Associations between insulin‐like growth factor‐1 and executive function in normoglycemia, prediabetes, and type 2 diabetes mellitus

Abstract Background The relationship between insulin‐like growth factor‐1 (IGF‐1) and cognition has been studied in healthy individuals, yet the results have been inconclusive. The aim of this study was to determine whether the association between IGF‐1 and executive function differs in individuals with normoglycemia, prediabetes, and type 2 diabetes mellitus (T2DM). Method The Midlife in the United States (MIDUS) study used the Brief Test of Adult Cognition by Telephone (BTACT) to assess cognitive function. A composite z‐score for executive function was created from the following tests: Digits backward span, category fluency, number series, backward counting, and Stop and Go Switch Task (SGST). IGF‐1 levels were measured from fasting blood samples using an immunochemiluminescent assay. Normoglycemia was defined as individuals without a physician diagnosis of diabetes and glycated hemoglobin (HbA1c) < 5.6%. Prediabetes was defined as those without a physician diagnosis of diabetes and HbA1c between 5.7%‐6.4%. T2DM was defined as anyone with a physician diagnosis of diabetes, or HbA1c ≥6.5%, or use of oral hypoglycemic medication. Multiple imputation was used to handle missing covariate data. A linear regression model controlling for demographic factors, homeostatic model of insulin resistance (HOMA‐IR), C‐reactive protein (CRP) levels, exercise, smoking, sleep disturbance, alcohol intake and medication use, was used to determine the cross‐sectional association between IGF‐1 and executive function across subgroups. Result The MIDUS dataset included 447 normoglycemia (47.0% female, mean age 53.4±9.6), 467 prediabetes (57.4% female, mean age 56.8±10.6), and 271 T2DM participants (53.1% female, mean age 57.5±9.8). In participants with prediabetes, IGF‐1 levels were associated with better executive function (β = 0.126, p = 0.007), particularly in males (β = 0.258, p<0.001). This association was absent in individuals with normoglycemia or T2DM. Compared to males with prediabetes, the opposite trend was observed in males with T2DM (β = ‐0.181, p = 0.062). Conclusion The findings of this study suggest that the association between IGF‐1 and executive function may be influenced by insulin resistance or T2DM. Gaining a better understanding of why the associations differ in T2DM compared to prediabetes may explain the inconsistency observed in the literature and help elucidate the mechanism behind cognitive decline in T2DM.