Absorption Kinetics and Biologic Effects of Subcutaneously Injected Insulin Preparations

Abstract

This paper describes systematic studies on the absorption kinetics of exogenous insulin from its subcutaneous tissue depot in 52 male nonobese volunteers (age 20-30 yr). Five experimental protocols were used: effect of changing injection site, effect of temperature change and local massage, effect of aprotinin and human serum, effect of mixing regular insulin with long-acting insulin preparations, and effect of temperature change, muscular exercise, and local massage on the absorption of long-acting insulin preparations. The fastest absorption of insulin occurred at the abdominal injection. Absorption after arm injection was faster than after thigh injection. A hot bath and local massage dramatically increased serum insulin levels in the first 90 min after injection; in contrast, a cold bath delayed absorption substantially. Both aprotinin and the subjects' own blood serum mixed with insulin caused a marked acceleration of the insulin absorption process. Absorption kinetics of two neutral regular insulins (Actrapid and Leo Regular) were virtually identical. Mixing Actrapid with Monotard caused higher serum insulin levels than the mixture of Leo Regular with NPH. A time lag of 5 min between the mixing of Actrapid and Monotard and the injection caused a delayed rise of serum insulin levels; in contrast, this delay could not be observed when Leo Regular and NPH were mixed. Volunteers performed bicycle exercise, applied a hot water bottle to the injection site, or rubbed the injection site 2 1/2 h after injection of long-acting insulin. Accelerated absorption of insulin was only observed after local massage of the injection site of Monotard, Leo NPH, and Mixtard. Local heat had no effect. Exercise caused only an increased absorption of insulin after the Mixtard injection but not after Monotard or NPH injection. These findings have clinical significance and should not be without potential benefit in the attempt to improve metabolic control in insulin-treated diabetic patients.

Subcutaneous adipose tissue blood flow varies between superior and inferior levels of the anterior abdominal wall

“…7 However, no differences in insulin absorption were found between superficial and deep subcutaneous adipose tissue. 12,13 It has been shown that the subcutaneous absorption of insulin varies according to adipose tissue depots, in nondiabetic 14 and diabetic 12,13,15 subjects. These differences have been found to correlate with blood flow in some studies [16][17][18][19] but not others.…”

Type 1 diabetes: treatment without tears?

“…It was -and is -a 5-day programme with a carefully constructed curriculum that aims to teach people with diabetes exactly how insulin works, using well-documented physiological and pharmacological data [5]. It was designed to transfer skills of insulin manipulation and dose adjustment to the patient, using recognised principles of adult learning.…”

Intranasal insulin therapy: the clinical realities

“…[Diabetologia (1995) The limitations of intensive insulin therapy are mainly due to the pharmacokinetic properties of subcutaneously injected insulin, resulting in an increased frequency of hypoglycaemia [2]. Whereas avoiding hypoglycaemia with intensive insulin therapy only seems possible by raising blood glucose levels, a more physiological insulin administration might potentially reduce blood glucose without increasing the frequency of hypoglycaemia [3]. In this context, intranasal insulin administration has gained considerable interest, since after intranasal application of insulin, plasma insulin concentrations increase more rapidly and return to basal levels more quickly than after subcutaneous insulin injections [4].…”