Insulin-Like Growth Factor (IGF) I, -II, and IGF Binding Protein-3 and Risk of Ischemic Stroke

Johnsen, Søren Paaske; Hundborg, Heidi Holmager; Sørensen, H T; Ørskov, Hans; Tjønneland, Anne; Overvad, Kim; Jørgensen, Jens Otto Lunde

doi:10.1210/jc.2004-2088

Cited by 160 publications

(141 citation statements)

References 30 publications

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“…Various studies have investigated the effect of serum IGF1 concentration on development of cardiovascular diseases (CVD) and mortality. Low-normal IGF1 levels have been associated with development of ischemic heart disease and stroke (3,4,5). The relationship of IGF1 with (cardiovascular) mortality is less clear.…”

Section: Introductionmentioning

confidence: 99%

Serum IGF1, metabolic syndrome, and incident cardiovascular disease in older people: a population-based study

Bunderen

Oosterwerff

Schoor

et al. 2013

European Journal of Endocrinology

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Objective: High as well as low levels of IGF1 have been associated with cardiovascular diseases (CVD). The relationship of IGF1 with (components of) the metabolic syndrome could help to clarify this controversy. The aims of this study were: i) to investigate the association of IGF1 concentration with prevalent (components of) the metabolic syndrome; and ii) to examine the role of (components of) the metabolic syndrome in the relationship between IGF1 and incident CVD during 11 years of follow-up. Methods: Data were used from the Longitudinal Aging Study Amsterdam, a cohort study in a representative sample of the Dutch older population (R65 years). Data were available in 1258 subjects. Metabolic syndrome was determined using the definition of the US National Cholesterol Education Program Adult Treatment Panel III. CVD were ascertained by self-reports and mortality data. Results: Levels of IGF1 in the fourth quintile were associated with prevalent metabolic syndrome compared with the lowest quintile (odds ratio: 1.59, 95% confidence interval (CI) 1.09-2.33). The middle up to the highest quintile of IGF1 was positively associated with high triglycerides in women. Metabolic syndrome was not a mediator in the U-shaped relationship of IGF1 with CVD. Both subjects without the metabolic syndrome and low IGF1 levels (hazard ratio (HR) 1.75, 95% CI 1.12-2.71) and subjects with the metabolic syndrome and high IGF1 levels (HR 2.28, 95% CI 1.21-4.28) demonstrated increased risks of CVD. Conclusions: In older people, high-normal IGF1 levels are associated with prevalent metabolic syndrome and high triglycerides. Furthermore, this study suggests the presence of different pathomechanisms for both low and high IGF1 levels and incident CVD.

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Section: Introductionmentioning

confidence: 99%

Serum IGF1, metabolic syndrome, and incident cardiovascular disease in older people: a population-based study

Bunderen

Oosterwerff

Schoor

et al. 2013

European Journal of Endocrinology

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“…IGFBP-3 controls the actions of the IGFs by regulating their distribution and bioavailability to target tissues. 20 The IGF-IGFBP-3 axis is involved in the pathogenesis of cardiovascular dysfunction, [17][18][19] ischemic stroke 21 and atherosclerosis. 22 Individuals with low circulating IGF-1 levels and high IGFBP-3 levels have been reported to have significantly increased risk of developing ischemic heart disease during a 15-year followup period.…”

Section: Introductionmentioning

confidence: 99%

Glucose–insulin homeostasis, lipid profiles and GH-IGF-IGFBP axis in clozapine-treated schizophrenic obesity versus non-psychiatric obesity

Huang

Liou

et al. 2007

Int J Obes

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Objective: Obese patients with schizophrenia being treated with clozapine and non-psychiatric obese are often assumed to share the same physiological changes in obesity. The aim of this study was to identify possible metabolic and hormonal differences between non-psychiatric obese subjects (OB) and obese patients with schizophrenia being treated with clozapine (OSC). Subjects: Fifty-one normal healthy subjects (Nor, body mass index (BMI):23.270.3), 50 OB (BMI:31.770.7) and 71 OSC (BMI:30.470.5). Measurements: Anthropometric, metabolic and hormonal parameters were determined by anthropometry, enzyme autoanalyzer, immunoassay and enzyme-linked immunosorbent assay. Results: Triglyceride, total cholesterol divided by high-density lipoprotein (HDL) cholesterol (TC/HDL) and leptin levels were significantly higher whereas the HDL and the molar ratio of insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein (IGFBP)-3 levels were significantly lower in both OB and OSC groups than those in the Nor group. Compared to normal subjects, insulin and homeostasis model assessment (HOMA) index levels were significantly higher in OSC, and, in OSC, insulin sensitivity and insulin-like growth factor (IGF)-1 were significantly lower. Although the anthropometric parameters in the OB and OSC groups were similar, in the OSC group the waist-to-hip ratio (WHR), insulin levels and HOMA index were significantly higher, while insulin sensitivity, cholesterol, low-density lipoprotein (LDL) cholesterol, TC/HDL, LDL/HDL, IGF-1 and IGF-1/IGFBP-3 molar ratio were lower, than those of the OB group. Conclusion: Insulin homeostasis and lipid profiles in clozapine-treated schizophrenic obesity were different from those in nonpsychiatric obesity with similar anthropometric parameters, body weight and BMI. Among the three groups, the highest fasting insulin, the lowest insulin sensitivity and the highest HOMA index occurred in the OSC group. The OSC group was characterized by impaired glucose-insulin homeostasis, abnormal lipid profiles and hormonal changes in the GH-IGF-IGFBP axis and in leptin.

