The effects of excess weight on glucose homeostasis in young adult females with β-thalassemia major (β-TM): a preliminary retrospective study: Excess weight and glucose homeostasis in β-thalassemia major

The effects of excess weight on glucose homeostasis in young adult females with β-thalassemia major (β-TM): a preliminary retrospective study

Excess weight and glucose homeostasis in β-thalassemia major

Authors

  • Vincenzo De Sanctis Quisisana Hospital, Ferrara https://orcid.org/0000-0002-6131-974X
  • Shahina Daar Department of Haematology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Sultanate of Oman
  • Ashraf T Soliman Department of Pediatrics, Hamad General Hospital, Doha, Qatar
  • Ploutarchos Tzoulis Department of Diabetes and Endocrinology, Whittington Hospital, University College London, London, UK
  • Mohamed Yassin Hematology Section, Medical Oncology, National Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation (HMC), Doha, Qatar
  • Christos Kattamis Τhalassemia Unit, First Department of Paediatrics, National Kapodistrian University of Athens 11527, Greece

Keywords:

Excess weight, oral glucose tolerance test, glucose homeostasis, insulin secretion and sensitivity, β-thalassemia major.

Abstract

Background: With the rising prevalence of obesity worldwide, it is becoming imperative to detect disturbed glucose metabolism as early as possible in order to prevent type 2 diabetes (T2D) development.

Study design: The present retrospective observational study aimed to evaluate the relationship between BMI and glucose metabolism, insulin secretion and sensitivity indices, derived from glucose tolerance test (OGTT), in β -TM female patients who were overweight (BMI 25-29.9 kg/m2) and follow its outcome over time.

Subjects and Methods: Eleven overweight and 11 females with ideal weight and β -TM, matched for age, were recruited. OGTT was undertaken and different indices for β-cell function, insulin sensitivity and insulin secretion were calculated.

Results: At first evaluation, 7 of 11 overweight β -TM patients (63.6%) and 3 of 11 normal weight β-TM patients (27.2%) had glucose dysregulation (GD) during OGTT. Overweight patients with β-TM had increased HOMA-IR and QUICKI indices associated with decreased Matsuda WBISI index. The mean ± SD duration of follow-up was 4.5 ± 1.2 years. At last observation, 2/11 overweight patients had developed T2D (18.1%). In patients with normal weight, GD increased from 3/11 (27.2%) to 5/11 (45.4%), but none developed T2DM. The difference between SF at first and last observation (1,220 ± 702 vs.1,091 ± 454 ng/mL; P: 0.61) was not significant.

Conclusion: Overweight seems to be an additional risk factor for the development of GD in β-TM patients. This is particularly important in clinical practice, due to the lack of appropriate guidelines dedicated to this group of patients.

References

Bannerman RM, Keusch G, Kreimer-Birnbaum M, Vernon K, Vance VK, Vaughan S. Thalassemia intermedia, with iron overload, cardiac failure, diabetes mellitus, hypopituitarism and porphyrinuria. Am J Med.1967;42(3);476-8. doi:101016/0002-9343(67)90276-8.

Farmakis D, Porter J, Taher A, Cappellini MD, Angastiniotis M, Eleftheriou A. 2021 Thalassaemia International Federation guidelines for the management of transfusion-dependent thalassemia. Hemasphere.2022;6(8):e732. doi:10.1097/HS9.0000000000000732.

Kattamis A, Kwiatkowski JL, Aydinok Y. Thalassemia.Lancet.2022;399(10343):2310-24. doi:10.1016/ S0140-6736(22)00536-0.

Noetzli LJ, Papudesi J, Coates TD, Wood JC. Pancreatic iron loading predicts cardiac iron loading in thalassemia major. Blood. 2009;114(19):4021-6. doi: 10.1182/blood-2009-06-225615.

Patel S, Jinjuvadia R, Patel R, Liangpunsakul S. Insulin Resistance is associated with significant liver fibrosis in chronic hepatitis C patients: a systemic review and meta-analysis. J Clin Gastroenterol. 2016; 50(1):80-4. doi: 10.1097/MCG.0000000000000400.

Ibrahim AS, Abd El-Fatah AH, Abd El-Halim AF, Mohamed FF. Serum ferritin levels and other associated parameters with diabetes mellitus in adult patients suffering from beta thalassemia major. J Blood Med. 2023;14: 67-81. doi: 10.2147/JBM.S390666.

Goldberg EK, Lal A, Fung EB. Nutrition in thalassemia: a systematic review of deficiency, relations to morbidity, and supplementation recommendations. J Pediatr Hematol Oncol. 2022; 44(1):1-11. doi: 10.1097/MPH.0000000000002291.

