Risk factors for Lipohypertrophy in People With Insulin-Treated Diabetes: A Systematic Meta-Analysis

Julia K Mader; Riccardo Fornengo; Ahmed Hassoun; Lutz Heinemann; Bernhard Kulzer; Magdalena Monica; Trung Nguyen; Jochen Sieber; Eric Renard; Yves Reznik; Przemysław Ryś; Anita Stożek-Tutro; Emma G Wilmot

doi:10.1177/19322968251325569

. 2025 Mar 20:19322968251325569. Online ahead of print. doi: 10.1177/19322968251325569

Risk factors for Lipohypertrophy in People With Insulin-Treated Diabetes: A Systematic Meta-Analysis

Julia K Mader ^1,^✉, Riccardo Fornengo ², Ahmed Hassoun ³, Lutz Heinemann ⁴, Bernhard Kulzer ⁵, Magdalena Monica ^6,⁷, Trung Nguyen ⁸, Jochen Sieber ⁹, Eric Renard ¹⁰, Yves Reznik ¹¹, Przemysław Ryś ⁶, Anita Stożek-Tutro ^6,⁷, Emma G Wilmot ¹²

PMCID: PMC11924065 PMID: 40109173

Abstract

Background:

Lipohypertrophy is a common skin complication in people with insulin-treated diabetes. Despite its high prevalence and potential impact on diabetes management and outcomes, published data regarding the risk factors for the development of this complication are contradictory. The study aimed to determine risk factors for lipohypertrophy related to patient characteristics and insulin therapy.

Method:

Medical databases (MEDLINE/PubMed, Embase, CENTRAL) were searched from 1990 to August 21, 2023. All relevant studies describing potential risk factors for lipohypertrophy in people with insulin-treated diabetes (eg, sex, age, body mass index [BMI], type of diabetes, and injection technique) were included. Data enabling calculations of prevalence odds ratios (pOR) and mean differences (MD) with 95% confidence intervals [95% CI] were extracted and pooled in meta-analyses.

Results:

Fifty-one studies of risk factors for lipohypertrophy were identified. Performed meta-analyses indicate that the strongest contributor to lipohypertrophy was incorrect injection site rotation (pOR = 8.85 [95% CI: 5.10-15.33]), followed by needle reuse (3.20 [1.99-5.13]), duration of insulin therapy >5 years (2.62 [1.70-4.04]) and >2 daily injections per day (2.27 [1.58-3.25]). Those with type 1 diabetes and obese/overweight individuals also had significantly higher odds of developing lipohypertrophy. Sex, age, and insulin device (pen, syringes) were not significant risk factors for lipohypertrophy.

Conclusions:

This systematic review with meta-analysis revealed that incorrect injection site rotation and needle reuse are the most substantial factors in developing lipohypertrophy. Notably, both factors are modifiable through patient education, emphasizing the importance of teaching proper injection techniques for better diabetes management.

Keywords: diabetes, insulin-injection technique, lipohypertrophy, meta-analysis, risk factors, systematic review

Introduction

Lipohypertrophy, a localized change in the structure of subcutaneous fatty tissue, is a prevalent side effect of insulin therapy among people with diabetes.¹ Previous studies have shown that people with lipohypertrophy more often experience episodes of unexplained hypoglycemia^2-9 and have significantly higher glycated hemoglobin (HbA1c)^6,10-14 than those without this skin complication.

Despite its high prevalence among individuals with diabetes, based on a recent meta-analysis (41·8% [95% CI: 35.9-47.6]),¹⁵ the precise etiology of lipohypertrophy remains elusive. Numerous risk factors for developing lipohypertrophy among insulin-injecting patients have been considered, including demographic variables,^11,13,16-20 injection technique,^{3,10,16,19,21,22} and disease course,^2,3,13,23 creating a complex web of potential contributors. For example, Vardar and Kizilci²⁴ identified that longer insulin therapy duration, incorrect injection site rotation, and needle reuse are independent risk factors for lipohypertrophy. Other researchers, including Blanco et al³ and Hajheydari et al,¹³ proposed that diabetes type also may contribute to lipohypertrophy development, with a higher prevalence observed in patients with type 1 diabetes compared with type 2 diabetes. At the same time, Gentile et al²⁵ and Lin et al²⁶ observed that the number of daily insulin injections is higher in people with lipohypertrophy compared with those without this condition. On the contrary, other authors found no associations between lipohypertrophy and site rotation,^20,27,28 needle reuse,^9,23,29,30 type of diabetes,^30-32 and the daily number of insulin injections.^7,20,27,33 These conflicting results leave important questions unanswered regarding what precisely predisposes people with diabetes to this condition.

This study aimed to address these contradictory data by conducting a systematic review and meta-analysis. The primary objective was to identify the risk factors associated with the development of lipohypertrophy in people with insulin-treated diabetes.

Materials and Methods

Selection Criteria and Search Strategy

This review focused on studies that included people with diabetes on subcutaneous insulin or glucagon-like peptide-1 (GLP-1) therapy administered via pens or syringes, excluding those using devices for continuous subcutaneous infusion of such drugs. The decision to include GLP-1 therapies was based on evidence indicating that subcutaneous nodules, resembling lipohypertrophy in imaging studies, have also been reported with GLP-1 analogs such as exenatide.^34,35 Due to substantial differences in insulin delivery methods using syringes/pens versus pumps, we chose not to mix results for these populations and we are working on a separate research extensively discussing the issue of lipohypertrophy in pump users. Of primary interest were studies that compared the frequency of lipohypertrophy in groups with and without potential risk factors, including variables related to patient characteristics (sex, diabetes type, body mass index [BMI] category, duration of diabetes, and subcutaneous therapy >5 years) and injection technique (needle reuse, site rotation, insulin type, needle size, number of daily injections >2). In addition, studies reporting mean BMI, duration of diabetes and subcutaneous therapy, insulin dose, number of injections per day, and insulin dose in individuals with and without lipohypertrophy studies were considered.

No restrictions regarding study design were made, allowing the inclusion of experimental and observational studies. Only studies presenting data unsuitable for cumulation in meta-analysis, published in languages other than English, and conference proceedings were excluded from our review. Furthermore, only research that was conducted and published after 1990 was included to ensure the applicability of study results to current clinical practice. Earlier work was considered outdated because of the widespread use of animal-derived insulin, which no longer represents the standard of care in diabetes management.

The systematic search was conducted on August 21, 2023, in MEDLINE (via PubMed), Embase, and CENTRAL (via The Cochrane Library) using keywords and queries related to diabetes and lipohypertrophy. Detailed search strategies for each database were shown in the supplementary appendix (Supplementary Tables 1-3). To retrieve other relevant publications not indexed in searched medical databases, a hand-search of the references of the included studies was also performed. The review process was conducted by two independent analysts (AST, MM) following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) 2020 guidelines³⁶ and registered PROSPERO protocol (CRD42023459726). Any disagreements between reviewers on the full-text stage of the selection process were resolved by consensus.

Data Analysis

Two reviewers performed data extraction independently (AST, MM). Any identified discrepancies in extraction between reviewers were discussed and resolved by consensus. In cases of concerns about the correctness of the reported data in the included studies, such data were not extracted. Extracted items related to the methodology of the included studies, characteristics of patients with emphasis on details of anti-hyperglycemic therapy, and risk factors of lipohypertrophy. Regarding risk factors, if available, we extracted results of comparisons and P values made by authors of the individual studies. We contacted the corresponding authors of studies conducted by the same research groups to ensure that published articles do not duplicate results for the same patient cohorts. The quality of the included studies was evaluated by Joanna Briggs Institute tools (JBI) for cross-sectional³⁷ and quasi-experimental³⁸ studies.

Meta-analyses were conducted using a random-effects model (DerSimonian & Laird) as significant between-study heterogeneity of results (P value for Cochrane Q test < 0.10 and I² > 50%) was observed for all comparisons. Outcomes were presented either as prevalence odds ratios (pOR) for the percentage of patients with lipohypertrophy among risk factors groups or as mean differences (MD) for variables expressed by mean values and standard deviations (SDs). All results were given with 95% confidence intervals [95% CI]. Funnel plots were also drawn for the assessment of the publication bias.

Subgroup analyses and meta-regression were performed to address heterogeneity in meta-analyses and explore the impact of various confounding variables on the obtained results. The considered factors for subgroup analyses included the geographic region of the study, the number of participating centers, diabetes type, the age of the study population, the definition of lipohypertrophy, publication date, and the population size. In addition, for meta-regression, the impact of continuous variables related to injection technique and duration of anti-diabetes therapy was investigated, among others. Meta-regression calculations were conducted using the random-effects model (REML, restricted maximum likelihood estimation). Subgroup analyses and meta-regression were performed exclusively for meta-analyses with statistically significant results that included at least 10 studies. OpenMEE software³⁹ was used for all calculations.

Results

Of the 4131 records identified during databases and references search, 273 full-text articles were selected for further analysis. Among these, 51 studies met the criteria for inclusion in this meta-analysis (Table 1), and 222 were excluded. Detailed reasons for exclusion and the PRISMA flow diagram describing the selection process are provided in the supplementary appendix (Supplementary Figure 1).

Table 1.

Summary of the Included Studies.

