Long-term effect of Libre on HbA1c persists after 3.5 years T1DM. 6 mmol/mol lower HbA1c.
Cajsa Naess, Erik Schwarcz, Örebro

 

Long-term effect on HbA1c in people with Type 1 diabetes mellitus who use Freestyle Libre. Longest follow-up study

The long-term effect of 3.5 years on HbA1c in 223 people with Type 1 diabetes who use Freestyle Libre is sustainable.

HbA1c has dropped from 66.1 to 60.1 mmol/l, i.e. 6.0 mmol/mol.

In people with a mean HbA1c value of 78, the value dropped by 11.3 mmol/mol. The study is the longest follow-up study

Örebro University, Medicine Program, Medical Sciences Department, Student thesis, 15 credits

Cajsa Naess, Medical student. Advisors: Erik Schwarcz, Chief Physician, M.D., Medical Clinic 1, Örebro University Hospital, Örebro, Sweden

Summary Background:

Type 1 diabetes mellitus is a chronic metabolic disease. Left untreated, or in the event of high HbA1c over long periods, the disease may cause tissue damage and increase the risk of serious complications. Achieving adequate insulin treatment requires self-monitoring of glucose, which may be accomplished using different methods. The most recent to be used is Freestyle Libre of the flash glucose monitoring (FGM) type, which monitors glucose in the tissue using a subcutaneous sensor electrode through intermittent scanning, isCGM. With this, the patient can monitor glucose without pricking themselves in the fingers, as well as view a history of and expected future glucose levels.

Purpose:

To investigate whether the positive trend observed after 12 months of Freestyle Libre use in patients with Type 1 diabetes mellitus continued another 30 months.

Materials and method:

The study has been conducted as a retrospective medical record review at Medical Clinic 1 at Örebro University Hospital, and as a long-term follow-up on a prior investigation. The HbA1c value (glycosylated hemoglobin) prior to starting Freestyle Libre was gathered and the values for every sixth month for a period of 42 months.

On this basis, a diagram was created in Microsoft Excel to see what the mean HbA1c value has been since the start of Freestyle Libre. The patients were also divided into groups according to patient characteristics to determine whether the effect of the glucose meter differed between these groups.

Result:

The study included 223 subjects with Type 1 diabetes mellitus, 121 men and 102 women with a mean age of 47 (SD±15.5) years. 61.4% of the subjects were treated with an insulin pen and 38.6% with an insulin pump.

The mean value for HbA1c prior to the start of Freestyle Libre was 66.1 (SD±15.2) mmol/mol.

After 12 months of use, the mean value for HbA1c dropped to 60.6 (SD±12.4) mmol/mol and after 42 months the mean value was 60.1 (SD±12.6) mmol/mol.

The group with a relatively high HbA1c prior to the start experienced a greater effect on FGM, while the group with a relatively low HbA1c experienced less of an effect.

Women showed a greater reduction in HbA1c than men. Subjects treated with a pump showed a greater reduction than subjects treated with pens. Subjects younger than the average age showed slightly more than older subjects.

Final conclusion:

The study demonstrates the positive trend observed after 12 months of Freestyle Libre use continues for another 30 months. Glucose monitoring with Freestyle Libre has a long-term, positive effect on HbA1c. Consequently, the metabolic checkup for subjects with Type 1 diabetes mellitus and the subjects showing the best effect from this, had a high HbA1c prior to the start.

Abbreviations

T1DM             Type 1 diabetes mellitus
HbA1c             Glycosylated hemoglobin

AGEs              Advanced Glycated Endproducts
SMBG             Self-monitoring of Blood Glucose
CGM               Continuous Glucose Monitoring
FGM isCGM     Flash glucose monitoring

Örebro University Hospital     Örebro University Hospital MC1  Medical Clinic 1

 

1.        INTRODUCTION

1.1        Type 1 diabetes mellitus

Type 1 diabetes mellitus (T1DM) is a chronic metabolic disease characterized by an insulin deficiency resulting from destruction of insulin-producing beta cells in the islets of Langerhans [1, 2]. The destruction of autoimmune genes occurs when self-reactive autoantibodies target insulin-producing beta cells or the insulin within them. The course is progressive and results in complete insulin deficiency [2].

