Recovery of epinephrine response but not hypoglycemic symptom threshold after intensive therapy in type 1 diabetes

Maris Davis, Michael Mellman, Seth Friedman, Chee Jen Chang, Harry Shamoon

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

purpose: Patients with intensively treated insulin-dependent diabetes mellitus (IDDM) exhibit more severe defects in counterregulatory hormone secretion and symptom recognition during hypoglycemia than do conventionally treated patients. In this prospective study in patients with preexisting defects in counterregulation, we examined the induction and reversibility of impaired symptomatic and adrenomedullary responses to hypoglycemia in 5 patients with IDDM (diabetes duration of 2 to 16 years; aged 19 to 36 years; 3 women, 2 men) who were receiving intensive therapy. methods: Counterregulatory responses were assessed by using a single-step (∼2.8 mmol/L plasma glucose) and multiple-step (from ∼5 mmol/L to 2.2 mmol/L plasma glucose) clamped hypoglycemia procedure. Patients were first studied after a stable period of conventional insulin therapy (glycosylated hemoglobin [HbA1c] 9.5 ± 1.2%), then after 3 to 5 months of intensive therapy (HbA1c 6.6 ± 0.2%), and a third time after resuming conventional therapy (HbA1c 8.7 ± 0.9%). results: Intensive therapy was associated with a 44% decline (P <0.01) in the average plasma epinephrine increase during hypoglycemia, and the plasma glucose level required to stimulate epinephrine secretion fell from 3.7 ± 0.2 to 3.0 ± 0.1 mmol/L (P <0.01). The threshold, but not the magnitude, of the plasma norepinephrine response was similarly altered. Hypoglycemic symptoms also decreased in intensity (by 67%, P <0.01), and the glucose level required for symptom activation fell from 3.4 ± 0.3 to 2.7 ± 0.2 mmol/L, P <0.01). When conventional therapy was resumed, the abnormalities in the epinephrine response due to intensive therapy were almost completely reversed. However, the reduction in symptoms and the altered thresholds for plasma norepinephrine were not reversed. conclusions: There is dissociation between the treatment-associated defects in hypoglycemia counterregulation in IDDM, and an increase in average glycemia produced by a return to conventional insulin therapy is not sufficient to reverse hypoglycemia unawareness worsened by intensive therapy.

Original languageEnglish (US)
Pages (from-to)535-542
Number of pages8
JournalThe American journal of medicine
Volume97
Issue number6
DOIs
StatePublished - 1994
Externally publishedYes

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Type 1 Diabetes Mellitus
Hypoglycemic Agents
Epinephrine
Hypoglycemia
Therapeutics
Glucose
Norepinephrine
Insulin
Glycosylated Hemoglobin A
Hormones
Prospective Studies

ASJC Scopus subject areas

  • Nursing(all)

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Recovery of epinephrine response but not hypoglycemic symptom threshold after intensive therapy in type 1 diabetes. / Davis, Maris; Mellman, Michael; Friedman, Seth; Chang, Chee Jen; Shamoon, Harry.

In: The American journal of medicine, Vol. 97, No. 6, 1994, p. 535-542.

