Introduction

According to the 2017 International Diabetes Federation Atlas the prevalence of diabetes is increasing worldwide and that by 2045 Turkey will be among the top ten countries in the world in terms of total number of people with diabetes [1]. The most recent TURDEP II study, which evaluated the prevalence of and risk factors for diabetes in Turkish adults, found that 13.7% of the general population has diabetes [2]. This translates into more than seven million Turks having diabetes, of whom 13.6% are on insulin therapy (more than a million people in total).

The insulin Injection Technique Questionnaire (ITQ) is a survey tool that is written in simple layman’s terms which assesses all important aspects of insulin injection, from the choice of injecting device to the disposal of used sharps, and from the essential techniques of injecting to the psychological and social aspects of the experience. The ITQ includes one questionnaire for patients and another for the diabetes healthcare professional caring for them. Both are administered in the healthcare setting during routine patient visits and usually took 30-45 min to complete.

A worldwide insulin ITQ study was conducted from February 2014 to June 2015. This survey involved 42 countries and 13,289 patients [3, 4]. Turkey was one of the principal countries which participated, with an input of 1376 patients from 56 centers that represented all of the major regions of the country (Table 1). Of interest to Turkish healthcare providers (HCP), this insulin ITQ evaluated the techniques used by Turkish insulin users when injecting themselves. Little was known on this subject until the present study. The various language versions of the ITQ questionnaire (including Turkish) are available at www.fitter4diabetes.com. The findings of the worldwide insulin ITQ study forms the basis for the New Insulin Delivery Guidelines which were recently published worldwide [5, 6] and in Turkey. A Turkish national guideline based on the results of this study has recently been published and distributed to all hospitals and HCP involved in diabetes management, with the endorsement and support of the Turkish Ministry of Health [7].

Table 1 The Insulin Injection Technique Questionnaire Turkey Study Group, 2014–2015
Full size table

The study reported here was undertaken to improve our understanding of the key injecting parameters of the estimated one million Turkish diabetic patients who use insulin daily. A correct injection technique is critical to achieving optimal insulin action; of equal importance is the type and dose of insulin used (with the latter usually receiving the most attention from the HCP). Unless insulin is delivered correctly, adjustments of dose and insulin type are unlikely to result in clinical improvements. Therefore, an understanding of exactly how Turkish patients inject insulin is essential to improve guidelines aimed at addressing deficiencies in the management of diabetics, to target training and to implement specific educational tools and approaches. The ITQ was administered with the aim of addressing these parameters in Turkish clinical practice and, in the long term, improving patient outcomes and lowering healthcare costs.

Methods

The ITQ study methodology has been previously described in publications on the worldwide [3] and Indian [8] results. Similar methods for data collection and analysis were used in Turkey as in these previous studies. This study was conducted according to Good Clinical Practice rules and the Helsinki declaration. No information which could lead to the identification of a participant was made available to the sponsor, and participants were informed that their care would not be affected in any way by their participation in the study. They were not put at risk through their participation in the study nor were they paid to participate. Ethics committee approval was therefore not required, but it was obtained whenever specifically requested by a center and/or by local regulations. All 56 participating centers from 29 cities in Turkey (as in the Rest of World [ROW]) did so willingly and without financial incentive. A total of 1376 Turkish participants with diabetes for whom both patient and nurse forms were filled out were included in the ITQ database. Worldwide as well as country-specific ITQ survey data (including Turkey) are available in an interactive form on Tableau Public Adam Young’s Profile website [9]. This database contains all of the raw ITQ data, both for Turkey and for ROW (by individual country), and it allows the user to select and view results for specific parameters or combinations of parameters.

Results

Population Descriptors

In order to ensure we had the most representative sample of Turkish insulin injectors, we took patients ‘as is’, meaning if they injected insulin and had done so for ≥ 6 months, they were included in the survey. Some of these patients had had extensive and best-in-class education and training in their injection technique of choice, while some had had no education or training at all; however, most fell somewhere in between these extremes. This variation in education and training on insulin injection is typical of Turkey and of the ROW.

