Medicina Interna e Scienze Endocrine e Metaboliche, Università di Perugia
Perugia, Italy
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Bruno Annibale;
Bruno Annibale
Cattedra di Gastroenterologia, II Clinica Medica, Università La Sapienza
Roma, Italy
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Pietro Compagnucci;
Pietro Compagnucci
Divisione di Medicina, Ospedale Civile di Camerino
Camerino, Italy
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Paolo Brunetti;
Paolo Brunetti
Dipartimento di Medicina Interna e Scienze Endocrine e Metaboliche, Università di Perugia
Perugia, Italy
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Geremia B Bolli
Geremia B Bolli
Dipartimento di Medicina Interna e Scienze Endocrine e Metaboliche, Università di Perugia
Perugia, Italy
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Address correspondence and reprint requests to Dr. Geremia B. Bolli, Di.M.I. S.E.M., Via E. Dal Pozzo, 06126 Perugia, Italy.
Diabetes 1995;44(5):513–519
Article history
Received:
June 07 1994
Revision Received:
January 03 1995
Accepted:
January 03 1995
PubMed:
7729608
Citation
Carmine Fanelli, Simone Pampanelli, Stella Calderone, Mauro Lepore, Bruno Annibale, Pietro Compagnucci, Paolo Brunetti, Geremia B Bolli; Effects of Recent, Short-Term Hyperglycemia on Responses to Hypoglycemia in Humans: Relevance to the Pathogenesis of Hypoglycemia Unawareness and Hyperglycemia-Induced Insulin Resistance. Diabetes 1 May 1995; 44 (5): 513–519. https://doi.org/10.2337/diab.44.5.513
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