Hypoglycaemia and atherosclerosis
Research type
Research Study
Full title
Hypoglycaemia worsens atherosclerosis through inflammatory pathways
IRAS ID
162092
Contact name
Ian Sabroe
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS Foundation Trust
Duration of Study in the UK
2 years, 11 months, 30 days
Research summary
Research Summary
People with diabetes are at increased risk of having heart attacks and strokes. During the treatment of diabetes, blood sugars sometimes run too high, and sometimes run too low. Many studies link high blood sugars with increased risk of heart disease, but it's now becoming clear that low blood sugars may also cause heart disease and strokes. We want to understand how this can happen. To do this, we will deliberately lower the blood sugar in healthy volunteers by giving them controlled doses of insulin. We will then see if this causes inflammatory cells to be released into the blood that could in theory damage the heart. We will follow this up by giving a low dose challenge to the same people two days later of a substance derived from dead bacteria. This will test whether the immune system has been stimulated by the episode of low blood sugar. These studies will help us understand how diabetes treatments might inadvertently make heart disease risks worse, and will enable us to develop new treatments to reduce the risk of heart disease and stroke in people with diabetes.Summary of Results
We sincerely thank all the individuals who participated in this study. Their involvement was crucial to advancing our understanding of how low blood sugar levels affect the body's immune response.Study Title
Hypoglycaemia worsens atherosclerosis through inflammatory pathways.Who Carried Out the Research?
This research was conducted by a team of scientists specialising in diabetes and immunology at Sheffield Teaching Hospitals and the University of Sheffield. Prof Ian Sabroe was the Chief Investigator and Dr Ahmed Iqbal led the study. The study was published in The Journal of Clinical Endocrinology & Metabolism. The study was funded by a personal research training fellowship awarded to Dr Ahmed Iqbal by the Medical Research Council. Sheffield Teaching Hospitals NHS Foundation Trust sponsored the study.Where and When Did the Study Take Place?
The study took place between 2015 and 2019 at the Clinical Research Facility, Northern General Hospital, Sheffield.Why Was the Research Needed and What was done?
People with diabetes are at increased risk of having heart attacks and strokes. During the treatment of diabetes, blood sugars sometimes run too high, and sometimes run too low. Many studies link high blood sugars with increased risk of heart disease, but it was becoming clear that low blood sugars may also cause heart disease and strokes. We wanted to understand how this could happen. To do this, we deliberately lowered the blood sugar in healthy people by giving them controlled doses of insulin. We then studied inflammatory cells released into the blood that could in theory damage the heart. We followed this up by giving a low dose challenge to the same people two days later of a substance derived from dead bacteria. This tested whether the immune system had been stimulated by the episode of low blood sugar. We wanted to understand how diabetes treatments might inadvertently make heart disease risks worse, and to enable us to develop new treatments to reduce the risk of heart disease and stroke in people with diabetes.What Were the Main Questions Studied?
The primary question was how low blood sugar levels influence the body's inflammatory response and its reaction to a mild immune system challenge.Who Participated in the Study?
Twenty-four healthy participants participated in the study.What Treatments or Interventions Did the Participants Receive?
Participants experienced controlled episodes of low blood sugar and a mild immune challenge two days later. The study then assessed their immune responses to these episodes.What Were the Results of the Study?
The study found that low blood sugar levels can trigger the body's immune response, making it react more strongly than usual. This increased response can lead to more inflammation, which might raise the risk of heart disease in people with diabetes who are already vulnerable.How Has This Study Helped Patients and Researchers?
These findings provide valuable insights into the connection between blood sugar levels and immune responses. This knowledge has informed future research.Details of Any Further Research Planned
This study led to further research that is currently ongoing to understand if commonly used medications and reduce inflammation caused by low blood sugar levels in people with diabetes (https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.hra.nhs.uk%2Fplanning-and-improving-research%2Fapplication-summaries%2Fresearch-summaries%2Fbest-in-t2d%2F&data=05%7C02%7Csheffield.rec%40hra.nhs.uk%7Ce2223a57e7af49e12e9608dd4623b1e9%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638743841298899999%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=WI2sTVrdolkqMX6fhj7RLlDD0zl3W0UshbdE4iWpRtQ%3D&reserved=0).Where Can I Learn More About This Study?
For more details, you can access the full study here:
https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Facademic.oup.com%252Fjcem%252Farticle%252F104%252F4%252F1187%252F5105934%2FNBTI%2FbS_7AQ%2FAQ%2F88aae03d-096b-41be-9541-7b2f80dcd77e%2F2%2FUrYg01Ezp7&data=05%7C02%7Csheffield.rec%40hra.nhs.uk%7Ce2223a57e7af49e12e9608dd4623b1e9%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638743841298911627%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=U3pry15MQYD0bbPUduEMW7blaR46nrzTAHciUCOCsnU%3D&reserved=0REC name
Yorkshire & The Humber - Sheffield Research Ethics Committee
REC reference
14/YH/1264
Date of REC Opinion
5 Nov 2014
REC opinion
Favourable Opinion