Unanticipated favorable effects of correcting iron deficiency in chronic hemodialysis patients.

BACKGROUND: Correction of anemia in hemodialysis patients is seldom completely attained, and the response of parameters other than hemoglobin concentration to anemia correction has not been evaluated in detail. METHODS: Laboratory parameters that suggest iron deficiency occurred in 10-15% of 206 recombinant human erythropoietin (rhEPO)-treated patients. Oral iron was given for 9 months and intravenous iron thereafter on a patient-specific basis when iron deficiency was evident. Eighty-seven hemodialysis patients with data for 12 months were followed for another 12 months. A computerized information system enabled data management and analysis. RESULTS: With oral iron, serum ferritin decreased (P < 0.001), indicating further iron depletion. With intravenous iron, hemoglobin increased, evidence of iron deficiency decreased, and less rhEPO was needed. Striking macrocytosis appeared. Serum albumin and serum creatinine/kg body weight (an index of muscle mass) increased, while blood pressure decreased. Data were reanalyzed in four mean corpuscular volume (MCV) quartiles and two ferritin subsets at study onset. Iron deficient erythropoiesis (low MCV, mean corpuscular hemoglobin [MCH], and transferrin saturation) was striking in quartile 1; low ferritin was prevalent in all quartiles. With intravenous iron, hemoglobin increased only in quartile 1, the quartile with the greatest decrease (52%) in rhEPO dose. MCV increased in all quartiles (P < 0.001). Serum albumin increased in all MCV quartiles and both ferritin subsets, but significant creatinine/kg increase and blood pressure decrease occurred only in the low-ferritin subset. CONCLUSIONS: Macrocytosis occurred with intravenous iron replacement. The universal MCV increase suggests unrecognized, inadequately treated, folic acid deficiency unmasked by an adequate iron supply. There was also improved well being. Effects were most clearly evident in patients with deficient iron stores.     

Relationships of serum ferritin, transferrin saturation, and HFE mutations and self-reported diabetes in the Hemochromatosis and Iron Overload Screening (HEIRS) study

OBJECTIVE: We evaluated the associations of self-reported diabetes with serum ferritin concentration, transferrin saturation (TfSat), and HFE C282Y and H63D mutations in six racial/ethnic groups recruited at five field centers in the Hemochromatosis and Iron Overload Screening (HEIRS) study. RESEARCH DESIGN AND METHODS: Analyses were conducted on 97,470 participants. Participants who reported a previous diagnosis of diabetes and/or hemochromatosis or iron overload were compared with participants who did not report a previous diagnosis. RESULTS: The overall prevalence of diabetes was 13.8%; the highest prevalence was in Pacific Islanders (20.1%). Of all participants with diabetes, 2.0% reported that they also had hemochromatosis or iron overload. The mean serum ferritin concentration was significantly greater in women with diabetes in all racial/ethnic groups and in Native-American men with diabetes than in those without diabetes. The mean serum ferritin concentration was significantly lower in Asian men with diabetes than in those without diabetes. Mean TfSat was lower in participants with diabetes from all racial/ethnic groups except Native-American women than in those without diabetes. There was no significant association of diabetes with HFE genotype. The mean serum ferritin concentration was greater (P < 0.0001) in women with diabetes than in those without diabetes for HFE genotypes except C282Y/C282Y and C282Y/H63D. Log serum ferritin concentration was significantly associated with diabetes in a logistic regression analysis after adjusting for age, sex, racial/ethnic group, HFE genotype, and field center. CONCLUSIONS: Serum ferritin concentration is associated with diabetes, even at levels below those typically associated with hemochromatosis or iron overload.     