Insulin is necessary for glucose from the body’s cells to be absorbed into the blood. In a healthy body, glucose is the most important stimulus for insulin synthesis. If the producing cells are destroyed, these cannot respond to stimuli. In the event of insulin deficiency, glucose is not absorbed by the tissue and organs. Rather, glucose remains in the blood and causes hyperglycemia, potentially with fatal consequences. Supply of exogenous insulin is vital for people with T1DM [1].

The disease often develops in childhood with onset during the teenage years, but may also occur at an adult age. In many cases, the disease may initially be asymptomatic and symptoms do not appear until more than 90% of the beta cells have been destroyed. Typical symptoms at onset are large quantities of urine, increase in thirst, and in more serious cases, acid poisoning. This is a complication of glucose deficiency in the liver leading to ketogenesis and observed from ketone bodies from fatty acids, which may be used as an alternativenenergy substrate. Ketogenesis may become overpowering and exceed the metabolism. If the body becomes dehydrated, or becomes dehydrated due to adrenalin rushes during stress, the created ketone bodies cannot be excreted through urine, but rather accumulate in the body and cause acid poisoning. Typical symptoms for this condition are nausea, vomiting and abdominal pain. Without insulin treatment, acid poisoning will result in death [1].

In the event of high HbA1c over a long period or T1DM does not receive adequate treatment, hyperglycemia has harmful effects on the body and causes long-term complications, primarily on the heart, vessels, kidneys, eyes and nerves [3]. The most common complications of long-term hyperglycemia are macrovascular complications, including atherosclerosis, which puts people with poorer control over diabetes at greater risk of developing a myocardial infarction and cardiovascular diseases than people without diabetes [1]. Atherosclerosis develops through production of free acid radicals and advanced glycosylated end products (AGEs), as well as activation of protein kinase C and inflammatory signal paths [4]. Hyperglycemia may also have microvascular complications by causing a thickening of the base membrane, making the capillaries more permeable than normal. This has the clearest effects on organs dependent upon functioning capillaries in the functional units, primarily in the kidney nephron with a risk for kidney failure or in retinae with a risk for blindness [1]. Diabetic retinopathy is globally the most common cause for this in adults of a working age [5]. The metabolic disease is also the most common cause for peripheral neuropathy, which occurs when the vessel changes contribute to ischemic damage to Schwann cells or the nerves themselves, and for metabolic causes of hyperglycemia, where reactive acid radicals form [1].

1.2        HbA1c

When glucose is present in the blood, a reaction occurs with hemoglobin. The reaction is a glycosylation, where sugar molecules are irreversibly added to the protein’s amino groups. While the glucose level in the blood may fluctuate as a result of food intake and exercise, for example, HbA1c remains relatively stable for a long period, which is a result of the erythrocyte lifetime of approximately 120 days. It can therefore be presumed, the measured HbA1c value is directly proportional to the blood glucose concentration over the past six to eight weeks in patients with a normal lifetime for erythrocytes [6].

The HbA1c value is stated as mmol/mol, which involves the proportion of glycosylated hemoglobin in the blood. For a person without diabetes ages 49 and below, the reference value is 27-42 mmol/mol, and for ages 50 and above, 31-46 mmol/mol. For a person with diabetes, the general goal is for HbA1c to be less than 52 mmol/mol, but this depends upon the individual life situation [7].

There is good scientific documentation that an increase in HbA1c directly increases the risk for serious complications of the disease.

Studies among patients with HbA1c >80 mmol/mol, demonstrate more than half were treated for serious eye changes. Every fifth patient had developed serious kidney damage.

No such complications developed in the patients with well-regulated HbA1c, despite a long-term Type 1 diabetes mellitus [8]. For values above 48 mmol/mol, the risk of microvascular complications begins to increase slowly. For values above 58-60 mmol/mol, there is a successive risk increase. For extremely high values, the risk appears to increase exponentially [9].

Conclusions can be drawn from this value regarding glycemic control, and together with the blood sugar value, can help form a basis for treatment recommendations. This makes it possible to reduce the risk for complications associated with high values [6].

