ACUTE GLYCEMIC EVENTS AND RISK OF DEMENTIA IN OLDER PATIENTS WITH TYPE 1 DIABETES

Abstract

Animal models show that acute hypoglycemic events harm the Ca-1 and Ca-4 region of the hippocampus and impact cognitive ability. Among people with type 2 diabetes (T2D) severe hypoglycemic or hyperglycemic episodes are strongly associated with a higher dementia risk. Hypoglycemic events are three times more common in the type 1 diabetes (T1D) population versus T2D; yet the possible association between acute glycemic events and dementia has not been explored in T1D. A dynamic cohort comprised of Kaiser Permanente Northern California (KPNC) members with T1D, aged >50 at any time during the study period (N=3742) was followed from 01/01/1996–09/30/2015 for incident dementia diagnoses made in primary care, neurology or psychiatry (ICD-9 codes 290.0–4x, 294.1x, 294.2x, 294.8x, 331.0x). Baseline history of hypo- and hyperglycemic events resulting in emergency room visit or hospitalization were identified in electronic medical records using ICD-9 codes for hypoglycemia (250.0–2) and hyperglycemia (250.1x, 250.2x, 249.2x). Cox proportional hazard models with age as time scale evaluated associations between hypo/hyper glycemic events and dementia. Participants were censored at time of dementia diagnosis, death, lapse in KPNC membership, or end of follow-up. Models were adjusted for sex, race and baseline glycosylated hemoglobin (HbA1c), end stage renal disease, and peripheral arterial disease. The mean age at baseline was 56.1, 47% of the sample was female, and 21% non-white. Five percent (N=182) of patients were diagnosed with dementia during follow-up. Those with dementia were more likely to have cardiovascular disease, stroke and diabetic foot. 18.7% (N=699) had >1 hypoglycemic and 12.6% (N=473) >1 hyperglycemic event at baseline. Compared to those without, patients with hypoglycemic events had a 47% higher risk of dementia (adjusted Hazards Ratio(aHR) 1.47, 95% CI 1.03–2.11) and those with hyperglycemic events a 129% increased risk (aHR 2.29, 95% CI 1.54–3.6) during follow up. This is the first study of acute glycemic events and dementia in T1D. Hypoglycemic and hyperglycemic events both increased dementia risk though the magnitude was stronger for hyperglycemic events. Elderly individuals with T1 are living longer than ever before, thus delineation of glycemic control and brain health needs to be further investigated.