Letters to the Editor

IRON DEFICIENCY AND GLYCOSYLATED HÆMOGLOBIN A₁

Iron deficiency tendency in individuals with hyperglycemia influences the HbA1c levels' ability to estimate the stationary blood glucose levels. This study investigated the associations of iron status indicators and HbA1c levels with anthropometric, inflammatory, regulatory, metabolic, and hematologic variables in women with hyperglycemia to most widely characterize this iron deficiency tendency.

A total of 143 volunteers (68 with normoglycemia and 75 with hyperglycemia) participated in this cross-sectional study. Mann–Whitney test was used to compare groups, and the search for associations between pairs of variables used the Spearman correlation method.

In women with hyperglycemia, decreased plasma iron level is associated directly with increased HbA1c (p < 0.001), and these changes are both related to C-reactive protein elevation (p = 0.02 and p < 0.05, respectively) and involve decreased mean hemoglobin concentration (p < 0.01 and p < 0.01), which in turn, involves enhanced osmotic stability (dX) (p < 0.05) and volume variability (RDW) (p < 0.0001) of erythrocytes, as well as decreased indirect bilirubin/total bilirubin ratio (p = 0.04). This indirect bilirubin/total bilirubin decrease, which expresses decreased hemoglobin catabolism, does not seem to be solely a process associated with diminished intracellular concentrations of this protein (p = 0.04) since it is associated with CRP elevation (p = 0.03) and reduced LDL cholesterol (p < 0.0001).

In women with hyperglycemia, decreased plasma iron levels were associated with inflammatory status and involved increased HbA1c, osmotic stability, and volume variability of red blood cells.

The patient, a man in his thirties, presented to our hospital for a secondary examination after a 2020 medical check-up found a high hemoglobin A1c (HbA1c) level on high-performance liquid chromatography (HPLC). The HbA1c level determined by HPLC (HA-8180V, fast mode) was elevated at 6.8%, but a 75-g glucose tolerance test showed normal glucose tolerance. The glycated albumin level was within the reference range at 14.6%. The continuous glucose monitoring-derived mean blood glucose and the percentage of time in range were 99 mg/dL and 98%, respectively. The HbA1c levels determined by HPLC (G9, fast mode), enzymatic assay, and immunoassay were all 5.3%. An isoelectric focusing analysis showed an abnormal band on the anode side of HbA2, and a globin gene analysis detected a heterozygous mutation at codon 144 [AAG (Lys) → TAG (stop codon)] in the δ-chain. Since this mutation is a novel δ-chain hemoglobin variant, it was given the name ‘Hb A2-Karatsu’.

Anemia is a common disorder among pregnant women; however, the effect of anemia on hemoglobin A1c (HbA1c) levels has not been adequately explored. We aim to examine the influence of anemia on the HbA1c concentration and investigate the relationship between erythrocyte indices and HbA1c levels during pregnancy.

We performed a retrospective analysis of 1369 pregnant Chinese women. The clinical and analytical data were collected. Independent t-test and Analysis of Variance were used for comparative studies, and multiple linear regression analysis was used to identify the association between erythrocyte indices and HbA1c.

The differences in HbA1c between non-anemia and mild anemia were negligible, and the differences in HbA1c between non-anemia and moderate anemia were well within the allowable variability for clinical practice (≥0.5% absolute changes). Mean corpuscular hemoglobin (MCH) correlated with HbA1c significantly, independent of pregnancy, trimester, and anemia. The distinction of HbA1c levels between grades of Hb became no significant (P = 0.955), while differences between trimesters persisted after adjusting for MCH.

Mild and moderate anemia should not be the primary concern when using HbA1c to monitor blood glucose in pregnancy. MCH showed negative correlations with HbA1c independently, suggesting a previously unknown mechanism affecting HbA1c levels.

Both diabetes mellitus (DM) and iron deficiency anemia (IDA) are prevalent in every area of the world, and so, the possibility of these two diseases co-existing is also very high. It is our belief that clinical results of any correlation between iron status of the body and glycosylated haemoglobin (HbA1c) would be beneficial to many patients, therefore in this study, the effect of IDA on HbA1c was investigated.

A total of 146 patients with DM and IDA were evaluated prospectively. While the patients were administered 270 mg/day of ferrous sulphate (80 mg elemental iron) orally for three months for the treatment of IDA, no interventions were made for the treatment of DM. Patient levels of hemoglobin (Hb), hematocrit, red blood cells (RBC), mean corpuscular volume (MCV), platelet, white blood cells (WBC), serum iron, serum iron binding capacity (SIBC), ferritin, fasting plasma glucose (FPG), HbA1c, body mass index (BMI), C-reactive protein (CRP) values were measured at baseline and at the third month of treatment with iron, and were compared.

