Autologous bone marrow-derived mononuclear cells transplantation in type 2 diabetes mellitus: Effect on β-cell function and insulin sensitivity NCT01759823 NCT

Shobhit Bhansali, Pinaki Dutta, Mukesh Kumar Yadav, Ashish Jain, Sunder Mudaliar, Meredith A. Hawkins, Anura V. Kurpad, Deepak Pahwa, Ashok Kumar Yadav, Ratti Ram Sharma, Vivekanand Jha, Neelam Marwaha, Shipra Bhansali, Anil Bhansali

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Insulin resistance and insulin deficiency are the cardinal defects in the pathogenesis of type 2 diabetes mellitus (T2DM). Despite the plethora of anti-diabetic medications, drugs specifically targeting the β-cells are still desired. Stem cell therapy has emerged as a novel therapeutics strategy to target β-cells; however, their mechanism of action has not been well defined. This study aims to examine the efficacy and safety of autologous bone marrow-derived mononuclear cells (ABM-MNCs) transplantation in T2DM, and explores the mechanistic insights into stem cells action through metabolic studies. Methods: Seven T2DM patients with the duration of disease ≥5 years, receiving triple oral anti-diabetic drugs along with insulin (≥0.4 IU per kg per day) and HbA1c ≤ 7.5% (≤58.0 mmol/mol) were enrolled for ABM-MNCs administration through a targeted approach. The primary end-point was a reduction in insulin requirement by ≥50% from baseline, while maintaining HbA1c < 7.0% (<53.0 mmol/mol) with improvement in insulin secretion, and/or insulin sensitivity after ABM-MNCs transplantation. Results: Six out of 7 (90%) patients achieved the primary end-point. At 6 months, there was a significant reduction in insulin requirement by 51% as compared to baseline (p < 0.003). This was accompanied by a significant increase in the 2nd phase C-peptide response during hyperglycemic clamp (p = 0.018), whereas there were no significant alterations in insulin sensitivity and glucose disposal rate during hyperinsulinemic-euglycemic clamp relative to the baseline. Other measures of β-cell indices like HOMA-β, and stimulated C-peptide response to glucagon and mixed meal tolerance test were non-contributory. Conclusion: ABM-MNCs transplantation results in significant reduction in insulin doses and improvement in C-peptide response in patients with T2DM. Metabolic studies may be more useful than conventional indices to predict β-cell function in patients with advanced duration of T2DM. Trial registration -Clinicaltrials.gov NCT01759823

Original languageEnglish (US)
Article number50
JournalDiabetology and Metabolic Syndrome
Volume9
Issue number1
DOIs
StatePublished - Jul 4 2017

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Cell Transplantation
Type 2 Diabetes Mellitus
Insulin Resistance
Bone Marrow
Insulin
C-Peptide
Stem Cells
Glucose Clamp Technique
Drug Delivery Systems
Cell- and Tissue-Based Therapy
Glucagon
Meals
Safety
Glucose
Pharmaceutical Preparations

Keywords

  • Autologous bone marrow-derived mononuclear cells
  • Stem cells
  • T2DM

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Autologous bone marrow-derived mononuclear cells transplantation in type 2 diabetes mellitus : Effect on β-cell function and insulin sensitivity NCT01759823 NCT. / Bhansali, Shobhit; Dutta, Pinaki; Yadav, Mukesh Kumar; Jain, Ashish; Mudaliar, Sunder; Hawkins, Meredith A.; Kurpad, Anura V.; Pahwa, Deepak; Yadav, Ashok Kumar; Sharma, Ratti Ram; Jha, Vivekanand; Marwaha, Neelam; Bhansali, Shipra; Bhansali, Anil.

In: Diabetology and Metabolic Syndrome, Vol. 9, No. 1, 50, 04.07.2017.

Research output: Contribution to journalArticle

Bhansali, S, Dutta, P, Yadav, MK, Jain, A, Mudaliar, S, Hawkins, MA, Kurpad, AV, Pahwa, D, Yadav, AK, Sharma, RR, Jha, V, Marwaha, N, Bhansali, S & Bhansali, A 2017, 'Autologous bone marrow-derived mononuclear cells transplantation in type 2 diabetes mellitus: Effect on β-cell function and insulin sensitivity NCT01759823 NCT', Diabetology and Metabolic Syndrome, vol. 9, no. 1, 50. https://doi.org/10.1186/s13098-017-0248-7
Bhansali, Shobhit ; Dutta, Pinaki ; Yadav, Mukesh Kumar ; Jain, Ashish ; Mudaliar, Sunder ; Hawkins, Meredith A. ; Kurpad, Anura V. ; Pahwa, Deepak ; Yadav, Ashok Kumar ; Sharma, Ratti Ram ; Jha, Vivekanand ; Marwaha, Neelam ; Bhansali, Shipra ; Bhansali, Anil. / Autologous bone marrow-derived mononuclear cells transplantation in type 2 diabetes mellitus : Effect on β-cell function and insulin sensitivity NCT01759823 NCT. In: Diabetology and Metabolic Syndrome. 2017 ; Vol. 9, No. 1.
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T1 - Autologous bone marrow-derived mononuclear cells transplantation in type 2 diabetes mellitus

T2 - Effect on β-cell function and insulin sensitivity NCT01759823 NCT

AU - Bhansali, Shobhit

AU - Dutta, Pinaki

AU - Yadav, Mukesh Kumar

AU - Jain, Ashish

AU - Mudaliar, Sunder

AU - Hawkins, Meredith A.

