Advertisement
Mayo Clinic Proceedings Home

Worldwide Injection Technique Questionnaire Study

Population Parameters and Injection Practices

      Abstract

      From February 1, 2014, through June 30, 2015, 13,289 insulin-injecting patients from 423 centers in 42 countries took part in one of the largest surveys ever performed in diabetes. The goal was to assess patient characteristics, as well as historical and practical aspects of their injection technique. Results show that 4- and 8-mm needle lengths are each used by nearly 30% of patients and 5- and 6-mm needles each by approximately 20%. Higher consumption of insulin (as measured by total daily dose) is associated with having lipohypertrophy (LH), injecting into LH, leakage from the injection site, and failing to reconstitute cloudy insulin. Glycated hemoglobin values are, on average, 0.5% higher in patients with LH and are significantly higher with incorrect rotation of sites and with needle reuse. Glycated hemoglobin values are lower in patients who distribute their injections over larger injection areas and whose sites are inspected routinely. The frequencies of unexpected hypoglycemia and glucose variability are significantly higher in those with LH, those injecting into LH, those who incorrectly rotate sites, and those who reuse needles. Needles associated with diabetes treatment are the most commonly used medical sharps in the world. However, correct disposal of sharps after use is critically suboptimal. Many used sharps end up in public trash and constitute a major accidental needlestick risk. Use of these data should stimulate renewed interest in and commitment to optimizing injection practices in patients with diabetes.

      Abbreviations and Acronyms:

      BMI (body mass index), FITTER (Forum for Injection Technique and Therapy: Expert Recommendations), HbA1c (glycated hemoglobin), IM (intramuscular), ITQ (Injection Technique Questionnaire), LH (lipohypertrophy), NPH (neutral protamine Hagedorn (also known as insulin N)), NSI (needlestick injury), SC (subcutaneous), T1DM (type 1 diabetes), T2DM (type 2 diabetes), TDD (total daily dose)
      In preparation for drafting the new insulin delivery recommendations (published in this issue),
      • Frid A.H.
      • Kreugel G.
      • Grassi G.
      • et al.
      New insulin delivery recommendations.
      a large international survey of current injection practices was undertaken. The rationale was to understand the nature of the problems before proposing the solutions. From February 1, 2014, through June 30, 2015, the insulin Injection Technique Questionnaire (ITQ) survey was conducted with 13,289 patients from 423 centers in 42 countries, making it one of the largest international surveys of its kind ever performed.
      The objectives of the ITQ were to chart the epidemiologic profiles for the major insulin injection parameters; to determine the degree of variability in injection technique and its causes, interactions, and associations with glucose control and other outcomes; and to understand patients' perceptions of the injection process, including the psychological aspects.
      Previous ITQs were performed in 1995,
      • Partanen T.M.
      • Rissanen A.
      Insulin injection practices.
      2000,
      • Strauss K.
      • De Gols H.
      • Hannet I.
      • Partanen T.M.
      • Frid A.
      A pan-European epidemiologic study of insulin injection technique in patients with diabetes.
      and 2009,
      • De Coninck C.
      • Frid A.
      • Gaspar R.
      • et al.
      Results and analysis of the 2008-2009 Insulin Injection Technique Questionnaire survey.
      each surveying an increasing number of patients, centers, and countries. The similarity in wording and design of the questionnaires in the 4 surveys permits comparison of injection practice across time and geographic locations. The results of the current ITQ were presented at the Forum for Injection Technique and Therapy: Expert Recommendations (FITTER) workshop.

      FITTER International Congress; October 23-24, 2015; Rome, Italy. BD website. https://www.bd.com/resource.aspx?IDX=33000. Accessed June 8, 2016.

      Methods

      The ITQ survey consists of an initial patient section (administered by an experienced diabetes nurse) followed by a section completed by the patient's nurse, physician, or diabetes educator after observation of injection technique and meticulous examination of all injection sites. Results are provided based on either the patient's or the health care provider's (or both) survey responses and are indicated as such. The various language versions of the ITQ (patient and professional forms) are available via the Fitter4Diabetes website.

      Fitter4Diabetes website. http://www.fitter4diabetes.com. Accessed June 7, 2016.

      Although 17 different languages were used, the content of each survey version was identical.
      Besides participant demographic information, the key insulin injection parameters queried by the questionnaire were as follows: current practice (injection device and needle length, number of injections per day, choice of injection site, use and characteristics of lifted skinfolds [pinch-up], needle entry angle, size of the injecting zone, site rotation, disinfecting before injecting, dwell time of needle under the skin, site inspection by a health care professional, needle reuse, sharps disposal, and injection through clothing), observed anomalies at injection sites (insulin leakage, bleeding, bruising, lipoatrophy, lipohypertrophy [LH], inflammation, and pain), knowledge about injections (identity of trainer, themes covered in injection training, adequacy of the coverage of these themes, and desire for more knowledge), blood glucose anomalies (episodes of hypoglycemia and hyperglycemia, hospitalizations for hypoglycemia, history of ketoacidosis, glucose variability, and unexpected hypoglycemia), and safety (needlestick injuries [NSIs], risk factors for blood-borne infections, and disposal habits for used sharps).
      Centers were selected to be, as much as possible, representative of diabetes care in the countries involved. Approximately a third were specialist diabetes clinics/hospitals, a third were community diabetes centers, and a third were general practice centers or private offices. All the selected centers participated willingly and without financial incentive.
      Participating centers were required to understand and agree with the ITQ. Each was expected to recruit approximately 25 patients within the allotted time frame. Patients were not placed at any risk by the study, therapy decisions were not based on the study, and no financial compensation was offered for participation. Verbal informed consent was obtained from all the participants.
      Patient identity was kept confidential at all times, and the study was conducted according to Good Clinical Practice and the Helsinki accords. The ITQ was organized in cooperation with BD (Becton, Dickinson & Co., Inc., Franklin Lakes, NJ). BD associates in each country distributed questionnaires to centers and collected them once filled out. BD played no role in the discussions with patients or in the completion of forms. No participant identifying information was made available to BD. Ethics committee approval, although not required for such a survey, was nevertheless obtained whenever specifically requested by a center or by local regulators.
      All the participants had insulin-treated diabetes and had been injecting with a pen, syringe, or both for at least 6 months before taking the survey. To eliminate selection bias, patients were recruited into the study on a sequential basis, ie, eligible and consenting participants were accessioned consecutively as they entered the clinic or health care setting. A total of 13,289 participants with diabetes who had both patient and nurse forms filled out were included in the database. Not every parameter will reflect this total number owing to the occasional skipping of an item in the survey. However, the large overall numbers help overcome any potential bias that missing data may introduce.
      Patient demographic data included age, sex, type of diabetes, years with diabetes, years injecting, and devices used. We recognize the importance of economic standing of patients, availability of health care resources, and rural vs urban settings in influencing outcomes. However, it was decided not to pursue such detailed socioeconomic data in an already-lengthy survey with so much intercountry variability. Although we do not have precise data on place of residence, we do know that most centers that performed the survey were in urban areas, especially in countries such as India and China.
      There were 3853 Chinese patients in the study, 29% of the total. Of these, 3354 were given a slightly shorter questionnaire (although with identical questions from the full study questionnaire) and 499 were given the complete questionnaire. Health care in China is often delivered in very rapid physician visits; it is not uncommon for a physician to see up to 100 outpatients in a day. In such a fast-moving system, it is difficult to complete a full ITQ survey. For this reason, the shorter questionnaire was used in most patients (n=3354), with the full questionnaire used in the remaining 499. To prevent undue weighting of the worldwide data by the Chinese data, the results were assessed with and without the additional 3354 patients. Results for nearly all the parameters remained unchanged, hence the extra Chinese patients were included in the overall analysis.
      One of us (K.W.S.) wrote the initial draft of this article, which was then reviewed and revised by the other authors. The content was also presented at the FITTER meeting in Rome, Italy, in 2015, where it was reviewed and commented on by the 183 diabetes experts gathered from 54 countries, which included the 42 countries in the survey.
      IBM SPSS Statistics for Windows software, Version 19 (IBM Corp) was used to perform the data analysis. Descriptive statistics, frequencies, and rankings were calculated. χ2 Analysis was performed where appropriate for contingency tables. The relationship between needle length and other clinically relevant parameters was assessed in R software using a linear model with log transformation of the needle length as response and was further analyzed using a type 2 analysis of variance (ANOVA) (which is better suited for unbalanced designs). Conversely, the most clinically relevant variables were also assessed with needle length as a predictor using multivariate models and adjusting whenever possible for other relevant variables. These models were compared using ANOVA and Tukey multiple comparisons for continuous responses and logistic models and adjusted odd ratios for binary categorical variables. The threshold for staying in the model was P<.05. Two-tailed tests were used in all the analyses. Initially, results from each of the 42 countries were analyzed independently, and only when the distributions of key demographic parameters (age, sex, body mass index [BMI], and duration of diabetes) were found to be comparable were all the data pooled into an overall database. Findings from individual countries will be the subject of additional, secondary analyses and publications.
      In a survey with such a large number of participants (n=13,289), even slight differences between groups generally reach statistical significance, often with P values as low as less than .001. Hence, our comments are based not only on statistical tests but also on the practical and clinical significance of each finding. All the findings from the ITQ survey data are available in an interactive form on Tableau Public Adam Yeung's Profile website.

