{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:15:00Z","timestamp":1789676100748,"version":"4.0.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Adiponectin and insulin-like growth factor (IGF) binding proteins IGFBP-1 and IGFBP-2 are biomarkers of insulin sensitivity. IGFBP-1 reflects insulin sensitivity in the liver, adiponectin in adipose tissue and IGFBP-2 in both tissues. Here, we study the power of the biomarkers adiponectin, IGFBP-1, IGFBP-2, and also included IGF-I and IGF-II, in predicting prediabetes and type 2 diabetes (T2D) in men and women with normal oral glucose tolerance (NGT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Subjects with NGT (35-56 years) recruited during 1992-1998 were re-investigated 8-10 years later. In a nested case control study, subjects progressing to prediabetes (133 women, 164 men) or to T2D (55 women, 98 men) were compared with age and sex matched NGT controls (200 women and 277 men).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The evaluation included questionnaires, health status, anthropometry, biochemistry and oral glucose tolerance test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After adjustment, the lowest quartile of adiponectin, IGFBP-1 and IGFBP-2 associated independently with future abnormal glucose tolerance (AGT) in both genders in multivariate analyses. High IGFs predicted weakly AGT in women. In women, low IGFBP-2 was the strongest predictor for prediabetes (OR:7.5), and low adiponectin for T2D (OR:29.4). In men, low IGFBP-1 was the strongest predictor for both prediabetes (OR:13.4) and T2D (OR:14.9). When adiponectin, IGFBP-1 and IGFBP-2 were combined, the ROC-AUC reached 0.87 for women and 0.79 for men, higher than for BMI alone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Differences were observed comparing adipocyte- and hepatocyte-derived biomarkers in forecasting AGT in NGT subjects. In women the strongest predictor for T2D was adiponectin and in men IGFBP-1, and for prediabetes IGFBP-2 in women and IGFBP-1 in men.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.1092307","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T11:02:23Z","timestamp":1672916543000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Adiponectin, IGFBP-1 and -2 are independent predictors in forecasting prediabetes and type 2 diabetes"],"prefix":"10.3389","volume":"13","author":[{"given":"Kerstin","family":"Brismar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agneta","family":"Hilding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishrath","family":"Ansurudeen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Flyvbjerg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Frystyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claes-G\u00f6ran","family":"\u00d6stenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(91)90086-8","article-title":"Insulin-like growth factor-binding protein-1: a role of glucose counter-regulation","volume":"79","author":"Lewitt","year":"1991","journal-title":"Mol.Cell Endocrinol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1210\/er.16.1.3","article-title":"Insulin-like growth factors and their binding proteins: Biological actions*","volume":"16","author":"Jones","year":"1995","journal-title":"Endocrine Rev"},{"key":"B3","doi-asserted-by":"publisher","first-page":"91","DOI":"10.2337\/diab.45.1.91","article-title":"Recombinant human insulin-like growth factor I increases insulin sensitivity and improves glycemic control in type II diabetes","volume":"45","author":"Moses","year":"1996","journal-title":"Diabetes"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1520-7560(199909\/10)15:5","article-title":"Circulating levels of free insulin-like growth factors in obese subjects: the impact of type 2 diabetes","volume":"15","author":"Frystyk","year":"1999","journal-title":"Diabetes Metab Res Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08655-5","article-title":"Circulating concentrations of insulin-like growth factor-1 and development of glucose intolerance: a prospective observational study","volume":"358","author":"Sandhu","year":"2002","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2009.01.002","article-title":"IGF-dependent and IGF-independent actions of IGF-binding protein-1 and -2: implications for metabolic homeostasis","volume":"20","author":"Wheatcroft","year":"2009","journal-title":"Trends Endocrinol Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-10-0963","article-title":"Prediction of incident diabetes mellitus by baseline IGF1 levels","volume":"164","author":"Schneider","year":"2011","journal-title":"Eur J Endocrinol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1089\/met.2011.0083","article-title":"The insulin-like growth factor system, metabolic syndrome, and cardiovascular disease risk","volume":"10","author":"Akanji","year":"2012","journal-title":"Metab syndrome related Disord"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12446","article-title":"Insulin-like growth factor-II: its role in metabolic and endocrine disease","volume":"80","author":"Livingstone","year":"2014","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2014.858698","article-title":"Insulin growth factor binding proteins as therapeutic targets in type 2 diabetes","volume":"18","author":"Hjortebjerg","year":"2014","journal-title":"Expert Opin Ther Targets"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1530\/JME-18-0016","article-title":"40 years of IGF1, role of IGF-binding proteins in regulating IGF responses to changes in metabolism","volume":"61","author":"Clemmons","year":"2018","journal-title":"J Mol Endocrinol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.1999.00775.x","article-title":"Splanchnic exchange of insulin-like growth factor binding protein-1 (IGFBP-1), IGF-I and acid-labile subunit (ALS) during normo- and hyperinsulinemia in healthy subjects","volume":"51","author":"Fernqvist-Forbes","year":"1999","journal-title":"Clin Endocrinol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(91)90092-B","article-title":"The insulin-like growth factor binding protein-1 in low and high insulin responders before and during dexamethasone treatment","volume":"40","author":"Brismar","year":"1991","journal-title":"Metabolism"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-1245","article-title":"Insulin-like growth factor binding protein 1 as a novel specific marker of hepatic insulin sensitivity","volume":"93","author":"Kotronen","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"B15","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.diabet.2008.11.003","article-title":"Low levels of insulin-like growth-factor-binding protein-1 (IGFBP-1) are prospectively associated with the incidence of type 2 diabetes and impaired glucose tolerance (IGT): The s\u00f6der\u00e5kra cardiovascular risk factor study","volume":"35","author":"Petersson","year":"2009","journal-title":"Diabetes Metab"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-008-1016-x","article-title":"Insulin-like growth factor-binding protein-1 in the prediction and development of type 2 diabetes in middle-aged Swedish men","volume":"51","author":"Lewitt","year":"2008","journal-title":"Diabetologia."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-10-0301","article-title":"IGF-binding protein 1 and abdominal obesity in the development of type 2 diabetes in women","volume":"163","author":"Lewitt","year":"2010","journal-title":"Eur J Endocrinol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2337\/db11-1488","article-title":"Insulin-like growth factor axis and risk of type 2 diabetes in women","volume":"61","author":"Rajpathak","year":"2012","journal-title":"Diabetes."},{"key":"B19","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.cmet.2009.11.007","article-title":"Antidiabetic effects of IGFBP2, a leptin-regulated gene","volume":"11","author":"Hedbacker","year":"2010","journal-title":"Cell Metab"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ghir.2014.04.006","article-title":"Circulating IGF-axis protein levels and their relation with levels of plasma adipocytokines and macronutrient consumption in women","volume":"24","author":"Beasley","year":"2014","journal-title":"Growth Hormone &IGF Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.2337\/db18-0620","article-title":"Insulin-like growth factor binding protein 2 (IGFBP-2) and the risk of developing type 2 diabetes","volume":"68","author":"Wittenbecher","year":"2019","journal-title":"Diabetes"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.2337\/db16-0514","article-title":"Insulin-like growth factor axis and gestational diabetes mellitus: A longitudinal study in a multiracial cohort","volume":"65","author":"Zhu","year":"2016","journal-title":"Diabetes."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2014.09.022","article-title":"Circulating IGFBP-2 levels are incrementally linked to correlates of the metabolic syndrome and independently associated with VLDL triglycerides","volume":"237","author":"Carter","year":"2014","journal-title":"Atherosclerosis."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.6.1375","article-title":"Adipocytokines attenuate the association between visceral adiposity and diabetes in older adults","volume":"27","author":"Kanaya","year":"2004","journal-title":"Diabetes Care"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.5.7463","article-title":"Hypoadiponectinemia in obesity and type 2 diabetes: Close association with insulin resistance and hyperinsulinemia","volume":"86","author":"Weyer","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.2337\/dc06-0952","article-title":"Associations of adiponectin levels with incident impaired glucose metabolism and type 2 diabetes in older men and women","volume":"29","author":"Snijder","year":"2006","journal-title":"Diabetes Care"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-2702","article-title":"Omentin 1, adiponectin, and the risk of developing type 2 diabetes","volume":"39","author":"Wittenbecher","year":"2016","journal-title":"Diabetes Care"},{"key":"B28","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1038\/s41598-017-18709-9","article-title":"Plasma adiponectin levels and type 2 diabetes risk: a nested case control study in a Chinese population and an updated meta-analysis","volume":"8","author":"Wang","year":"2018","journal-title":"Sci Rep"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1210\/clinem\/dgaa953","article-title":"A panel of 6 biomarkers significantly improves the prediction of type 2 diabetes in the MONICA\/KORA study population","author":"Thorand","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"B30","doi-asserted-by":"publisher","first-page":"dc21","DOI":"10.2337\/dc21-1328","article-title":"An insulin resistance score improved diabetes risk assessment in the malm\u00f6 prevention project\u2013a longitudinal population-based study of older europeans","author":"Shiffman","year":"2021","journal-title":"Diabetes Care"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2008.02463.x","article-title":"Psychological distress and risk of pre-diabetes and type 2 diabetes in a prospective study of Swedish middle-aged men and women","volume":"25","author":"Eriksson","year":"2008","journal-title":"Diabetic Med"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1530\/acta.0.1070563","article-title":"Cross-reaction of serum somatomedin-binding protein in a radioimmunoassay developed for somatomedin-binding protein isolated from human amniotic fluid","volume":"107","author":"P\u00f3voa","year":"1984","journal-title":"Acta Endocrinol (Copenh)"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021349","article-title":"Free and total insulin-like growth factor (IGF)-I, -II, and IGF binding protein-1, -2, and -3 serum levels in patients with active thyroid eye disease","volume":"88","author":"Krassas","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-2310","article-title":"Gender differences of oligomers and total adiponectin during puberty: a cross-sectional study of 859 Danish school