dc.contributor.author | Balungi, P | |
dc.date.accessioned | 2021-08-10T12:32:04Z | |
dc.date.issued | 2021-08-02 | |
dc.description.abstract | Background: Diabetes mellitus is a metabolic disorder associated with chronic hyperglycaemia resulting from defects in beta cell insulin secretion or insulin action. Diabetes is a growing problem in sub-Saharan Africa (SSA), but the availability of biochemical and immunological tests to help with the diagnosis and management of diabetes has been limited. In this thesis, we carried out two projects to improve laboratory diagnostic methods for diabetes in an African population. Project 1: HbA1c assays: HbA1c is commonly used for diagnosis and monitoring of diabetes. However, it is affected by a number of pre-analytical factors like haemoglobinopathies, which are highly prevalent in SSA. We aimed to: 1) determine the performance and comparability of four major HbA1c methodologies; immunoassay, capillary electrophoresis, boronate affinity, and anion exchange high performance liquid chromatography, and 2) determine the impact of haemoglobinopathies on HbA1c measurement by comparing to mean continuous glucose monitoring measurements. We found good agreement between all four HbA1c methodologies, suggesting whichever methodology a laboratory uses results are comparable. There was a good correlation (>0.80) between all HbA1c methodologies and mean glucose values from continuous glucose monitoring did not differ in those with haemoglobinopathies. Project 2: Islet autoantibodies: Glutamic acid decarboxylase autoantibody (GAD65Ab), tyrosine phosphatase autoantibody (IA-2A) and zinc transporter 8 autoantibody (ZNT8A) are autoimmune biomarkers in diabetes. Studies in SSA have shown associations between these islet autoantibodies and type 1 diabetes development, however presence / prevalence of autoantibodies was defined based on White Caucasian population-based cut offs, which may not be appropriate for the African population. We aimed to determine population based cut offs for positivity at the 97.5th and 99th percentile in the Ugandan population. The 97.5th and 99th percentile cut-offs were; GAD65Ab; ≥44.8, ≥144 U/ml; IA-2A ≥57, ≥107 U/ml; ZNT8A ≥97.6, ≥351 U/ml, respectively. Applying the manufacturer cut offs (GAD65Ab ≥5, IA-2A ≥7.5, ZNT8A ≥15) to the Ugandan non-diabetic controls, led to higher proportions classed as positive for a single autoantibody compared with using our cut offs: (5% GAD65Ab, 12% IA-2A, 8.4% ZNT8A). This implies that using the manufacturer’s cut-offs overestimates the number of positives in our population. | en_GB |
dc.description.sponsorship | National Institute for Health Research (NIHR) | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/126730 | |
dc.publisher | University of Exeter | en_GB |
dc.rights.embargoreason | None | en_GB |
dc.subject | HbA1c testing methodologies | en_GB |
dc.subject | GAD, IA-2A,ZNT8A cutoffs in sub-Saharan Africa | en_GB |
dc.title | Developing and improving laboratory methods, for diabetes diagnostics for sub-Saharan Africa | en_GB |
dc.type | Thesis or dissertation | en_GB |
dc.date.available | 2021-08-10T12:32:04Z | |
dc.contributor.advisor | Shields, B | en_GB |
dc.contributor.advisor | McDonald, T | en_GB |
dc.contributor.advisor | Rodgers, L | en_GB |
dc.contributor.advisor | Nice, R | en_GB |
dc.contributor.advisor | Hughes, P | en_GB |
dc.publisher.department | Post graduate study | en_GB |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | en_GB |
dc.type.degreetitle | Masters By research in medical studies | en_GB |
dc.type.qualificationlevel | Masters | en_GB |
dc.type.qualificationname | MbyRes Dissertation | en_GB |
exeter.funder | ::National Institute for Health Research (NIHR) | en_GB |
rioxxterms.version | NA | en_GB |
rioxxterms.licenseref.startdate | 2022-03-14 | |
rioxxterms.type | Thesis | en_GB |
refterms.dateFOA | 2021-08-10T12:32:38Z | |