Mean Serum Transferrin Saturation Research Articles

Ferritin and serum iron as surrogate markers of poor glycemic control and microvascular complications in type 2 diabetes mellitus

This study was designed to find the correlation of iron indices with HbA1c levels and microvascular complications among patients with type 2 DM. Results were consistent with our hypothesis that high iron indices (serum iron and serum ferritin) not high enough to cause hemochromatosis but were still associated with poor glycemic control and its complications. The mean age of study group was 58.57 ± 3.17 years; whereas, the mean age of control group was 53.95 ± 4.43. The mean HbA1c of study group was 9.46 ± 1.31; whereas, the mean HbA1c of control group was 6.42 ± 0.28. The duration of diabetes in study group was 9.69 ± 2.69 years; whereas, it is 5.26 ± 2.81 years in control group. The mean serum iron level in study group was 155.08 ± 22.13 μg/dl; whereas, it is 88.81 ± 38.04 μg/dl in control group. The mean serum ferritin level in study group was 284.79 ± 50.06 ng/ml; whereas, it is 181.31 ± 54.08 ng/ml in control group. The mean serum transferrin saturation in study group was 30.25 ± 9.94; whereas, it is 28.92 ± 6.03 in control group. Out of the 100 patients in the study group, 40 patients had nephropathy, 33 patients had retinopathy, and 31 patients had neuropathy. In 100 patients in the control group, 12 patients had nephropathy, 11 patients had retinopathy, and 12 patients had neuropathy. On applying Pearson’s coefficient of correlation, a moderately significant correlation was obtained between serum iron, ferritin, and HbA1c in study group. However, no significant correlation was obtained with transferrin saturation. On applying regression analysis among HbA1c, serum ferritin, and serum iron, it was observed (the sum of squares of the group was 30.5) that variation is not due to chance.

Iron Profile and Glycaemic Control in Patients with Type 2 Diabetes Mellitus

Iron overload is increasingly being connected to insulin resistance in Type 2 Diabetes Mellitus (T2DM) patients. Free iron causes the assembly of reactive oxygen species that invariably steer the body’s homeostasis towards oxidative stress-mediated diabetic complications. This study aims to assess the serum iron, total iron binding capacity (TIBC), and percentage transferrin saturation (Tsat) of 150 subjects divided into three groups (I,II,III) of 50. Healthy individuals (controls) constituted Group I. Group II consisted of T2DM patients with optimal glycaemic control. T2DM patients with suboptimal glycaemic control formed group III. Mean serum free iron concentration was 105.34 ± 3.5, 107.33 ± 3.45, and 125.58 ± 3.45 μg/dL in Group I, Group II, and Group III, respectively. Mean serum TIBC concentration in Group I, Group II, and Group III was 311.39 ± 5.47, 309.63 ± 6.1, and 284.2 ± 3.18μg/dL, respectively. Mean serum transferrin saturation (%) in Group I, Group II, and Group III was 34.17 ± 1.21, 35.02 ± 1.2, and 44.39 ± 1.07, respectively. The difference between TIBC, mean serum free iron concentration, and transferrin saturation between Group I and Group III (for all, p values <0.001), as well as between Group II and Group III (p values 0.0012, 0.0015, and <0.0001, respectively) was statistically significant. The fasting plasma glucose values of Groups II and III were significantly higher than those of Group I, (p < 0.0001). Glycated haemoglobin (HbA1c) values were also shown to increase from Group I to II and then III, and the increase was highly significant (all p values <0.0001). Thus, decreased glycaemic control and an increase in the glycation of haemoglobin was the key to elevation in serum iron values and alterations in other parameters. However, a significant correlation was absent between serum iron and HbA1c (r = 0.05) and transferrin saturation (r = 0.0496) in Group III.

Effect of Native American ancestry on iron-related phenotypes of Alabama hemochromatosis probands with HFEC282Y homozygosity

BackgroundIn age-matched cohorts of screening study participants recruited from primary care clinics, mean serum transferrin saturation values were significantly lower and mean serum ferritin concentrations were significantly higher in Native Americans than in whites. Twenty-eight percent of 80 Alabama white hemochromatosis probands with HFE C282Y homozygosity previously reported having Native American ancestry, but the possible effect of this ancestry on hemochromatosis phenotypes was unknown.MethodsWe compiled observations in these 80 probands and used univariate and multivariate methods to analyze associations of age, sex, Native American ancestry (as a dichotomous variable), report of ethanol consumption (as a dichotomous variable), percentage transferrin saturation and loge serum ferritin concentration at diagnosis, quantities of iron removed by phlebotomy to achieve iron depletion, and quantities of excess iron removed by phlebotomy.ResultsIn a univariate analysis in which probands were grouped by sex, there were no significant differences in reports of ethanol consumption, transferrin saturation, loge serum ferritin concentration, quantities of iron removed to achieve iron depletion, and quantities of excess iron removed by phlebotomy in probands who reported Native American ancestry than in those who did not. In multivariate analyses, transferrin saturation (as a dependent variable) was not significantly associated with any of the available variables, including reports of Native American ancestry and ethanol consumption. The independent variable quantities of excess iron removed by phlebotomy was significantly associated with loge serum ferritin used as a dependent variable (p < 0.0001), but not with reports of Native American ancestry or reports of ethanol consumption. Loge serum ferritin was the only independent variable significantly associated with quantities of excess iron removed by phlebotomy used as a dependent variable (p < 0.0001) (p < 0.0001; ANOVA of regression).ConclusionWe conclude that the iron-related phenotypes of hemochromatosis probands with HFE C282Y homozygosity are similar in those with and without Native American ancestry reports.

