Low serum insulin-like growth factor-binding protein-1 is associated with an unfavourable cardiovascular risk profile in elderly men

Harrela, Maija; Koistinen, Riitta; Tuomilehto, Jaakko; Nissinen, Aulikki; Seppälä, Markku

doi:10.3109/07853890008995950

Cited by 29 publications

(16 citation statements)

References 18 publications

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“…Another cross-sectional study found that lower IGFBP1 levels were associated with known cardiovascular risk factors in 273 adults aged 20-74 years (32). Our results are in keeping with a previous smaller study involving 331 Finnish men aged 70-89 years in which IGFBP1 levels correlated with insulin sensitivity (33). The inverse relationship between IGFBP1 and metabolic syndrome could be explained by its role as a marker of insulin sensitivity, as IGFBP1 correlates closely to whole-body and hepatic insulin sensitivity (34,35).…”

Section: Discussionsupporting

confidence: 91%

“…This is consistent with previous studies in men of varying ages in linking IGFBP1 levels with insulin sensitivity (19,20,32,33). Thus, lower IGFBP1 levels were associated with impaired glucose tolerance in an ethnically diverse sample of 272 adults from Manchester (19) and with metabolic syndrome in 839 adults aged 40-65 years in the Cambridgeshire study (20).…”

Section: Discussionsupporting

confidence: 91%

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IGF1 and its binding proteins 3 and 1 are differentially associated with metabolic syndrome in older men

Yeap¹,

Chubb²,

Ho³

et al. 2010

European Journal of Endocrinology

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Objective: Circulating IGF1 declines with age, and reduced circulating IGF1 is associated with increased cardiovascular mortality in some but not all studies. The relationship between IGF-binding proteins 3 and 1 (IGFBP3 and IGFBP1) with risk of cardiovascular disease remains unclear. We sought to examine associations between IGF1, IGFBP3 and IGFBP1 with metabolic syndrome in older men. Design: Cross-sectional analysis of 3980 community-dwelling men aged R70 years. Methods: Morning plasma levels of IGF1, IGFBP3 and IGFBP1 were assayed. Metabolic syndrome was defined according to National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) criteria. Results: For IGF1 and IGFBP3, there was a U-shaped relationship, with middle quintiles possessing the lowest odds ratios (OR) for metabolic syndrome (reference Q1, Q3 IGF1: OR 0.74, 95% confidence intervals 0.57-0.96, Q3 IGFBP3: OR 0.67, 0.51-0.87). Increasing IGFBP1 was associated with reduced risk of metabolic syndrome with a dose-response gradient (reference Q1, OR for Q2 to Q5 IGFBP1: 0.56, 0.33, 0.22 and 0.12 respectively, P!0.001). IGF1 was associated with two, IGFBP1 with four and IGFBP3 with all five components of the metabolic syndrome. The ratio of IGF1/IGFBP3 was not associated with metabolic syndrome. Conclusions: In older men, both lower and higher IGF1 and IGFBP3 levels may be metabolically unfavourable. IGFBP1, as a marker of insulin sensitivity, is relevant in the assessment of metabolic syndrome, while the IGF1/IGFBP3 ratio is less informative. Longitudinal follow-up of this cohort would be needed to determine whether these distributions of IGF1, IGFBP3 and IGFBP1 predict incidence of cardiovascular events during male ageing.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

IGF1 and its binding proteins 3 and 1 are differentially associated with metabolic syndrome in older men

Yeap¹,

Chubb²,

Ho³

et al. 2010

European Journal of Endocrinology

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“…A potential role of IGFs in the pathogenesis of cardiovascular disease has long been recognised. In cross-sectional studies low serum IGFBP-1 levels are associated with an unfavourable cardiovascular risk profile in diabetes and in populations without diabetes [10,11,45,46]. Low IGF-I is also associated with cardiovascular risk factors [45,47], independently of low IGFBP-1 [12,15].…”