      ITQ survey data. Tableau Public Adam Yeung's Profile website. http://tabsoft.co/23V6ofi. Accessed June 8, 2016.

      Results

      Population Descriptors

      The number and identity of centers in each country are given in Supplemental Table 1 (available online at http://www.mayoclinicproceedings.org).

      Fitter4Diabetes website. http://www.fitter4diabetes.com. Accessed June 7, 2016.

      Table 1 gives the population statistics for the study participants. Overall, 90.5% of participants were adults, 4.9% were adolescents, 2.4% were children, and 2.2% were parents giving injections to children. Of the total, 51.3% were female. Nearly 34% of patients had type 1 diabetes mellitus (T1DM), 65% had type 2 diabetes mellitus (T2DM), and 1% had gestational diabetes.
      Table 1Population Descriptive Characteristics
      CharacteristicValue (mean ± SD)Patients (No.)
      Age (y)51.9±18.113,225
      BMI26.6±6.212,806
      Years with DM13.2±9.79197
      Age DM diagnosed (y)39.9±17.212,737
      Years taking pills8.3±7.26607
      Years taking insulin8.7±8.98242
      Daily dose of rapid insulin (IU)27.0±20.71422
      Daily dose of fast analogue (IU)31.9±21.63467
      Daily dose of NPH (IU)31.6±24.41134
      Daily dose of basal analogue (IU)27.6±19.54709
      Daily dose of premixes (IU)43.0±25.31796
      Total daily dose of insulins (IU)48.5±32.47756
      Glycated hemoglobin (% [mmol/mol])8.47±2.14 (69.1±17.5)7663
      BMI = body mass index (calculated as the weight in kilograms divided by the height in meters squared); DM = diabetes mellitus; NPH = neutral protamine Hagedorn.

      Medications and Devices

      Overall, 56.5% of participants took insulin only, 40.5% of participants took both insulin and pills, and 2.0% took glucagon-like peptide-1 receptor agonists alone or combined with other treatments. In total, 85.6% of participants used an insulin pen alone, 9.6% used a syringe alone, 2.8% used both, and 1.4% used a pen and another device (usually an insulin pump).

      Needle Length

      Patients were asked what needle length they used. Table 2 lists their answers for this ITQ and for the ITQ performed in 2009. In the 5 years between ITQs there was a clear shift away from 12.7- and 8-mm needles and toward the 5- and especially 4-mm ones, which has sometimes been called the “shift to short.” The percentage of 6-mm needle use remained essentially unchanged during this period. As an additional check on the patients' statement, nurses were asked to examine the device the patients used and to report on the length and gauge of the needle(s). Their observations are also listed in Table 2. Eliminating the 12.7-mm needle (1% of patient answers) and the “Unknown” responses (we assumed that the nurses reported needle length accurately), there is extremely good agreement between the patient and nurse responses (Table 2).
      Table 2Needle Lengths Used in 2015 vs 2009 as Reported by Patients and in 2015 as Reported by Nurses vs Patients, and TDD of Insulin in 2015 (n=12,554 for the 2015 Survey)
      ITQ = Injection Technique Questionnaire; NA = not available; TDD = total daily dose.
      Needle length (mm)Compared with previous ITQ (%)2015 ITQ results
      Excludes 12.7 mm and Unknown answers.
      20092015Nurses (%)Patients (%)Mean TDD (IU)
      12.75.31.0NANANA
      848.616.029.229.254.0
      615.815.120.321.147.0
      521.628.621.821.747.6
      4020.928.728.044.9
      Unknown7.013.2NANANA
      a ITQ = Injection Technique Questionnaire; NA = not available; TDD = total daily dose.
      b Excludes 12.7 mm and Unknown answers.
      In summary, for the nearly 6000 patients for whom we have both a patient report and a nurse observation, the 4- and 8-mm needles are each used by approximately 30% of the total and the 5- and 6-mm needles each by approximately 20%. However, there are substantial country-to-country differences in these percentages (data not shown). When viewed by age category (Supplemental Table 2, available online at http://www.mayoclinicproceedings.org),

      Fitter4Diabetes website. http://www.fitter4diabetes.com. Accessed June 7, 2016.

      it is evident that using longer needles is more prevalent in the adult groups, whereas adolescents, children, and parents injecting children use the shorter needles more frequently.
      Table 3 shows the use of different needle lengths by injection sites. A considerable percentage of patients continue to use 6- and 8-mm needles in the limbs despite recent evidence that the intramuscular (IM) injection risk is very high in these regions
      • Hirsch L.
      • Byron K.
      • Gibney M.
      Intramuscular risk at insulin injection sites-measurement of the distance from skin to muscle and rationale for shorter-length needles for subcutaneous insulin therapy.
      (Supplemental Table 3, available online at http://www.mayoclinicproceedings.org).

      Fitter4Diabetes website. http://www.fitter4diabetes.com. Accessed June 7, 2016.

      Multivariate analyses (type 2 ANOVAs) revealed that needle length was associated with country, BMI, age, total daily dose (TDD) of insulin, number of fingersticks per day (all at P<.001), needle reuse (P=.003), unexplained hypoglycemic reactions (P=.02), LH (P=.02), and glucose variability (P=.04). Note that although not significant, number of injections per day had a P value very close to the threshold (P=.058). Multivariate analysis showed that significant differences in TDD were observed between 4-mm and other needles, with lower doses used with 4-mm needles (ANOVA), and significantly less LH for 4-mm compared with 8-mm needles (logistic regression).
      Table 3Use of Needle Lengths by Injection Site
      Injection siteNeedle length used (%)Patients (No.)
      4 mm5 mm6 mm8 mm
      Abdomen alone26.623.322.327.81995
      Thigh alone29.519.426.524.6268
      Arm alone22.621.920.534.9146
      Abdomen/thigh29.820.420.329.51510
      Abdomen/arm22.825.319.432.4438
      Thigh/arm28.216.821.533.6298
      Abdomen/thigh/arm31.318.719.131.01253
      All 4 sites37.519.420.023.0664

      Needle Gauge

      In the same way that needle length has trended shorter, the gauge (diameter) of needles has also moved toward thinner options (ie, higher gauge numbers). Supplemental Tables 4 and 5 (both available online at http://www.mayoclinicproceedings.org)

      Fitter4Diabetes website. http://www.fitter4diabetes.com. Accessed June 7, 2016.

      show the needle gauge as observed by the nurses and the relationship of needle length to gauge, respectively. In general, the shorter the needle, the more frequently it has a thinner gauge.
      There is still a great deal of variation between countries in the distribution of different-gauge needles. The 32-gauge needle is almost exclusively used in shorter-length needles, which helps explain the more common use in the pediatric/adolescent populations. For unknown reasons, LH is less frequent with 32-gauge needles than with thicker gauges. Correspondingly, needle reuse is lower with this gauge, and correct rotation is more frequent. In addition, 32-gauge needles are also associated with less bleeding (data not shown for all statements; all differences P<.05).