Fung EB, Gildengorin G, Talwar S, Hagar L, Lal A. Zinc status affects glucose homeostasis and insulin secretion in patients with thalassemia. Nutrients. 2015;7(6):4296-307. doi: 10. 3390/nu7064296.

Saudek CD, Hemm RM, Peterson CM. Abnormal glucose tolerance in β-thalassemia major. metabolism. 1977; 26 (1):43-52. doi.org/10.1016/0026-0495(77)90126-3.

Matter RM, Allam KE, Sadony AM. Gradient-echo magnetic resonance imaging study of pancreatic iron overload in young Egyptian beta-thalassemia major patients and effect of splenectomy.Diabetol Metab Syndr. 2010;2:23. doi: 10.1186/1758-5996-2-23.

Bordbar M, Bozorgi H, Saki F, et al. Prevalence of endocrine disorders and their associated factors in transfusion-dependent thalassemia patients: a historical cohort study in Southern Iran. J Endocrinol Invest.2019; 42:1467–76.doi:10.1007/s40618-019-01072-z.

De Sanctis V, Soliman A, Daar S, et al. Insulin-Like Growth Factor -1 (IGF-1) and Glucose Dysregulation in Young Adult Patients with β-Thalassemia Major: Causality or Potential Link? Acta Biomed. 2022; 93(6): e2022331. doi: 10.23750/abm.v93i6.13288.

Mauvais-Jarvis F. Gender differences in glucose homeostasis and diabetes. Physiol Behav. 2018; 187:20–3. doi:10.1016/j.physbeh.2017.08.016.

Tuomilehto J, Lindström J, Eriksson JG , et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344:1343 50.doi:10.1056/ NEJM 200 105033441801.

Yumuk V,Tsigos C, Fried M, et al. European guidelines for obesity management in adults. Obes Facts. 2015;8:402–24. doi: 10.1159/000442721.

De Sanctis V, Soliman AT, Elsedfy H, et al. Growth and endocrine disorders in thalassemia: The international network on endocrine complications in thalassemia (I‑CET) position statement and guidelines. Indian J Endocrinol Metab. 2013;17(1):8‑18. doi:10.4103/2230-8210.107808.

American Diabetes Association. Classification and diagnosis of diabetes: standards of medical care in diabetes - 2020. Diabetes Care. 2020; 43(Suppl.1): S14-S31. doi.org/ 10. 2337/dc20-S002.

De Sanctis V, Soliman A, Tzoulis P, et al. The clinical characteristics, biochemical parameters and insulin response to oral glucose tolerance test (OGTT) in 25 transfusion dependent β-thalassemia (TDT) patients recently diagnosed with diabetes mellitus (DM): Diabetes mellitus in β-thalassemia. Acta Biomed. 2022;92 (6):e2021488. doi.org/10.2 3750/abm.v92i6.12366.

Kasim N, Khare S, Sandouk Z, Chan C. Impaired glucose tolerance and indeterminate glycemia in cystic fibrosis. J Clin Transl Endocrinol. 2021;26:100275. doi: 10.1016/ j. jcte.2021.100275.

Chen Z, Shao L, Jiang M, Ba X, Ma B, Zhou T. Interpretation of HbA1c lies at the intersection of analytical methodology, clinical biochemistry and hematology (Review). Exp Ther Med. 2022; 24(6): 707. doi: 10.3892/ etm.2022.11643.

Chatzianagnostou K, Di Piazza S, Tirelli AS, et al. Low concordance between HbA1c and OGTT to diagnose prediabetes and diabetes in overweight or obesity. Clin Endocrinol. 2019;91(3):411-6. doi.org /10.1111/cen.14043.

Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care.1999;22(9):1462-70. doi:10.2337/ diacare. 22.9.1462.

Sluiter WJ, Erkelens DW, Reitsma WD, Doorenbos H. Glucose tolerance and insulin release, a mathematical approach I. Assay of the β-cell response after oral glucose loading. Diabetes. 1976; 25:241–4. doi: 10.2337/diab.25.4.245.

Gutch M, Kumar S, Razi SM, Gupta KK, Gupta A. Assessment of insulin sensitivity/ resistance. Indian J Endocr Metab. 2015;19:160-4. doi: 10.4103/2230-8210.146874.

Park SY, Gautier JF, Suk Chon S. Assessment of Insulin Secretion and Insulin Resistance in Human. Diabetes Metab J 2021;45:641-54. doi: 10.4093/ dmj. 2021.0220.

Hayashi T, Boyko EJ, Sato KK, et al. Patterns of insulin concentration during the OGTT predict the risk of type 2 diabetes in Japanese Americans. Diabetes Care. 2013;36(5):1229-35. doi:10.2337/ dc12-0246.

Utzschneider KM, Prigeon RL, Faulenbach MV, et al. Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels. Diabetes Care. 2009;32(2):335-41. doi: 10.2337/dc08-1478.