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“…Lower circulating IGF1 has been associated with an increased risk of heart failure and occlusive atherosclerotic disease such as stroke and CHD (9,10,18). In several studies, lower IGF1 levels have also been associated with all-cause or CVD-related mortality (19,20,21).…”

Section: Discussionmentioning

confidence: 99%

“…Increasing age and male gender are key risk factors for AAA (7). IGF1, IGF1 receptors and IGFBPs are expressed in vascular smooth muscle cells (VSMC) of human atherosclerotic plaques (8), and lower circulating levels of IGF1 have been associated with the incidence of cardiovascular events and stroke in previous studies (9,10). IGF1 concentration was reported to be decreased in human AAA tissue while concentrations of IGFBP1 and IGFBP3 were increased, raising the possibility that the IGF1 system contributes to the pathophysiology of AAA (11).…”

Section: Introductionmentioning

confidence: 99%

Associations of IGF1 and its binding proteins with abdominal aortic aneurysm and aortic diameter in older men

Yeap

Chubb

McCaul

et al. 2012

European Journal of Endocrinology

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Objective: Abdominal aortic aneurysm (AAA) is most prevalent in older men. GH secretion declines with age resulting in reduced IGF1 levels. IGF1 and its binding proteins (IGFBPs) are expressed in vasculature, and lower IGF1 levels have been associated with cardiovascular risk factors and disease. However, the relationship of the IGF1 system with aortic dilation and AAA is unclear. We tested the hypothesis that circulating IGF1 and IGFBPs are associated with AAA and aortic diameter in older men. Design: A cross-sectional analysis involving 3981 community-dwelling men aged 70-89 years was performed. Methods: Abdominal aortic diameter was measured by ultrasound. Plasma total IGF1, IGFBP1 and IGFBP3 were measured by immunoassays. Results: After adjustment for age, body mass index, waist:hip ratio, smoking, hypertension, dyslipidemia, diabetes, coronary heart disease and serum creatinine, a higher IGF1 level was associated with AAA (odds ratio (OR)/1 S.D. increase 1.18, 95% confidence interval (CI) 1.05-1.33, PZ0.006), as was the ratio of IGF1/IGFBP3 (ORZ1.22, 95% CI 1.10-1.35, P!0.001). Highest IGF1 concentrations compared with lowest quintile were significantly associated with AAA (quintile (Q) 5 vs Q1: ORZ1.80, 95% CI 1.20-2.70, PZ0.004) as were IGF1/IGFBP3 ratios (Q5 vs Q1: ORZ2.52, 95% CI 1.59-4.02, P!0.001). IGF1 and IGFBP1 were independently associated with aortic diameter (bZ0.200, 95% CI 0.043-0.357, PZ0.012 and bZ0.274, 95% CI 0.098-0.449, PZ0.002 respectively). Conclusions: In older men, higher IGF1 and an increased ratio of IGF1/IGFBP3 are associated with AAA, while IGFBP1 is independently associated with increased aortic diameter. Components of the IGF1 system may contribute to, or be a marker for, aortic dilation in ageing men.

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Insulin-Like Growth Factor (IGF) I, -II, and IGF Binding Protein-3 and Risk of Ischemic Stroke

Abstract: These findings give some support to the hypothesis that the IGF axis is involved in the pathogenesis of ischemic stroke.

Cited by 160 publications

References 30 publications

Serum IGF1, metabolic syndrome, and incident cardiovascular disease in older people: a population-based study

Serum IGF1, metabolic syndrome, and incident cardiovascular disease in older people: a population-based study

Glucose–insulin homeostasis, lipid profiles and GH-IGF-IGFBP axis in clozapine-treated schizophrenic obesity versus non-psychiatric obesity

Associations of IGF1 and its binding proteins with abdominal aortic aneurysm and aortic diameter in older men

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