      Insulin Use

      The mean TDD of insulin was just less than 50 IU for the entire group and did not differ significantly between T1DM and T2DM. However, there was greater variability of TDD in patients with T2DM (Supplemental Table 6, available online at http://www.mayoclinicproceedings.org).

      Fitter4Diabetes website. http://www.fitter4diabetes.com. Accessed June 7, 2016.

      There is also large variability in mean TDD from country to country. The lowest TDD is associated with the use of 4-mm needles and the highest with 8-mm needles (Table 2).
      The TDD is also lower for syringe use and correct rotation of injection sites (both differences P<.05). A higher TDD is associated with leakage from the site, failing to reconstitute cloudy insulin, skipping injections, frequent hypoglycemia and hyperglycemia, the presence of injection pain, having LH, and injecting into LH (data not shown; for all differences P<.05).

      Glucose Control

      For this study, we defined hypoglycemia as the occurrence of at least 1 symptom of low blood sugar levels (eg, palpitations, tiredness, sweating, hunger, dizziness, or tremor) and a confirmed blood glucose meter reading of 60 mg/dL or less (to convert to mmol/L, multiply by 0.0555). Because there is no consistent definition of hypoglycemia across the board, we chose this strict one to increase specificity. Frequent unexplained hypoglycemia was defined as hypoglycemia occurring 1 or more times weekly in the absence of a definable precipitating event, such as a change in medication or dose, diet, or activity. We defined glycemic variability as the presence of blood glucose oscillations from less than 60 mg/dL to more than 250 mg/dL at least 3 times a week in an unpredictable and unexplained manner and evidence that such a pattern has been present for at least the previous 6 months.
      Nurses were asked to review the medical records of each patient and to assess how many qualified as having frequent unexplained hypoglycemia and glucose variability. Nurses reported approximately 1 of 5 insulin injectors to have frequent unexplained hypoglycemia and more than 1 of 3 to have glucose variability (Table 4). An overlap between those with unexplained hypoglycemia and glucose variability exists, but there are still 24% of patients with glucose variability who do not have unexplained hypoglycemia and 18% of those with hypoglycemia who do not have variability (Table 5).
      Table 4Frequency of Hypoglycemia and Glucose Variability
      ItemPatients (No. [%])
      Unexpected hypoglycemia
       Yes1580 (19.4)
       No6558 (80.6)
      Glucose variability
       Yes2872 (35.4)
       No5251 (64.6)
      Table 5Correlation of Hypoglycemia and Glucose Variability
      Glucose variabilityUnexpected hypoglycemia (No. [%])
      YesNo
      Yes1282 (81.8)1558 (24.0)
      No286 (18.2)4929 (76.0)
      Glycated hemoglobin (HbA1c) values do not differ between T1DM and T2DM injectors, but patients with T1DM have significantly higher frequencies of unexplained hypoglycemia and glucose variability than those with T2DM. The HbA1c values do not differ among the different needle lengths, but injectors using the 6-mm needle have higher frequencies of unexplained hypoglycemia and glucose variability for unknown reasons. The HbA1c values are approximately 0.5% higher in injectors having LH (for both T1DM and T2DM; similar to recent findings in China

      Wang W, Guo X, Shen G, et al. Skin and subcutaneous thickness at insulin injection sites in Chinese patients with diabetes: clinical implications. Diabetes Metab. 2016 Jun 8. [Epub ahead of print] pii: S1262-3636(16)30402-5. http://dx.doi.org/10.1016/j.diabet.2016.04.010.

      • Sun Z.
      • Li Q.
      • Ji L.
      • et al.
      Lipohypertrophy: prevalence, risk factors, clinical characteristics, and economic burden of insulin-requiring patients in China: poster, EASD Stockholm, 2015.
      ) and are significantly higher with incorrect rotation of sites and needle reuse. The HbA1c values are lower in patients who spread their injections out over larger injection areas and whose sites are inspected routinely.
      The frequencies of unexplained hypoglycemia and glucose variability are significantly higher in those with LH, with injecting into LH, with incorrect rotation of sites, and with needle reuse, findings similar to those in a recent study in Spain.
      • Blanco M.
      • Hernández M.T.
      • Strauss K.W.
      • Amaya M.
      Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes.
      Rates of unexplained hypoglycemia and glucose variability are lower when the abdomen is used exclusively as an injection site, but as one adds use of the limbs, the rates of both disorders increase. Receiving injection training from a diabetes nurse is associated with significantly lower HbA1c levels and less frequent unexpected hypoglycemia and glucose variability (data not shown but all differences at P<.05).

      Injection Practices

      Table 6 shows the frequency of injections in the present population, with 33.7% of the total giving 4 a day. The recommended injection sites are the abdomen, thigh, arm, and buttock.
      • Bantle J.P.
      • Neal L.
      • Frankamp L.M.
      Effects of the anatomical region used for insulin injections on glycaemia in type 1 diabetes subjects.
      • Frid A.
      • Lindén B.
      Intraregional differences in the absorption of unmodified insulin from the abdominal wall.
      • Koivisto V.A.
      • Felig P.
      Alterations in insulin absorption and in blood glucose control associated with varying insulin injection sites in diabetic patients.
      • Annersten M.
      • Willman A.
      Performing subcutaneous injections: a literature review.
      • Vidal M.
      • Colungo C.
      • Jansà M.
      The abdomen was used by 90.9% of the patients, the thigh by 43.0%, the arm by 31.9%, and the buttock by 13.8% (percentages sum to >100% because many patients use >1 site). Table 7 presents percentages for specific injecting zones or combinations of zones. Patients using pens were asked how long they leave the needle under the skin after the plunger has been completely pushed in (Supplemental Table 7, available online at http://www.mayoclinicproceedings.org).

      Fitter4Diabetes website. http://www.fitter4diabetes.com. Accessed June 7, 2016.

      Only 31.9% of patients left it the recommended 10 seconds or longer. Patients were also asked to perform a mock injection while the nurse observed the technique. One of the parameters checked was whether the patient lifted a skinfold and, if so, whether it was lifted correctly and released appropriately. Overall, 63.7% of patients lifted a skinfold, and 75.0% of these did it correctly. However, less than half of these patients released the fold appropriately (option 3 in Supplemental Table 8, available online at http://www.mayoclinicproceedings.org).

      Fitter4Diabetes website. http://www.fitter4diabetes.com. Accessed June 7, 2016.

      Table 6Frequency of Injections
      Injections per dayPatients (No. [%])
      11523 (16.0)
      22480 (26.0)
      31240 (13.0)
      43213 (33.7)
      5735 (7.7)
      6197 (2.1)
      770 (0.7)
      >771 (0.7)
      Total9529 (100.0)
      Table 7Injection Sites Used
      Injection sitePatients (No. [%])
      Abdomen alone5365 (42.0)
      Thigh alone372 (2.9)
      Arm alone264 (2.1)
      Abdomen/thigh2125 (16.6)
      Abdomen/arm852 (6.7)
      Thigh/arm358 (2.8)
      Abdomen/thigh/arm1648 (12.9)
      All 4 sites996 (7.8)

      Needle Reuse

      Approximately half of the patients worldwide use their needles more than once (Table 8). Pen users tend to reuse more frequently than syringe users, although there is huge variability across countries in this practice (data not shown). There is also a large degree of variability in terms of the number of times a needle is used. Most reuse is 5 times or less, but up to 30% of persons who reuse do so 6 times or more (Table 8). A variety of reasons for reuse are cited in Table 8, but convenience and cost are clearly driving forces, especially in pen users.
      Table 8Needle Reuse by Pen and Syringe Users
      ItemPen users (%)Syringe users (%)
      Reuse needles (n=11,961 pen users; n=2711 syringe users)
       Yes55.838.8
       No44.261.2
      Frequency of reuse (n=3985 pen users; n=1126 syringe users)
       2 times30.735.4
       3-5 times39.744.0
       6-10 times16.011.4
       >10 times13.69.2
      Reasons for reuse (n=3891 pen users; n=1117 syringe users)
       Because I did not have another pen needle available9.214.5
       To save money23.338.4
       To prevent excess waste (environmental concern)6.86.6
       For convenience41.226.1
      Lipohypertrophy is more frequent in persons who reuse the needle, but reuse is a less powerful factor than incorrect rotation, smaller injection areas, and longer time taking insulin in regression analysis. Use of the 4-mm needle is associated with less LH compared with use of the 8-mm needle. Pain is also associated with needle reuse and seems to increase as a function of the number of times the needle is reused. Reuse is associated with unexplained hypoglycemia, glycemic variability, hyperglycemia, and slightly higher HbA1c levels. Reuse is not associated with insulin leakage from the skin. Interestingly, reuse is less frequent when general nurses, diabetes nurses, or diabetes educators give injection training than when physicians, pharmacists, or representatives of industry did it (data not shown but all differences at P<.05).

