Background: Despite the growing burden of type 2 diabetes in sub-Saharan Africa (SSA), its aetiopathogenesis has not been robustly investigated. The overarching aim of this thesis was to describe the clinical, metabolic, and immunologic profile of adult Ugandan patients with new-onset diabetes to develop a pragmatic approach to the categorisation of diabetes subgroups. Methods: Relevant clinical, metabolic, and immunologic data were collected from 568 adult participants with new-onset diabetes. All participants were subjected to an assessment of markers of pancreatic function, glucose metabolism, and three islet autoantibodies. Randomly selected participants were screened for diabetic nephropathy and peripheral arterial disease. Results: The narrative review showed that diabetes manifests differently in Africans compared to white populations of European descent. A low prevalence of islet autoantibody positivity (6.4%) was observed and was independently associated with living in a rural area and being initiated on insulin therapy at the time of diagnosis. Confirmed new-onset type 2 diabetes in lean individuals (negative status for islet autoantibodies and BMI <25 kg/m2) was noted in approximately a third of participants (32%). This “lean type 2 diabetes phenotype” was associated with minimal insulin resistance, visceral adiposity, metabolic syndrome, and features of pancreatic beta-cell dysfunction predominated. Peripheral arterial disease and diabetic nephropathy were relatively prevalent. Female sex, urine albumin creatinine ratio, and fasting blood glucose independently predicted peripheral arterial disease while hypertension comorbidity and obesity independently predicted diabetic nephropathy. Conclusions: This research shows that pancreatic autoimmunity is an uncommon cause of adult-onset diabetes in our study population. We also showed that the lean type 2 diabetes phenotype is relatively common and is associated with reduced pancreatic beta-cell function. The prevalence of peripheral arterial disease and diabetic nephropathy was also relatively high. These study findings have broad implications for the screening, management, and prevention of diabetes in Uganda.