Prevalence and Associated Factors of Lipohypertrophy (LH) Among Diabetes Mellitus (DM) Patients Receiving Insulin Injections in the District Area of Sarawak

ABSTRACT

Aim: To identify prevalence and associated factors of lipohypertrophy (LH) among insulin injection users and assess their knowledge, perception, and practices regarding insulin injection rotation techniques. Methods: A multicentre cross-sectional study was conducted by recruiting 375 patients with Diabetes Mellitus who use insulin injections from June 2022 to October 2022 at selected hospitals and clinics with Diabetes Medication Therapy Adherence Clinic services in Sarawak. The presence of LH was determined by inspecting and palpating the insulin injection sites. Potential contributing factors were predetermined from the literature review and included in adapted questionnaires that underwent face and content validation. The questionnaires comprised three sections: demographic data; knowledge, perception, and practice (KPP) questions; and an assessment of LH. Knowledge was evaluated using six dichotomous questions, while perception and practice were assessed with eight and nine questions, respectively, each rated on a 4-point Likert scale. The resulting scores were interpreted using Bloom’s cut-off points: 80–100% (good/positive), 60–79% (moderate), and below 60% (low/negative). A pilot study yielded Cronbach’s alpha values of 0.732 and 0.795 for questions assessing patient’s perceptions and insulin injection rotation practices, respectively. Results: The prevalence of LH was 5.3%. Overall, patients showed high knowledge (mean score 5.09 ±1.00), perception (mean score 17.39 ±3.38), and practice scores (mean score 20.20 ±3.87). For each one-point increase in the total practice score, the odds of developing LH decrease by 27%, confirming that higher practice scores are protective against LH [OR. 0.738; 95% CI 0.643-0.848; P< 0.001]. Conclusion: The prevalence of LH was low, and the only associated factor found was practice scores. Most patients exhibited good knowledge, moderate perception, and practice scores regarding insulin injection rotation techniques. Future research should explore strategies to enhance patients’ insulin injection practices, investigate the underlying reasons for the gap between knowledge and practice, and evaluate targeted educational or behavioural interventions to further reduce the occurrence of LH. Larger or longitudinal studies could also be conducted to confirm the relationship between practice scores and LH development.

INTRODUCTION

The National Health and Morbidity Survey (NHMS) conducted by the Ministry of Health, Malaysia (MOH) in 2023 revealed that 15.6% of the population suffers from diabetes, a number that has been steadily increasing over the years [1]. Insulin

injection is a common treatment worldwide for type 1 and type 2 diabetes mellitus (DM), but its use is associated with dermatological complications such as lipohypertrophy (LH) [2-4], defined as visible and palpable fatty swelling of subcutaneous adipose tissue at the insulin injection site [5]. 

The development of LH affects glycaemic control, possibly by influencing the number of blood vessels near the insulin depot in the subcutaneous tissue, which varies depending on the nature of the lipodystrophic changes, or by hampering the diffusion of insulin due to structural changes in this tissue [6]. LH usually presents as soft dermal nodules, such as lipomas, or fibro-collagenous poorly vascularized lesions or scar tissue within the subcutaneous adipose tissue [7, 8]. It is characterized by fibrous and poorly vascularized lesions in the subcutaneous adipose tissue and can vary in size [6-9]. When larger areas are involved, the appearance may not be easily noticeable, and the initial stages of skin changes could be subtle, manifesting as skin thickening [10]. Insulin absorption diminishes in areas of LH, increasing the risk of hyperglycemia and also posing a high risk of hypoglycemia when the same dose of insulin is injected into an area without LH [2]. This inconsistency in diabetes control puts patients at risk of developing chronic complications, such as major organ failure [4].

The gold standard for detecting LH is through skin ultrasound; however, many studies rely on observing and palpating the injection sites of insulin users [5].  Currently, there is no standardized method for visual inspection or palpation [5]. Therefore, it is recommended to stroke the patient’s injection site firmly in a sweeping motion rather than relying solely on visual inspection or traditional light and deep palpation techniques [9].

The prevalence of LH varies across different countries and among different diabetes populations. Among patients with type 2 diabetes patients, the prevalence of LH was reported to be 37.3% in Saudi Arabia and 43.8% in Turkey [2][3]. In Spain, the prevalence was 64.4% among type 1 and type 2 diabetes patients, while in China, it was 35.26% among diabetes patients [10] [11]. A recent meta-analysis of 26 studies reported an overall prevalence of LH at 38% (95% CI:29-46%). This analysis also found that LH is more prevalent among type 2 DM patients than type 1 DM patients [5]. 