      Resuspending Insulin and Skipping Injections

      Patients were asked whether they use cloudy insulin (neutral protamine Hagedorn [NPH], also known as insulin N, or premixed insulin) and, if so, how many times they roll or tip to reconstitute it before injecting. In total, 65.5% use cloudy insulins, and Supplemental Table 9 (available online at http://www.mayoclinicproceedings.org)

      Fitter4Diabetes website. http://www.fitter4diabetes.com. Accessed June 7, 2016.

      shows the frequency of rolling or tipping. Patients were also asked whether they ever skipped injections and, if so, how often and why. In total, 44.7% of patients said that they skipped injections; Supplemental Table 10

      Fitter4Diabetes website. http://www.fitter4diabetes.com. Accessed June 7, 2016.

      (available online at http://www.mayoclinicproceedings.org) shows the frequency.

      Fitter4Diabetes website. http://www.fitter4diabetes.com. Accessed June 7, 2016.

      The main reasons given for skipping injections were forgetting (51.6%), not eating (8.8%), and the glucose level being too low (7.2%).

      Insulin Storage and Skin Disinfection

      Patients were asked where they stored their insulin before opening it, and 88.6% reported in the refrigerator. After opening it, 43.0% continued to store it in the fridge. Of these, only 56.3% let it warm up to room temperature before injecting it (Supplemental Table 11, available online at http://www.mayoclinicproceedings.org).

      Fitter4Diabetes website. http://www.fitter4diabetes.com. Accessed June 7, 2016.

      Nearly 57% of patients indicated that they disinfected the skin before injections. (Of vial users, 28.8% reported disinfecting the vial cap before drawing up their insulin.) Only 8.0% of patients injected through clothing.

      NSIs and Sharps Disposal

      Nearly 15% of patients reported that there were persons in their immediate surroundings who might get accidentally stuck with sharps (Table 9). When asked whether any sharps injuries had already occurred, 8.6% of the total population said yes. Less than 4% said that risk factors existed for the transmission of blood-borne pathogens (Table 9). Patients were asked how they dispose of their used sharps and where they take the container once it is full (Table 10). A very large number of used diabetes sharps still end up in the general community trash.
      Table 9Risk of Needlestick Injuries
      ItemPatients (%)
      Vulnerable persons in immediate proximity to patient (n=1576)
       Children23.4
       Other family members (eg, spouse)39.5
       Nurse or other professional4.6
       Housekeeper or trash collector8.2
      Reasons for risk (n=2140)
       I do not use devices that prevent injuries to others (safety devices)22.9
       I do not have appropriate disposal containers for my used sharps35.5
       Used sharps are sometimes left in places where others might get stuck19.1
       I am positive for hepatitis or another bloodborne illness3.7
      Table 10Initial and Final Disposal of Sharps
      ItemPatients (%)
      Initial disposal (n=12,785): Where do you put the used sharp?
       Into a container specially made for used sharps20.7
       Into a home container such as an empty bottle23.0
       Into the trash with the cap on48.1
       Into the trash without recapping6.9
       I clip off the needle and it stays in the clipper1.3
      Final disposal (n=12,785): What do you do with the waste?
       Put it into the trash40.3
       Take it to a pharmacist12.8
       Take it to a physician's office6.3
       Take it to a laboratory0.4
       Take it to the hospital or clinic22.1
       Take it to a local deposit or collection service11.0
       None of the above7.1

