Glucagon-Like Peptide 1 Increases Secretory Burst Mass of Pulsatile Insulin Secretion in Patients With Type 2 Diabetes and Impaired Glucose Tolerance

Glucagon-Like Peptide 1 Increases Secretory Burst Mass of Pulsatile Insulin Secretion in Patients With Type 2 Diabetes and Impaired Glucose Tolerance Robert Ritzel 1 , Miriam Schulte 1 , Niels Pørksen 2 , Markus S. Nauck 3 , Jens J. Holst 4 , Claus Juhl 2 , Winfried März 3 , Ole Schmitz 2 , Wolff H. Schmiegel 1 and Michael A. Nauck 1 1 Department of Internal Medicine, Ruhr-University, Knappschafts-KH, Bochum, Germany 2 Department of Endocrinology and Metabolism, University of Aarhus, Aarhus, Denmark 3 Department of Clinical Chemistry, University of Freiburg, Freiburg, Germany 4 Department of Medical Physiology, Panum Institute, University of Copenhagen, Copenhagen, Denmark Abstract The insulinotropic gut hormone glucagon-like peptide (GLP)-1 increases secretory burst mass and the amplitude of pulsatile insulin secretion in healthy volunteers without affecting burst frequency. Effects of GLP-1 on secretory mechanisms in type 2 diabetic patients and subjects with impaired glucose tolerance (IGT) known to have impaired pulsatile release of insulin have not yet been studied. Eight type 2 diabetic patients (64 ± 9 years, BMI 28.9 ± 7.2 kg/m 2 , HbA 1c 7.7 ± 1.3%) and eight subjects with IGT (63 ± 10 years, BMI 31.7 ± 6.4 kg/m 2 , HbA 1c 5.7 ± 0.4) were studied on separate occasions in the fasting state during the continued administration of exogenous GLP-1 (1.2 pmol · kg − 1 · min − 1 , started at 10:00 p.m . the evening before) or placebo. For comparison, eight healthy volunteers (62 ± 7 years, BMI 27.7 ± 4.8 kg/m 2 , HbA 1c 5.4 ± 0.5) were studied only with placebo. Blood was sampled continuously over 60 min (roller-pump) in 1-min fractions for the measurement of plasma glucose and insulin. Pulsatile insulin secretion was characterized by deconvolution, autocorrelation, and spectral analysis and by estimating the degree of randomness (approximate entropy). In type 2 diabetic patients, exogenous GLP-1 at ∼90 pmol/l improved plasma glucose concentrations (6.4 ± 2.1 mmol/l vs. placebo 9.8 ± 4.1 mmol/l, P = 0.0005) and significantly increased mean insulin burst mass (by 68%, P = 0.007) and amplitude (by 59%, P = 0.006; deconvolution analysis). In IGT subjects, burst mass was increased by 45% ( P = 0.019) and amplitude by 38% ( P = 0.02). By deconvolution analysis, insulin secretory burst frequency was not affected by GLP-1 in either type 2 diabetic patients ( P = 0.15) or IGT subjects ( P = 0.76). However, by both autocorrelation and spectral analysis, GLP-1 prol