Identification and Characterization of Diabetes in Low-resource Populations

The specific objectives will be to; (1) To determine the true prevalence of diabetes and prediabetes in a population-based cohort (2) To identify and characterize the different phenotypes of type 2 diabetes (3) To establish a base-line cohort of well-characterised people with diabetes to understand disease progression of the different phenotypes, including uptake and response to treatment. (4) To identify and recruit a cohort of non-diabetic volunteers (including prediabetes i.e., at high risk of developing diabetes) for longitudinal follow-up.

Study setting: This will be a population-based survey nested within the General Population Cohort (GPC). The GPC is a rural population-based cohort study of people living within the 25 villages of Kyamulibwa sub-county of Kalungu District in rural southwest Uganda. The primary study will be conducted in Uganda. The study shall recruit from 2 sites (rural and urban areas) across the greater Masaka region in southwest Uganda in order to explore the differences in lifestyle, and how these influence prevalence of diabetes and its outcomes; General Population Cohort (GPC) in Kyamulibwa will provide the rural population, and the town of Lukaya the urban population. Both rural and urban sites are established research areas. The entire adult population of the GPC will be eligible for this survey. Data from the most recent Census (2020-2021) in the GPC shows that there are 8,864 adults (aged 18+) of the total population of 20,751 in Kyamulibwa.

Eligibility: All adults aged 18 years and above will be invited to take part in the study. We will recruit all adults who are able to provide written informed consent and are residents at a household (i.e. not a temporary member with intent to leave) in either of the study areas. Individuals will be excluded from the study based on the following criteria: pregnant women (can participate six months after childbirth), live outside the geographical sampling frame for the relevant site or are unable to give informed consent, living outside the relevant site's catchment area.

Sampling method: This study is powered to estimate the prevalence of diabetes and other primary outcomes like prediabetes Impaired fasting glycaemia (IFG), isolated postprandial hyperglycaemia (IPH), isolated-IFG and isolated-Impaired Glucose Tolerance) with sufficient precision. We have conservatively based our assumptions on results from the 2014 Ugandan nation-wide cross-sectional survey suggesting that the prevalence of IFG and diabetes in Uganda is 2% (95% CI: 1.5-2.5%) and 1.4% (95% CI: 0.9 - 1.9%) respectively.3 That survey detected dysglycaemia using fasting blood glucose alone, rather than OGTT. Applying a rule of thumb that the margin of error should not exceed 0.25 of the prevalence and based on the following assumptions: A margin of error of 0.5% (a margin of error of 0.5% to 1% would be acceptable for low prevalent conditions) and Diabetes prevalence of 5% (assuming OGTT would detect more cases of diabetes thus doubling the prevalence) and estimated 5% level of significance (z-value = 1.96). We aim to screen a minimum of 11700 adults across all sites; a minimum of 5,850 from each site. All the adults in Kyamulibwa- the rural site (8, 864) will be invited to take part in our survey. For Lukaya-the urban site; initially, 3 of the 5 cells will be randomly selected and all the adults in the selected cells (approximate total adult population of 6000) invited to take part in the survey. Recruitment will be restricted to individuals who reside within defined areas (villages).

Enrollment: This study will consist of overlapping phases as described below: