Glucagon-like peptide 1 increases secretory burst mass of pulsatile insulin secretion in patients with type 2 diabetes and impaired glucose tolerance

The insulinotropic gut hormone glucagon-like peptide (GLP)-1 increases secr etory burst mass and the amplitude of pulsatile insulin secretion in health y volunteers without affecting burst frequency. Effects of GLP-1 on secreto ry mechanisms in type 2 diabetic patients and subjects with impaired glucos e tolerance (IGT) known to have impaired pulsatile release of insulin have not yet been studied. Eight type 2 diabetic patients (64 +/- 9 years, BMI 2 8.9 +/- 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 administratio n of exogenous GLP-1 (1.2 pmol kg-l min-l, started at 10:00 P.M. the evenin g before) or placebo. For comparison, eight healthy volunteers (62 +/- 7 ye ars, 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 insu lin secretion was characterized by deconvolution, autocorrelation, and spec tral analysis and by estimating the degree of randomness (approximate entro py). In type 2 diabetic patients, exogenons GLP-1 at similar to 90 pmol/l i mproved 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 m ass (by 68%, P = 0.007) and amplitude (by 59%, P = 0.006; deconvolution ana lysis). In IGT subjects, burst mass was increased by 45% (P = 0.019) and am plitude by 38% (P = 0.02). By deconvolution analysis, insulin secretory bur st 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 prolonged the period (lag time) between subsequent maxima of insulin concentrations significantly from similar to9 to similar to 13 min in both type 2 diabetic patients and IGT subjects. Under placebo conditions, parameters of pulsatile insulin secretion were similar in norm al subjects, type 2 diabetic patients, and IGT subjects based on all method ological approaches (P > 0.05). In conclusion, intravenous GLP-1 reduces pl asma glucose in type 2 diabetic patients and improves the oscillatory secre tion pattern by amplifying insulin secretory burst mass, whereas the oscill atory period determined by autocorrelation and spectral analysis is signifi cantly prolonged. This was not the case for the interpulse interval determi ned by deconvolution. Together, these results suggest a normalization of th e pulsatile pattern of insulin secretion by GLP-1, which supports the futur e therapeutic use of GLP-1-derived agents.