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Insulin absorption: a factor affecting variability in glycemic response
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You may have heard statements similar to the following from your patients:
“I noticed a little bit of insulin leaking out of my skin after I injected.”
“My blood sugars seem to be different when I inject in different places on my stomach.”
These are examples of the effects that variations in insulin absorption may have on varying glycemic control. This article will review factors that should be considered when determining if variable glycemic control may be related to changes in insulin absorption.
The physicochemical characteristics of insulin have been manipulated to bestow either long-acting or rapid-acting characteristics to an insulin product. The newer basal insulin analogs are hexamer-aggregated mixtures, which must slowly dissociate into the physiologically active, absorbable monomeric form. Rapid-acting insulin analogs have reduced self-aggregation to hexameric insulin and are composed of predominantly monomeric forms. Glargine (Lantus, Sanofi Aventis) insulin has delayed absorption due to its acidic pH that causes microprecipitate formation of insulin crystals in the presence of neutral physiologic pH. Detemir (Levemir, Novo Nordisk) owes its delay in absorption to its slow dissociation from albumin binding sites. These newer basal analogs have an advantage over NPH not only because of these factors but also because they are soluble and do not require resuspension prior to each injection, a factor that contributes to absorption variability.
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Temperature
One study by Polaschegg in 24 healthy men found no difference in the rate or extent of absorption between regular or lispro (Humalog, Eli Lilly) insulin when it was injected at a product temperature of 8° or 37°C. They concluded that there was no increased hexameric dissociation caused by warming the insulins. Skin temperature, however, does appear to alter the rate of insulin absorption as evidenced by trials that demonstrate correlations between insulin levels and increased skin temperature.
Individual patient factors
Linde et al studied the absorption of rapid-acting Actrapid (Novo Nordisk) human soluble insulin in 10 obese and 10 non-obese patients with type 2 diabetes. Absorption of insulin was significantly slower in these type 2 patients compared with rates observed previously in healthy people and patients with type 1 diabetes. Absorption rates between sites in the obese group were not significantly different but rates in the non-obese group indicated site-based absorption differences.
Site of injection
Providers have known for some time that the rate of insulin absorption varies between anatomical sites. The fastest rate of absorption occurs in the abdominal area followed by the thighs, arms and buttocks. It has also been known that massaging an injection site immediately after injection will accelerate the rate of absorption of insulin, and is not recommended. Frid and Linde conducted studies using radiolabeled Actrapid insulin in diabetes patients. One study in nine lean patients with type 1 diabetes found that injecting Actrapid into the epigastric area (120 mm above the umbilicus) resulted in more rapid insulin absorption and greater glucose-lowering effect compared with injecting 40 mm below the umbilicus. Adipose tissue flow was not different between the sites and could not explain the difference in absorption. The authors theorized that a higher capillary diffusion capacity, caused by higher capillary permeability, could be the mechanism for the difference.
Injection depth/needle length
Injection into subcutaneous tissue avoids inadvertent intramuscular injection that may result in more rapid insulin absorption. Determining the appropriate needle length and teaching proper technique, such as pinching up abdominal skin, will ensure that the insulin is injected into subcutaneous tissue. A commonly used needle length is 8 mm (5/16”), but either a shorter length (5 mm, 3/16”) or longer length (12.7 mm, 1/2”) may be used depending on patient body type, age and other factors. Longer needle length may be needed for morbidly obese patients with substantial abdominal adipose tissue, especially if insulin leakage is noted.
Patients should be questioned about these and other factors, such as exercise, injection angle, or injection in areas of lipohypertrophy, to rule out variability in insulin absorption as a factor in varying or suboptimal glycemic control.
June Felice Johnson, BS, PharmD, FASHP, BC-ADM, is an Associate Professor of Pharmacy Practice and the Director of Faculty & Site Development at Drake University College of Pharmacy & Health Sciences, in Des Moines, Iowa.
For more information:
- Clauson PG, Linde B. Absorption of rapid-acting insulin in obese and nonobese NIDDM patients. Diabetes Care. 1995;18(7):986-91.
- Frid A, Linde B. Clinically important differences in insulin absorption from abdomen in IDDM. Diab Research Clin Pract. 1993;21:137-41.
- Goldman-Levine JD, Lee KW. Insulin detemir-A new basal insulin analog. Ann Pharmacother. 2005;39:502-7.
- Luzio SD et al. Comparison of the subcutaneous absorption of insulin glargine (Lantus) and NPH insulin in patients with type 2 diabetes. Horm Metab Res. 2003;35:434-38.
- Polaschegg E. Effect of physicochemical variables of regular insulin formulations on their absorption from the subcutaneous tissue. Diab Research Clin Pract. 1998;40:39-44.
- Position Statement. Insulin administration. American Diabetes Association. Diabetes Care. 2002; 25: S112-15.
- Sindelka G et al. Effect of insulin concentration, subcutaneous fat thickness and skin temperature on subcutaneous insulin absorption in healthy subjects. Diabetologia. 1994;37:377-80.
- Thow J, Home P. Insulin injection technique. Depth of injection is important. BMJ. 1990;301 (6742):3-4.
- www.bddiabetes.com/us