Case Report

Prolonged clinical remission of type 1 diabetes sustained by calcifediol and low-dose basal insulin: a case report

*Author for correspondence:

E-mail Address: marco.infante@unicamillus.org

https://orcid.org/0000-0003-2032-8735

CTO Andrea Alesini Hospital, Division of Endocrinology & Diabetes, Department of Systems Medicine, University of Rome Tor Vergata, Via San Nemesio 21, Rome, 00145, Italy

Division of Cellular Transplantation, Diabetes Research Institute (DRI), University of Miami Miller School of Medicine, 1450 NW 10th Ave, Miami, FL 33136, USA

Section of Diabetes & Metabolic Disorders, UniCamillus, Saint Camillus International University of Health Sciences, Via di Sant’Alessandro 8, Rome, 00131, Italy

Network of Immunity in Infection, Malignancy & Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Via Cola di Rienzo 28, Rome, 00192, Italy

Search for more papers by this author

Laura Vitiello

Laboratory of Flow Cytometry, IRCCS San Raffaele, Via di Val Cannuta 247, Rome, 00166, Italy

Search for more papers by this author

Andrea Fabbri

https://orcid.org/0000-0003-2269-1554

Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, Rome, 00133, Italy

Search for more papers by this author

Camillo Ricordi

https://orcid.org/0000-0001-8092-7153

Division of Cellular Transplantation, Diabetes Research Institute (DRI), University of Miami Miller School of Medicine, 1450 NW 10th Ave, Miami, FL 33136, USA

Search for more papers by this author

Nathalia Padilla

Network of Immunity in Infection, Malignancy & Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Colonia Centroamérica L-823, Managua, 14048, Nicaragua

Search for more papers by this author

Francesca Pacifici

Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, Rome, 00133, Italy

Search for more papers by this author

Pasquale Di Perna

CTO Andrea Alesini Hospital, Division of Endocrinology & Diabetes, Department of Systems Medicine, University of Rome Tor Vergata, Via San Nemesio 21, Rome, 00145, Italy

Search for more papers by this author

Marina Passeri

CTO Andrea Alesini Hospital, Division of Endocrinology & Diabetes, Department of Systems Medicine, University of Rome Tor Vergata, Via San Nemesio 21, Rome, 00145, Italy

Search for more papers by this author

David Della-Morte

https://orcid.org/0000-0002-4054-5318

Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, Rome, 00133, Italy

Department of Human Sciences & Promotion of the Quality of Life, San Raffaele Roma Open University, Via di Val Cannuta 247, Rome, 00166, Italy

Department of Neurology, Evelyn F. McKnight Brain Institute, University of Miami Miller School of Medicine, 1120 NW 14th St, Miami, FL 33136, USA

Search for more papers by this author

Massimiliano Caprio

https://orcid.org/0000-0003-0722-7163

Department of Human Sciences & Promotion of the Quality of Life, San Raffaele Roma Open University, Via di Val Cannuta 247, Rome, 00166, Italy

Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele, Via di Val Cannuta 247, Rome, 00166, Italy

Search for more papers by this author

Luigi Uccioli

CTO Andrea Alesini Hospital, Division of Endocrinology & Diabetes, Department of Systems Medicine, University of Rome Tor Vergata, Via San Nemesio 21, Rome, 00145, Italy

Search for more papers by this author

Published Online:4 Jul 2023https://doi.org/10.2217/imt-2022-0266

View article

Abstract

Herein, we describe an unusually prolonged duration (31 months) of the clinical remission phase in a 22-year-old Italian man with new-onset type 1 diabetes. Shortly after the disease diagnosis, the patient was treated with calcifediol (also known as 25-hydroxyvitamin D3 or calcidiol), coupled with low-dose basal insulin, to correct hypovitaminosis D and to exploit the anti-inflammatory and immunomodulatory properties of vitamin D. During the follow-up period, the patient retained a substantial residual β-cell function and remained within the clinical remission phase, as evidenced by an insulin dose-adjusted glycated hemoglobin value <9. At 24 months, we detected a peculiar immunoregulatory profile of peripheral blood cells, which may explain the prolonged duration of the clinical remission sustained by calcifediol as add-on treatment to insulin.

