Diagnostic Thresholds for Diabetes: The Association of Retinopathy and Albuminuria with Glycaemia

Tapp RJ, Zimmet PZ, Harper CA, et al. Diabetes Res Clin Pract. 2006;73:315-321.

Diagnostic criteria for diabetes have evolved over time. Current glycemic thresholds for diagnosing diabetes have been defined using the development of retinopathy and microalbuminuria as endpoints. Thresholds for these endpoints have been identified using deciles* of glycemia— fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), and HbA1c (A1C)—as the criteria for determining diabetes. This is done by taking the lower limit of the decile, in which there is increased occurrence of the endpoint. However, large deciles contribute to uncertainty in the thresholds. The aim of this study was to assess the association of FPG, 2hPG, and A1C with retinopathy and microalbuminuria using deciles and continuous change point models to analyze the relationship of each glycemic measure with retinopathy and microalbuminuria as a way to identify therapeutic thresholds and validate current diagnostic criteria.

The Australian Diabetes, Obesity and Lifestyle Study (AusDiab) was initiated as a population-based study of 11,247 individuals randomly selected from 42 different areas. Eligible individuals were those aged 25 years or older, with known diabetes mellitus (KDM) or newly diagnosed diabetes mellitus. Additional inclusion criteria consisted of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and a random sample of those with normal glucose tolerance (NGT). After exclusions for lack of information regarding retinopathy or microalbuminuria status, data were available for 2182 participants in the retinopathy study and 2389 participants in the microalbuminuria study. The level of retinopathy was determined using retinal photos and a simplified version of the Wisconsin grading system. Diabetic retinopathy in this study was defined as the presence of 1 or more retinal hemorrhage and/or microaneurysm. Random samples of 162 photos were re-graded to check for repeatability of grading; overall there was consistency between the first and second grading. Additionally, plasma glucose levels and urinary albumin and creatinine were measured using enzyme tests through which microalbuminuria (defined as an albumin-to-creatinine ratio of >2.5 mg/mmol in men and ≥3.5 mg/mmol in women) was assessed.

Results for retinopathy showed a similar trend between FPG, 2hPG, and A1C. The prevalence of retinopathy in the first 8 deciles of FPG and A1C was 7.2% and 6.6%, respectively, and 6.3% in the first 9 deciles of 2hPG. There was no change in retinopathy prevalence with increasing glucose or A1C levels in these deciles. However, above these deciles, the prevalence for retinopathy sharply increased to 18.6% and 21.3% in the top 2 deciles of FPG and A1C and to 10.9% in the top decile of 2hPG. The thresholds for retinopathy were established at 7.1 mmol/L for FPG, 6.1% for A1C, and 13.1 mmol/L for 2hPG. Similarly, prevalence for microalbuminuria in the first 8 deciles of FPG and A1C was 11.1% and 11.2%, respectively. However, in contrast to the retinopathy results, microalbuminuria showed a gradual increase with increasing glucose and A1C. Prevalence for microalbuminuria drastically rose in the top 2 deciles of FPG and A1C to 28.9% and 29.8%, respectively. The profile for 2hPG did not manifest a threshold effect for microalbuminuria. The thresholds for microalbuminuria were 7.2 mmol/L for FPG and 6.1% for A1C.

Additional consideration of retinopathy prevalence by glycemic cutpoints was conducted by comparing it to the World Health Organization (WHO) diagnostic criteria. The study found that FPG values for both retinopathy and microalbuminuria were well correlated to the WHO criteria. However, the 2hPG cutpoint for retinopathy did not correspond with the current WHO 2hPG value of 11.1 mmol/L. Previous studies have also demonstrated values different than the WHO diagnostic criteria for 2hPG value.

* The first, second, third, etc deciles are the tenth, twentieth, thirtieth, etc percentiles.