Update on pre-diabetes: Focus on diagnostic criteria and cardiovascular risk

Abstract

Pre-diabetes, which is typically defined as blood glucose concentrations higher than normal but lower than the diabetes threshold, is a high-risk state for diabetes and cardiovascular disease development. As such, it represents three groups of individuals: Those with impaired fasting glucose (IFG), those with impaired glucose tolerance (IGT) and those with a glycated haemoglobin (HbA_1c) between 39-46 mmol/mol. Several clinical trials have shown the important role of IFG, IGT and HbA_1c-pre-diabetes as predictive tools for the risk of developing type 2 diabetes. Moreover, with regard to cardiovascular disease, pre-diabetes is associated with more advanced vascular damage compared with normoglycaemia, independently of confounding factors. In view of these observations, diagnosis of pre-diabetes is mandatory to prevent or delay the development of the disease and its complications; however, a number of previous studies reported that the concordance between pre-diabetes diagnoses made by IFG, IGT or HbA_1c is scarce and there are conflicting data as to which of these methods best predicts cardiovascular disease. This review highlights recent studies and current controversies in the field. In consideration of the expected increased use of HbA_1c as a screening tool to identify individuals with alteration of glycaemic homeostasis, we focused on the evidence regarding the ability of HbA_1c as a diagnostic tool for pre-diabetes and as a useful marker in identifying patients who have an increased risk for cardiovascular disease. Finally, we reviewed the current evidence regarding non-traditional glycaemic biomarkers and their use as alternatives to or additions to traditional ones.

Keywords: Cardiovascular risk; Diagnostic criteria; Glycated haemoglobin; Non-traditional glycaemic markers; Pre-diabetes.

Figure 1

Agreement between glycated haemoglobin pre-diabetes, impaired fasting glucose and impaired glucose tolerance[2]. IFG: Impaired fasting glucose; IGT: Impaired glucose tolerance; HbA1c: Glycated haemoglobin.

Figure 2

Intima media thickness, endogenous receptor for advanced glycation end-products, S100A12 and 5-hydroxyvitamin D according to glucose tolerance and glycated haemoglobin levels. A: IMT, ^aP < 0.05 vs CTRL; B: esRAGE, ^aP < 0.05 vs CTRL; C: S100A12, ^aP < 0.05 vs CTRL; D: 25(OH)D, ^aP < 0.05 vs CTRL. IMT: Intima-media thickness; esRAGE: Endogenous receptor for advanced glycation end-products; 25(OH)D: 25-hydroxyvitamin D; NFG: Normal fasting glucose; NGT: Normal glucose tolerance; IFG: Impaired fasting glucose; IGT: Impaired glucose tolerance; T2DM: Type 2 diabetes mellitus; HbA_1c: Glycated haemoglobin.