Skip to main content

Advertisement

Log in

Ultrasound characterization of insulin induced lipohypertrophy in type 1 diabetes mellitus

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Objective

Subcutaneous insulin absorption is one of the key factors affecting glycemic control in patients with diabetes mellitus under insulin therapy. Insulin-induced subcutaneous lipohypertrophy has been reported to impair insulin regular absorption and hence glycemic control. So far, lipohypertrophy diagnosis has only been clinical. This study aims at evaluating the possible role of ultrasound scan in the assessment of subcutaneous lipohypertrophy in patients affected by type 1 diabetes mellitus.

Methods

A pilot observational retrospective study was performed in 20 patients affected by type 1 diabetes mellitus. In these patients the areas with clinical evidence of lipohypertrophy dependent on the insulin injections were characterized by the presence of tissues that at the ultrasound scan resulted similar to fibrotic tissues (hyperechogenic) or to an interstitial edema or to fat tissues (hypoechogenic). It was utilized a multi frequency linear probe (6–18 MHz). The patients were advised to avoid insulin injections on the areas with lipohypertrophy scanned by the ultrasound and the HbA1c changes were evaluated 3 months later.

Results

The lipohypertrophic areas presented at least three different aspects upon ultrasound assessment: the iso-hyperechogenic one, with a predominant fibrotic component; the isoechogenic one, with “large tangles” fibrotic elements and the iso-hypoechogenic aspect with no fibrotic elements. When patients were advised to avoid insulin injections on areas with lipohypertrophy defined by ultrasound scan, 3 months after the first evaluation HbA1c had significantly improved (basal HbA1c 7.87 ± 0.56 versus 7.67 ± 0.52 3 months later, p = 0.029). No significant improvements of the HbA1c were found in the control matched group in which lipohypertrophy was only clinically valued through inspection and palpation.

Conclusions

Ultrasound scan can help identify and characterize the lipohypertrophic areas and this might be useful to improve glycemic control.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

CSII:

Continuous subcutaneous insulin infusion

MDI:

Multiple daily injections

HbA1c:

Glycated hemoglobin

References

  1. DeVries JH (2013) Glucose variability: where it is important and how to measure it. Diabetes 62:1405–1408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Thow JC, Johnson AB, Marsden S, Taylor R, Home PD (1990) Morphology of palpably abnormal injection sites and effects on absorption of isophane (NPH) insulin. Diabet Med 7:795–799

    Article  CAS  PubMed  Google Scholar 

  3. Young RJ, Hannan WJ, Frier BM, Steel JM, Duncan LJ (1994) Diabetic lipohypertrophy delays insulin absorption. Diabetes Care 7:479–480

    Article  Google Scholar 

  4. Chowdhury TA, Escudier V (2003) Poor glycaemic control caused by insulin induced lipohypertrophy. BMJ 327:383–384

    Article  PubMed  PubMed Central  Google Scholar 

  5. Beckley JR, Longyhore DS (2013) Effect of changing insulin injection site on glycemic variability. Am J Health Syst Pharm 70:938–940

    Article  CAS  PubMed  Google Scholar 

  6. Radermecker RP, Scheen AJ (2007) Allergy reactions to insulin: effects of continuous subcutaneous insulin infusion and insulin analogues. Diabetes Metab Res Rev 23:348–355

    Article  CAS  PubMed  Google Scholar 

  7. Radermecker RP, Piérard GE, Scheen AJ (2007) Lipodystrophy reactions to insulin: effects of continuous insulin infusion and new insulin analogs. Am J Clin Dermatol 8:21–28

    Article  PubMed  Google Scholar 

  8. Holstein A, Stege H, Kovacs P (2010) Lipoatrophy associated with the use of insulin analogues: a new case associated with the use of insulin glargine and review of the literature. Expert Opin Drug Saf 9:225–231

    Article  CAS  PubMed  Google Scholar 

  9. Del Olmo MI, Campos V, Abellán P, Merino-Torres JF, Piñón F (2008) A case of lipoatrophy with insulin detemir. Diabetes Res Clin Pract 80:20–21

    Article  Google Scholar 

  10. Hussein SF, Siddique H, Coates P, Green J (2007) Lipoatrophy is a thing of the past, or is it? Diabet Med 24:1470–1472

    Article  CAS  PubMed  Google Scholar 

  11. Babiker A, Datta V (2011) Lipoatrophy with insulin analogues in type I diabetes. Arch Dis Child 96:101–102

    Article  PubMed  Google Scholar 

  12. Hajheydari Z, Kashi Z, Akha O, Akbarzadeh S (2011) Frequency of lipodystrophy induced by recombinant human insulin. Eur Rev Med Pharmacol Sci 15:1196–1201

