Why does insulin cause lipodystrophy

Lipohypertrophy in turn was associated with the use of higher dose of insulin and nonoptimal glycemic control. Findings of this study revealed that in spite of using recombinant human insulin, the magnitude of the lipohypertrophy still remained high. Therefore, a routine workup of insulin-injecting patients for such complication is necessary, especially in the individuals who have a nonoptimal glycemic control. Diabetes mellitus is a huge and growing global health problem which demands modern therapy involving greater and earlier use of intensive insulin regimens in order to achieve better control of blood glucose levels and reduce the long-term risks associated with the condition [ 1 ].

However, a study recently reported an alarming magnitude of diabetic patients having poor glycemic control in spite of their routine insulin use [ 2 ]. An obvious explanation for this condition is lacking; however, a study linked this poor glycemic control with insulin administration, storage, handling, and skin complications [ 3 ]. Lipoatrophy or local fat loss is one of the skin complications of insulin injection and is clinically characterized by visible cutaneous depression and palpable atrophy of subcutaneous fat tissue at the injection site.

It may result from a local immune reaction against impurities of the insulin preparations and due to the use of purified human insulin preparations; this condition has dramatically decreased since the s [ 4 , 5 ]. Lipohypertrophy is characterized by a tumor-like swelling of fatty tissue around subcutaneous insulin injection sites [ 8 ]. Histologically, the hypertrophic adipocytes are twice as large as those from normal subcutaneous areas and contained numerous small lipid droplets.

Electron microscopic analysis also revealed a minor population of small adipocytes, suggesting active differentiation or proliferation [ 7 ]. Lipohypertrophy area becomes hyposensitive. Once the patient feels pain when injecting elsewhere, but not in the lipohypertrophic area, he or she tends to continue injecting in the same site even if aware of the need to rotate sites [ 4 ].

The injection of insulin into a site of lipodystrophy may lead to erratic absorption of the insulin, with the potential for poor glycemic control and unpredictable hypoglycemia [ 7 , 9 , 10 ]. Factors such as insulin use time, gender, body mass index, injection site, recurrent tissue trauma from failure to rotate injection sites, and the frequency of needle reuse have been reported to be associated with the development of lipohypertrophy [ 6 , 11 , 12 ].

Despite factors which lead to lipohypertrophy have been identified, it is still continuing to be high. However, scanty data are available regarding lipodystrophy in Ethiopia. Therefore, this study was done to determine magnitude of lipodystrophy and identify associated factors as well as to assess the impact of lipodystrophy on glycemic control.

The study was conducted at diabetic center of Tikur Anbessa Specialized Hospital, Ethiopia using a cross sectional study design. All children and adolescent patients who used insulin for a minimum of one year and visited the center from April to July were enrolled in the study. Participants were included to this study based on their availability during their routine outpatient clinic visit within the study period. A total of type 1 diabetic patients were screened within the predetermined period, and patients who have fulfilled inclusion criteria were included using the consecutive sampling technique.

Data collectors were not having knowledge of the lipodystrophy status of patients at study entry, when an assessment of their injection technique as well as examination of their injection sites was made later. Glycated hemoglobin HgbA1c test is the most reliable form of diabetes diagnostic assessment, providing a good indication of glycemic control over several months [ 14 ].

Unlike lots of studies, in this study, glycemic control was not assessed by glycemic variability of participants since most of them were not performing self-blood glucose monitoring. Observation and palpation techniques were used in assessing lipodystrophy in these diabetics [ 6 ]. A thorough palpation technique slow circular and vertical fingertip movements followed by repeated horizontal attempts on the same spot was done.

Health professionals were also advised to be gentle while touching the skin at the beginning and start to progressively increase finger pressure thereafter. They were also suggested to perform the pinch maneuver when perceiving a harder skin, to confirm their first impression by comparing the thickness of the suspected spot to that of surrounding areas.

Smaller and flatter lesions were best identified by repeating all abovementioned palpation maneuvers [ 16 , 17 ]. The presence of a noticeable or palpable lump at the injection site indicated that lipodystrophy was present.

Accordingly, lipodystrophy was defined to have different grades based on morphology and pathogenesis. Five experienced nurses working in diabetes clinic were recruited to extract data and to examine cases. One of them was extracting all the necessary data based on the questionnaire and the second nurse was performing the visual inspection and palpation of injection sites to detect lipodystrophy.