      Discussion

      The ITQ survey covered all major aspects of injections, including patient demographic characteristics, key injecting practices and parameters, complications, and education, as well as feelings about and psychological hurdles regarding injecting. The 2014-2015 version was the latest in a series of ITQs, thus permitting comparison and trend detection.
      A total of 13,289 patients from 423 centers in 42 countries participated in the ITQ. They were almost equally divided by sex, with one-third having T1DM and two-thirds having T2DM. All had been injecting insulin with a pen, syringe, or both for at least 6 months. Almost 57% of patients took insulin only, 41% took both insulin and pills, and 2% took glucagon-like peptide-1 receptor agonists. Approximately 30% of participants were found to have LH, and the frequencies of unexplained hypoglycemia and glucose variability were significantly higher in those with LH compared with those without. The consumption of insulin was also a mean of 10 IU/d higher in patients with LH than in those without LH.
      Another key parameter measured was needle length. This factor is a key determinant of the risk of IM injection, one of the main causes of glucose variability and hypoglycemia.
      • Frid A.
      • Gunnarson R.
      • Guntner P.
      • Lindén B.
      Effects of accidental intramuscular injection on insulin absorption in IDDM.
      • Vaag A.
      • Handberg A.
      • Lauritzen M.
      • Henriksen J.E.
      • Pedersen K.D.
      • Beck-Nielsen H.
      Variation in absorption of NPH insulin due to intramuscular injection.
      • Thow J.
      • Johnson A.
      • Fulcher G.
      • Home P.
      Different absorption of Isophane (NPH) Insulin from subcutaneous and intramuscular sites suggests a need to reassess recommended insulin injection technique.
      In recent decades, needle length has decreased steadily in an effort to diminish this risk while at the same time lessening injection pain and anxiety. The latest ITQ found that the shortest pen needle, 4 mm (which was not introduced until 2010), is now used as commonly as the 8-mm needle, which as recently as 2009 was used by more than half of the patients in the world.
      • De Coninck C.
      • Frid A.
      • Gaspar R.
      • et al.
      Results and analysis of the 2008-2009 Insulin Injection Technique Questionnaire survey.
      Concern has been raised that needles as short as 4 mm might deposit insulin in the skin rather than in the subcutaneous (SC) fat. Skin thickness in adults with diabetes varies from approximately 1.25 to 3.25 mm for more than 90% of patients but averages approximately 2.0 to 2.5 mm.
      • Vidal M.
      • Colungo C.
      • Jansà M.
      • Jain S.M.
      • Pandey K.
      • Lahoti A.
      • Rao P.K.
      Evaluation of skin and subcutaneous tissue thickness at insulin injection sites in Indian, insulin naïve, type-2 diabetic adult population.
      • Catambing I.
      • Villa M.
      Ultrasonographic measurement of skin and subcutaneous thickness at insulin injection sites among adult Filipinos with diabetes.
      • Sim K.H.
      • Hwang M.S.
      • Kim S.Y.
      • Lee H.M.
      • Chang J.Y.
      • Lee M.K.
      The appropriateness of the length of insulin needles based on determination of skin and subcutaneous fat thickness in the abdomen and upper arm in patients with type 2 diabetes.
      Gibney et al found that in more than 350 adults with diabetes there is remarkable consistency of skin thickness regardless of race, age, sex, or BMI.
      • Gibney M.A.
      • Arce C.H.
      • Byron K.J.
      • Hirsch L.J.
      Skin and subcutaneous adipose layer thickness in adults with diabetes at sites used for insulin injections: implications for needle length recommendations.
      Children's skin is slightly thinner than that of adults but increases with age to adult levels after puberty.
      • Lo Presti D.
      • Ingegnosi C.
      • Strauss K.
      Skin and subcutaneous thickness at injecting sites in children with diabetes: ultrasound findings and recommendations for giving injection.
      • Seidenari S.
      • Giusti G.
      • Bertoni L.
      • et al.
      Thickness and echogenicity of the skin in children as assessed by 20-MHz ultrasound.
      • Marran K.
      • Segal D.
      SKINNY—Skin thickness and Needles in the Young.
      However, these changes make little difference for insulin delivery. The stability of this parameter (skin thickness) ensures that all currently available needles, including the shortest (4 mm), pass easily through the skin and into the SC (Table 2).
      However, there is large variability in SC thickness throughout adult life, and it is this parameter that most strongly influences IM risk. The SC tissue patterns are virtually the same in both sexes until puberty, after which girls gain adipose mass and in boys SC tissue thickness actually declines slightly
      • Smith C.P.
      • Sargent M.A.
      • Wilson B.P.
      • Price D.A.
      Subcutaneous or intramuscular insulin injections.
      (Paul Hofman, MD, oral communication, October 23, 2015). Hence, older boys and men are generally at higher risk for IM injections site for site.
      • Lippert W.C.
      • Wall E.J.
      Optimal intramuscular needle-penetration depth.
      • Birkebaek N.H.
      • Johansen A.
      • Solvig J.
      Cutis/subcutis thickness at insulin injection sites and localization of simulated insulin boluses in children with type 1 diabetes mellitus: need for individualization of injection technique?.
      • Thow J.
      • Home P.
      Insulin injection technique: depth of injection is important.
      • Tafeit E.
      • Möller R.
      • Jurimae T.
      • Sudi K.
      • Wallner S.J.
      Subcutaneous adipose tissue topography (SAT-Top) development in children and young adults.
      Hirsch et al
      • Hirsch L.
      • Byron K.
      • Gibney M.
      Intramuscular risk at insulin injection sites-measurement of the distance from skin to muscle and rationale for shorter-length needles for subcutaneous insulin therapy.
      recently reported that sex, BMI, and body site are the most important factors affecting SC fat thickness in adults and, by consequence, IM injection risk, results that confirm those of earlier studies.
      • Gibney M.A.
      • Arce C.H.
      • Byron K.J.
      • Hirsch L.J.
      Skin and subcutaneous adipose layer thickness in adults with diabetes at sites used for insulin injections: implications for needle length recommendations.
      • Thow J.
      • Home P.
      Insulin injection technique: depth of injection is important.
      • Strauss K.
      Insulin injection techniques.
      • Thow J.
      • Coulthard A.
      • Home P.
      Insulin injection site tissue depths and localization of a simulated insulin bolus using a novel air contrast ultrasonographic technique in insulin treated diabetic subjects.
      • Vora J.P.
      • Peters J.R.
      • Burch A.
      • Owens D.R.
      Relationship between absorption of radiolabeled soluble insulin subcutaneous blood flow, and anthropometry.
      • Hildebrandt P.
      Skinfold thickness, local subcutaneous blood flow and insulin absorption in diabetic patients.
      Women have approximately 5 mm more SC fat than men for the same BMI. Hence, men are at considerably higher risk for IM injections than women (2-4 times). Lower BMI similarly increases the IM injection risk. Body site is also critical. Injections in the thigh (closely followed by the arm) have 2- to 4-fold higher IM risk at any needle length than injections given in the abdomen. The thigh and abdomen are the most common sites that patients use (Table 3).
      The SC fat tissue may be surprisingly thin at commonly used injection sites, especially the limbs.
      • Hirsch L.
      • Byron K.
      • Gibney M.
      Intramuscular risk at insulin injection sites-measurement of the distance from skin to muscle and rationale for shorter-length needles for subcutaneous insulin therapy.
      • Vidal M.
      • Colungo C.
      • Jansà M.
      • Gibney M.A.
      • Arce C.H.
      • Byron K.J.
      • Hirsch L.J.
      Skin and subcutaneous adipose layer thickness in adults with diabetes at sites used for insulin injections: implications for needle length recommendations.
      • Thow J.
      • Coulthard A.
      • Home P.
      Insulin injection site tissue depths and localization of a simulated insulin bolus using a novel air contrast ultrasonographic technique in insulin treated diabetic subjects.
      • Vora J.P.
      • Peters J.R.
      • Burch A.
      • Owens D.R.
      Relationship between absorption of radiolabeled soluble insulin subcutaneous blood flow, and anthropometry.
      • Hildebrandt P.
      Skinfold thickness, local subcutaneous blood flow and insulin absorption in diabetic patients.
      However, if injections are consistently given into SC tissue, the depth of such injections (shallow vs deep SC tissue) does not affect the absorption or pharmacokinetics of insulin.
      • Frid A.
      • Lindén B.
      Intraregional differences in the absorption of unmodified insulin from the abdominal wall.
      • de la Peña A.
      • Yeo K.P.
      • Linnebjerg H.
      • et al.
      Subcutaneous injection depth does not affect the pharmacokinetics or glucodynamics of insulin lispro in normal weight or healthy obese subjects.
      This is important when we consider the dramatic shift to short needle length that this survey documents.
      The present data show that there has been a veritable sea change in needle length during the past 5 to 6 years, away from 8 mm and toward 4 and 5 mm. This accelerates a trend toward shorter needles that began 2 to 3 decades ago. Currently, 4- and 8-mm needles are each used by nearly 30% of patients; 5- and 6-mm needles are each used by just more than 20%. There is large variability, however, between countries. Considerable percentages of patients continue to use the 8-mm needle in high-risk sites (Table 3 and Supplemental Table 4).

      Fitter4Diabetes website. http://www.fitter4diabetes.com. Accessed June 7, 2016.

