Circulating IGF1 and IGFBP3 in relation to the development of β-cell autoimmunity in young children

Peet, Aleksandr; Hämäläinen, Anu‐Maaria; Kool, Pille; Ilonen, Jorma; Knip, Mikael; Tillmann, Vallo; _, _

doi:10.1530/eje-14-1078

Cited by 12 publications

(10 citation statements)

References 44 publications

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“…Herein, we report that IGF1 and IGF2 defects exist prior to type 1 diabetes onset. In agreement with our results, Peet et al (23) found IGF1 levels to be significantly lower in AAb 1 versus AAb 2 subjects, but in this previous study, the difference was only apparent at 12 months of age. IGFBP3 concentrations were not significantly different when comparing AAb 1 against AAb 2 individuals at all ages (23), again in agreement with our cross-sectional data.…”

Section: Discussionsupporting

confidence: 93%

Insulin-Like Growth Factor Dysregulation Both Preceding and Following Type 1 Diabetes Diagnosis

et al. 2020

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Insulin-like growth factors (IGFs), specifically IGF1 and IGF2, promote glucose metabolism, with their availability regulated by IGF-binding proteins (IGFBPs). We hypothesized that IGF1 and IGF2 levels, or their bioavailability, are reduced during type 1 diabetes development. Total serum IGF1, IGF2, and IGFBP1–7 levels were measured in an age-matched, cross-sectional cohort at varying stages of progression to type 1 diabetes. IGF1 and IGF2 levels were significantly lower in autoantibody (AAb)+ compared with AAb− relatives of subjects with type 1 diabetes. Most high-affinity IGFBPs were unchanged in individuals with pre–type 1 diabetes, suggesting that total IGF levels may reflect bioactivity. We also measured serum IGFs from a cohort of fasted subjects with type 1 diabetes. IGF1 levels significantly decreased with disease duration, in parallel with declining β-cell function. Additionally, plasma IGF levels were assessed in an AAb+ cohort monthly for a year. IGF1 and IGF2 showed longitudinal stability in single AAb+ subjects, but IGF1 levels decreased over time in subjects with multiple AAb and those who progressed to type 1 diabetes, particularly postdiagnosis. In sum, IGFs are dysregulated both before and after the clinical diagnosis of type 1 diabetes and may serve as novel biomarkers to improve disease prediction.

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Section: Discussionsupporting

confidence: 93%

Insulin-Like Growth Factor Dysregulation Both Preceding and Following Type 1 Diabetes Diagnosis

et al. 2020

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“…23 Selected were those with positive test results for DQA1*05-DQB1*02, DQB1*032/4, or both but without DRB1*0403/6 (DR4-DQ8) and with negative results for protective haplotypes. 8 The risk was defined by the presence and combination of these HLA alleles. 23 The 3 highest risk classes, conferring susceptibility to T1D, were grouped together against the no or very low risk class.…”

Section: Outcome Definitionsmentioning

confidence: 99%

“…7 In addition, a genetic predisposition has been proposed for T1D, which was encoded predominantly by HLA loci. 8 Atopy is known to be associated with allergic [9][10][11][12] and autoimmune [13][14][15] diseases. Because these conditions emerge from different pathologies, the question arises whether they relate to different aspects of atopy and how these aspects can be disentangled.…”

mentioning

confidence: 99%

Development of atopic sensitization in Finnish and Estonian children: A latent class analysis in a multicenter cohort