The development of LH has been reported to be influenced by factors such as the duration of insulin therapy, daily insulin dose, number of injections per day, gender, body mass index (BMI), injection site, failure to rotate injection sites, use of a pen or syringe, needle length, frequency of needle exchange, and poor glycaemic control [2][3][10][12][13]. Insulin type is also a contributing factor in the development of LH. Studies have shown that LH is twice as common with medium or long-acting insulin injections compared to regular short-acting insulin injections, as the former stay longer at the injection site and provide a source for local antigen [14].

Aside from patient-related factors, another issue is the lack of attention to insulin injection techniques (IT) by healthcare providers. A previous international survey revealed that 28% of participants could not recall their injection sites ever being checked by healthcare providers [15]. While most physician visits with insulin-injecting patients focus on discussions about glucose control and dose adjustments, very little time is spent on improving IT [16]. However, IT can be as important as the type of insulin or dosage used for diabetes management. Physicians are advised to inspect and physically examine injection sites and discuss this with their patients at each visit [17].

LH can potentially be reversed by simple interventions such as daily changes of needles, frequent rotation of injection sites (with 2-4 week spacing), using shorter needles (4-6mm), or switching to recombinant human insulin analogues, without the need of direct medical interventions to treat LH [6][14][17][18]. In extreme cases, liposuction or surgical removal may be required [19]. Therefore, proper rotation of insulin injection site is crucial to prevent the development of LH [5]. It is essential for healthcare professionals (HCPs) recognize this condition early by regularly inspecting insulin injection sites and encouraging site rotation [2].

In Malaysia, the prevalence of LH reported in a study in Negeri Sembilan was 39.6%, which is alarming [20]. Furthermore, inspecting patients’ insulin injection sites during visits or follow-ups is not widely practiced. Therefore, it is necessary to obtain baseline data on the prevalence of LH among insulin injection patients in Malaysia to formulate better strategies to address this issue. This study aimed to identify the prevalence of LH among insulin injection users, as well as their knowledge, perception, and practices regarding insulin injection rotation techniques. Additionally, this study also investigated the association between knowledge, perception, practices of insulin injection rotation techniques, social demographic data, and the development of LH among insulin injection users.

METHOD

This was a multicentre cross-sectional study to determine the prevalence and risk factors of LH among patients with DM using insulin injections in Sarawak. Data were collected from June 2022 until October 2022 in selected hospitals and health clinics with Diabetes Medication Therapy Adherence Clinic (DMTAC) services in Sarawak. All patients aged 18 years and older who were diagnosed with DM and using insulin injection pens were included in this study. Those who refused consent were excluded from this study.  

The presence of LH was determined by inspection and palpation of insulin injection sites and was classified into grades 0 through 3: grade 0, no changes; grade 1, visible hypertrophy of fat tissue but palpably normal consistency; grade 2, massive thickening of fat tissue with higher consistency; and grade 3, lipoatrophy [3]. It was also measured based on the surface area defined as largest (postcard: 15 cm x 10.5cm), medium (playing card: 9 cm x 6.5 cm), small (credit card: 8cm x 5cm), smallest (postage stamp: 2.5cm x 2cm) [15]. The inspection for the development of LH was done by medical officers in the respective facilities.

Based on a recent meta-analysis of 26 studies, the prevalence of LH in DM patients using insulin pen injections was found to be 38% [5]. Using sample size calculators for prevalence with a study confidence interval of 95%, normal distribution, and a 5% margin of error, the minimal sample size calculated is 363 [21]. Proportionate stratified systematic random sampling was employed based on the ratio estimation of DM patients with insulin injections in each facility and the distribution of the facilities. Considering a 10% dropout rate, a total of 400 respondents was planned to be surveyed across the facilities. Participants were selected systematically during the data collection period, inviting every other DM patient with insulin injections who visited the clinics to participate in the study.

Selected hospitals and health clinics served as points for conducting the survey, and the pharmacist in charge of the outpatient service in each facility was designated as the data collector. This study focused on LH and insulin injection rotation techniques as key factors affecting the development of LH. Therefore, the questionnaire was adapted from several studies examining knowledge, perception, and practices related to insulin injection rotation techniques [18][19][22][24].