Iron status among 3005 women aged 20-55 years in Central Norway: the Nord-Trøndelag Health Study (the HUNT study)

OBJECTIVE: To describe the iron status of Norwegian women of fertile age, to show the prevalence of iron-deficiency anemia and iron overload, and to demonstrate possible factors connected to and/or influencing iron status. MATERIAL AND METHODS: The diagnostic criteria were: (a) anemia: hemoglobin (Hb) < 120, < 117, or < 115 g/l; (b) depleted iron stores: serum ferritin (SF) < 10 or 12 microg/l; iron-deficiency anemia: (a)+(b). Iron overload: SF > or = 110 microg/l. The study was conducted in Central Norway where a total of 3005 women aged 20 to 55 years were enrolled in a health survey program (the HUNT Study). None of the women were pregnant and none had been blood donors in the two previous years. RESULTS: Median SF was 31.0 microg/l. Depleted iron stores were present in 10.9 and 15.1%, respectively. The Hb 2.5%tile among the iron-replete women was 117 g/l. With this cut-off value, anemia was present in 4.7% and iron-deficiency anemia in about 3%. Iron overload was present among 5.2%, and homozygous primary hemochromatosis among 0.4%. CONCLUSIONS: The prevalence of iron-deficiency anemia was relatively low and similar to that found earlier in small groups of Norwegian women. The prevalence is comparable with results from other developed countries.     

Diabetes and serum ferritin concentration among U.S. adults

OBJECTIVE: We examined the association between serum ferritin concentration and the risk of diabetes. RESEARCH DESIGN AND METHODS: We examined the cross-sectional associations among ferritin concentration, glucose tolerance status, and concentrations of insulin, glucose, and glycosylated hemoglobin in 9,486 U.S. adults aged > or = 20 years from the Third National Health and Nutrition Examination Survey (1988-1994). RESULTS: After adjusting for age, sex, ethnicity, education, BMI, alcohol consumption, alanine aminotransferase concentration, C-reactive protein concentration, and examination session attended, and after dichotomizing ferritin concentration into < 300 and > or = 300 micrograms/l for men and < 150 and > or = 150 micrograms/l for women, the odds ratios for newly diagnosed diabetes were 4.94 (95% CI 3.05-8.01) for men and 3.61 (2.01-6.48) for women. The increased risk of newly diagnosed diabetes was concentrated among participants with transferrin saturations < 45%. All multiple linear regression coefficients between ferritin concentration and concentrations of insulin, glucose, and glycosylated hemoglobin were positive and significant for both men and women. CONCLUSIONS: Elevated serum ferritin concentration was associated with an increased risk of diabetes. We were unable to eliminate conclusively the possibility that the observed association reflected inflammation rather than excess body iron stores.     

Soluble transferrin receptor level: a new marker of iron deficiency anemia, a common manifestation of gastric autoimmunity in type 1 diabetes

OBJECTIVE: A total of 15-20% of type 1 diabetic patients have parietal cell antibodies (PCAs). PCA+ subjects are at increased risk for iron deficiency anemia and atrophic gastritis. Recently, soluble transferrin receptor (sTfR) levels have proven to be a sensitive indicator for iron deficiency They are, in contrast with ferritin levels, independent of inflammation, liver and hormonal status, and sex. We are the first to evaluate sTfR levels in type 1 diabetes and tested the hypothesis of higher sTfR levels in patients with PCAs and/or autoimmune gastritis. RESEARCH DESIGN AND METHODS: We examined 148 type 1 diabetic patients (85 men and 63 women; 50 were PCA+) and 59 sex- and age-matched control subjects (30 men and 29 women). The main outcome measures were sTfR levels, iron deficiency anemia, and atrophic gastritis. Logistical regression analysis tested risk factors for iron deficiency RESULTS: Iron deficiency was present in 38 subjects. Iron (P<0.0001) and ferritin (P<0.0001) levels but not sTfR levels were lower in women. sTfR levels were similar in diabetic and control subjects but were higher in PCA+ subjects (P = 0.015). In diabetic subjects, iron deficiency anemia was more prevalent in PCA+ than in PCA- patients (odds ratio 3.07, P = 0.013) and was associated with sex (P = 0.0001), age (P = 0.046), and sTfR (P = 0.0008) levels. Atrophic gastritis was present in 15 of 28 PCA+ and in 1 of 11 PCA diabetic subjects (P = 0.014). sTfR levels tended to be higher in patients with atrophic gastritis (P = 0.062). CONCLUSIONS: In type 1 diabetes, sTfR levels can be used to diagnose iron deficiency anemia, which is more prevalent in PCA+ subjects. sTfR levels are higher in PCA+ individuals who are at risk for developing atrophic gastritis.     

