Using nephropathy as an outcome to determine the HbA1c diagnostic threshold for type 2 diabetes

Objective The hemoglobin A1c (HbA1c) diagnostic threshold for type 2 diabetes (T2D) of 6.5% (48mmol/mol) was based on the prevalence of retinopathy found in populations not known to have T2D. It is unclear if nephropathy has a similar HbA1c threshold, partly because it is a rarer complication of early diabetes. This cohort study investigated a very high diabetes prevalence population to determine if a better diagnostic HbA1c value can be established for predicting nephropathy rather than retinopathy in subjects without T2D. Methods The urine albumin:creatinine ratios (UACRs) of 2,920 healthy individuals from the Qatar Biobank who had an HbA1c≥5.6%. were studied. Nephropathy was defined as a UACR≥30mg/g and its prediction by HbA1c was assessed using cut-points ranging from 5.7 to 7.0% to dichotomize high from low HbA1c. Results Although there was a significant trend for an increased prevalence of abnormal UACR as the HbA1c threshold increased (p<0.01), significance was due mostly to subjects with HbA1c ≥ 7.0% (53mmol/mol). The odds ratios for abnormal UACR were similar over the 5.7 to 6.9% HbA1c threshold range, with a narrow odds ratio range of 1.2-1.6. Utilizing area-under-receiver-operating characteristic curves, no HbA1c threshold <7.0% was identified as the best predictor of nephropathy. Conclusion Even in a population with a high prevalence of known and unknown diabetes, no HbA1c threshold <7.0% could be found predicting an increased prevalence of nephropathy. This means there is not a requirement to change the existing retinopathy-based HbA1c threshold of 6.5% to also accommodate diabetes nephropathy risk.