Dynamics of Sex Hormones in Men with Diabetes Mellitus After Autologous Mesenchymal Stem Cell Transplant.

OBJECTIVES: Our goal was to determine levels of sex hormones in men with type 1 diabetes mellitus and type 2 diabetes mellitus after autologous mesenchymal stem cell transplant. MATERIALS AND METHODS: We examined 10 male patients (32-56 years old) with type 1 diabetes mellitus and type 2 diabetes mellitus, whom we subsequently divided into 2 groups and examined. Group 1 comprised 5 male patients who received autologous mesenchymal stem cell transplant (cells were obtained from patient's iliac crest and cultured for 3-4 weeks) by intravenous infusion. Group 2 comprised 5 male patients (control group) who were on hypoglycemic tablet therapy or insulin therapy. The quantity of autologous mesenchymal stem cells infused was 95 × 106 to 97 × 106 cells. We analyzed levels of testosterone, luteinizing hormone, estradiol, and glycated hemoglobin in patients both before and 3 months after the autologous mesenchymal stem cell transplant procedure. RESULTS: In men with type 1 diabetes mellitus and type 2 diabetes mellitus, autologous mesenchymal stem cell transplant led to an increase in testosterone levels from 5.31 ± 2.12 to 6.33 ± 2.12 ng/mL (P = .82), a decrease in luteinizing hormone from 8.43 ± 1.25 to 5.94 ± 1.57 mIU/mL (P = .04), and a decrease in glycated hemoglobin from 9.45 ± 1.24% to 8.53 ± 1.08% (P = .25) after 3 months. The increase in testosterone in men with autologous mesenchymal stem cell transplant group of 6.33 ± 2.12 ng/mL was significant compared with men in the control group (3.9 ± 1.18 ng/mL; P = .01). CONCLUSIONS: Testosterone level increased and luteinizing hormone level decreased within 3 months after autologous mesenchymal stem cell transplant in men with diabetes mellitus.

Elevated Levels of Plasma Collagen Triple Helix Repeat Containing 1 (CTHRC1) Are Strongly Associated with eGFR and Albuminuria in Chronic Kidney Disease.

Background: Chronic kidney disease (CKD) has various etiologies, making it impossible to fully understand its complex pathophysiology. Elevated levels of plasma creatinine, proteinuria, and albuminuria and declined eGFR are traits observed in CKD patients. The current study attempts to highlight the collagen triple helix repeat containing 1 (CTHRC1) protein as a putative blood biomarker for CKD in addition to existing recognized indicators of CKD progression. Methods: A total of 26 CKD patients and 18 healthy controls were enrolled in this study. Clinical characteristics and complete blood and biochemical analyses were collected, and human ELISA kits were used to detect possible CKD biomarkers. Results: The study's findings showed that CTHRC1 correlates with key clinical markers of kidney function such as 24 h urine total protein, creatinine, urea, and uric acid. In addition, CTHRC1 demonstrated a strong significant difference (p ≤ 0.0001) between the CKD and control group. Conclusions: Our research demonstrates that the plasma level of CTHRC1 can distinguish between those with CKD and healthy patients. Plasma CTHRC1 levels may aid in the diagnosis of CKD given the current state of knowledge, and these results call for further investigation in a wider, more diverse patient group.

Urinary Protein Profiling for Potential Biomarkers of Chronic Kidney Disease: A Pilot Study.

Proteinuria is a risk factor for chronic kidney disease (CKD) progression and associated complications. However, there is insufficient information on individual protein components in urine and the severity of CKD. We aimed to investigate urinary proteomics and its association with proteinuria and kidney function in early-stage CKD and in healthy individuals. A 24 h urine sample of 42 individuals (21-CKD and 21-healthy individuals) was used for mass spectrometry-based proteomics analysis. An exponentially modified protein abundance index (emPAI) was calculated for each protein. Data were analyzed by Mascot software using the SwissProt database and bioinformatics tools. Overall, 298 unique proteins were identified in the cohort; of them, 250 proteins belong to the control group with median (IQR) emPAI 39.1 (19−53) and 142 proteins belong to the CKD group with median (IQR) emPAI 67.8 (49−117). The level of 24 h proteinuria positively correlated with emPAI (r = 0.390, p = 0.011). The emPAI of some urinary proteomics had close positive (ALBU, ZA2G, IGKC) and negative (OSTP, CD59, UROM, KNG1, RNAS1, CD44, AMBP) correlations (r < 0.419, p < 0.001) with 24 h proteinuria levels. Additionally, a few proteins (VTDB, AACT, A1AG2, VTNC, and CD44) significantly correlated with kidney function. In this proteomics study, several urinary proteins correlated with proteinuria and kidney function. Pathway analysis identified subpathways potentially related to early proteinuric CKD, allowing the design of prospective studies that explore their response to therapy and their relationship to long-term outcomes.