Iron deficiency anemia

The prevalence of iron deficiency anemia is 2 percent in adult men, 9 to 12 percent in non-Hispanic white women, and nearly 20 percent in black and Mexican-American women. Nine percent of patients older than 65 years with iron deficiency anemia have a gastrointestinal cancer when evaluated. The U.S. Preventive Services Task Force currently recommends screening for iron deficiency anemia in pregnant women but not in other groups. Routine iron supplementation is recommended for high-risk infants six to 12 months of age. Iron deficiency anemia is classically described as a microcytic anemia. The differential diagnosis includes thalassemia, sideroblastic anemias, some types of anemia of chronic disease, and lead poisoning. Serum ferritin is the preferred initial diagnostic test. Total iron-binding capacity, transferrin saturation, serum iron, and serum transferrin receptor levels may be helpful if the ferritin level is between 46 and 99 ng per mL (46 and 99 mcg per L); bone marrow biopsy may be necessary in these patients for a definitive diagnosis. In children, adolescents, and women of reproductive age, a trial of iron is a reasonable approach if the review of symptoms, history, and physical examination are negative; however, the hemoglobin should be checked at one month. If there is not a 1 to 2 g per dL (10 to 20 g per L) increase in the hemoglobin level in that time, possibilities include malabsorption of oral iron, continued bleeding, or unknown lesion. For other patients, an endoscopic evaluation is recommended beginning with colonoscopy if the patient is older than 50.     

The value of routine ferritin measurement in blood donors

BACKGROUND: Iron store deficiency is a common side effect of whole blood donation. Early recognition and reversal of excessive iron loss may avoid symptomatic iron store depletion in blood donors and reduce volunteer loss due to iron deficiency (ID) anemia. STUDY DESIGN AND METHODS: Between 1996 and 2009, a total of 160,612 visits with the intention to donate blood by 23,557 healthy volunteers were recorded at our center. As of 2004, routine serum ferritin testing and additional counseling of donors at risk for donation‐induced anemia were implemented. We analyzed the impact of this measure on the hemoglobin (Hb) levels and anemia occurrence in our donor population and in particular in women of childbearing age. Donation rejections due to low Hb counts, the intervals to next donation, and return rates thereafter were also assessed. RESULTS: The introduction of routine serum ferritin analysis resulted in an increase of mean Hb levels in blood donors particularly in women of childbearing age. The incidence of predonation anemia and donation ineligibility due to a low Hb concentration decreased significantly. The return intervals of donors rejected on account of low Hb levels were shortened; however, the return rates thereafter were also curtailed. CONCLUSIONS: Systematic serum ferritin measurements allowed an optimized management of ID in our donors and efficacious prevention of ID anemia.     

Predictors of endoscopic and laboratory evaluation of iron deficiency anemia in hospitalized patients

