Insulin Resistance is Accompanied by Increased Fasting Glucagon and Delayed Glucagon Suppression in Individuals With Normal and Impaired Glucose Regulation

TY - JOUR

T1 - Insulin Resistance is Accompanied by Increased Fasting Glucagon and Delayed Glucagon Suppression in Individuals With Normal and Impaired Glucose Regulation

AU - Faerch, Kristine

AU - Vistisen, Dorte

AU - Pacini, Giovanni

AU - Torekov, Signe S

AU - Johansen, Nanna Borup

AU - Witte, Daniel R

AU - Jonsson, Anna

AU - Pedersen, Oluf

AU - Hansen, Torben

AU - Lauritzen, Torsten

AU - Jørgensen, Marit E

AU - Ahrén, Bo

AU - Holst, Jens Juul

N1 - © 2016 by the American Diabetes Association.

PY - 2016/11

Y1 - 2016/11

N2 - Hyperinsulinemia is an adaptive mechanism that enables the maintenance of normoglycemia in the presence of insulin resistance. We assessed whether glucagon is also involved in the adaptation to insulin resistance. A total of 1,437 individuals underwent an oral glucose tolerance test with measurements of circulating glucose, insulin, and glucagon concentrations at 0, 30 and 120 min. Early glucagon suppression was defined as suppression in the period from 0 to 30 min, and late glucagon suppression as 30 to 120 min after glucose intake. Insulin sensitivity was estimated by the validated insulin sensitivity index. Individuals with screen-detected diabetes had 30% higher fasting glucagon levels and diminished early glucagon suppression, but greater late glucagon suppression when compared with individuals with normal glucose tolerance (P 0.014). Higher insulin resistance was associated with higher fasting glucagon levels, less early glucagon suppression, and greater late glucagon suppression (P < 0.001). The relationship between insulin sensitivity and fasting glucagon concentrations was nonlinear (P < 0.001). In conclusion, increased fasting glucagon levels and delayed glucagon suppression, together with increased circulating insulin levels, develop in parallel with insulin resistance. Therefore, glucose maintenance during insulin resistance may depend not only on hyperinsulinemia but also on the ability to suppress glucagon early after glucose intake.

AB - Hyperinsulinemia is an adaptive mechanism that enables the maintenance of normoglycemia in the presence of insulin resistance. We assessed whether glucagon is also involved in the adaptation to insulin resistance. A total of 1,437 individuals underwent an oral glucose tolerance test with measurements of circulating glucose, insulin, and glucagon concentrations at 0, 30 and 120 min. Early glucagon suppression was defined as suppression in the period from 0 to 30 min, and late glucagon suppression as 30 to 120 min after glucose intake. Insulin sensitivity was estimated by the validated insulin sensitivity index. Individuals with screen-detected diabetes had 30% higher fasting glucagon levels and diminished early glucagon suppression, but greater late glucagon suppression when compared with individuals with normal glucose tolerance (P 0.014). Higher insulin resistance was associated with higher fasting glucagon levels, less early glucagon suppression, and greater late glucagon suppression (P < 0.001). The relationship between insulin sensitivity and fasting glucagon concentrations was nonlinear (P < 0.001). In conclusion, increased fasting glucagon levels and delayed glucagon suppression, together with increased circulating insulin levels, develop in parallel with insulin resistance. Therefore, glucose maintenance during insulin resistance may depend not only on hyperinsulinemia but also on the ability to suppress glucagon early after glucose intake.

U2 - 10.2337/db16-0240

DO - 10.2337/db16-0240

M3 - Journal article

C2 - 27504013

SN - 0012-1797

VL - 65

SP - 3473

EP - 3481

JO - Diabetes

JF - Diabetes

IS - 11

ER -