Insulin-Like Growth Factor-I and Risk of Type 2 Diabetes and Coronary Heart Disease: Molecular Epidemiology

Sandhu, Manjinder S.

doi:10.1159/000085755

Cited by 38 publications

(24 citation statements)

References 62 publications

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“…A number of epidemiological studies have suggested that IGF-I levels in the lower normal range are associated with an increased risk of ischemic heart disease, stroke, hypertension, reduced glucose tolerance, and diabetes (II, [21][22][23][24]. Although the relationship between IGF-I and cardiovascular disease is still unknown, a protective role in the development of atherosclerosis was suggested for free IGFI levels (24).…”

Section: Discussionmentioning

confidence: 99%

Insulin-like Growth Factor-1, Psoriasis, and Inflammation: A Ménage à Trois?

et al. 2011

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Psoriatic patients have an accumulation of metabolic syndrome (MS) and cardiovascular diseases (CVD), likely mediated by systemic inflammation, and exhibiting low circulating levels of insulin-like growth factor (IGF)-I, a marker of MS and CVD in the general population. The aim of this study is to determine the association of IGF-I and inflammation, and to assess the cardio-metabolic risk calculating the visceral adiposity index (VAI), in a group of psoriatic patients without MS. IGF-I, fibrinogen, C-reactive protein (CRP), and interleukin (IL)-6 levels were determined in 20 patients with moderate to severe psoriasis (age range 23–77 yrs) without MS, according to criteria of the National Cholesterol Education Program's Adult Panel III (ATP III), and 20 age- and BMI-matched controls. The standard deviation score (SDS) of IGF-I levels according to age (zSDS), the homeostasis model assessment of insulin resistance (HOMA-IR), the whole-body insulin sensitivity index (ISI), and VAI were also calculated. Psoriasis Area and Severity Index (PASI) mean value was 17.8±11. HDL cholesterol and IGF-I zSDS values were lower (p<0.001) and waist circumference (p<0.001), VAI, fibrinogen, and IL-6 (p<0.005) were higher compared with controls, while HOMA-IR and ISI were not statistically different. Lower IGF-I zSDS values were associated to higher values of BMI (p=0.04), waist circumference, VAI (p<0.001), PASI (p=0.011), or IL-6 (p<0.001). At the multivariate analysis PASI was the major determinant of IGF-I zSDS (p=0.016), accounting for 37% of its variability. In a subset of psoriatic patients without MS, chronic inflammation might be an important modulator of low IGF-I status, as a further possible mechanistic link between psoriasis and associated metabolic co-morbidities. The negative correlation between age-related IGF-I values and VAI suggest the involvement of adipocyte dysfunction in low IGF-I status more than MS per se. Further studies are needed to address whether these results are valid also for other psoriatic patients.

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Section: Discussionmentioning

confidence: 99%

Insulin-like Growth Factor-1, Psoriasis, and Inflammation: A Ménage à Trois?

et al. 2011

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“…47 Recent prospective epidemiological studies suggest that relatively higher IGF-I levels may reduce the risk of type 2 diabetes and CHD. 48 Increasing evidence indicates, instead, that IGF-1 protects against endothelial dysfunction, an initial step in the development of atherosclerotic lesions, through activation of a suicidal pathway that leads to endothelial cell apoptosis. 49,50 IGF-1 can directly oppose endothelial dysfunction in a number of ways: by interacting with high-affinity endothelial binding sites that lead to nitric oxide (NO) production, 51 by promoting insulin sensitivity 52 and potassium-channel opening, 53 and by preventing postprandial dyslipidemia.…”

Section: Igf Pathway In Cancer and Vascular Diseasementioning

confidence: 99%

Targeting c-Myc, Ras and IGF Cascade to Treat Cancer and Vascular Disorders

Nigris¹,

Balestrieri

Napoli

2006

Cell Cycle

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Cancer and vascular diseases remain the predominant causes of morbidity and mortality in industrialized countries worldwide. The course of atherosclerosis with initiation, progression, and complication parallels the three stages of carcinogenesis with induction, growth, and invasion of tissue and neoangiogenesis. Within this framework, the oncogene c-Myc and growth factors pathways are acquiring increasing importance. Insulin-like growth factor-1 (IGF-1) pathway emerges among them for its versatile pleiotropic actions. A number of genes that permit extensive communication between IGF-1-AKT, p53, and mammalian target of rapamycin (mTOR) pathways have been identified. In turn these pathways lead to p53 transcriptional program, the forkhead transcriptional programs, autophagy, and translational controls, which determine cell growth or arrest, cell survival or death. The increased understanding of the extensive communication and coordination between all these pathways may enable to targeting these events and to prevent neoplastic and vascular diseases. Great effort has been focused on the development of new agents designed to target various steps of c-Myc, Ras, and IGF cascade. However, what have we recently learned about their safety and effectiveness? Here, we review the very recent advances in the identification of novel inhibitors as well as antisense oligonuleotides (ASOs) and siRNA that are proving their usefulness in ongoing clinical trials both in therms of toxicity and specificity.

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“…There is increasing evidence that IGF1 has a protective effect against metabolic syndrome, endothelial dysfunction, atherosclerotic plaque development, and ischemic myocardial damage . There are studies that indicate that high plasma levels of IGF1 may reduce risk of type 2 diabetes and coronary disease [Sandhu, 2005]. Puglielli [2008] concluded that the IGF1 pathway and the IGF1 receptor were involved in the progressive loss of neurogenic capacity in the ageing brain and to the pathogenesis of Alzheimer's disease.…”

Section: Discussionmentioning

confidence: 99%

Genetic association and sequencing of the insulin-like growth factor 1 gene in bipolar affective disorder

et al. 2011

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Insulin-like growth factor 1 (IGF1) has been shown to have an important role in brain development and function. Studies of IGF1 administration in rodents have shown that it has an anxiolytic and antidepressant effect. A genome-wide association study (GWAS) of the first University College London (UCL) cohort of 506 bipolar affective disorder subjects and 510 controls was carried out. The exons and flanking regions of IGF1 were resequenced, any new polymorphisms found were genotyped in an enlarged UCL sample of 937 cases and 941 controls. GWAS data gave good evidence of allelic and haplotypic association between multiple IGF1 SNP's and bipolar disorder (BD). New polymorphisms were found by resequencing IGF1 region. Data from GWAS and the new markers showed that twelve out of 43 SNPs showed association with BD with the four most significant SNPs having values of 3.7 × 10(-5) , 8.4 × 10(-4) , 2.6 × 10(-4) , and 2.5 × 10(-4) . A 5' promoter microsatellite polymorphism previously correlated with plasma lipoprotein concentration was also associated with BD (P = 0.013). Haplotypic association confirmed association with BD with significance values similar to the single marker SNP values. The marker rs12426318 has also been found to be associated with BD in a second sample. A test of gene wide significance with permutation testing for all markers genotyped at IGF1 was also significant. These data implicate IGF1 as a candidate gene to cause genetic susceptibility to BD.

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Insulin-Like Growth Factor-I and Risk of Type 2 Diabetes and Coronary Heart Disease: Molecular Epidemiology

Cited by 38 publications

References 62 publications

Insulin-like Growth Factor-1, Psoriasis, and Inflammation: A Ménage à Trois?

Insulin-like Growth Factor-1, Psoriasis, and Inflammation: A Ménage à Trois?

Targeting c-Myc, Ras and IGF Cascade to Treat Cancer and Vascular Disorders

Genetic association and sequencing of the insulin-like growth factor 1 gene in bipolar affective disorder

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