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Type 1 diabetes is a chronic autoimmune disease characterised by severe endogenous insulin deficiency resulting from the progressive destruction of insulin-secreting beta cells of the pancreatic islets. The detection of one or more circulating islet autoantibodies is fundamental in confirming the diagnosis of the condition.
Type 1 diabetes has been poorly characterised in Africa, especially in sub-Saharan Africa, due to the lack of robust observational data. Previous studies conducted amongst young people in sub-Saharan Africa have reported an atypical phenotype suggesting a non-autoimmune aetiology. Whether this is true is uncertain as many of these previous studies were limited by small sample sizes and the use of non-standardised methods. Examining the phenotype and aetiology of type 1 diabetes in African populations will be fundamental in providing insights into the progression of the disease and strategies for prevention and treatment. Furthermore, type 1 diabetes is historically associated with high mortality in the African continent. The mortality is thought to be highest amongst young children and those close to diabetes diagnosis. Whether high mortality introduces a survival bias with the possible enrichment of a particular phenotype of diabetes has not been previously studied.
The aim of this thesis is to examine the phenotype and aetiology of diabetes amongst young people with a clinician diagnosis of type 1 diabetes in sub-Saharan Africa. The thesis also seeks to investigate the association between the phenotype of diabetes and survival in sub-Saharan Africa.
In Chapter 1, we present an overview of type 1 diabetes and review current evidence on the phenotype of type 1 diabetes in sub-Saharan Africa. We also describe the datasets and clinical studies used in the subsequent chapters of this thesis.
In Chapter 2, we describe the clinical utility of the urinary C-peptide to creatinine ratio in assessing endogenous insulin secretion in patients with diabetes in Cameroon and demonstrate that the use of home meal stimulation may not be appropriate in this setting.
In Chapter 3, we describe the performance of home-collected dried blood spot C-peptide measurements in assessing endogenous insulin secretion in people with young-onset diabetes in Cameroon. We show that simple dried blood spot C-peptide measurements provide a robust method of assessing endogenous insulin secretion in this population.
In Chapter 4, we examine the phenotype and markers of type 1 diabetes aetiology in people with a clinician diagnosis of type 1 diabetes in Cameroon. We show that most young people diagnosed with type 1 diabetes likely have atypical non-autoimmune diabetes and do not have features suggestive of autoimmune type 1 or type 2 diabetes.
In Chapter 5, we examine the mortality rate within a group of children and adolescents with a clinician diagnosis of type 1 diabetes in Cameroon. We demonstrate that mortality was substantially high and mainly associated with place of care and education.
Chapter 6 presents an overview of the main findings, conclusions, limitations, and perspectives for future research generated by this thesis. |
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