Dataset Information

Effects of ACE-inhibition on IGF-1 and IGFBP-3 concentrations in older adults with high cardiovascular risk profile.

ABSTRACT: OBJECTIVES:The present study evaluates the effects of a 6-month treatment with an ACE-inhibitor (ie, fosinopril) on serum concentrations of total IGF-1 and IGF binding protein (IGFBP)-3 in older adults at high risk for cardiovascular disease. DESIGN:Data are from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study, a double-blind, crossover, randomized, placebo-controlled trial. SETTING:Participants were recruited from the communities of Winston Salem, NC, and Greensboro, NC. PARTICIPANTS:Subjects > or = 55 years old with high cardiovascular disease risk profile. INTERVENTION:The intervention consisted of 6-month administration of fosinopril vs. placebo. MEASUREMENTS:Serum concentrations of total IGF-1 and IGFBP-3 were measured in 100 participants of the TRAIN study at baseline, 6-month and 12-month follow-up visits. Differences in total IGF-1 and IGFBP-3 concentrations were assessed using two-sided paired ttests. RESULTS:The mean age of participants (47% women) was 66.5 (standard deviation 7.2) years. Serum concentrations of total IGF-1 were significantly higher after 6-month treatment with fosinopril compared to placebo (203.73 ng/mL vs 194.24 ng/mL; p=0.02): After ACE-inhibitor intervention, significantly higher serum IGFBP-3 concentrations compared to controls (4308.81 ng/mL vs 4086.93 ng/mL; p=0.03) were also reported. CONCLUSIONS:A six-month treatment with fosinopril increases systemic levels of total IGF-1 and IGFBP-3 in older adults with high cardiovascular risk profile. This may represent a potential biological explanation to the beneficial effects of ACE-inhibition on stroke, ischemic heart disease and insulin resistance.

SUBMITTER: Giovannini S

PROVIDER: S-EPMC4311891 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Effects of ACE-inhibition on IGF-1 and IGFBP-3 concentrations in older adults with high cardiovascular risk profile.

Giovannini S S Cesari M M Marzetti E E Leeuwenburgh C C Maggio M M Pahor M M

The journal of nutrition, health & aging 20100601 6

<h4>Objectives</h4>The present study evaluates the effects of a 6-month treatment with an ACE-inhibitor (ie, fosinopril) on serum concentrations of total IGF-1 and IGF binding protein (IGFBP)-3 in older adults at high risk for cardiovascular disease.<h4>Design</h4>Data are from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study, a double-blind, crossover, randomized, placebo-controlled trial.<h4>Setting</h4>Participants were recruited from t ...[more]

PMID: 20617288

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Project description:BackgroundThe insulin/insulin-like signaling (IIS) pathways, including insulin-like growth factors (IGFs), vary with age. However, their association with late-life cognition and neuroimaging parameters is not well characterized.MethodsUsing data from the British 1946 birth cohort, we investigated associations of IGF-I, IGF-II and IGF binding protein 3 (IGFBP-3; measured at 53 and 60-64 years of age) with cognitive performance [word-learning test (WLT) and visual letter search (VLS) at 60-64 years and 69 years of age] and cognitive state [Addenbrooke's Cognitive Exam III (ACE-III) at 69-71 years of age], and in a proportion, quantified neuroimaging measures [whole brain volume (WBV), white matter hyperintensity volume (WMHV), hippocampal volume (HV)]. Regression models included adjustments for demographic, lifestyle, and health factors.ResultsHigher IGF-I and IGF-II at 53 years of age was associated with higher ACE-III scores [ß 0.07 95% confidence interval (CI) (0.02, 0.12); scoreACE-III 89.48 (88.86, 90.1), respectively). IGF-II at 53 years of age was additionally associated with higher WLT scores [scoreWLT 20 (19.35, 20.65)]. IGFBP-3 at 60 to 64 years of age was associated with favorable VLS score at 60 to 64 and 69 years of age [ß 0.07 (0.01, 0.12); ß 0.07 (0.02, 0.12), respectively], higher memory and cognitive state at 69 years of age [ß 0.07 (0.01, 0.12); ß 0.07 (0.01, 0.13), respectively], and reduced WMHV [ß -0.1 (-0.21, -0.00)]. IGF-I/IGFBP-3 at 60 to 64 years of was associated with lower VLS scores at 69 years of age [ß -0.08 (-0.15, -0.02)].ConclusionsIncreased measure in IIS parameters (IGF-I, IGF-II, and IGFBP-3) relate to better cognitive state in later life. There were apparent associations with specific cognitive domains (IGF-II relating to memory; IGFBP-3 relating to memory, processing speed, and WMHV; and IGF-I/IGFBP-3 molar ratio related to slower processing speed). IGFs and IGFBP-3 are associated with favorable cognitive function outcomes.

Project description:ContextPost-challenge hyperglycemia (PCH) is common in older adults and is associated with increased cardiovascular disease (CVD) risk and total mortality. However, PCH is rarely recognized in clinical settings, and the glycemic exposure and CVD risk profile of elderly individuals with PCH has not been defined.ObjectiveThe aim of the study was to characterize metabolic and CVD risk profile of elderly subjects with PCH and to determine the effect of acute postprandial metabolic changes on vascular biomarkers.DesignWe conducted a cross-sectional study with a standard meal challenge protocol.ParticipantsOlder adults with normal glucose tolerance (n = 30) or PCH (fasting glucose <126 mg/dl and 2-h glucose >or=170 mg/dl; n = 28) participated in the study.Main outcome measuresWe assessed fasting and postprandial levels of glucose, insulin, lipids, high sensitivity C-reactive protein, plasminogen activator inhibitor-1, and adiponectin and endothelial function using reactive hyperemia peripheral arterial tonometry.ResultsNormal glucose tolerance and PCH subjects were matched for age, sex, body mass index, and ethnicity. Fasting glucose (102 +/- 3 vs. 93 +/- 2 mg/dl; P < 0.001) and glycosylated hemoglobin (5.7 vs. 5.4%; P = 0.01) were modestly higher in the PCH group, which was also more insulin resistant (homeostasis model assessment for insulin resistance, 7.0 +/- 1.3 vs. 4.1 +/- 0.6; P = 0.03). Fasting high sensitivity C-reactive protein was higher (2.6 +/- 0.5 vs. 1.3 +/- 0.2 mg/dl; P = 0.05), and adiponectin was lower (11.6 +/- 1.6 vs. 14.0 +/- 1.3 microg/ml; P = 0.03) in subjects with PCH. Peak and 6-h postprandial area under the curve glucose, insulin, and lipids were higher in PCH subjects, who also had higher fasting and postprandial levels of plasminogen activator inhibitor-1. Reactive hyperemia peripheral arterial tonometry declined postprandially only in PCH.ConclusionsOlder adults with PCH experience significant fasting and postprandial metabolic dysregulation, which is accompanied by a proatherosclerotic and prothrombotic vascular profile.

Dataset Information

Effects of ACE-inhibition on IGF-1 and IGFBP-3 concentrations in older adults with high cardiovascular risk profile.

Publications

Effects of ACE-inhibition on IGF-1 and IGFBP-3 concentrations in older adults with high cardiovascular risk profile.

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