The PhD defense will take place

Friday 8th July, 2022
Auditorium in Medicinerhuset, Aalborg University Hospital
Mølleparkvej 4, 9000 Aalborg

After the defense there will be held a reception. All are welcome.

Supervisors

Professor Jens Brøndum Frøkjær, Department of Radiology, Aalborg University Hospital and Department of Clinical Medicine, Aalborg University, Denmark

Professor Niels Ejskaer, Department of Endocrinology, Steno Diabetes Center North Jutland, Aalborg University Hospital and Department of Clinical Medicine, Aalborg University, Denmark

Associate Professor Tine Maria Hansen, Department of Radiology, Aalborg University Hospital and Department of Clinical Medicine, Aalborg University, Denmark

Assessment Committee

Dr. Prashanth R.J. Vas, Senior clinical Lecturer, King's College Hospital, United Kingdom.

Associate Professor, Simon Fristed Eskildsen, Aarhus University, Denmark.

Associate Professor, Suzette Sørensen, Associate Professor, Aalborg University, Denmark.

About the PhD thesis

One of the major complications of diabetes mellitus is diabetic peripheral neuropathy (DPN) characterized by dysfunction of the peripheral nerves. DPN manifests with sensory abnormalities including neuropathic pain. Unfortunately, early diagnosis and proper treatment of neuropathic complications remain complex and challenging. This is mainly due to the limited knowledge about the underlying mechanisms. Growing evidence has suggested that the central nervous system (CNS) may be involved in the sensory abnormalities experienced in individuals with DPN and neuropathic pain. However, the full extent of the CNS involvement remains largely unknown and needs further investigation. This PhD thesis aims to provide a deeper understanding of CNS alterations in individuals with type 1 diabetes and neuropathic complications using cognitive tests and non-invasive structural and functional magnetic resonance imaging (MRI) of the brain.

This PhD thesis was based on a cross-sectional study named MEDON (Methods of Early Detection of diabetic peripheral Neuropathy). The study included four groups of participants: 1) type 1 diabetes with neuropathic pain, 2) type 1 diabetes with DPN, 3) type 1 diabetes without DPN, and 4) healthy controls. Paper I investigated cognitive alterations in the four groups. The main finding of the study showed poorer memory in the DPN group compared to healthy controls. The cognitive alteration was not associated with peripheral nerve functions or diabetes-related clinical parameters. Paper II aimed to investigate structural brain changes in the four groups included. Compared to the healthy controls total gray matter volume was lower in the diabetes group with neuropathic pain and the diabetes group without DPN. Regional GMV loss, including regions relevant for sensory processing, was found in all three diabetes groups compared to healthy controls. Overall, gray matter volume alterations were observed in individuals with diabetes regardless of the presence of DPN and neuropathic pain. Finally, Paper III investigated functional connectivity at rest in brain regions involved in pain processing (thalamus, primary somatosensory cortex, and insula). Hyper-connectivity was observed between thalamus/primary somatosensory cortex and cortical motor areas in diabetes without DPN compared to diabetes with neuropathic pain and healthy controls. Most remarkably, higher connectivity patterns were associated with poorer peripheral nerve function and higher pain intensity.

Overall, this PhD thesis demonstrated CNS alterations regardless of the presence of DPN and neuropathic pain in individuals with type 1 diabetes. The method used to assess different CNS parameters is of essential value in connecting the CNS alterations to underlying neuropathic complications. Especially, functional parameters of brain regions involved in sensory processing have shown great potential in the pathogenesis of DPN and neuropathic pain and in developing early biomarkers for risk stratification of DPN patients.