children","volume":"92","author":"Andersen","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)00602-4","article-title":"Non-competitive time-resolved immune-fluorometric assays for determination of human insulin-like growth factor I and II","volume":"5","author":"Frystyk","year":"1995","journal-title":"Growth Regul"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1530\/acta.0.1240620","article-title":"Comparison of acid ethanol extraction and acid gel filtration prior to IGF-I and IGF-II radioimmune-assays: improvement of determinations in acid ethanol extracts by the use of truncated IGF-I as radioligand","volume":"124","author":"Bang","year":"1991","journal-title":"Acta Endocrinol (Copenh)"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-25-10-1375","article-title":"Coated charcoal immunoassay of insulin","volume":"25","author":"Herbert","year":"1965","journal-title":"J Clin Endocrinol Metab"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0563-7","article-title":"Contribution of genetics to visceral adiposity and its relation to cardiovascular and metabolic disease","volume":"25","author":"Karlsson","year":"2019","journal-title":"Nat Med"},{"key":"B39","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1002\/ajhb.22279","article-title":"Leptin and adiponectin: distribution and associations with cardiovascular risk factors in men and women of the general population","volume":"24","author":"Andreasson","year":"2012","journal-title":"Am J Hum Biol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.2337\/db06-0436","article-title":"IGF-binding protein-2 protects against the development of obesity and insulin resistance","volume":"56","author":"Wheatcroft","year":"2007","journal-title":"Diabetes."},{"key":"B41","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.ghir.2020.01.003","article-title":"Development of a novel assay for IGFBP-2 complexed with IGF-I and -II in human serum","volume":"51","author":"Wheatcroft","year":"2020","journal-title":"GHIR"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.genm.2009.09.006","article-title":"Gender differences in adiponectin and low-grade inflammation among individuals with normal glucose tolerance, prediabetes and type 2 diabetes","volume":"6","author":"Saltevo","year":"2009","journal-title":"Gender Med"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-015-0261-2","article-title":"IGFBP-2-taken the lead in growth metabolism and cancer","volume":"9","author":"Yau","year":"2015","journal-title":"J Cell Commun Signal"},{"key":"B44","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.beem.2015.07.002","article-title":"Physiology and pathophysiology of IGFBP-1 and IGFBP-2 \u2013 consensus and dissent on metabolic control and malignant potential","volume":"29","author":"Agerholm","year":"2015","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2018.10.008","article-title":"The insulin like growth factor and binding protein family: Novel therapeutics targets in obesity and diabetes","volume":"19","author":"Haywood","year":"2019","journal-title":"Review Mol Metab"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.81.5.8626837","article-title":"Quantitative genetic analyses of insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1), and insulin levels in middle-aged and elderly twins","volume":"81","author":"Hong","year":"1996","journal-title":"JCEM"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1740289","article-title":"IGF-binding protein-1 inhibits IGF effects on adipocyte function: implications for insulin-like actions at the adipocyte","volume":"174","author":"Siddals","year":"2002","journal-title":"J Endocrinol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.8.2075","article-title":"Vascular endothelial function and blood pressure homeostasis in mice overexpressing IGF binding protein-1","volume":"52","author":"Wheatcroft","year":"2003","journal-title":"Diabetes."},{"key":"B49","doi-asserted-by":"publisher","first-page":"18","DOI":"10.15252\/embj.201592903","article-title":"IGFBP1 increases \u03b2-cell regeneration by promoting \u03b1- to \u03b2-cell trans-differentiation\u201d","volume":"35","author":"Lu","year":"2016","journal-title":"EMBO J"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.3390\/ijms20051190","article-title":"Beneficial effects of adiponectin on glucose and lipids metabolism and atherosclerotic progression: Mechanisms and perspectives","volume":"20","author":"Yanai","year":"2019","journal-title":"Review Int J Mol Sci"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c170046","article-title":"Adiponectin regulation and function","volume":"8","author":"Fang","year":"2018","journal-title":"Am Physiol Society: Compr Physiol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwv188","article-title":"Insulin-like growth factor 1 and insulin-like growth factor\u2013binding protein 3 in relation to the risk of type 2 diabetes mellitus: Results from the EPIC\u2013potsdam study","volume":"183","author":"Drogan","year":"2016","journal-title":"Am J Epidemiol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.ghir.2004.06.001","article-title":"Free insulin-like growth factors \u2013 measurements and relationships to growth hormone secretion and glucose homeostasis","volume":"14","author":"Frystyk","year":"2004","journal-title":"Growth Horm IGF Res"},{"key":"B54","doi-asserted-by":"publisher","first-page":"7797","DOI":"10.3390\/ijms22157797","article-title":"Hyperinsulinemia and its pivotal role in aging, obesity, type 2 diabetes, cardio vascular disease and cancer","volume":"22","author":"Janssen","year":"2021","journal-title":"Review Int J Mol Sci"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.1092307\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T11:02:26Z","timestamp":1672916546000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.1092307\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,5]]},"references-count":54,"alternative-id":["10.3389\/fendo.2022.1092307"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.1092307","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,5]]},"article-number":"1092307"}}