Increased circulating IL-8 is associated with reduced IGF-1 and related to poor metabolic control in adolescents with type 1 diabetes mellitus

Abstract

Background-A dysregulated growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis is well-recognized in children and adolescents with type 1 diabetes mellitus (T1DM). Decreased IGF-1 levels can also be found in chronic inflammatory diseases, while hyperglycemia promotes inflammatory cytokine production. Therefore, inflammatory cytokines may link poor metabolic control with GH/IGF-1 axis changes. This study examined the relationship between serum inflammatory cytokines and IGF-1 in adolescents (age 13-18) with TIDM in chronic poor (n=17) or favorable (n=19) glucose control. Poor control (PC) was defined as ≥ 3, consistent HbA1C > 9% during the previous 2 years, while favorable control (FC) was consistent levels of HbA1C < 9%.Results-HbA1C (FC: 7.5±0.6%; PC: 10.5±0.9%, p<0.001) and interleukin (IL)-8 (FC: 3.7±4.0 pg/ml; PC: 7.4±4.3 pg/ml, p=0.01) were increased and IGF-1 (FC: 536.5±164.3 ng/ml; PC: 408.9 ±157.1 ng/ml, p=0.03) was decreased in patients with poor control compared to patients with favorable control. Moreover, IL-8 was inversely correlated with IGF-1 (r=−0.40, p=0.03) and positively correlated with HbA1C (r=0.36, p=0.03).Conclusions-In adolescents with T1DM and chronic, poor glucose control, increased serum IL-8 is associated with reduced IGF-1 suggesting a pro-inflammatory milieu that may contribute to alterations in the GH/IGF-1 axis.

Impaired osteogenesis of T1DM bone marrow-derived stromal cells and periosteum-derived cells and their differential in-vitro responses to growth factor rescue

“…Previous studies reported lower serum IGF-1 along with higher inflammatory cytokines and lower bone mineral density in T1DM patients with poor glycemic control than those with good glycemic control [29–31]. We first confirmed that the proliferation and osteogenesis of these diabetic BMSCs and PDCs were differentially impaired and these impairments were exacerbated in high glucose cultures.…”

CXCR1/2 Inhibition Blocks and Reverses Type 1 Diabetes in Mice

“…Human pancreatic islets produce and secrete the proinflammatory CXCL8 and CXCL1 ligands (12,15,17,22,23), whereas lipopolysaccharide-induced production of CXCL8 by neutrophils is increased in prediabetic and T1D patients. In parallel, circulating concentrations of CXCL8 are elevated in children with T1D compared with nondiabetic controls (24)(25)(26). Specifically, concentrations of CXCL8 correlate with glycemic control; higher concentrations are associated with poor or inadequate glucose control.…”

“…In fact, pancreatic islets produce and secrete the CXCR1/2 chemokine ligands (named CXCL8, CXCL1, and CXCL2) in response to proinflammatory cytokines (12,15,17,22,23). Furthermore, the concentration of CXCR1/2 ligands is elevated in the blood of both rodents and humans with autoimmune diabetes (24)(25)(26); most important, recent reports support the notion that neutrophils (the major target of CXCR1/2 inhibitors) play a key role in the etiopathogenesis of T1D (27)(28)(29). We therefore extensively characterized the consequences of CXCR1/2 inhibition on inflammation-and autoimmunity-mediated diabetes in preclinical models.…”

Bone health in type 1 diabetes: focus on evaluation and treatment in clinical practice

“…Moreover, the low levels of insulin-like growth factor-1 (IGF-1) [19,20,[28][29][30][31] and vitamin D [32], which also usually accompany diabetes, may be additional factors responsible for poor bone health (see Fig. 1).…”