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Lipodystrophy at the insulin injection sites: current trends in epidemiology, diagnostics and prevention

Vadim V. Klimontov, Mikhail M. Lazarev, Andrey Ju. Letyagin, Dinara M. Bulumbaeva, Natalia P. Bgatova

https://doi.org/10.14341/DM12095

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Abstract

Lipodystrophy at the injection sites is most common local complication of insulin therapy. The history of its study started in 1926, when first cases of lipoatrophy at the sites of insulin injections were described. As we moved to human insulin and insulin analogues, immune mediated atrophic form of lipodystrophy has been replaced by hypertrophic one, which reflects anabolic and mitogenic effect of insulin.

Lipohypertrophy at the injection sites is detected by physical examination in 40-70% of insulin-treated subjects. The detection efficiency depends on health care provider`s skills. Therefore, training of medical doctors and nurses in physical examination of injection sites seems to be reasonable.

In recent years, ultrasound was introduced for diagnostics of insulin-induced lipohypertrophy. The method is more sensitive compared to palpation; ultrasound-verified lipohypertropthy was detected in more than 80% of cases. In patients with wide-spread lipohypertrophy ultrasound can be used to find suitable sites for injections (“ultrasound injection map”). Strain sonoelastography and 3D-power Doppler ultrasound can be used for quantitative estimation of rigidity and vascularization of lipohypertrophy. Both MRI and infrared images are considered as promising diagnostic tools.

In a number of studies, it has been shown that the presence of lipohypertrophy is associated with high HbA_1c levels, enhanced glycemic variability, «unexplained» hypoglycemia, and increased insulin doses. Thereby, lipohypertrophy aggravates the diabetes-related costs.

The main risk factor for lipohypertrophy is inappropriate injection technique, including the lack of the site rotation, injections into lipodystrophic lesions, small injection area, reuse or excessive length of the needles. Accordingly, training patients in the injection technique is the basis for prevention of complication. The cessation of injections in lipohypertrophy areas and regular site rotation is essential for adequate titration of insulin dose and achievement of glycemic targets.

Keywords

diabetes mellitus, insulin, injections, subcutaneous tissue, lipodystrophy, ultrasonography

