O R I G I N A L A R T I C L E
`
`A pan-European epidemiologic study of
`insulin injection technique in patients with
`diabetes
`
`Kenneth Strauss*, Heidi De Gols, Irene Hannet, Tuula-Maria Partanen, Anders Frid
`
`ABSTRACT
`Aim. A large pan-European epidemiologic survey of insulin injection techniques was performed in order to determine the epidemi-
`ologic profile by centre, country and continent of major issues surrounding insulin injection.
`Methods. European insulin-injecting, type 1 or 2 diabetes patients, using insulin for at least 6 months via an insulin pen or syringe;
`22 sites in seven countries, 1002 patients in total, 51% female, 58% type 1.
`Results. Nearly 70% of patients inject using a pinch-up and this practice is associated with improved HbA1c. Thirty per cent of
`patients reported having lipohypertrophy. Concurrent nurse evaluation found the prevalence to be 27%. Independent risk factors for
`lipohypertrophy were found to be failure by the patients to check injection sites regularly, failure to rotate sites and longer duration
`of DM. Less than 50% of patients reported that they were taught about lipohypertrophy. Needles were used 3.3 times on average in
`Europe, with wide variation by country. Male sex, type 1 diabetics, a high daily number of injections and the use of the 12.7 mm
`length needle were factors associated with high needle reuse. Needle reuse, even more than once, increased the risk of lipohypertro-
`phy by 31%. Nearly half of patients dispose of their needles directly into the trash after protecting the needle (recapping or clipping).
`Alarmingly, 22% dispose directly into the trash without protection.
`Conclusion. There is a considerable way to go in ensuring optimal insulin injection practices. The issues raised by this study must
`be addressed by focused and intensive HCP efforts. Copyright © 2002 John Wiley & Sons, Ltd.
`Practical Diabetes Int 2002; 19(3): 71–76
`
`KEY WORDS
`epidemiology; diabetes; insulin injection; lipodystrophy; lipohypertrophy; sharps disposal; insulin needles; glucose control; blood
`glucose monitoring; diabetic education
`
`Introduction
`Diabetes nurses and observant patients
`have long known that the technique of
`injection is critical to the successful use of
`insulin, but the medical community at
`large and most insulin-using patients
`remain woefully unaware of the impor-
`tance of proper injection technique. Recent
`
`Kenneth Strauss*, Heidi De Gols, Irene
`Hannet, Medical Department, Becton
`Dickinson - Europe, Erembodegem,
`Belgium, Tuula-Maria Partanen, North-
`Savo Polytechnic, School of Social and
`Health Professions, Kuopio, Finland, Email
`address: tuula-maria.partanen@pspt.fi,
`Anders Frid, Department of Medicine,
`University Hospital of Lund, Lund, Sweden,
`Email address: dr.frid@telia.com
`
`*Correspondence to: Kenneth Strauss, MD,
`24 Denderstraat, POB 13, Erembodegem-
`Aalst, 9320 Belgium. Email address:
`Kenneth_Strauss@Europe.bd.com
`
`Received: 25 January 2001
`Accepted in revised form:
`22 November 2001
`
`years have seen increased emphasis on
`intensive insulin therapy and on the critical
`role of blood glucose measurements, but
`few realize that correct insulin injection
`technique is as important to good glucose
`control as the type and dose of insulin
`delivered1-5. The incorrect choice of sites
`and techniques may modify insulin absorp-
`tion parameters, leading to an uncoupling
`of maximum glucose load and peak insulin
`effect. This can lead to both unexpected
`hyperglycemia and an increased risk of
`nocturnal hypoglycemia6-10.
`The first Insulin Injection Technique
`Workshop, held in June 1997 in Stras-
`bourg, brought together over 40 injection
`experts from across Europe and the world.
`This meeting and the paper that fol-
`lowed11 highlighted large areas of uncer-
`tainty in the field and called for a large
`study to examine the way patients actually
`inject insulin. It was felt that without a
`sound epidemiologic foundation it would
`be impossible to evaluate the effectiveness
`of current teaching approaches or to make
`general recommendations for change.
`An attendee at the Strasbourg meeting,
`Diabetes Nurse Specialist Tuula Maria
`
`Partanen, of Finland, developed and tested
`an anonymous, voluntary questionnaire
`covering all aspects of insulin injection
`techniques. This questionnaire consisted
`of an initial patient section (administered
`by an experienced diabetes nurse) followed
`by a section completed by a nurse after an
`actual injection was observed and a metic-
`ulous examination made of all injection
`sites.
