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 % (48 mmol/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 2920 healthy individuals from the Qatar Biobank who had an HbA1c >= 5.6 %. were studied. Nephropathy was defined as a UACR >= 30 mg/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 % (53 mmol/mol). The odds ratios for abnormal UACR were similar over the 5.7 -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.