The specific objectives will be to; (1) characterise a population with clinically diagnosed
type 1 diabetes and to determine the proportion of islet autoantibody positivity rates and to
compare with a similar cohort of patients in the UK, (2) to determine the proportion of
participants with retained endogenous insulin secretion (C-peptide > 600pmol/l) and whether
they have evidence of autoimmunity as assessed by islet autoantibody and the type 1 diabetes
genetic risk score
Study setting: This study will be a multi-center cross-sectional study of clinically
diagnosed type 1 diabetes patients who are currently on insulin treatment who are being
followed-up in existing diabetes care centers in 4 sub-Saharan African countries; Cameroon,
Uganda, Tanzania and South Africa. Recruitment will take place at regional diabetes care
centers which usually serve as the main diabetes treatment hub for many smaller spoke clinics
in the sub-region. In Cameroon, the Yaounde Central Hospital and the Bafoussam Regional
Hospital will serve as main clinical sites. In Uganda the clinical sites involved are the
Mulago National Referral and Teaching Hospital, St. Francis Hospital Nsambya, all in Kampala
and the Masaka Regional Referral Hospital. The Muhimbili National Hospital in Dar Es Salaam
will serve as the main clinical site in Tanzania. Cameroon, Uganda and Tanzania will carry
out primary data collection over the study period while South Africa (University of
Witwatersrand Medical School) will provide secondary data consisting of a minimal dataset and
relevant collected samples for analysis. All these centers have existing diabetes care
clinics with experienced staff who are used to collecting and providing data for research
purposes.
Eligibility: All patients with a clinical diagnosis of type 1 diabetes or young-onset insulin
treated diabetes, who were diagnosed before the age of 30 years will be eligible to be
enrolled into the study. We estimated a minimum total sample size of 500 participants will
have a high precision with 95% confidence intervals of 17-25% around a prevalence of 20% for
a clinical or biological characteristics (e.g. retained C-peptide or presence of islet
auto-antibodies) and 46-54% around a prevalence of 50%.
Sampling method: We will follow a systematic sampling method, enrolling consecutive eligible
participants from the different primary collection clinical sites.
Enrollment: All consented patients will be interviewed using a structured pre-tested
questionnaire (Data Collection Form) by a trained study staff to collect relevant
information; demographic, socioeconomic, lifestyle, family history, history of diabetes and
diabetes complications. The questionnaire used in this study is available in English and has
been translated into the major local language(s); the appropriate questionnaire is used
according to the participant's preference. After the interview, a short clinical examination
will be performed to record anthropometric characteristics (weight, height, waist and hip
circumferences) and blood pressure.
Using standardized operating procedures (SOPs), saliva, blood and urine samples will be
collected from all study participants for biochemical analysis, and biobanking for future
studies. Saliva will be used for DNA extraction and for the determination of type 1 genetic
risk score (T1D GRS) using a 67 single nucleotide polymorphism score as described by Sharp et
al. 2019. Venous whole blood will be used for full blood count and A1c determination. Plasma
will be used for random C-peptide determination on the 801 module of the Cobas 8000 analyser
and the measuring range will be truncated to <3pmol/L. Serum creatinine will be measured to
assist in the interpretation of the C-peptide result. Islet autoantibodies, GAD, IA2 and ZnT8
will be measured in serum on the RSR Limited ELISA (RSR Limited, Cardiff, U.K.). Dipstick
urinalysis will be done, with urinary C-peptide and creatinine measurement for the
determination of the urinary C-peptide to creatinine ration (UCPCR). .
Data collected from the different clinical sites using the data collection form will be
entered into a centralized data management tool (REDCap). All data will be anonymised before
being stored in the data management system.
Ethical consideration: All participants will be required to provide a written informed
consent before participating in the study. Refusal to participate will not affect the quality
of care of the participants at the clinical sites. The study has received ethical clearance
from the National Ethics Committee of Cameroon ( No 2018/12/1252/L/CNERSH/SP), and the Uganda
Virus Research Institute (GC/127/19/12/736), Muhimbili National Hospital (MNH/IRB/I/2020/019)
and Human Research Ethics Committe, South Africa (M200174).