Schmidt¹,

Hose

Mueller-Rompa³

et al. 2019

Journal of Allergy and Clinical Immunology

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Background: The prevalence of atopy is associated with a Western lifestyle, as shown by studies comparing neighboring regions with different socioeconomic backgrounds. Atopy might reflect various conditions differing in their susceptibility to environmental factors. Objective: We sought to define phenotypes of atopic sensitization in early childhood and examine their association with allergic diseases and hereditary background in Finland and Estonia. Methods: The analysis included 1603 Finnish and 1657 Estonian children from the DIABIMMUNE multicenter young children cohort. Specific IgE levels were measured at age 3, 4, and 5 years, respectively, and categorized into 3 CAP classes. Latent class analysis was performed with the statistical software package poLCA in R software. Results: Both populations differed in terms of socioeconomic status and environmental determinants, such as pet ownership, farm-related exposure, time spent playing outdoors, and prevalence of allergic diseases (all P < .001). Nevertheless, we found similar latent classes in both populations: an unsensitized class, a food class, 2 inhalant classes differentiating between seasonal and perennial aeroallergens, and a severe atopy class. The latter was characterized by high total and specific IgE levels and strongly associated with wheeze (odds ratio [OR], 5.64 [95% CI, 3.07-10.52] and 4.56 [95% CI, 2.35-8.52]), allergic rhinitis (OR, 22.4 [95% CI, 11.67-44.54] and 13.97 [95% CI, 7.33-26.4]), and atopic eczema (OR, 9.39 [95% CI, 4.9-19.3] and 9.5 [95% CI, 5.2-17.5] for Finland and Estonia, respectively). Environmental differences were reflected in the larger seasonal inhalant atopy class in Finland, although composition of classes was comparable between countries. Conclusion: Despite profound differences in environmental exposures, there might exist genuine patterns of atopic sensitization. The distribution of these patterns might determine the contribution of atopic sensitization to disease onset. (J

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“…Several studies have indicated alterations in IGFBPs in T1D patients ( 1 , 17 – 19 ); however, these studies have used relatively smaller sample sets. Due to large inter-individual variation in levels of the IGFBPs, larger sample sizes are needed to draw definite conclusions.…”

Section: Introductionmentioning

confidence: 99%

IGF-Binding Proteins in Type-1 Diabetes Are More Severely Altered in the Presence of Complications

et al. 2016

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AimsReduced levels of free and total insulin-like growth factor 1 (IGF-I) have been observed in type-1 diabetes (T1D) patients. The bioavailability of IGF-I from the circulation to the target cells is controlled by multifunctional IGF-binding proteins (IGFBPs). The aim of this study was to profile serum IGFBPs in T1D and its complications.DesignWe measured the IGFBP levels in 3662 patient serum samples from our ongoing Phenome and Genome of Diabetes Autoimmunity (PAGODA) study. IGFBP levels of four different groups of T1D patients (with 0, 1, 2, and ≥3 complications) were compared with healthy controls.ResultsThree serum IGFBPs (IGFBP-1, -2, and -6) are significantly higher in T1D patients, and these alterations are greater in the presence of diabetic complications. IGFBP-3 is lower in patients with diabetic complications. Analyses using quintiles revealed that risk of T1D complications increases with increasing concentrations of IGFBP-2 (fifth quintile ORs: 18–60, p < 10−26), IGFBP-1 (fifth quintile ORs: 8–20, p < 10−15), and IGFBP-6 (fifth quintile ORs: 3–148, p < 10−3). IGFBP-3 has a negative association with T1D complications (fifth quintile ORs: 0.12–0.25, p < 10−5).ConclusionWe found that elevated serum levels of IGFBP-1, -2, and -6 were associated with T1D, and its complications and IGFBP-3 level was found to be decreased in T1D with complications. Given the known role of these IGFBPs, the overall impact of these alterations suggests a negative effect on IGF signaling.

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Circulating IGF1 and IGFBP3 in relation to the development of β-cell autoimmunity in young children

Cited by 12 publications

References 44 publications

Insulin-Like Growth Factor Dysregulation Both Preceding and Following Type 1 Diabetes Diagnosis

Insulin-Like Growth Factor Dysregulation Both Preceding and Following Type 1 Diabetes Diagnosis

Development of atopic sensitization in Finnish and Estonian children: A latent class analysis in a multicenter cohort

IGF-Binding Proteins in Type-1 Diabetes Are More Severely Altered in the Presence of Complications

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