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

Abstract

Abstract 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.