Section: Discussionmentioning

confidence: 99%

Insulin-like growth factor-binding protein-1 in the prediction and development of type 2 diabetes in middle-aged Swedish men

et al. 2008

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Aims/hypothesis Insulin-like growth factor-binding protein-1 (IGFBP-1) production in the liver is inhibited by insulin, and low circulating levels are associated with the metabolic syndrome. The aim of this study was to evaluate the predictive role and change in IGFBP-1 concentrations during development of abnormal glucose regulation. Methods IGFBP-1 levels were determined at baseline and at 10 years in an incident case-control prospective study of Swedish white men aged 35-56 years. Individuals with normal glucose tolerance at baseline who developed abnormal glucose tolerance during a 10 year period (n=355) according to WHO criteria were pair-matched to controls for age and family history of diabetes. Results Fasting IGFBP-1 concentrations were lower in individuals who later developed abnormal glucose regulation and correlated inversely with fasting proinsulin values (r =−0.48; p<0.0001), and both were significant predictors. Individuals in the highest quartile at baseline for an algorithm incorporating fasting IGFBP-1, blood glucose, proinsulin and waist and height had a 40-fold increased risk of developing type 2 diabetes compared with the lowest quartile (95% CI 7.7-214). IGFBP-1 increased 32% (95% CI 17-49%) during the 10 years in those developing diabetes and was increased in relation to insulin levels, suggesting the emergence of hepatic insulin resistance. Moreover, elevated IGFBP-1 levels at follow-up were associated with higher 2 h glucose values during an OGTT. Conclusions/interpretation Low IGFBP-1 predicts the development of abnormal glucose regulation and, as an inhibitor of the insulin-like actions of insulin-like growth factors, elevated levels of IGFBP-1 after the development of diabetes may also play a pathophysiological role.

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“…IGF1 and IGFBP1, -2, and -3 are considered components of two axes: the GH/IGF1 axis, including IGF1 and IGFBP3, and the obesity-insulin resistance axis, including IGFBP1 and -2. IGFBP1 and -2 are inversely correlated with insulin and BMI, and are expectedly to be negatively associated with components of insulin resistance syndrome, namely, hypertension, diabetes, and dyslipidemia (24,25). Conversely, the role of IGF1 is less clear.…”

Section: Discussionmentioning

confidence: 99%

Relationships between serum IGF1 levels, blood pressure, and glucose tolerance: an observational, exploratory study in 404 subjects

Colao¹,

Somma

Cascella³

et al. 2008

European Journal of Endocrinology

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Background: In the general population, low IGF1 has been associated with higher prevalence of cardiovascular disease and mortality. Objective: To investigate the relationships between IGF1 levels, blood pressure (BP), and glucose tolerance (GT). Subjects: Four-hundred and four subjects (200 men aged 18-80 years). Exclusion criteria: personal history of pituitary or cardiovascular diseases; previous or current treatments with drugs interfering with BP, GT, or lipids, corticosteroids (O2 weeks), estrogens, or testosterone (O12 weeks); smoking of O15 cigarettes/day and alcohol abuse (O3 glasses of wine/day). Results: Two hundred and ninety-six had normal BP (73.3%), 86 had mild (21.3%), and 22 had severe (5.4%) hypertension; 322 had normal GT (NGT (79.7%)), 53 had impaired glucose tolerance (IGT (13.1%)), 29 had diabetes mellitus (7.2%). Normotensive subjects had significantly higher IGF1 levels (0.11G0.94 SDS) than those with mild (K0.62G1.16 SDS, P!0.0001) or severe (K1.01G1.07 SDS, P!0.0001) hypertension. IGF1 SDS (tZK3.41, PZ0.001) independently predicted systolic and diastolic BP (tZK2.77, PZ0.006) values. NGT subjects had significantly higher IGF1 levels (0.13G 0.90 SDS) than those with IGT (K0.86G1.14 SDS, P!0.0001) or diabetes mellitus (K1.31G1.13 SDS, P!0.0001). IGF1 SDS independently predicted fasting glucose (tZK3.49, PZ0.0005) and homeostatic model assessment (HOMA)-R (tZK2.15, PZ0.033) but not insulin (tZK1.92, PZ0.055) and HOMA-b (tZK0.19, PZ0.85). Conclusion: IGF1 levels in the low normal range are associated with hypertension and diabetes in subjects without pituitary and cardiovascular diseases.

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Low serum insulin-like growth factor-binding protein-1 is associated with an unfavourable cardiovascular risk profile in elderly men

Cited by 29 publications

References 18 publications

IGF1 and its binding proteins 3 and 1 are differentially associated with metabolic syndrome in older men

IGF1 and its binding proteins 3 and 1 are differentially associated with metabolic syndrome in older men

Insulin-like growth factor-binding protein-1 in the prediction and development of type 2 diabetes in middle-aged Swedish men

Relationships between serum IGF1 levels, blood pressure, and glucose tolerance: an observational, exploratory study in 404 subjects

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