`The objectives of this study were to
`understand the epidemiologic profiles for
`the major insulin injection parameters, to
`determine the leading causes of variability
`in injection technique, their ranking and
`their
`interactions and to query the
`patients' perception of the injection
`process, the psychological barriers and the
`aids.
`
`Methods
`Subjects
`Over 18 months, from October 1998 to
`March 2000, 1002 insulin-injecting type 1
`and 2 diabetic patients from 22 centres in
`seven European countries participated in
`the study. (For the names of participating
`centres and investigators see the acknowl-
`
`Pract Diab Int April 2002 Vol. 19 No. 3
`
`Copyright © 2002 John Wiley & Sons, Ltd.
`
`71
`
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`

`

`O R I G I N A L A R T I C L E
`
`European study of insulin injections
`
`Table 1: Number of subjects per European country
`Country
`Number of
`Percent Cumulative
`patients
`percent
`
`Number of
`centers
`
`Sweden
`Belgium
`Germany
`France
`Italy
`Spain
`UK
`Total
`
`101
`66
`258
`178
`149
`129
`121
`1002
`
`10.1
`6.6
`25.7
`17.8
`14.9
`12.9
`12.1
`100.0
`
`10.1
`16.7
`42.4
`60.2
`75.0
`87.9
`100.0
`
`1
`1
`6
`4
`3
`3
`4
`22
`
`Table 2: Overall descriptive statistics
`N
`Mean
`
`Age (years)
`Weight (kg)
`Height (cm)
`Body Mass Index*
`Duration of
`diabetes (years)
`Injections/day
`Dose of Insulin
`(IU)/day
`Times patient uses
`a single needle
`HbA1c according
`to patient
`HbA1c according
`to nurse
`Glucose controls/
`day
`
`998
`995
`995
`994
`
`993
`992
`
`992
`
`812
`
`724
`
`968
`
`335
`
`46.9
`75.0
`168.0
`26.5
`
`14.7
`3.3
`
`48.8
`
`3.3
`
`7.9
`
`8.0
`
`3.4
`
`*BMI=height (in meters)/(weight in kg)2
`
`edgements section at the end of the arti-
`cle.) Subjects were 13 years of age or over
`and had used insulin for at least 6 months.
`In order to eliminate selection bias subjects
`were accessioned to the study on a sequen-
`tial basis, i.e. consecutive eligible and con-
`senting patients entering the clinic were
`accessioned. Injections were performed
`with an insulin pen or syringe or both and
`participants gave verbal consent to partici-
`pate. Becton Dickinson sponsored the
`study. No patient identifying information
`was made available to the sponsor and
`patients were informed that their care
`would not be affected in any way by their
`participation. They were not put at risk by
`the study and were not paid to participate.
`Ethics committee approval was obtained.
`
`72 Pract Diab Int April 2002 Vol. 19 No. 3
`
`Std.
`Deviation
`
`Minimum Maximum
`
`18.4
`15.8
`9.3
`5.2
`
`10.6
`1.2
`
`23.5
`
`3.1
`
`1.8
`
`1.7
`
`1.3
`
`13.00
`40.00
`140.00
`15.79
`
`0.40
`1.00
`
`3.00
`
`1.00
`
`4.20
`
`4.30
`
`1.00
`
`89.00
`168.00
`200.00
`62.46
`
`58.00
`8.00
`
`178.00
`
`11.00
`
`16.00
`
`16.20
`
`8.00
`
`Questionnaire
`Besides patient demographic information,
`the key insulin injection parameters
`queried by the questionnaire were the fol-
`lowing.
`Current practice: injection device and nee-
`dle length, insulin type, number of injec-
`tions/day, frequency of dosage adjustment,
`choice of injection site, use and character-
`istics of skin folds (pinch-up), needle entry
`angle, size of injecting zone, site rotation,
`disinfecting prior to injecting, dwell time
`of needle under the skin, site inspection by
`patient and professional, needle reuse,
`sharps disposal, injection through cloth-
`ing.
`Observed anomalies at injection sites: insulin
`reflux, bruising, lipoatrophy, lipohypertro-
`
`phy, inflammation, induration, scarring.
`Knowledge about injections:
`identity of
`teacher, themes covered in training, ade-
`quacy of coverage, desire for more knowl-
`edge.
