Lypohypertrophy in patients receiving insulin therapy: state of the art

Abstract

As known insulin therapy is associated with induration of subcutaneous fat at injections sites called lypohypertrophy. It develops at any age and at anysite regardless of duration of the treatment. The size of lypohypertrophy varies in a wide range. Numerous studies have been conducted to elucidatemechanisms of lypohypertrophy (LH) and its risk factors including young age, low or high body mass index, frequency of the change of needles andinjection sites, female gender, and type 1 diabetes mellitus. It was shown that insulin crystals induce a local immune reaction and thereby interfere withadipocyte differentiation. At the same time, patients with LH have elevated titters of anti-insulin antibodies. The problem with LH is uncontrollableabsorption of insulin from injection sites. We noticed that patients with a target glucose level due to insulin therapy undergo its apparently causelessperiodic rises. Comparative ultrasonic examination of subcutaneous fat at different injection sites and control body areas revealed specific pathologicalchanges in adipose issue. This finding provided a basis for the hypothesis that LH can be detected by ultrasonography of subcutaneous fat. It wasconfirmed by the results of examination of 50 patients with DM1 treated with insulin of whom 41 were found to have pathological changes at injectionsites.

Ultrasound detection of insulin‐induced lipohypertrophy in Type 1 and Type 2 diabetes

“…Furthermore, it was demonstrated that ultrasonound-detected lesions consistent with lipohypertrophy more frequently than did clinical palpation, with a subset of participants exclusively having 'subclinical lipohypertrophy,' defined as lesions found only by ultrasonography. Findings of changes on ultrasonography and not on clinical examination have also been reported in one other series in which locations of lipohypertrophy had already been established [17]. In the Volkova study [17], the presence of these lesions was noted in 66% of individuals, results similar to those of the present study in which 52.4% of participants were found to have subclinical lesions.…”

“…Findings of changes on ultrasonography and not on clinical examination have also been reported in one other series in which locations of lipohypertrophy had already been established [17]. In the Volkova study [17], the presence of these lesions was noted in 66% of individuals, results similar to those of the present study in which 52.4% of participants were found to have subclinical lesions. Half of the individuals with subclinical lesions (24.3%) had no other findings of lipohypertrophy.…”

“…This indicates that current methods are subject to error and that cysts, haematomas and lipomas can have consistencies and textures similar to lipohypertrophy. Case reports indicate that clinical palpation has also failed to detect lipohypertrophy with improvement in glycaemic indices once identified by ultrasonography . With accumulating evidence of altered insulin absorption dynamics at known sites of clinical lipohypertrophy , dedicated studies are required to determine if subclinical lesions such as those characterized in the present study also contribute to glycaemic variability.…”

“…Previous characterizations of lipohypertrophy have included variable descriptions of hypo-, iso-and hyperechogenic densities, which leads to more reliance on operator interpretation [1,10,22]. Disorganization and thickening or depth of surrounding subcutaneous tissue has also been described in some participants, but inter-individual variations in abdominal adipose tissue composition as influenced by body composition and BMI could affect these variables [10,17,22]. The comprehensive echo signature described in the present study reduces variability by further defining several features that are in keeping with known underlying histological changes of lipohypertrophy.…”

“…A separate team comprising two research associates received clinical training in bedside ultrasonography by a certified educator and further instruction by a radiologist specializing in ultrasonography. The associates were blinded to the clinical findings and subsequently conducted an examination of the abdomen using a portable GE LOGIQe machine with an L8-18i-D probe (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) MHz; GE Healthcare, Frankfurt, Germany). Both research associates were involved in the ultrasound analysis of participants to reduce inter-operator variability.…”