Low IGF1 and high IGFBP1 predict diabetes onset in prediabetic patients

Abstract

Some individuals develop T2DM despite significant metabolic improvements through lifestyle intervention. We tested the hypotheses that IGF1 and its binding proteins 1 and 2 a) predict the onset of T2DM in prediabetes patients, b) determine the capacity for metabolic regeneration. Design We measured fasting serum IGF1, IGFBP1 and IGFBP2 in 3 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. 345 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), IS (HOMA-IR: -6.3%, p<0.001) and insulin secretion (Disposition index: +35%, p <0.001) in the cohort. 14 % 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 NAFLD 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 higher (3.32 vs. 2.09 µg/L) in subjects who developed T2DM (n=57), resulting in a significant prediction of diabetes incidence (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 and hepatic fat as response to one 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.

Co-differential genes between DKD and aging: implications for a diagnostic model of DKD

“…Consistent with our study, significantly decreased serum IGF1 and decreased renal Igf1 RNA levels were found in db/db mice with DKD in a previous study ( Segev et al, 2007 ). A lifestyle intervention trial also found that low IGF1 levels predicted DM onset in patients with prediabetes ( Meyer et al, 2022 ). However, unlike our study, which demonstrated low IGF1 expression in DKD patients, some studies have reported that IGF expression increases with DKD progression ( Dong et al, 2019 ).…”

Transcriptome Analysis to Elucidate the Effects of Milk Replacer Feeding Level on Intestinal Function and Development of Early Lambs

“…IGFBP1 is a multifunctional protein that regulates the biological effects of insulin-like growth factors, regulates glucose and lipid metabolism, and participates in apoptosis and other biological processes [31]. When insulin levels decrease, IGFBP1 expression increases, leading to a decrease in the release of glucose; this consequently affects lipid metabolism and promotes fatty acid oxidation [32]. Kim et al reported that overproduction of ITIH1 after loss of Gα13 in the liver exacerbates systemic insulin resistance in mice [33].Moreover, the expression levels of ITIH3 (log 2 FC = 10.89) and ITIH2 (log 2 FC = 10.79) were significantly upregulated.…”

Exome sequencing reveals aggregates of rare variants in glycosyltransferase and other genes influencing immunoglobulin G and transferrin glycosylation

“…On the other hand, using publicly available repositories of gene-based associations in the UK Biobank data, we found that rare missense variants from MSR1 (associated with transferrin glycosylation) were also associated with blood levels of insulin-like growth factor 1 (IGF1). IGF1 is a hormone with significant structural and functional similarities to insulin: lower levels of IGF1 are associated with higher risk of Type 1 and 2 diabetes mellitus 41,42 . Recently, a rare deleterious missense variant in IGF1 receptor (IGF1R) was found to be significantly associated with Type 2 diabetes in UK Biobank, further corroborating the link between IGF1 and diabetes 43 .…”