Short answer: Insulin labels name two causes: lipohypertrophy, a thickening of the fat under the skin, and localized cutaneous amyloidosis, where insulin builds up as protein deposits. Both are linked to injecting into the same spot again and again. Insulin injected into a lump may be absorbed less, which can raise blood sugar, and the labels warn that a sudden switch to normal skin has been reported to cause low blood sugar.
The Humalog label says long-term use of insulin can cause lipodystrophy at the site of repeated injections. Lipodystrophy covers lipohypertrophy (thickening of fat tissue) and lipoatrophy (thinning of fat tissue), and the label says it may affect insulin absorption. The label also says localized cutaneous amyloidosis has occurred at injection sites. This is a deposit of insulin-derived protein in the skin, sometimes called an insulin ball.
The Humalog, NovoLog and Lantus labels all say to rotate injection sites within the same region from one injection to the next to lower the risk of both, and not to inject into areas of lipodystrophy or amyloidosis. Similar wording appears for other injected medicines; the Zepbound vial instructions, for example, describe pits, thickened skin and lumps as things to avoid.
| Study | People | Finding |
|---|---|---|
| Famulla 2016 | 13 people with type 1 diabetes, insulin lispro into lipohypertrophy vs normal tissue | Less insulin absorbed (peak 61 vs 79 mU/L), much more day-to-day variation, and blood sugar after a meal at least 26% higher |
| Nagase 2014 | 7 people with insulin-derived amyloidosis | Absorption at amyloid sites was 34% of normal sites; after moving injections, the average daily dose fell from 57 to 27 units |
| Blanco 2013 | 430 outpatients injecting insulin in Spain | 64.4% had lipohypertrophy; it was strongly linked to not rotating sites and to reusing needles more than 5 times |
These are small studies, and the Spanish figure comes from one clinic sample. They point the same way as the labels: insulin into a lump is absorbed less and less predictably.
The Lantus label says repeated injections into areas of lipodystrophy or amyloidosis have been reported to cause high blood sugar, and a sudden change to an unaffected area has been reported to cause low blood sugar. It says any change to the insulin regimen should be made under close medical supervision with more frequent blood sugar checks, and that people who have been injecting into these areas should move to unaffected areas and watch closely for lows.
The Nagase case series shows why: once injections moved off the amyloid sites, the same dose was absorbed better, and the daily dose had to come down by about half. How much to change a dose is a question for the prescriber, who may suggest extra checks in the first days after moving sites.
The Blanco study found that only 5% of people who rotated sites correctly had lipohypertrophy. Rotation is easier to follow when each site is written down. Dose Track can log the site of every injection, so it is easy to see which areas have been used most and which have rested.
Read more on Dose Track: Lipohypertrophy · Why injection site rotation matters · Injection site rotation guide · Humalog side effects