Overall 82.4% of Turkish participants were adults, 51.3% were female, 33.2% had type 1 diabetes (T1DM) and 66.8% had type 2 diabetes (T2DM). These Turkish patients had had diabetes for a mean of 11.3 years and had been using insulin for an average of 6.9 years. Additional population statistics for the Turkish participants in our study, compared side to side with the ROW data, are given in Table 2. The ROW data are the mean values of the 41 ITQ countries combined, excluding data from Turkey, which participated in the worldwide insulin ITQ study. Table 3 shows the breakdown in patient age and identity of the injector, and Table 4 shows the characteristics of Turkish participants compared to ROW data. The majority of Turkish patients used short- and long-acting insulin analogs, and the mean total daily dose (TDD), all insulins included, was 54.0 international units (IU) compared to 47.4 IU in ROW (Table 2). As in ROW, the mean TDD of Turkish adolescents was nearly the same as that of adults (52.1 IU), while school-age children used an average of only 37.0 IU/day, and children receiving injections from parents used only 24.7 IU/day (Table 4). The TDD was not significantly associated with body mass index (BMI).

Table 2 Population demographics for Turkish and Rest of World patients
Full size table
Table 3 Identity of patient (or healthcare provider) who filled out the Injection Technique Questionnaire (ITQ) for the Turkey insulin ITQ survey (n = 1306) and for the Rest of World ITQ survey (n = 8225)
Full size table
Table 4 Comparison of patient characteristics in Turkish ITQ survey (n = 1376) and Rest of World ITQ survey (n = 11,913)
Full size table

Devices and Key Injection Practices

The injection devices used and needle reuse practices in Turkey versus ROW are shown in Table 5. These data clearly show that insulin pens are much more commonly used in Turkey than in ROW and that needle lengths differ significantly between Turkey and ROW. The 4-mm needle is used more commonly in Turkey (35.1%) than ROW (21.8%), while the 5-mm needle is used by < 10% of adult Turkish patients on insulin. However, in Turkey use of the 8-mm needle is still almost as common as that of the 4-mm needle. The average number of times an individual pen needle is used is significantly lower in Turkey (3.42) than in ROW (4.98) (Table 5) Furthermore, among patients still reusing needles, the number of reuse times is lower among Turkish patients than among those in ROW. When asked why they reused, over 66.9% of Turkish patients who answered said that it was ‘for convenience’.

Table 5 Comparison of devices used and reuse practice in Turkey (n = 1366) and in Rest of World (n = 11,712)
Full size table

Injections/day and Injection Sites

The number of injections per day in both Turkey and ROW is shown in Table 6. More than one-half of Turkish patients inject themselves or others four times per day, which is a far higher percentage than found in ROW. The percentages of Turkish patients giving themselves or others two or five injections/day are similar to those for ROW, while the percentages giving one or three injections/day are considerably lower.

Table 6 Comparison of the number of injections administered by patients in Turkey (n = 1352) and Rest of World (n = 8165)
Full size table

The recommended injection sites are the abdomen, thigh, arm and buttocks [10–14]. Table 7 shows the sites used by Turkish patients and compares them to those used by patients in ROW, and Table 8 presents percentages for specific injecting zones or combinations of zones for both Turkey and ROW. Note that the combination of zones most commonly used are different for the bottom two rows (shown in italics), with a larger percentage of Turkish patients using a combination of abdomen/thigh/arm sites or all four sites.