The adapted questionnaire consisted of three parts: demographic data; questions on knowledge, perception, and practice; and assessment on LH. Part 2 included three subsections measuring patients’ knowledge, perception, and practice. Six dichotomous questions were developed to assess patient knowledge about the rotation of insulin injections, covering four domains: rotation of insulin injection sites, spacing distance between injections, last injection site, and functions of insulin injection rotation. These questions were developed based on the key points in the insulin injection rotation counselling provided to patients [15][16].

From these four domains, additional questions were expanded to explore perceptions and practices regarding insulin injection rotation. Additional domains included in the perception and practice questions were the ease of insulin rotation techniques and the use of insulin injection rotation grid. These domains were not assessed under knowledge because the use of an insulin rotation grid is not mandatory and is not mentioned in local counselling guidelines, while the ease of the insulin injection rotation techniques can only be assessed through perception and practice.

In total, eight perception questions and nine practice questions were developed using a 4-point Likert scale based on the above-mentioned domains [3][10][13]. The knowledge, perception, and practice scores were categorized according to Bloom’s cut-off points to understand the level of mastery. Based on Bloom’s cut off points, scores of 80–100% indicate a good or positive level of mastery, 60–79% represent a moderate level, and below 60% reflect a low or negative level of mastery. This categorization helps in interpreting performance of participants and identifying areas that require improvement or further intervention [25]. Part 3 consisted of questions assessing the physical appearance and grading of LH. All these questions underwent face and content validation by three expert clinical pharmacists.

After questionnaire development, pre-testing was conducted, and only minor changes were made. Subsequently, a pilot study was conducted among 41 patients, and the internal consistency of the questionnaire was tested with Cronbach’s alpha, yielding results of 0.732 for questions assessing patient perception towards insulin injection rotation and 0.795 for questions exploring patients’ practices regarding insulin injection rotation.

Patients were recruited while waiting for their medications at the pharmacy. The purpose of this study was explained, and informed consent was obtained prior to the study. Answers were recorded by the data collectors (the respective pharmacists in each facility). Afterwards, patients underwent a physical examination by medical doctors on their injection sites to look for any signs of LH or other injection-related complications, and all findings were recorded.

If participants showed signs of LH or other injection-related complications, they were informed; and with their permission, referred to a pharmacist for further counselling sessions to improve their insulin injection technique. This study was registered with ID NMRR-21-1899-58276; 21-1899-58276(2) and was approved by the Medical Research Ethic Committee (MREC).

RESULT

A total of 16 health facilities in Sarawak participated in this study, with 375 participants enrolled. Among them, 20 participants (5.3%) were diagnosed with grade 1 or 2 LH. The mean age of the participants was 55.9 years, and most were female (n = 254). The majority (72.1%) were overweight or obese, with a mean BMI of 28.3 ± 5.5 kg/m². The sample predominantly comprised Iban individuals, and about half had education below the secondary level. The majority (69.3%) had a household income lower than RM1400, with a mean income of RM1283.20. Most participants had been using insulin injections for less than 5 years.

All participants used insulin pens for their insulin administration, and half of them chose to use a 4mm needle

Table I. Patients’ Socio-Demographic Data.

Variables	Mean (SD)	Frequency, n (%)
Age	55.9 (11.0)
Gender
Male		121 (32.3)
Female		254 (67.7)
Height	157.0 (8.2)
Weight	69.7 (15.0)
BMI	28.3 (5.5)
Underweight (<18.5kg/m2)		6 (1.6)
Normal (18.5-24.9kg/m2)		98 (26.1)
Overweight (25-29.9kg/m2)		153 (41.0)
Obesity (≥30.0kg/m2)		116 (31.1)
Race
Iban		173 (46.1)
Malay		68 (18.1)
Chinese		37 (9.9)
Bidayuh		43 (11.5)
Others		53 (14.1)
Highest Education
No Formal Education		66 (17.6)
Primary School		119 (31.7)
Secondary School		172 (45.9)
Diploma/Degree		18 (4.8)
Master/PHD		0 (0)
Administration Method
Pen		375 (100.0)
Syringe		0 (0)
Monthly Household Income	1283.2 (1863.5)
≤RM1400		260 (69.3)
>RM1400		115 (30.7)
Needle Length
6mm		67 (17.9)
5mm		96 (25.6)
4mm		195 (52.0)
Others		17 (4.5)
Needle Exchange Frequency
Change when necessary		32 (8.5)
After 3 Injection		117 (31.2)
After 2 Injection		188 (50.2)
Every Injection		38 (10.1)

Continued Table I. Patients’ Socio-Demographic Data.

