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Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: a prospective observational study
Abstract
Background Results of experimental and clinical studies suggest that insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) could be important determinants of glucose homoeostasis. However, experimental models might also reflect compensatory and adaptive metabolic processes. We therefore prospectively examined the associations between circulating concentrations of IGF-I and IGFBP-1 and development of glucose tolerance.Methods Participants in this cohort study were a random sample of 615 normoglycaemic men and women aged 45-65 years. Participants underwent oral glucose tolerance testing based on WHO definitions and criteria in 1990-92 and 1994-96. At the baseline visit, we measured serum concentrations of IGF-I and IGFBP-1, and assessed the relation between these peptides and subsequent glucose intolerance.Findings At 4.5 years of follow-up, 51 (8%) of 615 participants developed impaired glucose tolerance or type-2 diabetes. After adjustment for correlates of IGF-I and risk factors for glucose intolerance, the odds ratio for risk of impaired glucose tolerance or type-2 diabetes for participants with IGF-I concentrations above the median (> or = 152 microg/L) compared with those with concentrations below the median (<152 microg/L) was 0.50 (0.26-0.95). Consistent with this finding, IGF-I also showed a significant inverse association with subsequent 2-h glucose concentrations, which was independent of correlates of IGF-I and risk factors for glucose tolerance (p for linear trend=0.026). We also found that this inverse association was independently modified by IGFBP-1 (p for interaction=0.011).Interpretation These data show that circulating IGF-I and its interaction with IGFBP-1 could be important determinants of glucose homoeostasis and provide further evidence for the possible protective role of IGF-I against development of glucose intolerance.
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“There is evidence that low plasma levels of IGF1 predict the development of type 2 diabetes and correlate with insulin resistance and increased risk of metabolic syndrome and cardiovascular disease [[231], [232], [233]] (Table 1).”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [231]
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Metadata
- Authors
- Sandhu, M. S., Heald, A. H., Gibson, J. M., Cruickshank, J. K., Dunger, D. B., & Wareham, N. J.
- Affiliations
- University of Cambridge (GB)
- University of Manchester (GB)
- Corresponding author
- Wareham, Nicholas J
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2002-05
- Volume
- 359
- Issue
- 9319
- Pages
- 1740-1745
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2140997600
- Cited by
- 470
- References
- 33
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 11 · 2023: 13 · 2022: 18 · 2021: 15 · 2020: 17 · 2019: 15 · 2018: 18 · 2017: 18 · 2016: 17 · 2015: 14 · 2014: 19 · 2013: 11 · 2012: 28
- FWCI
- 15.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- insulin-like growth factor I, IGF-binding protein-1, impaired glucose tolerance, type 2 diabetes, glucose homeostasis, 2-hour plasma glucose, middle-aged adults
- MeSH terms
- Aged, Blood Glucose, Fasting, Female, Homeostasis, Humans, Insulin-Like Growth Factor I, Male, Middle Aged, Prospective Studies, Glucose Intolerance, Insulin-Like Growth Factor Binding Protein 1
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