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In a large cohort of Pima individuals, the frequency of retinopathy – defined as the presence of at least one hemorrhage, one microaneurysm, or proliferative retinopathy – was directly related to baseline FPG and 2‐h PG [55]. Beginning at a baseline FPG threshold of 6.0–6.4 mmol/L and 2‐h PG threshold of 9.0–10.6 mmol/L, there was a significant increase in period prevalence (10‐year interval) of retinopathy. Additional data from the Pima individuals illustrated that beyond a HbA1c threshold of 6.2% there was a significant increase in the prevalence of retinopathy [12]. Similar glycemic thresholds for an increase in the prevalence of retinopathy were observed in a cross‐sectional study of Egyptians and data from the Third National Health and Nutrition Examination Survey [13, 14]. Additionally, in the Diabetes Prevention Program (DPP), diabetic retinopathy was detected in 7.9% of the subjects with IGT and in 12.6% of the subjects who developed DM [56]. The prevalence of retinopathy is significantly higher in subjects with DM, but retinopathy can develop in subjects with prediabetic range dysglycemia.

Pooled data analysis of nine studies from five countries examined glycemic thresholds for diabetes‐specific retinopathy (defined as moderate or more severe retinopathy) in 44 623 subjects [57]. A curvilinear relationship was found to exist for FPG and HbA1c when diabetic retinopathy was plotted against continuous glycemic measures. Diabetes‐specific retinopathy began to increase from a FPG of 6.0–6.4 mmol/L and from a HbA1c of 6.0–6.4%. Based on vigintile distributions, glycemic thresholds for diabetes‐specific retinopathy were observed over the range of 6.4–6.8 mmol/L for FPG, 9.8–10.6 mmol/L for 2‐h PG, and 6.3–6.7% for HbA1C. Compared with the first vigintile, the odds ratios for diabetes‐specific retinopathy for the above vigintile distributions were 2.5 (95% CI 1.2–5.2) for FPG, 10.1 (95% CI 1.3–79.4) for 2 h PG, and 4.5 (95% CI 1.4–15.2) for HbA1c.

A major limitation of many studies that examine the prevalence of retinopathy is the diagnostic criteria used to define diabetes‐specific retinopathy [57]. The use of an overly broad definition for retinopathy leads to the inclusion of subjects with mild retinopathy, which may have etiologies other than hyperglycemia. Overall, the rate of retinopathy increases with the degree and duration of hyperglycemia [56, 57]. Subjects with prediabetes have a higher prevalence of retinopathy than subjects with NFG/NGT, although the prevalence remains relatively low. In many populations, the glycemic threshold for retinopathy occurs in the prediabetic range of dysglycemia [57, 58].