Circulating IGFBP-2 levels are incrementally linked to correlates of the metabolic syndrome and independently associated with VLDL triglycerides

Carter, Sophie; Li, Zhuo; Lemieux, Isabelle; Alméras, Natalie; Tremblay, Angelo; Bergeron, Jean; Poirier, Paul; Deshaies, Yves; Després, Jean‐Pierre; Picard, Frédéric

doi:10.1016/j.atherosclerosis.2014.09.022

Cited by 43 publications

(49 citation statements)

References 41 publications

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“…They also exhibited decreased insulin sensitivity assessed according to higher fasting insulin levels and HOMA index. These findings are consistent with previous reports [11][12][13][14] and might suggest that IGFBP-2 could be used as a biomarker of metabolic alterations linked to visceral obesity. Interestingly, SV indexed to the 2.04 power of height or "ideal BSA" remained associated with IGFBP-2 levels.…”

Section: Discussionsupporting

confidence: 93%

“…8,9 Recent experimental studies showed that overexpression of human IGFBP-2 in rodents protects against age and diet-induced insulin resistance. 10 Consistently, lower circulating levels of IGFBP-2 have been associated with obesity, insulin resistance, and dyslipidemia in humans, [11][12][13] leading to the postulate that plasma IGFBP-2 could be a biomarker for the MetS. 14 We therefore hypothesized that circulating levels of IGFBP-2 could be associated with the worsening of myocardial structure and function in AS.…”

mentioning

confidence: 96%

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Relationship Between Insulin-Like Growth Factor Binding Protein-2 and Left Ventricular Stroke Volume in Patients With Aortic Stenosis

Carter

Capoulade

Arsenault

et al. 2015

Canadian Journal of Cardiology

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Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 96%

Relationship Between Insulin-Like Growth Factor Binding Protein-2 and Left Ventricular Stroke Volume in Patients With Aortic Stenosis

Carter

Capoulade

Arsenault

et al. 2015

Canadian Journal of Cardiology

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“…In the present study, total circulating IGFBP-2 levels were within the range reported in men with mild dyslipidemia and increased adiposity Log-transformed variables. [8,12,33,34]. Following the 1-year intervention, average IGFBP-2 levels were increased by 43%, which is consistent with the upregulation observed after weight loss achieved by dieting alone [19].…”

Section: Discussionsupporting

confidence: 78%

“…Additional transversal associations between IGFBP-2 levels and components of the lipoprotein-lipid profile, mostly TG and HDL cholesterol, were also described by others [11,13]. Further analyses suggested that subjects with low IGFBP-2 levels display an increased number of TG-rich particles as assessed by elevated apo B concentrations [12]. In turn, both overexpression of IGFBP-2 in mice and IGFBP-2 treatment to 3T3-L1 adipocyte cultures enhance uptake and metabolism of energy substrates, through yet unclear, partially IGF-1-independent mechanisms, including a possible attenuation of α5β1 integrins and intracellular PTEN signaling [14,15].…”

Section: Introductionmentioning

confidence: 52%

“…Lower circulating levels of insulin-like growth factor (IGF) binding protein-2 (IGFBP-2) have been associated with increased fat mass, insulin resistance and abnormalities in the lipoprotein-lipid profile in children [7] and adults [8][9][10][11]. We recently showed that human subjects with low IGFBP-2 levels have an increased risk of showing metabolic alterations linked to the metabolic syndrome [12]. Additional transversal associations between IGFBP-2 levels and components of the lipoprotein-lipid profile, mostly TG and HDL cholesterol, were also described by others [11,13].…”

Section: Introductionmentioning

confidence: 99%

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Changes in IGFBP-2 levels following a one-year lifestyle modification program are independently related to improvements in plasma apo B and LDL apo B levels

