Effects of the Artificial Pancreas on Glucose Control, Cardiac Arrhythmia Risk and Sleep in Older People with Type 1 Diabetes
Lead Research Organisation:
University of Manchester
Department Name: School of Medical Sciences
Abstract
Research questions: This proposal will help me to answer three key research questions: In older people with type 1 diabetes, does the artificial pancreas: a) improve glucose control, b) reduce arrhythmia risk and c) improve sleep parameters when compared to usual care?
Background: Type 1 diabetes (T1D) is a life-long condition, with affected individuals requiring daily insulin treatment to survive and avoid serious complications. As life expectancy of people with T1D increases, the number of older people living with the condition grows. Recommended treatment goals for specific age groups with T1D have been published, but achieving these remains challenging due to the ever-present risk of low blood glucose levels (hypoglycaemia). In addition, older people with diabetes are often disadvantaged due to unequal access to new treatments and technologies. Older people with type 1 diabetes often face unique challenges and have a higher risk of severe hypoglycaemia (extremely low blood glucose leading to loss of consciousness)due to loss of usual hypoglycaemia symptoms such as feeling hungry or anxious, which in some cases, can be fatal.
Some researchers have speculated that frequent and severe hypoglycaemia can make the heart beat too fast or irregularly, which can lead to death. A number of studies have tried to prove a link between the two. However until recently, simultaneous continuous monitoring of glucose levels and heart rhythm have been rarely performed, especially in older people with T1D. Compared to younger age groups, a disproportionate number of older people suffer from severe hypoglycaemia, which is a possible mechanism of sudden or heart-related deaths in older people with T1D.
Several studies have shown higher rates of sleep disturbance (poor sleep quality and shorter sleep duration) in people with T1D compared to those without T1D, which can have negative effects on glucose levels and psychosocial health. The impact of sleep disturbance in older people with T1D, specifically in relation to self-management and adherence behaviours, is unknown.
Current continuous glucose monitoring and insulin pump devices do not automatically alter insulin delivery or insulin dose, and still require the person to make self-adjustments to their insulin. This may lead to potentially high or low sugar levels, and its associated risks. In contrast, the artificial pancreas automatically controls insulin delivery, which is carefully altered by computer software according to minute-to-minute changes in sugar levels detected by the continuous glucose monitoring. However, access to this technology designed to reduce the burden of diabetes remains limited in older people. Evaluation of new treatment strategies to improve health outcomes in this under-served population is needed.
Research environment: In partnership with Manchester Heart Centre, University of Manchester's Centre for Biological Timing and Cambridge Artificial Pancreas Group,I will compare glucose control with the artificial pancreas against usual insulin therapy in older people (>60 years old) with T1D, and study whether low and high glucose levels in this group affect changes in heart rate, rhythm and sleep patterns. Up to 40 participants will be invited to the study. Each participant will wear an artificial pancreas device, and a portable heart and sleep monitor during the study to record and analyse their glucose, sleep and heart rhythm respectively.
Expected impact and conclusions: The results will improve our understanding of the impact of the artificial pancreas in this age group, and define the links between glucose levels, cardiac arrhythmia and sleep traits. The results are expected to have major benefits for older people with T1D, their carers, healthcare providers and policy makers. This proposal will support my academic career in developing new research skills and knowledge beyond my current areas of expertise.
Background: Type 1 diabetes (T1D) is a life-long condition, with affected individuals requiring daily insulin treatment to survive and avoid serious complications. As life expectancy of people with T1D increases, the number of older people living with the condition grows. Recommended treatment goals for specific age groups with T1D have been published, but achieving these remains challenging due to the ever-present risk of low blood glucose levels (hypoglycaemia). In addition, older people with diabetes are often disadvantaged due to unequal access to new treatments and technologies. Older people with type 1 diabetes often face unique challenges and have a higher risk of severe hypoglycaemia (extremely low blood glucose leading to loss of consciousness)due to loss of usual hypoglycaemia symptoms such as feeling hungry or anxious, which in some cases, can be fatal.
