Circulating IGF binding protein-1 is inversely associated with leptin in non-obese men and obese postmenopausal women

Söderberg, Stefan; Åhrén, Bo; Eliasson, Mats; Dinesen, Bo; Brismar, Kerstin; Olsson, Tommy

doi:10.1530/eje.0.1440283

Cited by 34 publications

(22 citation statements)

References 35 publications

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“…We also observed that differences in median levels of IGFBP-1 and the OR (10th percentile) are slightly higher in women than men. A recent study by Söderberg et al (15) showed similar results with regard to IGFBP-1 levels, further supporting these findings. Like the Bedford survey of CHD (16), our data indicated no gender differences between serum levels and MI risk inferred by high levels of serum insulin and HOMA.…”

Section: Igfbp-1 (Or (95% Ci))supporting

confidence: 70%

The risk of myocardial infarction is enhanced by a synergistic interaction between serum insulin and smoking

Bennet

Brismar²,

Hallqvist³

et al. 2002

European Journal of Endocrinology

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Objectives: To evaluate the relationship between levels of serum insulin, the homeostasis model assessment (HOMA) and IGF-binding protein-1 (IGFBP-1) as factors related to myocardial infarction (MI) risk, and their interaction with lifestyle-related risk factors. Design: The Stockholm epidemiology programme (SHEEP), a case-control study, consisting of 749 first-time MI cases (510 men, 239 women) and 1101 healthy controls (705 men, 396 women) was used. Methods: The risk of developing MI was assessed by calculating odds ratios (OR) and synergistic interactions (SI) between serum insulin, IGFBP-1, HOMA and other variables related to MI risk (including smoking) in men and women. Results: Subjects with elevated levels of insulin and HOMA (. 75th percentile) had increased MI risks when compared with individuals with low levels. ORs for elevated insulin and HOMA (adjusted for age and residential area) for men: insulin 1.6 (95% confidence interval (CI) 1.3-2.1) and HOMA 1.5 (95% CI 1.1-1.9) and for women: insulin 2.1 (95% CI 1.5-2.9) and HOMA 1.9 (95% CI 1.3 -2.8). Women with low levels of IGFBP-1 (,10th percentile) showed a tendency towards elevated MI risk even if this was not statistically significant (OR 1.5 (95% CI 0.9-2.6)). Smokers with high levels of serum insulin had greatly increased MI risk (OR for men: 4.7 (95% CI 3.0-7.2) and OR for women: 8.1 (95% CI 4.5 -14.8)). SI scores based upon these interactions were statistically significant. Conclusions: These results might have preventive cardiovascular implications as they clearly suggest that subjects with insulin resistance are particularly susceptible to the hazards of smoking.

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Section: Igfbp-1 (Or (95% Ci))supporting

confidence: 70%

The risk of myocardial infarction is enhanced by a synergistic interaction between serum insulin and smoking

Bennet

Brismar²,

Hallqvist³

et al. 2002

European Journal of Endocrinology

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“…33 Several studies have examined the associations between leptin and IGF-1 and IGFBP-3. [40][41][42][43] We observed a statistically significant interaction between LEP polymorphisms and both IGF1 and IRS2 genotypes. Those without a 19 CA repeat of the IGF1 gene had the greatest reduction in risk of colon cancer if they also had the AA genotype of the rs2167270 LEP gene.…”

Section: Discussionmentioning

confidence: 60%

Leptin and leptin receptor genotypes and colon cancer: Gene–gene and gene–lifestyle interactions

Slattery

Wolff

Herrick

et al. 2008

Intl Journal of Cancer

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Leptin may play an important role in colorectal cancer because of its role in energy balance, insulin and inflammation. We evaluated the LEP rs2167270 (19 G > A) and rs7799039 (22548 G > A) poly-morphisms and the leptin receptor, LEPR rs6588147 (located in intron 2), polymorphism with risk of developing colon cancer in a study of 1,567 cases and 1,965 controls. We evaluated the effects of the polymorphisms with body mass index (BMI), recent use of aspirin/NSAIDs and genetic variations in genes related to insulin signaling pathways including insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), and insulin related substrates 1 and 2 (IRS1, IRS2) and the vitamin D receptor (VDR). We observed a slight reduction in colon cancer risk with the AA LEP rs2167270 genotype (OR 0.79 95% CI 0.64, 0.98) and although not reaching statistical significance, with the combined GG LEP rs2167270 and GG LEPR rs6588147 (OR 0.70, 95% CI 0.49, 1.02) genotypes. BMI did not interact with any of these polymorphisms to alter colon cancer risk. However, recent aspirin/NSAID use significantly interacted with both LEP poly-morphisms. Likewise, variants of IGF1 and IRS2 interacted with the LEP rs2167270 polymorphism. VDR polymorphisms interacted with all LEP and LEPR polymorphisms. These data support an association between LEP and colon cancer. They also suggest that the mechanisms linking leptin to colon cancer may be independent of energy balance. ' 2007 Wiley-Liss, Inc. Leptin is a 16 kDa glycolprotein product of the leptin gene (LEP), which is expressed almost exclusively (>95%) by adipo-cytes. 1 Initial interest in leptin focused on its role in obesity but it is rapidly becoming evident that its physiological properties extend beyond those associated with energy homeostasis. In addition to regulation of energy balance, leptin, has been associated with reproductive factors, inflammatory response, insulin signal-ing, bone remodeling and neuroendocrine function. 2 The leptin receptor , a class I pro-inflammatory cytokine, is a member of the cytokine receptor family that includes IL-6. The leptin receptor plays a key role in how leptin functions. When leptin binds to the leptin receptor, Janus kinase (JAK2), a tyrosine kinase is activated to initiate downstream signaling of suppressors of cytokine signal-ing 1 and 3 (SOCS) and signal transducer and activator of transcription -3 (STAT). 2-4 Of particular importance for cancer is the influence of leptin on SOCS which in turn limits insulin signaling; SOCS3 has been shown to limit leptin signaling. Studies have shown that leptin also can stimulate expression of the inflamma-tory marker CRP (C-reactive protein). 5 There is growing evidence that nuclear hormone receptors regulate the action of leptin and other class I cytokines. 6 However, data also suggest that hormone receptors, such as the vitamin D receptor , might play an important role in regulating leptin; vitamin D 3 has been shown to inhibit leptin secretion in human adipose tissue. 7 Leptin has been ...