Study	Study design (location)	Number of analyzed patients (LH+/LH−)	Diabetes type	Population	Duration of diabetes (years)	Duration of insulin therapy (years)
Abujbara⁴⁰	Cross-sectional, single-center (Jordan)	851 (477/374)	T1DM, T2DM	Unknown	12.3 (8.1)	7.0 (6.2)
Al Ajlouni¹⁶	Cross-sectional, single-center (Jordan)	1090 (407/683)	Only T2DM	Only adults	13.5 (9-20)^a	4.6 (5.0)
Al Hayek²	Cross-sectional, single-center (Saudi Arabia)	174 (83/91)	Only T1DM	Only children	6.1 (4.5)	Unknown
Al Jaber⁴¹	Cross-sectional, multicenter (Saudi Arabia)	202 (80/122)	Only T2DM	Only adults	16.9 (8.5)	8.5 (5.8)
Arora¹⁰	Cross-sectional, single-center (India)	500 (290/210)	T1DM, T2DM	Unknown	Unknown	3.0 (2.5-5.0)^a
Barlas⁴²	Cross-sectional, single-center (Turkey)	35 (30/5)	Only T1DM	Only adults	13 (5-17)^b	Unknown
Barola¹¹	Cross-sectional, single-center (India)	372 (231/141)	Only T1DM	Children, adults	5.6 (5.3)	Unknown
Baruah²¹	Cross-sectional, single-center (India)	748 (94/654)	Only T2DM	Children, adults	12.2 (7.6)	3.4 (4.2)
Blanco³	Cross-sectional, multicenter (Spain)	430 (277/153)	T1DM, T2DM	Children, adults	NA (6-15)^b	NA (1-5)^b
Bochanen⁴	Prospective, quasi-experimental, multicenter (Belgium)	146 (92/54)	T1DM, T2DM	Only adults	Unknown	Unknown
Cunningham²⁹	Cross-sectional, multicenter(Ireland)	55 (28/27)	T1DM, T2DM	Unknown	Unknown	15.0 (12.6)
De Coninck⁴³	Cross-sectional, multicenter (World)	4352 (2089/2263)	Unknown	Children, adults	14 (10.6)	11 (NA)
Deeb⁴⁴	Cross-sectional, single-center (United Arab Emirates)	119 (42/77)	Only T1DM	Children, adults	Unknown	Unknown
Elsayed²⁰	Cross-sectional, single-center (Egypt)	115 (57/58)	Only T1DM	Children	4.4 (3.3)	4.4 (3.3)
Frid⁴⁵	Cross-sectional, multicenter (World)	13 289 (3855/9344)	T1DM, T2DM	Children, adults	13.2 (9.7)	8.7 (8.9)
Gentile¹²	Cross-sectional, multicenter (Italy)	296 (169/127)	T1DM, T2DM	Only adults	7.0 (2.0)	3.0 (1.0)
Gentile⁵	Cross-sectional, multicenter (Italy)	1227 (718/509)	Only T2DM	Only adults	10.6 (7.9)	7.6 (6.0)
Gentile⁶	Cross-sectional, multicenter (Italy)	780 (360/420)	T1DM, T2DM	Only adults	18.0 (11.0)	10.1 (2.1)
Gentile²⁵	Prospective, quasi-experimental, multicenter (Italy)	1160 (487/673)	Only T2DM	Only adults	15.8 (7.6)	7.6 (2.2)
Gunhan⁴⁶	Cross-sectional, single-center (Turkey)	345 (98/247)	Only T2DM	Only adults	37.0 (8.5)	8.9 (5.7)
Gupta⁷	Cross-sectional, single-center (India)	139 (97/42)	Only T1DM	Children, adults	8.7 (7.5)	Unknown
Hajheydari¹³	Cross-sectional, single-center (Iran)	230 (35/185)	T1DM, T2DM	Unknown	14.0 (8.5)	5.4 (6.0)
Hauner¹⁷	Cross-sectional, single-center (Germany)	279 (66/213)	T1DM, T2DM	Unknown	14.1 (9.5)	Unknown
Hawa²⁷	Cross-sectional, multicenter (Malaysia)	506 (200/306)	Only T2DM	Adults	12.6 (6.96)	4.8 (3.82)
Ji²³	Cross-sectional, multicenter (China)	401 (213/188)	T1DM, T2DM	Only adults	11.8 (7.3)	5.8 (4.5)
Kakourou⁴⁷	Cross-sectional, single-center (Greece)	148 (40/108)	Only T1DM	Only children	4.5 (3.7)	4.5 (3.7)
Kiraç¹⁸	Cross-sectional, single-center (Turkey)	140 (91/49)	Only T2DM	Only adults	Unknown	Unknown
Klimontov⁴⁸	Cross-sectional, single-center (Russia)	82 (80/2)	T1DM, T2DM	Only adults	16 (NA)^b	Unknown
Korkmaz³¹	Cross-sectional, single-center (Turkey)	136 (119/17)	T1DM, T2DM	Only adults	15.8 (9.2)	11.4 (8.3)
Kumar¹⁴	Cross-sectional, single-center (India)	88 (60/28)	T1DM, T2DM	Only adults	21.8 (9.9)	6.5 (6.6)
Li⁴⁹	Cross-sectional, multicenter (China)	736 (540/196)	Only T2DM	Only adults	10 (6.9)	Unknown
Lin²⁶	Cross-sectional, single-center (China)	120 (83/37)	Only T2DM	Only adults	Unknown	6.6 (4.3)
Luo⁵⁰	Cross-sectional, single-center (China)	316 (270/46)	T1DM, T2DM	Only adults	12.8 (16.6-19.2)^a	6.2 (2.9-10.4)^a
Nain⁵¹	Cross-sectional, single-center (Malaysia)	128 (66/62)	Only T2DM	Only adults	Unknown	Unknown
Nawaz¹⁹	Cross-sectional, single-center (Pakistan)	363 (83/280)	Unknown	Children, adults	7.9 (4.5)	6.5 (3.7)
Omar⁵²	Cross-sectional, single-center (Egypt)	119 (62/51)	Only T1DM	Only children	Unknown	Unknown
Pahuja²⁸	Cross-sectional, single-center (India)	96 (65/31)	Only T2DM	Only adults	19.8 (NA)	6.8 (NA)
Pozzuoli³⁰	Cross-sectional, single-center (Italy)	352 (151/201)	T1DM, T2DM	Unknown	20.4 (9.9)	9.1 (8.6)
Saeed⁵³	Cross-sectional, single-center (Pakistan)	360 (157/203)	T1DM, T2DM	Unknown	14.7 (7.6)	8.5 (6.1)
Saez de Ibarra⁵⁴	Cross-sectional, single-center (Spain)	150 (78/72)	T1DM, T2DM	Unknown	13.3 (8.8)	11.4 (7.9)
Sawatkar⁵⁵	Cross-sectional, single-center (India)	500 (205/295)	Only T1DM	Unknown	4.4 (4.4)	4.4 (4.4)
Sharma⁵⁶	Prospective, quasi-experimental, single-center (India)	121 (103/18)	Only T1DM	Only children	1.4 (1.8)^a	1.4 (1.8)^a
Shetty³²	Cross-sectional, unknown (India)	50 (13/37)	T1DM, T2DM	Unknown	11 (9.8)	Unknown
Singha⁵⁷	Cross-sectional, single-center (India)	95 (46/45)	Only T1DM	Unknown	Unknown	Unknown
Strollo³³	Cross-sectional, multicenter (Italy)	387 (298/98)	T1DM, T2DM	Only adults	13.0 (9.0)	10.0 (9.0)
Sürücü⁸	Cross-sectional, single-center (Turkey)	436 (191/245)	Only T2DM	Only adults	Unknown	Unknown
Thewjitcharoen⁹	Cross-sectional, single-center (Thailand)	400 (149/251)	T1DM, T2DM	Unknown	23.0 (10.2)	11.4 (8.7)
Tsadik⁵⁸	Cross-sectional, single-center (Ethiopia)	176 (103/73)	Only T1DM	Only children	Unknown	Unknown
van Munster⁵⁹	Cross-sectional, single-center (Netherlands)	65 (31/34)	Only T1DM	Only children	Unknown	Unknown
Vardar²⁴	Cross-sectional, multicenter (Turkey)	215 (104/111)	T1DM, T2DM	Only adults	Unknown	Unknown
Zureik⁶⁰	Cross-sectional, single-center (France)	955 (356/599)	Only T2DM	Only adults	Unknown	Unknown

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Continuous data are given as mean (SD) unless otherwise stated. ^aMedian (IQR). ^bMedian (range). LH+/-, patients with/without lipohypertrophy; NA, not available; T1DM, type 1 diabetes; T2DM, type 2 diabetes.

All eligible studies—except three prospective studies (Bochanen et al,⁴ Gentile et al,²⁵ Sharma et al⁵⁶)—were cross-sectional. Most studies were conducted in East Asia (19 studies), primarily in India (10 studies); 15 originated from Europe, while 14 described patients from Western Asia or Arab countries. In addition, two studies included global data (multinational studies) and one was conducted in Ethiopia. Of the 51 included studies, 69% were single-center studies.

The sample size in the included studies varied from 35 (Barlas et al⁴²) to 13 289 (Frid et al⁴⁵) patients; however, the majority of them included less than 500 participants (38 studies). Most of the included studies were conducted on a mixed population in terms of age and type of diabetes. Only 13 studies exclusively targeted people with type 1 diabetes, and 14 studies concentrated on those with type 2 diabetes. Notably, seven studies included a pediatric type 1 diabetes population. All studies included participants on insulin therapy, only two studies featured a small subset of patients on GLP-1 analogs (Frid et al,⁴⁵ Kiraç et al¹⁸). As a result of the systematic search, no studies allowed assessment of the risk factors in those on GLP-1 agonists therapy.