Table 7 Comparison of injection sites used by Turkish insulin injectors to those used by Rest of World
Full size table
Table 8 Comparison of injection sites used (alone or in combination) by Turkish insulin injectors and those used by Rest of World
Full size table

Injecting Process

Turkish patients using pens were asked how long they left the needle under the skin after the plunger had been completely pushed down (dwell time; recommendations suggest 10 s or longer). Compliance with this guideline by Turkish patients was 48.3%, which is much higher than the average compliance rate in ROW (Table 9). The size of the injection sites, skin folds and injection angles for both patients of Turkey and ROW are compared in Table 10.

Table 9 Comparison of dwell times after pen injection in Turkish insulin injectors and those of Rest of World
Full size table
Table 10 Comparison of size of injection sites, skin folds and injection angle in Turkish insulin injectors and those of Rest of World
Full size table

Turkish patients were asked to make a mock injection while a nurse observed the technique. One of the parameters evaluated was whether the patient lifted a skin fold and, if so, whether it was lifted properly and released correctly. In Turkey, 52.3% of patients were observed to lift a skin fold and, of those who do so, 79.2% do it correctly (with one or two fingers plus the thumb). However, less than half were observed to release the fold appropriately (option three in Table 11). We also found (data not shown) that 45.9% of Turkish patients lift a skin fold when using the 4-mm needle (where a fold is not required), while 52.2% do with the 6-mm needle and 60.5% do so with the 8-mm needle (both needle lengths generally require a skin fold).

Table 11 Timing of release of skin fold
Full size table

Insulins

The breakdown of the major categories of insulin used in Turkey compared to ROW is shown in Table 12. The values show that considerably more patients are using the newer analogs in Turkey, both short or long-acting, than in ROW.

Table 12 Type of insulins used in Turkey and Rest of World
Full size table

Patients were queried about where they stored their insulin prior to opening it; 81.7% of Turkish patients reported storing unopened insulin in the refrigerator. After opening it, 73.3% of Turkish patients continued to store it in the fridge. Of these, only 51.6% let it stand at room temperature prior to injecting.

Turkish patients using cloudy insulin (NPH, N or pre-mixed insulin) were asked if they reconstituted the insulin before injecting, and 54.2% said yes. They were then asked how many times they rolled or tipped their vial or pen to reconstitute the insulin before injecting it (recommendations suggest 20 rolls or tips are necessary to completely remix crystalline insulin). Table 13 shows that only 13.6% of Turkish patients using cloudy insulins comply with this guideline. Of these, patients, 80.8% tip or roll them only 10 times or less.

Table 13 Number of times cloudy insulin tipped or rolled before Injecting
Full size table

Patients were queried about whether they ever skipped injections and, if so, how often and why. In Turkey, 48.8% of patients admitted they skip injections; the frequency of skipping injections is shown in Table 14. The most common reason given was ‘I forgot’ (49.1%). Patients were also asked if they disinfected the skin before injections, and 28.3% said they did. Only 2.5% of Turkish patients give their injections through clothing.

Table 14 Frequency of skipping injections
Full size table

Needlestick Injuries

When asked if there was anyone in their immediate surroundings who might accidentally receive a sharps injury, 10.9% of Turkish patients said yes (Table 15). Over 16% of patients reported a sharps injury had already occurred to one of these persons. The conditions patients may have which might put others at risk for a blood-borne pathogen are shown in Table 16. Table 17 shows how used sharps are disposed, and Table 18 shows what happens to containers when they are full.

Table 15 Persons in household at risk for sharps Injury
Full size table
Table 16 Risk factors for sharps injury
Full size table
Table 17 Disposal habits for used sharps
Full size table
Table 18 Ultimate disposal of sharps waste
Full size table

Discussion

Until our ITQ survey little was known about where, when and how Turkish patients use insulin. Our study covered the entire country, with 1376 patients surveyed from 56 centers in 29 cities (Table 1). Our demographic data (Table 2) shows that our patient population is representative of Turkish T1DM and T2DM patients who inject insulin.