Research output: Contribution to journalArticle

Davis, Maris ; Mellman, Michael ; Friedman, Seth ; Chang, Chee Jen ; Shamoon, Harry. / Recovery of epinephrine response but not hypoglycemic symptom threshold after intensive therapy in type 1 diabetes. In: The American journal of medicine. 1994 ; Vol. 97, No. 6. pp. 535-542.
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title = "Recovery of epinephrine response but not hypoglycemic symptom threshold after intensive therapy in type 1 diabetes",
abstract = "purpose: Patients with intensively treated insulin-dependent diabetes mellitus (IDDM) exhibit more severe defects in counterregulatory hormone secretion and symptom recognition during hypoglycemia than do conventionally treated patients. In this prospective study in patients with preexisting defects in counterregulation, we examined the induction and reversibility of impaired symptomatic and adrenomedullary responses to hypoglycemia in 5 patients with IDDM (diabetes duration of 2 to 16 years; aged 19 to 36 years; 3 women, 2 men) who were receiving intensive therapy. methods: Counterregulatory responses were assessed by using a single-step (∼2.8 mmol/L plasma glucose) and multiple-step (from ∼5 mmol/L to 2.2 mmol/L plasma glucose) clamped hypoglycemia procedure. Patients were first studied after a stable period of conventional insulin therapy (glycosylated hemoglobin [HbA1c] 9.5 ± 1.2{\%}), then after 3 to 5 months of intensive therapy (HbA1c 6.6 ± 0.2{\%}), and a third time after resuming conventional therapy (HbA1c 8.7 ± 0.9{\%}). results: Intensive therapy was associated with a 44{\%} decline (P <0.01) in the average plasma epinephrine increase during hypoglycemia, and the plasma glucose level required to stimulate epinephrine secretion fell from 3.7 ± 0.2 to 3.0 ± 0.1 mmol/L (P <0.01). The threshold, but not the magnitude, of the plasma norepinephrine response was similarly altered. Hypoglycemic symptoms also decreased in intensity (by 67{\%}, P <0.01), and the glucose level required for symptom activation fell from 3.4 ± 0.3 to 2.7 ± 0.2 mmol/L, P <0.01). When conventional therapy was resumed, the abnormalities in the epinephrine response due to intensive therapy were almost completely reversed. However, the reduction in symptoms and the altered thresholds for plasma norepinephrine were not reversed. conclusions: There is dissociation between the treatment-associated defects in hypoglycemia counterregulation in IDDM, and an increase in average glycemia produced by a return to conventional insulin therapy is not sufficient to reverse hypoglycemia unawareness worsened by intensive therapy.",
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N2 - purpose: Patients with intensively treated insulin-dependent diabetes mellitus (IDDM) exhibit more severe defects in counterregulatory hormone secretion and symptom recognition during hypoglycemia than do conventionally treated patients. In this prospective study in patients with preexisting defects in counterregulation, we examined the induction and reversibility of impaired symptomatic and adrenomedullary responses to hypoglycemia in 5 patients with IDDM (diabetes duration of 2 to 16 years; aged 19 to 36 years; 3 women, 2 men) who were receiving intensive therapy. methods: Counterregulatory responses were assessed by using a single-step (∼2.8 mmol/L plasma glucose) and multiple-step (from ∼5 mmol/L to 2.2 mmol/L plasma glucose) clamped hypoglycemia procedure. Patients were first studied after a stable period of conventional insulin therapy (glycosylated hemoglobin [HbA1c] 9.5 ± 1.2%), then after 3 to 5 months of intensive therapy (HbA1c 6.6 ± 0.2%), and a third time after resuming conventional therapy (HbA1c 8.7 ± 0.9%). results: Intensive therapy was associated with a 44% decline (P <0.01) in the average plasma epinephrine increase during hypoglycemia, and the plasma glucose level required to stimulate epinephrine secretion fell from 3.7 ± 0.2 to 3.0 ± 0.1 mmol/L (P <0.01). The threshold, but not the magnitude, of the plasma norepinephrine response was similarly altered. Hypoglycemic symptoms also decreased in intensity (by 67%, P <0.01), and the glucose level required for symptom activation fell from 3.4 ± 0.3 to 2.7 ± 0.2 mmol/L, P <0.01). When conventional therapy was resumed, the abnormalities in the epinephrine response due to intensive therapy were almost completely reversed. However, the reduction in symptoms and the altered thresholds for plasma norepinephrine were not reversed. conclusions: There is dissociation between the treatment-associated defects in hypoglycemia counterregulation in IDDM, and an increase in average glycemia produced by a return to conventional insulin therapy is not sufficient to reverse hypoglycemia unawareness worsened by intensive therapy.

AB - purpose: Patients with intensively treated insulin-dependent diabetes mellitus (IDDM) exhibit more severe defects in counterregulatory hormone secretion and symptom recognition during hypoglycemia than do conventionally treated patients. In this prospective study in patients with preexisting defects in counterregulation, we examined the induction and reversibility of impaired symptomatic and adrenomedullary responses to hypoglycemia in 5 patients with IDDM (diabetes duration of 2 to 16 years; aged 19 to 36 years; 3 women, 2 men) who were receiving intensive therapy. methods: Counterregulatory responses were assessed by using a single-step (∼2.8 mmol/L plasma glucose) and multiple-step (from ∼5 mmol/L to 2.2 mmol/L plasma glucose) clamped hypoglycemia procedure. Patients were first studied after a stable period of conventional insulin therapy (glycosylated hemoglobin [HbA1c] 9.5 ± 1.2%), then after 3 to 5 months of intensive therapy (HbA1c 6.6 ± 0.2%), and a third time after resuming conventional therapy (HbA1c 8.7 ± 0.9%). results: Intensive therapy was associated with a 44% decline (P <0.01) in the average plasma epinephrine increase during hypoglycemia, and the plasma glucose level required to stimulate epinephrine secretion fell from 3.7 ± 0.2 to 3.0 ± 0.1 mmol/L (P <0.01). The threshold, but not the magnitude, of the plasma norepinephrine response was similarly altered. Hypoglycemic symptoms also decreased in intensity (by 67%, P <0.01), and the glucose level required for symptom activation fell from 3.4 ± 0.3 to 2.7 ± 0.2 mmol/L, P <0.01). When conventional therapy was resumed, the abnormalities in the epinephrine response due to intensive therapy were almost completely reversed. However, the reduction in symptoms and the altered thresholds for plasma norepinephrine were not reversed. conclusions: There is dissociation between the treatment-associated defects in hypoglycemia counterregulation in IDDM, and an increase in average glycemia produced by a return to conventional insulin therapy is not sufficient to reverse hypoglycemia unawareness worsened by intensive therapy.

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