Background: The DNA-binding High Mobility Group Box-1 (HMGB1) is an intracellular gene regulator that can be secreted also in response to inflammatory mediators, including interleukins, binding subsequently to both RAGE and Toll-like receptors forming a self-reinforcing inflammatory circle. Cystic fibrosis (CF) is a condition characterized by chronic inflammation. Elevated serum HMGB1 concentrations were described in serum of obese children and to be associated with the metabolic syndrome that originates from a state of insulin-insensitivity. This latter is a feature of cystic fibrosis related diabetes also (CFRD).
Objective and Hypotheses: We aimed to assess HMGB1 serum concentrations in CF patients and verify whether there were any relationships with the state of glucose tolerance.
Method: Forty-three CF patients in stable clinical conditions and 21 controls of comparable age, sex, and pubertal stage (18.73±1.74 years, 6M, 15F) were enrolled. Glucose tolerance was established in patients based on a five point oral glucose tolerance test, according to actual American Diabetes Association criteria for CF. Three groups were considered: normal tolerant subjects (14.54±1.21 years, 8M, 12F), glucose intolerant (15.56±2.74 years, 7M, 8F), with CFRD at diagnosis (21.47±2.17 years, 2M, 6F). HMGB1 was assayed using a specific ELISA Kit (IBL-America).
Results: HMGB1 concentrations were similar in control subjects and in glucose tolerant patients (2.7±0.3 ng/ml vs 2.8±0.3 ng/ml respectively), and increased progressively in glucose intolerant subjects (3.96±0.96 ng/ml) and in CF subjects at onset of diabetes (7.66±1.7 ng/ml, P<0.05). In all subjects analysed HMGB1 concentrations were positively correlated with the fasting glucose/insulin ratio (R: 0.34; P: 0.042).
Conclusion: HMGB1 concentrations increased with worsening of glucose tolerance. The high concentrations at onset of diabetes could be related with the well described decline in clinical conditions from thereafter. The relationship with the fasting glucose to insulin ratio suggested it might be involved in the regulation of insulin sensitivity, as in obesity.
Further studies are warranted to verify whether HMGB-1 could become a marker of onset of CFRD and/or of severe worsening of clinical conditions and lung disease in CF.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology