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