Introduction: Type 2 diabetes (T2D) and cardiovascular disease (CVD) risk associate with
ferritin and percent transferrin saturation (%TS) levels. However, increased risk has been observed at
levels considered within the “normal range” for these markers.
Objective: To define normative ferritin and %TS levels associated with T2D and CVD risk.
Methods: Six-monthly ferritin, %TS and hemoglobin levels from 1,277 iron reduction clinical trial
participants with CVD (peripheral arterial disease, 37% diabetic) permitted pair-wise analysis using
Loess Locally Weighted Smoothing plots. Curves showed continuous quantitative ferritin, hemoglobin
(reflecting physiologic iron requirements), and %TS (reflecting iron transport and sequestration) levels
over a wide range of values. Inflection points in the curves were compared to ferritin and %TS levels
indicating increased T2D and CVD risk in epidemiologic and intervention studies.
Results: Increasing ferritin up to about 80 ng/mL and %TS up to about 25% TS corresponded to increasing
hemoglobin levels, and minimal T2D and CVD risk. Displaced Loess trajectories reflected
lower hemoglobin levels in diabetics compared to non-diabetics. Ferritin levels up to about 100 ng/mL
paralleled proportionately increasing %TS levels up to about 55%TS corresponding to further limitation
of T2D and CVD risk. Ferritin levels over 100 ng/mL did not associate with hemoglobin levels
and coincided with increased T2D and CVD risk.
Conclusions: Recognition of modified normal ranges for ferritin from about 15 ng/mL up to about 80-
100 ng/mL and %TS from about 15% up to about 25-55% may improve the value of iron biomarkers
to assess and possibly lower T2D and CVD risk.