Insulin Use and CKD Are Risk Factors for Mild Cognitive Impairment (MCI) or Dementia in Persons with Type 2 Diabetes

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Background: Both insulin use and CKD are risk factors for hypoglycemic episodes in patients with diabetes. Recurrent hypoglycemia is associated with increased risk of dementia. Hence, we examined whether insulin use and CKD are associated with increased risk of MCI/dementia. Methods: We analyzed a national VA cohort (N =855,133) with T2DM defined by ICD-9 codes and outpatient serum creat from 1/2008 to 12/2010. Index date was the date of first outpatient serum creatinne measurement. Baseline comorbidities were defined by ICD-9 codes from 10/1999 to the index date. MCI/ dementia were defined by ICD9/10 codes. Those with baseline MCI/dementia were excluded and new onset of MCI/dementia was tracked from index date to 12/31/2020. A multivariate logistic regression model of baseline variables was used to develop propensity scores of baseline insulin use (24% were on insulin at baseline). A propensity score matched cohort (N = 288,374) was used to relate baseline insulin use and CKD stages with subsequent MCI/dementia in Cox regression models. Results: Baseline mean age was 65 ±11 yrs, 20% black and mean eGFR 72±24. There were 40,299 MCI/dementia events over 2,439,244 years of follow up. There was a graded increase in incidence rate of MCI/dementia by CKD stages and insulin use (Fig1). In a Cox regression model adjusted for propensity scores and covariates, both insulin use and advanced CKD were associated with higher risk of MCI/dementia (Fig 2). Conclusions: Both insulin use and advanced CKD are associated with higher risk of MCI/dementia in persons with T2DM. Funding: NIDDK Support, Other NIH Support - NHLBI, Veterans Affairs Support

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