Variables	Mean (SD)	Frequency n (%)
Duration of Insulin Use	4.4 (3.3)
≤5Years		266(70.9)
5-10Years		89 (23.7)
>10Years		20 (5.3)
Total Daily Insulin Use	36.9 (24.1)
Frequency of Insulin Injection Therapy Per Day
1 time per day		127 (33.9)
2 times per day		164 (43.7)
3 times per day		3 (0.8)
4 times per day		81 (21.6)
HbA1c	10.0 (5.5)
Well-Controlled ≤7.0%		39 (10.4)
Poor-Controlled > 7.0%		322 (85.9)
Unexplained Hypoglycemia Event
Yes		242 (64.5)
No		133 (35.5)
Patients found to Developed LH
Yes		20 (5.3)
Grading 1		19 (5.1)
Grading 2		1 (0.3)
No (Grading 0)		355 (94.7)
Total Knowledge Score	5.1 (1.0)
Total Perception Score	17.4 (3.3)
Total Practice Score	20.2 (3.9)

length. Most patients (77.6%) injected insulin twice or less per day, while the mean total daily insulin usage was 36.9 units. Overall, 85.9% had an HbA1c greater than 7%, while 64.5% experienced unexplained hypoglycemia events during their treatment (Table Ⅰ).

This study revealed that respondents had a high knowledge score about insulin rotation and LH, with a mean score of 5.09 (±1.0) out of 6, which is approximately 83%. The majority (85.6%) disagreed with administering insulin at the same site each time and agreed that injection sites should be rotated.Most participants were aware of the need to avoid a 2-finger area around the navel and remembered their previous insulin injection sites. Additionally, 84.8% agreed that properly rotating injection sites would minimize complications such as LH, bruises, and bleeding. However, nearly one-third of the participants claimed that properly rotating the insulin injection site did not help to maximize insulin absorption (Table Ⅱ).

Table Ⅱ. Knowledge Regarding Insulin Rotation (IR) and Lipohypertrophy (LH).

Item	Yes n (%)	No n (%)
Insulin should be injected at the same site every time.	54 (14.4)	321 (85.6)
Insulin injection sites need to be rotated, and the distance between each injection site is usually “one thumb (1.5cm)”.	321 (85.6)	54 (14.4)
Insulin injection should avoid the area within 2 fingers (2.5cm)  around your belly button.	351 (93.6)	24 (6.4)
Remembering your last insulin injection site is necessary to rotate and inject your insulin consistently.	348 (92.8)	27 (7.2)
Properly rotating the insulin injection site for every injection does not help to maximize the absorption of insulin.	126 (33.6)	249 (66.4)
Properly rotating the insulin injection site for every injection minimize complications (such as lipohypertrophy, bruises, and bleeding).	318 (84.8)	57 (15.2)

The study also found that participants had a moderate perception score regarding insulin rotation and LH, with a mean score of 17.4 (±3.3) out of 24, which is approximately 73%. Most participants agreed on the importance and necessity of rotating injection sites during each insulin administration (95.7%) and rotating according to a fixed distance (89.6%). Nearly all (93.1%) participants agreed that it was easy for them to rotate every injection to different sites as instructed by healthcare providers, and 70.1% denied having trouble remembering the last injection site. The majority believed that proper insulin injection site rotation would improve glucose absorption and achieve better glycaemic control, and they also agreed on the importance of following health care providers’ instructions. Most (85.3%) concurred that poor insulin injection rotation would lead to LH, and 71.7% agreed that they could rotate the insulin injection site better with the use of an insulin rotation grid (Table Ⅲ).

This study also revealed that respondents had a moderate practice score on insulin rotation, with a mean score of 20.2 (±3.9) out of 27, which is approximately 75%. About 83.5% of participants always practiced rotating their insulin injection sites; however, only half of them claimed that they rotated injection sites to avoid formation of LH and achieve better glycaemic control. Nearly half (51.7%) always measured their insulin injection sites at a fixed distance. About half of the participants reported being at least sometimes confused about their last injection site and the distance between injection sites. Slightly more than half (67.5%) claimed that they never injected into the same injection site twice, and 61.6% reported never experiencing difficulties remembering and following instructions to rotate their injection sites. Most participants did not use any insulin injection rotation grid to assist them in rotating insulin injections (Table Ⅳ).

