Diabetes & Metabolism Journal

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Glycosylated Hemoglobin in Subjects Affected by Iron-Deficiency Anemia: Jari Intra, Giuseppe Limonta, Fabrizio Cappellini, Maria Bertona, Paolo Brambilla; Diabetes Metab J. 2019;43(4):539-544. Published online November 28, 2018; DOI: https://doi.org/10.4093/dmj.2018.0072

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Previous studies have suggested that iron-deficiency anemia affects glycosylated hemoglobin (HbA1c) measurements, but the results were contradictory. We conducted a retrospective case-control study to determine the effects of iron deficiency on HbA1c levels. Starting with the large computerized database of the Italian Hospital of Desio, including data from 2000 to 2016, all non-pregnant individuals older than 12 years of age with at least one measurement of HbA1c, cell blood count, ferritin, and fasting blood glucose on the same date of blood collection were enrolled. A total of 2,831 patients met the study criteria. Eighty-six individuals were diagnosed with iron-deficiency anemia, while 2,745 had a normal iron state. The adjusted means of HbA1c were significantly higher in anemic subjects (5.59% [37.37 mmol/mol]), than those measured in individuals without anemia (5.34% [34.81 mmol/mol]) (P<0.0001). These results suggest that clinicians should be cautious about diagnosing prediabetes and diabetes in individuals with anemia.

Citations

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Fingerprinting hyperglycemia using predictive modelling approach based on low-cost routine CBC and CRP diagnostics
Amna Tahir, Kashif Asghar, Waqas Shafiq, Hijab Batool, Dilawar Khan, Omar Chughtai, Safee Ullah Chaudhary
Scientific Reports.2024;[Epub] CrossRef
Implications of Iron Deficiency Anaemia on Glycemic Dynamics in Diabetes Mellitus: A Critical Risk Factor in Cardiovascular Disease
Eman Elsheikh, Sereen S Aljohani , Munirah M Alshaikhmubarak, Meshari A Alhawl, Alhanouf W Alsubaie, Norah Alsultan, Asmaa F Sharif, Sayed Ibrahim Ali
Cureus.2023;[Epub] CrossRef
Usefulness of glucose management indicator derived from continuous glucose monitoring to assess glycemic condition in hospitalized patients with diabetic kidney disease treated with insulin pumps
Yi Lu, Qian Zhang, Xiangyu Wang, Ya Jiang, Yaoming Xue
Journal of Diabetes and its Complications.2023; 37(11): 108613. CrossRef
Serum Iron Profile in Type 2 Diabetes, A Role Beyond Anemic Marker!
Happy Chutia, Sungdirenla Jamir, Md Yasir, Gautam Handique
The Journal of Medical Research.2023; 9(5): 129. CrossRef
Association between Anemia and Myopia in Korean Adults
Minyi Seo, Sangshin Park
Journal of Health Informatics and Statistics.2023; 48(4): 314. CrossRef
Large-scale retrospective analyses of the effect of iron deficiency anemia on hemoglobin A1c concentrations
Lokinendi V. Rao, George W. Pratt, Caixia Bi, Martin H. Kroll
Clinica Chimica Acta.2022; 529: 21. CrossRef
Integrity loss of glycosylated hemoglobin with deepening anemia
Bünyamin AYDIN, Aysun GÖNDEREN
Journal of Health Sciences and Medicine.2022; 5(3): 839. CrossRef
Association between hemoglobin within the normal range and hemoglobin A1c among Chinese non-diabetes adults
Yi Lai, Zhihong Lin, Zhongxin Zhu
BMC Endocrine Disorders.2021;[Epub] CrossRef
The Association between Daily Total Dietary Nutrient Intake and Recent Glycemic Control States of Non-Pregnant Adults 20+ Years Old from NHANES 1999–2018 (Except for 2003–2004)
Yin Bai, Hao Zhang, Jie Yang, Lei Peng
Nutrients.2021; 13(11): 4168. CrossRef

Original Articles

The Relationship between Anemia and the Initiation of Dialysis in Patients with Type 2 Diabetic Nephropathy: Sun Hee Kim, Kyung Ae Lee, Heung Yong Jin, Hong Sun Baek, Tae Sun Park; Diabetes Metab J. 2015;39(3):240-246. Published online April 22, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.3.240

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Abstract PDF PubReader

Background

Anemia is associated with various poor clinical outcomes in chronic kidney disease patients. The aim of this study was to investigate the relationship between anemia and the initiation degree and time of dialysis in type 2 diabetic nephropathy patients.

