The majority of people with type 1 diabetes and multiple daily insulin injection benefit from using Continuous Glucose Monitoring: An analysis based on the GOLD randomised trial (GOLD-5)
Ólafsdóttir AF, PgD, Bolinder J, MD, Ph3, Heise T, MD, Polonsky W, PhD, Ekelund M, MD, PhD, Wijkman M, MD PhD, Pivodic A, MSc, Ahlén E MD, Schwarcz E, MD, PhD, Nyström T, MD, PhD, Hellman J, MD, Hirsch IB, MD, Lind M, MD, PhD
Denna rapport är baserad på data från 142 patienter i Gold studien publicerad 2017.
Målet var att identifiera personer som uppnådde minst 4,7 mmol/mol förbättring i HbA1c och de som uppnådde minst 20 minuters/dygn och 30 minuters/dygn förbättring av tid i hypoglykemi när de bytte från kapillära mätningar till CGM.
Studien analyserar även vilka baseline variabler är associerade med dessa förbättringar.
Gold studien var en multi-center randomiserad studie med cross-over design
Vuxna patienter med typ 1 diabetes, behandlade med flerdos insulin, randomiserades till att börja med CGM eller kapillära mätningar i 26 veckor, därefter hade de 17 veckor wash-out period innan de bytte behandling.
att mindre förbättring av HbA1c var relaterad till mer förbättring av tid i hypoglykemi.
• Nästan hälften (47%) av studiedeltagarna förbättrade sina HbA1c värden med 4,7 mmol/mol och
• lika många förbättrade sin tid i hypoglykemi med 20 min/dygn.
• 78% förbättrade sin HbA1c eller tid i hypoglykemi
• men enbart 14% förbättrade både sitt HbA1c med minst 4,7 mmol/mol eller sin tid i hypoglykemi med 20 min/dygn.
De baseline variabler som var relaterade till förbättrad HbA1c var:
• Högre HbA1c,
• mindre tid procentuellt med blodsocker under 3,0 mmol/l och 3,9 mmol/l,
• lägre coefficient of variation (CV) och
• mer tid procentuellt med blodsocker över 13,9 mmol/l.
De baseline variabler som var relaterade till förbättrad tid i hypoglykemi var:
• mer tid procentuellt med glukosvärden under 3,0 mmol/l,
• högre CV, och
• de som kände sig tryggare angående hypoglykemier.
Studien visar att de flesta som byter från kapillära mätningar till CGM upplever en förbättring av sina glukosvärden men vissa upplever en förbättring av sitt HbA1c och andra minskar sin tid i hypoglykemi.
Autoreferat Arndís Ólafsdóttir, doktorand, diabetessjuksköterska, Göteborgs Universitet, Diabetesmottagningen, NÄL, Uddevalla sjukhus
The majority of people with type 1 diabetes and multiple daily insulin injections benefit from using continuous glucose monitoring: An analysis based on the GOLD randomized trial (GOLD‐5)First published: 16 November 2020
To identify responders to continuous glucose monitoring (CGM) in relation to reductions in HbA1c and percentage of time spent in hypoglycaemia after initiation of CGM for individuals with type 1 diabetes treated with multiple daily insulin injections.
Materials and Methods
We analysed data from 142 participants in the GOLD randomized clinical trial. We evaluated how many lowered their HbA1c by more than 0.4% (>4.7 mmol/mol) or decreased the time spent in hypoglycaemia over 24 hours by more than 20 or 30 minutes, and which baseline variables were associated with those improvements.
Lower reduction of HbA1c was associated with greater reduction of hypoglycaemia (r = −0.52; P < .0001). During CGM, 47% of participants lowered their HbA1c values by more than 0.4% (>4.7 mmol/mol) than with self‐measurement of blood glucose, and 47% decreased the time spent in hypoglycaemia by more than 20 minutes over 24 hours. Overall, 78% either reduced their HbA1c by more than 0.4% (>4.7 mmol/mol) or the time spent in hypoglycaemia by more than 20 minutes over 24 hours, but only 14% improved both. Higher HbA1c, a lower percentage of time at less than 3.0 or 3.9 mmol/L, a lower coefficient of variation (CV) and a higher percentage of time above 13.9 mmol/L (P = .016) were associated with greater HbA1c reduction during CGM. The variables associated with a greater reduction of time in hypoglycaemia were female sex, greater time with glucose levels at less than 3.0 mmol/L, higher CV, and higher hypoglycaemia confidence as evaluated by a hypoglycaemic confidence questionnaire.