The value should be verified, as monitoring uncertainties and variations may occur. For example, iron deficiency anemia may show a falsely high HbA1c value [10], and certain hemoglobin pathologies, such as thalassemia minor, may show a falsely low HbA1c value. The value may also vary widely between individuals as a result of different capabilities of hemoglobin glycation [9]. An infection or other stress on the body, such as anxiety, may cause a falsely high HbA1c value [11].

1.3        Insulin treatment

People treat their diabetes based on their HbA1c and blood sugar values. There are two treatment options, one being injection with an insulin pen and the other an insulin pump. For treatment with an insulin pen, the pen is set to inject the correct amount adapted to the blood sugar level, then injected into the thigh or stomach. Insulin pens are available in disposable type, which are discarded after use, or a multi-use type, which is reloaded with a new ampoule when the insulin runs out. For treatment with an insulin pump, the pump is worn on a belt, for example, from which insulin is administered into the body through a plastic tube and flows into a needle inserted in the stomach. Another variant of an insulin pump can be controlled by remote control and is inserted into the subcutaneous fat with a needle. The big difference between the treatment methods is, the pump injects small amounts of insulin 24 hours a day, while the treatment with the insulin pen involves intermittent injections as needed. Consequently, the pump may be the best alternative for people who have a difficult time sensing blood sugar swings, while the pen may be the best alternative for people experiencing better control over their blood sugar and sense these swings more clearly [12]. 

1.4        Self-monitoring

 Monitoring the glucose level in some manner is a prerequisite for knowing the quantity of insulin to be administered. Various methods are available now, and the most recent among these is flash glucose monitoring (FGM) with intermittent scanning, isCGM. The other two methods for glucose monitoring are self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) with real-time values, rtCGM.

1.4.1          SMBG

Self-monitoring of blood glucose (SMBG) is the traditional and most commonly used method for monitoring glucose content in the blood for people with diabetes [13]. The system facilitates insulin treatment with the goal of preventing hyperglycemia, while avoiding hypoglycemia [14].

The method involves the person pricking themselves in the finger with a lancet to collect capillary blood. There are two parts to this process: an enzymatic reaction, which takes place on a disposable strip, or a reaction cuvette, and a detector. In the enzymatic portion of the process, the blood reacts with enzyme (glucose oxidase, glucose hydrogenase and hexokinase), and then creates a product, which the detector is able to detect [15]. Since SMBG requires the person prick themselves in the finger every day, the method is deemed to be more difficult and uncomfortable over the long-term, compared to sensor-based techniques [14].

1.4.2          rtCGM

Development of sensors with properties to monitor glucose levels in interstitial fluid has made a system for continuous glucose monitoring in the blood possible. Implanting a subcutaneous electrode allows tissue glucose to be monitored [13], which corresponds well with blood glucose. This spares the person from pricking themselves in the fingers.

The subcutaneous electrode registers power strength, which correlates with the glucose content in the interstitial fluid. The sensor can then convert this to a value for glucose content in the blood and send this information to a sensor on the skin, which in turn sends information to a monitor [13].

This method provides continuous glucose level monitoring. The sensor itself can detect glucose values, which are too high, too low or whether a rapid change occurs, which may lead to such values [13]. The sensor has an alarm function, which can alert the person wearing the sensor, should the glucose value be outside of the desired range. This may be valuable for people with diabetes, who have a difficult sensing when the glucose level changes (so-called hypoglycemic unawareness), and in that manner be reminded or awakened by this. With continuous monitoring, a history of glucose levels during the past hours, trends in the glucose level and changes expected in the near future are displayed on the monitor [6]. The method also provides an opportunity for the person to learn about the effects of nutrition and physical activity on their individual glucose level [16].

1.4.3          FGM, now the most common term isFGM

Flash glucose monitoring (FGM) is very similar to CGM, yet there are some differences. Both have a subcutaneous sensor electrode, which sends information to a monitor [13]. The sensors for FGM are placed on the upper arm, are calibrated at the factory and have a lifetime of 14 days, after which the sensor is replaced [17]. This means the person does not have to prick themselves in the finger for calibration.

