%0 Journal Article
%T Insulin Sensitivity Assessed by Stable Isotopes with Oral Glucose Administration: Validation with Euglycaemic Clamp
%A Leslie Bluck
%A Rachel Williams
%A Sarah Jackson
%A Burak Salgin
%A Carlo Acerini
%A David Dunger
%J ISRN Endocrinology
%D 2013
%R 10.1155/2013/189412
%X Methods of determining insulin sensitivity that use an oral challenge of glucose are preferred to those using intravenous administration since the measurement is made in conditions more akin to normal physiology. One previously reported protocol (ODILE) studies glucose uptake in isolation from absorption and endogenous production by the intravenous administration of tracer approximately forty-five minutes after the oral dose is given. However, this methodology has not been validated against other accredited procedures. This study utilizes the euglycemic hyperinsulinemic clamp in order to validate the ODILE method. 1. Introduction The determination of the parameters of glucose metabolism, and in particular peripheral insulin sensitivity, is of great interest to clinicians and researchers interested in the aetiology of type 2 diabetes and the metabolic syndrome. Currently, there are two procedures accredited with providing estimates of peripheral insulin sensitivity on a cardinal scale [1]: the euglycaemic clamp [2] and the intravenous glucose tolerance test (IVGTT) interpreted via the minimal model [3]. The clamp methodology is clinically intensive and usually applicable only to studies with relatively few subjects ( ). The IVGTT is more widely employed and has been used in intervention studies with many hundreds of participants [4, 5]. The IVGTT, however, fails to conform to Groop¡¯s [6] list of desirable properties of a methodology to measure insulin sensitivity, inasmuch as it creates unphysiological conditions. Intravenous administration of a glucose bolus gives an almost instantaneous increase in plasma glucose from basal (fasting) levels to a condition where the renal threshold is frequently exceeded, and because of the transitory nature of the glucose input, the period of hyperglycemia is generally less than one hour in normal subjects. During this time, the concentration of glucose in the peripheral circulation exceeds that in the portal vein, in contrast to normal post-prandial conditions. As a consequence, only first phase insulin secretion can be reliably determined, yet such a response never occurs in isolation in the normal state. Secondly, in the absence of incretin effects, the endogenous insulin response is too small (~200£¿pM) and too transitory to be a satisfactory stimulus for peripheral glucose uptake. Although the latter can be ameliorated to some extent by exogenous insulin administration [7], this removes the physiological conditions of the test even further from reality. These objections could be overcome if oral administration of
%U http://www.hindawi.com/journals/isrn.endocrinology/2013/189412/