02982nas a2200277   4500000000100000008004100001100001900042700001100061700001600072700002100088700001700109700001700126700001600143700002000159700002100179700001700200700001700217700001700234700002000251700001800271245015000289300000700439490000600446520223800452022001402690       2017                            d1 aMarwaha Neelam1 aJha V.1 aYadav Ashok1 aBhansali Shobhit1 aDutta Pinaki1 aYadav Mukesh1 aJain Ashish1 aMudaliar Sunder1 aHawkins Meredith1 aKurpad Anura1 aPahwa Deepak1 aSharma Ratti1 aBhansali Shipra1 aBhansali Anil00aAutologous bone marrow-derived mononuclear cells transplantation in type 2 diabetes mellitus: effect on β-cell function and insulin sensitivity.  a500 v93 a<p>
<b>BACKGROUND: </b>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.
</p>

<p>
<b>METHODS: </b>Seven T2DM patients with the duration of disease&nbsp;≥5&nbsp;years, receiving triple oral anti-diabetic drugs along with insulin (≥0.4&nbsp;IU per kg per day) and HbA1c&nbsp;≤&nbsp;7.5% (≤58.0&nbsp;mmol/mol) were enrolled for ABM-MNCs administration through a targeted approach. The primary end-point was a reduction in insulin requirement by&nbsp;≥50% from baseline, while maintaining HbA1c&nbsp;&lt;&nbsp;7.0% (&lt;53.0&nbsp;mmol/mol) with improvement in insulin secretion, and/or insulin sensitivity after ABM-MNCs transplantation.
</p>

<p>
<b>RESULTS: </b>Six out of 7 (90%) patients achieved the primary end-point. At 6&nbsp;months, there was a significant reduction in insulin requirement by 51% as compared to baseline (p&nbsp;&lt;&nbsp;0.003). This was accompanied by a significant increase in the 2nd phase C-peptide response during hyperglycemic clamp (p&nbsp;=&nbsp;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.
</p>

<p>
<b>CONCLUSION: </b>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.
</p>
  a1758-5996