title: Low fructosamine and mortality - A long term follow-up of 215,011 non-diabetic subjects in the Swedish AMORIS study.
abstract: Both high and low fasting glucose has been associated with an increased mortality among individuals without diabetes. This J-shaped association has also been shown for HbA1c in relation to all-cause mortality. High fructosamine is associated with increased mortality. In this study we aim to evaluate if low fructosamine is also associated with increased mortality in non-diabetic subjects.
  
  
  
  We included 215,011 subjects from the AMORIS cohort undergoing occupational health screening or primary care in Stockholm, Sweden. Cause specific mortality was obtained from the Swedish Cause-of-Death Register by record linkage. Hazard ratios for the lowest decile of fructosamine were estimated by Cox regression for all-cause (n = 41,388 deaths) and cause-specific mortality during 25 years of follow-up. We observed gradually increased mortality with lower fructosamine in a large segment of the population. In the lowest decile of fructosamine the sex, age, social class and calendar adjusted hazard ratio was 1.20 (95% CI; 1.18-1.27) compared to deciles 2-9. This increased mortality was attenuated after adjustment for six other biomarkers (HR = 1.11 (95% CI; 1.07-1.15)). Haptoglobin, an indicator of chronic inflammation, made the greatest difference in the point estimate. In sensitivity analyses we found an association between low fructosamine and smoking and adjustment for smoking further attenuated the association between low fructosamine and mortality.
  
  
  
  Low levels of fructosamine in individuals without diabetes were found to be associated with increased mortality. Smoking and chronic inflammation seem to at least partially explain this association but an independent contribution by low fructosamine cannot be excluded.
authors.affiliation: Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: hakan.malmstrom@ki.se.
authors.forename: H
authors.initials: H
authors.lastname: Malmström
authors.affiliation: Division of Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
authors.forename: P E
authors.initials: PE
authors.lastname: Wändell
authors.affiliation: Department of Emergency Medicine, Karolinska University Hospital, Huddinge, Sweden; Department of Internal Medicine, Karolinska Institutet, Solna, Sweden.
authors.forename: M J
authors.initials: MJ
authors.lastname: Holzmann
authors.affiliation: Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Ärnlöv
authors.affiliation: Department of Medicine, Clinical Epidemiological Unit, Karolinska Institutet, Stockholm, Sweden; CALAB Research, Stockholm, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Jungner
authors.affiliation: Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Medical Evidence & Observational Research, AstraZeneca R&D, Mölndal, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Hammar
authors.affiliation: Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Walldius
authors.affiliation: Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: A C
authors.initials: AC
authors.lastname: Carlsson
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002423:Cause of Death; D015536:Down-Regulation; D005260:Female; D005500:Follow-Up Studies; D019270:Fructosamine / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000097:blood / Q000401:mortality*; D013548:Sweden; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D019270:Fructosamine
keywords: Cancer; Cardiovascular; Fructosamine; Glucose; Inflammation; Mortality; Smoking