      • Hirsch L.
      • Byron K.
      • Gibney M.
      Intramuscular risk at insulin injection sites-measurement of the distance from skin to muscle and rationale for shorter-length needles for subcutaneous insulin therapy.
      • Frid A.
      • Lindén B.
      Intraregional differences in the absorption of unmodified insulin from the abdominal wall.
      Often these patients are obese in truncal areas but slim in the limbs (especially males).
      Obese patients are frequently prescribed longer needles. Recently, 4-mm needles were found to provide equivalent glycemic control (HbA1c), less pain, and no increase in insulin leakage compared with 8- and 12.7-mm needles in a randomized, prospective crossover trial in obese patients with BMI up to 59.
      • Hirsch L.J.
      • Gibney M.A.
      • Albanese J.
      • et al.
      Comparative glycemic control, safety and patient ratings for a new 4 mm x 32G insulin pen needle in adults with diabetes.
      • Bergenstal R.M.
      • Strock E.S.
      • Peremislov D.
      • Gibney M.A.
      • Parvu V.
      • Hirsch L.J.
      Safety and efficacy of insulin therapy delivered via a 4mm pen needle in obese patients with diabetes.
      These findings confirm previous trials reporting the lack of change in HbA1c levels or leakage/backflow from the skin comparing 5- and 8-mm needles or 6- and 12.7-mm needles, respectively, in obese patients.
      • Schwartz S.
      • Hassman D.
      • Shelmet J.
      • et al.
      A multicenter, open-label, randomized, two-period crossover trial comparing glycemic control, satisfaction, and preference achieved with a 31 gauge x 6mm needle versus a 29 gauge x 12.7mm needle in obese patients with diabetes mellitus.
      • Kreugel G.
      • Keers J.C.
      • Kerstens M.N.
      • Wolffenbuttel B.H.
      Randomized trial on the influence of the length of two insulin pen needles on glycemic control and patient preference in obese patients with diabetes.
      Hence, there is no medical rationale for using long needles (pen or syringe) in overweight or obese patients. Even in these patients, the shortest needles can be protective against IM injection and they hurt less.
      The association we found of lower TDD with use of the 4-mm pen needle is probably due to the fact that such needles are used more frequently in younger patients who require lower doses of insulin. Lower LH rates are also associated with the use of 4-mm needles (for various reasons, not necessarily causative). Finally, 4-mm pen needles are used more frequently in intensively treated patients (both T1DM and T2DM), who may require less insulin overall.
      The present data show that intensive insulin therapy is common, with nearly 45% of the patients in this study giving 4 or more injections per day (Table 6). Most of these injections are given in the abdomen (Table 7). In general the recommended injection sites are the abdomen, thigh, buttock, and upper arm.
      • Bantle J.P.
      • Neal L.
      • Frankamp L.M.
      Effects of the anatomical region used for insulin injections on glycaemia in type 1 diabetes subjects.
      • Koivisto V.A.
      • Felig P.
      Alterations in insulin absorption and in blood glucose control associated with varying insulin injection sites in diabetic patients.
      • Annersten M.
      • Willman A.
      Performing subcutaneous injections: a literature review.
      • Vidal M.
      • Colungo C.
      • Jansà M.
      • Fleming D.
      • Jacober S.J.
      • Vanderberg M.
      • Fitzgerald J.T.
      • Grunberger G.
      The safety of injecting insulin through clothing.
      The abdomen can be used within the following boundaries: approximately 1 cm above the symphysis pubis, approximately 1 cm below the lowest rib, approximately 1 cm away from the umbilicus, and laterally at the flanks. Patients can also use the upper third anterior lateral aspect of both thighs, the posterior lateral aspect of both upper buttocks and flanks, and the middle third posterior aspect of the upper arm.
      The absorption of human soluble (regular) insulin and NPH seems to differ by site, with most evidence suggesting that abdominal injections provide the fastest pharmacokinetics.
      • Frid A.
      • Lindén B.
      Intraregional differences in the absorption of unmodified insulin from the abdominal wall.
      • Annersten M.
      • Willman A.
      Performing subcutaneous injections: a literature review.
      • Frid A.
      • Lindén B.
      Clinically important differences in insulin absorption from the abdomen in IDDM.
      • Zehrer C.
      • Hansen R.
      • Bantle J.
      Reducing blood glucose variability by use of abdominal insulin injection sites.
      • Henriksen J.E.
      • Djurhuus M.S.
      • Vaag A.
      • et al.
      Impact of injection sites for soluble insulin on glycaemic control in type 1 (insulin-dependent) diabetic patients treated with a multiple insulin injection regimen.
      • Sindelka G.
      • Heinemann L.
      • Berger M.
      • Frenck W.
      • Chantelau E.
      Effect of insulin concentration, subcutaneous fat thickness and skin temperature on subcutaneous insulin absorption in healthy subjects.
      This is important because regular insulin needs to work rapidly to cover meal glucose excursions. The absorption of NPH has been found to be slower when it is injected into the thigh or buttock.
      • Bantle J.P.
      • Neal L.
      • Frankamp L.M.
      Effects of the anatomical region used for insulin injections on glycaemia in type 1 diabetes subjects.
      • Henriksen J.E.
      • Vaag A.
      • Hansen I.R.
      • Lauritzen M.
      • Djurhuus M.S.
      • Beck-Nielsen H.
      Absorption of NPH (isophane) insulin in resting diabetic patients: evidence for subcutaneous injection in the thigh as preferred site.
      This property can be useful when giving bedtime injections because the slower pharmacokinetics of NPH from these sites may be protective against nighttime hypoglycemia. Absorption properties by injection site of the new analogues have, paradoxically, been less studied than those of the older insulins. However, the data to date suggest that there is little or no influence on absorption as a function of injection sites.
      • Mudaliar S.R.
      • Lindberg F.A.
      • Joyce M.
      • et al.
      Insulin aspart (B28 asp-insulin): a fast-acting analog of human insulin: absorption kinetics and action profile compared with regular human insulin in healthy nondiabetic subjects.
      • Rave K.
      • Heise T.
      • Weyer C.
      • et al.
      Intramuscular versus subcutaneous injection of soluble and lispro insulin: comparison of metabolic effects in healthy subjects.
      • Frid A.
      Fat thickness and insulin administration: what do we know?.
      • Guerci B.
      • Sauvanet J.P.
      Subcutaneous insulin: pharmacokinetic variability and glycemic variability.
      • Ter Braak E.W.
      • Woodworth J.R.
      • Bianchi R.
      • et al.
      Injection site effects on the pharmacokinetics and glucodynamics of insulin lispro and regular insulin.
      • Owens D.R.
      • Coates P.A.
      • Luzio S.D.
      • Tinbergen J.P.
      • Kurzhals R.
      Pharmacokinetics of 125I-labeled insulin glargine (HOE 901) in healthy men: comparison with NPH insulin and the influence of different subcutaneous injection sites.
      More studies are clearly needed in the case of insulin analogues.
      Inadequate resuspension of NPH insulin occurs frequently and can lead to large dosing errors.
      • Brown A.
      • Steel J.M.
      • Duncan C.
      • Duncan A.
      • McBain A.M.
      An assessment of the adequacy of suspension of insulin in pen injectors.
      Jehle et al
      • Jehle P.M.
      • Micheler C.
      • Jehle D.R.
      • Breitig D.
      • Boehm B.O.
      Inadequate suspension of neutral protamine Hagendorn (NPH) insulin in pens.
      reported that adequate NPH resuspension could be achieved only after mixing (tipping or rolling) the vial or pen 20 times before injection.
      • Kaiser P.
      • Maxeiner S.
      • Weise A.
      • et al.
      Assessment of the mixing efficiency of neutral protamine Hagedorn cartridges.
      We found that only approximately 1 of 10 patients performs this critical task appropriately. Hence, this is a clear education and training opportunity.
      The present results show that many patients do not know basic timing issues regarding injections. If they use a pen they should inject until the button is completely pressed down and then wait 10 seconds more before removing the needle from the skin. This allows for full evacuation of insulin from the pen and better dispersion into the SC tissue. Less than a third of patients in this survey perform this vital task correctly
      • Broadway C.A.
      Prevention of insulin leakage after subcutaneous injection.
      (Supplemental Table 6).

      Fitter4Diabetes website. http://www.fitter4diabetes.com. Accessed June 7, 2016.

      Patients should be taught to count for 10 seconds after the button has been fully depressed and then remove the needle from the skin. In certain cases (eg, smaller doses), this time may be reduced, but only on a trial and error basis. If leakage is observed, either from the needle tip or from the skin, the waiting time should be extended.
      • Annersten M.
      • Frid A.
      Insulin pens dribble from the tip of the needle after injection.
      Patients often do not know the correct steps to injecting into a skinfold. The steps are as follows: (1) gently lift a skinfold, (2) inject the insulin slowly at a 90° angle to the surface of the skinfold, (3) let the needle remain in the skin for a count of 10 after the plunger is pressed down (when using a pen), (4) withdraw the needle from the skin at the same angle it was inserted, (5) release the skinfold, and (6) dispose of the used needle safely.
      The use of safety devices wherever there is the risk of a dangerous NSI has been mandated in the United States,
      Occupational Safety and Health Administration
      Occupational exposure to bloodborne pathogens: needlesticks and other sharps injuries: finale rule.
      the European Union,

      Council Directive 2010/32/EU. Official Journal of the European Union website. http://eurlex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2010:134:0066:0072:EN:PDF. Accessed June 9, 2016.

      The Directive specifically requires: ‘eliminating the unnecessary use of sharps by implementing changes in practice and on the basis of the results of the risk assessment, providing medical devices incorporating safety-engineered protection mechanisms.’ Council Directive 2010/32/EU, Official Journal of the European Union, L134/71 and L134/69.

      India,

      NACO (National AIDS Control Organisation) guidelines from India. National AIDS Control Organisation website. http://www.naco.gov.in/NACO. Accessed June 8, 2016.

      and elsewhere, but compliance remains suboptimal in the diabetes community. This obligation covers all diabetes injections in the hospital and those given in distributed institutional settings (eg, nursing homes, ambulatory clinics, schools, prisons, nurseries, and third-party injectors in home health settings).

      Fitter4Diabetes website. http://www.fitter4diabetes.com. Accessed June 7, 2016.

      Most NSIs are preventable with the provision of effective training, safer working procedures, and safety-engineered medical devices, which shield or retract the needle after use. Nevertheless, uptake of these practices and devices is suboptimal worldwide, as the survey showed. Additional awareness campaigns and training on safety devices are clearly needed.
      We believe that the ITQ data should be made available in the widest and most transparent manner possible; therefore, we are making the results accessible in an interactive format at the Tableau Public Adam Yeung's Profile website.