While CGM continuously shows the current value of tissue glucose, FGM needs to be scanned with the monitor to show the glucose value [18]. This can therefore be considered as a substitute for SMBG, and according to a study, prompts people with Type 1 diabetes mellitus monitor their glucose value more frequently than with the use of SMBG [19]. In addition to avoiding pain, FGM displays the glucose value in real time together with an eight-hour history, including a trend arrow showing the direction the glucose levels are going [5].

From a financial standpoint, FGM is clearly cheaper than CGM, yet both are more expensive than SMBG [16, 20].

1.4.3.1 Freestyle Libre

Glucose monitoring in the form of isCGM arrived in Sweden during the autumn of 2014, with Freestyle Libre being the first glucose monitor of this type on the market [20]. As a result of a high and rapidly growing demand, the national program council for diabetes compiled a care program with guidelines and indications for the use of Freestyle Libre in adults with T1DM. For prescribing Freestyle Libre, these indications are listed below (Table 1) and followed by MM1, Örebro University Hospital.

2.        PURPOSE, QUESTION AND HYPOTHESIS

 2.1        Purpose

To investigate further the positive trend observed after 12 months of Freestyle Libre use in patients with Type 1 diabetes mellitus at MM1, Örebro University Hospital, the study continued for another 30 months. 

2.2        Question

Does the positive effect of HbA1c with the use of Freestyle Libre persist in people with T1DM for another 30 months after the first examination? Which patient characteristics (age, gender, treatment and start HbA1c value) have an effect on HbA1c value levels with the use of Freestyle Libre?

 2.3        Hypothesis

The hypothesis is the positive effect observed on HbA1c after 12 months use of Freestyle Libre in people with T1DM also persists in all patient groups for another 30 months after the first examination.

3.        MATERIALS AND METHOD

3.1        Study design

The study has been conducted as a retrospective medical records study at MC1, Örebro University Hospital. In a prior study from January 2017, 364 medical records were reviewed for people with T1DM using Freestyle Libre for glucose monitoring to evaluate the effect on HbA1c. These medical records were reviewed once again for a follow-up. The method was selected for the purpose of gathering data required to answer the questionnaire. 

3.2        Study population

 Approximately 1,400 patients with T1DM were treated at MM1, Örebro University Hospital. In January 2017, 364 of these patients used FGM to control their blood sugar. 164 of these patients used the monitor for at least 12 months, and were therefore selected for review.

For this study, 223 (62.3%) of these patients were selected, as they fulfilled inclusion criteria for the follow-up study, which was having used Freestyle Libre for minimum 36 months and having provided HbA1c values to MC1 during this period. 141 patients (37.7%) were excluded for periods of use that were too brief, long pauses in the treatment or death

The patients in the study included patients sorted into groups according to patient characteristics for the purpose of detecting any differences in HbA1c between different patient groups during the use of Freestyle Libre. These patient characteristics were gender, age, HbA1c value prior to the start of Freestyle Libre and treatment type (insulin pump or insulin pen).

The mean age and HbA1c values prior to the start of Freestyle Libre were calculated to separate the groups into relatively high and low values respectively.

3.3        Data collection

All patients with T1DM treated at MC1 are registered in the National Diabetes Register (NDR) www.ndr.nu. From this register, 364 patients were selected from a prior study conducted for the purpose of studying the effect of HbA1c after 12 months of Freestyle Libre use. Medical records for each of these 364 patients were reviewed once again, in a structured manner, in the “Clinical Portal” after authorization was granted. A search was performed according to the date for the start of Freestyle Libre use. Next a search was performed for the most recently measured HbA1c value prior to the start, thereafter at intervals of approximately six months (±3 months). The subjects with these measured values and who had died during the period met the inclusion criteria and were therefore included in the study. The study values were documented in Microsoft Excel. 

3.4        Data processing and analysis

After reviewing and gathering of HbA1c values for the 223 study subjects, all HbA1c values were compared. The mean value for HbA1c prior to the start was calculated as well as the mean HbA1c value which was registered every six months (±3 months). On this basis, a line chart was produced from which a trend can be presented. The same method was applied for the various groups to produce a graph presenting a trend in HbA1c values between the different patient characteristics.