`Psychological perceptions of injections: ease
`of injection, pain, needle phobia, missed
`injections and reasons.
`Glucose control: latest HbA1c, knowledge
`about normal value for HbA1c, frequency
`of fingersticks, use of glucose control
`results.
`There were also a number of open-
`ended questions, which allowed the sub-
`jects to express opinions not covered in
`other parts of the questionnaire.
`
`Validation
`The questionnaire was first tested in 100
`patients in two centres in Finland. Further
`validation studies were performed on
`another 100 patients in Lund, Sweden, in
`1998, and once the questionnaire was fully
`validated the wider study was begun.
`
`Analysis
`SPSS software was used. Descriptive statis-
`tics,
`frequencies and rankings were
`obtained. Chi-squared analysis was per-
`formed where appropriate for contingency
`tables. Log-linear analysis and ANOVA
`were used for the analysis of individual
`parameters and multiple regression and
`correlation analysis were used for multi-
`parametric analysis. Two-tailed tests were
`used in all analyses. Initially each of the 22
`sites was analysed independently and only
`when the distributions of key demograph-
`ic parameters (age, sex, BMI and duration
`of diabetes) were shown to be equivalent
`were sites pooled into country groupings.
`The same process was followed for each
`country grouping before pooling all the
`data into a total Europe database.
`
`Results
`Table 1 presents the contributions by
`country to the study. The percentages from
`each country correspond roughly to the
`proportion of that country's population to
`the total European population. Of the 22
`centres approximately one-third (n = 8)
`were specialist diabetes clinics, one-third
`(n = 7) were community care centres and
`one-third (n = 7) were general practice
`centres. Half (n = 11) were urban and the
`other half were town or sub-urban. Table 2
`shows the descriptive statistics of the
`patient population. Four hundred and
`ninety-one subjects were male (49.2%).
`The age distribution was bi-modal because
`
`Copyright © 2002 John Wiley & Sons, Ltd.
`
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`

`O R I G I N A L A R T I C L E
`
`European study of insulin injections
`
`Figure 1. HbA1c values by country as a
`function of type of diabetes.
`
`Figure 2. Number of injections per day by
`country.
`
`Figure 3. Percentage of patients using var-
`ious injection sites; numbers add to more
`than 100% because of use of multiple sites.
`
`Figure 4. Relationship between the num-
`ber of times a single needle is used to the
`presence of lipodystrophy for the two most
`common needles used, the 8 and 12.7
`mm.
`
`one out of two patients pinch in Belgium.
`Patients who pinch up had lower HbA1c
`values than those who do not pinch, 7.9
`versus 8.2; p = 0.032). There was a signifi-
`cant relationship (p = 0.001) between leav-
`ing the pen needle in longer and a lower
`HbA1c. Over 10 seconds seemed to be the
`ideal dwell time. Patients who regularly
`inspect their injection sites have signifi-
`cantly (p = 0.03) lower HbA1c values.
`HbA1c was not significantly related to
`
`Figure 5. Needle use by country.
`
`of the mixture of type 1 and 2 patients.
`There were 562 type 1 patients (58% of
`total), with a mean age of 36.3 years (SD
`15.4), and 404 type 2 patients, with a
`mean age of 61.8 years (SD 10.3). HbA1c
`did not differ as a function of type of dia-
`betes; country breakdowns are shown in
`Figure 1. The average number of injections
`given in this study was 3.3/day (SD 1.1).
`Figure 2 shows three main groupings by
`country: approximately four injections/day
`were the average in Sweden and Germany,
`approximately three injections/day in
`Belgium, Italy and Spain and between 2.5
`and 3 injections/day in France and the
`UK. Nineteen per cent of patients used
`syringes, 64% insulin pens and 15% both
`devices. Four per cent of subjects use the 5
`mm needle, 5.5% the 6 mm needle, 55%
`the 8 mm needle and 36% the 12.7 mm
`needle. The most commonly used injec-
`tion site was the abdomen, followed by the
`thigh (Figure 3). Use of the buttocks (by
`222 patients out of 967 total) was associat-
`ed with lower HbA1c values (p = 0.050).
