We have read with great interest the comprehensive and ambitious review on the pathophysiology of type 2 diabetes in individuals from sub-Saharan Africa (SSA) by Goedecke and Mendham, published in Diabetologia [1]. The authors discuss pathophysiological mechanisms in the pathogenesis of insulin resistance and type 2 diabetes, with an emphasis on the role of adipose tissue and ectopic fat, as well as sex differences. The authors call for longitudinal and intervention studies, of which there are very few involving Black African individuals in the current context, and we applaud them for raising awareness of such initiatives. These studies are particularly required in relation to insulin secretion, clearance and sensitivity in this population as a result of interventions including exercise, nutrition and/or body weight change.

While the review by Goedecke and Mendham discusses some environmental aspects of type 2 diabetes risk, including infections and epigenetics [1], these were not discussed as rigorously or in as much detail as were aspects of so-called ‘lifestyle interventions’. In our view, the impact of infectious diseases and fetal programming by epigenetics need to be discussed in much more detail as such environmental aspects are likely to be common in African populations, and may, therefore, confound results obtained by future lifestyle intervention studies [2].

We propose that infectious diseases, such as tuberculosis (TB) with or without co-infection with HIV, in sub-Saharan African populations should be emphasised more with regard to the risk of developing type 2 diabetes. Every year, the SSA region contributes to ~30% of the total number of global TB cases (~10 million cases), and it is estimated that the annual number of TB/HIV cases is 600,000, which is equivalent to three-quarters of the global estimate [3]. For various reasons, in sub-Saharan Africans there is a considerable delay in TB diagnosis. This delay in diagnosis contributes to persistent inflammation, which partly affects pancreatic beta cells and, which in the pancreatic islets, results in infiltration of immune cells, increased proinflammatory cytokines and chemokines, apoptosis, and amyloid deposits that induce fibrosis and, at least in part, pancreatic beta cell dysfunction [4, 5]. Hyperglycaemia is a common phenomenon in individuals with TB, with 50% of those infected being found to have persistent dysglycaemia despite receiving anti-TB treatment [6]. Furthermore, HIV has been recognised as a dominant risk factor for persistent dysglycaemia in individuals treated for TB [6]. Stress from severe chronic infection is likely to enhance insulin resistance in key tissues (liver, skeletal muscle etc.) and unmask an underlying beta cell deficiency, leading to chronic hyperglycaemia. Thus, the increased risk of type 2 diabetes among people with TB is plausible [7]. Longitudinal studies aiming to estimate incidence of type 2 diabetes in individuals with TB-induced hyperglycaemia are, therefore, essential to guide strategies for the prevention and control of type 2 diabetes in order to reduce the risk of increasing the proportion of manifest type 2 diabetes in Africa. Figure 1a provides a visual overview of the association between TB and type 2 diabetes