Risk factors and Prevalence of lipohypertrophy in insulin injection treated Diabetic patients in Wuhan Union Hospital Between 2017 november and 2018 march Abstract Skin lesions at the site of subcutaneous insulin injections are named as lipodystrophy

Risk factors and Prevalence of lipohypertrophy in insulin injection treated Diabetic patients in Wuhan Union Hospital Between 2017 november and 2018 march Abstract Skin lesions at the site of subcutaneous insulin injections are named as lipodystrophy

Risk factors and Prevalence of lipohypertrophy in insulin injection treated Diabetic patients in Wuhan Union Hospital
Between 2017 november and 2018 march

Skin lesions at the site of subcutaneous insulin injections are named as lipodystrophy. It has two types of clinical presentations namely lipoatrophy and lipohypertrophy. The prevalence of lipoatrophy and lipohypertrophy has wide variations which proves the need for accurate identification method. lipohypertrophy surely distorts insulin absorption. So further subcutaneous insulin injections shouldn’t be admisnistered into these lesions and correct site rotation will surely help to prevent them. Patients on insulin should be aware of and educated on the importance of a) acceptable needle size b) accurate injection delivery c) how to avoid complications such as lipohypertrophy and infections and d ) various other apects of injection techniques such as site rotations. Since the clinical manifestation was not evident, we have maily relied of ultrasound imaging for detection of lipohypertrophy.

– Definition
Lipohypertrophy (LH) is defined as a thick mass of rubber like tissue swelling which usually appears firm but occasionally may present as soft swelling/lesion. During early stages the swelling is usually not evident and so this might easily be missed during a clinical evaluation. Etiology of lipohypertrophy is still unclear. There are several causative local factors like a) growth promoting properties of Insulin b) improper injection site rotations c) recurrent trauma caused by poor injection techniques by patients d) frequent needle reuse. High BMI (Body mass index), long duration and higher doses of insulin are also associated with LH. LH can be accurately identified by careful clinical examination and ultrasound imaging (USG) . The steps to identify LH are not yet laid out clearly in many published journals.
– Blanco M, Herna ?ndez MT, Strauss KW, Amaya M. Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes. Diabetes Metab. 2013;39:445–53. ?
– Al Ajlouni M, Abujbara M, Batieha A, Ajlouni K. Prevalence of lipohypertrophy and associated risk factors in insulin-treated patients with type 2 diabetes mellitus. Int J Endocrinol Metab. 2015;13:e20776.
– Gentile S, Guarino G, Guida P, Strollo F, On behalf of the AMD-OSDI Italian Injection Technique Study Group. A suitable palpation technique allows to identify skin lipohypertrophic lesions in insulin-treated people with diabetes. SpringerPlus. 2016;5:563. doi:10.1186/s40064-016-1978-y.
– Gentile S, Strollo F, Guarino G, Giancaterini A, Ames PRJ, et al. Factors hindering correct identification of unapparent lipohypertrophy. J Diabetes Metab Disord Control. 2016;3:00065. doi:10.15406/jdmdc.2016.03.00065.

– Pathology

Lipodystrophy is a disorder of fat tissue. There are 2 main types of lipodystrophy: lipoatrophy, which is loss of adipocytes that clinically manifests as indenting and cratering, and LH, which is enlargement of adipocytes that manifests as swelling or induration of fat tissue.151 An even rarer type of lipodystrophy is amyloidosis,152-155 for which a biopsy and pathologic diagnosis are usually necessary. Insulin injected into amyloid deposits may have substantially impaired absorption. Usually, LH regresses after stopping insulin injections into the lesions, whereas local- ized amyloidosis does not. Distinguishing these lesions is clinically important.
Lipohypertrophy is common, although studies vary on the exact frequency. A Spanish study156 found LH in nearly two-thirds of injecting patients (64.4%) (type 1 diabetes, 72.3% vs type 2 diabetes, 53.4%). An Italian study143 found the prevalence to be 48.7%, and in a Chinese study157 it was 53.1%. The absorption of insulin injected into LH lesions may be erratic and unpredictable, which can lead to hyperglycemia, unexpected hypoglyce- mia, or increased glucose variability.158,159 Conversely, patients who switch from injecting into LH lesions to normal tissue are at risk for hypoglycemia unless they lower their doses. A summary of additional studies in LH and pointers for optimizing the physical examina- tion for LH are presented in Supplemental Appendix 6 (available online at http://www. mayoclinicproceedings.org) (Irl B. Hirsch, MD, oral communication, October 24, 2015).88,160-177 Lipoatrophy studies are also summarized at this site.