Factors selected for analysis included perception score, knowledge score, practice score, gender, age, race, highest education level, body mass index, monthly household income, needle length, needle exchange frequency, duration of insulin use, total daily insulin dose, frequency of insulin injection per day, HbA1c results, and unexpected hypoglycaemic events, supported by literature searches.

After performing single logistic regression for all the above factors, the study revealed that significant factors included practice score, perception score, and needle length. A multiple logistic regression analysis was conducted, and only the practice score was found to be statistically significant in affecting the development of LH (OR: 0.738; 95% CI: 0.643- 0.848; P< 0.001). For each one-point increase in the total practice score, the odds of developing LH decrease by 27%, confirming that higher practice scores are protective against LH.

No multicollinearity was detected among the independent variables. The Hosmer–Lemeshow goodness-of-fit test was conducted and found to be statistically insignificant (P=0.231), indicating that the dataset fits the logistic regression model well. The Receiver Operating Characteristic (ROC) curve was generated to evaluate the discriminative performance of the final logistic regression model. The area under the ROC curve (AUC) was approximately 0.817, indicating excellent model discrimination. This suggests that the model has a high ability to correctly classify participants according to the outcome variable. In the univariate (simple) logistic regression analysis, three factors were found to be statistically significant. Interaction effects among these factors were examined, and no significant interactions were detected (Table Ⅴ).

DISCUSSION

The minimum sample size required for this study was 363. Taking into account a possible dropout rate of around 10%, a total of 400 patients were needed. However, only 375 participants were recruited for this study, which corresponds to 93.8% of the initial plan. This shortfall was due to difficulties in recruiting eligible patients through the systematic random sampling method. Some patients were excluded due to protocol restrictions on recruitment. Furthermore, clinics or district hospitals were sometimes overcrowded with patients and had limited manpower among pharmacists, who had to prioritize their core duty of serving patients. While they complied with the requirements by alternatively selecting patients without violating the protocols, this led to an extension of the data collection period to a total of 5 months.

Table Ⅲ. Perception Regarding Insulin Rotation (IR) and Lipohypertrophy (LH).

Item	Strongly Disagree n (%)	Disagree n (%)	Agree n (%)	Strongly Agree n (%)
It is important and necessary to rotate your insulin injection site each time you inject insulin.	9 (2.4)	7 (1.9)	153 (40.8)	206 (54.9)
It is important to rotate your insulin injection site according to fixed distance each time you inject insulin.	6 (1.6)	33 (8.8)	206 (54.9)	130 (34.7)
It is troublesome to remember your last injection site each time you inject insulin.	75 (20.0)	188 (50.1)	90 (24.0)	22 (5.9)
It is important to rotate your insulin injection site each time you inject insulin as instructed by your health care providers.	1 (0.3)	13 (3.5)	189 (50.4)	172 (45.9)
It is easy to rotate your insulin injection site each time you inject insulin as instructed by your health care providers.	1 (0.3)	25 (6.7)	240 (64.0)	109 (29.1)
Good insulin injection rotation each time you inject insulin would improve your insulin absorption and achieve better glycaemic control.	2 (0.5)	15 (4.0)	237 (63.2)	121 (32.3)
Poor insulin injection rotation would lead to LH.	2 (0.5)	53 (14.1)	215 (57.3)	105 (28.0)
Using an insulin rotation grid each time you inject insulin would help you rotate your insulin injection site better.	44 (11.7)	62 (16.5)	195 (52.0)	74 (19.7)

Table Ⅳ. Practice on Insulin Rotation.