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“…The hepatic production of IGFBP-1 is downregulated by insulin (13). Accordingly, in the general population, there is a correlation between low levels of IGFBP-1 and hyperinsulinemia, and these findings may link to an increased cardiovascular risk (14,15). However, IGFBP-1 concentrations rise during the development of type 2 diabetes, despite persisting hyperinsulinemia, indicating increased hepatic insulin resistance during disease progression (16,17).…”

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confidence: 99%

IGF Binding Protein 1 Predicts Cardiovascular Morbidity and Mortality in Patients With Acute Myocardial Infarction and Type 2 Diabetes

et al. 2007

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OBJECTIVE -There are indications that the IGF system is related to both type 2 diabetes and cardiovascular disease (CVD). We tested the hypothesis that low IGF-I and high IGFbinding protein (IGFBP)-1 predict future cardiovascular mortality and morbidity in patients with acute myocardial infarction (AMI) and type 2 diabetes. RESEARCH DESIGN AND METHODS -The Diabetes MellitusInsulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Trial recruited 1,253 patients with type 2 diabetes and AMI, of whom 575 were enrolled in a biochemical program with repeated blood sampling. Primary and secondary end points included adjudicated cardiovascular mortality and a composite of cardiovascular events (cardiovascular death, reinfarction, or stroke). Multiple Cox proportional hazard regression was used to study the relationship between the end points and the variables. Admission variables were used for the survival analysis and for blood glucose, and A1C updated mean values during follow-up were also available. CONCLUSIONS -High levels of IGFBP-1 at admission are associated with increased risk for cardiovascular mortality and morbidity in type 2 diabetes patients with AMI. RESULTS Diabetes Care 30:2343-2348, 2007P atients with type 2 diabetes have an increased risk for cardiovascular disease (CVD) (1). The prognosis after an acute myocardial infarction (AMI) does, indeed, already deteriorate at glucose levels in the upper normal range (2,3). The importance is underlined by the high prevalence of AMI patients with previously undetected glucose abnormalities (4 -6). The increased cardiovascular risk cannot be completely explained by traditional risk factors, and mechanisms amplifying their impact are not fully understood (7). Thus, the search for novel risk factors linking type 2 diabetes and CVD is important (8).The IGF-I system has been related to poor glucose control, and low levels of IGF-I have been related to future type 2 diabetes (9). In addition, the IGF-I system and especially low IGF-I, low IGF binding protein (IGFBP)-1, and high IGFBP-3 relate to increased cardiovascular risk (10,11). Thus, it is of interest to explore the IGF-I system as a potential novel risk factor and as a possible link between type 2 diabetes and subsequent cardiovascular complications (12). The hepatic production of IGFBP-1 is downregulated by insulin (13). Accordingly, in the general population, there is a correlation between low levels of IGFBP-1 and hyperinsulinemia, and these findings may link to an increased cardiovascular risk (14,15). However, IGFBP-1 concentrations rise during the development of type 2 diabetes, despite persisting hyperinsulinemia, indicating increased hepatic insulin resistance during disease progression (16,17). These observations were supported by van den Berghe et al. (18), who demonstrated that patients admitted to the intensive care unit with elevated levels of IGFBP-1 presented a poor prognosis regarding mortality, a finding that related to acute hepatic insulin resistance. Furthermore, there is a correla...

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Circulating IGF binding protein-1 is inversely associated with leptin in non-obese men and obese postmenopausal women

Cited by 34 publications

References 35 publications

The risk of myocardial infarction is enhanced by a synergistic interaction between serum insulin and smoking

The risk of myocardial infarction is enhanced by a synergistic interaction between serum insulin and smoking

Leptin and leptin receptor genotypes and colon cancer: Gene–gene and gene–lifestyle interactions

IGF Binding Protein 1 Predicts Cardiovascular Morbidity and Mortality in Patients With Acute Myocardial Infarction and Type 2 Diabetes

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