      ITQ survey data. Tableau Public Adam Yeung's Profile website. http://tabsoft.co/23V6ofi. Accessed June 8, 2016.

      Conclusion

      This ITQ, involving more than 13,000 patients from 42 countries, is one of the largest surveys of its kind in diabetes, and perhaps in medicine. Its scope covers injection practices from beginning to end: choice of device through disposal. It elucidates the common habits that patients practice as well as the complications and other obstacles they face. Only in this manner can practical and targeted recommendations be made. Use of these data should stimulate renewed interest in and commitment to optimizing injection practices in patients with diabetes. A separate article in this issue covers the remainder of the ITQ and is titled “Worldwide Injection Technique Questionnaire Study: Injecting Complications and the Role of the Professional.”
      • Frid A.H.
      • Hirsch L.J.
      • Menchior A.R.
      • Morel D.R.
      • Strauss K.W.
      Worldwide Injection Technique Questionnaire study: injecting complications and the role of the professional.
      A new set of insulin delivery recommendations based on the ITQ survey has been developed and is also published in this issue.
      • Frid A.H.
      • Kreugel G.
      • Grassi G.
      • et al.
      New insulin delivery recommendations.
      Individual countries and local regions should revise and publish their own ITQ findings and insulin delivery guidelines in light of the new recommendations and the worldwide ITQ survey data reported herein.

      Acknowledgments

      Our sincerest thanks to the 423 centers in 42 countries throughout the world (see Supplemental Table 1) for opening their doors and hearts to the ITQ survey. The thousands of professionals and the 13,289 patients who participated have given an invaluable gift to the world of diabetes and medicine. We salute them.

      Supplemental Online Material

      Supplemental Online Material

      Supplemental material can be found online at http://www.mayoclinicproceedings.org. Supplemental material attached to journal articles has not been edited, and the authors take responsibility for the accuracy of all data.

      References

        • Frid A.H.
        • Kreugel G.
        • Grassi G.
        • et al.
        New insulin delivery recommendations.
        Mayo Clin Proc. 2016; 91: 1231-1255
        • Partanen T.M.
        • Rissanen A.
        Insulin injection practices.
        Pract Diabetes Int. 2000; 17: 252-254
        • Strauss K.
        • De Gols H.
        • Hannet I.
        • Partanen T.M.
        • Frid A.
        A pan-European epidemiologic study of insulin injection technique in patients with diabetes.
        Pract Diabetes Int. 2002; 19: 71-76
        • 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: 168-179
      1. FITTER International Congress; October 23-24, 2015; Rome, Italy. BD website. https://www.bd.com/resource.aspx?IDX=33000. Accessed June 8, 2016.

      2. Fitter4Diabetes website. http://www.fitter4diabetes.com. Accessed June 7, 2016.

      3. ITQ survey data. Tableau Public Adam Yeung's Profile website. http://tabsoft.co/23V6ofi. Accessed June 8, 2016.

        • Hirsch L.
        • Byron K.
        • Gibney M.
        Intramuscular risk at insulin injection sites-measurement of the distance from skin to muscle and rationale for shorter-length needles for subcutaneous insulin therapy.
        Diabetes Technol Ther. 2014; 16: 867-873
      4. Wang W, Guo X, Shen G, et al. Skin and subcutaneous thickness at insulin injection sites in Chinese patients with diabetes: clinical implications. Diabetes Metab. 2016 Jun 8. [Epub ahead of print] pii: S1262-3636(16)30402-5. http://dx.doi.org/10.1016/j.diabet.2016.04.010.