This type of data collection technique was intentionally applied to reduce bias that would happen if a single data collector was involved in both activities. Multivariate logistic regression was used for the adjustment of potential confounders.

Children , Insulin injectors with the primary level of education constituted the highest percentage 85, Comparable proportions of parents 99, About three-fourths , Approximately two-thirds , Almost all , Higher frequency , Only few 33, One in three 54, Above half , Forty-four percent of the participants injected on multiple injection sites. Injection on arms 50, The prevalence of insulin-induced lipodystrophy was The lipohypertrophic site was commonly observed on arms 64, Since almost all lipodystrophies were lipohypertrophy in type, it will be used to refer to these lesions in the rest of this report.

Patients with lipohypertrophy and without lipohypertrophy did not differ significantly by gender, educational level of injectors, BMI, insulin use time, insulin type, space measurement on injection, and frequent unexplained hypoglycemia.

The presence of insulin-induced lipohypertrophy was significantly associated with the occurrence of nonoptimal glycemic control. However, severity of lipohypertrophy and site of lipohypertrophy were not significantly associated with the occurrence of nonoptimal glycemic control Table 2.

In the present study, This finding was not in line with the previous studies which reported that grade 1 was the commonest type of lipodystrophy [ 7 , 15 ]. However, like the previous studies [ 6 , 19 ], grade 3 lipoatrophy was still continuing to be a rare 2. This could be due to the introduction of high purity human recombinant insulin.

Lipohypertrophy was seen to develop mostly in the arms; this might be tied to the high number of patients injected in their arms, and mostly, admonition was by parents. This result was also congruent with the reports of other studies [ 7 , 19 ]. Injection site lipohypertrophy occurred almost 3 times higher among children compared to adolescents. This was also reported similarly by other studies [ 11 , 19 ]. I learned that the best type 2 diabetes diet is the one that works for you.

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Health Conditions Discover Plan Connect. Type 2 Diabetes. Medically reviewed by Natalie Olsen, R. Repeated insulin injections in the same location can cause fat and scar tissue to accumulate. Symptoms of lipohypertrophy. Treating lipohypertrophy. Causes of lipohypertrophy. Risk factors. Preventing lipohypertrophy. When to call a doctor. Read this next. Ventrogluteal Injection. Medically reviewed by Debra Sullivan, Ph. Medically reviewed by Stacy Sampson, D.

A Look at Testosterone Injections. Medically reviewed by Zara Risoldi Cochrane, Pharm. Medically reviewed by Kelly Wood, MD. Medically reviewed by Marina Basina, M. Therefore, leptin down-regulation together with FFA increase could contribute to the observed recruitment of fat cell precursors.

Nevertheless, the relative abundance of interstitial fluid hampering the cell-to-cell adhesion, a well-known trigger of cell differentiation, and local alterations in insulin responsiveness could inhibit the neoadipogenesis. In this regard, the presence of small adipocytes with abundant glycogen accumulation could suggest a blunted process of differentiation together with an impairment of liposynthesis In fact, the glycogen granules inside the delipidized cells could be seen as an attempt to recover the adipose triglyceride stores, as reported in an animal model investigating the fasting to fed transition Finally, the reduction of fat cells and the relative enlargement of the interstitial space could justify the increase of the capillary network as previously reported by other authors 7.

The focal amyloid deposition in the interstitial space could be assigned to insulin itself as previously reported 25 , but we cannot exclude the production of amyloid from adipocytes It is a common clinical observation, as was also the case in our patients, that LA lesions recover spontaneously by changing the site of insulin infusion or insulin type.

Therefore, what occurs in the LA areas is a reversible phenomenon, far from permanent cellular damage or dedifferentiation and from a complete disappearance of adipose tissue cells and precursors. Our data clearly show that adipocytes in the LA areas undergo an unrestrained lipolysis, and preadipocytes are then recruited while resting. In conclusion, we suggest that adipose tissue metabolic alterations could play a role in the pathogenesis of LA. Am J Clin Dermatol 8 : 21 — Google Scholar.

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Volume Article Contents Patients and Methods. Milan , G. Oxford Academic. Cite Cite G. Select Format Select format. Permissions Icon Permissions. TABLE 1. Clinical and biological characteristics of the patients.