TY - JOUR

T1 - Glucagonostatic Potency of GLP-1 in Patients with Type 2 Diabetes, in Patients with Type 1 Diabetes, and Healthy Control Subjects

AU - Bagger, Jonatan I.

AU - Grøndahl, Magnus

AU - Lund, Asger

AU - Holst, Jens J

AU - Vilsbøll, Tina

AU - Knop, Filip K

PY - 2021

Y1 - 2021

N2 - Hyperglucagonemia is a well-known contributor to diabetic hyperglycemia, and glucagon-like peptide-1 (GLP-1) suppresses glucagon secretion. Reduced inhibitory effects of glucose and GLP-1 on glucagon secretion may contribute to the hyperglucagonemia in diabetes and influence the success of GLP-1 receptor agonist therapy. We examined the dose-response relationship for GLP-1 on glucose-induced glucagon suppression in healthy individuals, patients with type 2 and type 1 diabetes. In randomized order, 10 healthy individuals with normal glucose tolerance, 10 patients with type 2 diabetes and 9 C-peptide negative patients with type 1 diabetes, underwent 4 separate stepwise glucose clamps (five 30-minute steps from fasting level to 15 mM plasma glucose) during simultaneous intravenous infusions of saline, 0.2, 0.4 or 0.8 pmol GLP-1/kg/min. In healthy individuals and patients with type 2 diabetes, GLP-1 potentiated the glucagon-suppressive effect of intravenous glucose in a dose-dependent manner. In patients with type 1 diabetes, no significant changes in glucagon secretion were observed during the clamps whether with saline or GLP-1 infusions. In conclusion, the glucagonostatic potency of GLP-1 during a stepwise glucose clamp is preserved in patients with type 2 diabetes, whereas our patients with type 1 diabetes were insensitive to the glucagonostatic effects of both glucose and GLP-1.

AB - Hyperglucagonemia is a well-known contributor to diabetic hyperglycemia, and glucagon-like peptide-1 (GLP-1) suppresses glucagon secretion. Reduced inhibitory effects of glucose and GLP-1 on glucagon secretion may contribute to the hyperglucagonemia in diabetes and influence the success of GLP-1 receptor agonist therapy. We examined the dose-response relationship for GLP-1 on glucose-induced glucagon suppression in healthy individuals, patients with type 2 and type 1 diabetes. In randomized order, 10 healthy individuals with normal glucose tolerance, 10 patients with type 2 diabetes and 9 C-peptide negative patients with type 1 diabetes, underwent 4 separate stepwise glucose clamps (five 30-minute steps from fasting level to 15 mM plasma glucose) during simultaneous intravenous infusions of saline, 0.2, 0.4 or 0.8 pmol GLP-1/kg/min. In healthy individuals and patients with type 2 diabetes, GLP-1 potentiated the glucagon-suppressive effect of intravenous glucose in a dose-dependent manner. In patients with type 1 diabetes, no significant changes in glucagon secretion were observed during the clamps whether with saline or GLP-1 infusions. In conclusion, the glucagonostatic potency of GLP-1 during a stepwise glucose clamp is preserved in patients with type 2 diabetes, whereas our patients with type 1 diabetes were insensitive to the glucagonostatic effects of both glucose and GLP-1.

U2 - 10.2337/db20-0998

DO - 10.2337/db20-0998

M3 - Journal article

C2 - 33722838

VL - 70

SP - 1347

EP - 1356

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 4

ER -