Insulin-like Growth Factor System In Patients Research Articles

The IGF system in patients with type 2 diabetes: associations with markers of cardiovascular target organ damage.

Perturbations in the insulin-like growth factor (IGF) system may contribute to the accelerated cardiovascular disease (CVD) that occurs in patients with type 2 diabetes (T2D). However, it remains unknown whether the IGF system is also involved in the development of early, subclinical CVD. We characterised the IGF system in T2D patients and matched controls and examined the associations with markers of subclinical target organ damage. The study included 99 patients with recently diagnosed T2D and 99 age- and sex-matched controls. IGF-1 and IGFBP-1 to -4 were measured by immunoassays, as were pregnancy-associated plasma protein-A (PAPP-A) and the PAPP-A-generated N-terminal (NT) and C-terminal (CT) IGFBP-4 fragments, which are novel CVD risk markers. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (PWV). Cerebral white matter lesions (WMLs) and carotid artery remodelling were determined by MRI. After multivariate adjustments, patients with T2D had lower concentrations of IGFBP-2, IGFBP-4, NT- and CT-IGFBP-4, when compared with controls. IGFBP-2 was inversely correlated to PWV in all subjects in multivariate analysis (P < 0.05), and IGFBP-3 was inversely associated with severity of WMLs (P < 0.05). The NT-IGFBP-4 fragment was associated with the degree of carotid artery remodelling among all subjects (regression coefficient (95% CI): 2.95 (0.70, 5.16), P = 0.011). Levels of NT- and CT-IGFBP-4 were reduced in T2D patients receiving metformin compared to those in controls and patients not receiving metformin. Even in recently diagnosed and well-controlled T2D patients, IGF protein levels are altered and associated with CVD risk factors.

The insulin-like growth factor (IGF) system and its relation to infliximab treatment in adult patients with Crohn's disease

Objective. Metabolic bone disease (MBD) and muscle wasting (MW) are serious complications in adult patients suffering from inflammatory bowel disease. These complications may be caused by alterations in the insulin-like growth factor (IGF) system. The aim of the present study was to assess changes in the IGF system in patients with active Crohn's disease (CD) before and during infliximab treatment. Material and methods. We studied 13 patients with therapy refractory CD, treated with infliximab (5 mg/kg body-weight) at baseline and after 2 weeks. The IGF system and markers of inflammation were examined at baseline, on days 2–5 and after 1, 4, and 8 weeks. Ten healthy age- and gender-matched persons served as controls. Results. Total IGF-I and IGF binding protein (IGFBP)-3 levels were reduced by 36% (p<0.05) and 27% (p<0.001), respectively, compared with those of controls, and normalized during the study period. Free IGF-I levels were reduced by 46% (p<0.05) compared with those of controls and remained suppressed. IGFBP-2 levels were increased at baseline by a factor 2.3 compared to controls (p<0.01) with partial normalization at the end of the study period. The Crohn's disease Activity Index, the Harvey Bradshaw Index, C-reactive protein, orosomucoid and albumin reached normal levels during infliximab treatment. Conclusions. Treatment with infliximab normalized circulating levels of total IGF-I and IGFBP-3, and partially normalized IGFBP-2, whereas free IGF-I remained suppressed. We suggest that the changes in the IGF system may be part of the catabolic state in active CD and may have an association with MBD and MW.

Local disruption of the insulin-like growth factor system in the arthritic joint.

To identify differences in levels of insulin-like growth factor (IGF) and IGF binding proteins (IG-FBPs) between 30 patients with arthritis (14 with rheumatoid arthritis [RA], 16 with osteoarthritis [OA]) and 11 normal control subjects. IGF and IGFBP levels were correlated to the disease activity marker C-reactive protein (CRP) to determine whether they were disease related. We also examined the degree of proteolytic modification of the IGFBPs. Radioimmunoassays were used for measuring IGF and IGFBP-3 levels; CRP was measured by enzyme-linked immunosorbent assay. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Western blotting, chemiluminescence, and autoradiography were used for visualizing binding proteins. There was a significant increase in synovial fluid levels of both IGF-1 and IGFBP-3 in both RA and OA. This resulted in an elevated IGFBP-3 to IGF molar ratio of 1.49 in the OA group and 1.47 in the RA group, compared with 0.86 in the normal control group (P = 0.0002 for both). A significantly lower degree of IGFBP-3 proteolysis was also seen in the synovial fluids from the patients compared with the controls. There were significant correlations between the CRP level and levels of IGF-1, IGF-2, and IGFBP-3 in the RA patients (r = 0.62-0.898, P = 0.04-0.0007). There was significant local disruption of the IGF system in patients with arthritis. This may result in a lower amount of IGF that is able to bind to IGF receptors in the arthritic joint. Levels of IGF-1 IGF-2, and IGFBP-3 all correlated with the CRP level in patients with RA, which indicates the possibility that the IGF system is involved in the disease process.