Regarding the risk of bias assessment, most included studies scored at least six points on the JBI scale, indicating good methodological quality. Only individual studies (De Coninck et al,⁴³ Gentile et al,²⁵ Kakourou et al,⁴⁷ Omar et al,⁵² and van Munster et al⁵⁹) presented average quality with four to five points on JBI scales. Nonetheless, no study was excluded from the systematic review due to methodological issues. Detailed methodology, patient characteristics, and JBI scores are shown in the supplementary appendix (Supplementary Tables 5-9).

Performed meta-analyses showed that incorrect rotation of injection sites was the strongest factor associated with an increased prevalence of lipohypertrophy (pOR = 8.85 [95% CI: 5.10-15.33]) in people with diabetes (Figure 1). The second most significant contributor to lipohypertrophy presence was needle reuse (3.20 [95% CI: 1.99-5.13]). Higher frequency of lipohypertrophy was also observed among those who used longer needles, that is, ≥8 mm (2.00 [95% CI: 1.35-2.97]) or ≥6 mm (1.52 [1.20-1.92]) and who injected insulin more than two times per day (2.27 [1.58-3.25]). The mean difference in daily injection between patients with lipohypertrophy and those without this complication was 0.40 [95% CI: 0.24-0.56], indicating a higher number of daily injections in the lipohypertrophy group (Figure 2). The type of injection device (pen, syringe) had no impact on lipohypertrophy prevalence (0.75 [95% CI: 0.49-1.14]). Interestingly, individuals treated with insulin analogs had lower odds of having lipohypertrophy than those treated with human insulins (0.67 [95% CI: 0.48-0.94]). The mean daily insulin dose was about 7.86 [95% CI: 5.57-10.15] units higher in patients with lipohypertrophy than in those without this condition.

Figure 1. — The pooled prevalence odds ratio for lipohypertrophy risk factors in people with diabetes.

Figure 2. — The pooled mean difference between lipohypertrophy and no lipohypertrophy groups.

Among variables related to patients’ characteristics, both longer (>5 years) duration of diabetes and insulin therapy were associated with increased odds of lipohypertrophy (1.56 [95% CI: 1.09-2.23] and 2.62 [1.70-4.04]). Mean differences in duration of diabetes and insulin therapy were higher among patients with lipohypertrophy, that is, 1.10 [95% CI: 0.25-1.94] years and 1.81 [0.87-2.75] years, respectively. Lipohypertrophy was slightly more prevalent in patients with type 1 diabetes compared with those with type 2 diabetes (1.56 [95% CI: 1.14-2.13]) and in overweight/obese individuals compared with those with normal BMI (1.52 kg/m² [1.07-2.17]). Nonetheless, patients with and without lipohypertrophy did not differ in mean BMI (MD = 0.35 kg/m² [95% CI: -0.36 to 1.05]). Sex and age were insignificant risk factors for lipohypertrophy development (Figures 1 and 2).

In the subgroup analyses, significant interactions for lipohypertrophy odds ratios were observed for specific comparisons depending on factors such as geographical region, the proportion of patients with type 1 diabetes, publication date, type of lipohypertrophy diagnosis (clinical, ultrasonographical), age of the population, and the number of patients in the studies. In most cases, interactions were noted for comparisons involving subgroups of a single study, suggesting that the observed discrepancies are more likely to be incidental rather than indicative of clear trends. Results of subgroup analyses were shown in the supplementary appendix (Supplementary Tables: 12, 15, 19, 23, 27, 31, 35, 38, 41, 44, 48, 52).

In many cases, meta-regression was conducted on fewer studies than the original comparisons, rendering these findings exploratory (Supplementary Tables: 13, 16, 20, 25, 28, 32, 36, 39, 42, 45, 49, 53). Nonetheless, the conducted meta-regression, in most cases, did not reveal any significant associations between the analyzed variables and the results of comparisons for specific risk factors regarding the frequency of lipohypertrophy occurrence. This suggests an independent nature of analyzed risk factors from other variables. However, the effect size of risk factors such as needle reuse and incorrect site rotation could be influenced by study size. In addition, as the odds ratio for incorrect rotation increased, the odds for reuse also rose, suggesting a co-occurrence of these injection technique-related issues among patients (Supplementary Table 13).

No publication bias was observed in funnel plots (Supplementary Figures: 3, 23, 38, 40, 52, 54, 68, 82, 84, 97, 99, 112, 125, 136, 149, 151, 166, 168).

Discussion

Lipohypertrophy is a recognized skin complication of subcutaneous insulin therapy, and understanding the risk factors is crucial for optimizing diabetes care. This meta-analysis, including 51 studies, is the first to systematically examine a wide range of potential risk factors associated with lipohypertrophy.

Our results indicate that incorrect rotation of injection sites and needle reuse are the two strongest contributors to lipohypertrophy, as evidenced by high odds ratios, emphasizing a robust and non-random association. These modifiable risk factors underscore the importance of patient education and health care provider guidance in promoting proper injection techniques and minimizing the risk of lipohypertrophy. Other factors with statistical significance for increased lipohypertrophy odds included type 1 diabetes, being overweight or obese, longer needle size (≥6 mm, ≥8 mm), a higher number of daily injections, and longer duration of insulin or diabetes. In contrast, using insulin analogs seemed to have a protective impact on lipohypertrophy development. However, it is crucial to note that most of these associations, while statistically significant, exhibit relatively low odds ratios (<2). Considering also the moderate quality of the studies, caution is warranted in interpreting these results. Sex, age, and insulin device (pens, syringe) were not associated with increased odds of lipohypertrophy in this meta-analysis.

While extended exposure to insulin therapy in terms of longer insulin therapy duration and frequent injections may seem intuitive as contributors to lipohypertrophy, explanations for other risk factors are not as straightforward. For instance, the relationship between type 1 diabetes and slightly increased lipohypertrophy prevalence raises questions about whether these patients are more susceptible to developing lipohypertrophy due to different pathogenesis or because of generally longer duration of insulin therapy or higher use of multiple daily injection schemes than patients with type 2 diabetes. Alternatively, it is also possible that lipohypertrophy is more easily identifiable in individuals with type 1 diabetes due to higher awareness of potential complications and better diabetes management education stemming from an early diagnosis in childhood, as suggested by our own clinical experience. Explaining the causes of these differences, however, requires further research to be thoroughly investigated and validated.

Similarly, higher occurrence of lipohypertrophy in individuals with increased BMI may result from excess sensitivity of adipose tissue itself or the fact that first signs of subcutaneous nodules in leaner patients may be visually detectable at an early stage, enabling taking preventive actions much earlier. Interestingly, this meta-analysis also showed that using shorter needles and insulin analogs is associated with a reduced prevalence of lipohypertrophy. However, it remains unclear whether these decreased odds are attributable to specific pharmacological properties of insulin analogs and mechanical advantages of shorter needles or if patients with access to modern interventions also receive better diabetes education with lipohypertrophy prevention. Further research, especially well-designed prospective studies, is needed to provide a more comprehensive understanding of these risk factors.

Previous meta-analyses^15,61 focused on the pooled prevalence of lipohypertrophy among people with diabetes. Only Wang et al¹⁵ attempted to identify risk factors for lipohypertrophy using meta-regression to assess factors such as sex, age, diabetes type, duration of insulin therapy, needle reuse, needle size, site rotation, HbA1c levels, insulin dose, and mean number of daily injections on pooled lipohypertrophy prevalence. However, their approach did not consider variations in the prevalence of these factors between patients with and without lipohypertrophy. Instead, they used a cumulative score for the entire study population as a confounding variable. As a result, they did not identify any significant influence of analyzed factors on the development of lipohypertrophy. Only the duration of insulin therapy was found to have a notable impact on its prevalence (β coefficient = 0.124 [0.026-0.221], P = 0.013). This contradicted the findings from several individual studies, which consistently indicated the presence of other risk factors, such as incorrect site rotation and needle reuse. Our systematic review examined the characteristics of patients with and without lipohypertrophy separately, which allowed the calculation of the odds ratio for each considered factor. Furthermore, our review encompassed a greater number of studies compared with Wang et al, enhancing the comprehensiveness of the systematic review.

Despite providing a comprehensive literature review and analysis of potential risks, this meta-analysis has certain limitation. The primary limitation lies in the composition of the included studies, which predominantly consisted of cross-sectional studies. Although these studies provide valuable insights into the potential risk factors, they cannot establish causality. This concern is particularly relevant when examining the associations between insulin dose and lipohypertrophy. It remains challenging to determine whether increased insulin requirements result from impaired insulin absorption from lipohypertrophic lesions or whether higher insulin doses accelerate the development of lipohypertrophy. Most likely, the relationship between insulin dose and lipohypertrophy is bidirectional, as evidence from prospective studies suggests that educational intervention aimed at improving injection technique can reduce both lipohypertrophy and insulin dose requirements. Grassi et al⁶² reported that correct injection techniques consisting of single-use of 4-mm needles and avoiding injection into lipohypertrophy decreased insulin dose by two units in the three months. In a randomized clinical trial conducted by the AMD-OSDI Study Group,⁶³ educational intervention significantly reduced insulin demand in patients with diabetes by 20.7%. These findings support the results of our meta-analysis.

