A human randomized controlled trial comparing metabolic responses to single and repeated hypoglycemia in type 1 diabetes

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A human randomized controlled trial comparing metabolic responses to single and repeated hypoglycemia in type 1 diabetes. / Bengtsen, Mads Bisgaard; Støy, Julie; Rittig, Nikolaj Fibiger et al.

I: The Journal of clinical endocrinology and metabolism, Bind 105, Nr. 12, dgaa645, 12.2020.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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Bengtsen MB, Støy J, Rittig NF, Voss TS, Magnusson NE, Svart MV et al. A human randomized controlled trial comparing metabolic responses to single and repeated hypoglycemia in type 1 diabetes. The Journal of clinical endocrinology and metabolism. 2020 dec.;105(12):dgaa645. doi: 10.1210/clinem/dgaa645

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@article{89fa3268d0454c3a8719e70b29757d30,
title = "A human randomized controlled trial comparing metabolic responses to single and repeated hypoglycemia in type 1 diabetes",
abstract = "AIMS: Hypoglycemia hinders optimal glycemic management in type 1 diabetes (T1D). Long diabetes duration and hypoglycemia impair hormonal counterregulatory responses to hypoglycemia. Our study was designed to test whether i) the metabolic responses and insulin sensitivity are impaired, and ii) affected by short-lived antecedent hypoglycemia in participants with T1D.MATERIALS AND METHODS: In a randomized, crossover, 2x2-factorial design, nine male participants with T1D and nine comparable control participants underwent 30 min hypoglycemia (p-glucose<2.9mmol/L) followed by a euglycemic clamp on two separate interventions: with and without 30 min hypoglycemia the day before the study day.RESULTS: During both interventions: insulin sensitivity was consistently lower, while counterregulatory hormones were reduced with 75% lower glucagon and 50% lower epinephrine during hypoglycemia in participants with T1D, who also displayed 40% lower lactate and 5-10-fold increased ketone bodies concentrations following hypoglycemia, whereas palmitate and glucose turnover, forearm glucose uptake and substrate oxidation did not differ between the groups. In participants with T1D, adipose tissue PTEN content, HSL phosphorylation and muscle GLUT4 content were decreased compared with controls. An antecedent hypoglycemic episodes lasting 30 minutes did not affect counter-regulation or insulin sensitivity.CONCLUSIONS: Participants with T1D displayed insulin resistance, and impaired hormonal counter-regulation during hypoglycemia, whereas glucose and fatty acid fluxes were intact, and ketogenic responses amplified. We observed subtle alterations of intracellular signaling, and no effect of short-lived antecedent hypoglycemia on subsequent counter-regulation. This plausibly reflects the presence of insulin resistance, and implies that T1D is a condition with defective hormonal but preserved metabolic responsiveness to short-lived hypoglycemia.",
author = "Bengtsen, {Mads Bisgaard} and Julie St{\o}y and Rittig, {Nikolaj Fibiger} and Voss, {Thomas Schmidt} and Magnusson, {Nils Erik} and Svart, {Mads Vadsted} and Niels Jessen and Niels M{\o}ller",
note = "{\textcopyright} Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.",
year = "2020",
month = dec,
doi = "10.1210/clinem/dgaa645",
language = "English",
volume = "105",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Oxford University Press",
number = "12",

}

RIS

TY - JOUR

T1 - A human randomized controlled trial comparing metabolic responses to single and repeated hypoglycemia in type 1 diabetes

AU - Bengtsen, Mads Bisgaard

AU - Støy, Julie

AU - Rittig, Nikolaj Fibiger

AU - Voss, Thomas Schmidt

AU - Magnusson, Nils Erik

AU - Svart, Mads Vadsted

AU - Jessen, Niels

AU - Møller, Niels

N1 - © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2020/12

Y1 - 2020/12

N2 - AIMS: Hypoglycemia hinders optimal glycemic management in type 1 diabetes (T1D). Long diabetes duration and hypoglycemia impair hormonal counterregulatory responses to hypoglycemia. Our study was designed to test whether i) the metabolic responses and insulin sensitivity are impaired, and ii) affected by short-lived antecedent hypoglycemia in participants with T1D.MATERIALS AND METHODS: In a randomized, crossover, 2x2-factorial design, nine male participants with T1D and nine comparable control participants underwent 30 min hypoglycemia (p-glucose<2.9mmol/L) followed by a euglycemic clamp on two separate interventions: with and without 30 min hypoglycemia the day before the study day.RESULTS: During both interventions: insulin sensitivity was consistently lower, while counterregulatory hormones were reduced with 75% lower glucagon and 50% lower epinephrine during hypoglycemia in participants with T1D, who also displayed 40% lower lactate and 5-10-fold increased ketone bodies concentrations following hypoglycemia, whereas palmitate and glucose turnover, forearm glucose uptake and substrate oxidation did not differ between the groups. In participants with T1D, adipose tissue PTEN content, HSL phosphorylation and muscle GLUT4 content were decreased compared with controls. An antecedent hypoglycemic episodes lasting 30 minutes did not affect counter-regulation or insulin sensitivity.CONCLUSIONS: Participants with T1D displayed insulin resistance, and impaired hormonal counter-regulation during hypoglycemia, whereas glucose and fatty acid fluxes were intact, and ketogenic responses amplified. We observed subtle alterations of intracellular signaling, and no effect of short-lived antecedent hypoglycemia on subsequent counter-regulation. This plausibly reflects the presence of insulin resistance, and implies that T1D is a condition with defective hormonal but preserved metabolic responsiveness to short-lived hypoglycemia.

AB - AIMS: Hypoglycemia hinders optimal glycemic management in type 1 diabetes (T1D). Long diabetes duration and hypoglycemia impair hormonal counterregulatory responses to hypoglycemia. Our study was designed to test whether i) the metabolic responses and insulin sensitivity are impaired, and ii) affected by short-lived antecedent hypoglycemia in participants with T1D.MATERIALS AND METHODS: In a randomized, crossover, 2x2-factorial design, nine male participants with T1D and nine comparable control participants underwent 30 min hypoglycemia (p-glucose<2.9mmol/L) followed by a euglycemic clamp on two separate interventions: with and without 30 min hypoglycemia the day before the study day.RESULTS: During both interventions: insulin sensitivity was consistently lower, while counterregulatory hormones were reduced with 75% lower glucagon and 50% lower epinephrine during hypoglycemia in participants with T1D, who also displayed 40% lower lactate and 5-10-fold increased ketone bodies concentrations following hypoglycemia, whereas palmitate and glucose turnover, forearm glucose uptake and substrate oxidation did not differ between the groups. In participants with T1D, adipose tissue PTEN content, HSL phosphorylation and muscle GLUT4 content were decreased compared with controls. An antecedent hypoglycemic episodes lasting 30 minutes did not affect counter-regulation or insulin sensitivity.CONCLUSIONS: Participants with T1D displayed insulin resistance, and impaired hormonal counter-regulation during hypoglycemia, whereas glucose and fatty acid fluxes were intact, and ketogenic responses amplified. We observed subtle alterations of intracellular signaling, and no effect of short-lived antecedent hypoglycemia on subsequent counter-regulation. This plausibly reflects the presence of insulin resistance, and implies that T1D is a condition with defective hormonal but preserved metabolic responsiveness to short-lived hypoglycemia.

U2 - 10.1210/clinem/dgaa645

DO - 10.1210/clinem/dgaa645

M3 - Journal article

C2 - 32927476

VL - 105

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 12

M1 - dgaa645

ER -