`When asked, 69.4% of patients claim to
`pinch a skin fold when they inject. Nurse
`observation found that 73% of patients
`asked to perform an injection used a skin
`fold. Three out of four patients pinch in
`Sweden, Germany and Spain, two out of
`three patients in France, Italy and UK and
`
`number of glucose controls performed/day
`(p = 0.384), rotation of injection sites (p =
`0.584), injecting perpendicularly into
`abdomen (p = 0.375) or not pinching up
`in the thigh (p = 0.890), but it was highly
`significantly associated with (p = 0.0001)
`adjusting insulin doses. Patients who
`adjusted their own insulin doses tended to
`have lower HbA1c values, and the more
`frequent the adjustment the lower the
`HbA1c. Sixty-two per cent of patients
`reported seeing bruising at the site of injec-
`tion, 30% reported fatty swelling at the
`site of injection consistent with lipohyper-
`trophy and 27% of patients had lipohy-
`pertrophy confirmed by nurse examina-
`tion. Only 38% reported rotating injec-
`tion sites each time they injected regular
`insulin. The presence of lipohypertrophy
`was not found to be significantly related to
`the length of needle (p = 0.390), the pres-
`ence of brusing at the site of injection (p =
`0.330), the sex of the patient (p = 0.797),
`the use or not of a pinch-up (p = 0.302),
`the angle of injection (p = 0.218), disin-
`fecting the skin before injecting (p =
`0.360) or the length of time the needle is
`left in the skin (p = 0.128).
`Needle reuse is more prevelant amongst
`12.7 mm needle users than amongst 8 mm
`users (Figure 4), but in both groups those
`who reuse needles more frequently are
`more likely to have lipos than those who
`do so less frequently. The number of times
`a single needle is used varied widely by
`country (Figure 5), with France and Italy
`having the lowest rates and Belgium and
`the UK the highest. Since the time of this
`study, pen needles have become available
`on prescription in the UK, and this may
`have affected the rate of needle reuse.
`Males reused needles significantly (p =
`0.003) more frequently than females, and
`type 1 patients more than type 2s (p =
`0.020). A possible explanation for the lat-
`ter may be the increased number of injec-
`
`Figure 6. Needle reuse as a function of the
`length of the needle.
`
`Pract Diab Int April 2002 Vol. 19 No. 3
`
`Copyright © 2002 John Wiley & Sons, Ltd.
`
`73
`
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`

`O R I G I N A L A R T I C L E
`
`European study of insulin injections
`
`Table 3: Needle use, one time vs. more than once
`Number of times
`Number of
`needle used
`patients
`
`1
`>1
`
`TOTAL
`
`410
`592
`1002
`
`Percentage
`patients
`
`40.9%
`59.1%
`100.0%
`
`tions given per day by type 1s. Needles are
`reused more often by patients who use the
`shortest (5 mm) and longest (12.7 mm)
`needles (Figure 6), although the former
`represented only a small fraction (4%) of
`the total needle count in this study. Needle
`length, in this study, was not related to
`bruising at the site of injection (p = 0.304)
`or to injection pain (p = 0.398).
`Table 3 gives the overall breakdown of
`patients who use the needle only once ver-
`sus those who use it more than once;
`40.9% of European patients use a needle
`only once and then discard it; 59.1% use it
`more than once. A significant number of
`patients use the same insulin needle more
`than 10 times. There is a strong tendency
`(p = 0.067) for patients who reuse needles
`to have more lipohypertrophic lesions than
`those who use the needle only once. The
`risk of lipohypertrophy rises as the mean
`number of needle uses increases. Although
`lipohypertrophy is sometimes found in
`persons who do not reuse needles, there is
`a 31% increased risk of having lipohyper-
`trophy if one reuses.
`The link between lipohypertrophy and
`needle reuse was looked at in sub-groups, to
`determine whether there were special popu-
`lations at risk. Pen users have a tendency to
`use the same needle more times than
`syringe users. Patients who use pens and
`reuse needles have a higher risk (p = 0.058)
`of having lipohypertrophy. Although lipo-
`hypertrophy is sometimes present in pen
`users who do not reuse, there is a 44%
`increased risk of lipohypertrophy for pen
`users if they reuse needles. Patients were
`asked to estimate the size of their injection
`area. Those who inject into small zones (5
`cm by 4 cm or one-quarter the size of a
`postcard) and reuse needles have a much
`higher risk (p = 0.0001) of having lipohy-
`pertrophy, nearly threefold greater, than if
`they did not reuse. Patients are often taught
`to rotate their injection sites regularly, but
`this study found that only 38% did. Those
`who do not rotate their injection sites and
`reuse needles have a 43% greater risk (p =
`0.088) of having lipohypertrophy than
`those who use a needle only once.
