Cees J Tack

Aims The article investigates whether chronic hyperglycaemia in Type 1 diabetes (T1D) is associated with a proinflammatory immune signature and with arterial wall inflammation, driving the development of atherosclerosis. Methods and results Patients with T1D (n = 41), and healthy age-, sex-, and body mass index–matched controls (n = 20) were recruited. Arterial wall inflammation and haematopoietic activity were measured with 2′-deoxy-2′-(18F)-fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography. In addition, flow cytometry of circulating leucocytes was performed as well as targeted proteomics to measure circulating inflammatory markers. 18F-FDG uptake in the wall of the abdominal aorta, carotid arteries, and iliac arteries was higher in T1D compared with that in the healthy controls. Also, 18F-FDG uptake in the bone marrow and spleen was higher in patients with T1D. CCR2 and CD36 expressions on circulating monocytes were higher in patients with T1D, as well as several circulating inflammatory proteins. In addition, several circulating inflammatory markers (osteoprotegerin, transforming growth factor-alpha, CX3CL1, and colony-stimulating factor-1) displayed a positive correlation with FDG uptake. Within T1D, no differences were found between people with a high and low HbA1c. Conclusion These findings strengthen the concept that chronic hyperglycaemia in T1D induces inflammatory changes that fuel arterial wall inflammation leading to atherosclerosis. The degree of hyperglycaemia appears to play a minor role in driving this inflammatory response in patients with T1D.

Context Type 1 diabetes (T1D) is associated with alterations of the immune response which persist even after the autoimmunity aspect is resolved. Clinical factors that cause dysregulation, however, are not fully understood. Objective To identify clinical factors that affect immune dysregulation in people with longstanding T1D. Design In this cross-sectional study, 243 participants with longstanding T1D were recruited between February 2016 and June 2017 at the Radboudumc, the Netherlands. Blood was drawn to determine immune cell phenotype and functionality, as well as circulating inflammatory proteome. Multivariate linear regression was used to determine the association between glycated hemoglobin (HbA1c) levels, duration of diabetes, insulin need, and diabetes complications with inflammation. Results HbA1c level is positively associated with circulating inflammatory markers (P < .05), but not with immune cell number and phenotype. Diabetes duration is associated with increased number of circulating immune cells (P < .05), inflammatory proteome (P < .05), and negatively associated with adaptive immune response against Mycobacterium tuberculosis and Rhizopus oryzae (P < .05). Diabetes nephropathy is associated with increased circulating immune cells (P < .05) and inflammatory markers (P < .05) Conclusion Disease duration and chronic complications associate with persistent alterations in the immune response of individuals with long standing T1D.

Aims Impaired awareness of hypoglycaemia (IAH) has been reported to affect up to a third of people with type 1 diabetes. Whether the increased use of sensor technology has changed its prevalence remains unknown. The aim of this study was to investigate the current prevalence of IAH and its change over time in a cohort of individuals with type 1 diabetes. Methods IAH was assessed using the modified Clarke questionnaire in adults with type 1 diabetes. Participants were recruited from the diabetes outpatient clinic from February 2020 through April 2021. The scores were compared to similar data collected during previous assessments in 2006, 2010 and 2016 respectively. Results A total of 488 individuals (51.2% male) with a mean (±SD) age of 51.3 ± 15.9 years, median [ Q 1– Q 3] diabetes duration of 30 [16–40] years and mean HbA 1c of 60 ± 12 mmol/mol (7.7 ± 1.1%) were included. Sensors were used by 85% of the study population. IAH was present among 78 (16.0%) participants, whereas 86 (17.6%) participants had a history of severe hypoglycaemia. By comparison, the prevalence of IAH equalled 32.5% in 2006, 32.3% in 2010 and 30.1% in 2016 ( p for trend <0.001), while the proportion of individuals reporting severe hypoglycaemia equalled 21.2%, 46.7% and 49.8% respectively ( p for trend 0.010). Comparing sequential assessments over time, the proportion of individuals with persistent IAH decreased from 74.0% and 63.6% between 2006 and 2016 to 32.5% in 2020. Conclusions Among individuals with type 1 diabetes and high use of sensor technology, the current prevalence of IAH was 16%, about 50% lower as compared to previous years.