**1. Introduction**

Current insulin therapy requires delivery into the subcutaneous (SC) tissue either by injection or by infusion. Optimal insulin delivery requires that accidental intramuscular (IM) or

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

intradermal (ID) delivery be avoided since the pharmacokinetics (PK) and pharmacodynamics (PD) of insulin are significantly altered in these tissue spaces. Optimal delivery also requires that sites of injection or infusion be rotated systematically in order to avoid the most common complication of insulin therapy, lipohypertrophy (LH). Insulin delivered into LH also has significantly altered PK and PD, which can lead to unexpected hypoglycemic episodes and glycemic variability. The latter are associated with worsened overall glucose control, increased short- and long-term complications, and higher costs.

However, the latest survey revealed that the longer lengths (8 mm and higher) are still being used by approximately 30% of patients worldwide and that the 5- and 6-mm needles are still used by approximately 20% each. This means that only 30% of patients worldwide currently use the recommended 4-mm needles. Longer needles are being used in sites where IM injection risk is very high (thighs and arms) and by patients who are at an increased risk because they have thin SC layers (slim and normal-weight adults as well as all adolescents

Optimal Insulin Delivery

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The same survey has shown that lipohypertrophy (LH) is very common at injection sites. LH was found in almost a third of patients worldwide, many of them having LH at multiple injection sites. Injecting into LH has serious consequences for glucose control as well as possibly adverse effects on long-term outcomes and costs. Patients with LH consume a mean of over 10 IU more insulin per day than those without LH, and their HbA1c is on average 0.55% higher. LH is associated with increased rates of unexplained hypoglycemia, glucose variabil-

The survey showed that LH is most frequently associated with an incorrect rotation of injection sites and reusing pen needles. Rotating injection sites carefully appears to be the best method of avoiding LH. HbA1c values are lower in patients who rotate their injections over larger injection areas and who get their sites inspected regularly. Checking of injection sites routinely by health-care givers is associated with less LH and lower HbA1c levels, yet nearly 40% of patients reported that they could not remember their injection sites ever being examined. Patients are also more likely to rotate correctly if they have obtained injection instruction from their carer in the last 6 months. However, less than two out of five claim to have obtained such instructions on injecting in that time period. Ten percent of total injectors claim that they have never obtained injection training at all. The survey also shows that incorrect disposal of sharps after use is rampant. The majority of used sharps end up in public trash and constitute a major risk factor for accidental

The skin is the main obstacle the needle must overcome. Needles must be at least long enough to traverse the skin and reach the SC tissue. Adult skin, according to a number of studies using imaging techniques ranging from ultrasound (US) to computer tomography (CT), has yielded remarkably similar results across genders, ethnicities, age groups, and body mass index (BMI) categories. The skin averages approximately 2–2.5-mm thick and varies in its 95% confidence interval (CI) between 1.25 and 3.25 mm. These studies included patients with type 2 diabetes (T2DM) from the Philippines [9], Korea [10], China [11], and India [12]; both type 1 diabetes (T1DM) and T2DM adults from the USA (including four different ethnic groups) [7];

and children).

needle sticks.

**3. Skin thickness**

ity, and more frequent diabetic ketoacidosis (DKA).

and children from South Africa [13] and Italy [14].

Recently, new recommendations have been published as a consensus document from international diabetes experts [1]. This publication was the collective output of 183 experts from 54 countries who wrote and vetted a practical, evidence-based roadmap for optimal insulin delivery at the FITTER (Forum for Injection Technique and Therapy: Expert Recommendations) workshop from October 23 to 24, 2015, in Rome. FITTER was the fourth in a sequence of workshops on optimal insulin delivery [2–4]. The FITTER recommendations were also based on the results of the fourth Injection Technique Questionnaire (ITQ) survey conducted from 2014 to 2015. In total, 13,289 insulin-injecting patients from 42 countries participated [5].

Each recommendation is followed by a grade (e.g., A2). The letter indicates the strength of each recommendation: A. Strongly recommended; B. Recommended; C. Unresolved issue. The number indicates the degree of scientific support for each recommendation: 1. At least one rigorously performed study which is peer-reviewed and published; 2. At least one observational, epidemiologic, or population-based study which is peer-reviewed and published; 3. Consensus expert opinion based on patient experience. Since FITTER, many diabetes groups from countries around the world have adapted and adopted these recommendations as local guidelines. We draw on certain of these recommendations in the review that follows as well as summarize studies that have been performed since FITTER and will follow a thematic format, beginning with the anatomy of injection sites.