We found a HbA1c of 9.1%, which is consistent with the results of the other multicenter studies conducted in Turkey [15, 16] and higher than the mean HbA1c of 8.35% reported for ROW (Table 2). This higher value could be attributable to higher levels of obesity among Turkish diabetics patients as the BMI values were 0.75 units higher in Turkey than in ROW. Most of this difference in BMI value is attributable to the adult patients (BMI of 30.1 vs. 27.9 for ROW), while Turkish children and adolescents had BMI values equivalent to those in ROW (Table 4). Turkish patients use insulin analogs (short and long-acting) more frequently than patients in ROW (Tables 2, 12). The majority of Turkish insulin users give four injections/day, which is higher than the number reported in ROW. Turkish patients inject insulin in multiple body sites, which is also more often than do patients in ROW. The two most popular injection site combinations are the abdomen/thigh/arm and abdomen/thigh/buttocks/arm (Tables 7, 8). These combinations, both involving the use of thighs and arms, are especially relevant when considering the shallow subcutaneous depth in the limbs with reference to the needle lengths used (Table 5).

Syringe use has almost disappeared in Turkey; at the present time syringes alone are used by less than half a percent of injectors while another 0.8% use them in combination with pens (Table 5). Thus, in the remainder of this discussion we focus on insulin pen use. The shortest pen needles (4 mm) are used by about one-third of patients in Turkey, but the longer ones (8 mm) are equally common. Our 2015 ITQ revealed that there has been a great change in the size of insulin needles used in Turkey. As recently as 2008, by far the majority (83.5%) of Turkish patients used 8-mm needles. While it is encouraging to see the ‘shift to shorts’ among Turkish patients, it is still worrying to find such high percentages of patients still using the 8-mm needle (Tables 4, 5). In all, more than half of Turkish patients (55.3%) are still on long pen needles.

A study of a large and heterogeneous population (four ethnic groups) of American adults with diabetes revealed that skin thickness at injection sites differed minimally by BMI (obese patients have equivalent skin thickness to thin and normal-weight ones) [17]. Strollo and Gentile recently summarized the influence of ethnic origin and skin thickness [18] and found that fat thickness (dimensions of the subcutaneous space) varies widely from individual to individual as a function of BMI, gender and injection site. Another recent study confirmed these anatomic findings in Chinese patients [19].

Hirsch at al. [20] showed that the risk of intramuscular (IM) injections with 8-mm needles is considerable in adults. This risk as a function of the length of the needle is shown in Table 19. The risk is especially high in those using the thigh and arm sites as injection sites (see values in italics in Table 19), where as many as one-fourth to one-fifth, respectively, of injections with the 8-mm needle may go into muscle. Many more Turkish patients use these sites for injections than those in ROW, with 80.1% using the thigh and 84.2% using the arm (Table 7). Our survey showed that 42.9% of adult Turkish injectors are still using the 8-mm needle, a figure much higher than the 29.3% in ROW (Table 4). Of these, 60.5% achieve a level of safety from IM injections by using a lifted skin fold, but that still leaves nearly two out of five injectors who do not.

Table 19 Estimated intramuscular injection risk by body site
Full size table

Almost 18% of our survey population was in the pediatric age range (Table 3). The risk of IM injections with the 8-mm needle in children is strikingly high. Lo Presti et al. [21] reported that in children aged less than 7 years, more than four of five injections would go into the muscle when the 8-mm needle was used perpendicularly. For school-age children (7–13 years old) and for adolescents (14–18 years old), two of three injections with the 8-mm needle would go into muscle. These higher than expected percentages of Turkish children in these age groups were found by our survey to be still using needles longer than the recommended 4 mm: 49.0, 29.3 and 23.9% of adolescents, children and those receiving injections from their parents, respectively, used needles longer than 4 mm (Table 4).