The majority of people with type 1 diabetes managed by multiple daily insulin injections benefit from CGM; some experienced reduced HbA1c while others reduced the time spent in hypoglycaemia. These factors need to be considered by healthcare professionals and decision‐makers for reimbursement and diabetes guidelines.
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Good glycaemic control is important for reducing the risk of long‐term complications in type 1 diabetes, including microvascular and macrovascular complications.1-3 It has also been shown to reduce excess risk of mortality.4, 5Many people with type 1 diabetes struggle to keep blood glucose at acceptable levels while avoiding periods of hypoglycaemia.1 Hypoglycaemia, if left untreated, can lead to loss of consciousness, seizures and, in the worst cases, death.6 It can also contribute to falls, injuries and motor vehicle accidents. Frequent periods of hypoglycaemia have also been shown to negatively influence quality of life.6
The use of continuous glucose monitoring (CGM) has been shown to reduce both HbA1c levels and the rate of hypoglycaemia for patients using multiple daily insulin injections (MDI) and subcutaneous insulin infusion.7-9
It is not fully understood how the effect of CGM in type 1 diabetes varies among CGM users and what factors may be related to successful treatment. Such knowledge is essential for resolving treatment barriers and improving the benefits of CGM use, as well as from a health‐economical perspective. Earlier research found that people aged 25 years or older and those with frequent self‐measurement of blood glucose (SMBG) used their CGM devices more frequently after 6 months of CGM use than younger people or those who performed less SMBG.10 It is also of interest to understand whether there are certain patient groups that respond with an overall beneficial effect of CGM, that is, in both reducing HbA1c and time in hypoglycaemia, whereas others are non‐responders. Furthermore, it may be of interest to determine whether the opposite pattern exists, where certain patient groups reduce HbA1c and others benefit with respect to time in hypoglycaemia.
The aim of this study was to identify responders to CGM therapy in relation to reductions in HbA1c and percentage of time in hypoglycaemia after initiation of CGM compared with SMBG among people with type 1 diabetes treated with MDI.
This study shows that the majority of people with type 1 diabetes treated with MDI and using CGM benefitted from the system. Almost half of users experienced an HbA1c benefit and equally as many decreased their time in hypoglycaemia and improved their TIR. Approximately 80% showed improvement in HbA1c, TIR or hypoglycaemia, but only 13.8% and 10.6% experienced an effect on time in hypoglycaemia and HbA1c or time in hypoglycaemia and TIR, respectively.
The baseline variables associated with greater reduction of HbA1c when using CGM were higher baseline HbA1c, less time with glucose levels below 3.9 mmol/L (<70 mg/dL) and 3.0 mmol/L (<54 mg/dL), lower CV, and greater time with glucose levels above 13.9 mmol/L (>250 mg/dL). The main predictive variable was baseline HbA1c. The participants who experienced the greatest effect in reducing time in hypoglycaemia were women, those with more time with blood glucose below 3.0 mmol/L (<54 mg/dL), greater CV, people with more confidence about their hypoglycaemias at baseline and those with greater diabetes duration and lower C‐peptide. The main predictive variables were time in hypoglycaemia and the hypoglycaemia confidence score at baseline.
Previous studies have found that CGM reduces HbA1c and can decrease the amount of time spent in hypoglycaemia.7, 9, 15 The GOLD study showed a decrease of 0.43% (4.7 mmol/mol), the DIAMOND study a decrease of 0.6%, and the Switch study a decrease of 0.41% (4.4 mmol/mol); both the GOLD and DIAMOND studies included patients treated with MDI while the Switch study included patients with insulin pumps. For time in hypoglycaemia (<3.9 mmol/L [<70 mg/dL]), the reductions were 29, 20 and 12 minutes, respectively.7, 9, 15Minimal data are available on how different baseline factors are associated with glycaemic improvements during CGM use, but the DIAMOND study did not find any interaction between baseline HbA1c and change in HbA1c during the study; however, in a post hoc analysis of the DIAMOND data, it was shown that the greater the HbA1c at baseline then the greater the reduction after 24 weeks of CGM use.7, 16 Semi‐closed loop and sensor‐augmented pumps probably show an even greater effect in reducing HbA1c and time in hypoglycaemia.17
Earlier, it was shown that psychosocial factors were associated with improved glycaemic control and decreased time spent in hypoglycaemia. People who were more analytical in their approach, could better cope with frustration, and had the support of their loved ones, had better results after initiating CGM.18 It has also been shown that those with greater compliance (i.e. they wore their CGM devices more frequently) had a greater improvement in glycaemic control.10, 19
To our knowledge there have been no previous analyses based on randomized trials that have evaluated which variables are associated with the effect on time in hypoglycaemia by CGM in people with type 1 diabetes treated with MDI. In the current study we show that CGM users seldom benefit both by decreasing their time spent in hypoglycaemia and HbA1c or TIR, but do appear to experience benefits within one of these areas. Few patients improved both HbA1c and time in hypoglycaemia or TIR and time in hypoglycaemia when using CGM. In this study we analysed the interaction of different baseline variables with regard to both improved hypoglycaemia for values below 3.0 mmol/L (<54 mg/dL) and 3.9 mmol/L (<70 mg/dL). Both of these hypoglycaemic cut‐offs interacted with the same baseline variables. We found that people with lower C‐peptide levels improved their time in hypoglycaemia by more than those with higher C‐peptide levels, probably because people with higher C‐peptide levels experience less hypoglycaemia and therefore probably benefit less from CGM.
