{"doi":"10.1111/bjh.16771","title":"Zinc supplementation improves markers of glucose homeostasis in thalassaemia","abstract":"Iron overload is a frequent complication of blood transfusions in thalassaemia major (TM). Elevated tissue iron increases the risk of endocrine deficiencies, including diabetes mellitus (DM) arising from pancreatic damage.1 Up to 18% of adult patients with TM will develop DM,2 yet little attention has been paid to factors other than iron that contribute to its development. The literature is rich with illustrations of the direct role zinc has in the development of, and treatment for, DM.3, 4 Zinc is involved in the delay in onset of DM, protection of pancreatic islet cells, and is crucial to glucose metabolism in the periphery.5 Supplementation with zinc has been shown to decrease hyperglycaemia and improve glycaemic control in Type 2 DM.6 Zinc is commonly reported to be deficient in TM.7, 8 While decreased circulating zinc has been associated with depressed insulin secretion and altered glucose homeostasis,8 there are no published reports exploring the effect of zinc supplementation on glucose homeostasis in patients with TM. We compared cross-sectional differences in markers of glucose homeostasis and zinc status in nine diabetic (TM+DM) and 20 non-diabetic TM patients (TM–DM), with 10 healthy controls. The TM–DM patients were then provided with a 25 mg/day zinc supplement for 3 months, to evaluate the effect on glucose homeostasis. There is no standard dose to restore normal circulating levels in all populations; however, previous supplementation studies in haemoglobinopathies have used between 25 and 75 mg zinc/day.9 The patients with TM+DM had a history of fasting glucose of ≥126 mg/dl, plasma glucose of ≥200 mg/dl at 2 h after an oral glucose tolerance test (OGTT10), or were currently on treatment with insulin or metformin. The controls, without TM or DM, were matched for age (±5 years), gender and race. Written consent was obtained for subjects aged >18 years, and assent for those aged 10–18 years. The present study was approved by the Institutional Review Board at the University of California, San Francisco (UCSF) Benioff Children's Hospital Oakland, and registered at ClinicalTrials.gov ID# NCT01772680. Patients with TM+DM and controls had only baseline assessments, while three assessments were conducted at 0, 12 and 24 weeks in the TM–DM patients. Zinc sulphate capsules, 25 mg zinc/day compounded by Abbott Pharmacy (Berkeley, CA, USA), were provided between 12 and 24 weeks, consumed each morning apart from nutritional supplements and at a minimum of 2 h before or after oral chelator. All but one patient tolerated zinc sulphate without incident and took the supplement >70% of the time. One patient became nauseated and discontinued the intervention at week 14. Blood and ‘spot’ urine were collected in the morning before transfusion from subjects who had fasted for a minimum of 8 h. Patients were instructed to avoid taking oral chelators for at least 24 h prior to blood collection for assessment of fructosamine, C-peptide, lipase, amylase, high-sensitivity C-reactive protein (hsCRP), glucose, and insulin. The liver iron concentration (LIC) was assessed in TM by Ferritometer.11 Plasma and urinary zinc and plasma copper were analysed using inductively coupled plasma optical emission spectrometry. Plasma zinc remains the best available biomarker of zinc deficiency in populations, the suggested lower cut-off for fasting morning zinc is <74 µg/dl for males and <70 µg/dl for females by the International Zinc Nutrition Consultative Group.12,13 A 2-h OGTT was conducted in TM–DM patients at 0, 12 and 24 weeks with a 75-g glucose load. Markers of β-cell function and insulin sensitivity calculated during OGTT included: area under the curve for glucose and insulin response to the glucose load; homeostatic model assessment of β-cell function (HOMA-B)14 and Oral Disposition Index (ODI),8 as an indicator of β-cell function, adjusted for insulin sensitivity. Also, the glucose clearance rate (GCR)15 and the Oral Glucose Sensitivity Index (","journal":"British Journal of Haematology","year":2020,"id":89056,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":277230,"name":"Tariq Ahmad","orcid":"0000-0002-0690-4604","position":1,"is_corresponding":false},{"id":450983,"name":"David W. Killilea","orcid":"0000-0002-8929-6527","position":2,"is_corresponding":false},{"id":452066,"name":"Rahim Hussain","orcid":null,"position":3,"is_corresponding":false},{"id":450984,"name":"Ashutosh Lal","orcid":"0000-0003-0082-3536","position":4,"is_corresponding":false},{"id":422114,"name":"Ellen B. Fung","orcid":"0000-0003-0745-2598","position":0,"is_corresponding":true}],"reference_count":22,"raw_metadata":null,"created_at":"2026-07-18T22:01:50.225871Z","pmid":"32488893","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}