Another significant challenge is the substantial heterogeneity observed across various analyses. To elucidate the potential sources of the heterogeneity, a series of subgroup meta-analyses and meta-regression were conducted considering confounding variables such as diabetes type, patient age, lipohypertrophy measurement, and other related to patient characteristics and injection techniques. Unfortunately, due to limited studies and data availability, only one confounding variable could be assessed at the time, often using fewer studies than initially included in the primary meta-analysis. Despite considerable efforts, most of the univariable analyses did not entirely explain the observed variability of results. Nonetheless, the subgroup and meta-regression analyses suggested that several factors may contribute to the observed effect size, including sample size. While ancillary analyses provide valuable hypotheses for further investigation, they should be interpreted cautiously. Specifically, generalizing results for subgroups consisting of one study could be inappropriate, as the publication of new studies in the future may dramatically change the effect size.

Furthermore, only research conducted and published after 1990 was included to ensure relevance to current clinical practice, given the shift from animal-derived insulin to modern insulin formulations. This approach was necessary to reflect contemporary treatment standards but inherently limits comparisons with older data. Further uncertainties in the results related to reporting errors were found in some publications included in the systematic review. For example, some data from Strollo et al³³ study were omitted in extraction due to incorrect calculations of percentages of patients with lipohypertrophy in the specific risk groups. In addition, variations in definitions of lipohypertrophy, methods of assessment, and different clinical practices across diabetes centers, including qualifications and technical skills of individuals assessing lipohypertrophy, may have influenced the meta-analysis results. Despite a comprehensive literature review, no evidence could be found describing risk factors for lipohypertrophy in patients treated with GLP-1 analogs. Future research should focus on this patient group. Moreover, it is important to emphasize that the results of this meta-analysis should not be directly extrapolated to patients using insulin pumps. This caution is due to the distinct nature of insulin delivery and the potential unique risk factors associated with continuous subcutaneous insulin infusion systems, which were not specifically addressed in our study. Further research is needed to understand lipohypertrophy in the context of insulin pump therapy and its potential differences from those receiving insulin via injections.

Conclusions

In conclusion, this study has identified several modifiable risk factors associated with lipohypertrophy in insulin-injecting patients. Incorrect rotation of injection sites, needle reuse, needle size, and insulin type are targets for educational interventions. Widespread education on safe and correct injection practices is a clear option to reduce the prevalence of lipohypertrophy and improve the overall quality of diabetes care.

Supplemental Material

sj-docx-1-dst-10.1177_19322968251325569 – Supplemental material for Risk factors for Lipohypertrophy in People With Insulin-Treated Diabetes: A Systematic Meta-Analysis

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Supplemental material, sj-docx-1-dst-10.1177_19322968251325569 for Risk factors for Lipohypertrophy in People With Insulin-Treated Diabetes: A Systematic Meta-Analysis by Julia K. Mader, Riccardo Fornengo, Ahmed Hassoun, Lutz Heinemann, Bernhard Kulzer, Magdalena Monica, Trung Nguyen, Jochen Sieber, Eric Renard, Yves Reznik, Przemysław Ryś, Anita Stożek-Tutro and Emma G Wilmot in Journal of Diabetes Science and Technology

sj-docx-2-dst-10.1177_19322968251325569 – Supplemental material for Risk factors for Lipohypertrophy in People With Insulin-Treated Diabetes: A Systematic Meta-Analysis

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Supplemental material, sj-docx-2-dst-10.1177_19322968251325569 for Risk factors for Lipohypertrophy in People With Insulin-Treated Diabetes: A Systematic Meta-Analysis by Julia K. Mader, Riccardo Fornengo, Ahmed Hassoun, Lutz Heinemann, Bernhard Kulzer, Magdalena Monica, Trung Nguyen, Jochen Sieber, Eric Renard, Yves Reznik, Przemysław Ryś, Anita Stożek-Tutro and Emma G Wilmot in Journal of Diabetes Science and Technology

Footnotes

Abbreviations: CI, confidence interval; GLP-1, glucagon-like peptide-1; HbA1c, glycated hemoglobin; JBI, Joanna Briggs Institute; LH+, patients with lipohypertrophy; LH-, patients without lipohypertrophy; MD, mean difference; pOR, prevalence odds ratio; SD, standard deviation, T1DM, type 1 diabetes; T2DM, type 2 diabetes.

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JKM is a member of the Advisory Board of Abbott Diabetes Care, Becton-Dickinson/embecta, Boehringer Ingelheim, Eli Lilly, embecta, Medtronic, Novo Nordisk A/S, Roche Diabetes Care, Sanofi-Aventis, Viatris; and received speaker honoraria from A. Menarini Diagnostics, Abbott Diabetes Care, AstraZeneca, Becton-Dickinson/embecta, Boehringer Ingelheim, Dexcom, Eli Lilly, Medtrust, MSD, Novo Nordisk A/S, Roche Diabetes Care, Sanofi, Servier, and Ypsomed. BK is a member of the advisory board of embecta. ER is a member of the Advisory Board of Eli Lilly, Novo Nordisk, and received speaker honoraria from embecta. JS was an employee of embecta as this research was conducted. He is stockholder of embecta and Becton&Dickinson. TN is an employee of embecta. LH is a consultant for several companies developing novel diagnostic and therapeutic options for diabetes treatment. He is a shareholder of the Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany. YR declares consultant/speaker fees from Medtronic, Insulet, embecta, Abbott, Novo Nordisk, Eli-Lilly, Sanofi, and Air Liquide Santé International. AH is a member of the advisory board of embecta. AST, MM, PR, and RF declare no conflict of interest. EGW is a member of the advisory board of Abbott Diabetes Care, Eli Lilly, embecta, Insulet, Medtronic, Novo Nordisk, Roche Diabetes Care, and Sanofi-Aventis. Research support from Abbott Diabetes Care, embecta, Insulet, Novo Nordisk, and Sanofi-Aventis, and has received speaker honoraria from Abbott Diabetes Care, AstraZeneca, Dexcom, Eli Lilly, embecta, Glooko, Insulet, Medtronic, Novo Nordisk, Sanofi, and Ypsomed.

Funding: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was sponsored by embecta. The sponsor had a role in the study design, interpreting data, writing the report, and in the decision to submit the paper for publication.

ORCID iDs: Julia K. Mader Inline graphic https://orcid.org/0000-0001-7854-4233

Lutz Heinemann Inline graphic https://orcid.org/0000-0003-2493-1304

Bernhard Kulzer Inline graphic https://orcid.org/0000-0001-9120-4479

Magdalena Monica Inline graphic https://orcid.org/0000-0001-5089-5349

Trung Nguyen Inline graphic https://orcid.org/0000-0003-3169-2460

Jochen Sieber Inline graphic https://orcid.org/0000-0002-3150-9657

Eric Renard Inline graphic https://orcid.org/0000-0002-3407-7263

Przemyslaw Ryś Inline graphic https://orcid.org/0009-0007-0513-7750

Anita Stożek-Tutro Inline graphic https://orcid.org/0000-0001-6315-681X

Emma G Wilmot Inline graphic https://orcid.org/0000-0002-8698-6207

Supplemental Material: Supplemental material for this article is available online.

