Prediabetes: a distinct clinical entity or earlu-stage diabetes?

Abstract

There are paradigmatic studies in diabetes (DM) that mark milestones in the understanding of this highly complex and prevalent pathology.

In 2007, the Diabetes Prevention Program Research Group (DPP) published the study "Prevalence of Retinopathy in Individuals with Impaired Glucose Tolerance and Recently Diagnosed Diabetes". In this study, after a mean follow-up of 3.1 years, retinopathy (DR) was detected in 12.6% of those who developed DM and in 7.9% of those who did not (P = 0.03), concluding that DR can be present starting from prediabetes. In the discussion, the authors commented: "the more careful characterization of long-term glycemia in the DPP cohort and documentation of retinopathy in the prediabetic state support the notion that retinopathy can occur across a wider continuum of glycemia than encompassed by current diagnostic criteria." Going deeper, they stated that "these findings suggest that current diagnostic criteria for DM, based predominantly on the associated risk of retinopathy, may require reconsideration."

The same group published in 2022 the study "Risk Factors for the Development of Retinopathy in Prediabetes and Type 2 Diabetes". It revealed that, 20 years after randomization, 14% of those who still had not developed DM already presented DR; a prevalence similar to that of those who had developed DM at 3 years. This demonstrates that the time of exposure to the noxious agent is a crucial element in the analysis of this pathology.

Turning to the macrovascular field, the DECODE Study Group published the paper "Is the current definition of diabetes relevant to mortality risk from all causes and cardiovascular and non-cardiovascular diseases?", concluding that the relationship between mortality and glycemia is continuous and does not have a defined biological threshold.

Finally, an ACCORD sub-study titled "The Hemoglobin Glycation Index Identifies Subpopulations with Risks or Benefits Derived from Intensive Treatment" showed that patients who glycated more at the same glycemic level suffered higher mortality in the intensive treatment group. Calculating the hemoglobin glycation index at baseline allowed the identification of subpopulations that experienced harm derived from strict glycemic control.

We should ponder deeply on these data—by no means new—which solidly challenge the current diagnostic criteria for DM.