Systemic inflammation is enhanced by acute hyperglycaemia and suppressed by insulin in COPD

Abstract

Introduction: Over half of COPD patients hospitalised for exacerbations have elevated blood glucose. Acute hyperglycaemia is associated with increased risk of death and prolonged hospital stay [Baker et al Thorax;61:284-9]. We investigated the effect of acute hyperglycaemia and insulin therapy on systemic inflammation.

Methods: 8 stable COPD patients (4male, 66±8yrs, FEV₁ 44±16%predicted) and 8 volunteers (8male, 24±5yrs, FEV₁ 89±12%) with fasting glucose <7mM received an octreotide infusion to inhibit pancreatic function. Glucose and insulin were infused for 4 consecutive 60min periods to achieve: Low glucose (fasting), low insulin (0.3mU.kg^-1.min^-1); high glucose (10mM above fasting levels), low insulin; high glucose, high insulin (1.5mU.kg^-1.min^-1); low glucose, high insulin. Cytokines were measured in blood sampled at the end of each 60min period using a Bio-Plex system (Bio-Rad).

Results: In COPD, high glucose, low insulin increased IP10 by 48 (12-181)% (median (interquartile range)), TNFa by 28 (8-54)% and IL-12 by 16 (2-34)% from low glucose, low insulin (p<0.05). IP10 increased significantly more in COPD than in volunteers (p=0.009). Subsequently, low glucose, high insulin suppressed IP10, TNFa and IL-12 to starting concentrations (p<0.05). Additionally low glucose, high insulin suppressed IL-1a, IL-1b, IL-16 and IL-4 by 4 to 26% (p<0.05). Suppression of IP10 and TNFa was significantly greater in COPD patients than in volunteers (p=0.038).

Conclusion: Acute hyperglycaemia amplifies systemic inflammation in COPD, which could be detrimental during exacerbations. The anti-inflammatory potential of blood glucose control with insulin for exacerbations requires further investigation.