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Association of Insulin Resistance With Cerebral Glucose Uptake in Late Middle-Aged Adults at Risk for Alzheimer Disease.

ABSTRACT: IMPORTANCE:Converging evidence suggests that Alzheimer disease (AD) involves insulin signaling impairment. Patients with AD and individuals at risk for AD show reduced glucose metabolism, as indexed by fludeoxyglucose F 18-labeled positron emission tomography (FDG-PET). OBJECTIVES:To determine whether insulin resistance predicts AD-like global and regional glucose metabolism deficits in late middle-aged participants at risk for AD and to examine whether insulin resistance-predicted variation in regional glucose metabolism is associated with worse cognitive performance. DESIGN, SETTING, AND PARTICIPANTS:This population-based, cross-sectional study included 150 cognitively normal, late middle-aged (mean [SD] age, 60.7 [5.8] years) adults from the Wisconsin Registry for Alzheimer's Prevention (WRAP) study, a general community sample enriched for AD parental history. Participants underwent cognitive testing, fasting blood draw, and FDG-PET at baseline. We used the homeostatic model assessment of peripheral insulin resistance (HOMA-IR). Regression analysis tested the statistical effect of HOMA-IR on global glucose metabolism. We used a voxelwise analysis to determine whether HOMA-IR predicted regional glucose metabolism. Finally, predicted variation in regional glucose metabolism was regressed against cognitive factors. Covariates included age, sex, body mass index, apolipoprotein E ?4 genotype, AD parental history status, and a reference region used to normalize regional uptake. MAIN OUTCOMES AND MEASURES:Regional glucose uptake determined using FDG-PET and neuropsychological factors. RESULTS:Higher HOMA-IR was associated with lower global glucose metabolism (??=?-0.29; P?

SUBMITTER: Willette AA

PROVIDER: S-EPMC4570876 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Association of Insulin Resistance With Cerebral Glucose Uptake in Late Middle-Aged Adults at Risk for Alzheimer Disease.

Willette Auriel A AA Bendlin Barbara B BB Starks Erika J EJ Birdsill Alex C AC Johnson Sterling C SC Christian Bradley T BT Okonkwo Ozioma C OC La Rue Asenath A Hermann Bruce P BP Koscik Rebecca L RL Jonaitis Erin M EM Sager Mark A MA Asthana Sanjay S

JAMA neurology 20150901 9

<h4>Importance</h4>Converging evidence suggests that Alzheimer disease (AD) involves insulin signaling impairment. Patients with AD and individuals at risk for AD show reduced glucose metabolism, as indexed by fludeoxyglucose F 18-labeled positron emission tomography (FDG-PET).<h4>Objectives</h4>To determine whether insulin resistance predicts AD-like global and regional glucose metabolism deficits in late middle-aged participants at risk for AD and to examine whether insulin resistance-predicte ...[more]

PMID: 26214150

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Project description:BackgroundAlthough dietary selenium (Se) deficiency or excess induces type 2 diabetes-like symptoms in mice, suboptimal body Se status usually causes no symptoms but may promote age-related decline in overall health.ObjectivesWe sought to determine the dietary Se requirement for protection against type 2 diabetes-like symptoms in mice.MethodsThirty mature (aged 4 mo) male C57BL/6J mice were fed a Se-deficient torula yeast AIN-93M diet supplemented with Na2SeO4 in graded concentrations totaling 0.01 (basal), 0.04, 0.07, 0.10, and 0.13 (control) mg Se/kg for 4 mo (n = 6) until they were middle-aged (8 mo). Droplets of whole blood were used to determine glucose tolerance and insulin sensitivity in the mice from ages 5 to 8 mo. Postmortem serum, liver, and skeletal muscle were collected to assay for selenoprotein expression and markers of glucose metabolism. Data were analyzed by 1-way ANCOVA with or without random effects for time-repeated measurements using live mice or postmortem samples, respectively.ResultsCompared with control, the consumption of basal diet increased (P < 0.05) fasting serum insulin (95% CI: 52%, 182%) and leptin (95% CI: 103%, 118%) concentrations in middle-aged mice. Dietary Se insufficiency decreased (P < 0.05) 1) glucose tolerance (13-79%) and insulin sensitivity (15-65%) at ≤0.10 mg Se/kg; 2) baseline thymoma viral proto-oncogene phosphorylation on S473 (27-54%) and T308 (22-46%) at ≤0.10 and ≤0.07 mg Se/kg, respectively, in the muscle but not the liver; and 3) serum glutathione peroxidase 3 (51-83%), liver and muscle glutathione peroxidase 1 (32-84%), serum and liver selenoprotein P (28-42%), and liver and muscle selenoprotein H (39-48%) and selenoprotein W (16-73%) protein concentrations at ≤0.04, ≤0.10, ≤0.07, and ≤0.10 mg Se/kg, respectively.ConclusionsMice fed diets containing ≤0.10 mg Se/kg display impaired glucose tolerance and insulin sensitivity, suggesting increased susceptibility to type 2 diabetes by suboptimal Se status at levels ≤23% of nutritional needs.

Dataset Information

Association of Insulin Resistance With Cerebral Glucose Uptake in Late Middle-Aged Adults at Risk for Alzheimer Disease.

Publications

Association of Insulin Resistance With Cerebral Glucose Uptake in Late Middle-Aged Adults at Risk for Alzheimer Disease.

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