Methods

This observational retrospective study included 130 type 2 diabetic nephropathy patients in Korea. The existence of anemia, the degree and time of dialysis initiation were reviewed. Clinical characteristics and variables were also compared.

Results

The levels of hemoglobin and serum creatinine were significantly correlated with the dialysis initiation (P<0.05) during the 10-year follow-up period. Patients with anemia showed rapid decline of renal function, causing significantly more dialysis initiation (54.1% vs. 5.4%, P<0.05) compare to the patients without anemia. Average time to initiate dialysis in patients with anemia was 45.1 months (range, 8.0 to 115.8 months), which was significantly faster than that (68.3 months [range, 23.3 to 108.8 months]) in patients without anemia (P<0.01). The risk to dialysis initiation was significantly increased in patients with anemia compared to the patients without anemia (adjusted hazard ratio, 8.1; 95% confidence interval, 2.4 to 27.0; P<0.05).

Conclusion

Anemia is associated with rapid decline of renal dysfunction and faster initiation of dialysis in diabetic nephropathy patients. Therefore, clinicians should pay an earlier attention to anemia during the management of diabetes.

Citations

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Microalbuminuria as the Tip of Iceberg in Type 2 Diabetes Mellitus: Prevalence, Risk Factors, and Associated Diabetic Complications
Sohaib Asghar, Shoaib Asghar, Tayyab Mahmood, Syed Muhammad Hassan Bukhari, Muhammad Habib Mumtaz, Ali Rasheed
Cureus.2023;[Epub] CrossRef
The Association between Serum Hemoglobin and Renal Prognosis of IgA Nephropathy
Tae Ryom Oh, Su Hyun Song, Hong Sang Choi, Chang Seong Kim, Seung Hyeok Han, Kyung Pyo Kang, Young Joo Kwon, Soo Wan Kim, Seong Kwon Ma, Eun Hui Bae
Journal of Clinical Medicine.2021; 10(2): 363. CrossRef
Prevalence of anemia in diabetic adult outpatients in Northeast Ethiopia
Temesgen Fiseha, Aderaw Adamu, Melkam Tesfaye, Angesom Gebreweld, Jennifer A. Hirst
PLOS ONE.2019; 14(9): e0222111. CrossRef
Targeted Clinical Metabolite Profiling Platform for the Stratification of Diabetic Patients
Ahonen, Jäntti, Suvitaival, Theilade, Risz, Kostiainen, Rossing, Orešič, Hyötyläinen
Metabolites.2019; 9(9): 184. CrossRef
Effect of high density lipoprotein cholesterol on the relationship of serum iron and hemoglobin with kidney function in diabetes
Ashley N. Williams, Baqiyyah N. Conway
Journal of Diabetes and its Complications.2017; 31(6): 958. CrossRef

Hemoglobin A1c May Be an Inadequate Diagnostic Tool for Diabetes Mellitus in Anemic Subjects: Jung Il Son, Sang Youl Rhee, Jeong-taek Woo, Jin Kyung Hwang, Sang Ouk Chin, Suk Chon, Seungjoon Oh, Sung Woon Kim, Young Seol Kim; Diabetes Metab J. 2013;37(5):343-348. Published online October 17, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.5.343

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Abstract PDF PubReader

Background

Recently, a hemoglobin A1c (HbA1c) level of 6.5% has been determined to be a criterion for diabetes mellitus (DM), and it is a widely used marker for the diagnosis of DM. However, HbA1c may be influenced by a number of factors. Anemia is one of the most prevalent diseases with an influence on HbA1c; however, its effect on HbA1c varies based on the variable pathophysiology of anemia. The aim of this study was to determine the effect of anemia on HbA1c levels.

Methods

Anemic subjects (n=112) and age- and sex-matched controls (n=217) who were drug naive and suspected of having DM were enrolled. The subjects underwent an oral glucose tolerance test and HbA1c simultaneously. We compared mean HbA1c and its sensitivity and specificity for diagnosing DM between each subgroup.

Results

Clinical characteristics were found to be similar between each subgroup. Also, when glucose levels were within the normal range, the difference in mean HbA1c was not significant (P=0.580). However, when plasma glucose levels were above the diagnostic cutoff for prediabetes and DM, the mean HbA1c of the anemic subgroup was modestly higher than in the nonanemic group. The specificity of HbA1c for diagnosis of DM was significantly lower in the anemic subgroup (P<0.05).

Conclusion

These results suggest that the diagnostic significance of HbA1c might be limited in anemic patients.