`
`74 Pract Diab Int April 2002 Vol. 19 No. 3
`
`Virtually all patients perform injections
`at home, but a surprisingly high percent-
`age inject in private locations such as toi-
`lets (53.8%) or at work (32.2%). Nearly
`70% of patients indicate the need to learn
`more about insulin injection, a remarkable
`percentage considering the mean duration
`of diabetes in this population was 14.7
`years. Less than 60% of patients state that
`certain key themes were covered in their
`training: prevention of lipodystrophy, mix-
`ing insulins, needle length, use of back-up
`syringes (in the event of pen failure) and
`the safe disposal of used needles. Figure 7
`shows disposal practices overall. Forty-
`seven per cent of patients dispose of their
`sharps in the trash after protecting the tip
`(recapping or clipping off the tip).
`Shockingly, 22% admit throwing their
`sharps away into the trash or flushing them
`without protecting the tip.
`
`Discussion
`This paper reports on the largest epidemi-
`ologic survey of insulin injection tech-
`nique yet published. Over a thousand
`insulin injecting patients across Europe
`were surveyed in a randomized fashion and
`then examined by trained diabetes nurses.
`
`Injection technique and
`glucose control
`The use of a pinch-up has been recom-
`mended by experts in the injection of
`insulin. The First Insulin Injection
`Technique Workshop in Strasbourg11
`issued the following recommendation:
`
`Figure 7. Disposal practices for the con-
`taminated needles.
`
`How do you dispose of needles?
`
`22%
`
`15%
`
`Sharps container
`
`16%
`
`Other sealed
`container
`
`Trash after
`protecting
`
`47%
`
`Into trash directly
`
`For everyday use in most patients, subcuta-
`neous rather than intramuscular, intraperi-
`toneal or intradermal injection of insulin is
`preferred. Recent research has allowed
`direct visualisations of insulin as it is
`injected into tissue (CT, US). Pinching up
`the skin is one method that has been docu-
`mented by CT scan and ultrasonography
`to increases the chance of subcutaneous
`injection. If one performs a pinch up it
`should be made with 2 fingers (thumb and
`index). The fold should be maintained
`throughout the injection, and 5-10 sec-
`onds afterwards, before removing the nee-
`dle.11
`
`Our study found that nearly 70% of
`patients inject using a pinch-up and that
`pinching up is associated with improved
`HbA1c. Leaving the pen needle in longer
`was also associated with improved HbA1c,
`possibly because this allows more time for
`insulin to diffuse into SQ tissues. A dwell
`time of over 10 seconds appeared to be
`optimal. Use of the buttocks as an injec-
`tion site is also associated with improved
`HbA1c, although it is practiced by fewer
`than 25% of patients in this survey.
`
`Injection technique and
`lipodystrophy
`Lipohypertrophy (often known by patients
`as a 'lipo') is described as a benign tumour-
`like swelling of the fatty tissue often seen at
`injection sites of insulin-administering
`diabetic subjects (up to 25% of insulin
`injecting diabetics in various studies)12-18.
`Lipos can rarely appear as shiny, firm areas
`on younger skin but typically are movable
`soft tissue lesions similar to lipomas. They
`vary greatly in size and are often felt more
`easily than seen. The etiology of these fatty
`lumps is not completely understood, but it
`is believed that, in susceptible subjects, an
`'incorrect' injection technique may facili-
`tate their occurrence.
`in children12
`and
`Recent studies
`adults14 demonstrated that lipos can be
`made to decrease in size by systematic and
`appropriate rotation of injection sites. In
`these studies significant size reduction (30-
`50%) of the lipos was achieved in 3
`months. In addition HbA1c values were
`also found to improve significantly and
`this improvement seemed to be correlated
`with the extent of lipo size reduction.
`Other studies13,15 have shown that insulin
`absorption from lipodystrophic tissue is
`erratic, resulting in poorer glucose control.
`Lipos may also be responsible for signifi-
`cant insulin 'over-usage' or 'wastage', since
`
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`
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`

`O R I G I N A L A R T I C L E
`
`European study of insulin injections
`
`appropriate rotation schemes not only
`reduce the size of lipos but allow the
`patient to reduce their daily insulin con-
`sumption by up to 50%19.