The median age of our patients was 45 (40–50) and median duration of diabetes was 3 years (1,75–5). While the baseline median Hb was 10.4 (mg/dL) (9.5–11.1), MCV was 74 (fL) (70.8–77), ferritin was 4 (ug/L) (3–6) at three months, Hb was measured at 12.6 (mg/dL) (12.1–13.2), MCV was measured at 82 (fL) (80–86), ferritin was measured at 15 (ug/L) (9–21.2) and was significantly higher compared to baseline values (p < 0.001). The baseline median HBA1c of patients was 7.09 ± 0.51 (%) and three month HBA1c was 6.69 ± 0.53 (%), which was significantly lower than when comparing baseline values with values at third month (p < 0.001). Baseline and three month values for FPG were 118 (mg/dL) (108–132) and 116 (mg/dL) (106–125) respectively, and there was no significant difference (p:0.07). A 2.2 mg/dL (1.5–3.5) increase in median Hb level accompanied a 0.4 % (0.2–0.6) decrease in median HbA1c levels (Spearman rho = −0.362; p < 0.001).

Our study has shown conclusivly that IDA is related to increased HbA1c concentrations and HbA1c decreases significantly following treatment with iron. IDA should be considered before making any decisions regarding diagnosis or treatment according to HbA1c.

South Africa is disproportionately impacted by non-communicable diseases (NCDs) and HIV/AIDS. We investigated the prevalence of known/unknown NCD risk factors, HIV, and NCD risk factor-HIV comorbidity; and treatment status on known diseases to determine the prevalence of controlled/uncontrolled disease.

This cross-sectional study (June 2018-March 2019) within an integrated testing centre in Soweto, South Africa, screened adults (aged ≥18 years) for body mass index (BMI), hypertension (HT), rapid glucose and cholesterol, and HIV. Results were stratified by age group, sex, HIV-status, and self-reported ART use. Analysis included Fisher's exact, chi-squared, Kruskal Wallis, and Student's T-tests.

Of 780 enrolled participants, 19.2% were HIV-positive, 37.5% were overweight/obese, 18.0% hypertensive, 10.8% hyperglycaemic, and 8.1% had hypercholesterolaemia. Significantly more women had overweight/obese BMI than men (46.8% vs 19.7%; p<0.0001), and women aged 25–34 years had significantly more hypercholesterolaemia than same-aged men (18.2% vs 5.6%; p = 0.02). HIV-positive participants had significantly more hyperglycaemia than HIV-negative participants (16.1% vs 9.6%; p = 0.02), and those on ART (63.9%) had significantly more hypercholesterolaemia than those not on ART (21.7% vs. 4.9%; p = 0.002). Of participants with HT, hyperglycaemia, and hypercholesterolaemia; 72.4%, 96.1%, and 93.3% were newly diagnosed. All participants with previously diagnosed NCDs remained with uncontrolled disease.

There is a high burden of HIV, NCD risk factors, and comorbidity in Soweto, and amongst young adults (18–34 years), especially women. Lowering age requirements for glucose/cholesterol screening to 18+ years, regardless of BMI, HIV-status, or ART use, may yield timely NCD diagnosis/management.

This project has been supported by the President's Emergency Plan for AIDS Relief (PEPFAR) through the Centres for Disease Control and Prevention (CDC) under the terms of CoAg 1U2GGH001150. JD, TD and GEG are funded by the South African Research Council; and TD and GEG also by the National Research Foundation.

Hemoglobin A1c (HbA1c) is gold-standard for the assessment of glycemic control in diabetic patients. Previous studies have reported that iron deficiency may elevate A1c concentrations, independent of glycemia. This study aimed to analyze the effect of iron status on HbA1c levels in diabetic patients.

661 patients 336 females (228 menopausal and 108 premenopausal) and 325 males (237 age> 50 years and 88 age < 50 years) were recruited.

HbA1c, ferritin, fasting plasma glucose, hemogram and medical history were recorded.

Analysis of variance ANOVA and Pearson’s regression were applied.

patients were divided according gender, age, glycemia and iron status (normal, latent iron deficiency LID, iron deficiency anemia IDA).All groups presented increasing HbA1c values in parallel with iron deficiency, subclinical and anemia, but the level of significance was not homogeneous in the different groups.

Controlled premenopausal women HbA1c in normal iron status and IDA groups P = 0.0048, between normal and LID, P = 0.033.

Not controlled premenopausal women Normal group and IDAP < 0.001, normal iron status and LID P = 0.019.

Controlled menopausal women normal group and IDAP < 0.0001, LID and IDA P = 0.01.

Not controlled menopausal women normal group and IDA P = 0.04.

Controlled men over 50 years normal and IDA groups P = 0.002, LID and IDA P = 0.02.

Controlled young men normal group and LID P = 0.03.

This study found a positive correlation between iron deficiency and increased HA1c levels. In diabetic patients with IDA should be interpreted with caution, due to the possibility of spurious increment in HbA1c.