Zacharski Leo R, Shamayeva Galina, Chow Bruce K, DePalma Ralph G
Research Service, Department of Veterans Affairs Medical Center, White River Jct., Vermont. United States.
Veterans Affairs Cooperative Studies Program, Research Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA. United States.
Curr Diabetes Rev. 2017;13(4):428-436. doi: 10.2174/1573399813666170504163138.
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.
To define normative ferritin and %TS levels associated with T2D and CVD risk.
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.
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.
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.
2型糖尿病（T2D）和心血管疾病（CVD）风险与铁蛋白及转铁蛋白饱和度百分比（%TS）水平相关。然而，在这些标志物被认为处于“正常范围”的水平时，已观察到风险增加。
确定与T2D和CVD风险相关的铁蛋白和%TS的正常水平。
对1277名患有CVD（外周动脉疾病，37%为糖尿病患者）的铁减少临床试验参与者每六个月检测一次铁蛋白、%TS和血红蛋白水平，使用局部加权散点平滑法（Loess）进行成对分析。曲线显示了在广泛数值范围内连续的定量铁蛋白、血红蛋白（反映生理铁需求）和%TS（反映铁转运和螯合）水平。将曲线中的拐点与流行病学和干预研究中表明T2D和CVD风险增加的铁蛋白和%TS水平进行比较。
铁蛋白增加至约80 ng/mL以及%TS增加至约25%时，对应血红蛋白水平增加，且T2D和CVD风险最小。与非糖尿病患者相比，糖尿病患者中局部加权散点平滑轨迹下移反映了较低的血红蛋白水平。铁蛋白水平高达约100 ng/mL时，%TS水平相应地按比例增加至约55%，这对应着T2D和CVD风险的进一步降低。铁蛋白水平超过100 ng/mL与血红蛋白水平无关，且与T2D和CVD风险增加相符。
认识到铁蛋白的正常范围从约15 ng/mL修改为约80 - 100 ng/mL，以及%TS从约15%修改为约25 - 55%，可能会提高铁生物标志物评估并可能降低T2D和CVD风险的价值。
