Evidence of non-linearity in the association of glycemic control with influenza/pneumonia mortality: a study of 19 000 adults from the US general population.

ABSTRACT

BACKGROUND: Diabetes is a major public health problem and thought to be a risk factor for infectious diseases, but pertinent epidemiological evidence is limited. This study aimed to analyse the associations of diabetes, disease duration and glycated haemoglobin levels (HbA1c) with infectious diseases mortality in the general population, including the investigation of potential non-linear relationships. METHODS: An observational, prospective study of 19 783 subjects included in the Third National Health and Nutrition Examination Survey, representing the adult non-institutionalized population of the United States of America, was conducted. The analysis was done by multiple Cox regression and restricted cubic spline modelling. RESULTS: Self-reported diabetes and diabetes duration were not significantly associated with the outcomes. However, there was evidence for a non-linear association of HbA1c with mortality from influenza, pneumonia or other acute lower respiratory infections. Spline regression suggested a roughly doubled risk of mortality beyond an HbA1c of 6.5% (48 mmol/mol) in reference to 5.2% (33 mmol/mol). CONCLUSIONS: Future studies on diabetes and infections should adequately address potential non-linearity, which may be necessary to better understand and characterize more precisely the relationship of diabetes with infectious diseases.