`Though the exact causes of lipos are
`unknown, the predisposing conditions are
`clearly trauma to the skin and SQ tissue,
`which is repeated in time and place in the
`presence of insulin20-24. We cannot control
`the increase in the dose of insulin, nor the
`increased number of
`injections that
`accompany intensive therapy, but we can
`diminish the trauma to the skin and SQ
`tissue (by avoiding excessive reuse of nee-
`dles) and we can decrease the exposure to
`place and time by careful site rotation.
`Thirty per cent of patients in this study
`reporting having lipohypertrophy at any
`one of their injection sites. Nurse evalua-
`tion found the prevalence to be 27%.
`There is a strong tendency to more lipohy-
`pertrophy in patients who engage in some
`kind of needle reuse (use needle more than
`once) than in those who never reuse.
`Certain sub-groups seem especially vulner-
`able to lipohypertrophy if they reuse nee-
`dles: patients who use insulin pens,
`patients who inject into small injection
`zones and patients who fail to rotate sites
`of injections on a regular basis. Although it
`is not possible to avoid all lipohypertro-
`phy, this study supports the advice that for
`each insulin injection patients should
`change to an area that is lipo-free, change
`to a fresh site for every injection and
`change to a new needle with every shot. At
`the time of this study, three of the authors
`were employees of BD, a manufacturer of
`needles and main sponsor of the study. We
`are only too aware of the potential for con-
`flict of interest in the above conclusion,
`and have done our best to eliminate this
`bias. We also invite others to perform sim-
`ilar studies in order that these conclusions
`might be challenged and validated.
`Surprisingly only 38% of patients in
`
`this study rotated sites each time they
`injected rapid-acting insulin. The known
`value of a rotation scheme and the rela-
`tively low percentage of patients who prac-
`tice rotation clearly highlight an important
`educational opportunity for those of us
`taking care of insulin-injecting diabetic
`patients. Less than 50% of patients report-
`ed they had been taught about effective
`means for preventing these unsightly and
`deleterious lesions. It should be empha-
`sized that simply telling patients to rotate
`sites is not enough. They must be given an
`organized scheme12,14 in order to plot a
`personal strategy for rotation and must be
`warned against blood sugar variations.
`Health care workers must check injection
`sites regularly and intervene appropriately
`before these lesions appear or enlarge.
`
`Injection technique and needle
`reuse
`Needles were used an average of 3.3 times
`throughout Europe, but there were wide
`country to country variations, with France
`and Italy having the lowest reuse rates.
`This fact seemed to be related to the
`instructions given by nurses in these coun-
`tries not to reuse needles. Needle reuse was
`associated with male sex, type 1 diabetes, a
`high daily number of injections and the
`use of the 5 or 12.7 mm needle. The asso-
`ciation of needle reuse with the presence of
`lipohypertrophy should give pause to those
`who actively endorse such practices.
`
`Injection technique and sharps
`disposal
`Forty-seven per cent of patients dispose of
`their syringe or pen needle directly into the
`trash after protecting the needle by recap-
`ping or clipping. Alarmingly, 22% dispose
`of needles without even this minimum
`precaution. This is clearly a public health
`hazard, which is under-appreciated at pres-
`ent. Forty per cent of patients reported
`
`Keypoints
`● Nearly 70% of European patients inject into a pinched skin fold and this practice is
`associated with lower HbA1c values.
`● 30% of patients reported having lipohypertrophy. Subsequent nurse evaluation
`confirmed this prevalence. Less than 50% of patients reported that they were taught
`about lipohypertrophy.
`● Independent risk factors for lipohypertrophy were found to be failure by patients to
`check injection sites regularly, failure to rotate sites and longer duration of DM.
`● Needles were used 3.3 times on average in Europe, with wide by country variation.
`Needle reuse, even >1 time, increased the risk of lipohypertrophy by 31%.
`● Nearly half of patients dispose of their needles directly into the rubbish after
`protecting the needle (recapping or clipping). But 22% dispose directly into the
`rubbish without protection.
`
`receiving no instruction on the safe dispos-
`al of used sharps, suggesting that education
`is an appropriate first step in addressing
`this problem. It is clear as well that more
`convenient means of safe disposal should
`be provided to patients.
