Glycaemic status, insulin resistance, and risk of infection-related mortality: a cohort study

Importance: The impact of non-diabetic hyperglycaemia and insulin resistance on infection-related mortality risk remains unknown. Objective: We investigated the association of glycaemic status and insulin resistance with infection-related mortality in individuals with and without diabetes. Design: Cohort study based on Kangbuk Samsung Health Study and national death records. Participants: About 666 888 Korean adults who underwent fasting blood measurements including glucose, glycated haemoglobin (HbA1c), and insulin during health-screening examinations were followed for up to 15.8 years. Main outcome and measures: Infection-related mortality, therefore we used Cox proportional hazards regression analyses to estimate hazard ratios (HRs) and 95% CIs for infection-related mortality. Vital status and infection-related mortality were ascertained through national death records. Variable categories were created based on established cut-offs for glucose and HbA1c levels and homeostatic model assessment of insulin resistance (HOMA-IR) quintiles. Results: During a median follow-up of 8.3 years, 313 infectious disease deaths were dentified. The associations of glucose and HbA1c levels with infection-related mortality were J-shaped (P for quadratic trend<.05). The multivariable-adjusted HR (95% CIs) for infection-related mortality comparing glucose levels <5, 5.6-6.9, and ≥7.0 mmol/L to 5.0–5.5 mmol/L (the reference) were 2.31 (1.47–3.64), 1.65 (1.05–2.60), and 3.41 (1.66–7.00), respectively. Among individuals without diabetes, the multivariable-adjusted HR for infection-related mortality for insulin resistance (HOMA-IR ≥75th centile versus <75th centile) was 1.55 (1.04–2.32). Conclusions and relevance: Both low and high glycaemic levels and insulin resistance were independently associated with increased infection-related mortality risk, indicating a possible role of abnormal glucose metabolism in increased infection-related mortality.