Objective This study explored the association of BMI and insulin sensitivity with cognitive performance in type 2 diabetes. Methods A cross‐sectional analysis of data from the baseline assessment of the Glycemia Reduction Approaches in Diabetes: a Comparative Effectiveness Study (GRADE) was conducted. BMI was used as a surrogate of adiposity and the Matsuda index as the measure of insulin sensitivity. Cognitive tests included the Spanish English Verbal Learning Test, the Digit Symbol Substitution Test, and the letter and animal fluency tests. Results Cognitive assessments were completed by 5018 (99.4%) of 5047 participants aged 56.7 ± 10.0 years, of whom 36.4% were female. Higher BMI and lower insulin sensitivity were related to better performance on memory and verbal fluency tests. In models including BMI and insulin sensitivity simultaneously, only higher BMI was related to better cognitive performance. Conclusions In this study, higher BMI and lower insulin sensitivity in type 2 diabetes were cross‐sectionally associated with better cognitive performance. However, only higher BMI was related to cognitive performance when both BMI and insulin sensitivity were considered simultaneously. The causality and mechanisms for this association need to be determined in future studies.
OBJECTIVE Differences in type 2 diabetes phenotype by age are described, but it is not known whether these differences are seen in a more uniformly defined adult population at a common early stage of care. We sought to characterize age-related clinical and metabolic characteristics of adults with type 2 diabetes on metformin monotherapy, prior to treatment intensification. RESEARCH DESIGN AND METHODS In the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), participants were enrolled who had type 2 diabetes duration <10 years, had HbA1c 6.8–8.5%, and were on metformin monotherapy. Participants were randomly assigned to one of four additional glucose-lowering medications. We compared baseline clinical and metabolic characteristics across age categories (<45, 45 to <55, 55 to <65, and ≥65 years) using ANOVA and Pearson χ2 tests. RESULTS Within the GRADE cohort (n = 5,047), we observed significant differences by age, with younger adults having greater racial diversity, fewer medications for common comorbidities, lower prevalence of CVD, higher weight and BMI, and more pronounced hyperglycemia and diabetic dyslipidemia and with metabolic profile indicating lower insulin sensitivity (inverse fasting insulin [1/(fasting insulin)], HOMA of steady-state insulin sensitivity, Matsuda index) and inadequate β-cell response (oral disposition index) (P < 0.05 across age categories). CONCLUSIONS Clinical and metabolic characteristics of type 2 diabetes differ by age within the GRADE cohort. Younger adults exhibit more prominent obesity-related characteristics, including higher obesity levels and lower insulin sensitivity and β-cell compensation. Given the increasing burden of type 2 diabetes and complications, particularly among younger populations, these age-related distinctions may inform risk factor management approaches and treatment priorities. Further study will determine whether age-related differences impact response to therapy.
<p><em>Objective:</em> Differences in type 2 diabetes phenotype by age are described, but it is not known whether these differences are seen in a more uniformly defined adult population at a common early stage of care. We characterize age-related clinical and metabolic characteristics of adults with type 2 diabetes on metformin monotherapy, prior to treatment intensification. </p> <p><em>Research Design and Methods</em>: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study enrolled participants with type 2 diabetes duration <10 years, A1c 6.8-8.5%, on metformin monotherapy, and randomly assigned to one of four additional glucose-lowering medications. We compared baseline clinical and metabolic characteristics across age categories (<45; 45-<55; 55-<65; <u>≥</u>65 years) using ANOVA and Pearson’s chi-squared tests.. </p> <p><em>Results: </em>Within the GRADE cohort (n=5,047), we observed significant differences by age with younger adults having greater racial diversity, fewer medications for common comorbidities, lower prevalence of CVD, higher weight and BMI, more pronounced hyperglycemia and diabetic dyslipidemia, with metabolic profile indicating lower insulin sensitivity (1/fasting insulin, HOMA-2S, Matsuda index) and inadequate β cell response (oral disposition index) (p < 0.05 across age categories). </p> <p><em>Conclusions: </em>Clinical and metabolic characteristics of type 2 diabetes differ by age within the GRADE cohort. Younger adults exhibit more prominent obesity-related characteristics, including higher obesity levels, lower insulin sensitivity and beta cell compensation. Given the increasing burden of type 2 diabetes and complications, particularly among younger populations, these age-related distinctions may inform risk factor management approaches and treatment priorities. Further study will determine whether age-related differences impact response to therapy. </p>
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