This study aimed to identify patient characteristics associated with the effectiveness of intensive glucose control (i.e., A1c<6.0% vs. A1c 7-8%) in preventing cognitive function decline (CFD) among individuals with type 2 diabetes (T2D) in the ACCORD trial. The Memory in Diabetes (MIND) study was sub trial of the ACCORD study, including 2,977 participants without a history of cognitive impairment or dementia. We applied the causal forest (CF) and causal tree (CT) algorithm to identify participant characteristics that modulate the effectiveness of intensive glucose control in preventing CFD from a list of 58 candidate variables (demographics, disease histories, medications, and biomarkers) at the study baseline. The study outcome was the change of cognitive function from the baseline to the 40th month, assessed through the Digit Symbol Substitution Test (DSST) , Rey Auditory Verbal Learning Test (RAVLT) , Mini-Mental State Examination (MMSE) , and Stroop test. A computer-driven approach identified a close relationship between renal function and the effectiveness of intensive glycemic control in preventing CFD: study participants with the urinary albumin less than 0.4 mg/dl (absolute function change (AFC) : 0.43 in MSSE) or urinary creatinine 120-200 mg/dl (AFC: 0.30 in RAVLT) had slower CFD associated with intensive glycemic control, while participants with GFR<60 (AFC:-0.51 in RVALT) , or GFR<90 (AFC:-1.7 in Stroop) had a faster CFD associated with intensive glycemic control. In addition, only participants with age below 60 years old benefited from the intensive glucose control (AFC:1.23 in DSST) in preventing CFD. All p<0.05. Our study tied renal function to the effectiveness of intensive glycemic control in preventing CFD. Clinicians may consider these individualized characteristics for better-targeted A1c goal setting, especially those at risk for CFD.


H.Kianmehr: None. J.Guo: None. V.Fonseca: Consultant; Abbott, Asahi Kasei Corporation, Bayer AG, Novo Nordisk, Sanofi, Research Support; Fractyl Health, Inc., Jaguar Gene Therapy, Stock/Shareholder; Abbott, Amgen Inc., BRAVO4Health, Mellitus Health. L.Shi: None. H.Shao: Board Member; BRAVO4HEALTH, LLC.

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