Age, glucose tolerance, and cognitive performance in female vervet monkeys

This study assessed relationships between age, glucose and insulin metabolism, and cognitive performance in vervet monkeys (Chlorocebus aethiops sabaeus) a valuable model for aging research. Executive function, working memory, body mass index (BMI), and glucose and insulin responses during intravenous glucose tolerance tests (IVGTTs) were assessed in 41 middle-aged to older (9.1-29.5 years), socially housed, female vervets. Cluster analyses yielded four distinct IVGTT response patterns relevant to type 2 diabetes development: (I) normal insulin response and euglycemia; (II) baseline euglycemia, hyperinsulinemic response, and adequate glucose clearance; (III) baseline euglycemia, impaired insulin response, and impaired glucose clearance; and (IV) baseline hyperglycemia, impaired insulin response, and hyperglycemia throughout the test. Age was associated with baseline glucose (β = 3.615; p < 0.001), glucose area under the curve (AUC) (β = 321.07; p = 0.002), glucose clearance (β =  - 0.145; p < 0.001), and insulin AUC (β =  - 40.603; p = 0.020). There was a main effect of aging over 1.5 years on insulin AUC (β =  - 392.026, p = 0.023). Older animals tended to exhibit more rapid increases in fasting glucose over time (β = 0.986; p = 0.051). Higher BMI was associated with greater insulin resistance (HOMA-IR: β = 0.167; p = 0.004), fasting hyperglycemia (β = 1.120; p = 0.010), and impaired glucose regulation (glucose AUC: β = 136.59; p = 0.001). Worsening glycemic control was associated at follow-up with poorer executive function (χ² = 8.134; p = 0.043) and tended to be associated with poorer working memory (χ² = 6.363; p = 0.095). Aging vervets undergo a decline in glucose sensitivity, increasing insulin resistance, and impaired glucose handling. Metabolic perturbations characteristic of worsening prediabetes predicted worse cognition; however, future study is needed identify mechanisms underlying these relationships.