– Recommendations
  insulin injection practice according to the reference of Forum for Injection Technique and Therapy: Expert Recommendations 20 by the Health Professionals 
– Frid A. H., Kreugel G., Grassi G., et al. New Insulin Delivery Recommendations. Mayo Clinic Proceedings. 2016;91(9):1231–1255. doi: 10.1016/j.mayocp.2016.06.010.  PubMed Cross Ref

– Relation to diabetes control

Materials and methods

This study was conducted among inpatients in Endocrinology department of Wuhan Union Hospital. We specifically choose inpatients as they were requiring admission due to uncontrolled diabetes, due to complications or referred from surgery department for control of diabetes prior to surgery.

In this study , the inclusion criteria were patients of both sex with type 1 or type 2 diabetes treated with insulin injection for atleast a year with insulin self administered by the patient or either by the hospital staff continuously without any break . outpatients were excluded. No age limit has been assigned. The variables studied were age, sex, type of diabetes, duration of insulin treatment, number of insulin injections per day, type of insulin used, needle length, frequency of reuse of needles, Body mass index ( BMI ), and correct injection site rotations from patient history. Correct injection site rotation was defined as spacing the injection sites 1 cm apart to avoid repeated tissue damage and changing the needle entry points for injections.

A total of 27 inpatients fit in the above inclusion criteria (with and without clinically evident lipohypertrophy ) were willing to participate in whom we performed ultrasound (USG) imaging at the injection sites to check for lipohypertrophy. USG was performed on the skin and soft tissue. USG was performed by Union Hospital department and was not performed by same technician. The duration of study was from November 2017 to March 2018.



