Effects of Exercise on the Absorption of Insulin Glargine in Patients With Type 1 Diabetes RAJESH PETER, MRCP 1 STEPHEN D. LUZIO, PHD 1 GARETH DUNSEATH, MPHIL 1 ANDY MILES, PHD 2 BARRY HARE, PHD 2 KARIANNE BACKX, PHD 2 VASSEN PAUVADAY, MRCP 1 DAVID R. OWENS, MD 1 OBJECTIVE — To study the effects of exercise on the absorption of the basal long-acting insulin analog insulin glargine (Lantus), administered subcutaneously in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS — A total of 13 patients (12 men, 1 woman) with type 1 diabetes on a basal-bolus insulin regimen were studied. 125 I-labeled insulin glargine at the usual basal insulin dose was injected subcutaneously into the thigh on the evening (2100) before the study day on two occasions 1 week apart. Patients were randomly assigned to 30 min intense exercise (65% peak oxygen uptake [VO 2peak ]) on one of these visits. The decay of radioactive insulin glargine was compared on the two occasions using a thallium-activated Nal gamma counter. Blood samples were collected at regular intervals on the study days to assess plasma glucose and insulin profiles. RESULTS — No significant difference was found in the 125 I-labeled insulin glargine decay rate on the two occasions (exercise vs. no exercise; repeated-measures ANOVA, P = 0.548). As expected, a significant fall in plasma glucose was observed over the exercise period (area under curve above fasting [AUC] glucose: -0.39  0.11 vs. -1.30  0.16 mmol  l -1  h -1 ; nonexercise vs. exercise; P = 0.001), but insulin levels did not differ significantly on the two occasions (AUC insulin: -2.1  3.9 vs. 1.5  6.2 pmol  l -1  h -1 ; nonexercise versus exercise; P = 0.507). CONCLUSIONS — An intense 30-min period of exercise does not increase the absorption rate of the subcutaneously injected basal long-acting insulin analog insulin glargine in patients with type 1 diabetes. Diabetes Care 28:560 –565, 2005 D espite wide fluctuations in nutri- tional intake and physical exercise, the concentration of plasma glucose in healthy individuals remains within a narrow range throughout the day (3.5– 7.0 mmol/l) (1). In contrast, patients with type 1 diabetes have an absolute defi- ciency of insulin secretion and are there- fore dependent on exogenous insulin to regulate their blood glucose concentra- tions. The purpose of intensive insulin therapy is to mimic physiological insulin secretion by providing a basal insulin re- placement together with insulin boluses to cover prandial glucose excursions. The basal replacement should provide a re- producible supply of insulin into the bloodstream, which remains as stable as possible over 24 h to suppress excess postabsorptive hepatic glucose produc- tion and to facilitate the action of the bo- lus insulin (2,3). The bolus insulin comprising a fast-acting insulin adminis- tered immediately before meals should prevent postprandial glycemic surges. The most challenging aspect of insulin therapy is to maintain insulin levels that keep blood glucose levels as close to nor- mal as possible without necessarily in- creasing the risk of hypoglycemia. Insulin glargine (21A-Gly-30Ba-L- Arg–30Bb-L-Arg-human insulin; Lantus) is a human insulin analog synthesized by recombinant DNA technology. It results from two modifications of human insulin. The first is the addition of two arginine molecules (two positive charges) to the COOH-terminus of the B-chain, which shifts the isoelectric point from a pH of 5.4 to 6.7, making the molecule less soluble at the physiological pH of subcu- taneous tissue. Also, asparagine 21 is re- placed with glycine, which is charge neutral. This results in delayed dissocia- tion into monomers providing stability to the resulting human insulin analog. In- jected subcutaneously as a clear solution at pH 4.0, insulin glargine forms a micro- precipitate in the physiological pH of the subcutaneous space, thereby delaying its absorption and prolonging its duration of action (4 – 6). Small amounts of zinc (30 g/ml), a hexamer-stabilizing agent, have been added to the insulin glargine formu- lation to further extend the duration of action following subcutaneous injection (4). With appropriate once-daily dosing, insulin glargine concentrations in the blood of patients with type 1 diabetes will closely mimic physiological basal insulin concentrations found in people without diabetes, providing a near 24-h duration of action. Previous clinical pharmacological ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● From the 1 Diabetes Research Unit, Llandough Hospital, Penarth, South Glamorgan, U.K.; and the 2 School of Sport, PE and Recreation, University of Wales Institute, Cardiff, South Glamorgan, U.K. Address correspondence and reprint requests to Prof. D.R. Owens, Diabetes Research Unit, First Floor, Academic Centre, Llandough Hospital, Penlan Road, Penarth, South Glamorgan CF64 2XX, Wales, U.K. E-mail: owensdr@cf.ac.uk. Received for publication 22 July 2004 and accepted in revised form 24 November 2004. D.R.O. is a member of the Aventis European Advisory Board and has received consultation fees and research grant funding from Aventis Pharma. Abbreviations: AUC, area under the curve above fasting. A table elsewhere in this issue shows conventional and Syste `me International (SI) units and conversion factors for many substances. © 2005 by the American Diabetes Association. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Clinical Care/Education/Nutrition O R I G I N A L A R T I C L E 560 DIABETES CARE, VOLUME 28, NUMBER 3, MARCH 2005