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Altered GH Elimination Kinetics in Type 1 Diabetes Mellitus Can Explain the Elevation in Circulating Levels: Bicompartmental Approach

Departments of Endocrinology (P.F.C.), Hospital Montecelo, Pontevedra 36.005-E, Spain; and Section of Endocrinology (M.A.A., R.V.G.-M.), Hospital Xeral-Cíes, Vigo 36.201-E, Spain; and Department of Functional Biology and Health Sciences (F.M.F.), University of Vigo, Vigo 36200-E, Spain

Address all correspondence and requests for reprints to: Federico Mallo, Ph.D., M.D., Laboratory of Endocrine Physiology, Department of Functional Biology and Health Sciences, Faculty of Sciences, Campus of Vigo, University of Vigo, 36200-E Vigo, Spain. E-mail: . fmallo{at}uvigo.es

Abstract

Type 1 diabetes mellitus (DM 1) is associated with elevated circulating GH concentrations. Because these high GH levels could be explained either by an augmented pituitary secretion and/or delayed elimination clearance or distribution, we sought to evaluate GH pharmacokinetics to propose a model that better explains the elimination kinetics in patients with DM 1 and assess possible differences with normal volunteers that could justify elevation in GH circulating levels in these patients. A multicompartmental analysis was applied to serum GH concentrations measured at different times for 150 min in six patients with DM 1 and six age-, sex-, and body mass index-matched normal subjects after the administration of an iv bolus of recombinant human GH (200 µg), previous suppression of endogenous GH release with octreotide.

The best fitting to the GH disappearance profiles was obtained with the biexponential equation in both groups. From it, we propose a bicompartmental model to explain GH kinetics in normal and diabetic patients. The mean transit time in both compartments and the mean residence time in patients with DM 1 were more than twice the values from control group. So in DM 1 elevated circulating GH concentrations are, at least partially, caused by a delayed GH plasmatic clearance. The DM 1 patients included in this study had a normal renal function; thus, our results agree with the hypothesis that DM 1 constitutes a GH-insensitivity state because a reduced GH clearance by its receptor-mediated mechanism might explain the delayed GH elimination kinetics shown in patients with DM 1. However, the possibility of additional factors contributing to the slowed GH removal from circulation is not completely excluded.

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