References

1. Abu Ghazaleh H, Hashem R, Forbes A, et al. A systematic review of ultrasound-detected lipohypertrophy in insulin-exposed people with diabetes. Diabetes Ther. 2018;9(5):1741-1756. doi: 10.1007/s13300-018-0472-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
2. 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(2):259-267. doi: 10.1007/s13300-016-0161-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
3. Blanco M, Hernández MT, Strauss KW, Amaya M. Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes. Diabetes Metab. 2013;39(5):445-453. doi: 10.1016/j.diabet.2013.05.006. [DOI] [PubMed] [Google Scholar]
4. Bochanen N, Decochez K, Heleu E, et al. Lipohypertrophy Monitoring Study (LIMO): effect of single use of 4 mm pen needles combined with education on injection site rotation on glycaemic control: confirmation of an unpleasant truth. Diabet Med. 2022;39(1):e14672. doi: 10.1111/dme.14672. [DOI] [PubMed] [Google Scholar]
5. The AMD-OSDI Study Group on Injection Techniques and Nefrocenter Research & Nyx Start-up Study Group; Gentile S, Guarino G, Corte TD, et al. Insulin-induced skin lipohypertrophy in type 2 diabetes: a multicenter regional survey in Southern Italy. Diabetes Ther. 2020;11(9):2001-2017. doi: 10.1007/s13300-020-00876-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
6. Gentile S, Guarino G, Della Corte T, et al. Bruising: a neglected, though patient-relevant complication of insulin injections coming to light from a real-life nationwide survey. Diabetes Ther. 2021;12(4):1143-1157. doi: 10.1007/s13300-021-01026-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
7. Gupta SS, Gupta KS, Gathe SS, Bamrah P, Gupta SS. Clinical implications of lipohypertrophy among people with type 1 diabetes in India. Diabetes Technol Ther. 2018;20(7):483-491. doi: 10.1089/dia.2018.0074. [DOI] [PubMed] [Google Scholar]
8. Sürücü HA, OKur Arslan H. Lipohypertrophy in individuals with type 2 diabetes: prevalence and risk factors. J Caring Sci. 2018;7(2):67-74. doi: 10.15171/jcs.2018.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
9. Thewjitcharoen Y, Prasartkaew H, Tongsumrit P, et al. Prevalence, risk factors, and clinical characteristics of lipodystrophy in insulin-treated patients with diabetes: an old problem in a new era of modern insulin. Diabetes Metab Syndr Obes. 2020;13:4609-4620. doi: 10.2147/DMSO.S282926. [DOI] [PMC free article] [PubMed] [Google Scholar]
10. Arora S, Agrawal NK, Shanthaiah DM, et al. Early detection of cutaneous complications of insulin therapy in type 1 and type 2 diabetes mellitus. Prim Care Diabetes. 2021;15(5):859-864. doi: 10.1016/j.pcd.2021.06.004. [DOI] [PubMed] [Google Scholar]
11. Barola A, Tiwari P, Bhansali A, et al. Insulin-related lipohypertrophy: lipogenic action or tissue trauma? Front Endocrinol. 2018;9:1-8. doi: 10.3389/fendo.2018.00638. [DOI] [PMC free article] [PubMed] [Google Scholar]
12. Gentile S, Strollo F, Satta E, et al. Insulin-related lipohypertrophy in hemodialyzed diabetic people: a multicenter observational study and a methodological approach. Diabetes Ther. 2019;10(4):1423-1433. doi: 10.1007/s13300-019-0650-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
13. Hajheydari Z, Kashi Z, Akha O, Akbarzadeh S. Frequency of lipodystrophy induced by recombinant human insulin. Eur Rev Med Pharmacol Sci. 2011;15(10):1196-1201. [PubMed] [Google Scholar]
14. Kumar R, Gupta RD, Shetty S, et al. Lipohypertrophy in insulin injecting patients with diabetes mellitus: an under-recognized barrier for glycemic control. Int J Diabetes Dev Ctries. 2021;41(2):329-336. doi: 10.1007/s13410-020-00889-2. [DOI] [Google Scholar]
15. Wang K, Zhang S, Liu C, Chen Y. A meta-analysis and meta-regression on the prevalence of lipohypertrophy in diabetic patients on insulin therapy. Therapie. 2021;76(6):617-628. doi: 10.1016/j.therap.2021.04.002. [DOI] [PubMed] [Google Scholar]
16. 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(2):e20776. doi: 10.5812/ijem.20776. [DOI] [PMC free article] [PubMed] [Google Scholar]
17. Hauner H, Stockamp B, Haastert B. Prevalence of lipohypertrophy in insulin-treated diabetic patients and predisposing factors. Exp Clin Endocrinol Diabetes. 1996;104(2):106-110. doi: 10.1055/s-0029-1211431. [DOI] [PubMed] [Google Scholar]
18. Kirac C, Gonullu C, Baldane S, et al. Effect of vitamin D deficiency on the frequency of lipohypertrophy occurrence in patients with type 2 diabetes mellitus under injectable treatment. Turk J Endocrinol Metab. 2020;24:184-188. doi: 10.25179/tjem.2020-74469. [DOI] [Google Scholar]
19. Nawaz A, Hasham MA, Shireen M, et al. Prevalence of lipohypertrophy and its associations in insulin-treated diabetic patients. Pak J Med Sci. 2022;39(1):209-213. doi: 10.12669/pjms.39.1.6134. [DOI] [PMC free article] [PubMed] [Google Scholar]
20. Elsayed S, Soliman AT, De Sanctis V, et al. Insulin-induced lipodystrophy and predisposing factors in children and adolescents with type 1 diabetes mellitus (T1DM) in a tertiary care Egyptian center. Acta Biomed. 2023;94(3):e2023078. doi: 10.23750/abm.v94i3.14117. [DOI] [PMC free article] [PubMed] [Google Scholar]
21. 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(3):443-452. doi: 10.4103/ijem.IJEM_548_16. [DOI] [PMC free article] [PubMed] [Google Scholar]
22. Gentile S, Guarino G, Della Corte T, et al. The economic burden of insulin injection-induced lipohypertrophy. role of education: the ISTERP-3 study. Adv Ther. 2022;39(5):2192-2207. doi: 10.1007/s12325-022-02105-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
23. Ji L, Sun Z, Li Q, et al. Lipohypertrophy in China: prevalence, risk factors, insulin consumption, and clinical impact. Diabetes Technol Ther. 2017;19(1):61-67. doi: 10.1089/dia.2016.0334. [DOI] [PubMed] [Google Scholar]
24. Vardar B, Kizilci S. Incidence of lipohypertrophy in diabetic patients and a study of influencing factors. Diabetes Res Clin Pract. 2007;77(2):231-236. doi: 10.1016/j.diabres.2006.12.023. [DOI] [PubMed] [Google Scholar]
25. Gentile S, Guarino G, Della Corte T, et al. Why do so many people with type 2 diabetes who take insulin have lipohypertrophy? Fate or educational deficiencies? Diabetes Ther. 2023;14(1):179-191. doi: 10.1007/s13300-022-01341-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
26. Lin Y, Lin L, Wang W, Hong J, Zeng H. Insulin-related lipohypertrophy: ultrasound characteristics, risk factors, and impact of glucose fluctuations. Endocrine. 2022;75(3):768-775. doi: 10.1007/s12020-021-02904-w. [DOI] [PubMed] [Google Scholar]
27. Hawa A, Teng CL, Devaraj NK, et al. Prevalence and associated factors of lipohypertrophy in insulin-injected patients with diabetes in selected primary care clinics in Peninsular Malaysian: a cross-sectional study. Malays Fam Physician. 2023;18:37. doi: 10.51866/oa.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
28. Pahuja V, Punjot P, Fernandes G, et al. Exploring the factors associated with lipohypertrophy in insulin-treated type 2 diabetes patients in a tertiary care hospital in Mumbai, India. Int J Diabetes Dev Ctries. 2019;39(3):426-431. doi: 10.1007/s13410-019-00735-0. [DOI] [Google Scholar]
29. Cunningham MT, McKenna M. Lipohypertrophy in insulin-treated diabetes: prevalence and associated risk factors. J Diabetes Nurs. 2013;17(9):340-343. [Google Scholar]
30. Pozzuoli GM, Laudato M, Barone M, Crisci F, Pozzuoli B. Errors in insulin treatment management and risk of lipohypertrophy. Acta Diabetol. 2018;55(1):67-73. doi: 10.1007/s00592-017-1066-y. [DOI] [PubMed] [Google Scholar]
31. Korkmaz FN, Gökçay Canpolat A, Güllü S. Determination of insulin-related lipohypertrophy frequency and risk factors in patients with diabetes. Endocrinología, Diabetes Y Nutrición. 2022;69(5):354-361. doi: 10.1016/j.endinu.2021.07.002. [DOI] [PubMed] [Google Scholar]
32. Shetty Z, Ps L, Kulkarni S, et al. Screening of Lipohypertrophy (LH) in type 1 and type 2 diabetes patients and factors influencing this condition. EMIJ. 2018;6(5):309-312. doi: 10.15406/emij.2018.06.00203. [DOI] [Google Scholar]
33. Strollo F, Guarino G, Armentano V. Unexplained hypoglycaemia and large glycaemic variability: skin lipohypertrophy as a predictive sign. Diabetes Res. 2016;2(1):24-32. [Google Scholar]
34. Wysham CH, Rosenstock J, Vetter ML, Wang H, Hardy E, Iqbal N. Further improvement in glycemic control after switching from exenatide two times per day to exenatide once-weekly autoinjected suspension in patients with type 2 diabetes: 52-week results from the DURATION-NEO-1 study. BMJ Open Diabetes Res Care. 2020;8(1):e000773. doi: 10.1136/bmjdrc-2019-000773. [DOI] [PMC free article] [PubMed] [Google Scholar]
35. Gentile S, Strollo F. Subcutaneous nodules during treatment with an exenatide long-actin once-weekly formulation: an ultrasound evaluation. Diver Equal Health Care. 2016;13(4):313-318. [Google Scholar]
36. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71. [DOI] [PMC free article] [PubMed] [Google Scholar]
37. Moola S, Munn Z, Tufanaru C, et al. Chapter 7: systematic reviews of etiology and risk. In: Joanna Briggs Institute Reviewer’s Manual. Adelaide, South Australia: The Joanna Briggs Institute; 2017. [Google Scholar]
38. Tufanaru C, Munn Z, Aromataris E, et al. Chapter 3: systematic reviews of etiology and risk. In: Joanna Briggs Institute Reviewer’s Manual. Adelaide, South Australia: The Joanna Briggs Institute; 2017. [Google Scholar]
39. Wallace B, Lajeunesse M, Dietz G, et al. OpenMEE: intuitive, open-source software for meta-analysis in ecology and evolutionary biology. Methods Ecol Evol. 2017;8:941-947. doi: 10.1111/2041-210X.12708. [DOI] [Google Scholar]
40. Abujbara M, Khreisat EA, Khader Y, Ajlouni KM. Effect of insulin injection techniques on glycemic control among patients with diabetes. Int J Gen Med. 2022;15:8593-8602. doi: 10.2147/IJGM.S393597. [DOI] [PMC free article] [PubMed] [Google Scholar]
41. AlJaber AN, Sales I, Almigbal TH, Wajid S, Batais MA. The prevalence of lipohypertrophy and its associated factors among Saudi patients with type 2 diabetes mellitus. J Taibah Univ Med Sci. 2020;15(3):224-231. doi: 10.1016/j.jtumed.2020.03.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
42. Barlas T, Yalcin MM, Coskun M, et al. Evaluation of lipohypertrophy in patients with type 1 diabetes mellitus on multiple daily insulin injections or continuous subcutaneous insulin infusion. Endocr Pract. 2023;29(2):119-126. doi: 10.1016/j.eprac.2022.11.008. [DOI] [PubMed] [Google Scholar]
43. De Coninck C, Frid A, Gaspar R, et al. Results and analysis of the 2008–2009 insulin injection technique questionnaire survey. J Diabetes. 2010;2(3):168-179. doi: 10.1111/j.1753-0407.2010.00077.x. [DOI] [PubMed] [Google Scholar]
44. Deeb A, Abdelrahman L, Tomy M, et al. Impact of insulin injection and infusion routines on lipohypertrophy and glycemic control in children and adults with diabetes. Diabetes Ther. 2019;10(1):259-267. doi: 10.1007/s13300-018-0561-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
45. Frid AH, Hirsch LJ, Menchior AR, Morel DR, Strauss KW. Worldwide injection technique questionnaire study: injecting complications and the role of the professional. Mayo Clin Proc. 2016;91(9):1224-1230. doi: 10.1016/j.mayocp.2016.06.012. [DOI] [PubMed] [Google Scholar]
46. Gunhan HG, Elbasan O, Imre E, Yavuz DG. Lipodystrophy frequency according to insulin treatment regimen in type 2 diabetic patients: is insulin injection frequency matters in analog insulin era. Acta Endocrinol (Buchar). 2022;18(2):202-208. doi: 10.4183/aeb.2022.202. [DOI] [PMC free article] [PubMed] [Google Scholar]
47. Kakourou T, Dacou-Voutetakis C, Kavadias G, Bakoula C, Aroni K. Limited joint mobility and lipodystrophy in children and adolescents with insulin-dependent diabetes mellitus. Pediatr Dermatol. 1994;11(4):310-314. doi: 10.1111/j.1525-1470.1994.tb00094.x. [DOI] [PubMed] [Google Scholar]
48. Klimontov W, Lazarev M, Makhotin A, et al. Insulin-induced lipohypertrophy: clinical and ultrasound characteristics. Diabetes Mellitus. 2018;21(4):255-263. doi: 10.14341/DM9549. [DOI] [Google Scholar]
49. Li FF, Fu SM, Liu ZP, et al. Injection sites lipohypertrophy among 736 patients with type 2 diabetes of different-grade hospitals. Int J Clin Exp Med. 2016;9(7):13178-13183. [Google Scholar]
50. Luo D, Shi Y, Zhu M, et al. Subclinical lipohypertrophy—easily ignored complications of insulin therapy. J Diabetes Complications. 2021;35(3):107806. doi: 10.1016/j.jdiacomp.2020.107806. [DOI] [PubMed] [Google Scholar]
51. Nain RA, Thomas DC. Lipohypertrophy prevalence and its associated risk factors in insulin-treated patients with type 2 diabetes in North Borneo, Malaysia. Belitung Nurs J. 2022;8(6):521-528. doi: 10.33546/bnj.2246. [DOI] [PMC free article] [PubMed] [Google Scholar]
52. Omar MA, El-Kafoury AA, El-Araby RI. Lipohypertrophy in children and adolescents with type 1 diabetes and the associated factors. BMC Res Notes. 2011;4(1):290. doi: 10.1186/1756-0500-4-290. [DOI] [PMC free article] [PubMed] [Google Scholar]
53. Saeed M, Aslam W, Ahmad M, et al. Frequency and risk factors of lipohypertrophy in insulin treated patients with diabetes: an experience from a tertiary care center in Multan. Med Forum Monthly. 2022;33(8):78-82. [Google Scholar]
54. Saez de Ibarra L, Gallego F. Factors related to lipohypertrophy in insulin-treated diabetic patients: role of educational intervention. Pract Diab Int. 1998;15(1):9-11. [Google Scholar]
55. Sawatkar GU, Kanwar AJ, Dogra S, Bhadada SK, Dayal D. Spectrum of cutaneous manifestations of type 1 diabetes mellitus in 500 South Asian patients. Br J Dermatol. 2014;171(6):1402-1406. doi: 10.1111/bjd.13077. [DOI] [PubMed] [Google Scholar]
56. Sharma M, Kumar R, Rohilla L, Angrup A, Yadav J, Dayal D. Effect of reuse of insulin needle on glycaemic control and related complications in children with type 1 diabetes mellitus: a prospective observational study. Indian J Endocrinol Metab. 2022;26(2):167-172. doi: 10.4103/ijem.ijem_407_21. [DOI] [PMC free article] [PubMed] [Google Scholar]
57. Singha A, Bhattacharjee R, Dalal BS, et al. Associations of insulin-induced lipodystrophy in children, adolescents, and young adults with type 1 diabetes mellitus using recombinant human insulin: a cross-sectional study. J Pediatr Endocrinol Metab. 2021;34(4):503-508. doi: 10.1515/jpem-2020-0556. [DOI] [PubMed] [Google Scholar]
58. Tsadik AG, Atey TM, Nedi T, Fantahun B, Feyissa M. Effect of insulin-induced lipodystrophy on glycemic control among children and adolescents with diabetes in Tikur Anbessa specialized hospital, Addis Ababa, Ethiopia. J Diabetes Res. 2018;2018:4910962-4910967. doi: 10.1155/2018/4910962. [DOI] [PMC free article] [PubMed] [Google Scholar]
59. Munster HE, van Sande CP, van de Voorhoeve PG, et al. Dermatological complications of insulin therapy in children with type 1 diabetes. Eur Diabetes Nurs. 2014;11(3):79-84. doi: 10.1002/edn.255. [DOI] [Google Scholar]
60. Zureik A, Julla JB, Erginay A, et al. Prevalence, severity stages, and risk factors of diabetic retinopathy in 1464 adult patients with type 1 diabetes. Graefes Arch Clin Exp Ophthalmol. 2021;259(12):3613-3623. doi: 10.1007/s00417-021-05298-7. [DOI] [PubMed] [Google Scholar]
61. Deng N, Zhang X, Zhao F, et al. Prevalence of lipohypertrophy in insulin-treated diabetes patients: a systematic review and meta-analysis. J Diabetes Investig. 2018;9(3):536-543. doi: 10.1111/jdi.12742. [DOI] [PMC free article] [PubMed] [Google Scholar]
62. Grassi G, Scuntero P, Trepiccioni R, Marubbi F, Strauss K. Optimizing insulin injection technique and its effect on blood glucose control. J Clin Transl Endocrinol. 2014;1(4):145-150. doi: 10.1016/j.jcte.2014.07.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
63. AMD-OSDI Study Group on Injection Technique, Nefrocenter Research and Nyx Start-Up; Gentile S, Guarino G, Della Corte T, et al. Role of structured education in reducing lypodistrophy and its metabolic complications in insulin-treated people with type 2 diabetes: a randomized multicenter case–control study. Diabetes Ther. 2021;12(5):1379-1398. doi: 10.1007/s13300-021-01006-0. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

