Detection of Lipohypertrophy in Patients Treated with Insulin


Background: Lipohypertrophy (LH) occurs as a result of repeated insulin injections into an area of subcutaneous tissue (SC). The reported prevalence of LH is high with estimates varying from 40 – 60% (Blanco, Hernandez, et al. 2013; Frid et al. 2016; Grassi et al. 2014; Ibarra and Gallego 1998). This variation in prevalence estimates may be related to the type of detection method used. Until recently LH detection has been based on palpation, but ultrasound (US) is now also being used as a potentially more sensitive measure (Gentile et al. 2016; Kapeluto et al. 2015; Seyoum and Abdulkadir 1996). However, there is currently no gold standard for LH detection and consequently no evidence-based guidance for best practice. Insulin injected into LH regions has been shown to be associated with glucose variability, increased risk of severe hypoglycaemia, and increased insulin requirements (Blanco, Hernández, et al. 2013). Therefore, information on reliability, accuracy and sensitivity of the different methods for LH detection is clinically important.
Aims: This systematic review aimed to evaluate the current knowledge base on the sensitivity of detecting LH using US or US and palpation.
Method: Embase, Medline and Web of Sciences were systematically searched to identify primary studies that assessed LH detection in insulin-treated individuals. Potential studies were scrutinised against the review inclusion criteria, with full data being extracted from the relevant studies. Study designs were critically using appropriate tools.
Results: Twelve articles were included in the review, with one publication including two independent studies. The median critical appraisal score was 50%, with the range being from 29% to 75%. Four studies (31%) employed US scanning, eight (62%) used a combination of palpation and US and one case report did not provide explicit details on the form of physical examination used alongside US scanning. Four studies (31%) employed US scanning, eight (62%) used a combination of palpation and US and one case report did not provide explicit details on the form of physical examination used alongside US scanning. Prevalence of LH among insulin pen needle users ranged between 14.5% to 88%, and 44% to 71% in those using continuous subcutaneous insulin infusion devices. LH was reported in all injection site areas, but most frequently in the abdomen. Though, no studies tested the likelihood of any one anatomical site developing LH more quickly or to a worse degree than any other area. Detection of LH was commonly diagnosed using multiple methods, including visual inspection, palpation and US. Three of the studies identified LH lesions using US alone and reported a prevalence range of 14.5% - 87%. The prevalence depicted through palpation was only reported in one paper and was 37%. Nine studies used US to confirm preliminary diagnoses deduced from clinical examinations. One observational study initially used US to identify a cohort with definite LH, and then two palpation methods were compared. These were trained nurses, employing a detailed palpation technique, which was 97% consistent in detecting LH; whilst the nurses applying traditional methods missed 28% of cases. Three studies comparing diagnostic sensitivity provide conflicting results; whereby one of these studies showed that palpation overestimated LH sites by 65%, and another study demonstrated that US overestimated LH regions by 50%; whilst one study provided comparable estimates between palpation and US scanning (97%). 
Discussion: The current literature highlights a lack of congruency in results pertaining to diagnostic sensitivity of ultrasound and palpation. Due to the low quality of most of the research there is a high possibility that results have been affected by bias, however, it is plausible that one technique may be too sensitive and likely to generate more false-positives. Pooled evidence from the current literature review suggests that US recordings may provide more accurate detection of LH than palpation. High quality research is needed to verify this and whether clinically palpation is sufficient to detect LH, or whether annual assessment should also be carried out with US to confirm or exclude this common problem that can so drastically affect glycaemic control. The use of US would also allow clinicians a visual aid to empower patients, and prompt effective education on injection practices to improve self-management.



References:
Blanco, M., M. T. Hernandez, K. W. Strauss, and M. Amaya. 2013. 'Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes', Diabetes & Metabolism, 39: 445-53.
De Coninck, Carina, Anders Frid, Ruth Gaspar, Debbie Hicks, Larry Hirsch, Gillian Kreugel, Jutta Liersch, Corinne Letondeur, Jean‐Pierre SAUVANET, and Nadia Tubiana. 2010. 'Results and analysis of the 2008–2009 Insulin Injection Technique Questionnaire survey', Journal Of Diabetes, 2: 168-79.
Frid, Anders H, Gillian Kreugel, Giorgio Grassi, Serge Halimi, Debbie Hicks, Laurence J Hirsch, Mike J Smith, Regine Wellhoener, Bruce W Bode, and Irl B Hirsch. 2016. "New insulin delivery recommendations." In Mayo Clinic Proceedings, 1231-55. Elsevier.
Gentile, Sandro, Giuseppina Guarino, Annalisa Giancaterini, Piero Guida, Felice Strollo, and AMD-OSDI Italian Injection Technique Study Group. 2016. 'A suitable palpation technique allows to identify skin lipohypertrophic lesions in insulin-treated people with diabetes', SpringerPlus, 5: 1-7.
Grassi, Giorgio, Paola Scuntero, Rosalba Trepiccioni, Francesca Marubbi, and Kenneth Strauss. 2014. 'Optimizing insulin injection technique and its effect on blood glucose control', Journal of Clinical & Translational Endocrinology, 1: 145-50.
Ibarra, L, and F Gallego. 1998. 'Factors related to lipohypertrophy in insulin‐treated diabetic patients: role of educational intervention', Practical Diabetes, 15: 9-11.
Kapeluto, Jordanna, Breay W Paty, Silvia D Chang, Christopher Eddy, and Graydon Meneilly. 2015. 'Criteria for the Detection of Insulin-induced Lipohypertrophy Using Ultrasonography', Canadian Journal of Diabetes, 39: 534.
Seyoum, Berhane, and Jemal Abdulkadir. 1996. 'Systematic inspection of insulin injection sites for local complications related to incorrect injection technique', Tropical doctor, 26: 159-61.

Detection of lipohypertrophy in people with diabetes treated with insulin: a systematic literature review