Plain language summary

We describe the case of a 22-year-old Italian man who was treated with a form of vitamin D called calcifediol shortly after the diagnosis of type 1 diabetes, which is an autoimmune condition leading to insulin deficiency and to the lifelong need for insulin therapy. Calcifediol was administered, coupled with low-dose insulin, to correct vitamin D insufficiency and to exploit the anti-inflammatory properties of vitamin D. During the follow-up period (31 months), the patient unexpectedly remained on once-daily insulin injection therapy and maintained near-normal blood glucose levels. These findings suggest that calcifediol administration may represent a valid add-on treatment to insulin, with the aim of reducing daily insulin requirements and improving glucose control in patients with recent-onset type 1 diabetes.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet 383(9911), 69–82 (2014). • Provides relevant information on the pathophysiology of type 1 diabetes (T1D).
MedlineGoogle Scholar
2. Ikegami H, Noso S, Babaya N, Kawabata Y. Genetics and pathogenesis of type 1 diabetes: prospects for prevention and intervention. J. Diabetes Investig. 2(6), 415–420 (2011).
Medline CASGoogle Scholar
3. Rewers M, Ludvigsson J. Environmental risk factors for type 1 diabetes. Lancet 387(10035), 2340–2348 (2016).
Medline CASGoogle Scholar
4. Infante M, Ricordi C, Sanchez J et al. Influence of vitamin D on islet autoimmunity and beta-cell function in type 1 diabetes. Nutrients 11(9), 2185 (2019).
Medline CASGoogle Scholar
5. Fabbri A, Infante M, Ricordi C. Editorial – Vitamin D status: a key modulator of innate immunity and natural defense from acute viral respiratory infections. Eur. Rev. Med. Pharmacol. Sci. 24(7), 4048–4052 (2020).
Medline CASGoogle Scholar
6. Mathieu C, Waer M, Laureys J, Rutgeerts O, Bouillon R. Prevention of autoimmune diabetes in NOD mice by 1,25 dihydroxyvitamin D3. Diabetologia 37(6), 552–558 (1994).
Medline CASGoogle Scholar
7. Mathieu C, Waer M, Casteels K, Laureys J, Bouillon R. Prevention of type I diabetes in NOD mice by nonhypercalcemic doses of a new structural analog of 1,25-dihydroxyvitamin D3, KH1060. Endocrinology 136(3), 866–872 (1995).
Medline CASGoogle Scholar
8. Mathieu C, Laureys J, Sobis H, Vandeputte M, Waer M, Bouillon R. 1,25-Dihydroxyvitamin D3 prevents insulitis in NOD mice. Diabetes 41(11), 1491–1495 (1992).
Medline CASGoogle Scholar
9. Littorin B, Blom P, Schölin A et al. Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects: results from the nationwide Diabetes Incidence Study in Sweden (DISS). Diabetologia 49(12), 2847–2852 (2006).
Medline CASGoogle Scholar
10. Daga RA, Laway BA, Shah ZA, Mir SA, Kotwal SK, Zargar AH. High prevalence of vitamin D deficiency among newly diagnosed youth-onset diabetes mellitus in north India. Arq. Bras. Endocrinol. Metabol. 56(7), 423–428 (2012).
MedlineGoogle Scholar
11. Cadario F, Prodam F, Savastio S et al. Vitamin D status and type 1 diabetes in children: evaluation according to latitude and skin color. Minerva Pediatr. 67(3), 263–267 (2015).
Medline CASGoogle Scholar
12. Harris SS. Vitamin D in type 1 diabetes prevention. J. Nutr. 135(2), 323–325 (2005).
Medline CASGoogle Scholar
13. Ilonen J, Lempainen J, Veijola R. The heterogeneous pathogenesis of type 1 diabetes mellitus. Nat. Rev. Endocrinol. 15(11), 635–650 (2019). • Provides relevant information on the pathophysiology of T1D.
Medline CASGoogle Scholar
14. Leete P, Willcox A, Krogvold L et al. Differential insulitic profiles determine the extent of β-cell destruction and the age at onset of type 1 diabetes. Diabetes 65(5), 1362–1369 (2016). •• Provides relevant information on different insulitic profiles in T1D.
