Review
Insulin related lipodystrophic lesions and hypoglycemia: Double standards?

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Abstract

Lipohypertophy (LH) is the most common skin complication of incorrect injection technique which does not only represent an aesthetic defect but also severely disrupts insulin pharmacokinetics/pharmacodynamics. As a consequence of that, hormone release is delayed and unexplained/unpredictable hypoglycemia occurs, both deteriorating metabolic control while negatively affecting adherence to treatment and quality of life. The economic burden due to unwanted intra-LH injections is accounted for by inappropriately high insulin requirements, increased emergency-related hospitalizations, and loss of work days. Greater attention has to be paid by diabetes care teams to education programs with periodic refreshers to achieve better metabolic control and reduce the economic burden of diabetes.

Section snippets

Definition

Lipohypertrophy (LH) is the most common form of LD and is characterized by thickened hard-elastic adipose tissue with large adipocytes and a dense fibrous texture [2]. Its structure makes insulin release slower and unpredictabl [1,3], as documented by studies analyzing the effects of injections performed directly into the nodules as either single shots [3] or euglycemic clamp infusions [4]. Ultrasonography is the gold standard for their identification but is not suited for daily activities [5],

Clinical impact

LH lesions are in fact clinically relevant rather than merely unpleasant to see: they always cause poor metabolic control indeed, along with large glycemic variability and unexpected/unpredictable episodes of hypoglycaemia (Hypo) [1,3,5,7]. Nevertheless we have to admit that just few authors seem to be interested in the association between LH and Hypo and fully delegate LH management to nurses, might be depending either on little attention to identification of skin lesions per se [8] or on

Insulin pharmacokinetics/pharmacodynamics and LH

In fact, based on drug pharmacokinetics and pharmacodynamics it is easy to understand why insulin injections into LH nodules are associated with large glycaemic excursions and poor metabolic control [3,4]. However sudden Hypos unrelated to well expected causes (including errors in hormone dosage or food intake, vomiting, diarrhoea and so on) are slightly harder to explain. One conceivable reason behind them might be the typical fibrous and firm texture [2] allowing LH to act as a reservoir

Clinical trials and Real life

During the last two decades pharmacologists prompted a number of randomized clinical trials investigating the effects of fast acting and basal insulin analogs and thus providing new therapeutic opportunities for physicians and patients. However, the literature never investigated patient compliance with best injection practice nor even mentioned needle length choice as apart from occasionally reporting on disposable pens devoted to specific insulin analogs. All this clearly shows that

Costs

The close relationship between LH and Hypo indicates that each insulin treated subject is at risk for at least five Hypos per year [1,9]. Due to the huge number of insulin-treated subjects with T2DM and to their high LH rate along with the relevant economic burden of hospitalization for severe hypoglycaemia (1081 € per episode) with direct medical costs accounting for about 80% of the total [20,21] the overall saving expected from a strong campaign against injection errors is warranted by all

Authorship

SG and FS planned and wrote the manuscript after critically interpreting the results of the database analysis performed by TDC, GM and GG. All authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.

Ethics guidelines

All procedures followed were in accordance with the Helsinki Declaration of 1964, as revised in 2013.

Conflicts of interest

Declare no conflicts of interest.

Acknowledgments

We thank the Associazione Medici Diabetologi (AMD) for its support. The components of Italian Study Group on Injection Techniques (ISGIT) are also acknowledged for critical reading and approval of the manuscript: Stefano De Riu, Nicoletta De Rosa, Giorgio Grassi, Gabriella Garrapa, Laura Tonutti, Katja Speese, Lia Cucco, Maria Teresa Branca, Amodio Botta

References (21)

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    There was a paucity of literature regarding employer-related economic burden. From an employer perspective, economic burden was related to indirect costs such as days of work lost due to SH and decreased productivity.16,47,61–63 In a survey of 1478 respondents with T2DM, 29.3% had more work and activity impairment which could also indirectly affect employers through loss of productivity.9

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    We are fully aware that our latest comments are highly subjective, despite being supported by comparisons between the above mentioned WD and WS groups, but we strongly feel like suggesting both training and experienced health professionals to exploit light and postural changes to better identify LH lesions. More accurate and long-lasting patient examinations including structured systematic efforts to identify LH lesions will increase diabetes teams’ professional competence in the field, and will efficiently prevent technical errors or correct initial educational shortcomings, thereby lowering LH prevalence and thus reducing the risk of metabolic complications and related costs [4,14–18]. The Authors declare no conflicts of interest.

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