About the Authors

Vadim V. Klimontov

Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation

MD, PhD, Professor

Mikhail M. Lazarev

Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation

MD, junior research associate

Andrey Ju. Letyagin

Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation

MD, PhD, Professor

Dinara M. Bulumbaeva

Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation

MD, junior research associate

Natalia P. Bgatova

Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation

PhD, Professor

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Supplementary files

	1. Fig. 1. The light-optical picture of insulin-induced lipohypertrophy in the subcutaneous fatty tissue of the anterior abdominal wall. A - plot of lipohypertrophy with fibrosis (arrow); B - a site of unchanged subcutaneous adipose tissue in an area free of lipodystrophy. Hematoxylin-eosin staining. Light microscopy. SW × 400
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	2. Fig. 2. Ultrastructural features of insulin-induced lipohypertrophy in the subcutaneous fatty tissue of the anterior abdominal wall. A - collagen fibers (arrows); B - a blood capillary with a large number of transport vesicles (arrows) in the endothelium. Electron microscopy. SW A - 12,000x; B - 40 000x.
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	3. Fig. 3. Plots of lipohypertrophy at the injection sites of insulin on the left and right shoulder in a patient with type 1 diabetes mellitus: F-nd F., 27 years old, type 1 diabetes mellitus for 26 years. Therapy with insulin analogues (degludec and aspart). On examination and palpation revealed areas of lipohypertrophy at the injection of insulin in the shoulder.
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	4. Fig. 4. The hyperechoic heterogeneous site of lipohypertrophy in the subcutaneous fatty tissue of the anterior abdominal wall in the area of insulin injection: scanning in B-mode. B-naya K., 32 years old, type 1 diabetes mellitus for 20 years, therapy with insulin analogues (glargin 100 U / ml, lyspro).
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	5. Fig. 5. A heterogeneous site of increased rigidity lipohypertrophy in the subcutaneous fatty tissue of the anterior abdominal wall in the area of insulin injection. A - gray-scale scan in B-mode; B - real-time compression sonoelastography: areas of increased stiffness are colored blue. Boy B., 48 years old, type 2 diabetes mellitus, insulin analogue therapy (levemir) for 6 months.
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	6. Fig. 6. Reconstruction of the site of lipohypertrophy in the subcutaneous tissue of the anterior abdominal wall in the area of insulin injection. 3D Angio mode. 1 - blood vessels of the subcutaneous tissue, 2 - avascular zone in the area of lipohypertrophy. B-naya K., 32 years old, type 1 diabetes mellitus for 20 years, therapy with insulin analogues (glargin 100 U / ml, lyspro).
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	7. Fig. 7. 3D reconstruction of MRI images of areas of lipohypertrophy in the subcutaneous tissue of the anterior abdominal wall in the area of insulin injection in a patient with diabetes mellitus: MR tomograph General Electric Discovery MR750W (magnetic field 3.0 T). Coil: Body 48 AA, reconstructed diameter 400 mm, matrix 320x320. Technology (from left to right): T1-WI (TR 195.0; TE 2.1; cut 3 mm); T2-WI Propeller (TR 4000.04 ms; TE 95.8 ms, 3 mm cut), T2-WI FS Rtr Propeller (selective grease suppression; TR 4000.04 ms; TE 95.76 ms, 3 mm cut). In all cases - synchronized coronal projection (slice thickness - 3 mm). Images were obtained in 3D-Volume Rendering mode (multi-planar surface reconstruction; Skin B / W was used in all cases) in the RadiAnt DICOM Viewer Ver program. 5.0.1.21910 (64-bit) [51]. On T1-WI, a green oval shows the zone of lipohypertrophy to the right of the umbilical ring; when comparing T2-WI and T2-WI FS, it is seen that the suppression of the lipid component is negligible (compared to the contralateral side). On T1-WI, the red circle shows the area of lipohypertrophy of adipose tissue to the left of the umbilical ring (mirror image). When comparing T2-WI and T2-WI FS, it is seen that the suppression of the lipid component is significant (compared to the contralateral side). Here and in fig. 8, 9: B-ya Ya., 25 years old, type 1 diabetes mellitus for 20 years, therapy with insulin analogues (glargin 100 U / ml and lizpro).
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	8. Fig. 8. 3D reconstruction of MRI images of the subcutaneous vessels of the anterior abdominal wall in a patient with diabetes mellitus: MR-tomograph General Electric Discovery MR750W (magnetic field 3.0 T). Coil: Body 48 AA, reconstructed diameter 400 mm, matrix 320x320. Technology: T2-WI FS Rtr Propeller (selective fat reduction; TR 4000.04 ms; TE 95.76 ms, 3 mm cut). The image was obtained in 3D-Volume Rendering mode (multi-planar surface reconstruction; Skin B / W was used in all cases) in the RadiAnt DICOM Viewer Ver program. 5.0.1.21910 (64-bit) [51]. In the zone of lipohypertrophy to the left of the umbilical ring (mirror image), the density of blood vessels is higher than in the contralateral zone, but the vascular tree is less structured (chaotic).
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	9. Fig. 9. Lipodystrophy at the injection site of insulin: clinical and economic consequences.
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	10. Fig. 7
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	11. Fig. 8
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	12. Fig. 9
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For citations:

Klimontov V.V., Lazarev M.M., Letyagin A.J., Bulumbaeva D.M., Bgatova N.P. Lipodystrophy at the insulin injection sites: current trends in epidemiology, diagnostics and prevention. Diabetes mellitus. 2020;23(2):161-173. (In Russ.) https://doi.org/10.14341/DM12095

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ISSN 2072-0351 (Print)
ISSN 2072-0378 (Online)