Medline CASGoogle Scholar
15. Roep BO. The role of T-cells in the pathogenesis of type 1 diabetes: from cause to cure. Diabetologia 46(3), 305–321 (2003).
Medline CASGoogle Scholar
16. Lindley S, Dayan CM, Bishop A, Roep BO, Peakman M, Tree TI. Defective suppressor function in CD4(+)CD25(+) T-cells from patients with type 1 diabetes. Diabetes 54(1), 92–99 (2005).
Medline CASGoogle Scholar
17. Brusko TM, Wasserfall CH, Clare-Salzler MJ, Schatz DA, Atkinson MA. Functional defects and the influence of age on the frequency of CD4⁺ CD25⁺ T-cells in type 1 diabetes. Diabetes 54(5), 1407–1414 (2005).
Medline CASGoogle Scholar
18. Haseda F, Imagawa A, Murase-Mishiba Y, Terasaki J, Hanafusa T. CD4⁺ CD45RA^- FoxP3^high activated regulatory T cells are functionally impaired and related to residual insulin-secreting capacity in patients with type 1 diabetes. Clin. Exp. Immunol. 173(2), 207–216 (2013).
Medline CASGoogle Scholar
19. Walker LS, von Herrath M. CD4 T cell differentiation in type 1 diabetes. Clin. Exp. Immunol. 183(1), 16–29 (2016).
Medline CASGoogle Scholar
20. Cox SL, Silveira PA. Emerging roles for B lymphocytes in type 1 diabetes. Expert. Rev. Clin. Immunol. 5(3), 311–324 (2009).
Medline CASGoogle Scholar
21. Fonolleda M, Murillo M, Vázquez F, Bel J, Vives-Pi M. Remission phase in paediatric type 1 diabetes: new understanding and emerging biomarkers. Horm. Res. Paediatr. 88(5), 307–315 (2017). •• Provides relevant information on the pathophysiology of the remission phase in patients with T1D.
Medline CASGoogle Scholar
22. Pinkey JH, Bingley PJ, Sawtell PA, Dunger DB, Gale EA. Presentation and progress of childhood diabetes mellitus: a prospective population-based study. The Bart’s–Oxford Study Group. Diabetologia 37(1), 70–74 (1994).
Medline CASGoogle Scholar
23. Zhong T, Tang R, Xie Y, Liu F, Li X, Zhou Z. Frequency, clinical characteristics, and determinants of partial remission in type 1 diabetes: different patterns in children and adults. J. Diabetes 12(10), 761–768 (2020).
Medline CASGoogle Scholar
24. Passanisi S, Salzano G, Gasbarro A et al. Influence of age on partial clinical remission among children with newly diagnosed type 1 diabetes. Int. J. Environ. Res. Public Health 17(13), 4801 (2020).
Medline CASGoogle Scholar
25. Abdul-Rasoul M, Habib H, Al-Khouly M. ‘The honeymoon phase’ in children with type 1 diabetes mellitus: frequency, duration, and influential factors. Pediatr. Diabetes 7(2), 101–107 (2006).
MedlineGoogle Scholar
26. Aly H, Gottlieb P. The honeymoon phase: intersection of metabolism and immunology. Curr. Opin. Endocrinol. Diabetes Obes. 16(4), 286–292 (2009).
Medline CASGoogle Scholar
27. Infante M, Fabbri A, Padilla N et al. BNT162b2 mRNA COVID-19 vaccine does not impact the honeymoon phase in type 1 diabetes: a case report. Vaccines (Basel) 10(7), 1096 (2022).
Medline CASGoogle Scholar
28. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 32(7), 1335–1343 (2009).
Medline CASGoogle Scholar
29. Saisho Y. Postprandial C-peptide to glucose ratio as a marker of β cell function: implication for the management of type 2 diabetes. Int. J. Mol. Sci. 17(5), 744 (2016).
MedlineGoogle Scholar
30. Mortensen HB, Hougaard P, Swift P et al. New definition for the partial remission period in children and adolescents with type 1 diabetes. Diabetes Care 32(8), 1384–1390 (2009).
Medline CASGoogle Scholar
31. Caprio M, Infante M, Calanchini M, Mammi C, Fabbri A. Vitamin D: not just the bone. Evidence for beneficial pleiotropic extraskeletal effects. Eat. Weight Disord. 22(1), 27–41 (2017).
MedlineGoogle Scholar
32. Caprio M, Mammi C, Rosano GM. Vitamin D: a novel player in endothelial function and dysfunction. Arch. Med. Sci. 8(1), 4–5 (2012).
MedlineGoogle Scholar
