The research analyzed clinical data from 1,732 participants, tracking 12 health-related traits including blood sugar levels, insulin resistance, kidney function, blood pressure, and cholesterol. To make sense of these long-term patterns, the team applied tensor decomposition to uncover longitudinal trajectories, and Gaussian mixture modeling to classify patients into clusters. Complication risks for each group were then compared using regression analyses.
The study identified 4 clear clusters of prediabetes progression:
- Cluster 1 and Cluster 2 (73% of participants): These individuals maintained stable blood sugar, blood pressure, and lipid levels over time. While nearly half in Cluster 1 and more than two-thirds in Cluster 2 eventually developed T2D, their risk of serious vascular complications remained low. Thus, diabetes progression did not automatically translate into organ damage for most.
- Cluster 3 (12% of participants): This group underwent the sharpest increase in insulin resistance and blood sugar. Nearly all (92%) went on to develop T2D. Also, the complication rates soared which showed an almost 9-fold increase in risk of retinopathy (eye disease) and more than triple the risk of neuropathy (nerve damage) compared to other groups.
- Cluster 4 (15% of participants): Unlike Cluster 3, members of this group displayed early kidney stress, marked by microalbuminuria, even before developing diabetes (73% eventually did). Their kidney function steadily declined, and they were twice as likely to experience cardiovascular events such as heart attacks or strokes, despite having cholesterol levels similar to the lower-risk groups.
The study points to a critical shift in how prediabetes should be viewed. Roughly two-thirds of individuals appear “metabolically resilient,” showing low long-term complication rates even if they progress to diabetes. However, the remaining third exhibit early metabolic signals that precede specific, severe complications.
Overall, this research emphasized that preventive strategies must be tailored accordingly. For those with early kidney issues, the window to prevent cardiovascular disease may actually come before diabetes fully develops. Also, aggressive management of insulin resistance in high-risk individuals could stave off vision and nerve damage.
Source:
Kobayashi, E., Linden-Santangeli, N. J., Chan, N., Toomey, C. B., Mudaliar, S., Temprosa, M., Edelstein, S., Goyal, R., Rangamani, P., Majithia, A. R., Diabetes Prevention Program Research Group, Bray, G. A., Gadde, K. M., Culbert, I. W., Arceneaux, J., Chatellier, A., Dragg, A., Champagne, C. M., Duncan, C., … Hivert, M.-F. (2025). Longitudinal metabolic trajectories in Diabetes Prevention Program participants reveal subgroups with varying micro- and macrovascular complication risks. Diabetes Care,. https://doi.org/10.2337/dc25-0866
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