BACKGROUND: Many hospitalized anemic patients do not undergo appropriate evaluation. We hypothesized that specific clinical variables were likely to be important in triggering evaluation for iron deficiency anemia. METHODS: We prospectively identified 637 consecutive anemic patients without acute gastrointestinal bleeding admitted over a three-month period to medical inpatient teams of two teaching hospitals and examined clinical variables that predicted diagnostic evaluation. RESULTS: Serum ferritin or serum transferrin saturation (TS) were measured in 43% (271/637) of subjects and were low in 38% (102/271). Predictors of serum ferritin or TS measurement included low hemoglobin concentration and a history of iron supplementation. Predictors of iron deficiency included low hemoglobin concentration (OR 1.9, 95% CI 1.06-3.5) and low mean cell volume (OR 4.6, 95% CI 2.5-8.6). Of 102 patients with iron deficiency anemia, 31% underwent endoscopic evaluation, and 39% had serious gastrointestinal lesions. The only significant predictor of having an endoscopic evaluation was a positive fecal occult blood test (FOBT) (OR 5.2, 95% CI 1.7-16.2). CONCLUSIONS: In patients with anemia, tests to ascertain iron status are not appropriately performed in hospitalized patients. Patients found to have iron deficiency anemia who are FOBT-positive undergo endoscopic evaluation more frequently than FOBT-negative patients.     

育龄期女性缺铁性贫血患者血清铁调素和erythroferrone水平的变化

目的:检测育龄期女性缺铁性贫血(Iron deficiency anemia,IDA)患者血清铁调素和erythroferrone(ERFE)含量,并探讨其与铁代谢各参数的相关性.方法:选取住院育龄期女性缺铁性贫血患者35例,年龄相匹配的健康女性对照人群30例.采用全自动电化学发光仪检测血清铁蛋白水平,全自动生化仪测定...     

Serum iron, transferrin saturation, ferritin, and dietary data in age-related macular degeneration.

Iron (Fe) is a tightly metabolically controlled mineral and growth factor for all living cells. Iron not bound in erythrocyte hemoglobin is transported by the plasma iron transport protein transferrin (Tf) and bound within cells by ferritin. Apo-Tf and apo-hemopexin are also known to be made locally in the retina. Free Fe is cytotoxic, promotes oxidation/lipid peroxidation, has been implicated as a risk factor in cardiac disease, and is itself associated with age-related macular degeneration (ARMD), the leading cause of blindness in aging western societies. The authors evaluated Fe overload serum markers and dietary intake in patients with atrophic ARMD. After obtaining informed consent, an Fe panel consisting of serum Fe, total Fe binding capacity (TIBC), and ferritin was performed on 75 veterans (70 men, five women) with an average age of 75 years with a diagnosis of atrophic ARMD by combined criteria of International Retinal Classification and psychophysical/symptom abnormalities. Tf saturation was calculated by dividing serum Fe concentration by TIBC. Dietary iron with and without supplementation and vitamin C intake were determined for 86 patients using the Harvard School of Public Health/Department of Nutrition Food Frequency Questionnaire. Statistically significant correlations (P <0.1) were found between serum and dietary Fe (r = -.26), between serum Fe and serum ferritin (r =.34), and between dietary Fe and dietary vitamin C (r =.30). The data on mostly male geriatric veterans with atrophic ARMD indicate that single time-point assessment of systemic Fe status and dietary Fe is not useful. However, serial multiple-year data, correlating Fe markers with disease, may still be important. Also, because Fe transport proteins do not cross the blood-retina barrier, the local cellular toxic effects of Fe must also be considered.     

Type 2 diabetes in older well-functioning people: who is undiagnosed? Data from the Health, Aging, and Body Composition study.

