Physiological responses during hypoglycaemia induced by regular human insulin or a novel human analogue, insulin glargine

Samuel Dagogo-Jack, H. Askari, B. Morrill, L. L. Lehner, B. Kim, X. Sha

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Aim: Glargine, a product of recombinant technology, has different structural and physico-chemical properties compared with native human insulin. We determined whether such differences are associated with alterations in the responses to hypoglycaemia induced by glargine. Methods: Nineteen adults (six healthy and 13 with type 1 diabetes) underwent a 5-h hyperinsulinaemic (2 mU/kg/min-1) stepped hypoglycaemic clamps (hourly targets of 4.7, 4.2, 3.6, 3.1 and 2.5 mmol/l, respectively) on two occasions using intravenous infusion of regular human insulin or glargine, in random sequence. Hypoglycaemic symptoms, counter-regulatory hormones and glucose disposal rates were assessed at intervals throughout the clamps. A 1-week 'wash out' period was observed between studies. Results: The peak total symptoms scores (mean ± s.e.m.) at nadir blood glucose (2.5 mmol/l) were 18.83 ± 2.68 (healthy) and 17.46 ± 3.62 (diabetic) during regular insulin, and 18.50 ± 3.20 (healthy) and 19.08 ± 3.83 (diabetic) during glargine infusion. The peak epinephrine levels during hypoglycaemia were 767.8 ± 140.4 pg/ml (regular insulin) and 608.8 ± 129.9 pg/ml (glargine) among healthy subjects, and 332.5 ± 54.8 pg/ml (regular insulin) and 321.8 ± 67.4 pg/ml (glargine) in diabetic patients. Diabetic patients had blunted glucagon responses during hypoglycaemia with either insulin. Both insulins also elicited similar rates of glucose disposal. Conclusions: We conclude that insulin glargine and regular human insulin elicit comparable symptomatic and counter-regulatory hormonal responses during hypoglycaemia in healthy or diabetic subjects, and induce similar rates of glucose disposal. Since glargine is designed for subcutaneous (s.c.) use, it is possible (though unlikely) that our findings obtained using an intravenous protocol could differ from responses to hypoglycaemia induced by the s.c. route.

Original languageEnglish (US)
Pages (from-to)373-383
Number of pages11
JournalDiabetes, Obesity and Metabolism
Volume2
Issue number6
DOIs
StatePublished - Jan 1 2000

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Insulin, Regular, Human
Hypoglycemia
Insulin
Hypoglycemic Agents
Glucose
Insulins
Insulin Glargine
Glucagon
Type 1 Diabetes Mellitus
Population Groups
Intravenous Infusions
Epinephrine
Blood Glucose
Healthy Volunteers
Hormones
Technology

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Physiological responses during hypoglycaemia induced by regular human insulin or a novel human analogue, insulin glargine. / Dagogo-Jack, Samuel; Askari, H.; Morrill, B.; Lehner, L. L.; Kim, B.; Sha, X.

In: Diabetes, Obesity and Metabolism, Vol. 2, No. 6, 01.01.2000, p. 373-383.

Research output: Contribution to journalArticle

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abstract = "Aim: Glargine, a product of recombinant technology, has different structural and physico-chemical properties compared with native human insulin. We determined whether such differences are associated with alterations in the responses to hypoglycaemia induced by glargine. Methods: Nineteen adults (six healthy and 13 with type 1 diabetes) underwent a 5-h hyperinsulinaemic (2 mU/kg/min-1) stepped hypoglycaemic clamps (hourly targets of 4.7, 4.2, 3.6, 3.1 and 2.5 mmol/l, respectively) on two occasions using intravenous infusion of regular human insulin or glargine, in random sequence. Hypoglycaemic symptoms, counter-regulatory hormones and glucose disposal rates were assessed at intervals throughout the clamps. A 1-week 'wash out' period was observed between studies. Results: The peak total symptoms scores (mean ± s.e.m.) at nadir blood glucose (2.5 mmol/l) were 18.83 ± 2.68 (healthy) and 17.46 ± 3.62 (diabetic) during regular insulin, and 18.50 ± 3.20 (healthy) and 19.08 ± 3.83 (diabetic) during glargine infusion. The peak epinephrine levels during hypoglycaemia were 767.8 ± 140.4 pg/ml (regular insulin) and 608.8 ± 129.9 pg/ml (glargine) among healthy subjects, and 332.5 ± 54.8 pg/ml (regular insulin) and 321.8 ± 67.4 pg/ml (glargine) in diabetic patients. Diabetic patients had blunted glucagon responses during hypoglycaemia with either insulin. Both insulins also elicited similar rates of glucose disposal. Conclusions: We conclude that insulin glargine and regular human insulin elicit comparable symptomatic and counter-regulatory hormonal responses during hypoglycaemia in healthy or diabetic subjects, and induce similar rates of glucose disposal. Since glargine is designed for subcutaneous (s.c.) use, it is possible (though unlikely) that our findings obtained using an intravenous protocol could differ from responses to hypoglycaemia induced by the s.c. route.",
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T1 - Physiological responses during hypoglycaemia induced by regular human insulin or a novel human analogue, insulin glargine

AU - Dagogo-Jack, Samuel

AU - Askari, H.