Our worldwide ITQ data [3] shows that 4-mm needles are associated with lower TDD, fewer hospitalizations for hypoglycemia, lower needle reuse rates and fewer cases of lipohypertrophy (LH) (all with p < 0.05 by multivariate analysis). In a large, randomized, prospective controlled crossover study of obese subjects taking large insulin doses, with two arms (4 vs. 8 mm and 4 vs. 12.7 mm), the 4-mm needles provided equivalent glycemic control (by HbA1c) as the 8-mm and 12.7-mm needles [22]. No additional skin leakage was seen with the 4-mm needles compared to the other sizes of needles. Furthermore, patients reported less pain with the 4-mm needle.

These results are consistent with those from other comparative studies of 4-, 5- or 6-mm needles [23–30]. Miwa et al. [29] compared 4-mm needles with their 6-mm counterparts and reported equivalent safety and effectiveness results. These authors reported that their Japanese subjects found the 4-mm needle to be less painful than the 6-mm needle as well as simpler and easier to use. Nagai et al. [30] compared 4- and 5-mm needles and reported similar results. Hirose et al. [31] conducted pharmacokinetic/pharmacodynamic (PK/PD) studies and determined bioequivalent maximum concentrations and similar areas under the curve for the 4-, 6- and 8-mm needles. A crossover study using the euglycemic clamp measuring PK/PD in both normal-weight and obese, healthy adults showed similar insulin uptake and action when insulin lispro was injected with a 5-mm needle on 1 day and an 8-mm needle on the next day [32].

Needle reuse has been a contentious subject, with financial interests being a confounding issue on both sides of the debate. However, a Spanish study [33] showed an association between LH (which the authors found in 52% of T2DM and 72% of T1DM patients) and the reuse of needles (p < 0.05). There was a clear trend to greater frequency of LH as the number of uses (reuse) of the needle increased. The presence of LH was highest when the needle was used six times or more. Of those who reused needles, 70% had LH (84% in T1DM) [33]. A more recent Chinese study has confirmed these findings [34].

Needle reuse, whether with pens or syringes, is lower in Turkey than in ROW, as is the number of times a reused needle is used (Table 5). When Turkish patients do reuse needles, the principal reason given is not cost as the needles have already ben fully reimbursed, but rather convenience [35].

Pen needles, syringes and lancets used in the treatment of diabetes are the most frequently used sharps in the world. Most of these are employed in the home setting, where their safe disposal after use is of critical public health importance. In Turkey, the ITQ data revealed that many persons are in the immediate surroundings of the person who is injecting/being injected, often children, who might accidentally be injured by the used sharps (Table 15). Appropriate disposal containers are not available to more than half of Turkish patients (Table 16), and conditions favorable to contamination exist even in the home setting; this includes a sero-positive rate for hepatitis and other blood-borne illnesses of 7.2% of patients, by indicated by self-reporting (Table 16). More than 75% of used sharps in Turkey go into the rubbish, with nearly 6% not even having the minimum protection of a cap (Tables 17, 18). This represents a risk for children, home healthcare nurses, maids and household cleaners, rubbish collectors, street animals and others in the community. Furthermore, 10.9% of our survey population reported that a needlestick injury had already occurred sometime during their years of injecting insulin. Hence, more safety measures, including a wider use of safety-engineered devices, are clearly needed in Turkey.

Conclusions

In summary, based on our comparison of ITQ data, many of the parameters of injection practice are better in Turkey than in ROW, but we are still far from achieving our goals The continued use of 8-mm needles by approximately one-third of Turkish patients increases the risk during IM injections. Additionally, more focus needs to be given to dwell times under the skin, reconstitution of cloudy insulins, correct use of skin folds and safe disposal of sharps. The Turkish Injection Delivery Guidelines, named the ‘Insulin Injection Techniques and Treatment Guideline for Health Care Professionals’, are a welcome step in this direction. These should be made available to all patients and professionals involved in insulin therapy in Turkey and should followed by all as a road map to optimal therapy. The authors plan to conduct another ITQ approximately 1 year after these guidelines are published with the aim to assess their impact on Turkish injection practice.