Novel Iron Parameters in Patients with Type 2 Diabetes Mellitus in Relation to Kidney Function

Background/aims: Anemia of chronic disease is a common feature in diabetes and chronic kidney disease. Hepcidin is the key element involved in iron metabolism; however, studies on new indices of iron status are still ongoing. The aim of the study was to assess novel iron parameters in patients with type 2 diabetes mellitus in relation to kidney function. Methods: The study included 80 type 2 diabetic patients and 23 healthy volunteers. Standard laboratory measurements were used to measure the iron status, complete blood count, creatinine, the estimated glomerular filtration rate (eGFR), serum lipids, and brain natriuretic peptides (BNPs). Commercially available kits were used to measure hepcidin-25, the soluble transferrin receptor (sTfR), growth differentiation factor-15 (GDF-15), and hypoxia-inducible factor-1 alpha. Results: Anemia was present in 65% of the studied patients. The control group was found to have significantly higher hepcidin, sTfR, and GDF-15, and lower hemoglobin and iron. When compared with patients with eGFR values ≥60 mL/min/1.73 m2 and <60 mL/min/1.73 m2, we found that patients with higher eGFR had higher hemoglobin, ferritin, and HIF-1 alpha, lower BNP, and were younger. We found that levels of HIF-1 alpha are negligible in the studied population and were related to age only in patients with eGFR values ≥60 mL/min/1.73 m2. Conclusion: A comprehensive assessment of iron status is rarely performed. Novel biomarkers of iron metabolism are not generally related to kidney function. Whether the assessment of HIF-1 alpha would be a marker of efficient anemia therapy with HIF-prolyl hydroxylase inhibitors is still a matter for further study.

POLA KONSUMSI DAN SANITASI LINGKUNGAN BALITA STUNTING DI POLEWALI MANDAR

This study aims to analyze the pattern of consumption and environmental sanitation in stunting children in the Wonomulyo Polewali Mandar district. Method The study design used was analytic observational. The total sample was 101 toddlers aged 6-36 months, using simple random sampling method. The determination of nutritional status was processed using the WHO AntroPlus 2010 including the Semi Quantitative Food Frequency Questionnaire and an environmental sanitation questionnaire. Results: The frequency of frequent consumption of carbohydrates 79.21%, the frequency of animal protein (48.52%), vegetable protein (41.58%), fruit (46.58%), and beverages (43.6%). ), snacks (47.52%), and rare frequency of vegetables (44.54%). The average intake of energy (773.87 kcal), protein (18.19 gr), calcium (471.61 mg), and iron (8.15 mg). There was no significant relationship with the adequacy of nutrients for energy (p = 0.422), protein (p = 0.428), calcium (p = 0.075) and iron parameters had a significant relationship (p = 0.049). The results of environmental quality measurement obtained data on toddlers with short and very short nutritional status in the healthy environmental sanitation category as much as 18 (17.8%) and toddlers with short and very short nutritional status in the category of unhealthy environmental sanitation by 83 (82.2%). So that the results of the sig value test (2-sided) of 0.951> 0.05, it can be concluded that there is no relationship between nutritional status and unhealthy sanitary conditions. Conclusion: Iron adequacy is related to stunting status, while environmental sanitation quality is not related to stunting status.

Common variants in the transmembrane protease serine 6 (TMPRSS6) gene alter hepcidin but not plasma iron in response to oral iron in healthy Gambian adults: a recall-by-genotype study

Background The role of genetic determinants in mediating iron status in Africans is not fully understood. Genome-wide association studies in non-African populations have revealed genetic variants in the TMPRSS6 gene that are associated with the risk of anemia. Objectives To investigated the effects of risk alleles for low iron status from TMPRSS6 rs2235321, rs855791 and rs4820268, on responses to oral iron in healthy Gambian adults. Methods Using a recall-by-genotype design, participants were selected from a pre-genotype cohort of 3000 individuals in the Keneba Biobank (MRCG at LSHTM). Participants were invited to participate in the study based on nine genotype combinations obtained from three TMPRSS6 SNPs (rs2235321, rs855791 and rs4820268). The participants fasted overnight and then ingested a single oral dose of ferrous sulfate (130 mg elemental iron). Blood samples were collected prior to iron ingestion and at 2 and 5 hours after the oral iron dose. The effects of genotype on hepcidin and plasma iron parameters were assessed. Results A total of 251 individuals were enrolled. Homozygous carriers of the major TMPRSS6 alleles at each of the SNPs had higher plasma hepcidin at baseline (rs2235321: GG vs AA 9.50 vs 6.60ng/ml, p = 0.035; rs855791: GG vs AG = 9.50 vs 4.96ng/mL, p = 0.015; rs4820268: AA vs GG = 9.50 vs 3.27ng/mL, p = 0.002) and at subsequent timepoints. There were no differences in delta plasma iron (a proxy for iron absorption) between genotypes. In most subjects, hepcidin levels increased following iron ingestion (overall group mean = 4.98 ± 0.98ng/ml at 5h, p &lt; 0.001), but double heterozygotes at rs2235321 and rs855791 showed no increase (0.36 ± 0.40ng/ml at 5h, p = 0.667). Conclusions This study revealed that common TMPRSS6 variants influence hepcidin concentrations, but not iron status indicators either at baseline or following a large oral dose of iron. These results suggest that genetic variations in the TMPRSS6 gene are unlikely to be important contributors to variations in iron status in Africans. This study was registered at ClinicalTrials.gov # NCT03341338.

Molecular analysis of Homeostatic iron regulator, trans-membrane protease serine-6, and BTB domain-containing protein-9 variants and iron parameters in blood donors

Genetic variants associated with iron homeostasis have been identified, but their association with iron-related indices and variables among different ethnic populations remains controversial. We aimed to explore the genotype frequency and allelic distribution of three iron-metabolism related variants in homeostatic iron regulator gene (HFE; rs1800562 G/A), Transmembrane Protease, Serine-6 gene (TMPRSS6; rs855791 A/G); and BTB domain-containing protein-9 gene (BTBD9; rs9357271 C/T) among a sample of the Middle Eastern blood donors and to detect the association of these variants on blood indices, and serum hepcidin/ferritin levels. Real-Time TaqMan genotyping assay for the specified variants was applied for 197 unrelated blood donors. Complete blood picture and serum hepcidin/ferritin levels were assessed. All participants were carriers of rs1800562*G/G genotype for HFE. The frequency of A/A and A/G genotypes of TMPRSS6 rs855791 variant was 55% and 45%, and for C/C, C/T, and T/T of BTBD9 rs9357271, were 15%, 43%, and 42%, respectively. Minor allele frequencies of rs855791*G and rs9357271*C were 0.23 and 0.37. The GGC genotype combination (for HFE/TMPRSS6/BTBD9, respectively) was more frequent in male participants. Higher serum hepcidin and hepcidin/ferritin ratio were observed in TMPRSS6 (A/G) carriers. While subjects with BTBD9 C/T and TT genotypes had lower serum ferritin values and higher levels of hepcidin and hepcidin/ferritin ratio compared with C/C genotype. No significant associations were found with any other blood parameters. &#160;In conclusion, TMPRSS6 rs855791 (A/G) and BTBD9 rs9357271 (C/T) variants were prevalent in the present blood donor population and may influence the serum hepcidin and/or ferritin levels.