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Volume: 15 Issue: 1 February 2017 - Supplement - 1

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Leptin Levels in Patients with Type 1 Diabetes Mellitus After Fetal Pancreatic Stem Cell Transplant

Objectives: Our objective was to determine leptin levels in patients with type 1 diabetes mellitus after fetal pancreatic stem cell transplant.

Materials and Methods: Seven patients, aged 20 to 42 years, with type 1 diabetes mellitus received a fetal pancreatic stem cell transplant by intravenous infusion. The quantity of fetal stem cells infused was ≥ 5 × 106, and the cells were of 12 to 14 weeks of gestation. We analyzed the levels of leptin, C-peptide, and antibodies to the islets of Langerhans before and 3 months after the transplant procedure.

Results: Fetal pancreatic stem cell transplant led to significant increases in leptin and C-peptide levels, from 4.63 ± 1.17 ng/mL and 0.09 ± 0.02 ng/mL to 7.71 ± 1.45 ng/mL (P < .05) and 0.22 ± 0.05 ng/mL (P < .005), respectively, without an increase in antibodies to the islets of Langerhans, which measured 0.64 ± 0.13 U/mL before transplant and 0.57 ± 0.18 U/mL 3 months later (P > .05).

Conclusions: Leptin levels increase significantly within 3 months of fetal pancreatic stem cell transplant in patients with type 1 diabetes mellitus.


Key words : Adipokines, C-peptide, Pancreatic islet cell regeneration

Introduction

Leptin is a peptide hormone, secreted by fat cells, that contributes to the control of glucose home­ostasis.1 Leptin receptors are widely expressed in the endocrine pancreas, liver, skeletal muscle, and adipose tissue.2 Leptin acts on the endocrine pancreas to inhibit insulin secretion from the β cells and glucagon secretion from the α cells. Leptin acts directly on skeletal muscle to either increase or decrease glucose uptake and insulin-stimulated glucose metabolism.1,2 Leptin also acts centrally on the hypothalamus, and this action concludes in the activation of leptin-responsive relays to the endocrine pancreas and insulin-sensitive tissues through the sympathetic and parasympathetic nervous systems.1-3 Leptin might have clinical relevance for treating hyperglycemia, particularly in patients with conditions of leptin deficiency such as lipodystrophy and type 1 diabetes mellitus (DM).

Fetal pancreatic stem cell transplant (FPSCT) is among the potentially effective therapeutic ap­proaches to regenerating islet cells.4,5 Thus, the dynamics of leptin levels in patients with type 1 DM after FPSCT is considered a scientifically interesting subject.

Materials and Methods

This case series included 7 patients, ranging in age from 20 to 42 years, with type 1 DM who underwent FPSCT. All patients were on insulin therapy. The stem cells were extracted from the pancreatic tissue of an aborted fetus at 12 to 14 weeks of gestation and infused intravenously at a rate of 50 mL/hour. The quantity of fetal stem cells infused was ≥ 5 × 106. Before the procedure and 3 months after FSCT, the levels of C-peptide, leptin, and antibodies to the islets of Langerhans were analyzed.

This study and its methods were approved by the Local Ethics Committee of the institute. All of the protocols conformed with the ethical guidelines of the 1975 Helsinki Declaration. All participants signed written informed consent.

Statistical analyses were performed using software (Statistica version 6.0, StatSoft Inc., Tulsa, OK, USA). Clinical assessments were calculated using average, margins of error, and standard deviations. To com­pare independent groups, we used the nonpa­ra­metric Mann-Whitney U test.

Results

Before the FPCST procedure, all the patients had poor glycemic control with a hemoglobin A1c level greater than 7%. Before FPSCT, all patients had mean leptin levels of 4.63 ± 1.17 ng/mL and mean C-peptide levels of 0.09 ± 0.02 ng/mL. These levels were below the lower limit of normal levels (Table 1).

On the day of FPSCT, the patients continued to receive intensified subcutaneous insulin therapy. The dose was adjusted according to the metabolism performance level, which was examined once every 3 hours during the first day after FPSCT. Over the subsequent 3 days, patients’ fasting and postprandial glucose levels were well controlled. We did not observe any complications after the FPSCT pro­cedure.

The initial laboratory data and the changes after FPSCT are presented in Table 1. A significant increase in leptin levels was seen 3 months after FPSCP, from 4.63 ± 1.17 ng/mL to 7.71 ± 1.45 ng/mL (P < .05). The C-peptide level also increased, from 0.09 ± 0.02 ng/mL to 0.22 ± 0.05 ng/mL (P < .005). Levels of antibodies to the islets of Langerhans did not show a significant change, with a mean value of 0.64 ± 0.13 U/mL before FPSCT and 0.57 ± 0.18 U/mL 3 months later (P > .05).

Discussion

Decreased baseline leptin levels in patients with type 1 DM are due to the presence of leptin deficiency and leptin resistance affecting glucose metabolism, a finding seen in both rodents and humans.6,7 Three months after FPSCT, patients with type 1 DM showed significantly increased leptin and C-peptide levels. Similar increases in C-peptide levels have been noted in previous studies. In these studies, as in our study, patients did not receive immuno­suppressive therapy.5,8,9 The observed significant increases in leptin and C-peptide levels in our study may indicate the efficacy of FPSCT.3

We observed that leptin and C-peptide levels increased significantly 3 months after FPSCT in patients with type 1 DM. These increased levels, without an increase in antibodies to the islets of Langerhans, may serve as confirmation of the efficacy of FPSCT in patients with type 1 DM.


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Volume : 15
Issue : 1
Pages : 194 - 195
DOI : 10.6002/ect.mesot2016.P77


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From the 1Department of Internal Medicine, 2Chairman of the Board, 3Department of Clinical Laboratory, and 4Department of Fetal Cells Transplantation, National Scientific Medical Research Center, Astana, Kazakhstan
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Olga Ulyanova, Department of Internal Medicine, National Scientific Medical Research Center, 010009, Ave. Abylay-khan #42, Astana, Kazakhstan
Phone: +7 70 1383 8107
E-mail: olga_ulyanova@rambler.ru