Item	Never n (%)	Sometimes n (%)	Frequently n (%)	Always n (%)
Did you rotate your insulin injection site each time you inject insulin?	3 (0.8)	10 (2.7)	49 (13.1)	313 (83.5)
Did you measure your insulin injection site in a fixed distance each time you inject insulin?	54 (14.4)	52 (13.9)	75 (20.0)	194 (51.7)
Were you ever confused about your last injection site?	207 (55.2)	130 (34.7)	21 (5.6)	17 (4.5)
Were you ever confused about the distance between insulin injection sites?	181 (48.3)	148 (39.5)	31 (8.3)	15 (4.0)
Did you ever inject your insulin at the same injection site?	253 (67.5)	109 (29.1)	9 (2.4)	4 (1.1)
Did you experience any difficulties remembering and following the instructions of your healthcare providers to rotate your injection site each time you inject insulin?	231 (61.6)	119 (31.7)	15 (4.0)	10 (2.7)
Did you try to rotate your insulin injection site each time you inject insulin to avoid the formation of LH?	36 (9.6)	28 (7.5)	111 (29.6)	200 (53.3)
Did you try to rotate your insulin injection site each time you inject insulin to achieve better glycaemic control?	21 (5.6)	20 (5.3)	119 (31.7)	215 (57.3)
Did you use any insulin rotation grid to assist you in rotating the insulin injection site each time you inject insulin?	234 (62.4)	47 (12.5)	36 (9.6)	58 (15.5)

Table Ⅴ. Factors Associated with the Development of Lipohypertrophy (Using Multivariable Logistic Regression).

Variables	SLRa			MLRb
	OR	(95% CI)	P Value	Adj. OR	(95% CI)	P Value
Age	0.977	0.937- 1.018	0.267
Gender
Female	1.467	0.520- 4.139	0.469
Male (Constant)
BMI (Mean)
Underweight (<18.5kg/m2)	0.000	0.000-0.000	0.999
Normal (18.5-24.9kg/m2)	0.525	0.156- 1.764	0.298
Overweight (25-29.9kg/m2)	0.506	0.175- 1.467	0.210
Obesity (≥30.0kg/m2) (Constant)
Race
Iban	1.424	0.298- 6.810	0.658
Malay	1.786	0.314-10.171	0.514
Chinese	1.562	0.209- 11.656	0.663
Bidayuh	1.923	0.306- 12.079	0.485
Others (Constant)
Education Level
No formal Education	0.517	0.044- 6.095	0.600
Primary School	1.111	0.130- 9.518	0.923
Secondary School	0.877	0.104- 7.398	0.904
Diploma/Degree (Constant)
Monthly Household Income
≤RM1400	0.802	0.311- 2.069	0.647
>RM1400 (Constant)
Needle Length Used
6nm	0.296	0.060; 1.475	0.137
5nm	0.104	0.016- 0.677	0.018
4nm	0.306	0.076- 1.224	0.094
Others (Constant)

SLR=Single logistic regression; CI=confidence interval; MLR=Multiple logistic regression; OR= Odd ratio; Adj. OR=adjusted odds ratio

ContinuedTable Ⅴ. Factors associated with the Development of Lipohypertrophy (Using Multivariable Logistic Regression).

Variables	SLRa			MLRb
	OR	(95% CI)	P Value	Adj. OR	(95% CI)	P Value
Needle Exchange Frequency
Change when necessary	2.267	0.196- 26.271	0.513
After 3 Injection	1.619	0.183- 14.345	0.665
After 2 Injection	2.458	0.309- 19.538	0.395
Every Injection (Constant)
Duration of Insulin use	1.026	0.899- 1.170	0.708
Total Daily Insulin Dose	1.003	0.985- 1.022	0.744
Frequency of Insulin Injection (Daily)
3-4 times per day	1.436	0.349- 5.915	0.616
2 times per day	2.317	0.728- 7.378	0.155
1 time per day (Constant)
HbA1c %
Well-Controlled ≤7.0%	2.520	0.787- 8.067	0.119
Poor-Controlled > 7.0% (Constant)
Unexplained Hypoglycemia Event
No	1.888	0.764- 4.667	0.169
Yes (Constant)
Total Knowledge Score	0.629	0.429- 0.921	0.017
Total Perception Score	0.883	0.761- 1.025	0.101
Total Practice Score	0.730	0.643- 0.829	<0.001	0.017	0.017	0.017

In this study, the prevalence of LH was found to be only 5.3%. According to a systematic review and meta-analysis, the overall prevalence of LH in insulin-treated diabetes patients was 38%. However, the prevalence varied widely across studies, ranging from 1.9 % to 73.4 % [5]. Despite these variations, most studies in the meta-analysis reported a higher prevalence of LH than this study. This discrepancy could be attributed to the different backgrounds of the study populations. Five of the studies with a mean duration of insulin use exceeding 10 years reported LH prevalence between 27.1% to 52% [5]. In contrast, the mean duration of insulin use in this study was 4.4 years, which justifies the lower prevalence of LH compared to studies with longer insulin use. Furthermore, one study reported a prevalence of LH of only 1.9% in patients with an insulin use duration of 4.2 ± 3.0 years, which is comparable to our findings [5].