Some researchers have speculated that frequent and severe hypoglycaemia can make the heart beat too fast or irregularly, which can lead to death. A number of studies have tried to prove a link between the two. However until recently, simultaneous continuous monitoring of glucose levels and heart rhythm have been rarely performed, especially in older people with T1D. Compared to younger age groups, a disproportionate number of older people suffer from severe hypoglycaemia, which is a possible mechanism of sudden or heart-related deaths in older people with T1D.
Several studies have shown higher rates of sleep disturbance (poor sleep quality and shorter sleep duration) in people with T1D compared to those without T1D, which can have negative effects on glucose levels and psychosocial health. The impact of sleep disturbance in older people with T1D, specifically in relation to self-management and adherence behaviours, is unknown.
Current continuous glucose monitoring and insulin pump devices do not automatically alter insulin delivery or insulin dose, and still require the person to make self-adjustments to their insulin. This may lead to potentially high or low sugar levels, and its associated risks. In contrast, the artificial pancreas automatically controls insulin delivery, which is carefully altered by computer software according to minute-to-minute changes in sugar levels detected by the continuous glucose monitoring. However, access to this technology designed to reduce the burden of diabetes remains limited in older people. Evaluation of new treatment strategies to improve health outcomes in this under-served population is needed.
Research environment: In partnership with Manchester Heart Centre, University of Manchester's Centre for Biological Timing and Cambridge Artificial Pancreas Group,I will compare glucose control with the artificial pancreas against usual insulin therapy in older people (>60 years old) with T1D, and study whether low and high glucose levels in this group affect changes in heart rate, rhythm and sleep patterns. Up to 40 participants will be invited to the study. Each participant will wear an artificial pancreas device, and a portable heart and sleep monitor during the study to record and analyse their glucose, sleep and heart rhythm respectively.
Expected impact and conclusions: The results will improve our understanding of the impact of the artificial pancreas in this age group, and define the links between glucose levels, cardiac arrhythmia and sleep traits. The results are expected to have major benefits for older people with T1D, their carers, healthcare providers and policy makers. This proposal will support my academic career in developing new research skills and knowledge beyond my current areas of expertise.
Technical Summary
Background: The prevalence of hypoglycaemia unawareness and severe hypoglycaemia is higher in older compared to younger people with type 1 diabetes (T1D). Hypoglycaemia has been hypothesised to increase the risk of cardiac arrhythmia through exaggerated sympathoadrenal responses and abnormal cardiac repolarisation. Poor glycaemic control has been hypothesised to be an important and modifiable cause of sleep disturbance in T1D. This proposal integrates artificial pancreas (AP), cardiac and sleep monitoring technologies to evaluate glucose control, cardiac arrhythmia risk and sleep traits in older T1D patients.
Objectives: To determine the impact of AP on 1) overall glycaemic control; 2) cardiac arrhythmia risk and relationship between hypoglycaemia, cardiac rate and rhythm; 3) sleep patterns and relationships between hypoglycaemia with measured sleep parameters.
Methods: Randomised, cross-over design trial comparing AP vs. conventional sensor-augmented pump therapy in older T1D patients (>60 years old). Outcomes assessment: 1) Glycaemic control analysis will be between-group comparison of time spent within target sensor glucose range (3.9-10 mmol/l). 2) Holter data from both groups will be analysed for arrhythmic events, heart rate variability and sympathetic/parasympathetic balance. Within-individual values in periods before and after intervention will be compared. 3) Actiwatch data will be analysed for sleep duration and quality, and automatically scored using validated software. AP impacts on sleep traits will be assessed by comparing within-individual data in periods before and after intervention.