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Supplementary Materials

sj-docx-1-dst-10.1177_19322968251325569 – Supplemental material for Risk factors for Lipohypertrophy in People With Insulin-Treated Diabetes: A Systematic Meta-Analysis

sj-docx-1-dst-10.1177_19322968251325569.docx^{(45.1KB, docx)}

sj-docx-2-dst-10.1177_19322968251325569 – Supplemental material for Risk factors for Lipohypertrophy in People With Insulin-Treated Diabetes: A Systematic Meta-Analysis

sj-docx-2-dst-10.1177_19322968251325569.docx^{(10.8MB, docx)}

[bibr1-19322968251325569] 1. Abu Ghazaleh H, Hashem R, Forbes A, et al. A systematic review of ultrasound-detected lipohypertrophy in insulin-exposed people with diabetes. Diabetes Ther. 2018;9(5):1741-1756. doi: 10.1007/s13300-018-0472-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr2-19322968251325569] 2. 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(2):259-267. doi: 10.1007/s13300-016-0161-3. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr3-19322968251325569] 3. Blanco M, Hernández MT, Strauss KW, Amaya M. Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes. Diabetes Metab. 2013;39(5):445-453. doi: 10.1016/j.diabet.2013.05.006. [DOI] [PubMed] [Google Scholar]

[bibr4-19322968251325569] 4. Bochanen N, Decochez K, Heleu E, et al. Lipohypertrophy Monitoring Study (LIMO): effect of single use of 4 mm pen needles combined with education on injection site rotation on glycaemic control: confirmation of an unpleasant truth. Diabet Med. 2022;39(1):e14672. doi: 10.1111/dme.14672. [DOI] [PubMed] [Google Scholar]