In addition, studies that used ultrasound, combined with observed and palpated (OAP) techniques for patients with 1-5 years of insulin use, found LH prevalence rates as high as 64.4% [5]. This suggests that even though the duration of insulin use was comparable to that in this study, different examination techniques also influence the prevalence of LH. Most studies in the meta-analysis, including this study, used OAP techniques because they are a low-cost yet effective alternative to ultrasound examination [26]. Furthermore, OAP techniques have been reported to achieve a 97% consistency rate compared to the gold standard of ultrasound in identifying LH [26]. In this study, almost all patients (n=19) diagnosed with LH exhibited thickening of the skin, but only 8 soft dermal nodules such as lipomas or fibrocollagenous scar tissue, and the affected surface areas were minimal.

The study also revealed that most patients reused their needles after insulin injection, with only 10.1% of patients changing their needles each time they injected their insulin. According to the 2019 Sarawak Household Income and Basic Amenities Survey report, the mean Poverty Line Income (PLI) value in Sarawak was RM2,131 per month [27]. In other words, 69.3% of the recruited participants (<RM1400.00) lived below PLI. With limited resources, patients may struggle to follow the best practices recommended by their HCPs. This explains the contrast in term frequency of insulin needle reuse compared to other studies, most of which recommend changing the needle after each insulin injection to achieve a lower prevalence of LH [2][13][18].

Interestingly, in one study reporting a low insulin needle reuse rate (46%), the prevalence of LH was surprisingly higher (47.7%) than in this study [13]. This could be due to the lower insulin injection rotation rate reported (57.5%) compared to 83.5% of patients in this study. In addition, patients in this study might have occasionally reused their insulin needles when facing financial constraints. Although this factor was not specifically assessed in this study, which could further contribute to the development of LH.  Furthermore, more than half of the participants in this study use 4mm needles.  According to recommendations, 4mm pen needles are shown to be safe and effective in adult patients of all sizes (i.e., achieving equivalent glycaemic control) [12].  In a study by Al Hayek AA et al. it was reported that majority of patients (63.8%) used either 6- or 8-mm insulin injection needles, which also increases the risk of LH [13].

Education plays a pivotal role in healthcare, particularly in diabetes education. A better understanding of medical conditions can lead patients to develop more positive beliefs, thereby increasing the likelihood of adherence to the instructions provided by their HCPs [28]. Although nearly half of the patients had low education levels, the majority showed good knowledge and positive perceptions toward insulin injection rotation techniques. This may be contributed by the ‘easy to understand counselling method’ adopted by the HCPs during the initiation of insulin therapy. Pictorial counselling tools used by pharmacists during DMTAC are easy to comprehend, even for patients with no formal education [29][30].  All these factors may further lower the prevalence of LH.

This study also revealed that most patients experienced unexplained hypoglycaemic events. This was slightly higher compared to a previous study, in which only 44% of patients experienced hypoglycaemia and 24.3% had recurrent hypoglycaemia [12].  Previous studies have also shown that the frequency of LH was higher among patients with hypoglycaemia, as LH was one of the leading causes of hypoglycaemia events [10, 12]. However, the prevalence of LH in patients with and without hypoglycaemia was not compared in this study, indicating that further research is warranted.

Knowledge, Perception, and Practice Toward Insulin Injection Rotation

In Malaysia, government sectors pharmacists are responsible for educating their patients about proper insulin techniques, including injection site rotation, as per the Malaysian Medication Counselling Guideline [31]. The mean knowledge score found in this study was 5.09 (1.00) points out of a total score of 6. Most patients (n=291; 77.6%) scored at least 5 points out of 6, indicating that patients had good knowledge, with nearly half of them (n=157; 41.9%) achieving perfect knowledge scores. This high knowledge level is comparable to other studies [22-24], likely due to patients undergoing drug counselling by pharmacists when they started insulin therapy in all government facilities.

The study revealed that most patients acknowledged the need to remember their last injection site to avoid administering insulin on the same site, to rotate at a fixed distance, and to avoid injections near the navel. All these measures aim to reduce insulin injection complications and improve insulin absorption. Improved knowledge of insulin injection techniques has been associated with better management of LH conditions [32].

