Effect of repeated glucagon doses on hepatic glycogen in type 1 Diabetes

Implications for a bihormonal Closed-Loop system

Jessica Castle, Joseph El Youssef, Parkash A. Bakhtiani, Yu Cai, Jade M. Stobbe, Deborah Branigan, Katrina Ramsey, Peter Jacobs, Ravi Reddy, Mark Woods, W. Kenneth Ward

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

OBJECTIVE To evaluate subjects with type 1 diabetes for hepatic glycogen depletion after repeated doses of glucagon, simulating delivery in a bihormonal closed-loop system. RESEARCH DESIGN AND METHODS Eleven adult subjects with type 1 diabetes participated. Subjects underwent estimation of hepatic glycogen using 13C MRS. MRS was performed at the following four time points: fasting and after a meal at baseline, and fasting and after a meal after eight doses of subcutaneously administered glucagon at a dose of 2 μg/kg, for a totalmean dose of 1,126μg over 16 h. The primary and secondary end points were, respectively, estimated hepatic glycogen by MRS and incremental area under the glucose curve for a 90-min interval after glucagon administration. RESULTS In the eight subjects with complete data sets, estimated glycogen stores were similar at baseline and after repeated glucagon doses. In the fasting state, glycogen averaged 21 ± 3 g/L before glucagon administration and 25 ± 4 g/L after glucagon administration (mean ± SEM) (P = NS). In the fed state, glycogen averaged 40 ± 2 g/L before glucagon administration and 34 ± 4 g/L after glucagon administration (P = NS).With the use of an insulin actionmodel, the rise in glucose after the last dose of glucagon was comparable to the rise after the first dose, as measured by the 90-min incremental area under the glucose curve. CONCLUSIONS In adult subjects with well-controlled type 1 diabetes (mean A1C 7.2%), glycogen stores and the hyperglycemic response to glucagon administration aremaintained even after receiving multiple doses of glucagon. This finding supports the safety of repeated glucagon delivery in the setting of a bihormonal closed-loop system.

Original languageEnglish (US)
Pages (from-to)2115-2119
Number of pages5
JournalDiabetes Care
Volume38
Issue number11
DOIs
StatePublished - Nov 1 2015

Fingerprint

Liver Glycogen
Glucagon
Type 1 Diabetes Mellitus
Glycogen
Fasting
Glucose
Area Under Curve
Meals

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Effect of repeated glucagon doses on hepatic glycogen in type 1 Diabetes : Implications for a bihormonal Closed-Loop system. / Castle, Jessica; El Youssef, Joseph; Bakhtiani, Parkash A.; Cai, Yu; Stobbe, Jade M.; Branigan, Deborah; Ramsey, Katrina; Jacobs, Peter; Reddy, Ravi; Woods, Mark; Ward, W. Kenneth.

In: Diabetes Care, Vol. 38, No. 11, 01.11.2015, p. 2115-2119.

Research output: Contribution to journalArticle

Castle, Jessica ; El Youssef, Joseph ; Bakhtiani, Parkash A. ; Cai, Yu ; Stobbe, Jade M. ; Branigan, Deborah ; Ramsey, Katrina ; Jacobs, Peter ; Reddy, Ravi ; Woods, Mark ; Ward, W. Kenneth. / Effect of repeated glucagon doses on hepatic glycogen in type 1 Diabetes : Implications for a bihormonal Closed-Loop system. In: Diabetes Care. 2015 ; Vol. 38, No. 11. pp. 2115-2119.
@article{965183d88aa745bba5ccba10eced392a,
title = "Effect of repeated glucagon doses on hepatic glycogen in type 1 Diabetes: Implications for a bihormonal Closed-Loop system",
abstract = "OBJECTIVE To evaluate subjects with type 1 diabetes for hepatic glycogen depletion after repeated doses of glucagon, simulating delivery in a bihormonal closed-loop system. RESEARCH DESIGN AND METHODS Eleven adult subjects with type 1 diabetes participated. Subjects underwent estimation of hepatic glycogen using 13C MRS. MRS was performed at the following four time points: fasting and after a meal at baseline, and fasting and after a meal after eight doses of subcutaneously administered glucagon at a dose of 2 μg/kg, for a totalmean dose of 1,126μg over 16 h. The primary and secondary end points were, respectively, estimated hepatic glycogen by MRS and incremental area under the glucose curve for a 90-min interval after glucagon administration. RESULTS In the eight subjects with complete data sets, estimated glycogen stores were similar at baseline and after repeated glucagon doses. In the fasting state, glycogen averaged 21 ± 3 g/L before glucagon administration and 25 ± 4 g/L after glucagon administration (mean ± SEM) (P = NS). In the fed state, glycogen averaged 40 ± 2 g/L before glucagon administration and 34 ± 4 g/L after glucagon administration (P = NS).With the use of an insulin actionmodel, the rise in glucose after the last dose of glucagon was comparable to the rise after the first dose, as measured by the 90-min incremental area under the glucose curve. CONCLUSIONS In adult subjects with well-controlled type 1 diabetes (mean A1C 7.2{\%}), glycogen stores and the hyperglycemic response to glucagon administration aremaintained even after receiving multiple doses of glucagon. This finding supports the safety of repeated glucagon delivery in the setting of a bihormonal closed-loop system.",
author = "Jessica Castle and {El Youssef}, Joseph and Bakhtiani, {Parkash A.} and Yu Cai and Stobbe, {Jade M.} and Deborah Branigan and Katrina Ramsey and Peter Jacobs and Ravi Reddy and Mark Woods and Ward, {W. Kenneth}",
year = "2015",
month = "11",
day = "1",
doi = "10.2337/dc15-0754",
language = "English (US)",
volume = "38",
pages = "2115--2119",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association Inc.",
number = "11",