[bibr5-19322968251325569] 5. The AMD-OSDI Study Group on Injection Techniques and Nefrocenter Research & Nyx Start-up Study Group; Gentile S, Guarino G, Corte TD, et al. Insulin-induced skin lipohypertrophy in type 2 diabetes: a multicenter regional survey in Southern Italy. Diabetes Ther. 2020;11(9):2001-2017. doi: 10.1007/s13300-020-00876-0. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr6-19322968251325569] 6. Gentile S, Guarino G, Della Corte T, et al. Bruising: a neglected, though patient-relevant complication of insulin injections coming to light from a real-life nationwide survey. Diabetes Ther. 2021;12(4):1143-1157. doi: 10.1007/s13300-021-01026-w. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr7-19322968251325569] 7. Gupta SS, Gupta KS, Gathe SS, Bamrah P, Gupta SS. Clinical implications of lipohypertrophy among people with type 1 diabetes in India. Diabetes Technol Ther. 2018;20(7):483-491. doi: 10.1089/dia.2018.0074. [DOI] [PubMed] [Google Scholar]

[bibr8-19322968251325569] 8. Sürücü HA, OKur Arslan H. Lipohypertrophy in individuals with type 2 diabetes: prevalence and risk factors. J Caring Sci. 2018;7(2):67-74. doi: 10.15171/jcs.2018.011. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr9-19322968251325569] 9. Thewjitcharoen Y, Prasartkaew H, Tongsumrit P, et al. Prevalence, risk factors, and clinical characteristics of lipodystrophy in insulin-treated patients with diabetes: an old problem in a new era of modern insulin. Diabetes Metab Syndr Obes. 2020;13:4609-4620. doi: 10.2147/DMSO.S282926. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr10-19322968251325569] 10. Arora S, Agrawal NK, Shanthaiah DM, et al. Early detection of cutaneous complications of insulin therapy in type 1 and type 2 diabetes mellitus. Prim Care Diabetes. 2021;15(5):859-864. doi: 10.1016/j.pcd.2021.06.004. [DOI] [PubMed] [Google Scholar]

[bibr11-19322968251325569] 11. Barola A, Tiwari P, Bhansali A, et al. Insulin-related lipohypertrophy: lipogenic action or tissue trauma? Front Endocrinol. 2018;9:1-8. doi: 10.3389/fendo.2018.00638. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr12-19322968251325569] 12. Gentile S, Strollo F, Satta E, et al. Insulin-related lipohypertrophy in hemodialyzed diabetic people: a multicenter observational study and a methodological approach. Diabetes Ther. 2019;10(4):1423-1433. doi: 10.1007/s13300-019-0650-2. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr13-19322968251325569] 13. Hajheydari Z, Kashi Z, Akha O, Akbarzadeh S. Frequency of lipodystrophy induced by recombinant human insulin. Eur Rev Med Pharmacol Sci. 2011;15(10):1196-1201. [PubMed] [Google Scholar]

[bibr14-19322968251325569] 14. Kumar R, Gupta RD, Shetty S, et al. Lipohypertrophy in insulin injecting patients with diabetes mellitus: an under-recognized barrier for glycemic control. Int J Diabetes Dev Ctries. 2021;41(2):329-336. doi: 10.1007/s13410-020-00889-2. [DOI] [Google Scholar]

[bibr15-19322968251325569] 15. Wang K, Zhang S, Liu C, Chen Y. A meta-analysis and meta-regression on the prevalence of lipohypertrophy in diabetic patients on insulin therapy. Therapie. 2021;76(6):617-628. doi: 10.1016/j.therap.2021.04.002. [DOI] [PubMed] [Google Scholar]

[bibr16-19322968251325569] 16. 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(2):e20776. doi: 10.5812/ijem.20776. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr17-19322968251325569] 17. Hauner H, Stockamp B, Haastert B. Prevalence of lipohypertrophy in insulin-treated diabetic patients and predisposing factors. Exp Clin Endocrinol Diabetes. 1996;104(2):106-110. doi: 10.1055/s-0029-1211431. [DOI] [PubMed] [Google Scholar]

[bibr18-19322968251325569] 18. Kirac C, Gonullu C, Baldane S, et al. Effect of vitamin D deficiency on the frequency of lipohypertrophy occurrence in patients with type 2 diabetes mellitus under injectable treatment. Turk J Endocrinol Metab. 2020;24:184-188. doi: 10.25179/tjem.2020-74469. [DOI] [Google Scholar]

[bibr19-19322968251325569] 19. Nawaz A, Hasham MA, Shireen M, et al. Prevalence of lipohypertrophy and its associations in insulin-treated diabetic patients. Pak J Med Sci. 2022;39(1):209-213. doi: 10.12669/pjms.39.1.6134. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr20-19322968251325569] 20. Elsayed S, Soliman AT, De Sanctis V, et al. Insulin-induced lipodystrophy and predisposing factors in children and adolescents with type 1 diabetes mellitus (T1DM) in a tertiary care Egyptian center. Acta Biomed. 2023;94(3):e2023078. doi: 10.23750/abm.v94i3.14117. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr21-19322968251325569] 21. 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(3):443-452. doi: 10.4103/ijem.IJEM_548_16. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr22-19322968251325569] 22. Gentile S, Guarino G, Della Corte T, et al. The economic burden of insulin injection-induced lipohypertrophy. role of education: the ISTERP-3 study. Adv Ther. 2022;39(5):2192-2207. doi: 10.1007/s12325-022-02105-5. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr23-19322968251325569] 23. Ji L, Sun Z, Li Q, et al. Lipohypertrophy in China: prevalence, risk factors, insulin consumption, and clinical impact. Diabetes Technol Ther. 2017;19(1):61-67. doi: 10.1089/dia.2016.0334. [DOI] [PubMed] [Google Scholar]

[bibr24-19322968251325569] 24. Vardar B, Kizilci S. Incidence of lipohypertrophy in diabetic patients and a study of influencing factors. Diabetes Res Clin Pract. 2007;77(2):231-236. doi: 10.1016/j.diabres.2006.12.023. [DOI] [PubMed] [Google Scholar]

[bibr25-19322968251325569] 25. Gentile S, Guarino G, Della Corte T, et al. Why do so many people with type 2 diabetes who take insulin have lipohypertrophy? Fate or educational deficiencies? Diabetes Ther. 2023;14(1):179-191. doi: 10.1007/s13300-022-01341-w. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr26-19322968251325569] 26. Lin Y, Lin L, Wang W, Hong J, Zeng H. Insulin-related lipohypertrophy: ultrasound characteristics, risk factors, and impact of glucose fluctuations. Endocrine. 2022;75(3):768-775. doi: 10.1007/s12020-021-02904-w. [DOI] [PubMed] [Google Scholar]

[bibr27-19322968251325569] 27. Hawa A, Teng CL, Devaraj NK, et al. Prevalence and associated factors of lipohypertrophy in insulin-injected patients with diabetes in selected primary care clinics in Peninsular Malaysian: a cross-sectional study. Malays Fam Physician. 2023;18:37. doi: 10.51866/oa.100. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr28-19322968251325569] 28. Pahuja V, Punjot P, Fernandes G, et al. Exploring the factors associated with lipohypertrophy in insulin-treated type 2 diabetes patients in a tertiary care hospital in Mumbai, India. Int J Diabetes Dev Ctries. 2019;39(3):426-431. doi: 10.1007/s13410-019-00735-0. [DOI] [Google Scholar]

[bibr29-19322968251325569] 29. Cunningham MT, McKenna M. Lipohypertrophy in insulin-treated diabetes: prevalence and associated risk factors. J Diabetes Nurs. 2013;17(9):340-343. [Google Scholar]

[bibr30-19322968251325569] 30. Pozzuoli GM, Laudato M, Barone M, Crisci F, Pozzuoli B. Errors in insulin treatment management and risk of lipohypertrophy. Acta Diabetol. 2018;55(1):67-73. doi: 10.1007/s00592-017-1066-y. [DOI] [PubMed] [Google Scholar]

[bibr31-19322968251325569] 31. Korkmaz FN, Gökçay Canpolat A, Güllü S. Determination of insulin-related lipohypertrophy frequency and risk factors in patients with diabetes. Endocrinología, Diabetes Y Nutrición. 2022;69(5):354-361. doi: 10.1016/j.endinu.2021.07.002. [DOI] [PubMed] [Google Scholar]

[bibr32-19322968251325569] 32. Shetty Z, Ps L, Kulkarni S, et al. Screening of Lipohypertrophy (LH) in type 1 and type 2 diabetes patients and factors influencing this condition. EMIJ. 2018;6(5):309-312. doi: 10.15406/emij.2018.06.00203. [DOI] [Google Scholar]

[bibr33-19322968251325569] 33. Strollo F, Guarino G, Armentano V. Unexplained hypoglycaemia and large glycaemic variability: skin lipohypertrophy as a predictive sign. Diabetes Res. 2016;2(1):24-32. [Google Scholar]

[bibr34-19322968251325569] 34. Wysham CH, Rosenstock J, Vetter ML, Wang H, Hardy E, Iqbal N. Further improvement in glycemic control after switching from exenatide two times per day to exenatide once-weekly autoinjected suspension in patients with type 2 diabetes: 52-week results from the DURATION-NEO-1 study. BMJ Open Diabetes Res Care. 2020;8(1):e000773. doi: 10.1136/bmjdrc-2019-000773. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr35-19322968251325569] 35. Gentile S, Strollo F. Subcutaneous nodules during treatment with an exenatide long-actin once-weekly formulation: an ultrasound evaluation. Diver Equal Health Care. 2016;13(4):313-318. [Google Scholar]

[bibr36-19322968251325569] 36. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr37-19322968251325569] 37. Moola S, Munn Z, Tufanaru C, et al. Chapter 7: systematic reviews of etiology and risk. In: Joanna Briggs Institute Reviewer’s Manual. Adelaide, South Australia: The Joanna Briggs Institute; 2017. [Google Scholar]

