Glycemic response during exercise after administration of insulin lispro compared with that after administration of regular human insulin

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Abstract

To examine the glycemic response during exercise after administration of short-acting insulin lispro, we compared changes in plasma glucose concentrations during exercise performed by patients with diabetes after the administration of either insulin lispro or regular human insulin. Seven patients with diabetes (two with type 1 and five with type 2) participated in this study. Each of the insulin-depleted subjects received the same number of units of either insulin lispro or regular human insulin, delivered subcutaneously to the abdomen. The next day, each subject received a similar injection of the solution not previously administered. After each injection, the subjects were fed a standard meal of approximately 9 kcal/kg body weight. One hour after eating the test meal, the subjects performed 30 min of cycle ergometer exercise at 50% maximal oxygen uptake. Plasma glucose, insulin, glucagon, growth hormone (GH), and catecholamine concentrations were then measured at specific intervals. Insulin concentrations were higher and peaked earlier after administration of insulin lispro than after administration of regular human insulin. The length of time, needed to reach minimum plasma glucose concentration after exercise was begun, was significantly shorter after administration of insulin lispro, and the percentage of plasma glucose decrease induced by exercise relative to the peak concentration was significantly greater. No differences were found in the concentration changes of counterregulatory hormones between the insulin lispro data and the regular human insulin data. Compared with regular human insulin, insulin lispro induces a more rapid and greater decrease in plasma glucose concentration during exercise because of its faster absorption.

Introduction

During exercise, glucose uptake to the skeletal muscles increases and the plasma glucose level decreases. In healthy men and women, the plasma glucose concentration is maintained at a relatively constant level by glucose production, glycogen degradation, and gluconeogenesis in the liver, in response to the decrease in insulin concentration and the increase in glucagon concentration that occur during exercise [1]. In patients with diabetes treated with insulin, serum insulin concentration cannot be lowered physiologically, therefore, glucose production in the liver cannot be activated during exercise [2]. Marked hypoglycemia could be induced during exercise. Thus, it is necessary to regulate the insulin dose and the food intake of patients with diabetes before they exercise to prevent exercise-induced hypoglycemia [3].

Regular human insulin, presently used to treat diabetes, consists of stable hexamers that are converted to monomers via dimers after subcutaneous administration and then absorbed into the bloodstream. This process of dissociation is the rate-determining step for absorption, and peak blood concentrations are observed as late as 2–4 h after subcutaneous administration. Short-acting insulin lispro has a structural characteristic that hinders the formation of dimers, therefore, it rapidly dissociates directly to monomers and shows peak concentrations within 1 h after subcutaneous administration [4]. Thus, insulin lispro shows greater physiological kinetic and induces less hypoglycemia than regular human insulin [5], [6]. However, the glycemic response and details of insulin kinetics during exercise after administration of insulin lispro remain unclear, and without further investigations, hypoglycemia may inadvertently be induced during exercise or daily activities when regular human insulin is replaced with insulin lispro.

To prevent this, we compared the glycemic response during exercise after administration of insulin lispro with that after administration of regular human insulin in patients with diabetes treated with insulin.

Section snippets

Subjects

Seven patients with diabetes (two with type 1 and five with type 2) participated in this study. In these cases of type 2 diabetes, urinary C-peptide had been depleted with less than 20 μg/day. The seven patients had the following characteristics: 36±5.9 years of age; BMI of 23.0±1.7 kg/m2; duration of diabetes 7.9±2.6 years; fasting plasma glucose level of 139.0±20.0 mg/dl; and HbA1c level of 10.7±0.7%. No complications such as diabetic retinopathy, nephropathy, or hypertension were observed in

Results

Insulin concentrations were significantly higher (P<0.01) and peaked earlier after administration of insulin lispro compared with regular human insulin (Fig. 1). The peak concentration of insulin after injection with insulin lispro was 64.0±3.4 mU/ml and that after injection with regular human insulin was 35.7±3.4 mU/ml.

Fig. 2 shows glycemic response. None of the subjects experienced hypoglycemia during exercise. At the beginning of exercise, the absolute glucose concentration after an

Discussion

Exercise is a basic therapy for type 2 diabetes; this therapy is also appropriate in the management of type 1 diabetes. The resulting increase in physical fitness and elevated psychological outlook thus has the potential to improve the quality-of-life for all patients with diabetes. Serum insulin concentration is well recognized to be an important determinant of glycemic response during exercise. In healthy men and women, the plasma glucose level is maintained when glucose production in the

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