RT Journal Article SR Electronic T1 Insulin sensitivity predicts cognitive decline in individuals with prediabetes JF BMJ Open Diabetes Research & Care JO BMJ Open Diab Res Care FD American Diabetes Association SP e001741 DO 10.1136/bmjdrc-2020-001741 VO 8 IS 2 A1 Willmann, Caroline A1 Brockmann, Kathrin A1 Wagner, Robert A1 Kullmann, Stephanie A1 Preissl, Hubert A1 Schnauder, Günter A1 Maetzler, Walter A1 Gasser, Thomas A1 Berg, Daniela A1 Eschweiler, Gerhard W A1 Metzger, Florian A1 Fallgatter, Andreas J A1 Häring, Hans-Ulrich A1 Fritsche, Andreas A1 Heni, Martin YR 2020 UL http://drc.bmj.com/content/8/2/e001741.abstract AB Introduction Epidemiological studies indicate an association between type 2 diabetes and cognitive dysfunction that appear to start already in the prediabetic state. Although cross-sectional studies have linked insulin resistance to impaired cognition, the potential predictive value of insulin resistance has not yet been sufficiently studied longitudinally without confounding by overt diabetes (and its pharmacological treatment).Research design and methods We investigated longitudinal data from participants of the ‘Tübinger Evaluation of Risk Factors for Early Detection of Neurodegeneration’ Study. Subjects underwent a neurocognitive assessment battery (CERAD Plus battery; Consortium to Establish a Registry for Alzheimer’s Disease) at baseline and followed every 2 years (median follow-up 4.0 Q1–3: 2.2–4.3 years). Subjects within a pre-diabetic glycated hemoglobin range of 5.6%–6.5% underwent 5-point 75 g oral glucose tolerance tests (OGTTs) with assessment of insulin sensitivity and insulin secretion (n=175). Subjects with newly diagnosed diabetes mellitus or with major depressivity (Beck Depression Inventory >20) were excluded (n=15). Data were analyzed by mixed models using sex, age and glycemic trait as fixed effects. Subject and time since first measurement were used as random effects.Results Insulin sensitivity was positively associated with the CERAD sum score (higher is better) in a time-dependent manner (p=0.0057). This result is mainly driven by a steeper decrease in the memory domain associated with lower insulin sensitivity (p=0.029). The interaction between age and insulin sensitivity was independent of glycemia (p=0.02). There was also no association between insulin secretion and cognition.Conclusions Insulin resistance rather than sole elevation of blood glucose predicts cognitive decline, specifically in the memory domain, in persons with prediabetes. Treatments of diabetes that improve insulin sensitivity might therefore have the potential to postpone or even prevent cognitive decline in patients with diabetes.