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Waist circumference and glycaemia are strong predictors of progression to diabetes in individuals with prediabetes in sub-Saharan Africa: 4-year prospective cohort study in Malawi
Wisdom P. Nakanga, Amelia C. Crampin, Joseph Mkandawire, Louis Banda, Rob C. Andrews, Andrew T. Hattersley, Moffat J. Nyirenda, Lauren R. Rodgers, Julia Robinson
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Implications of Iron Deficiency Anaemia on Glycemic Dynamics in Diabetes Mellitus: A Critical Risk Factor in Cardiovascular Disease
Eman Elsheikh, Sereen S Aljohani , Munirah M Alshaikhmubarak, Meshari A Alhawl, Alhanouf W Alsubaie, Norah Alsultan, Asmaa F Sharif, Sayed Ibrahim Ali
Cureus.2023;[Epub] CrossRef
Serum Iron Profile in Type 2 Diabetes, A Role Beyond Anemic Marker!
Happy Chutia, Sungdirenla Jamir, Md Yasir, Gautam Handique
The Journal of Medical Research.2023; 9(5): 129. CrossRef
Large-scale retrospective analyses of the effect of iron deficiency anemia on hemoglobin A1c concentrations
Lokinendi V. Rao, George W. Pratt, Caixia Bi, Martin H. Kroll
Clinica Chimica Acta.2022; 529: 21. CrossRef
Glycemic Abnormalities Assessment on Children and Adolescents with Beta-Thalassemia Major
Siska Mayasari Lubis, Bidasari Lubis, Nadhira Anindita Ralena
Open Access Macedonian Journal of Medical Sciences.2022; 10(B): 697. CrossRef
Integrity loss of glycosylated hemoglobin with deepening anemia
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Effect of anemia and erythrocyte indices on hemoglobin A1c levels among pregnant women
Zong-Hui Guo, Huai-Liang Tian, Xiao-Qian Zhang, Deng-Han Zhang, Zhi-Min Wang, Kun Wang, Wen-Wen Su, Fei Chen
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Glycosylated Hemoglobin in Subjects Affected by Iron-Deficiency Anemia
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Diabetes & Metabolism Journal.2019; 43(4): 539. CrossRef
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The Clinical Characteristics of Anemia in Type 2 Diabetic Patients Without Overt Nephropathy.: Eun Young Ko, Se In Kim, Yong Bum Jang, Kyoung Hun Min, Sung Hun Kim, Kyu Sun Lee, So Ri Kim, Eun Kyoung Choi, Ji Hyun Park, Tae Sun Park, Hong Sun Paek; Korean Diabetes J. 2004;28(5):425-431. Published online October 1, 2004

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Abstract PDF: BACKGROUND
It is well known that anemia occurs early in diabetic patients before they reach to end stage renal failure. This anemia is considered to be due to the reduced endogenous erythropoietin synthesis, tubulointerstitial damage, autonomic dysfunction, and to the use of angiotensin-converting- enzyme inhibitors. Because anemia has a significant impact on the quality of life for diabetic patients, we examined the clinical characteristics of anemia in those diabetic patients who did not have overt nephropathy. METHODS: We retrospectively reviewed the medical records of 200 type 2 diabetic patients with anemia who had been followed up from 1998 to 2002 by Chonbuk University Medical School Hospital. We measured the total cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, and the presence of complications (retinopathy or neuropathy) for about 90 diabetic patients who were under the age of 65, they were without other underlying disease and they had a hemoglobin concentration 110g/L, GFR 1.0 mL/s. We excluded the causes of anemia as being from malignancy, liver disease, coexisting iron deficiency, chronic inflammatory disease and chronic infection. RESULTS: The clinical characteristics of the patients are as follows; the mean age was 59.6 +/- 8.4 years, the mean HbA1C was 9.4 +/- 2.3%, and the mean Hb concentration was 96 +/- 12 g/L. Our results showed that an inverse relation existeds between Hb concentration and total cholesterol (p<0.04), LDL cholesterol (p<0.05), age (p<0.02), and the duration of diabetes (p<0.01).Our results also showed that a linear relation existed between the Hb concentration, HDL cholesterol (p<0.02), and the GFR (p<0.01). CONCLUSION: Diabrtic patients with anemia are in need of intensive management for the lipid and GFR that causes thair anemia.