[bibr38-19322968251325569] 38. Tufanaru C, Munn Z, Aromataris E, et al. Chapter 3: systematic reviews of etiology and risk. In: Joanna Briggs Institute Reviewer’s Manual. Adelaide, South Australia: The Joanna Briggs Institute; 2017. [Google Scholar]

[bibr39-19322968251325569] 39. Wallace B, Lajeunesse M, Dietz G, et al. OpenMEE: intuitive, open-source software for meta-analysis in ecology and evolutionary biology. Methods Ecol Evol. 2017;8:941-947. doi: 10.1111/2041-210X.12708. [DOI] [Google Scholar]

[bibr40-19322968251325569] 40. Abujbara M, Khreisat EA, Khader Y, Ajlouni KM. Effect of insulin injection techniques on glycemic control among patients with diabetes. Int J Gen Med. 2022;15:8593-8602. doi: 10.2147/IJGM.S393597. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr41-19322968251325569] 41. AlJaber AN, Sales I, Almigbal TH, Wajid S, Batais MA. The prevalence of lipohypertrophy and its associated factors among Saudi patients with type 2 diabetes mellitus. J Taibah Univ Med Sci. 2020;15(3):224-231. doi: 10.1016/j.jtumed.2020.03.006. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr42-19322968251325569] 42. Barlas T, Yalcin MM, Coskun M, et al. Evaluation of lipohypertrophy in patients with type 1 diabetes mellitus on multiple daily insulin injections or continuous subcutaneous insulin infusion. Endocr Pract. 2023;29(2):119-126. doi: 10.1016/j.eprac.2022.11.008. [DOI] [PubMed] [Google Scholar]

[bibr43-19322968251325569] 43. De Coninck C, Frid A, Gaspar R, et al. Results and analysis of the 2008–2009 insulin injection technique questionnaire survey. J Diabetes. 2010;2(3):168-179. doi: 10.1111/j.1753-0407.2010.00077.x. [DOI] [PubMed] [Google Scholar]

[bibr44-19322968251325569] 44. Deeb A, Abdelrahman L, Tomy M, et al. Impact of insulin injection and infusion routines on lipohypertrophy and glycemic control in children and adults with diabetes. Diabetes Ther. 2019;10(1):259-267. doi: 10.1007/s13300-018-0561-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr45-19322968251325569] 45. Frid AH, Hirsch LJ, Menchior AR, Morel DR, Strauss KW. Worldwide injection technique questionnaire study: injecting complications and the role of the professional. Mayo Clin Proc. 2016;91(9):1224-1230. doi: 10.1016/j.mayocp.2016.06.012. [DOI] [PubMed] [Google Scholar]

[bibr46-19322968251325569] 46. Gunhan HG, Elbasan O, Imre E, Yavuz DG. Lipodystrophy frequency according to insulin treatment regimen in type 2 diabetic patients: is insulin injection frequency matters in analog insulin era. Acta Endocrinol (Buchar). 2022;18(2):202-208. doi: 10.4183/aeb.2022.202. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr47-19322968251325569] 47. Kakourou T, Dacou-Voutetakis C, Kavadias G, Bakoula C, Aroni K. Limited joint mobility and lipodystrophy in children and adolescents with insulin-dependent diabetes mellitus. Pediatr Dermatol. 1994;11(4):310-314. doi: 10.1111/j.1525-1470.1994.tb00094.x. [DOI] [PubMed] [Google Scholar]

[bibr48-19322968251325569] 48. Klimontov W, Lazarev M, Makhotin A, et al. Insulin-induced lipohypertrophy: clinical and ultrasound characteristics. Diabetes Mellitus. 2018;21(4):255-263. doi: 10.14341/DM9549. [DOI] [Google Scholar]

[bibr49-19322968251325569] 49. Li FF, Fu SM, Liu ZP, et al. Injection sites lipohypertrophy among 736 patients with type 2 diabetes of different-grade hospitals. Int J Clin Exp Med. 2016;9(7):13178-13183. [Google Scholar]

[bibr50-19322968251325569] 50. Luo D, Shi Y, Zhu M, et al. Subclinical lipohypertrophy—easily ignored complications of insulin therapy. J Diabetes Complications. 2021;35(3):107806. doi: 10.1016/j.jdiacomp.2020.107806. [DOI] [PubMed] [Google Scholar]

[bibr51-19322968251325569] 51. Nain RA, Thomas DC. Lipohypertrophy prevalence and its associated risk factors in insulin-treated patients with type 2 diabetes in North Borneo, Malaysia. Belitung Nurs J. 2022;8(6):521-528. doi: 10.33546/bnj.2246. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr52-19322968251325569] 52. Omar MA, El-Kafoury AA, El-Araby RI. Lipohypertrophy in children and adolescents with type 1 diabetes and the associated factors. BMC Res Notes. 2011;4(1):290. doi: 10.1186/1756-0500-4-290. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr53-19322968251325569] 53. Saeed M, Aslam W, Ahmad M, et al. Frequency and risk factors of lipohypertrophy in insulin treated patients with diabetes: an experience from a tertiary care center in Multan. Med Forum Monthly. 2022;33(8):78-82. [Google Scholar]

[bibr54-19322968251325569] 54. Saez de Ibarra L, Gallego F. Factors related to lipohypertrophy in insulin-treated diabetic patients: role of educational intervention. Pract Diab Int. 1998;15(1):9-11. [Google Scholar]

[bibr55-19322968251325569] 55. Sawatkar GU, Kanwar AJ, Dogra S, Bhadada SK, Dayal D. Spectrum of cutaneous manifestations of type 1 diabetes mellitus in 500 South Asian patients. Br J Dermatol. 2014;171(6):1402-1406. doi: 10.1111/bjd.13077. [DOI] [PubMed] [Google Scholar]

[bibr56-19322968251325569] 56. Sharma M, Kumar R, Rohilla L, Angrup A, Yadav J, Dayal D. Effect of reuse of insulin needle on glycaemic control and related complications in children with type 1 diabetes mellitus: a prospective observational study. Indian J Endocrinol Metab. 2022;26(2):167-172. doi: 10.4103/ijem.ijem_407_21. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr57-19322968251325569] 57. Singha A, Bhattacharjee R, Dalal BS, et al. Associations of insulin-induced lipodystrophy in children, adolescents, and young adults with type 1 diabetes mellitus using recombinant human insulin: a cross-sectional study. J Pediatr Endocrinol Metab. 2021;34(4):503-508. doi: 10.1515/jpem-2020-0556. [DOI] [PubMed] [Google Scholar]

[bibr58-19322968251325569] 58. Tsadik AG, Atey TM, Nedi T, Fantahun B, Feyissa M. Effect of insulin-induced lipodystrophy on glycemic control among children and adolescents with diabetes in Tikur Anbessa specialized hospital, Addis Ababa, Ethiopia. J Diabetes Res. 2018;2018:4910962-4910967. doi: 10.1155/2018/4910962. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr59-19322968251325569] 59. Munster HE, van Sande CP, van de Voorhoeve PG, et al. Dermatological complications of insulin therapy in children with type 1 diabetes. Eur Diabetes Nurs. 2014;11(3):79-84. doi: 10.1002/edn.255. [DOI] [Google Scholar]

[bibr60-19322968251325569] 60. Zureik A, Julla JB, Erginay A, et al. Prevalence, severity stages, and risk factors of diabetic retinopathy in 1464 adult patients with type 1 diabetes. Graefes Arch Clin Exp Ophthalmol. 2021;259(12):3613-3623. doi: 10.1007/s00417-021-05298-7. [DOI] [PubMed] [Google Scholar]

[bibr61-19322968251325569] 61. Deng N, Zhang X, Zhao F, et al. Prevalence of lipohypertrophy in insulin-treated diabetes patients: a systematic review and meta-analysis. J Diabetes Investig. 2018;9(3):536-543. doi: 10.1111/jdi.12742. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr62-19322968251325569] 62. Grassi G, Scuntero P, Trepiccioni R, Marubbi F, Strauss K. Optimizing insulin injection technique and its effect on blood glucose control. J Clin Transl Endocrinol. 2014;1(4):145-150. doi: 10.1016/j.jcte.2014.07.006. [DOI] [PMC free article] [PubMed] [Google Scholar]

[bibr63-19322968251325569] 63. AMD-OSDI Study Group on Injection Technique, Nefrocenter Research and Nyx Start-Up; Gentile S, Guarino G, Della Corte T, et al. Role of structured education in reducing lypodistrophy and its metabolic complications in insulin-treated people with type 2 diabetes: a randomized multicenter case–control study. Diabetes Ther. 2021;12(5):1379-1398. doi: 10.1007/s13300-021-01006-0. [DOI] [PMC free article] [PubMed] [Google Scholar]

PERMALINK

Risk factors for Lipohypertrophy in People With Insulin-Treated Diabetes: A Systematic Meta-Analysis

Julia K Mader, MD

Riccardo Fornengo, MD

Ahmed Hassoun, MD

Lutz Heinemann, PhD

Bernhard Kulzer, PhD

Magdalena Monica, MSc

Trung Nguyen, PhD

Jochen Sieber, PhD

Eric Renard, PhD

Yves Reznik, MD

Przemysław Ryś, PhD

Anita Stożek-Tutro, MSc

Emma G Wilmot, PhD