Do patients with Addison’s disease experience low sugar levels at night?
Patients with Addison’s disease frequently complain of impaired well-being, particularly a lack of energy and fatigue. This is most common immediately on waking when cortisol levels are at their lowest, being before the morning steroid tablet (hydrocortisone/prednisolone) has been swallowed and absorbed in to the circulation. The findings of reduced quality of life are supported from large population-based studies of patients with Addison’s disease. Additionally, population-based studies of patients with Addison’s disease suggest an increase in mortality rates in this group, particularly from heart disease. Blood sugar (glucose) is tightly regulated by the secretion of hormones that lower blood glucose levels (insulin) and those that increase blood glucose levels (cortisol, growth hormone). These hormones act in concert to maintain blood glucose levels within the normal range. As a consequence of lack of the counter-regulatory hormone, cortisol, it may be that patients with Addison’s disease struggle to control their glucose levels as effectively as otherwise healthy subjects. Cortisol levels are highest in the early morning hours (4-7am) at a point when we are generally fasted. The fact that the body has not eaten for several hours, and thus has no glucose from food, highlights the important role cortisol plays in preventing glucose levels becoming too low overnight. Addison’s disease is also frequently associated with type 1 diabetes mellitus (T1DM), further complicating glucose regulation in the subset of individuals who have both Addison’s disease and T1DM.
Putting together the observations of impaired well-being and the possibility that patients with Addison’s disease cannot regulate their glucose levels, we hypothesise that low glucose levels (hypoglycaemia) overnight in patients with Addison’s disease contribute to the observed impaired well-being. With the aid of support from the ADSHG we aim to investigate this hypothesis. Firstly, to examine if hypoglycaemia does occur overnight, we will use continuous glucose monitoring (CGM). CGM is a relatively new tool, which allows recording of glucose levels by use of a small device worn on the skin and which has a small probe inserted in to the skin. The device we will use is the Freestyle Libre Pro. Each single Freestyle Libre Pro probe records glucose levels every 30 minutes for 14 days. We aim to collect data from 15 patients with Addison’s disease and TIDM, and 15 patients with Addison’s disease without T1DM; as well as individually-matched age, gender, and body mass index (BMI) matched controls. During CGM, a diary will be kept of any medications and the times these were taken, along with times of food intake. This is particularly important for the steroid replacement the patient is taking, to estimate times during which steroid levels will be low. Secondly, at the end of the study the patients will complete three self-rating questionnaires regarding their subjective health status over the preceding 14 days. This will allow us to determine if there is an association between glucose levels and well-being. Finally, we will undertake a 24-hour heart rate recording to examine if there are any abnormalities of heart rhythm at the time that glucose levels are at their lowest.
Patients with Addison’s disease are reported to have impaired quality of life and excess cardiovascular mortality, which we hypothesise may be associated with unrecognised hypoglycaemia. If we can demonstrate this to be the case, then this could be addressed relatively simply (i.e. diet). We hope to have preliminary data within the year from this study, and thank the ADSHG for supporting us in this endeavour. If you are interested in participating in this study, please contact Julie Lynch, who is an Endocrine Research Nurse at St James’s Hospital, Leeds, on 0113 206 4660. Participants must have Addison’s disease, with or without type 1 diabetes mellitus, and cannot have type 2 diabetes mellitus or any other drugs or conditions that affect glucose levels, and no history of heart disease.
Dr Robert Murray and Dr Khyatisha Seejore
Dr Robert Murray is a Consultant Endocrinologist and Honorary Associate Professor, and Dr Khyatisha Seejore is a Clinical Research Fellow in Endocrinology, at Leeds Teaching Hospitals NHS Trust. Dr Murray has both clinical and research interests in the field of adrenal insufficiency. One of his largest projects has been as part of the European Adrenal Insufficiency Registry (EU-AIR) which collects observational data on a large cohort of patients with adrenal insufficiency. Dr Murray serves on the Clinical and Public & Patient involvement committees of the Society for Endocrinology, and is on the Editorial Board of several endocrine journals. Dr Seejore works closely with Dr Murray.
More information about the Award can be found on the ADSHG website here or you can email enquiries to the Trustees. Recipients are asked to provide regular reports, for publication in the ADSHG newsletter.
Two further recipients of ADSHG grants have also provided reports on their work.
This article was first published in the September 2018 edition of the ADSHG newsletter.