}

TY - JOUR

T1 - Effect of repeated glucagon doses on hepatic glycogen in type 1 Diabetes

T2 - Implications for a bihormonal Closed-Loop system

AU - Castle, Jessica

AU - El Youssef, Joseph

AU - Bakhtiani, Parkash A.

AU - Cai, Yu

AU - Stobbe, Jade M.

AU - Branigan, Deborah

AU - Ramsey, Katrina

AU - Jacobs, Peter

AU - Reddy, Ravi

AU - Woods, Mark

AU - Ward, W. Kenneth

PY - 2015/11/1

Y1 - 2015/11/1

N2 - OBJECTIVE To evaluate subjects with type 1 diabetes for hepatic glycogen depletion after repeated doses of glucagon, simulating delivery in a bihormonal closed-loop system. RESEARCH DESIGN AND METHODS Eleven adult subjects with type 1 diabetes participated. Subjects underwent estimation of hepatic glycogen using 13C MRS. MRS was performed at the following four time points: fasting and after a meal at baseline, and fasting and after a meal after eight doses of subcutaneously administered glucagon at a dose of 2 μg/kg, for a totalmean dose of 1,126μg over 16 h. The primary and secondary end points were, respectively, estimated hepatic glycogen by MRS and incremental area under the glucose curve for a 90-min interval after glucagon administration. RESULTS In the eight subjects with complete data sets, estimated glycogen stores were similar at baseline and after repeated glucagon doses. In the fasting state, glycogen averaged 21 ± 3 g/L before glucagon administration and 25 ± 4 g/L after glucagon administration (mean ± SEM) (P = NS). In the fed state, glycogen averaged 40 ± 2 g/L before glucagon administration and 34 ± 4 g/L after glucagon administration (P = NS).With the use of an insulin actionmodel, the rise in glucose after the last dose of glucagon was comparable to the rise after the first dose, as measured by the 90-min incremental area under the glucose curve. CONCLUSIONS In adult subjects with well-controlled type 1 diabetes (mean A1C 7.2%), glycogen stores and the hyperglycemic response to glucagon administration aremaintained even after receiving multiple doses of glucagon. This finding supports the safety of repeated glucagon delivery in the setting of a bihormonal closed-loop system.

AB - OBJECTIVE To evaluate subjects with type 1 diabetes for hepatic glycogen depletion after repeated doses of glucagon, simulating delivery in a bihormonal closed-loop system. RESEARCH DESIGN AND METHODS Eleven adult subjects with type 1 diabetes participated. Subjects underwent estimation of hepatic glycogen using 13C MRS. MRS was performed at the following four time points: fasting and after a meal at baseline, and fasting and after a meal after eight doses of subcutaneously administered glucagon at a dose of 2 μg/kg, for a totalmean dose of 1,126μg over 16 h. The primary and secondary end points were, respectively, estimated hepatic glycogen by MRS and incremental area under the glucose curve for a 90-min interval after glucagon administration. RESULTS In the eight subjects with complete data sets, estimated glycogen stores were similar at baseline and after repeated glucagon doses. In the fasting state, glycogen averaged 21 ± 3 g/L before glucagon administration and 25 ± 4 g/L after glucagon administration (mean ± SEM) (P = NS). In the fed state, glycogen averaged 40 ± 2 g/L before glucagon administration and 34 ± 4 g/L after glucagon administration (P = NS).With the use of an insulin actionmodel, the rise in glucose after the last dose of glucagon was comparable to the rise after the first dose, as measured by the 90-min incremental area under the glucose curve. CONCLUSIONS In adult subjects with well-controlled type 1 diabetes (mean A1C 7.2%), glycogen stores and the hyperglycemic response to glucagon administration aremaintained even after receiving multiple doses of glucagon. This finding supports the safety of repeated glucagon delivery in the setting of a bihormonal closed-loop system.

UR - http://www.scopus.com/inward/record.url?scp=84962393713&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962393713&partnerID=8YFLogxK

U2 - 10.2337/dc15-0754

DO - 10.2337/dc15-0754

M3 - Article

VL - 38

SP - 2115

EP - 2119

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 11

ER -