33. Pinheiro MM, Fabbri A, Infante M. Cytokine storm modulation in COVID-19: a proposed role for vitamin D and DPP-4 inhibitor combination therapy (VIDPP-4i). Immunotherapy 13(9), 753–765 (2021).
CASGoogle Scholar
34. Pinheiro MM, Pinheiro FMM, Diniz SN, Fabbri A, Infante M. Combination of vitamin D and dipeptidyl peptidase-4 inhibitors (VIDPP-4i) as an immunomodulation therapy for autoimmune diabetes. Int. Immunopharmacol. 95, 107518 (2021).
Medline CASGoogle Scholar
35. Maia Pinheiro M, Moura Maia Pinheiro F, Pires Amaral Resende LL, Nogueira Diniz S, Fabbri A, Infante M. Improvement of pure sensory mononeuritis multiplex and IgG1 deficiency with sitagliptin plus Vitamin D3. Eur. Rev. Med. Pharmacol. Sci. 24(15), 8151–8159 (2020).
MedlineGoogle Scholar
36. Maia Pinheiro M, Maia Pinheiro FM, Amaral Resende LLP, Diniz SN, Fabbri A, Infante M. 36-month follow-up of a pure sensory mononeuritis multiplex and IgG1 deficiency improved after treatment with sitagliptin and vitamin D3. Eur. Rev. Med. Pharmacol. Sci. 25(4), 1768–1769 (2021).
MedlineGoogle Scholar
37. Charoenngam N, Holick MF. Immunologic effects of vitamin D on human health and disease. Nutrients 12(7), 2097 (2020).
Medline CASGoogle Scholar
38. Erlich H, Valdes AM, Noble J et al. HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families. Diabetes 57(4), 1084–1092 (2008).
Medline CASGoogle Scholar
39. Van der Auwera B, Van Waeyenberge C, Schuit F et al. DRB1*0403 protects against IDDM in Caucasians with the high-risk heterozygous DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 genotype. Belgian Diabetes Registry. Diabetes 44(5), 527–530 (1995).
MedlineGoogle Scholar
40. Garcia-Prat M, Álvarez-Sierra D, Aguiló-Cucurull A et al. Extended immunophenotyping reference values in a healthy pediatric population. Cytometry B Clin. Cytom. 96(3), 223–233 (2019).
Medline CASGoogle Scholar
41. Yazidi M, Mahjoubi S, Oueslati I, Chaker F, Chihaoui M. The remission phase in adolescents and young adults with newly diagnosed type 1 diabetes mellitus: prevalence, predicting factors and glycemic control during follow-up. Arch. Endocrinol. Metab. 66(2), 222–228 (2022).
MedlineGoogle Scholar
42. Erlich HA, Zeidler A, Chang J et al. HLA class II alleles and susceptibility and resistance to insulin dependent diabetes mellitus in Mexican–American families. Nat. Genet. 3(4), 358–364 (1993).
Medline CASGoogle Scholar
43. Payami H, Joe S, Farid NR et al. Relative predispositional effects (RPEs) of marker alleles with disease: HLA-DR alleles and Graves disease. Am. J. Hum. Genet. 45(4), 541–546 (1989).
Medline CASGoogle Scholar
44. Rickels MR, Evans-Molina C, Bahnson HT et al. High residual C-peptide likely contributes to glycemic control in type 1 diabetes. J. Clin. Invest. 130(4), 1850–1862 (2020).
Medline CASGoogle Scholar
45. Davis AK, DuBose SN, Haller MJ et al. Prevalence of detectable C-peptide according to age at diagnosis and duration of type 1 diabetes. Diabetes Care 38(3), 476–481 (2015).
Medline CASGoogle Scholar
46. Gomez-Muñoz L, Perna-Barrull D, Caroz-Armayones JM et al. Candidate biomarkers for the prediction and monitoring of partial remission in pediatric type 1 diabetes. Front. Immunol. 13, 825426 (2022).
Medline CASGoogle Scholar
47. Palmer JP. C-peptide in the natural history of type 1 diabetes. Diabetes Metab. Res. Rev. 25(4), 325–328 (2009).
Medline CASGoogle Scholar
48. Nigi L, Maccora C, Dotta F, Sebastiani G. From immunohistological to anatomical alterations of human pancreas in type 1 diabetes: new concepts on the stage. Diabetes Metab. Res. Rev. 36(4), e3264 (2020).
MedlineGoogle Scholar
