Impact of injection sites for soluble insulin on glycaemic control in Type 1 (insulin-dependent) diabetic patients treated with a multiple insulin injection regimen

Abstract

Summary.The absorption rate of rapid acting (soluble) insulin is slow from the subcutaneous tissue of the thigh compared to intramuscular injection into the thigh and s. c. injection into the abdominal wall. The aim of the study was to evaluate the impact of soluble insulin injected either intramuscularly into the thigh (IMT), s. c. into the abdominal wall (SCA) or s.c. into the thigh (SCT) on glycaemic control in Type 1 (insulin-dependent) diabetic outpatients treated with the basal bolus insulin delivery regimen. Fifty-five, C-peptide negative Type 1 diabetic outpatients were included in a randomised 3-month intervention study. The insulin doses were adjusted frequently by blinded observers based on the patients' self-monitored blood glucose values and reported hypoglycaemic episodes. The serum fructosamine value was within normal limits in three patients in the IMT group, in six patients in the SCA group and in none of the patients in the SCT group following the intervention period (p < 0.01). However, the difference in mean serum fructosamine values did not reach statistical significance (IMT: 1.24 retool/1 (95 % confidence interval; 1.17 to 1.31), SCA: 1.25 mmol/1 (1.18 to 1.32), SCT: 1.34 mmol/1 (1.26 to 1.41), (p = 0.09)). Blood glucose excursions were larger in the SCT group than in the SCA and IMT group from post-lunch to pre-dinner measurements and from pre-to post-dinner measurements. A higher number of measured low nocturnal blood glucose values (less than 4 mmol/1) was observed in the SCT group (34 of 85) than in the IMT (14 of 64) and SCA (21 of 81) group (p < 0.05). Three patients in the IMT group, two in the SCA group, and seven in the SCT group experienced severe hypoglycaemic episodes (p = 0.14). In conclusion s. c. injection of soluble insulin into the abdominal wall is preferable compared to s. c. injection into the thigh in the basal bolus insulin delivery regimen. Furthermore, soluble insulin injection s. c. into the thigh during daytime has important clinical implications for the development of nocturnal hypoglycaemia independently of the NPH insulin injection at bedtime. Key words: Insulin pharmacokinetics, intramuscular insulininjection, subcutaneous insulin injection, blood glucose control, nocturnal hypoglycaemia.The multiple insulin injection regimen (basal bolus insulin delivery regimen) is based on injections of soluble (rapid acting) insulin at mealtimes and injections of NPH (intermediate acting) insulin at bedtime. The purpose of this insulin regimen is to mimic the normal diurnal plasma insulin profile [1]. Thus, the purpose of the bolus component is to provide insulin delivery adequately timed to the absorption of the meal, whereas the purpose of the basal component is to provide adequate insulinisation during the night time and between meals. Obviously, insulin delivery depends on the absorption rate of the injected insulin and this has been demonstrated to vary considerably between different anatomical regions [2][3][4][5][6][7][8][9][10][11][12].It has been shown, that the p...

Glucose-lowering Effect of Insulin Degludec is Independent of Subcutaneous Injection Region

“…For example, some studies have reported slower insulin absorption and decreased glucose-lowering effects of short-acting insulins when injected SC in the thigh than in the abdomen [4][5][6][7][8] or deltoid [4,5]. The same finding has also been observed following administration of regular human insulin or neutral protamine Hagedorn (NPH) insulin in the thigh, compared with injection in the abdomen [7].…”

“…However, differences can exist in the pharmacokinetic and pharmacodynamic properties of insulin following subcutaneous (SC) administration in different regions [4][5][6][7][8][9][10].…”

A pan‐European epidemiologic study of insulin injection technique in patients with diabetes

“…The incorrect choice of sites and techniques may modify insulin absorption parameters, leading to an uncoupling of maximum glucose load and peak insulin effect. This can lead to both unexpected hyperglycemia and an increased risk of nocturnal hypoglycemia6–10.…”

Optimal Insulin Delivery

“…• The abdomen is the preferred site for soluble human insulin (regular), since absorption of this insulin is fastest there [35,[42][43][44][45][46]. A1…”