An investigation into the prevalence of prediabetes in Durban, South Africa, as well as the associated hormonal imbalances and MicroRNA expression patterns in patients with prediabetes.

Abstract

Background Prediabetes constitutes a metabolic state linked with an elevated risk of all-cause mortality. The International diabetes federation has projected a substantial increase in the prevalence of pre-diabetes, particularly in middle-income countries. Despite this, there is a lack of research looking into pre- diabetes in middle-income countries, leading to a significant number of undiagnosed cases. Additionally, there exists a limited understanding of hormonal imbalances and their correlation with pre-diabetes. The exploration of the link between epigenetic factors and pre-diabetes is also insufficient, particularly in developing countries such as South Africa. There is a compelling need for more pre- diabetes-related research that will represent middle-income populations in order to assist in mitigating the anticipated surge in prediabetes and type 2 diabetes mellitus (T2DM). Therefore, this research project aimed to assess the systematic prevalence of pre-diabetes and its correlates in South Africa and the specific prevalence of pre-diabetes in King Edward Hospital, the second-largest tertiary hospital in Southern Africa, based in Durban, South Africa. The paucity of pre-diabetes-related research on hormonal imbalances relative to T2DM led us to quantify the difference in hormone concentration levels between persons with pre-diabetes and those without pre-diabetes. Lastly, the miRNA expression changes in pre-diabetes participants and the association between microRNAs and HbA1c-determined dysglycemia were examined for the first time in a population based in Durban. Methods Per the PRISMA 2020 guidelines, a first-of-its-kind systematic and meta-analysis review was conducted to estimate the overall prevalence of pre-diabetes and its correlates in South Africa. Then, a retrospective study design was adopted, with a sample size of 364, to investigate the prevalence of pre- diabetes in a clinical setting based in Durban. After that, hormone concentrations were measured from stored plasma samples through multiplexing using the Luminex MAGPIX System to determine the occurrence of hormonal imbalances in subjects with pre-diabetes. Lastly, microRNAs were extracted from plasma samples and converted to cDNA in order to perform RT-qPCR. The RT-qPCR quantified the expression of microRNA targets previously unexplored in the study population (miRNA-34a-5p, miRNA-145-5p, and let-7f-5p) between persons with pre-diabetes and normoglycemia. Results The meta-analysis generated a pre-diabetes pooled prevalence of 15,56 % in the South African population. The prevalence differed across the ethnic groups, mainly affecting the Indian, Coloured, African and then white ethnic groups, respectively. The common correlates of pre-diabetes were hypertension, obesity and a sedentary lifestyle. The retrospective prevalence study showed a mammoth 54 % and 67 % prevalence of pre-diabetes when using the respective WHO and ADA diagnostic criteria for pre-diabetes. The following hormones, c-peptide, cortisol, progesterone, estradiol, T3, T4, and adiponectin, were dysregulated in persons with pre-diabetes and significantly correlated with HbA1c. Of the three candidate miRNAs, only miRNA-34a-5p showed a significant relative fold expression difference between pre-diabetes and individuals with normoglycaemia. Moreover, the receiver operator characteristic curve analysis for miR-34a-5p produced an AUC of 0.806, Conclusion The meta-analysis study showed a substantial prevalence of pre-diabetes across the country, and the study’s prevalence analysis in King Edward Hospital indicates that it is burgeoning. The growing pre- diabetes prevalence suggests a looming incidence of overt T2DM if left unattended. Hence, the outcomes highlight the need to strengthen pre-diabetes surveillance in order to implement diabetes prevention policies and interventions effectively. Moreover, the management of pre-diabetes care may need to consider a more holistic approach by monitoring the hormonal imbalances that were found to correlate with HbA1c. Future research should explore the therapeutic potential of targeting these hormonal pathways, including the possibility of hormone replacement interventions. Notably, miR-34a-5p was found to be associated with dysglycemia and a potential future risk marker or diagnostic marker for pre-diabetes.