`
`Conclusions
`This initial survey of insulin injection
`technique in Europe should be considered
`a pilot study. Despite the high degree of
`agreement in the results from site to site
`and across regions in Europe there is some
`degree of risk in drawing conclusions for
`an entire continent or even for a single
`country from samples of only a few hun-
`dred subjects. More extensive studies are
`clearly needed, and patient populations
`not specifically targetted here (e.g. pedi-
`atrics, geriatric populations and gestation-
`al diabetics) should be the subjects of sep-
`arate studies. Nevertheless, this survey has
`revealed sobering deviations from optimal
`injection practice and should provide the
`impetus for renewed and more innovative
`educational approaches, as well as pointing
`the way towards technology- and product-
`oriented solutions. The willingness is cer-
`tainly there: more than 70% of patients
`indicate their need for more injection
`knowledge.
`
`Acknowledgements
`Bedford General Hospital, Bedford - UK -
`Mrs J. Pledger - Mrs Lesley Cowley, Mrs
`Julie de Souza.
`Bradford Royal Infirmary, Bradford -
`UK - Mrs F. Preston.
`Clinique Medicale Villecresnes,
`Villecresnes - France - Dr J.P. Le Floch.
`Hôpital Civil de Jumet, Jumet -
`Belgium - Dr G. Krzentowski - Mrs C.
`Fadeur
`Hôpital de Rangqueil, Toulouse -
`France - Dr S. Crognier.
`Hôpital Jeanne d'Arc, Nancy - France -
`Mrs D. Durain.
`Hôpital St Louis, Paris - France - Mrs
`M.L. Cottez.
`Hospital 'Cruces', Bilbao - Spain - Dr
`Vazquez Garcia - Mrs A. Moreno Alvarez.
`Hospital Universitario 'La Paz', Madrid
`- Spain - Mrs L. Saez de Ibarra.
`Hospital Universitario 'San Carlos',
`Madrid - Spain - Mrs E. Gil Zorzo.
`Olgahospital, Stuttgart - Germany - Dr
`W. Hecker - Mrs Bareiter.
`Ospedale Garibaldi, Catania - Italy -
`Prof. Purello - Dr M. Anello - Dr R.
`Maiorana.
`Ospedale Niguarda Ca'Granda, Milano
`
`Pract Diab Int April 2002 Vol. 19 No. 3
`
`Copyright © 2002 John Wiley & Sons, Ltd.
`
`75
`
`Novo Nordisk A/S Ex. 2019, P. 5
`Mylan Institutional v. Novo Nordisk
`IPR2020-00324
`
`

`

`O R I G I N A L A R T I C L E
`
`European study of insulin injections
`
`- Italy - Dr C. Fossati - Dr O. Disoteo -
`Mrs G. Grieco.
`Ospedale San Bortolo, Vicenza - Italy -
`Dr Mingardi.
`Praxis Dr Betzholz, Neuss - Germany -
`Dr Betzholz - Mrs B. Johnen - Mrs K.
`Breuer.
`-
`Praxis Dr Eversmann, Munich
`Germany - Dr Eversmann - Mrs E.
`Bernhard.
`Praxis Dr Klausmann, Aschaffenburg -
`Germany - Dr Klausmann - Mrs S.
`Streitenberger.
`Queen Elizabeth Hospital, Tyne &
`Wear - UK - Dr C. Smith - Mrs B. Foster
`Royal Hospital for Sick Children,
`Edinburgh - UK - Dr C. Kelnar - Mrs
`Carol Carson.
`-
`Städtische Kliniken, Offenbach
`Germany - Dr D. Klein - Mrs B. Stapfer -
`Mrs E. Reinecke.
`Städtisches Krankenhaus Bogenhausen,
`Munich - Germany - Dr Renner - Dr
`Rendschmidt - Mrs G. Hubert.
`University Hospital, Lund - Sweden -
`Dr A. Frid - Mrs Magdalena Annersten.
`This study was partially sponsored by
`Becton Dickinson.
`
`References
`1. Thow JC, Johnson AB, Fulcher G, Home PD.
`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.
`2. Thow JC, Home PD. Insulin injection technique:
`depth of injection is important. BMJ 1990; 301: 3-4.
`3. Engstrom L. Technique of insulin injection: is it
`important? Practical Diabetes 1994; 11: 39.
`4. Kolendorf K, Bojsen J, Deckert T. Clinical factors
`influencing the absorption of 125 I-NPH insulin in
`diabetic patients. Horm Metab. Res 1983; 15: 274-
`278.
