Prediction of lipohypertrophy in patients with diabetes mellitus

V Brijeetha; Jonita Evett Fernandes; Jyothi Idiculla

doi:10.4103/jmgims.jmgims_58_19

ORIGINAL ARTICLE

Year : 2020 | Volume : 25 | Issue : 2 | Page : 86-89

Prediction of lipohypertrophy in patients with diabetes mellitus

V Brijeetha¹, Jonita Evett Fernandes², Jyothi Idiculla²
¹ Department of Medicine, MAGJ Hospital, Ernakulum, Kerala, India
² Department of Medicine, St. Johns Medical College, Bengaluru, Karnataka, India

Date of Submission	05-Sep-2019
Date of Acceptance	12-Jun-2020
Date of Web Publication	15-Dec-2020

Correspondence Address:
Dr. Jonita Evett Fernandes
B5, Apartment 207, L and T South City, Arekere Mico Layout, Bengaluru - 560 076, Karnataka
India

Source of Support: None, Conflict of Interest: None

Check

DOI: 10.4103/jmgims.jmgims_58_19

Abstract

Introduction: Lipohypertrophy (LH) may result in variable absorption of insulin and affect glycemic control. Objectives: This study aimed to study the risk factors and prevalence of lipohypertrophy in diabetic patients at a tertiary hospital in South India. Methodology: 206 patients with diabetes mellitus aged over 18 years of age, on insulin therapy for over two years, were included in this study conducted at St Johns Medical Hospital to explore the prevalence and risk factors for development of lipohypertrophy. Demographics, duration of diabetes and insulin therapy, type of needles used, times of reuse, injection technique was recorded. The injection sites were inspected meticulously for the presence of lipohypertrophy. Results: 66 patients (32%) were found to have LH of which 62 had Type 2 diabetes and 4 had Type 1 diabetes. The median duration of diabetes was 15 years (IQR 10-20) and was higher in the group with LH (P=0.000). The duration of insulin therapy was 10 years (IQR 5-10.5) and was significantly higher in the group with LH (P=0.000). The commonest site for insulin injection was the abdomen and it was associated with LH (P=0.000).Patients reusing the needles over 6 times and those who failed to rotate injection sites had the highest frequency of LH(P=0.000). Conclusions: Patients on long term insulin should be advised against the reuse of needles to save on cost of therapy in view of increased risk of LH and glycemic variability. Physicians must reinforce proper insulin injection technique periodically and document lipohypertrophy if present.

Keywords: Lipohypertrophy, reuse of insulin needles, type 2 diabetes mellitus

How to cite this article:
Brijeetha V, Fernandes JE, Idiculla J. Prediction of lipohypertrophy in patients with diabetes mellitus. J Mahatma Gandhi Inst Med Sci 2020;25:86-9

How to cite this URL:
Brijeetha V, Fernandes JE, Idiculla J. Prediction of lipohypertrophy in patients with diabetes mellitus. J Mahatma Gandhi Inst Med Sci [serial online] 2020 [cited 2023 Jun 4];25:86-9. Available from: https://www.jmgims.co.in/text.asp?2020/25/2/86/303421

Introduction

The economic implications of the burden of diabetes mellitus are immense. Half of the population with diabetes remains undiagnosed and presents with debilitating or life-threatening complications. According to the International Diabetes Federation estimates, around 77 million people in India had diabetes mellitus in 2019, accounting for 8.8% of the population between 20 and 79 years.^[1]

Patients with Type 2 diabetes mellitus are initiated on insulin if glycemic control is not achieved with oral anti-diabetic agents.^[2] Insulin injection technique is core to success in this drug delivery system as the site of injection, the timing, the type of insulin, and the method of injection contribute to the absorption of this drug.^[3] Repeated subcutaneous administration of insulin into the skin results in rubbery swellings due to fatty lumps, resulting in lipohypertrophy (LH) in the area.^[4],[5] This may result in marked variability in insulin absorption and either poor glycemic control or hypoglycemia.^[6],[7],[8] Identifying the predictors of LH is imperative to minimize this highly prevalent unwanted effect of insulin therapy. This study investigates the prevalence and risk factors of LH in insulin-treated patients in a Southern Indian state.