49. Planas R, Carrillo J, Sanchez A et al. Gene expression profiles for the human pancreas and purified islets in type 1 diabetes: new findings at clinical onset and in long-standing diabetes. Clin. Exp. Immunol. 159(1), 23–44 (2010).
Medline CASGoogle Scholar
50. Li Y, Liu Y, Chu CQ. Th17 cells in type 1 diabetes: role in the pathogenesis and regulation by gut microbiome. Mediators Inflamm. 2015, 638470 (2015).
MedlineGoogle Scholar
51. Martin-Orozco N, Chung Y, Chang SH, Wang YH, Dong C. Th17 cells promote pancreatic inflammation but only induce diabetes efficiently in lymphopenic hosts after conversion into Th1 cells. Eur. J. Immunol. 39(1), 216–224 (2009).
Medline CASGoogle Scholar
52. Visperas A, Vignali DA. Are regulatory T cells defective in type 1 diabetes and can we fix them? J. Immunol. 197(10), 3762–3770 (2016).
Medline CASGoogle Scholar
53. Hull CM, Peakman M, Tree TIM. Regulatory T cell dysfunction in type 1 diabetes: what’s broken and how can we fix it? Diabetologia 60(10), 1839–1850 (2017).
Medline CASGoogle Scholar
54. Sanda S, Roep BO, von Herrath M. Islet antigen specific IL-10⁺ immune responses but not CD4⁺CD25⁺FoxP3⁺ cells at diagnosis predict glycemic control in type 1 diabetes. Clin. Immunol. 127(2), 138–143 (2008).
Medline CASGoogle Scholar
55. Simon Q, Pers JO, Cornec D, Le Pottier L, Mageed RA, Hillion S. In-depth characterization of CD24(high)CD38(high) transitional human B cells reveals different regulatory profiles. J. Allergy Clin. Immunol. 137(5), 1577–1584.e10 (2016).
Medline CASGoogle Scholar
56. Federico G, Focosi D, Marchi B et al. Administering 25-hydroxyvitamin D3 in vitamin D-deficient young type 1A diabetic patients reduces reactivity against islet autoantigens. Clin. Nutr. 33(6), 1153–1156 (2014). •• Provides insights into the protective actions of calcifediol against β-cell autoimmunity in patients with new-onset type 1 diabetes.
Medline CASGoogle Scholar
57. Yu J, Sharma P, Girgis CM, Gunton JE. Vitamin D and beta cells in type 1 diabetes: a systematic review. Int. J. Mol. Sci. 23(22), 14434 (2022).
Medline CASGoogle Scholar
58. Nwosu BU, Parajuli S, Jasmin G et al. Ergocalciferol in new-onset type 1 diabetes: a randomized controlled trial. J. Endocr. Soc. 6(1), bvab179 (2022).
MedlineGoogle Scholar
59. Charoenngam N, Shirvani A, Holick MF. Vitamin D and its potential benefit for the COVID-19 pandemic. Endocr. Pract. 27(5), 484–493 (2021).
MedlineGoogle Scholar
60. Infante M, Ricordi C, Baidal DA et al. VITAL study: an incomplete picture? Eur. Rev. Med. Pharmacol. Sci. 23(7), 3142–3147 (2019).
Medline CASGoogle Scholar
61. Infante M, Sears B, Rizzo AM et al. Omega-3 PUFAs and vitamin D co-supplementation as a safe–effective therapeutic approach for core symptoms of autism spectrum disorder: case report and literature review. Nutr. Neurosci. 23(10), 779–790 (2018).
MedlineGoogle Scholar
62. Infante M, Fabbri A, Della-Morte D, Ricordi C. The importance of vitamin D and omega-3 PUFA supplementation: a nonpharmacologic immunomodulation strategy to halt autoimmunity. Eur. Rev. Med. Pharmacol. Sci. 26(18), 6787–6795 (2022).
Medline CASGoogle Scholar
63. Overbergh L, Decallonne B, Valckx D et al. Identification and immune regulation of 25-hydroxyvitamin D-1-alpha-hydroxylase in murine macrophages. Clin. Exp. Immunol. 120(1), 139–146 (2000).
Medline CASGoogle Scholar
64. Korf H, Wenes M, Stijlemans B et al. 1,25-Dihydroxyvitamin D3 curtails the inflammatory and T cell stimulatory capacity of macrophages through an IL-10-dependent mechanism. Immunobiology 217(12), 1292–1300 (2012).
Medline CASGoogle Scholar
65. Ferreira GB, van Etten E, Verstuyf A et al. 1,25-Dihydroxyvitamin D3 alters murine dendritic cell behaviour in vitro and in vivo. Diabetes Metab. Res. Rev. 27(8), 933–941 (2011).
Medline CASGoogle Scholar
