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Cited by 449Diabetes and associated disordersPancreatic function and diabetesDiabetes Management and Research

C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus

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Couri, Carlos E. B.·2009·JAMA
DOI 10.1001/jama.2009.470
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Abstract

CONTEXT: In 2007, the effects of the autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) in 15 patients with type 1 diabetes mellitus (DM) were reported. Most patients became insulin free with normal levels of glycated hemoglobin A(1c) (HbA(1c)) during a mean 18.8-month follow-up. To investigate if this effect was due to preservation of beta-cell mass, continued monitoring was performed of C-peptide levels after stem cell transplantation in the 15 original and 8 additional patients. OBJECTIVE: To determine C-peptide levels after autologous nonmyeloablative HSCT in patients with newly diagnosed type 1 DM during a longer follow-up. DESIGN, SETTING, AND PARTICIPANTS: A prospective phase 1/2 study of 23 patients with type 1 DM (aged 13-31 years) diagnosed in the previous 6 weeks by clinical findings with hyperglycemia and confirmed by measurement of serum levels of anti-glutamic acid decarboxylase antibodies. Enrollment was November 2003-April 2008, with follow-up until December 2008 at the Bone Marrow Transplantation Unit of the School of Medicine of Ribeirão Preto, Ribeirão Preto, Brazil. Hematopoietic stem cells were mobilized via the 2007 protocol. MAIN OUTCOME MEASURES: C-peptide levels measured during the mixed-meal tolerance test, before, and at different times following HSCT. Secondary end points included morbidity and mortality from transplantation, temporal changes in exogenous insulin requirements, and serum levels of HbA(1c). RESULTS: During a 7- to 58-month follow-up (mean, 29.8 months; median, 30 months), 20 patients without previous ketoacidosis and not receiving corticosteroids during the preparative regimen became insulin free. Twelve patients maintained this status for a mean 31 months (range, 14-52 months) and 8 patients relapsed and resumed insulin use at low dose (0.1-0.3 IU/kg). In the continuous insulin-independent group, HbA(1c) levels were less than 7.0% and mean (SE) area under the curve (AUC) of C-peptide levels increased significantly from 225.0 (75.2) ng/mL per 2 hours pretransplantation to 785.4 (90.3) ng/mL per 2 hours at 24 months posttransplantation (P < .001) and to 728.1 (144.4) ng/mL per 2 hours at 36 months (P = .001). In the transient insulin-independent group, mean (SE) AUC of C-peptide levels also increased from 148.9 (75.2) ng/mL per 2 hours pretransplantation to 546.8 (96.9) ng/mL per 2 hours at 36 months (P = .001), which was sustained at 48 months. In this group, 2 patients regained insulin independence after treatment with sitagliptin, which was associated with increase in C-peptide levels. Two patients developed bilateral nosocomial pneumonia, 3 patients developed late endocrine dysfunction, and 9 patients developed oligospermia. There was no mortality. CONCLUSION: After a mean follow-up of 29.8 months following autologous nonmyeloablative HSCT in patients with newly diagnosed type 1 DM, C-peptide levels increased significantly and the majority of patients achieved insulin independence with good glycemic control. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00315133.

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  • The effects of autologous haematopoietic stem-cell transplantation waned over time, with loss of insulin independence in most patients after 5 years.

    “However, the effects of this invasive treat ment waned over time, with loss of insulin independence in most patients after 5 years.145”

    From Type 1 diabetes (2014) · cites this paper as [145]

    The Results (page not provided) report that 8 of 20 patients who became insulin-free later resumed insulin, supporting some waning of the effect. But 12 remained insulin-free during follow-up, which lasted at most 58 months; this paper does not establish that most patients lost insulin independence after five years. (LLM, conf=0.90)

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  • Autologous haemopoietic stem-cell transplantation and autologous T-regulatory cell administration are other novel approaches.

    “Other novel approaches include autologous haemopoietic stem-cell transplantation165,166 and autologous T-regulatory cell administration.167–169”

    From Type 1 diabetes (2018) · cites this paper as [166]

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Research works printed but not linked: 2

  1. The Diabetes Control and Complications Trial Re- search Group. Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the Diabetes Control and Complications Trial. Ann In- tern Med. 1998;128(7):517-523.
  2. Eisenbarth GS, Gottlieb PA. Autoimmune poly- endocrine syndromes. N Engl J Med. 2004;350 (20):2068-2079.

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Authors
Couri, C. E. B.
Affiliations
Universidade de São Paulo (BR)
Corresponding author
Couri, Carlos E. B.
ORCID
Couri, Carlos E. B.
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2009-04-15
Volume
301
Issue
15
Pages
1573
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2009.470
OpenAlex
W2115936490
Cited by
449
References
27
Citations by year
2026: 5 · 2025: 9 · 2024: 23 · 2023: 14 · 2022: 18 · 2021: 19 · 2020: 14 · 2019: 14 · 2018: 20 · 2017: 24 · 2016: 28 · 2015: 25 · 2014: 44 · 2013: 43 · 2012: 42
FWCI
28.50
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
type 1 diabetes, autologous stem cell transplantation, nonmyeloablative conditioning, insulin independence, beta-cell function, newly diagnosed diabetes, HbA1c, mixed meal tolerance test, glutamic acid decarboxylase antibodies, insulin requirement, recurrence, stem cell mobilization, young adults, children and adolescents, long-term follow-up
MeSH terms
Adolescent, Adult, C-Peptide, Diabetes Mellitus, Type 1, Female, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin, Male, Prospective Studies, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation, Transplantation Conditioning, Hematopoietic Stem Cell Mobilization, Young Adult

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