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Meyer, N.M.T.* ; Kabisch, S.* ; Dambeck, U.* ; Honsek, C.* ; Kemper, M.* ; Gerbracht, C.* ; Arafat, A.M.* ; Birkenfeld, A.L. ; Schwarz, P.E. ; Machann, J. ; Osterhoff, M.A.* ; Weickert, M.O.* ; Pfeiffer, A.F.H.*

Low IGF1 and high IGFBP1 predict diabetes onset in prediabetic patients.

Eur. J. Endocrinol. 187, 555-565 (2022)
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Objectives: Some individuals develop type 2 diabetes mellitus (T2DM) despite significant metabolic improvements through lifestyle intervention. We tested the hypotheses that insulin growth factor 1 (IGF1) and its binding proteins 1 and 2 predict the onset of T2DM in prediabetes patients and determine the capacity for metabolic regeneration. Design: We measured fasting serum IGF1, insulin growth factor-binding protein 1 (IGFBP1) and IGFBP2 in three randomized controlled lifestyle intervention trials, covering at least 1 year of intervention period and 1 year of additional follow-up. Methods: Within a sample of 414 high-risk prediabetes patients (58% women; 28-80 years), we analyzed fasting serum concentrations of IGF1, IGFBP1 and IGFBP2 in relation to diabetes incidence and metabolic parameters over 2 years. Three hundred and forty-five subjects finished the first year of intervention. Results: The interventions significantly improved body weight (BMI: -3.24%, P < 0.001), liver fat (-36.8%, P < 0.001), insulin sensitivity (IS) (homeostatic model assessment-insulin resistance: -6.3%, P < 0.001) and insulin secretion (disposition index: +35%, P < 0.001) in the cohort. Fourteen percent developed T2DM within 2 years. Mean IGFBP1 levels at baseline were lower in prediabetes compared to a healthy population. Also, prediabetes patients with obesity and nonalcoholic fatty liver disease had lower IGFBP1. Those with impaired glucose tolerance had higher IGFBP1 compared to those with only impaired fasting glucose. Baseline IGF1 was lower (122.5 vs 146.6 µg/L) and IGFBP1 was higher (3.32 vs 2.09 µg/L) in subjects who developed T2DM (n = 57), resulting in a significant prediction of diabetes incidence (hazard ratio (HR) IGF1: 0.991 µg/L, P = 0.003; HR IGFBP1: 1.061 µg/L, P = 0.002). This translates into a 20% and 9% difference in T2DM incidence for IGF1 and IGFBP1, respectively. Despite reduced weight, visceral fat and hepatic fat in response to 1 year of lifestyle intervention, those who developed T2DM had not improved insulin sensitivity, glucose tolerance or IGFBP1. Conclusions: Lower IGF1 and higher IGFBP1 in prediabetes predicted the incidence of T2DM, indicating an impairment of beta-cell function, which explains the unresponsiveness to lifestyle intervention.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 0804-4643
e-ISSN 1479-683X
Journal European Journal of Endocrinology
Quellenangaben Volume: 187, Issue: 4, Pages: 555-565 Article Number: , Supplement: ,
Publisher BioScientifica
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute for Pancreatic Beta Cell Research (IPI)
Grants California Walnut Commission
Diabetes-Stiftung
German Center for Diabetes Research