66. Zhang X, Zhou M, Guo Y, Song Z, Liu B. 1,25-Dihydroxyvitamin D₃ promotes high glucose-induced M1 macrophage switching to M2 via the VDR-PPARγ signaling pathway. Biomed. Res. Int. 2015, 157834 (2015).
MedlineGoogle Scholar
67. Jeffery LE, Burke F, Mura M et al. 1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J. Immunol. 183(9), 5458–5467 (2009).
Medline CASGoogle Scholar
68. Overbergh L, Decallonne B, Waer M et al. 1α,25-dihydroxyvitamin D3 induces an autoantigen-specific T-helper 1/T-helper 2 immune shift in NOD mice immunized with GAD65 (p 524–543). Diabetes 49(8), 1301–1307 (2000).
Medline CASGoogle Scholar
69. Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, O’Garra A. 1α,25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J. Immunol. 167(9), 4974–4980 (2001).
Medline CASGoogle Scholar
70. Bouillon R, Lieben L, Mathieu C, Verstuyf A, Carmeliet G. Vitamin D action: lessons from VDR and Cyp27b1 null mice. Pediatr. Endocrinol. Rev. 10(Suppl. 2), 354–366 (2013).
MedlineGoogle Scholar
71. Holick MF. The use and interpretation of assays for vitamin D and its metabolites. J. Nutr. 120(Suppl. 11), 1464–1469 (1990).
Medline CASGoogle Scholar
72. Wootton AM. Improving the measurement of 25-hydroxyvitamin D. Clin. Biochem. Rev. 26(1), 33–36 (2005).
MedlineGoogle Scholar
73. Smith JE, Goodman DS. The turnover and transport of vitamin D and of a polar metabolite with the properties of 25-hydroxycholecalciferol in human plasma. J. Clin. Invest. 50(10), 2159–2167 (1971).
Medline CASGoogle Scholar
74. Infante M, Ricordi C. Editorial – Moving forward on the pathway of targeted immunotherapies for type 1 diabetes: the importance of disease heterogeneity. Eur. Rev. Med. Pharmacol. Sci. 23(19), 8702–8704 (2019).
Medline CASGoogle Scholar
75. Infante M, Alejandro R, Fabbri A, Ricordi C. Chapter 5. The heterogeneity of type 1 diabetes: from immunopathology to immune intervention. In: Translational Autoimmunity (1st Edition), Volume 4. Rezaei N (Ed.). Academic Press, MA, USA, 83–104 (2022).
Google Scholar
76. Nwosu BU. The theory of hyperlipidemic memory of type 1 diabetes. Front. Endocrinol. 13, 819544 (2022). • Provides relevant information on the pathophysiology of the remission phase in patients with T1D.
MedlineGoogle Scholar

Vol. 15, No. 13

Supplemental Materials

Metrics

Downloaded 76 times

History

Received 21 October 2022

Accepted 15 June 2023

Published online 4 July 2023

Published in print September 2023

Information

Keywords

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/imt-2022-0266

Author contributions

Conceptualization, writing (original draft preparation) and patient management: M Infante. Literature search: M Infante, L Vitiello and N Padilla. Flow cytometric immunophenotyping of peripheral blood lymphocytes: L Vitiello. Visualization: P Di Perna, A Fabbri, F Pacifici, M Passeri, M Caprio, D Della-Morte. Supervision: C Ricordi, L Uccioli. All authors have read and agreed to the published version of the manuscript.

Acknowledgments

The authors thank the patient for giving consent to publish this manuscript.

Financial & competing interests disclosure

L Vitiello was partly supported by the Italian Ministry of Health (‘Ricerca corrente’ granted to IRCCS San Raffaele Roma). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript, apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties. This research received no external funding, and the authors declare no conflict of interest.

No writing assistance was utilized in the production of this manuscript.

Informed consent disclosure

The authors state that they have obtained verbal and written informed consent from the patient/patients for the inclusion of their medical and treatment history within this case report.

PDF download