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 Caroline Willmann
A1 Kathrin Brockmann
A1 Robert Wagner
A1 Stephanie Kullmann
A1 Hubert Preissl
A1 Günter Schnauder
A1 Walter Maetzler
A1 Thomas Gasser
A1 Daniela Berg
A1 Gerhard W Eschweiler
A1 Florian Metzger
A1 Andreas J Fallgatter
A1 Hans-Ulrich Häring
A1 Andreas Fritsche
A1 Martin Heni
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.