Characteristics and morphology of lipohypertrophic lesions in adults with type 1 diabetes with ultrasound screening: an exploratory observational study

Abstract

IntroductionLipohypertrophy is a common complication of exposure to insulin therapy. Despite the prevalence of lipohypertrophy and its potentially hazardous effects on glucose regulation, it remains a relatively understudied problem in diabetes. The objective of this study was to characterize lipohypertrophic tissue using ultrasound in adults with type 1 diabetes.Research design and methodsAn observational study of 74 people with type 1 diabetes from a diabetes center in South East London. Participants’ insulin exposed areas were scanned with ultrasound, with a high-frequency linear probe (6–13 MHz). The observed tissue changes were described, measured and graded according to nodule size and thickness of the dermal layer.ResultsParticipants mean age and diabetes duration were 40.6 (±14.2) and 18.3 (±10.9) years, respectively, and 60% (n=44) were male. A total of 740 lipohypertrophic nodules were observed, ranging from 1.8 mm to 40 mm in width. The mean (SD/range) number of nodules per participants was 10.4 (±6.2/1–29). Delineation between the dermal layers was disrupted in all current injection sites. In 52 participants (70%), there was a 30% increase in dermal thickness compared with local none injected tissue, and in 36 participants (48%) the increase was 50%. The level of thickness was >3 mm in the abdominal areas of 22 (40%) of these participants and in thighs of eight participants (17.8%). Hypoechogenic areas suggestive of necrotic tissue were observed within the lipohypertrophic nodules of 22 (30%) participants. Needle length and nodule depth were correlated (r=0.69, p<0.001). A conceptual model of the insulin exposed tissue changes observed was constructed.ConclusionsThe study confirms that insulin-exposed tissue changes are heterogenous and has provided conceptual and grading frameworks for classifying these changes. Further studies are required to establish the clinical implications of these classifications, in relation to glucose regulation and other clinical parameters.

Lipohypertrophy and Insulin: An Update From the Diabetes Technology Society

“…38 To determine the severity of each LH area, a severity indicator based on the size and the number of nodules to produce a parameter on potential severity, as shown in Figure 5, has been described. 37 Increasing severity, as indicated by this model, is associated with increasing size and number of LH nodules and increasing amounts of inflammation, thickening, and loss of differentiation between the dermis and SC tissue. The insulin antibody load was also examined in individuals with varying severity of LH, and the antibody titer was associated with the severity of LH as defined in the model.…”

“…Hypoechogenic areas suggestive of necrotic tissue were also observed within the LH nodules in 30% of participants. 37 In addition, a recent cross-sectional study of adolescents and young adults (n = 95) with T1D found that participants with LH had significantly higher levels of TNFα, which is an inflammatory marker. 4 Studies suggest an average of 10 nodules per individual affected by LH, widely distributed but mainly located in the abdomen and thighs.…”

“…36 However, its clinical utility for widespread use outside of a research setting remains unclear. In a study conducted by Hashem et al, 37 74 individuals with T1D underwent an ultrasound examination of LH regions with unaffected areas as reference regions. Ultrasound images revealed that healthy tissues had clearly defined demarcation lines of the muscle sheath, SC tissue, and dermis, whereas LH-affected areas were blurred with diffuse borders, which had generally increased reflectivity without a defined structure (Figure 4).…”

“…Source: Figure reproduced from Hashem et al 37 under the Creative Commons Attribution—Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work noncommercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is noncommercial. See http://creativecommons.org/licenses/by-nc/4.0/.…”

Insulin-induced Lipo hypertrophy and factors affecting it in children and adolescents with type 1 diabetes mellitus: Review of Literature in the past 12 years

“…The echo signature for LD is described as well-circumscribed hyperechoic foci with defined borders or a nodular shape with a hypoechoic halo, heterogeneous in echotexture compared with surrounding tissue, associated with distortion of surrounding connective tissue in the absence of vascularity and absence of capsule. A relatively recent study confirmed that insulin-exposed tissue changes are heterogenous, and the authors provided a theoretical grading system for categorizing these changes (52,53).…”