Genotypic and phenotypic heterogeneity of African Americans with primary iron overload

Primary iron overload may be relatively common in African Americans, but its cause is incompletely understood. Thus, we evaluated genotype and phenotype characteristics of unselected African American index patients with primary iron overload who reside in central Alabama. All had hepatic iron concentration ≥30 μmol/g dry wt or ≥2.0 g of iron mobilized by phlebotomy to achieve iron depletion. Genotype analyses were performed in African American control subjects from the same region. There were 23 patients (19 men, 4 women); mean age at diagnosis was 52 ± 12 years (1 SD) (range 32–69 years). Nine (39.1%) reported that they consumed ≥45 g of ethanol daily; five had chronic hepatitis C. Eight had some form of hemoglobinopathy or thalassemia. Mean serum transferrin saturation was 56 ± 28% (range 15–100%). The geometric mean serum ferritin at diagnosis was 1076 ng/mL [95% confidence interval 297–3473 ng/mL]. Increased stainable liver iron was observed in hepatocytes only in 4 patients, in macrophages only in 8 patients, and in hepatocytes and macrophages in 8 patients. The mean quantity of iron mobilized by phlebotomy (corrected for iron absorbed during treatment) was 5.3 ± 2.0 g (range 4.0–8.4 g). Iron removed by phlebotomy was greater in patients with hemoglobinopathy or thalassemia than in those without these forms of anemia (6.6 ± 1.3 g vs 3.9 ± 1.6 g, respectively; P = 0.0144). Daily consumption of ≥45 g of ethanol or chronic hepatitis C was not associated with an increased or decreased amount of phlebotomy-mobilized iron, on the average. The percentage of index patients positive for HFE C282Y was greater than that of controls ( P = 0.0058). The respective percentages of phenotype positivity for HFE H63D, D6S105(8), and HLA-A*03 were similar in patients and controls. HFE S65C, I105T, and G93R were not detected in index or control subjects. Two of 13 patients were heterozygous for the ferroportin allele nt 744 G→T (Q248H), although the phenotype frequency of this allele was similar in patients and 39 controls. Synonymous ferroportin alleles were also detected in some patients. The ceruloplasmin mutation nt 1099C→T (exon 6; Arg367Cys) was detected in 1 of 2 patients tested. Abnormal alleles of β-2 microglobulin, Nramp2, TFR2, hepcidin, or IRP2 alleles were not detected in either of the 2 patients so tested. We conclude that primary iron overload in African Americans is not the result of the mutation of a single gene. HFE C282Y, ferroportin 744 G→T, and common forms of heritable anemia appear to account for increased iron absorption or retention in some patients.

Relative contributions of body iron status and uremia severity to anemia in patients with advanced chronic renal failure.

Anemia in chronic renal failure is predominantly caused by diminished erythropoietin synthesis by diseased kidneys. While iron deficiency is often stated as a cause of anemia in chronic renal failure prior to end-stage renal disease, its relative contribution is debated. It is speculated that rather than frank 'iron deficiency', many patients with chronic renal failure may indeed have impaired utilization of iron. We analyzed 139 consecutive patients with chronic renal failure starting maintenance hemodialysis to determine the relationship between hematocrit, measures of renal function (blood urea nitrogen and serum creatinine concentration), and measures of iron availability (serum transferrin saturation, serum iron level and serum ferritin). The 139 study subjects (60 men, 79 women) comprised 116 blacks (83%), 15 hispanics (11%), and 8 whites (6%) of a mean age 56 +/- 15 years. Only 23 (17%) of 139 subjects had positive hemoccult stool test for blood. Their mean hematocrit was 24 +/- 4.5%, mean blood urea nitrogen concentration was 121 +/- 38, mean serum creatinine concentration was 12.6 +/- 5.2 mg/dl, mean serum transferrin saturation was 22 +/- 14%, mean serum ferritin level was 235 +/- 194 U/l, mean serum iron level was 55 +/- 40 U/l, and mean total iron binding capacity was 254 +/- 93%. Multiple regression analysis with hematocrit as the outcome variable, and blood urea nitrogen level, serum creatinine concentration, serum albumin concentration, serum transferrin saturation, and serum ferritin level as the independent variables, showed an inverse correlation between hematocrit and serum creatinine concentration (p = 0.002). We conclude that in patients with chronic renal failure starting uremia therapy, anemia does not correlate with any of the commonly measured indices of body iron stores. We infer that impaired utilization of iron may be a significant factor in the anemia of chronic renal failure.