AU - Kurpad, Anura V.

AU - Pahwa, Deepak

AU - Yadav, Ashok Kumar

AU - Sharma, Ratti Ram

AU - Jha, Vivekanand

AU - Marwaha, Neelam

AU - Bhansali, Shipra

AU - Bhansali, Anil

PY - 2017/7/4

Y1 - 2017/7/4

N2 - Background: Insulin resistance and insulin deficiency are the cardinal defects in the pathogenesis of type 2 diabetes mellitus (T2DM). Despite the plethora of anti-diabetic medications, drugs specifically targeting the β-cells are still desired. Stem cell therapy has emerged as a novel therapeutics strategy to target β-cells; however, their mechanism of action has not been well defined. This study aims to examine the efficacy and safety of autologous bone marrow-derived mononuclear cells (ABM-MNCs) transplantation in T2DM, and explores the mechanistic insights into stem cells action through metabolic studies. Methods: Seven T2DM patients with the duration of disease ≥5 years, receiving triple oral anti-diabetic drugs along with insulin (≥0.4 IU per kg per day) and HbA1c ≤ 7.5% (≤58.0 mmol/mol) were enrolled for ABM-MNCs administration through a targeted approach. The primary end-point was a reduction in insulin requirement by ≥50% from baseline, while maintaining HbA1c < 7.0% (<53.0 mmol/mol) with improvement in insulin secretion, and/or insulin sensitivity after ABM-MNCs transplantation. Results: Six out of 7 (90%) patients achieved the primary end-point. At 6 months, there was a significant reduction in insulin requirement by 51% as compared to baseline (p < 0.003). This was accompanied by a significant increase in the 2nd phase C-peptide response during hyperglycemic clamp (p = 0.018), whereas there were no significant alterations in insulin sensitivity and glucose disposal rate during hyperinsulinemic-euglycemic clamp relative to the baseline. Other measures of β-cell indices like HOMA-β, and stimulated C-peptide response to glucagon and mixed meal tolerance test were non-contributory. Conclusion: ABM-MNCs transplantation results in significant reduction in insulin doses and improvement in C-peptide response in patients with T2DM. Metabolic studies may be more useful than conventional indices to predict β-cell function in patients with advanced duration of T2DM. Trial registration -Clinicaltrials.gov NCT01759823

AB - Background: Insulin resistance and insulin deficiency are the cardinal defects in the pathogenesis of type 2 diabetes mellitus (T2DM). Despite the plethora of anti-diabetic medications, drugs specifically targeting the β-cells are still desired. Stem cell therapy has emerged as a novel therapeutics strategy to target β-cells; however, their mechanism of action has not been well defined. This study aims to examine the efficacy and safety of autologous bone marrow-derived mononuclear cells (ABM-MNCs) transplantation in T2DM, and explores the mechanistic insights into stem cells action through metabolic studies. Methods: Seven T2DM patients with the duration of disease ≥5 years, receiving triple oral anti-diabetic drugs along with insulin (≥0.4 IU per kg per day) and HbA1c ≤ 7.5% (≤58.0 mmol/mol) were enrolled for ABM-MNCs administration through a targeted approach. The primary end-point was a reduction in insulin requirement by ≥50% from baseline, while maintaining HbA1c < 7.0% (<53.0 mmol/mol) with improvement in insulin secretion, and/or insulin sensitivity after ABM-MNCs transplantation. Results: Six out of 7 (90%) patients achieved the primary end-point. At 6 months, there was a significant reduction in insulin requirement by 51% as compared to baseline (p < 0.003). This was accompanied by a significant increase in the 2nd phase C-peptide response during hyperglycemic clamp (p = 0.018), whereas there were no significant alterations in insulin sensitivity and glucose disposal rate during hyperinsulinemic-euglycemic clamp relative to the baseline. Other measures of β-cell indices like HOMA-β, and stimulated C-peptide response to glucagon and mixed meal tolerance test were non-contributory. Conclusion: ABM-MNCs transplantation results in significant reduction in insulin doses and improvement in C-peptide response in patients with T2DM. Metabolic studies may be more useful than conventional indices to predict β-cell function in patients with advanced duration of T2DM. Trial registration -Clinicaltrials.gov NCT01759823

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