OBJECTIVE: To assess, in an older population, the prevalence of diagnosed and undiagnosed diabetes, the number needed to screen (NNTS) to identify one individual with undiagnosed diabetes, and factors associated with undiagnosed diabetes. RESEARCH DESIGN AND METHODS: Socioeconomic and health-related factors were assessed at the baseline examination of the Health, Aging, and Body Composition (Health ABC) Study, a cohort of 3,075 well-functioning people aged 70-79 years living in Memphis, Tennessee and Pittsburgh, Pennsylvania (42% blacks and 48% men). Diabetes was defined according to the 1985 World Health Organization criteria (fasting glucose > or =7.8 mmol/l or 2-h glucose > or =11.1 mmol/l) and the 1997 American Diabetes Association criteria (fasting glucose > or =7.0 mmol/l). RESULTS: The prevalence of diagnosed and undiagnosed diabetes was 15.6 and 8.0%, respectively, among all participants (NNTS 10.6), 13.9 and 9.1% among white men (NNTS 9.5), 7.8 and 7.4% among white women (NNTS 12.4), 22.7 and 9.1% among black men (NNTS 8.5), and 21.6 and 6.2% among black women (NNTS 12.6). In multivariate analyses, compared with individuals without diabetes, individuals with undiagnosed diabetes were more likely to be men and were more likely to have a history of hypertension, higher BMI, and larger waist circumference. NNTS was lowest in men (9.1), individuals with hypertension (8.7), individuals in the highest BMI quartile (6.9), and individuals in the largest waist circumference quartile (6.8). CONCLUSIONS: In approximately one-third of all older people with diabetes, the condition remains undiagnosed. Screening for diabetes may be more efficient among men and individuals with hypertension, high BMI, and large waist circumference.     

The influence of iron,vitamin B(12), and folate levels on soluble transferrin receptor concentration in pregnant women

BACKGROUND: Soluble transferrin receptor (sTfR) concentration is high in iron deficiency and in conditions of increased erythropoiesis. In developing countries like Brazil, pregnant women usually have concurrent iron, vitamin B(12), and folate deficiencies. This study investigated the relationship between serum sTfR concentration and iron, vitamin B(12), and folate status in pregnant women. METHODS: The concentration of the sTfR, hematocrit (Hct), hemoglobin (Hb), red blood cell (RBC) and white blood cell (WBC) counts, serum iron (SI), total iron-binding capacity (TIBC), transferrin saturation, serum ferritin, zinc protoporphyrin (ZPP), vitamin B(12), and serum and RBC folate were determined in 40 healthy pregnant women who delivered term babies. RESULTS: sTfR concentration was significantly higher when the women had iron deficiency (serum ferritin <10 microg/l, p<0.01), but there was no significant difference in sTfR concentration according to vitamin B(12), serum, and RBC folate concentrations. Women who had serum ferritin <10 microg/l also had lower vitamin B(12) values (p<0.01). There was no significant correlation between vitamin B(12) and serum folate with sTfR concentration. According to a regression analysis, sTfR concentration was associated with serum iron, serum ferritin, RBC count, and hemoglobin concentration. CONCLUSION: Iron was the only micronutrient that influenced the sTfR concentration. Vitamin B(12) and folate concentrations were probably not sufficiently low to have an impact on the sTfR concentration.     

Sensitivity and predictive value of serum ferritin and free erythrocyte protoporphyrin for iron deficiency

The sensitivity and predictive value of serum ferritin (SF) and free erythrocyte protoporphyrin (FEP) for iron deficiency (ID) was evaluated by studying 272 subjects with uncomplicated ID (174 with anemia and 98 without) in whom diagnosis was confirmed by the response to iron supplementation. Overall, the sensitivity, at 95% specificity, was 82% (79% in women, 94% in men) for SF and 61% (60% in women, 65% in men) for FEP. The sensitivity varied as a function of hemoglobin values, dropping from over 90% for both tests in the case of severe anemia, to approximately 70% for SF and less than 50% for FEP in the absence of anemia. The predictive value decreases more sharply for FEP than for SF with increasing hemoglobin levels. It is concluded that SF is preferable to FEP for the detection of ID, particularly in the absence of anemia. However, owing to the unsatisfactory predictive value at low prevalence, SF should be used as a screening test for ID without anemia only when the prevalence is at least 20%.     