Materials and Methods

A cross-sectional, descriptive study was conducted in St. John's Medical College Hospital, Bangalore, in both inpatient and outpatient settings after obtaining clearance from the institutional ethics committee. Adults over the aged 18 years seen were recruited after obtaining informed written consent if they were on daily insulin therapy for over 2 years. The details of the participants fulfilling the above criteria were entered into the prescribed pro forma after obtaining written informed consent. This included age, gender, educational status type and duration of diabetes, duration of insulin therapy, type of needles used, times of reuse, injection techniques including sites, and if insulin was initiated by the physician or the endocrinologist. The injection sites were inspected meticulously for the presence of LH against direct and tangential light. Following this, the injection area was palpated by slow circular, vertical, and horizontal fingertip movements and also by pinching in case of hard skin.^[7]

Sample size

A sample size of 206 was calculated with a power of 96% and an alpha error of <0.05% based on the study done in the National Centre for Diabetes, Endocrinology and Genetics in Amman, Jordan.^[9]

Statistical analysis

Data were analyzed using the SPSS (IBM SPSS Statistics for Windows, Version 20. Armonk, NY, USA: IBM Corp.). Descriptive statistics such as mean and standard deviation values for continuous variables were computed. Analysis of numerical variables was done using t-test for parametric data and Mann–Whitney U-test for nonparametric data. Chi-square test was used for assessing association between categorical data and hierarchical stepwise logistic regression to predict LH from multiple risk factors.

Results

A total of 206 patients were enrolled into the study of which 48% were females. The male: female ratio was 1.07. There was no statistically significant association between gender and the presence of LH (p = 0.417). The mean age of the patients was 62.08 ± 10.08 years. The mean age of the patients with LH was 63.5 ± 13.5 years and the mean age in those without LH was 61.5 ± 13 years (p = 0.034).

On dividing the participants into four groups based on education status (below 10^th Grade, 10^th Grade, 12^th Grade, and any degree), there was no significant association with LH. The body mass index and the presence of comorbidities also did not show any significant association with the presence of LH.

LH was seen in four out of ten patients with Type 1 diabetes mellitus (40%) and in 62 out of 196 patients with Type 2 diabetes mellitus (31.7%). The median duration of diabetes mellitus in the group with LH was 15 years (interquartile range [IQR] 10–20) and in the group without LH was 10 years (IQR 7–15) (p = 0.000). The duration of insulin therapy in the group with LH was 10 years (IQR 5–10.5) and was higher than the group without LH, namely 5 years (IQR 4–6) (p = 0.000).

Fasting blood glucose, postprandial blood glucose, and HbA1c had a significant association with LH [Graph 1], [Graph 2], [Graph 3].

LH was significantly associated with the number of hypoglycemic episodes [Graph 4].

There was no association between the size of the needle, number of injections, type of insulin, or type of injection administrator.

The site of insulin, however, had a significant association with LH [Graph 5] and [Table 1].

Table 1: Association between injection sites and lipohypertrophy

Click here to view

Reuse of needles, especially usage more than six times, had the highest frequency of LH. The needle sites were not rotated by 26 (12.6%) participants, and 80% of this group (21 patients) had LH which was significantly higher than the group which rotated [Graph 6]. There was a significant association between LH and need for change in insulin dose (P = 0.001) [Graph 7].

The injection technique did not have an association with LH (angle 8.25% and pinch 91.75%). Twenty-nine percent of the patients seen by an endocrinologist and 32% of the patients seen by the physician developed LH, and there was no difference in LH between these two groups.

On multivariate analysis, the predictors of LH were lack of rotation, duration of insulin therapy, reuse of needles, number of injections, and glycemic control as indicated by fasting blood sugar [Table 2].

Table 2: Predicting lipohypertrophy from risk factors using logistic regression

Click here to view

Discussion

In this cross-sectional study, a high prevalence of LH was observed. The factors associated with LH were the duration of diabetes mellitus and insulin therapy, reuse of injection needles, and the sites of injection. Glycemic control had an association as did hypoglycemic episodes. The level of education, type of educator, or the specialty of the doctor who initiated insulin had no influence on the prevalence of LH.

The prevalence of LH has been reported to range from 3.6% to 64% in studies from different parts of the world.^{[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17]} The differences may be due to variability in the method used to detect the LH (inspection, palpation, or soft-tissue ultrasound). The impact of education on the presence of LH was not significant in this study, although those in the lowest category of education had the highest prevalence of LH.