Carter

Lemieux

et al. 2019

Atherosclerosis

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A 1-year lifestyle modification program increased circulating IGFBP-2 levels by 43% in men.• Changes in IGFBP-2 levels contributed to improvements in plasma apo B. • This association was independent from those between IGFBP-2, insulin resistance, and fat mass. A R T I C L E I N F O Keywords:Obesity Human IGFBP-2 Dyslipidemia LDL Apolipoprotein B A B S T R A C TBackground and aims: Recent transversal studies have associated insulin-like growth factor binding protein (IGFBP)-2 levels with glucose tolerance and parameters of the lipoprotein-lipid profile. Here, we aimed at determining the longitudinal effects of a one-year lifestyle modification program on IGFBP-2 levels and to identify specific metabolic improvements impacted by the changes in IGFBP-2. Methods: 99 middle-aged Caucasian men were involved in a lifestyle modification program consisting in personalized healthy eating and physical activity counseling, combined to elicit a daily 500 kcal deficit. Anthropometric and metabolic parameters as well as circulating IGFBP-2 levels were measured before and after one year of the lifestyle modification program. Results: The intervention triggered positive changes in many metabolic parameters and a 43% (p < 0.0001) increase of IGFBP-2 levels. Subjects with the most substantial increases in IGFBP-2 also experienced the most important metabolic improvements. Changes in IGFBP-2 levels (both absolute and relative) were correlated with markers of body fat distribution and lipoprotein-lipid profile, and independently associated with changes in LDL apolipoprotein (apo) B but not VLDL apo B concentrations. Further analyses showed that for similar changes in BMI, waist circumference and visceral adipose tissue volume, large changes in IGFBP-2 levels were required to observe improvements in LDL apo B levels. Conclusions: The 1-year lifestyle modification program was associated with increased IGFBP-2 concentrations. Increases in IGFBP-2 levels were closely associated with reduced LDL apo B concentrations and independently of the modifications in fat mass and insulin sensitivity. Further mechanistic studies are required to assess the effects of IGFBP-2 levels on LDL metabolism.

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Circulating IGFBP‐2: a novel biomarker for incident dementia

McGrath

Himali

Levy

et al. 2019

Ann Clin Transl Neurol

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Objective To determine the association between plasma insulin‐like growth factor binding protein 2 (IGFBP‐2) and cognitive outcomes. Methods We measured plasma IGFBP‐2 levels in 1596 (53% women, mean age 68.7 [SD 5.7] years) dementia‐free Framingham Offspring cohort participants between 1998 and 2001. Multivariable Cox proportional hazards models related plasma IGFBP‐2 to subsequent risk of incident dementia and Alzheimer’s disease. MRI brain measures and cognitive performance were included as secondary outcomes. Results During a median follow‐up of 11.8 (Q1, Q3: 7.1, 13.3) years, 131 participants developed incident dementia, of whom 98 were diagnosed with Alzheimer’s disease. The highest tertile of IGFBP‐2, compared to the lowest tertile, was associated with an increased risk of incident all‐cause dementia (hazard ratio [HR] 2.89, 95% CI 1.63–5.13) and Alzheimer’s disease (HR 3.63, 95% CI 1.76–7.50) in multivariable analysis. Higher circulating IGFBP2 levels were also cross‐sectionally associated with poorer performance on tests of abstract reasoning but not with MRI‐based outcomes. After adding plasma IGFBP‐2 levels to a conventional dementia prediction model, 32% of individuals with dementia were correctly assigned a higher predicted risk, while 8% of individuals without dementia were correctly assigned a lower predicted risk (overall net reclassification improvement index, 0.40, 95% CI 0.22–0.59). Interpretation Elevated circulating IGFBP‐2 levels were associated with an increased risk of both all‐cause dementia and Alzheimer’s disease. Addition of IGFBP2 plasma levels to a model of traditional risk factors significantly improved dementia risk classification. Manipulation of insulin‐like growth factor signaling via IGFBP‐2 may be a promising therapeutic target for dementia.

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Circulating IGFBP-2 levels are incrementally linked to correlates of the metabolic syndrome and independently associated with VLDL triglycerides

Cited by 43 publications

References 41 publications

Relationship Between Insulin-Like Growth Factor Binding Protein-2 and Left Ventricular Stroke Volume in Patients With Aortic Stenosis

Relationship Between Insulin-Like Growth Factor Binding Protein-2 and Left Ventricular Stroke Volume in Patients With Aortic Stenosis

Changes in IGFBP-2 levels following a one-year lifestyle modification program are independently related to improvements in plasma apo B and LDL apo B levels

Circulating IGFBP‐2: a novel biomarker for incident dementia

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