HBsAg carrier status and the association between gestational diabetes with increased serum ferritin concentration in Chinese women

OBJECTIVE: To determine whether the high prevalence of hepatitis B surface antigen (HBsAg) carriage in our population can explain the previous observation of an association between increased maternal serum ferritin concentration and gestational diabetes in Hong Kong Chinese women. RESEARCH DESIGN AND METHODS: A retrospective study was performed on 767 nonanemic women with singleton pregnancy who had iron status assessed at 28-30 weeks. The result of the routine antenatal HBsAg screening was retrieved from patient records. The HBsAg-positive and -negative groups were compared for maternal characteristics, prevalence of gestational diabetes in the third trimester, prevalence of high serum ferritin and iron concentrations, and transferrin saturation, which is defined as a value in the highest quartile established by the measurements obtained from the HBsAg-negative group. RESULTS: The incidences of oral glucose tolerance test and gestational diabetes were significantly increased in the HBsAg-positive group. The HBsAg-positive women with gestational diabetes had significantly increased prevalence of high serum ferritin compared with the HBsAg-negative women, irrespective of the latter's gestational diabetes status. Multiple logistic regression analysis confirmed the independent association between HBsAg carrier status with gestational diabetes (relative risk 3.51, 95% CI 1.83-6.73) but excluded high ferritin as an independent factor. CONCLUSIONS: Our results indicate that maternal HBsAg carriage could explain in part the association between increased serum ferritin concentration with gestational diabetes in Hong Kong Chinese women, and that HBsAg carrier status is an independent risk factor for gestational diabetes.     

Screening with zinc protoporphyrin for iron deficiency in non-anemic female blood donors

Iron-depleted donors are at increased risk of developing anemia; if these donors could be identified by a screening test, iron supplementation or decreased donation frequency could be considered. Tests to determine serum ferritin, blood hemoglobin, and erythrocyte (Erc)-zinc protoporphyrin concentrations were examined in 679 consecutive female blood donors to identify donors with non-anemic iron deficiency. The test to determine serum ferritin is expensive and slow, whereas the two latter tests are rapid and less costly and could therefore be used for screening. Women in the fertile age groups had the lowest average serum ferritin values. In all, 93 women (13.7%) had depleted iron stores, as indicated by serum ferritin concentrations less than 14 micrograms/L. In these women, a much better correlation was found between Erc-zinc protoporphyrin and serum ferritin (rs = -0.49, P less than 0.001) than between blood hemoglobin and serum ferritin (rs = 0.31, P less than 0.01). These findings suggest that measurement of Erc-zinc protoporphyrin is superior to that of blood hemoglobin in identifying donors with non-anemic iron deficiency.     

Serum ferritin and risk of the metabolic syndrome in U.S. adults

OBJECTIVE: We examined the relationship among iron stores, the metabolic syndrome, and insulin resistance. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study of 6,044 adults >20 years of age who participated in the Third National Health and Nutrition Examination Survey. Metabolic syndrome was defined as the presence of at least three of the following: elevated blood pressure, low HDL cholesterol, elevated serum triglycerides, elevated plasma glucose, and abdominal obesity. Insulin resistance was estimated using homeostasis model assessment (for insulin resistance), fasting insulin, and triglyceride-to-HDL cholesterol ratio. RESULTS: After excluding individuals with likely hemochromatosis, mean serum ferritin values in premenopausal women, postmenopausal women, and men were 33.6, 93.4, and 139.9 microg/l, respectively. Metabolic syndrome was more common in those with the highest compared with the lowest levels of serum ferritin in premenopausal women (14.9 vs. 6.4%, P = 0.002), postmenopausal women (47.5 vs. 28.2%, P < 0.001), and men (27.3 vs. 13.8%, P < 0.001). Insulin resistance also increased across quartiles of serum ferritin for men and postmenopausal women and persisted after adjustment for age, race/ethnicity, C-reactive protein, smoking, alcohol intake, and BMI. CONCLUSIONS: Elevated iron stores were positively associated with the prevalence of the metabolic syndrome and with insulin resistance.     