The effect to which HbA1c varies for different patient groups has not been well studied, but in the current study we have shown that people with higher HbA1c experience a greater reduction when CGM is introduced. This represents a strong argument for providing CGM devices to patients with high HbA1c levels because they may be able to avoid diabetes complications through subsequent improvements in HbA1c.
A CGM device gives continuous feedback to the user regarding current glucose values and trends, and leads to increased awareness. The possibility of alarms providing warnings about values being too high or low enables users to react quickly and thereby improves their overall glucose control. It is important to understand that it is not just those with very high HbA1c or very low HbA1c who experience the benefits of CGM use, but also those with moderate glycaemic control (HbA1c ~7.92%‐8.83% [~63‐73 mmol/mol]) can experience both decreased HbA1c and a reduction in time in hypoglycaemia, and even improved TIR.
4.3 Frequency of SMBG
Different reimbursement guidelines frequently state that patients must perform at least four SMBG tests to be prescribed CGM. It is worth stating that this study found no interaction between improved HbA1c and time in hypoglycaemia in relation to the number of SMBG tests taken before starting CGM.
This study implies that the majority of people with type 1 diabetes and MDI benefit from using CGM devices. It is important to view all patients with type 1 diabetes as potential candidates for CGM, but to also recognize that they might benefit in different ways. Patients with moderate glycaemic control who have problems with too much time spent in hypoglycaemia may not substantially improve their HbA1c after CGM initiation, but will probably substantially decrease their time in hypoglycaemia, which in turn decreases the risk of developing hypoglycaemia unawareness.20, 21 The study also shows that higher hypoglycaemia confidence was a predictor of greater reduction of time in hypoglycaemia; the current study cannot explain this relationship but it needs to be examined in future research.
The impression given by healthcare professionals is that it is mainly those patients who can improve their HbA1c who are prioritized to receive CGM treatment, but this study shows that an equal number may improve their time spent in hypoglycaemia. Hypoglycaemia is related to an increased risk of severe hypoglycaemia and cardiovascular events and reduced quality of life.22-24 It is important to view all patients as possible candidates for CGM to improve HbA1c, TIR or time in hypoglycaemia.
A limitation of the current study is that treatment could not be blinded, thereby participants were aware of the intervention. This may have influenced the effects of treatment to some extent. In addition, the current results are restricted to adults with an HbA1c greater than 58 mmol/mol (>7.5%). These analyses were not the original endpoint of the Gold study, therefore they should be viewed as exploratory. Another limitation was that there was no possibility of evaluating how patients used their own data uploads to improve their glucose management.
A strength of the study is its randomized, cross‐over design, where each participant acted as their own control between the two treatments, and that a masked CGM was used during the SMBG period, which enabled more efficient analysis of glycaemic ranges.
In conclusion, the majority of adults with type 1 diabetes treated with MDI experience benefits when initiating treatment with CGM, and these benefits are equally divided between improvements in HbA1c and time spent in hypoglycaemia. There is no association between frequency of SMBG and these improvements. Patients who have a longer time in hypoglycaemia experience greater effects in reducing their time in hypoglycaemia, while patients with a shorter time in hypoglycaemia and higher HbA1c levels primarily benefit through HbA1c reduction. It is important that healthcare professionals and decision‐makers for reimbursement and diabetes guidelines consider these factors and that there are no clear factors predictive of whom will respond to CGM monitoring or not.
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