The mean value for age and HbA1c value prior to the start of Freestyle Libre use was calculated to divide the groups into relatively high and low values respectively, depending upon whether the values were above or below the mean value.

3.5       Ethical considerations

A review of medical records was required to conduct this study. Authorization was granted by the operations manager at Medical Clinic 1 at Örebro University Hospital, supervisors and the course coordinator.

The personal data was handled very carefully by never storing the personal identification number and data in the same device. Before starting the medical record review, all personal identification numbers were deidentified through coding, making the tracing of a personal identification number to data impossible without having joint access to the document. Lists with personal identification numbers were never transferred to personal computers, but stored on an external device.

The study contributes by improving the prerequisites for patients with diabetes to best control their blood sugar and receive support for insulin treatment. 

4.     RESULT

4.1 Effect on HbA1c

The mean value for the 223 study subjects was 66.1 mmol/mol (SD±15.2) prior to the start. After 42 months of glucose monitor use, the mean value was 60.1 mmol/mol, or a reduction of 6.0 mmol/mol (see Figure 2, Table 3). This corresponds to a percentage reduction of 9.1% from the start HbA1c value. The results are shown below in Figure

Gender division

For the 102 women included in the study, the mean HbA1c value was 68.5 (SD±16.9) mmol/mol prior to the start.

For the 121 men included in the study, the mean value was 64.1 (SD±13.4) mmol/mol prior to the start (see Figure 3, Table 4). After 42 months of Freestyle Libre use, the mean value for women was 59.1 (SD±12.6) mmol/mol, and for men 60.9 (SD±12.6) mmol/mol (see Figure 3, Table 4).

This means a reduction in the HbA1c value of 9.4 mmol/mol (13.7% from the start value) and 3.2 mmol/mol (5.0% from the start value) respectively.

Insulin pen treatment method

For the group treated with the insulin pen method, the mean HbA1c value was 66.1 (SD±14.9) mmol/mol prior to start. For further division according to gender, the mean value for women was 68.2 (SD±16.9) mmol/mol and 64.5 (SD±13.1) mmol/mol for men respectively (see Figure 4, Table 5). 

After 42 months of Freestyle Libre use, the mean value for the entire group was 61.8 (SD±12.0) mmol/mol, which means a reduction of 4.3 mmol/mol or 6.5% from the start value.

After 42 months, women showed a value of 59.8 (SD±11.8) mmol/mol, are reduction of 8.4 mmol/mol or 12.3% from the start value. Men showed a value of 63.1 (SD±12.0) mmol/mol, corresponding to a reduction of 1.4 mmol/mol or 2.2% from the start value.

Insulin pump treatment method

The mean HbA1c value for the group undergoing insulin pump treatment was 66.1 (SD±15.7) mmol/mol prior to start. Men in the group had a mean value of 63.3 (SD±14.0) mmol/mol and women 69.0 (SD±17.1) mmol/mol (see Figure 5, Table 6).

After 42 months of Freestyle Libre use, the mean value for for entire group was 57.4 (SD±13.1) was mmol/mol, for men 56.6 (SD±12.7) mmol/mol and for women 58.0 (SD±13.8) mmol/mol. In all, the group showed a reduction of 8.7 mmol/ mol or 13.2% from the start value.

In the male portion of the group, HbA1c was reduced by 6.7 mmol/mol or 10.6% from the start value, and in the female portion of the group, 11.0 mmol/mol or 15.9% from the start value.

Age

The mean HbA1c value for the portion of the group younger than the mean age (46 years of age) was 66.7 (SD±16.1) mmol/mol prior to start (see Figure 6, Table 7). After 42 months of use, the mean value was 60.0 (SD±13.1) mmol/mol, corresponding to a reduction of 6.7 mmol/mol or 10% from the start value. In the group older than the mean age, the mean value was 65.6 (SD±14.0) mmol/mol and after 42 months of Freestyle Libre use, the mean value was 60.2 (SD±12.1) mmol/mol, corresponding to a reduction in HbA1c value of 5.4 mmol/mol or 8.3% from the start value.

