Association of prediabetes by fasting glucose and/or haemoglobin A1c levels with subclinical atherosclerosis and impaired renal function: Observations from the Dallas Heart Study

Background: Prediabetes defined by fasting plasma glucose (FPG) and glycosylated haemoglobin (HbA1c) predicts incident diabetes, but their individual and joint associations with micro- and macro-vascular risk remain poorly defined. Methods: FPG, HbA1c, coronary artery calcium (CAC), carotid wall thickness, estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) were measured in adults free from prior diabetes or cardiovascular disease (CVD) in the Dallas Heart Study 2 (DHS-2), a population-based cohort study. Prediabetes was defined by FPG 100-125 mg/dL and/or HbA1c 5.7%-6.4%. Multivariable logistic regression was used to analyse associations of HbA1c and/or FPG in the prediabetes range with subclinical atherosclerosis and renal measures. Results: The study comprised 2340 participants, median age = 49 years; 60% women and 50% black. Those with prediabetes were older (52 vs 48 years), more often men (63% vs 53%), black (53% vs 47%) and obese (58% vs 40%; p < 0.001 for each). Prediabetes was captured by FPG alone (43%), HbA1c alone (30%) or both (27%). Those with prediabetes by HbA1c or FPG versus normal HbA1c/FPG had more CAC [odds ratio (OR) = 1.8; 95% confidence interval (CI) = 1.5-2.2], higher carotid wall thickness (1.32 vs 1.29 mm, p < 0.001), eGFR < 60 mL/min [OR = 1.6 (95% CI = 1.1-2.4)], UACR > 30 mg/dL [OR = 1.8 (95% CI = 1.2-2.7)] and a higher odds for the composite eGFR + UACR [chronic kidney disease (CKD) 2] [OR = 1.9 (95% CI = 1.5-2.6)]. After multivariable adjustment, none of these associations remained significant. Conclusion: Prediabetes defined by HbA1c and/or FPG criteria is crudely associated with markers of diabetic macro- and micro-vascular disease, but not after statistical adjustment, suggesting the relationships are attributable to other characteristics of the prediabetes population.