De Sanctis V, Elsedfy H, Soliman AT, et al. Clinical and biochemical data of adult thalassemia major patients (TM) with multiple endocrine complications (MED) versus TM patients with normal endocrine functions: a long-term retrospective study (40 years) in a tertiary care center in Italy. Mediterr J Hematol Infect Dis 2016, 8(1): e2016022. doi: 10.4084/ MJHID. 2016.022.

Alder R, Roesser EB. Introduction to probability and statistics. WH Freeman and Company Eds. Sixth Edition. San Francisco (USA), 1975. PMID:1674139.

Swinscow TDV. Statistics at square one. XVI-The chi squared 2 tests. BMJ.1976; 2:573–4. doi: 10. 1136/ bmj.2. 6035. 573.

Tzoulis P. Review of Endocrine Complications in Adult Patients with β-thalassaemia Major. Thalass Rep. 2014;4(3):4871. doi: 10.4081/thal.2014.4871.

De Sanctis V, Soliman AT, Daar S, Tzoulis P, Fiscina B, Kattamis C, international network of clinicians for endocrinopathies in thalassemia and adolescence medicine (ICET-A). Retrospective observational studies: lights and shadows for medical writers. Acta Biomed. 2022;93(5):e2022319. doi:10.23750/abm.v93i5.13179.

Fontbonne A, Currie A, Tounian P, et al. Prevalence of overweight and obesity in france: the 2020 obepi-roche study by the “Ligue Contre l’Obésité”. J Clin Med.2023;12(3): 925. doi:10.3390/ jcm 12030925.

Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia. 2003;46:3–19. doi:10.1007/s00125-002-1009-0.

DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979;237:E214–E23. PIMD:382871.

Singh B, Saxena A. Surrogate markers of insulin resistance: a review. World J Diabetes. 2010;1(2): 36–47. doi:10.4239/wjd.v1.i2.36.

Srikanthan P, Hevener AL, Karlamangla AS. Sarcopenia exacerbates obesity-associated insulin resistance and dysglycemia: findings from the national health and nutrition examination survey III. PLoS ONE.2010;5(5): e10805. doi:10.1371/journal.pone.0010805.

Seltzer HS, Allen EW, Herron AL Jr, Brennan MT. Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus. J Clin Invest.1967;46(3):323-35. doi: 10.1172/JCI105534.

Kosaka K, Kuzuya T, Yoshinaga H, Hagura R. A prospective study of health check examinees for the development of non-insulin-dependent diabetes mellitus: relationship of the incidence of diabetes with the initial insulinogenic index and degree of obesity. Diabetic Medicine,.1996;13 (9) Suppl. 6: S120–S 6. PIMD:8894495.

Ferrannini E. Insulin resistance versus insulin deficiency in non-insulin-dependent diabetes mellitus: problems and prospects. Endocr Rev. 1998;19:477-90. doi: 10.1210/edrv.19.4.0336.

De Sanctis V, Soliman AT, Tzoulis P, et al. Glucose metabolism and insulin response to oral glucose tolerance test (OGTT) in prepubertal patients with transfusion-dependent β-thalassemia (TDT): a long-term retrospective analysis. Mediterr J Hematol Infect Dis. 2021;13:e2021051. doi: 10.4084/MJHID.2021.051.

De Sanctis V, Soliman A, Daar S, et al. Insulin-Like Growth Factor -1 (IGF-1) and glucose dysregulation in young adult patients with β-thalassemia major: causality or potential link? IGF-1 and glucose dysregulation in thalassemia. Acta Biomed. 2022;93(6):e2022331. doi: 10.23750/abm.v92i6.13288.

Clemmons DR. Role of Insulin-Like Growth Factor I in maintaining normal glucose homeostasis. Horm Res. 2005; 62 (Suppl. 1):77–82. doi: 10.1159000080763.

Jagannathan R, Neves JS, Dorcely B, et al.The oral glucose tolerance test :100 years later. Syndr Obes.2020;13:387-3805. doi: 10.2147/DMSO.S246062.

Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006;444(7121):840–6. doi: 10.1038/nature05482.

Muniyappa R, Madan R, Varghese RT. Assessing Insulin Sensitivity and Resistance in Humans. MDText.com, Inc.2021.PIMD25905189.

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Published

17-10-2023

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Section

HEMOGLOBINOPATHIES

How to Cite

1.
De Sanctis V, Daar S, Soliman AT, Tzoulis P, Yassin M, Kattamis C. The effects of excess weight on glucose homeostasis in young adult females with β-thalassemia major (β-TM): a preliminary retrospective study: Excess weight and glucose homeostasis in β-thalassemia major. Acta Biomed. 2023;94(5):e2023225. doi:10.23750/abm.v94i6.14909