A strong association between reuse of needles and LH was observed, strengthened further in multivariate analysis. The American Diabetes Association recommends that needles should not be reused.^[3],[13] Many studies have reiterated that using the injection needle multiple times is a risk factor for LH.^{[12],[13],[14],[15],[16]} In the current study, the needle reuse rate was 95% and the occurrence of LH was higher when the same needle was used more than thrice. In countries such as India, where financial concerns are high, patients continue to inject with the same needle till the needle gets blunt and injections are painful. This tendency can be eliminated only by persistent education of patient in primary care settings and meticulous supervision of injection sites. In this study, there was a significant association between LH at the abdomen followed by the arm, and similar results were seen in other studies.^{[11],[14],[15]} Glycemic control was negatively associated with LH. This was noted across the spectrum of fasting and postprandial glucose levels and HbA1C. The link with hypoglycemia was also statistically significant. Unpredictable and delayed absorption may lead to wide unpredictable excursions in blood glucose levels.^{[6],[16],[17]}

Conclusion

The main risk factors for LH in our study included lack of rotation of insulin injection site and reuse of needles. Patients with Type 2 diabetes mellitus requiring long-term insulin therapy need to be educated about prevention and screening for LH. Periodic training and reinforcement of insulin administration technique by physicians including checking of injection sites every 3–6 months may reduce LH and improve glycemic control.

Ethical considerations

The study was conducted in accordance with the standards of the institutional ethics committee. Informed consent was taken individually from all the participants included in the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	International Diabetes Federation. IDF Diabetic Atlas 9^th Edition. Available from: http://www.idf.org/idf-diabetes-atlas-ninth-edition. [Last accessed on 2020 Feb 02].
2.	Luigi F. Early insulin treatment in type 2 diabetes. Meneghini Diabetes Care Nov 2009;32 Suppl 2:S266-9.
3.	American Diabetes Association. Insulin administration. Diabetes Care 2004;27 Suppl 1 Suppl 1:S106-9.
4.	Richardson T, Kerr D. Skin-related complications of insulin therapy. Am J Clin Dermatol 2003;4:661-7.
5.	Deng N, Zhang X, Zhao F, Wang Y, He H. Prevalence of lipohypertrophy in insulin-treated diabetes patients: A systematic review and meta-analysis. Diabetes Investig 2018;9:536-43.
6.	Famulla S, Hövelmann U, Fischer A, Coester HV, Hermanski L, Kaltheuner M, et al. Insulin injection into lipohypertrophic tissue: blunted and more variable insulin absorption and action and impaired postprandial glucose control. Diabetes Care 2016;39:1486-92.
7.	Gentile S, Strollo F, Corte T Della, Marino G, Guarino G, Italian Study Group on Injection Techniques. Skin complications of insulin injections: A case presentation and a possible explanation of hypoglycaemia. Diabetes Res Clin Pract 2018;138:284-7.
8.	Ji L, Sun Z, Li Q, Qin G, Wei Z, Liu J, et al. Lipohypertrophy in China: Prevalence, risk factors, insulin consumption, and clinical impact. Diabetes Technol Ther 2017;19:61-7.
9.	Gentile S, Guarino G, Giancaterini A, Guida P, Strollo F. suitable palpation technique allows to identify skin lipohypertrophic lesions in insulin-treated people with diabetes. Springerplus 2016;5:563.
10.	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.
11.	Al Hayek AA, Robert AA, Braham RB, Al Dawish MA. Frequency of lipohypertrophy and associated risk factors in young patients with type 1 diabetes: A cross-sectional study. Diabetes Ther 2016;7:259-67.
12.	Strauss K, Gols HD, Hannet I, Partanen TM, Frid A. A pan-European epidemiologic study of insulin injection technique in patients with diabetes. Practical Diab 2002;19:71-6.
13.	Frid AH, Kreugel G, Grassi G, Halimi S, Hicks D, Hirsch LJ, Smith MJ, et al. New insulin delivery recommendations. Mayo Clin Proc 2016;91:1231-55.
14.	Blanco M, Hernández MT, Strauss KW, Amaya M. Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes. Diabetes Metab 2013;39:445-53.
15.	Heinemann L. Insulin absorption from lipodystrophic areas: A (neglected) source of trouble for insulin therapy? J Diabetes Sci Technol 2010;4:750-3.
16.	Baruah MP, Kalra S, Bose S, Deka J. An Audit of Insulin Usage and Insulin Injection Practices in a Large Indian Cohort. Indian J Endocrinol Metab 2017;21:443-52.
17.	Gentile S, Agrusta M, Guarino G, Carbone L, Cavallaro V, Carucci I, et al. Metabolic consequences of incorrect insulin administration techniques in aging subjects with diabetes. Acta Diabetol 2011;48:121-5.