    CAS  PubMed  Google Scholar 

  13. Fujikura J, Fujimoto M, Yasue S, Noguchi M, Masuzaki H, Hosoda K, Tachibana T, Sugihara H, Nakao K (2005) Insulin-induced lipohypertrophy: report of a case with histopathology. Endocr J 52:623–628

    Article  PubMed  Google Scholar 

  14. Vardar B, Kizilci S (2007) Incidence of lipohypertrophy in diabetic patients and a study of influencing factors. Diabetes Res Clin Pract 77:231–236

    Article  PubMed  Google Scholar 

  15. Conwell LS, Pope E, Artiles AM, Mohanta A, Daneman A, Daneman D (2008) Dermatological complications of continuous subcutaneous insulin infusion in children and adolescents. J Pediatr 152:622–628

    Article  CAS  PubMed  Google Scholar 

  16. Blanco M, Hernández MT, Strauss KW, Amaya M (2013) Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes. Diabetes Metab 39:445–453

    Article  CAS  PubMed  Google Scholar 

  17. Wallymahmed ME, Littler P, Clegg C, Haqqani MT, Macfarlane IA (2004) Nodules of fibrocollagenous scar tissue induced by subcutaneous insulin injections: a cause of poor diabetic control. Postgrad Med J 80:732–733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bode BW (2011) Comparison of pharmacokinetic properties, physicochemical stability, and pump compatibility of 3 rapid-acting insulin analogues-aspart, lispro, and glulisine. Endocr Pract 17:271–280

    Article  PubMed  Google Scholar 

  19. Ratner RE, Phillips TM, Steiner M (1990) Persistent cutaneous insulin allergy resulting from high-molecular-weight insulin aggregates. Diabetes 39:728–733

    Article  CAS  PubMed  Google Scholar 

  20. Johansson UB, Amsberg S, Hannerz L, Wredling R, Adamson U, Arnqvist HJ, Lins PE (2005) Impaired absorption of insulin aspart from lipohypertrophic injection sites. Diabetes Care 28:2025–2027

    Article  PubMed  Google Scholar 

  21. Richardson T, Kerr D (2003) Skin-related complications of insulin therapy: epidemiology and emerging management strategies. Am J Clin Dermatol 4:661–667

    Article  PubMed  Google Scholar 

  22. Babar GS, Ali O, Parton EA, Hoffmann RG, Alemzadeh R (2009) Factors associated with adherence to continuous subcutaneous insulin infusion in pediatric diabetes. Diabetes Technol Ther 11:131–137

    Article  CAS  PubMed  Google Scholar 

  23. Frid A, Hirsch L, Gaspar R, Hicks D, Kreugel G, Liersch J, Letondeur C, Sauvanet JP, Tubiana-Rufi N, Strauss K, Scientific Advisory Board for the Third Injection Technique Workshop (2010) New injection recommendations for patients with diabetes. Diabetes Metab 36(Suppl 2):S3–S18

    Article  PubMed  Google Scholar 

  24. Hambridge K (2007) The management of lipohypertrophy in diabetes care. Br J Nurs 16:520–524

    Article  PubMed  Google Scholar 

  25. Heinemann L (2010) Insulin absorption from lipodystrophic areas: a (neglected) source of trouble for insulin therapy? J Diabetes Sci Technol 4:750–753

    Article  PubMed  PubMed Central  Google Scholar 

  26. DeSalvo DJ, Maahs DM, Messer L, Wadwa LP, Payne S, Ly TL, Buckingham BA (2015) Effect of lipohypertrophy on accuracy of continuous glucose monitoring in patients with type 1 diabetes. Diabetes Care 38:e166–e167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Overland J, Molyneaux L, Tewari S, Fatouros R, Melville P, Foote D, Wu T, Yue DK (2009) Lipohypertrophy: does it matter in daily life? A study using a continuous glucose monitoring system. Diabetes Obes Metab 11:460–466

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank dott.ssa Giusy Coppola for the English revision of the text.

Author Contribution

All the authors gave a substantial contribution to conception, design and critically revision of the final version. In particular: E.M., E.B participated in the research design and the performance of the research; M.N. participated in data analysis, L.L. participated in the research design and writing of the manuscript, O.E. participated in the research design and performance of the research. F.B. participated in performance of the research, research design and writing of the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to F. Bertuzzi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Statement of human and animal rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. The local responsible Ethics Committee has given specific approval. Informed consent was obtained from all patients for being included in the study when it was required. The ClinicalTrials.gov Identifier number is NCT02278926.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bertuzzi, F., Meneghini, E., Bruschi, E. et al. Ultrasound characterization of insulin induced lipohypertrophy in type 1 diabetes mellitus. J Endocrinol Invest 40, 1107–1113 (2017). https://doi.org/10.1007/s40618-017-0675-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-017-0675-1

Keywords

Navigation