Basic and clinical science posters: Brain function
P36
The relationship between mid-life hyperglycaemia and later-life brain outcomes: Focus on amyloidosis, whole brain volume and white matter disease
N Fatih2, SN James1,2, CA Lane1, J Barnes1, TD Parker1, A Keshavan1, A Wong2, NC Fox1, JM Schott1, M Richards2
1Dementia Research Centre, University College London Queen Square Institute of Neurology, University College London, London, UK, 2MRC Unit for Lifelong Health and Ageing at University College London, London, UK
Type 2 diabetes is associated with poor cognitive outcomes and Alzheimer's disease (AD) (1). Hyperglycaemia is an underlying trait of type 2 diabetes (2). We investigated whether midlife hyperglycaemia is associated with worse neuroimaging outcomes at age 69–71.
Participants from Insight46, a neuroscience substudy of the National Survey of Health and Development (NSHD) birth cohort, underwent combined MR/18F-florbetapir PET imaging at age 69–73 (3). Linear and logistic regressions were conducted to explore the relationship between midlife haemoglobin 1ac (HbA1c) (age 53[n=393], 63[n=347] and 69[n=403]) with white matter hyperintensity volume (WMHV), whole brain volume (WBV) and Ab-status.
There was no evidence of an association between HbA1c and Ab-status or WMHV (all p > 0.71). Higher HbA1c at all ages were associated with lower WBV, adjusted for total intercranial volume. Higher HbA1C at age 69 was associated with lower WBV, even when adjusting for sex, social class, BMI, systolic blood pressure and cholesterol; for every increase in 1mmol/l in HbA1c at age 69, there was a reduction of 7.16ml/l of WBV (b=−7.25, 95% Cl=−11.42, −3.07, p < 0.001).
The findings suggest that hyperglycaemia in mid-life, particularly at age 69, is associated with later-life smaller brain volume. However, midlife hyperglycaemia did not appear to be associated with white matter pathology or amyloidosis. Future work will further explore these relationships as the cohort continues to be followed up.
P37
Abstract withdrawn
P38 
Cellular metabolism and Ca2+ signalling are modified differentially in rat hypothalamic and cortical primary astrocytes by acute and recurrent low glucose
PG Weightman Potter, A Randall, C Beall
College of Medicine and Health, University of Exeter, Exeter, UK
Aims Hindbrain astrocytes can directly sense changes in glucose levels mediate aspects of the counterregulatory response (CRR). This is reflected and likely mediated by changes to [Ca2+]i signalling. The precise aetiology of blunted CRR following recurrent hypoglycaemia (RH) and the effect on astrocytic calcium signalling remains poorly defined. In addition, in the rat hypothalamus, the typical enhancement of glutamatergic signalling induced by hypoglycaemia is lost after RH. As astrocytes are critical for the glutamate–glutamine (G–G) cycle, they are a potential regulator of glutamate-mediated CRR.
Methods Primary cultures of rat hypothalamic (HTAS) and cortical (CRTAS) astrocytes were exposed to acute and recurrent low glucose (RLG), for 4 days with and without glutamate (100μM). Intracellular Ca2+ signalling was measured using the ratiometric dye Fura-2 AM, and mitochondrial and glycolytic flux using a Seahorse Bioanalyser.
Results One hour of low glucose (LG) in vitro increased and decreased [Ca2+]i of CRTAS and HTAS, respectively, mimicking a glucose-inhibited (GI) and glucose-excited (GE) phenotype in each cell type. Mitochondrial oxygen consumption rates (OCR) were increased by LG in CRTAS but not HTAS, corresponding to the changes in [Ca2+]i. RLG increased basal OCR and glycolytic rates in both cell types, with prior treatment of glutamate partially rescuing the response in HTAS but exacerbating it in CRTAS.
Conclusions HTAS have a GE response whereas CRTAS have a GI response to acute LG in vitro. These data demonstrate, for the first time, heterogeneity in the response to acute and recurrent low glucose in astrocytes isolated from different brain regions.