        • Sun Z.
        • Li Q.
        • Ji L.
        • et al.
        Lipohypertrophy: prevalence, risk factors, clinical characteristics, and economic burden of insulin-requiring patients in China: poster, EASD Stockholm, 2015.
        Diabetologia. 2015; 58: S438-S439
        • Blanco M.
        • Hernández M.T.
        • Strauss K.W.
        • Amaya M.
        Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes.
        Diabetes Metab. 2013; 39: 445-453
        • Bantle J.P.
        • Neal L.
        • Frankamp L.M.
        Effects of the anatomical region used for insulin injections on glycaemia in type 1 diabetes subjects.
        Diabetes Care. 1993; 16: 1592-1597
        • Frid A.
        • Lindén B.
        Intraregional differences in the absorption of unmodified insulin from the abdominal wall.
        Diabet Med. 1992; 9: 236-239
        • Koivisto V.A.
        • Felig P.
        Alterations in insulin absorption and in blood glucose control associated with varying insulin injection sites in diabetic patients.
        Ann Intern Med. 1980; 92: 59-61
        • Annersten M.
        • Willman A.
        Performing subcutaneous injections: a literature review.
        Worldviews Evid-Based Nurs. 2005; 2: 122-130
        • Vidal M.
        • Colungo C.
        • Jansà M.
        Av Diabetol. 2008; 24: 255-269
        • Frid A.
        • Gunnarson R.
        • Guntner P.
        • Lindén B.
        Effects of accidental intramuscular injection on insulin absorption in IDDM.
        Diabetes Care. 1988; 11: 41-45
        • Vaag A.
        • Handberg A.
        • Lauritzen M.
        • Henriksen J.E.
        • Pedersen K.D.
        • Beck-Nielsen H.
        Variation in absorption of NPH insulin due to intramuscular injection.
        Diabetes Care. 1990; 13: 74-76
        • Thow J.
        • Johnson A.
        • Fulcher G.
        • Home P.
        Different absorption of Isophane (NPH) Insulin from subcutaneous and intramuscular sites suggests a need to reassess recommended insulin injection technique.
        Diabet Med. 1990; 7: 600-602
        • Jain S.M.
        • Pandey K.
        • Lahoti A.
        • Rao P.K.
        Evaluation of skin and subcutaneous tissue thickness at insulin injection sites in Indian, insulin naïve, type-2 diabetic adult population.
        Indian J Endocrinol Metab. 2013; 17: 864-870
        • Catambing I.
        • Villa M.
        Ultrasonographic measurement of skin and subcutaneous thickness at insulin injection sites among adult Filipinos with diabetes.
        J ASEAN Fed Endocr Soc. 2014; 29: 24-32
        • Sim K.H.
        • Hwang M.S.
        • Kim S.Y.
        • Lee H.M.
        • Chang J.Y.
        • Lee M.K.
        The appropriateness of the length of insulin needles based on determination of skin and subcutaneous fat thickness in the abdomen and upper arm in patients with type 2 diabetes.
        Diabetes Metab J. 2014; 38: 120-133
        • Gibney M.A.
        • Arce C.H.
        • Byron K.J.
        • Hirsch L.J.
        Skin and subcutaneous adipose layer thickness in adults with diabetes at sites used for insulin injections: implications for needle length recommendations.
        Curr Med Res Opin. 2010; 26: 1519-1530
        • Lo Presti D.
        • Ingegnosi C.
        • Strauss K.
        Skin and subcutaneous thickness at injecting sites in children with diabetes: ultrasound findings and recommendations for giving injection.
        Pediatr Diabetes. 2012; 13: 525-533
        • Seidenari S.
        • Giusti G.
        • Bertoni L.
        • et al.
        Thickness and echogenicity of the skin in children as assessed by 20-MHz ultrasound.
        Dermatology. 2000; 201: 218-222
        • Marran K.
        • Segal D.
        SKINNY—Skin thickness and Needles in the Young.
        S Afr J CH. 2014; 8: 92-95
        • Smith C.P.
        • Sargent M.A.
        • Wilson B.P.
        • Price D.A.
        Subcutaneous or intramuscular insulin injections.
        Arch Dis Child. 1991; 66: 879-882
        • Lippert W.C.
        • Wall E.J.
        Optimal intramuscular needle-penetration depth.
        Pediatrics. 2008; 122: e556-e563
        • Birkebaek N.H.
        • Johansen A.
        • Solvig J.
        Cutis/subcutis thickness at insulin injection sites and localization of simulated insulin boluses in children with type 1 diabetes mellitus: need for individualization of injection technique?.
        Diabet Med. 1998; 15: 965-971
        • Thow J.
        • Home P.
        Insulin injection technique: depth of injection is important.
        BMJ. 1990; 301: 3-4
        • Tafeit E.
        • Möller R.
        • Jurimae T.
        • Sudi K.
        • Wallner S.J.
        Subcutaneous adipose tissue topography (SAT-Top) development in children and young adults.
        Coll Antropol. 2007; 31: 395-402
        • Strauss K.
        Insulin injection techniques.
        Pract Diabetes Int. 1998; 15: 181-184
        • Thow J.
        • Coulthard A.
        • Home P.
        Insulin injection site tissue depths and localization of a simulated insulin bolus using a novel air contrast ultrasonographic technique in insulin treated diabetic subjects.
        Diabet Med. 1992; 9: 915-920
        • Vora J.P.
        • Peters J.R.
        • Burch A.
        • Owens D.R.
        Relationship between absorption of radiolabeled soluble insulin subcutaneous blood flow, and anthropometry.
        Diabetes Care. 1992; 15: 1484-1493
        • Hildebrandt P.
        Skinfold thickness, local subcutaneous blood flow and insulin absorption in diabetic patients.
        Acta Physiol Scand. 1991; 603: S41-S45
        • de la Peña A.
        • Yeo K.P.
        • Linnebjerg H.
        • et al.
        Subcutaneous injection depth does not affect the pharmacokinetics or glucodynamics of insulin lispro in normal weight or healthy obese subjects.
        J Diabetes Sci Technol. 2015; 9: 824-830
        • Hirsch L.J.
        • Gibney M.A.
        • Albanese J.
        • et al.
        Comparative glycemic control, safety and patient ratings for a new 4 mm x 32G insulin pen needle in adults with diabetes.
        Curr Med Res Opin. 2010; 26: 1531-1541
        • Bergenstal R.M.
        • Strock E.S.
        • Peremislov D.
        • Gibney M.A.
        • Parvu V.
        • Hirsch L.J.
        Safety and efficacy of insulin therapy delivered via a 4mm pen needle in obese patients with diabetes.
        Mayo Clin Proc. 2015; 90: 329-338
        • Schwartz S.
        • Hassman D.
        • Shelmet J.
        • et al.
        A multicenter, open-label, randomized, two-period crossover trial comparing glycemic control, satisfaction, and preference achieved with a 31 gauge x 6mm needle versus a 29 gauge x 12.7mm needle in obese patients with diabetes mellitus.
        Clin Ther. 2004; 26: 1663-1678
        • Kreugel G.
        • Keers J.C.
        • Kerstens M.N.
        • Wolffenbuttel B.H.
        Randomized trial on the influence of the length of two insulin pen needles on glycemic control and patient preference in obese patients with diabetes.
        Diabetes Technol Ther. 2011; 13: 737-741
        • Fleming D.
        • Jacober S.J.
        • Vanderberg M.
        • Fitzgerald J.T.
        • Grunberger G.
        The safety of injecting insulin through clothing.
        Diabetes Care. 1997; 20: 244-247
        • Frid A.
        • Lindén B.
        Clinically important differences in insulin absorption from the abdomen in IDDM.
        Diabetes Res Clin Pract. 1993; 21: 137-141
        • Zehrer C.
        • Hansen R.
        • Bantle J.
        Reducing blood glucose variability by use of abdominal insulin injection sites.
        Diabetes Educ. 1985; 16: 474-477
        • Henriksen J.E.
        • Djurhuus M.S.
        • Vaag A.
        • et al.
        Impact of injection sites for soluble insulin on glycaemic control in type 1 (insulin-dependent) diabetic patients treated with a multiple insulin injection regimen.
        Diabetologia. 1993; 36: 752-758
        • Sindelka G.
        • Heinemann L.
        • Berger M.
        • Frenck W.
        • Chantelau E.
        Effect of insulin concentration, subcutaneous fat thickness and skin temperature on subcutaneous insulin absorption in healthy subjects.
        Diabetologia. 1994; 37: 377-380
        • Henriksen J.E.
        • Vaag A.
        • Hansen I.R.
        • Lauritzen M.
        • Djurhuus M.S.
        • Beck-Nielsen H.
        Absorption of NPH (isophane) insulin in resting diabetic patients: evidence for subcutaneous injection in the thigh as preferred site.
        Diabet Med. 1991; 8: 453-457
        • Mudaliar S.R.
        • Lindberg F.A.
        • Joyce M.
        • et al.
        Insulin aspart (B28 asp-insulin): a fast-acting analog of human insulin: absorption kinetics and action profile compared with regular human insulin in healthy nondiabetic subjects.
        Diabetes Care. 1999; 22: 1501-1506
        • Rave K.
        • Heise T.
        • Weyer C.
        • et al.
        Intramuscular versus subcutaneous injection of soluble and lispro insulin: comparison of metabolic effects in healthy subjects.
        Diabet Med. 1998; 15: 747-751
        • Frid A.
        Fat thickness and insulin administration: what do we know?.
        Infusystems Int. 2006; 5: 17-19
        • Guerci B.
        • Sauvanet J.P.
        Subcutaneous insulin: pharmacokinetic variability and glycemic variability.
        Diabetes Metab. 2005; 31: S7-S24
        • Ter Braak E.W.
        • Woodworth J.R.
        • Bianchi R.
        • et al.
        Injection site effects on the pharmacokinetics and glucodynamics of insulin lispro and regular insulin.
        Diabetes Care. 1996; 19: 1437-1440
        • Owens D.R.
        • Coates P.A.
        • Luzio S.D.
        • Tinbergen J.P.
        • Kurzhals R.
        Pharmacokinetics of 125I-labeled insulin glargine (HOE 901) in healthy men: comparison with NPH insulin and the influence of different subcutaneous injection sites.
        Diabetes Care. 2000; 23: 813-819
        • Brown A.
        • Steel J.M.
        • Duncan C.
        • Duncan A.
        • McBain A.M.
        An assessment of the adequacy of suspension of insulin in pen injectors.
        Diabet Med. 2004; 21: 604-608
        • Jehle P.M.
        • Micheler C.
        • Jehle D.R.
        • Breitig D.
        • Boehm B.O.
        Inadequate suspension of neutral protamine Hagendorn (NPH) insulin in pens.
        Lancet. 1999; 354: 1604-1607
        • Kaiser P.
        • Maxeiner S.
        • Weise A.
        • et al.
        Assessment of the mixing efficiency of neutral protamine Hagedorn cartridges.
        J Diabetes Sci Technol. 2010; 4: 652-657
        • Broadway C.A.
        Prevention of insulin leakage after subcutaneous injection.
        Diabetes Educ. 1991; 17: 90
        • Annersten M.
        • Frid A.
        Insulin pens dribble from the tip of the needle after injection.
        Pract Diabetes Int. 2000; 17: 109-111
        • Occupational Safety and Health Administration
        Occupational exposure to bloodborne pathogens: needlesticks and other sharps injuries: finale rule.
        Fed Regist. 2001; 66: 5317
      5. Council Directive 2010/32/EU. Official Journal of the European Union website. http://eurlex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2010:134:0066:0072:EN:PDF. Accessed June 9, 2016.

      6. The Directive specifically requires: ‘eliminating the unnecessary use of sharps by implementing changes in practice and on the basis of the results of the risk assessment, providing medical devices incorporating safety-engineered protection mechanisms.’ Council Directive 2010/32/EU, Official Journal of the European Union, L134/71 and L134/69.

      7. NACO (National AIDS Control Organisation) guidelines from India. National AIDS Control Organisation website. http://www.naco.gov.in/NACO. Accessed June 8, 2016.

        • Frid A.H.
        • Hirsch L.J.
        • Menchior A.R.
        • Morel D.R.
        • Strauss K.W.
        Worldwide Injection Technique Questionnaire study: injecting complications and the role of the professional.
        Mayo Clin Proc. 2016; 91: 1224-1230