Hemoglobin and iron indices in nonanemic premenopausal blood donors predict future deferral from whole blood donation

BACKGROUND: Iron deficiency anemia is an important reason for blood donor deferral. We prospectively determined whether screening donors with hemoglobin (Hb) and iron indices before donation can predict subsequent deferral due to anemia. STUDY DESIGN AND METHODS: We recruited premenopausal, eligible (nonanemic) female donors. Hb, ferritin, soluble transferrin receptor (sTfR), and hepcidin were measured, and the sTfR/(log)ferritin (sTfR‐F) index was calculated. After 6 months, the donor database was reviewed and whether donors had returned and undergone successful donation was recorded. RESULTS: Of donors, 59 of 261(22.6%) were iron depleted (ferritin < 15 ng/mL). Iron‐depleted donors had donated more often in the previous year, were younger, and had lower Hb. After a minimum of 6 months, 145 eligible donors had returned; of these 10 (6.9%) were deferred for anemia. Donors who developed anemia had significantly lower Hb, ferritin, and hepcidin and higher sTfR and sTfR‐F at baseline. The area under the receiver operating characteristic curve for Hb as a predictor of deferral was 0.86, and for ferritin was 0.88. Hb of less than 130 g/L and ferritin of less than 10 ng/mL combined had sensitivity 80% and specificity 96% in predicting deferral. CONCLUSION: Screening with Hb and iron indices enables prediction of donors at risk of subsequent anemia and who would most benefit from prevention strategies.     

Iron Balance in Regular Blood Donors

SUMMARY: BACKGROUND: Numerous reports have shown that iron stores decrease in blood donors after donation. As we need healthy donors, it is essential to test hemoglobin and ferritin levels for preventing reduced of iron stores in donors. METHODS: This study was conducted on 235 healthy men. The donors were divided into three groups: group I) control group with no donation; group II) case group 1 with two donations within 1 year; group III) case group 2 with three donations within 1 year. RESULTS: The mean level of hemoglobin was 15.9 and 14.7 g/dl in the control group and in the case group, respectively (p < 0.0000). The mean level of serum ferritin in group I, II and III, was 108, 56 and 26 μg/l, respectively (p < 0.0000). When studying various stages of iron deficiency in donors, it could be shown that 58% of group III donors but only 1% of control group donors had a negative iron balance. Moreover, iron deficiency anemia was observed in 20% of group III donors. CONCLUSION: Just measuring the hemoglobin level is not sufficient for selecting donors. In addition, testing of the ferritin level and iron supplementation are recommended in regular donors with more than one donation per year.     

Serum ferritin compared with other indices of iron status in children and teenagers undergoing maintenance hemodialysis.

To determine how best to assess iron status, I studied 12 young renal patients (ages 5.5 to 20 years) undergoing regular hemodialysis treatments. Iron balance was estimated by monitoring iron loss ascribable to blood loss during dialysis and diagnostic testing, and iron intake in the form of oral and intravenous iron supplements and blood transfusions. Traditional methods of evaluating iron status--measurement of hemoglobin, erythrocyte indices, reticulocyte count, iron, and transferrin--were compared with measurement of serum ferritin. The serum ferritin measurements provided superior information. In three cases this method was superior to visual assessment of bone marrow stained for iron.     

Sex Differences in the Association Between Serum Ferritin and Fasting Glucose in Type 2 Diabetes Among South Asian Surinamese,African Surinamese,and Ethnic Dutch: The population-based SUNSET study

OBJECTIVE

Moderately elevated iron stores below the levels commonly associated with hemochromatosis have been implicated in the etiology of diabetes. Studies suggest that iron status (measured by serum ferritin) differs significantly according to sex, but inconsistent findings have been reported. Our aim is to test the association between serum ferritin and the prevalence of type 2 diabetes and fasting glucose concentrations in a population-based, multiethnic, cross-sectional study including men and women of African Surinamese, South Asian Surinamese, and ethnic Dutch origin.