Reliability of the Multiplex CytoBead CeliAK Immunoassay to Assess Anti-tTG IgA for Celiac Disease Screening.

Background and Objective: The diagnosis of Celiac Disease (CD) is first based on the positivity for specific serological markers. The CytoBead CeliAK immunoassay simultaneously measures antibodies (IgA) directed to tissue transglutaminase (tTG), endomysium (EMA), and deamidated gliadin (DG), in addition to providing a control for total IgA levels. The aim of this study is to assess the reliability of this multiplex assay to detect anti-tTG IgA positive patients, compared with a conventional single-parameter enzyme-linked immunosorbent assay (ELISA). Methods: Serum samples from 149 pediatric patients were assessed by both CytoBead CeliAK immunoassay and ELISA, in order to evaluate their concordance for the measurement of anti-tTG IgA. Results: The measurement of anti-tTG IgA by CytoBead CeliAK immunoassay basically showed a complete concordance rate with the conventional and single-parameter ELISA, according to the respective cutoff values (3 U/ml and 10 U/ml). Conclusions: Our comparative analysis demonstrates a substantial equivalency between multiplex CytoBead CeliAK assay and the single-parameter conventional ELISA to assess anti-tTG IgA antibody in the context of the screening for CD in children. Importantly, CytoBead CeliAK assay could present some preanalytic, analytic, and economic advantages.

Integral Hematologic Indices in the Evaluation of the Immunologic Reactivity of the Organism in a Patient With Complication of Type 1 Diabetes Mellitus: A Case of Diabetic Retinopathy After Autologous Mesenchymal Stem Cell Transplant.

The search continues for pathogenetically effective measures in autoimmune processes for a number of complications of type 1 diabetes mellitus, in particular, diabetic retinopathy. However, there are few studies of the prognostic and therapeutic values of the systemic autoimmune response in this pathology after transplant of autologous mesenchymal stem cells. Here, we present a 40-year-old patient with complications of type 1 diabetes mellitus (diabetic retinopathy) after mesenchymal stem cell transplant. Based on peripheral blood results, we were able to calculate integral hematologic parameters, allowing us to indirectly assess the patient's immune system after autologous mesenchymal stem cell transplant. One month after autologous mesenchymal stem cell transplant, we observed a positive immune response, with a 40% decrease in leukocyte intoxication index and a 22% increase from the initial lymphocyte and eosinophil ratio index values, which indicated the formation of a delayed-type hypersensitivity reaction. Two months after transplant, stem cell leukocyte intoxication index, in contrast, increased by 10%, indicating a possible metabolic shift. At the same time, changes were observed in the lymphocyte stimulation index value, which increased by 11%. This observation indicated negative immunologic reactivity, namely, poor function of factors of nonspecific resistance due to autointoxication of the organism. However, 3 months after transplant, the hematologic parameters of this patient returned to levels before treatment. The use of integral hematologic parameters can indirectly interpret parallels between immunologic reactivity and metabolic disorders in type 1 diabetes mellitus complications (diabetic retinopathy) after autologous mesenchymal stem cell transplant. These parameters could become a diagnostic indicator in the correction of pathogenetic therapy.

Autologous Mesenchymal Stem Cell Transplant in Patients with Type 1 Diabetes Mellitus.

