Higher ferritin levels, but not serum iron or transferrin saturation, are associated with Type 2 diabetes mellitus in adult men and women free of genetic haemochromatosis

Clin Endocrinol (Oxf). 2015 Apr;82(4):525-32. doi: 10.1111/cen.12529. Epub 2014 Jul 23.

Abstract

Context: Iron overload predisposes to diabetes and higher ferritin levels have been associated with diabetes. However, it is unclear whether ferritin reflects differences in iron-related parameters between diabetic and nondiabetic persons. We examined associations of serum ferritin, iron and transferrin saturation with Type 2 diabetes in adults without genetic predisposition to iron overload.

Design, participants and measurements: Cross-sectional analysis of community-dwelling men and women aged 17-97 years from the Busselton Health Survey, Western Australia. Men and women carrying genotypes associated with haemochromatosis (C282Y/C282Y or C282Y/H63D) were excluded. Serum ferritin, iron and transferrin saturation were assayed.

Results: There were 1834 men (122 with diabetes, 6·6%) and 2351 women (141 with diabetes, 6%). In men, higher serum ferritin was associated with diabetes after adjusting for age, smoking, alcohol, cardiovascular history, body mass index (BMI), waist, blood pressure, lipids, C-reactive protein (CRP), adiponectin, alanine transaminase (ALT) and gamma-glutamyl transpeptidase (GGT) [odds ratio (OR): 1·29 per 1 unit increase log ferritin, 95% confidence interval (CI) = 1·01-1·65, P = 0·043]. In women, higher serum ferritin was associated with diabetes [fully adjusted OR: 1·31 per 1 unit increase log ferritin, 95% CI = 1·04-1·63, P = 0·020; 1·84 for tertile (T) 3 vs T1, 95% CI = 1·09-3·11]. Neither iron levels nor transferrin saturation were associated with diabetes risk in men or women. Higher ferritin was not associated with insulin resistance in nondiabetic adults.

Conclusions: In adults, higher ferritin levels are independently associated with prevalent diabetes while iron and transferrin saturation are not. Ferritin is a robust biomarker for diabetes risk, but further investigation is needed to clarify whether this relationship is mediated via iron metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Pressure
  • Cohort Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Female
  • Ferritins / blood*
  • Genotype
  • Hemochromatosis / genetics
  • Humans
  • Insulin Resistance
  • Iron / blood*
  • Iron Overload / blood*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Regression Analysis
  • Transferrin / metabolism*
  • Young Adult

Substances

  • Transferrin
  • Ferritins
  • Iron