RESEARCH DESIGN AND METHODS

We analyzed data on 508 ethnic Dutch, 597 African Surinamese, and 339 South Asian Surinamese aged 35–60 years. Type 2 diabetes was defined as a fasting plasma glucose level ≥7.0 mmol/L or a self-reported diagnosis.

RESULTS

Serum ferritin was positively associated with type 2 diabetes and fasting glucose, but differences in the associations according to sex were observed. Serum ferritin concentration was positively associated with type 2 diabetes among women in all ethnic groups (odds ratio [OR] ethnic Dutch: 1.07 [95% CI 1.01–1.13]; OR South Asian Surinamese: 1.05 [1.00–1.10]; OR African Surinamese: 1.05 [1.01–1.10]), but not among men. Serum ferritin was also more strongly associated with fasting glucose in women than in men. Moreover, the magnitude of sex differences in the association between serum ferritin and fasting glucose, but not type 2 diabetes, was more pronounced in the African Surinamese group than in the other ethnic groups (P for interaction ≤0.0001).

CONCLUSIONS

We found a positive association between serum ferritin and type 2 diabetes and fasting glucose in our multiethnic population, which appeared stronger among women than men. Further evaluation of the variation in sex differences between ethnic groups is warranted, particularly among the African Surinamese, to understand the mechanisms behind these sex differences.Moderately elevated iron stores below the levels commonly associated with hemochromatosis have been implicated in the etiology of type 2 diabetes (1–3). Although a mechanism linking iron concentrations and diabetes is yet to be established, it is known that iron is a catalyst in the formation of hydroxyl radicals (4), which may contribute initially to insulin resistance, subsequently to decreased insulin secretion, and ultimately to the development of type 2 diabetes (5). Animal models suggest that iron excess may result in β-cell oxidative stress and decreased insulin secretion (6). Levels of serum ferritin, a predominant iron-storage protein and a biomarker of iron stores, are elevated in persons with prevalent diabetes as compared with nondiabetic controls (7) and correlate with impaired fasting glucose levels (8), an early marker of type 2 diabetes. In addition, several cross-sectional or case-control studies and two prospective studies have identified an independent association between baseline elevations in iron stores and the occurrence of type 2 diabetes (2,5,9–12). However, several questions remain unanswered.It is yet unclear whether the association between serum ferritin and diabetes differs among men and women. Some have found that differences in iron status exist according to sex (8,13–16), which might have implications for the association with the etiology of diabetes (13). Others have suggested that sex differences might exist due to differences in iron accumulation in the peripheral muscles, which may cause derangement of muscle glucose uptake because of muscle damage (17,18). However, robust studies on the influence of sex on the association between serum ferritin and diabetes are rather inconsistent. Some have reported sex differences in the association (9,18), whereas others have not demonstrated this (19–21). Moreover, in those studies in which different associations between serum ferritin and type 2 diabetes were found for men and women, it appeared that the direction of the differences varied across studies (7–9).These discrepancies might be the result of differences in the ethnic composition of study populations. A first argument to support this is a study reporting variations in the serum ferritin and type 2 diabetes associations across men and women from different ethnic populations, including white, black, Hispanic, Asian, and Pacific Islander populations (9). This study reported that the association between serum ferritin and type 2 diabetes differed significantly between the ethnic groups among women but not among men. Unfortunately, other multiethnic studies have not considered differential sex effects across ethnic groups (10,19,20). Another argument for the potential role of ethnicity is a difference in body composition that may occur between ethnic groups. For instance, in the Netherlands, differences in waist circumference or waist-to-height ratio have been reported among ethnic Dutch, South Asian Surinamese, and African Surinamese (22,23). This is relevant, as body composition is suggested to affect the association between serum ferritin and the insulin resistance syndrome (17,18).The aim of this exploratory study is: 1) to test whether the association between serum ferritin and diabetes and fasting glucose differs between men and women of African Surinamese, South Asian Surinamese, and ethnic Dutch origin, and 2) to test whether the differences in the association between serum ferritin between men and women varies between these populations.