The effect of blood glucose regulation on iron metabolism and hepcidin in uncontrolled type 2 diabetic patients

Abstract

Type 2 diabetes is a chronic progressive disease. In diabetes, where multiple systems are involved, iron metabolism is also affected. Nevertheless, it is unknown how blood glucose regulation and iron metabolism are effected and whether there are changes in hematologic parameters. The aim of our study was to investigate whether blood glucose regulation during diabetes has an effect on iron metabolism, hemoglobin, and hepcidin levels. Methods: Patients included in this study were aged between 30-70 years, who had previously been diagnosed as having diabetes and were under treatment with antidiabetics, with hemoglobin A1c (HbA1c) level >= 7%, hemoglobin level >= 13 gr/dL in men and >= 12 gr/dL in women. Patients with active infection, chronic kidney failure, liver disease, malignancy, and those using pioglitazone were excluded from the study. Seventy-six patients were enrolled in this study. Complete blood count, fasting blood glucose, HbA1c, C-peptide, C-reactive protein, hepcidin levels, iron, total iron binding capacity, and ferritin levels were measured. Albumin/creatinine ratio in spot urine was checked. Patients followed an appropriate diet program and received intensive medical treatment for 3 months. After 3 months, parameters were repeated and compared with previous values. Findings: Fifty-four patients (mean age 54.7 +/- 8.3 years; women/men: 30/24) were enrolled in the study after 3 months of follow-up. A statistically significant decrease in HbA1c was observed (11.0% +/- 1.8 vs 7.4 +/- 1.2, P < 0.001). Although increased hepcidin levels showed no change (mu g/L) (177.1 +/- 146.5 vs 185 +/- 172.9, p: NS), a significant decrease in ferritin and iron levels was seen (129.6 +/- 121 vs 107.0 +/- 94.8 ng/mL, P = 0.002, 83.3 +/- 28.6 vs 75.3 +/- 21.4 mu g/L, P = 0.035, respectively). In patients whose body mass indexes were not changed, neutrophil/lymphocyte ratio and urinary albumin/creatinine excretion rate significantly decreased (2.33 +/- 1.45 vs 1.93 +/- 0.81, P = 0.035, 0.22 +/- 0.2 vs 0.02 +/- 0.02, P = 0.019, respectively). A significant decrease in hemoglobin levels was observed after 3 months (13.8 +/- 1.4 vs 13.4 +/- 1.4 g/dL, P < 0.001). This decrease was more prominent in those who progressed to insulin from oral antidiabetics (14.04 +/- 1.2 vs 13.3 +/- 1.21 g/dL, P < 0.001). It was seen that hepcidin levels increased as HbA1c levels increased. No association between hepcidin levels and development of anemia or hemoglobin values was found. Results: Serum hepcidin and ferritin levels increased in patients with poorly controlled diabetes. Whereas some of the inflammation markers and ferritin level decreased with blood glucose regulation, there was no change in hepcidin levels. No association between hepcidin levels, hemoglobin, and development of anemia was observed. There was a significant decrease in hemoglobin level, especially in those who were started on insulin after oral antidiabetics.