Central and peripheral neurodegeneration in diabetes and dementia

Ponirakis, Georgios (2020) Central and peripheral neurodegeneration in diabetes and dementia. Doctoral thesis (PhD), Manchester Metropolitan University.

Preview

Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (3MB) | Preview

Abstract

Background: Diabetic peripheral neuropathy (DPN) affects ~50% of people with diabetes and leads to painful DPN (pDPN), diabetic foot ulceration (DFU) and amputation imposing a significant health and economic burden. Given that there are currently no European Medicines Agency (EMA) and FDA approved therapies for DPN it is important to establish the current prevalence and modifiable risk factors for DPN and assess the benefit of treatments utilizing corneal confocal microscopy (CCM), a sensitive technique to quantify early nerve regeneration in DPN. Furthermore, CCM has shown corneal nerve loss in central neurodegenerative disorders such as Parkinson’s disease and multiple sclerosis, therefore the diagnostic utility of this technique was assessed in subjects with mild cognitive impairment (MCI) and dementia. Aims: This work established the prevalence and risk factors of DPN and those at high risk of DFU in Chapter 3; the prevalence and risk factors of pDPN in Chapter 4 and the prevalence of DPN and pDPN in both primary (PHC) and secondary health care (PHC) in type 2 diabetes (T2D) in Qatar in Chapter 5. It investigated the effect of hypertension on neuropathic symptoms and deficits in type 1 diabetes (T1D) in Chapter 6, the association between metformin induced B12 deficiency and DPN in Chapter 7, and the effect of exenatide and pioglitazone or basal-bolus insulin on DPN in patients with poorly controlled T2D as an exploratory sub-study of the Qatar study, an open-label, randomized controlled trial (clinicaltrials.gov identifier NCT02887625) in Chapter 8. It assessed the association of corneal nerve morphology with cognitive impairment in MCI and dementia in Chapter 9 and compared the diagnostic ability of CCM to visual rating of medial temporal lobe atrophy (MTA) on brain MRI to distinguish subjects with MCI or dementia from subjects with no cognitive impairment (NCI) in Chapter 10. Methods: All the research work was conducted in Qatar apart from Chapter 6 which was performed in Manchester, UK. The study design, inclusion and exclusion criteria, diagnosis and assessments for each study are described in detail in the methods section in each chapter. Subjects were randomly enrolled and screened for eligibility on the day they attended the clinic. Demographic, clinical and metabolic characteristics and list of medications were recorded.