Most studies suggest that insulin absorption at areas affected by LH may be both delayed and erratic, leading to the need for ever increasing doses of insulin and worsening metabolic control 10–14 . This in turn causes unacceptable glucose oscillations due to a high rate of serious hypoglycemic episodes followed by rebound glucose spikes whenever patients suddenly switch from affected injection sites to normal ones. Under these conditions, the economic burden of the disease increases for both patients and the healthcare system. Therefore, it is crucial that as many areas affected by LH as possible are systematically identified in order to educate patients on good insulin injection habits. The reported prevalence of LH in patients receiving insulin injections varies widely in published studies 6, possibly due to the lack of a well-structured diagnostic flow-chart despite the world-wide availability of suitable ultrasound and radiological methods 1, 15–24. We recently published a methodological paper on a palpation technique that enables the clinician to identify skin lipohypertrophic lesions in diabetic patients receiving insulin 6. We therefore propose that diabetes teams be formed at medical institutions which would systematically follow that simple procedure we describe for the diagnosis of LH at all insulin injection sites and then implement and hopefully progressively refine this procedure in large-scale studies. In particular, unexplained variations in glucose levels and/or unexplained hypoglycemic episodes may alert healthcare providers to look for LH in diabetic patients receiving insulin injections.
Numerous studies have suggested that further insulin administration at LH affected areas may lead to both erratic and delayed insulin absorption which will lead to increased insulin dosage and poor glycemic control.
10. Gentile S, Agrusta M, Guarino G, Carbone L, Cavallaro V, et al. Metabolic consequence of incorrect insulin administration techniques in aging subjects with diabetes. Acta Diabetol. 2011;48:121–5.
11. Young RJ, Hannan WJ, Frier BM, Steel JM, Duncan LJ. Diabetic lipohypertrophy delays insulin absorption. Diabetes Care. 1984;7:479–80.
12. Frid A, Linden B. Computed tomography of injection sites in patients with diabetes mellitus. Injection and absorption of insulin. Stockholm 1992: Thesis.
13. Chowdhury TA, Escudier V. Poor glycaemic control caused by insulin induced lipohypertrophy. Br Med J. 2003;327:383–4.
14. Johansson UB, Amsberg S, Hannerz L, Wredling R, Adamson U, Arnqvist HJ, Lins PE. Impaired absorption of insulin aspart? From lipohypertrophic injection sites. Diabetes Care. 2005;28:2025–7.
Under these circumstances the economic burden on both the patient and healthcare system increases. LH is associated with wide range levels of glucose oscillations , hypoglycemic episodes to hyperglycemic episodes of same patient when switching injection sites from LH affected areas to non affected areas. There is lack of well structured clinical diagnostic flowchart and clinical negligence from physicians and radiologists regarding effects of LH on glycemic control ; its detection even though we have availability of USG imaging technique which we have encountered during our study.
15. Grassi G, Scuntero P, Trepiccioni R, Marubbi F, Strauss K. Optimizing insulin injection technique and its effect on blood glucose control. J Clin Translat Endocrinol. 2014;1:145–50.
16. Vardar B, Kizilci S. Incidence of lipohypertrophy in diabetic patients and a study of influencing factors. Diabetes Res Clin Pract. 2007;77:231–6.
17. Seyoum B, Abdulkadir J. Systematic inspection of insulin injection sites for local complications related to incorrect injection technique. Trop Dr. 1996;26:159–61.
1. Hauner H, Stockamp B, Haastert B. Prevalence of lipohypertrophy in insulin-treated diabetic patients and predisposing factors. Exp Clin Endocrinol Diabetes. 1996;104:106–10. ?
2. McNally PG, Jowett NI, Kurinczuk JJ, Peck RW, Hearnshaw JR. Lipohypertrophy and lipoatrophy complicating treatment with highly purified bovine and porcine insulin. Postgrad Med J. 1988;64:850–3. ?
3. Partanen T, Rissanen A. Insulin injection practices. Pract Diabetes Int. 2000;17:252–4. ?
4. Raile K, Noelle V, Schawarz HP. Insulin antibodies are associated with lipoatrophy but also with lipohypertrophy in children and adolescents with type 1 diabetes. Exp Clin Endocrinol Diabetes. 2001;109:393–6. ?
5. Teft G. Lipohypertrophy: patient awareness and implications for practice. January–February/2002. http://www.findsarticle.com. Accessed 7 May 2016. ?
6. Kordonouri O, Lauterborn R, De?ss D. Lipohypertrophy in young patients with type 1 diabetes. Diabetes Care. 2002;25:634. ?
7. Hajheydari Z, Kashi Z, Akha O, Akbarzadeh S. Frequency of lipodystrophy induced by recombinant human insulin. Eur Rev Med Pharmacol Sci. 2011;15:1196–201. ?

In a clinical journal of diagnosis and research, a case reported in 2016. It showed a T1DM patients on insulin whose improper site rotation had resulted in high grade lipohypertrophy with compromised glycaemic control and also required an increased insulin dose to manage. The report also explained that the blood sugar levels were back to normal after 6 months of correct administration of insulin injections with site rotation and avoiding the hypertrophied sites. The lipohypertrophy was significantly reduced in six months period.

Sahasrabudhe RA, Limaye TY, Gokhale VS. Unexplained Persistent Hyperglycaemia in a Type I Diabetes Patient – Is Injection Site Lipohypertrophy the Cause? Journal of Clinical and Diagnostic Research?: JCDR. 2016;10(9):OD05-OD06. doi:10.7860/JCDR/2016/22215.8483.

Most chinese patients considered the LH as unimportant and were unwilling to participate despite the explanation on its importance. Unexplained glucose level variations should definitely alert clinicians to check for LH in the patients as well.


Despite the advantages such as earlier onset of action (fast acting insulin analogues like lispro , aspart and glulisine ) and longer duration of action ( detemir, degludec, glargine ) in using insulin analogues in comparison to human insulin , a study conducted In 2008 by the Canadian Agency for Drugs and Technologies in Health (CADTH) found that when comparing the effects of insulin analogues with biosynthetic human insulin, insulin analogues failed to prove any clinically relevant differences whether in terms of glycemic control and in hypoglycemic adverse events.

Banerjee S, Tran K, Li H, Cimon K, Daneman D, Simpson S, Campbell K. “Short-acting insulin analogues for diabetes mellitus: meta-analysis of clinical outcomes and assessment of cost-effectiveness,” Technology Report No 87. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2007.

So correct injection technique and site rotation are the most important factors determining the incidence of lipohypertrophy .



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