Potential impact: My study is expected to establish: a) efficacy & safety of AP in older T1D patients; b)whether AP reduces cardiac arrhythmia risk; c) whether AP improves sleep traits. It is also expected to: i) define links between glycaemia, cardiac arrhythmia and sleep traits and ii) improve current treatment paradigm for older people with T1D.
Objectives: To determine the impact of AP on 1) overall glycaemic control; 2) cardiac arrhythmia risk and relationship between hypoglycaemia, cardiac rate and rhythm; 3) sleep patterns and relationships between hypoglycaemia with measured sleep parameters.
Methods: Randomised, cross-over design trial comparing AP vs. conventional sensor-augmented pump therapy in older T1D patients (>60 years old). Outcomes assessment: 1) Glycaemic control analysis will be between-group comparison of time spent within target sensor glucose range (3.9-10 mmol/l). 2) Holter data from both groups will be analysed for arrhythmic events, heart rate variability and sympathetic/parasympathetic balance. Within-individual values in periods before and after intervention will be compared. 3) Actiwatch data will be analysed for sleep duration and quality, and automatically scored using validated software. AP impacts on sleep traits will be assessed by comparing within-individual data in periods before and after intervention.
Potential impact: My study is expected to establish: a) efficacy & safety of AP in older T1D patients; b)whether AP reduces cardiac arrhythmia risk; c) whether AP improves sleep traits. It is also expected to: i) define links between glycaemia, cardiac arrhythmia and sleep traits and ii) improve current treatment paradigm for older people with T1D.
Planned Impact
This project is anticipated to widely benefit patients and their carers, researchers and healthcare policy-makers.
a) Older people with type 1 diabetes (T1D): This project will establish the efficacy, safety and acceptability of artificial pancreas technology in high-risk older people with T1D. Our PPI group informs us that the artificial pancreas as a technological intervention, is very appealing for many older patients (see below). Other treatment approaches to improve glucose control such as islet transplantation or pancreas transplantation are limited by their risks including the need for life-long immunosuppression. Showing that the artificial pancreas can prevent severe hypoglycaemia, and is also safe and acceptable, will lead to a global step change in the management of these older high-risk individuals.
The case for a change in management strategy will be significantly strengthened if we also show that artificial pancreas technology can reduce the risk of arrhythmias and sleep disturbance in older people with T1D. If we demonstrate that both high and low sugars adversely affect risks for cardiac arrhythmia and sleep disturbance then this will emphasise the benefits of normalising glucose levels using artificial pancreas technology, and challenge the current treatment paradigm. This will ultimately lead to clinical benefits for older people with T1D.
b) Scientific value and knowledge transfer: Simultaneous gathering of data related to continuous glucose levels, insulin delivery, cardiac rhythm and sleep patterns, and the impact of the artificial pancreas on these parameters, have not been performed before. A better understanding of the temporal and potentially causal relationship between hypoglycaemia and cardiac arrhythmias and sleep disturbance will have major scientific and clinical benefits. Data from our study can be utilised by other academic researchers and healthcare innovators, and therefore will support future research and technological strategies that are likely to benefit this vulnerable population.
c) Social and NHS benefits: Other key direct and indirect beneficiaries of this proposal are carers of older people with T1D and the NHS. Carers of people with T1D will benefit from reduced stress and psychological burden associated with caring for an older family member with T1D. These benefits will reduce societal costs as a whole and would be anticipated to have added economic benefits. The costs of managing diabetes-related complications and hospital admissions due to severe hypoglycaemia currently account for a significant proportion of the annual national healthcare budget - in excess of £39 billion per year. The NHS will therefore benefit through lower Health Service usage by people with T1D and their carers.
a) Older people with type 1 diabetes (T1D): This project will establish the efficacy, safety and acceptability of artificial pancreas technology in high-risk older people with T1D. Our PPI group informs us that the artificial pancreas as a technological intervention, is very appealing for many older patients (see below). Other treatment approaches to improve glucose control such as islet transplantation or pancreas transplantation are limited by their risks including the need for life-long immunosuppression. Showing that the artificial pancreas can prevent severe hypoglycaemia, and is also safe and acceptable, will lead to a global step change in the management of these older high-risk individuals.
