1268-P: Associations between ß-Cell Function and Cognitive Measures following Treatment in Youth with Impaired Glucose Tolerance (IGT) or Recently Diagnosed Type 2 Diabetes (T2D)

In cross-sectional studies, adolescents with T2D show poorer cognition than normoglycemic youth. In the Restoring Insulin Secretion (RISE) Study, we assessed longitudinal relationships between insulin sensitivity, β-cell function and cognition in 72 youth (mean age 14.3±2.0, 10-18 y) with IGT or recently diagnosed T2D, randomized to 12 months of metformin (MET) or 3 months of glargine followed by 9 months of metformin (G/M). Hyperglycemic clamps were used to measure insulin sensitivity and β-cell responses: acute (0-10 min) C-peptide response to glucose, steady-state C-peptide (SSCP) at glucose of 11.1 mmol/L, and arginine-stimulated maximum C-peptide response (ACPRmax) at glucose >25 mmol/L. A cognitive battery (CogState^TM and story recall) assessed 1) reaction time; 2) visual discrimination; 3) attention and working memory; and 4) learning and episodic memory. A composite measure of cognition was constructed by scaling the sum of the four domain scores. Linear regression models were fit to assess relationships between cognition, treatment and β-cell function. Treatment group models were adjusted for baseline cognitive function, HbA1c and fasting glucose. β-cell models were adjusted for baseline cognitive and β-cell function. Cognitive composite scores improved over the 12-month treatment period (p<0.001), with no differences between treatment arms. Greater baseline ACPRmax predicted greater improvement in composite scores over 12 months in the G/M (p<0.05), but not MET group (p=0.61). Change in SSCP over the 12-month treatment was positively associated with increased composite scores in the G/M (p<0.05) but not MET group (p=0.35). Thus, improved cognition over the 12-month treatment with G/M in adolescents with IGT or early T2D may be related to practice effects with repeated testing, to changes in β-cell function or to other impacts of insulin treatment.