Prediabetes in youth with overweight/obesity associated with lower baseline cognition, stable over 2 years

Type 2 diabetes (T2D) is associated with cognitive impairment, but it remains unclear whether this reflects primary effects of metabolic dysfunction or secondary consequences of comorbid conditions, as most studies have focused on older adults. To address this, we examined the relationship between prediabetes and cognition in youth with overweight/obesity in a 2-year longitudinal study (n=67 at baseline; n=42 at follow-up). Participants underwent comprehensive cognitive testing, metabolic phenotyping, and structural and functional neuroimaging. At baseline, youth with prediabetes exhibited lower IQ and poorer performance in executive function, psychomotor speed, and visuospatial processing compared to those with normal glucose control, independent of adiposity. Across the full sample, reduced peripheral insulin sensitivity was associated with slower processing speed and altered central insulin sensitivity in the intraparietal sulcus. Longitudinally, cognitive differences between groups were stable over 2 years and were not explained by changes in adiposity or glucose tolerance. In contrast, expected developmental reductions in cortical surface area were observed only in youth with normal glucose control. These findings demonstrate that prediabetes in youth is associated with a broad and stable neurocognitive disadvantage that is independent of adiposity and not readily reversible with short-term changes in metabolic status. The early emergence and persistence of these differences suggest that altered neurocognitive function may be a feature of metabolic risk prior to overt disease onset.