AU - Morrill, B.

AU - Lehner, L. L.

AU - Kim, B.

AU - Sha, X.

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Aim: Glargine, a product of recombinant technology, has different structural and physico-chemical properties compared with native human insulin. We determined whether such differences are associated with alterations in the responses to hypoglycaemia induced by glargine. Methods: Nineteen adults (six healthy and 13 with type 1 diabetes) underwent a 5-h hyperinsulinaemic (2 mU/kg/min-1) stepped hypoglycaemic clamps (hourly targets of 4.7, 4.2, 3.6, 3.1 and 2.5 mmol/l, respectively) on two occasions using intravenous infusion of regular human insulin or glargine, in random sequence. Hypoglycaemic symptoms, counter-regulatory hormones and glucose disposal rates were assessed at intervals throughout the clamps. A 1-week 'wash out' period was observed between studies. Results: The peak total symptoms scores (mean ± s.e.m.) at nadir blood glucose (2.5 mmol/l) were 18.83 ± 2.68 (healthy) and 17.46 ± 3.62 (diabetic) during regular insulin, and 18.50 ± 3.20 (healthy) and 19.08 ± 3.83 (diabetic) during glargine infusion. The peak epinephrine levels during hypoglycaemia were 767.8 ± 140.4 pg/ml (regular insulin) and 608.8 ± 129.9 pg/ml (glargine) among healthy subjects, and 332.5 ± 54.8 pg/ml (regular insulin) and 321.8 ± 67.4 pg/ml (glargine) in diabetic patients. Diabetic patients had blunted glucagon responses during hypoglycaemia with either insulin. Both insulins also elicited similar rates of glucose disposal. Conclusions: We conclude that insulin glargine and regular human insulin elicit comparable symptomatic and counter-regulatory hormonal responses during hypoglycaemia in healthy or diabetic subjects, and induce similar rates of glucose disposal. Since glargine is designed for subcutaneous (s.c.) use, it is possible (though unlikely) that our findings obtained using an intravenous protocol could differ from responses to hypoglycaemia induced by the s.c. route.

AB - Aim: Glargine, a product of recombinant technology, has different structural and physico-chemical properties compared with native human insulin. We determined whether such differences are associated with alterations in the responses to hypoglycaemia induced by glargine. Methods: Nineteen adults (six healthy and 13 with type 1 diabetes) underwent a 5-h hyperinsulinaemic (2 mU/kg/min-1) stepped hypoglycaemic clamps (hourly targets of 4.7, 4.2, 3.6, 3.1 and 2.5 mmol/l, respectively) on two occasions using intravenous infusion of regular human insulin or glargine, in random sequence. Hypoglycaemic symptoms, counter-regulatory hormones and glucose disposal rates were assessed at intervals throughout the clamps. A 1-week 'wash out' period was observed between studies. Results: The peak total symptoms scores (mean ± s.e.m.) at nadir blood glucose (2.5 mmol/l) were 18.83 ± 2.68 (healthy) and 17.46 ± 3.62 (diabetic) during regular insulin, and 18.50 ± 3.20 (healthy) and 19.08 ± 3.83 (diabetic) during glargine infusion. The peak epinephrine levels during hypoglycaemia were 767.8 ± 140.4 pg/ml (regular insulin) and 608.8 ± 129.9 pg/ml (glargine) among healthy subjects, and 332.5 ± 54.8 pg/ml (regular insulin) and 321.8 ± 67.4 pg/ml (glargine) in diabetic patients. Diabetic patients had blunted glucagon responses during hypoglycaemia with either insulin. Both insulins also elicited similar rates of glucose disposal. Conclusions: We conclude that insulin glargine and regular human insulin elicit comparable symptomatic and counter-regulatory hormonal responses during hypoglycaemia in healthy or diabetic subjects, and induce similar rates of glucose disposal. Since glargine is designed for subcutaneous (s.c.) use, it is possible (though unlikely) that our findings obtained using an intravenous protocol could differ from responses to hypoglycaemia induced by the s.c. route.

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