`5. Bantle J, Neal L, Frankamp L. Effects of the anatom-
`ical region used for insulin injections on glycemia in
`type I diabetes subjects. Diabetes Care 1993; 16:
`1592-1597.
`6. Galloway J, Spradlin C, Nelson R, Wentworth S,
`Davidson J, Swarner J. Factors influencing the
`absorption, serum insulin concentration, and blood
`glucose responses after injections of regular insulin
`and various insulin mixtures. Diabetes Care 1981; 4:
`366-376.
`7. Sindelka G, Heinemann L, Berger M, Frenck W,
`Chantelau E. Effect of insulin concentration, subcu-
`taneous fat thickness and skin temperature on subcu-
`taneous insulin absorption in healthy subjects.
`Diabetologia 1994; 37: 377-380.
`8. Henriksen JE, Djurhuus MS, Vaag A, Thye-Ronn P,
`Knudsen D, Hother-Nielsen O, Beck-Nielsen H.
`Impact of injection sites for soluble insulin on gly-
`caemic control in type 1 (insulin-dependent) diabetic
`patients treated with a multiple insulin injection reg-
`imen. Diabetologia 1993; 36: 752-758.
`9. Henriksen J, Vaag A, Ramsgaard Hansen I, Lauritzen
`M, Djurhuus M, Beck-Nielsen H. Absorption of
`NPH (isophane) insulin in resting diabetic patients:
`evidence for subcutaneous injection in the thigh as
`the preferred site. Diabet Med 1991; 8: 453-457.
`10. Koivisto V, Felig P. Alterations in insulin absorption
`and in blood glucose control associated with varying
`insulin injection sites in diabetic patients. Ann Intern
`Med 1989; 92: 59-61.
`11. Strauss K (compiler). Insulin injection techniques:
`report from the 1st International Insulin Injection
`Technique Workshop, Strasbourg, France - June 1997.
`Practical Diabetes International 1998; 15: 16-20.
`
`12. Franzén I, Ludvigsson J. Specific instructions gave
`reduction of lipomas and improved metabolic control
`in diabetic children. July 1997 IDF, Helsinki
`(abstract).
`13. Young RJ, Hannan WJ, Frier BM, Steel JM, Duncan
`Leslie JP. Diabetic lipohypertrophy delays insulin
`absorption. Diabetes Care 1984; 7 (5).
`14. Saez-de Ibarra, Gallego F. Factors related to lipohyper-
`trophy in insulin treated diabetic patients: role of
`educational intervention. Practical Diabetes Int 1998;
`15 (1).
`15. Thow JC, Johnson AB, Marsden S, Taylor R, Home
`PD. Morphology of palpably abnormal injection sites
`and effects on absorption of isophane (NPH) insulin.
`Diabet Med 1990; 7: 795-799.
`16. Roper NA, Bilous RW. Resolution of lipohypertrophy
`following change of short-acting insulin to insulin
`lispro (Humalog). Diabet Med 1998; 15 (12): 1063-
`1064.
`17. Chantelau E, Reuter M, Schotes S, Starke AA. A case
`of lipoatrophy with human insulin-therapy. Exp Clin
`Endocrinol 1993; 101 (3): 194-196.
`18. Hauner H, Stockamp B, Haastert B. Prevalence of
`lipohypertrophy in insulin-treated diabetic patients
`and predisposing factors. Exp Clin Endocrinol
`Diabetes 1996; 2: 106-110.
`19. Hannerz L, Strauss K. Lipodystrophy - it hasn't gone
`away! EASD Conference, Barcelona, 1998 (abstract).
`20. Samdal F, Amland PF, Sandsmark M, Birkeland KI.
`Diabetic lipohypertrophy treated with suction-assist-
`ed lipectomy. J Intern Med 1993; 234 (5): 489-492.
`21. Hardy KJ, Gill GV, Bryson JR. Severe insulin-induced
`lipohypertrophy successfully treated by liposuction.
`Diabetes Care 1993; 16 (6): 929-930.
`22. Gilbert C. Injection d'insuline et lipodystrophie. Soins
`2001; 651: 23-25.
`23. Reach G, Chane M, Vias M, Papoz L, Forhan A,
`Guillemin C. Hba1c in children attending summer
`camps organized by L'aide Aux Jeunes Diabetiques.
`Evidence for a harmful effect o