Correspondence

Coffee consumption and risk of type 2 diabetes mellitus

Purinergic signaling, a concept originally formulated by the late Geoffrey Burnstock (1929–2020), was found to modulate pathways in every physiological system. In metabolic disorders there is a role for both adenosine receptors and P2 (nucleotide) receptors, of which there are two classes, i.e. P2Y metabotropic and P2X ionotropic receptors. The individual roles of the 19 receptors encompassed by this family have been dissected – and in many cases the effects associated with specific cell types, including adipocytes, skeletal muscle, liver cells and immune cells. It is suggested that ligands selective for each of the four adenosine receptors (A₁, A_2A, A_2B and A₃), and several of the P2 subtypes (e.g. P2Y₆ or P2X7 antagonists) might have therapeutic potential for treating diabetes and obesity. This is a developing story with some conflicting conclusions relevant to drug discovery, which we summarize here.

Type 2 diabetes represents a significant worldwide public health problem because of an alarming increase in its incidence over recent decades and because of associated morbidity and mortality. These aspects underscore the need for effective strategies to treat and, even more important, prevent the disease. In this scenario, many epidemiological studies have consistently indicated a protective effect of coffee intake on the risk of developing type 2 diabetes among different populations, even after adjusting for various potential confounding factors. Although the descriptive nature of the data from these studies cannot establish causality in the relationship between coffee intake and diminished type 2 diabetes risk, these findings may be viewed as an initial indication that coffee consumption has the potential to be a simple dietary intervention with significant benefits.

This review provides the epidemiologic and research evidences documenting the effects of coffee consumption on type 2 diabetes mellitus (T2DM). We summarize the literature concerning the effects of coffee consumption on different mechanistic factors involving in pathogenesis of T2DM, such as glucose tolerance, insulin sensitivity, insulin resistance, glucose-6-phosphatase, intestinal glucose absorption, antioxidant activity, inflammatory biomarkers, nuclear factor-κB inhibition, glucose uptake, glucose homeostasis, glucose metabolism, and insulin secretion. These factors play a crucial role in influencing the normal levels of glucose in blood. Overall, the experimental and epidemiologic evidences presented here elucidate the protective effects of coffee consumption on T2DM, involving multiple preventive mechanisms. Despite the firm evidences available through a growing literature base, it is still uncertain whether the use of coffee should be recommended to patients with diabetes and/or any patient who might be at the risk of T2DM as a supplementary therapy to prevent further progression of T2DM.