The case for a change in management strategy will be significantly strengthened if we also show that artificial pancreas technology can reduce the risk of arrhythmias and sleep disturbance in older people with T1D. If we demonstrate that both high and low sugars adversely affect risks for cardiac arrhythmia and sleep disturbance then this will emphasise the benefits of normalising glucose levels using artificial pancreas technology, and challenge the current treatment paradigm. This will ultimately lead to clinical benefits for older people with T1D.
b) Scientific value and knowledge transfer: Simultaneous gathering of data related to continuous glucose levels, insulin delivery, cardiac rhythm and sleep patterns, and the impact of the artificial pancreas on these parameters, have not been performed before. A better understanding of the temporal and potentially causal relationship between hypoglycaemia and cardiac arrhythmias and sleep disturbance will have major scientific and clinical benefits. Data from our study can be utilised by other academic researchers and healthcare innovators, and therefore will support future research and technological strategies that are likely to benefit this vulnerable population.
c) Social and NHS benefits: Other key direct and indirect beneficiaries of this proposal are carers of older people with T1D and the NHS. Carers of people with T1D will benefit from reduced stress and psychological burden associated with caring for an older family member with T1D. These benefits will reduce societal costs as a whole and would be anticipated to have added economic benefits. The costs of managing diabetes-related complications and hospital admissions due to severe hypoglycaemia currently account for a significant proportion of the annual national healthcare budget - in excess of £39 billion per year. The NHS will therefore benefit through lower Health Service usage by people with T1D and their carers.
Organisations
Publications
Bashir B
(2022)
Real world effectiveness of clinically approved hybrid closed loop systems in a UK Secondary Care Diabetes Service.
in Diabetic medicine : a journal of the British Diabetic Association
Boughton CK
(2022)
Hybrid closed-loop glucose control compared with sensor augmented pump therapy in older adults with type 1 diabetes: an open-label multicentre, multinational, randomised, crossover study.
in The lancet. Healthy longevity
Thabit H
(2023)
Impact of the CamAPS FX hybrid closed-loop insulin delivery system on sleep traits in older adults with type 1 diabetes.
in Diabetes, obesity & metabolism
| Title | Artificial pancreas glucose sensor and sleep watch measurements dataset |
| Description | This project has generated a unique and well phenotyped data set, containing continuous integrated data extracted from glucose sensors and sleep watch in individuals with type 1 diabetes using artificial pancreas systems to stabilise their glucose levels. The dataset is being finalised, and will be archived accordingly. Once archived, this dataset may be shared with others, following reasonable request to the investigators. |
| Type Of Material | Data analysis technique |
| Year Produced | 2022 |
| Provided To Others? | No |
| Impact | The data contained in the dataset was created and developed, through research carried out together with my MRC CARP project collaborator Professor Roman Hovorka and his team. It will have an impact on advancing scientific knowledge related to diabetes technology and diabetes management. The development of this dataset will also advance future technological knowledge in collecting and analyzing sensor glucose data, sleep pattern data and cardiac rhythm data. |
| Description | Patient Public Involvement engagement meeting, to inform them of current research and activities. |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | 10 members of the public who are part of a PPI group participated in a PPI engagement meeting which highlighted research in progress. The meeting sparked significant interest in the project, as well as other research topics which many in the PPI group deemed important for advancing scientific knowledge in type 1 diabetes and its related complications. The meeting managed to highlight key advances in technology which they were not aware about, and led to an interest in many of them to disseminate this information to others as well. It also managed to inform members of the public who otherwise would not have known about ongoing research activities in their local region, and which they can help support and participate in. |
| Year(s) Of Engagement Activity | 2021 |