Most patients perceived it as important and necessary to rotate their insulin injections in a fixed distance in each insulin injection as instructed by their HCPs. More than half of them never felt it was difficult to follow the instruction of HCPs to rotate their insulin injections and did not find it troublesome to remember their last injection site. Most patients agreed that proper insulin injection techniques improve insulin absorption and help achieve better glycaemic control, while poor technique may lead to development of LH. However, a good level of knowledge and a positive perception did not lead to satisfactory HbA1c control, as the majority of the patients had HbA1c levels exceeding 7%. The study highlighted that high HbA1c level may be associated with non-compliance to injection site rotation as recommended [12]. This non-compliance may stem from complexity of the recommended insulin injection rotation techniques, which patients might find challenging to consistently follow, leading to perceived compliance by simply avoiding injecting insulin at the exact same site, rather than adhering to proper insulin injection rotation techniques. In contrast, the referenced study identified various reasons influencing injection site selection, including the development of pain or bleeding in the arm or leg after insulin injection (27.0%), physical difficulty in gripping the arm or removing clothes from the legs (25.1%), concern about abdominal fattening or LH (24.0%), the perception that injecting into the abdomen or arm was more practical (20.0%), fear of injecting into the abdomen or arm (3.0%), and a preference for abdominal injections due to the larger surface area available (0.9%) [12].

In this study, nearly half of the participants did not always rotate their insulin injection sites at a fixed distance and were at least occasionally confused about their last injection site and the distance between injections. Nearly one-third claimed that they sometimes administered insulin at the same injection site. This implies that those who reported rotating injection sites may not fully comply with the instructions. They might lack accurate rotation techniques and administer according to their preference rather than strictly following the fixed distance, despite the instructions and counselling provided [33]. This may also be due to patients perceiving compliance with insulin injection rotation by randomly rotating and never injecting at the same injection site again. This is further supported by previous studies, which found that most patients who reported rotating injection sites did not perform the rotation technique properly [10][34][35]. Currently, this malpractice does not seem to have an impact on the development of LH, as the duration of insulin use in this study was only 4.4 years, which is relatively short compared to the study that showed a high prevalence of LH [5]. Therefore, if improper insulin injection practices are not addressed, future studies may reveal a higher prevalence of LH in this patient group [5][33].

In addition, this issue could be mitigated by introducing the use of an insulin injection rotation grid. This grid would help patients predefine their injection sites and follow a sequence for insulin administration. Thus, systematic rotation of insulin injections at a fixed distance, without confusion and with traceable last injections, could be achieved [33]. However, the majority of patients reported never using an insulin injection rotation grid. This may be because the counselling guidelines in Malaysia do not require or recommend the use of insulin injection grids during counselling sessions [31]. Consequently, the introduction and use of insulin injection rotation grid depend on the preferences of pharmacists. Patient access to this rotation grid is minimal; therefore, it is not surprising that the majority of patients do not use it.

Limitations of the Study

This study is subject to response and recall bias, as some of the data was self-reported. Since patients’ insulin injection rotation techniques were not assessed, we were unable to verify their claims regarding knowledge, perception, and practice. In addition, there are limitations related to the sampling methods; while we used systematic random sampling; the lack of manpower at the respective facilities forced some data collection efforts to be cancelled or postponed, which delayed the overall data collection process.

CONCLUSION

The prevalence of lipohypertrophy (LH) was low, with practice score identified as the only significant associated factor. Overall, patients demonstrated good knowledge, a moderate level of perception and practice regarding insulin injection rotation and LH. However, nearly 30% of patients did not measure rotation distances, indicating unsystematic rotation practices. Although most reported no difficulty recalling previous injection sites, the use of an insulin injection rotation grid during counselling and self-administration is recommended to promote consistent injection rotation and reduce the risk of LH. Future research should explore strategies to enhance patients’ insulin injection practices, investigate the underlying reasons for the gap between knowledge and practice, and evaluate targeted educational or behavioral interventions to further reduce the occurrence of LH. Larger or longitudinal studies could also be conducted to confirm the relationship between practice scores and LH development.

ACKNOWLEDGEMENT

We would like to thank all participants in this study. No funding or sponsorship was received for this study or for the publication of this article. We would also like to acknowledge the Director General of Health Malaysia for granting permission to publish this article.

CONFLICT OF INTEREST

All the investigators declare that they have no conflicts of interest.

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