Randomized Controlled Trial

Therapeutic Effect of Recombinant Human Erythropoietin on Anemia with Erythropoietin Deficiency in Early Diabetic Nephropathy.: Dae Jung Kim, Soo Kyung Kim, Hyeung Jin Kim, Yoo Mee Kim, Yong Seok Yun, Chul Woo Ahn, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyeong Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2001;25(5):364-373. Published online October 1, 2001

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Abstract PDF: BACKGROUND
We have previously reported that reduced erythropoietin (Epo) responsiveness to anemia could explain the anemia in diabetic patients before advanced diabetic nephropathy. Thus, the aim of this randomized prospective study is to investigate the therapeutic effect of recombinant human erythropoietin (rHuEpo) on anemia with Epo deficiency in early diabetic nephropathy. METHODS: Twenty-nine diabetic patients with the normocytic normochromic anemia of Epo deficiency were randomized into Epo-treatment group (n=20, M:F= 8:12, mean age=52.9+/-9.2) and control group (n=9, M:F=4:5, mean age=53.6+/-12.4). Twenty patients of Epo-treatment group were treated with rHuEpo (Epokine (CheilJedang Co.) 4,000unit/day SC., 3 times/week) for 8 weeks. The Epo- treatment group were divided into the responder or non-responder. Patients with increments in Hemoglobin (Hb) during the follow-up duration was above 2 g/dL, or with the final Hb was above 14 g/dL in men or 13g/dL in women were decided the responder. In order to analyze factors affecting the therapeutic effects of rHuEpo, the clinical and biochemical characteristics were compared between the responder and non-responder group. RESULTS: There was no difference in the clinical and biochemical characteristics between the Epo-treatment and the control group at randomization. The responder group (n=14) had significant increments in Hb, compared to the non-responder group (n=6) or the control group (13.6+/-1.0 vs. 10.1+/-1.5 vs 11.2+/-1.2 g/dL, p < 0.001, respectively). The treatment duration of rHuEpo in the responder group was 4.9+/-2.3 weeks. Among the Epo-treatment group, there was no differences between the responder and the non-responder group in sex, age, duration of diabetes, serum creatinine level, 24 hour urinary albumin excretion rates, HbA1C, frequency or severity of microangiopathy, and serum Epo level. However, the responder group had higher serum ferritin (240.3+/-108.4 vs 25.8+/-3.0 g/L, p<0.05) and transferin saturation level (32.7+/-7.9 vs 21.2+/-5.3 %, p<0.05). CONCLUSION: These results concluded that the administration of rHuEpo could be useful in treating anemia with Epo deficiency in early diabetic nephropathy and that the degree of iron storage and functional iron deficiency might affect the therapeutic effects of rHuEpo on this type of anemia.

Original Article

Reduced Erythropoietin Responsiveness to Anemia in Diabetic Patients before Advanced Diabetic Nephropathy.: Yong Seok Yun, Sung Cheol Kim, Nae Chun Yoo, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Jee Sook Hahn, Kap Bum Huh; Korean Diabetes J. 1999;23(5):669-677. Published online January 1, 2001

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Abstract PDF: BACKGROUND
We have often encountered some diabetie patients, in whom the causes of anemia were not clearly identified, despite differential hematologic studies. We, therefore, studied the clinical and biochemical characteristics of diabetic patients with anemia of uncertain cause. The study measured erythropoietin levels in diabetic subjects without significant diabetic renal disease. METHODS: Among 62 medical records of diabetic patients with anemia, showing no evidence of advanced diabetic nephropathy (creatinine clearance > 30 mL/min/1.73m2), the causes of the anemia were evaluated. In addition, we recruited 35 diabetic patients with uncertain causes of anemia, in order to evaluate the serum erythropoietin(Epo) responsiveness. Also, we compared their Epo levels to a group of non-diabetie subjects with similar degree of anemia. RESULT: The causes of anemia were not able to be identified in 28 (45.2 %) of 62 patients. The serum Epo levels of diabetic patients with anemia of uncertain cause (17.6+/-8.1), were significantly lower than those of non-diabetic patients with the same degree of decrease in hemoglobin levels (144.9+/-108.0 mIU/mL, p<0.001). The hemoglobin levels of diabetic patients were correlated with creatinine clearance (r=0.34, p=0.03), serum creatinine levels (r=-0.49, p=0.003), and albumin excretion rate (r=-0.44, p=0.009). But, showed no relation with age, duration of diabetes, glycated hemoglobin, presence of retinopathy or neuropathy. CONCLUSION: We concluded that reduced Epo responsiveness to anemia could explain the anemia present in diabetic patient but without advanced diabetic nephropathy. This may reflect early renal interstitial damage.

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