Start value for HbA1c

In the group with HbA1c above the mean value, the mean value was 78.0 (SD±11.8) mmol/mol prior to start (see Figure 7, Table 8). After 42 months of Freestyle Libre use, the mean HbA1c value for the entire group was 66.7 (SD±10.5) mmol/mol, corresponding to a reduction of 11.3 mmol/mol or 16.9% from the start value.

The group having an initial HbA1c value below the mean value instead, started with a mean value of 54.0 (SD±6.6) mmol/mol, and after 42 months of FGM use, showed a mean value of 53.1 (SD±10.8) mmol/mol. This corresponds to a reduction of 0,9 mmol/mol or 1.7% from the start value.

The results are presented below in figures and tables for the predetermined subgroups. 

5.        DISCUSSION

 5.1        Discussion

The purpose of the study was to investigate the long-term effect on HbA1c in people with Type 1 diabetes mellitus who use Freestyle Libre. The study is a follow-up on a previous study, which showed a positive effect on HbA1c after 12 months use of the glucose monitor. The hypothesis was the positive effect would be sustained and provide a stable HbA1c value below the start value.

The result shows the long-term effect on HbA1c is positive for glucose monitoring with Freestyle Libre. This means the glucose monitor has a positive effect on metabolic control in people with T1DM. The reduction in HbA1c shown after the start of Freestyle Libre has clinical significance through a long-term reduction in the risk of serious complications and therefore provides health financial motivation. 

The patient group showing the greatest reduction in HbA1c was the group, which had a relatively high initial value before using the monitor, while the group with a relatively low HbA1c initial value below the mean value showed the least effect of all groups. Since the patients continue to use the method, an improvement in patient quality of life with FGM may be presumed. Although we did not look at quality of life in this study, other studies have demonstrated this improvement [17]. 

A clear difference in the effect on HbA1c was observable between men and women. For women, the HbA1c value dropped by 13.7% from the start value. For men, the HbA1c value dropped by 5.0% from the start value. To divide these groups further, the women undergoing insulin pump treatment showed the greatest reduction, and the men undergoing insulin pen treatment showed the least reduction. The entire group undergoing insulin pump treatment showed a greater reduction in the HbA1c value than the entire group undergoing insulin pen treatment (13.2% and 6.5% respectively from the start value). As the group undergoing pump treatment often has a type diabetes which is difficult to diagnose, this addition of steady, ongoing administration appears to be a way of counteracting certain blood sugar spikes with insulin, which this group might not have detected without Freestyle Libre. 

With the knowledge of the group with relatively high HbA1c values prior to the start having showed a far greater reduction than the group with low values, the difference can be seen between women and men, and between the insulin pump and pen treatments from a different perspective. The female group, as the group with the insulin pump, had a higher mean HbA1c value before this group began FGM than the respective group of men with insulin pens. Please note: In drawing a conclusion, the group with high HbA1c values had the best effect from the monitor and was probably aware their values were associated with a high risk for serious complications and had heard about the importance of dropping their values on several occasions. Receiving a new monitor may give them an opportunity to start again, and thereby have an effect on the motivation and result. The group with relatively low HbA1c values likely did not have the same motivation to reduce their values, because the values were not as seriously associated with these complications. This may also have played a role in the group consisting of men or people with diabetes undergoing insulin pen treatment. Moreover

Other factors may affect the result and are important to note when drawing a conclusion and treatment is initiated based on HbA1c. As discussed in the introduction, an infection, stress [11] or variations in the hemoglobin may contribute to generating falsely high or low HbA1c values. The ability for hemoglobin glycation varies individually, and has also proven to increase with advancing age [9]. This may affect the result within the group, which is divided into relatively older and younger patients. The younger half showed an HbA1c reduction of 10.0% from the start value, and the older half a reduction of 8.3% from the start value. 

The younger half had a somewhat higher HbA1c value than the older (66.7 mmol/mol and 65.6 mmol/mol respectively). This is a slight difference, which cannot be presumed to be due to a difference in motivation as a result from the start value as discussed for previous groups. Another perspective to consider in this group could be the ability to adapt to new technical products and use these in everyday life, which often comes more naturally to younger generations than older.

