Insulin resistance and impaired β-cell function are associated with risk of cognitive decline in adults over 65 y of age. Their impact on cognition in youth and adults <65 y is less clear. We assessed the relationship between insulin sensitivity, β-cell function and cognition in never or briefly-treated youth (n=71, mean age 14.2±2.0, 10-18 y) and treatment-naïve adults (n=236, mean age 54.4±8.6, 26-66 y) with IGT or early T2D in the Restoring Insulin Secretion (RISE) Study. Hyperglycemic clamps were used to measure insulin sensitivity (steady state glucose infusion rate/insulin [M/I]) and β-cell responses: acute (0-10 min) C-peptide (ACPRg) response to glucose, steady-state C-peptide (SSCP) at a serum glucose of 11.1 mmol/L, and arginine-stimulated maximum C-peptide (ACPRmax) responses at glucose >25 mmol/L. The cognitive battery (CogStateTM and story recall) assessed 1) psychomotor speed; 2) visual pattern separation; 3) visual attention and working memory; and 4) verbal learning and episodic memory. Linear regression models were fit to assess relationships between cognition and clamp measures by age group, adjusted for age, education (adults only), race, sex, and diabetes status. Models including β-cell responses were also adjusted for M/I to account for the role of insulin sensitivity to modulate β-cell function. M/I was not associated with cognitive outcomes for adults or children. For adults, reaction time was slower for participants with worse β-cell function assessed by ACPRg and ACPRmax (p<0.05). Lower SSCP in adults was associated with worse visual pattern separation (p<0.05), a test sensitive to risk for age-related cognitive decline, whereas in youth higher SSCP associated with trends for lower scores for learning (p=0.065) and memory (p=0.052). These results suggest that the relationships between β-cell function and specific cognitive domains differ in a developmentally-dependent manner.


S. Craft: Advisory Panel; Self; vTv Therapeutics. Research Support; Self; Eli Lilly and Company. A. Claxton: Employee; Self; Alkermes. M. Tripputi: None. S. Edelstein: None. S.A. Arslanian: None. K.A. Temple: None. K.J. Nadeau: None. A. Sanderlin: None. M. Espeland: Research Support; Self; National Institutes of Health. Other Relationship; Self; Boehringer Ingelheim International GmbH, Ironwood Pharmaceuticals, Inc. B. Mokhlesi: None. K.J. Mather: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. P. Zeitler: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Research & Development, Merck & Co., Inc., Novo Nordisk Inc. R. Consortium: None.


National Institute of Diabetes and Digestive and Kidney Diseases

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