OBJECTIVES: Our goal was to determine the efficacy of autologous mesenchymal stem cell transplant for treatment in patients with type 1 diabetes mellitus. MATERIALS AND METHODS: We examined 5 patients (4 male, 1 female; age 20-42 y) with type 1 diabetes mellitus who received autologous mesenchymal stem cell transplant (cells were obtained from the patient's iliac crest and cultured for 3-4 weeks) performed by intravenous infusion. The quantity of autologous mesenchymal stem cells infused was 95 to 97 × 106. We analyzed daily insulin dosages and leptin and glycated hemoglobin levels in patients before and 1, 2, and 3 months after their autologous mesenchymal stem cell transplant procedure. RESULTS: In patients with type 1 diabetes mellitus, autologous mesenchymal stem cell transplant led to a decrease in daily insulin dosage levels, from 63 ± 8.83 to 50.2 ± 12.1 U (P = .064) after 1 month, with significantly increased leptin levels and trend to decreased glycated hemoglobin levels, from 6.86 to 10.77 ng/mL (P = .016) and 9.11% to 8.74% (P = .84) after 3 months, respectively. CONCLUSIONS: Daily insulin dosage level decreased within 1 month and leptin levels increased significantly within 3 months after autologous mesenchymal stem cell transplant in patients with type 1 diabetes mellitus.

Transforming Growth Factor ß1 in Patients with Type 2 Diabetes Mellitus After Fetal Pancreatic Stem Cell Transplant.

OBJECTIVES: Our objective was to determine transforming growth factor ß1 levels in patients with type 2 diabetes mellitus after fetal pancreatic stem cell transplant. MATERIALS AND METHODS: We examined 10 patients (age range, 41-65 y) with type 2 diabetes mellitus, which we subsequently divided into 2 groups. Group 1 comprised 5 patients who received fetal pancreatic stem cell transplant (cells were 16-18 wk gestation) performed by intravenous infusion. Group 2 comprised 5 patients (control group) who were on hypoglycemic tablet therapy or insulin therapy. The quantity of fetal stem cells infused was 5 to 6 × 106. We analyzed transforming growth factor ß1, C-peptide, and glycated hemoglobin levels in patients before and 3 months after fetal pancreatic stem cell transplant. RESULTS: In patients with type 2 diabetes mellitus, fetal pancreatic stem cell transplant led to a significant increase in transforming growth factor ß1 levels, from 16 364.8 to 35 730.4 ng/mL (P = .008), with trend in decreased glycated hemoglobin levels, from 7.96% to 6.98% (P = .088) after 3 months. CONCLUSIONS: Transforming growth factor ß1 levels increased significantly within 3 months after fetal pancreatic stem cell transplant in patients with type 2 diabetes mellitus.

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.

Leptin Level in Patients with Type 2 Diabetes Mellitus after Fetal Pancreatic Stem Cell Transplant.

OBJECTIVES: We aimed to determine leptin level in patients with type 2 diabetes mellitus after fetal pancreatic stem cell transplant. MATERIALS AND METHODS: We examined 14 patients (aged 43-63 years old) with type 2 diabetes mellitus, which we subsequently divided into 2 groups and examined. Group 1 comprised 8 patients who received fetal pancreatic stem cell transplant (cells were 16-18 wk gestation) performed by intravenous infusion; group 2 comprised 6 patients in the control group who were on hypoglycemic tablet therapy or insulin therapy. The quantity of fetal stem cells infused was 5 to 6 × 106. We analyzed leptin and C-peptide levels in patients both before and 3 months after the fetal pancreatic stem cell transplant procedure. RESULTS: In patients with type 2 diabetes mellitus, fetal pancreatic stem cell transplant led to a significant increase in leptin levels, from 11.01 ng/mL to 16.29 ng/mL, after 3 months (P < .05). CONCLUSIONS: Leptin level increase significantly within 3 months after fetal pancreatic stem cell transplant in patients with type 2 diabetes mellitus.

Fetal Pancreatic Stem-Cell Transplant in Patients With Diabetes Mellitus.

OBJECTIVES: To determine the efficacy of fetal stem cell transplant for treating patients with diabetes mellitus types 1 and 2. MATERIALS AND METHODS: Five patients with diabetes mellitus type 1 and 5 patients with diabetes mellitus type 2 (aged 18-56 years) received a fetal pancreatic stem-cell transplant (cells were 16-18 wk gestation) performed by intravenous infusion at 50 mL/hour. The quantity of fetal stem cells infused was ≥ 5-8*106. We analyzed the patients' C-peptide and glycated hemoglobin levels both before and 3 months after fetal stem cell transplant. RESULTS: In patients with diabetes mellitus type 1, fetal stem-cell transplant led to a significant increase in C-peptide levels, from 0.09 ± 0.01 ng/mL to 0.20 ± 0.07 ng/mL, after 3 months (P < .008). CONCLUSIONS: Treatment with fetal pancreatic stem cells may be beneficial for treating patients with type 1 or type 2 diabetes.