It would be interesting to study the number of times per day a person scans their glucose value, and the influential effect on HbA1c with Freestyle Libre use. This has not been included in this study.

After FGM became available in Belgium in January 2016, a study was conducted on people with T1DM using FGM for glucose monitoring for 12 months to determine any effect on HbA1c. This study also took into consideration the number of scans the subjects performed daily to see whether this correlates to the effect on HbA1c. The conclusion drawn in this study is a negative correlation between the number of scans per day and effect on HbA1c.

As with this study regarding the effect on HbA1c, the study demonstrated a positive effect on HbA1c throughout the study population after 12 months of Freestyle Libre use [21].

Another study from 2017 examines the effect of Freestyle Libre on health-related quality of life and fear of hypoglycemia in children and adolescents with T1DM. The result showed frequent use of the glucose monitor not only reduced the HbA1c value, but also the anxiety and fear of hypoglycemia among the study participants. In general, the study participants experienced an improved quality of life after beginning the use of Freestyle Libre than before. Compared to SMGB, the study also demonstrated FGM increased the frequency of self-monitoring. In this study, the conclusion was drawn that this contributed to improved metabolic control [19]. This is contrary to the study mentioned previously, which demonstrated a negative correlation between the number of scans per day and metabolic control.

A study from 2017 studied the effect on HbA1c in subjects with Type 1 diabetes mellitus with the introduction and FGM for a period of 16 weeks. As in this study, the result of the study demonstrates a significant reduction in the HbA1c value, and the group showing the greatest effect from the glucose monitor was women. The study also took into consideration patient quality of life, measured on a ”Diabetes Distress Scale”. The scale showed a significant reduction, meaning the people experienced an improved quality of life [17].

As mentioned above, this study demonstrated a reduction in the HbA1c value, which was also demonstrated in other studies, but was conducted over a shorter timeframe. One important strength of this study is no other study has been conducted with such a long follow-up period.

The change that takes place in HbA1c after the start of FGM therefore appears to be long-term. The results are very interesting, because these demonstrate the reduction that takes place in the beginning is neither incidental nor stems from the “novelty effect” of a new technical product.

The results demonstrate FGM is a sustainable and effective manner of measuring glucose level, reducing HbA1c and facilitating good metabolic control in people with Type 1 diabetes mellitus over the long term.

5.2        Limitations

 One weakness of the study is the difficulty in being certain the patients have used the monitor consistently during this period. Another weakness is the reliability of HbA1c results being correct on each monitoring occasion. For example, an iron deficiency anemia may show a falsely high HbA1c value [10] or unusual genetic forms on the hemoglobin beta chain [22]. An infection or other stress on the body, such as anxiety, may also cause a falsely high HbA1c value [11]. As the people self-monitor in this study, the risk for these types of sources for errors is reduced.

Further follow-up on the study after 10 years, for example, would be interesting to verify the positive effect on HbA1c demonstrated in previous studies, as well as studies on how nausea, fear of hypoglycemia or quality of life are affected in people with T1DM using Freestyle Libre over the long term. 

6.        FINAL CONCLUSION

The study demonstrates the positive trend observed after 12 months of Freestyle Libre use is long-term up to 3,5 years. As demonstrated in previous studies, Freestyle Libre can help people with T1DM maintain good metabolic control. The group with a relatively high HbA1c value (>65 mmol/mol) prior to monitor use had the best effect.

The group with an already lower HbA1c value (<65 mmol/mol) prior to monitor use did experience a smaller positive HbA1c effect from Freestyle Libre with respect to HbA1c, but experienced a significant improvement in quality of life or other benefits. This was not investigated in this study. 

The study demonstrates women have a greater effect from Freestyle Libre than men. Subjects undergoing insulin pump treatment have a greater effect than subjects undergoing insulin pen treatment.

7.        AUTHOR WISHES TO THANK

Many thanks to Erik Schwarcz at Medical Clinic 1, Örebro University Hospital, for your guidance throughout the project. I appreciate you making yourself available, your quick responses and clear guidance. You made me feel welcome among the staff at MC1 from the beginning, which made conducting the study an enjoyable experience!

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Diabetic News June 24 2019
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