ABSTRACT
OBJECTIVE: Low-dose antithymocyte globulin (ATG) (2.5 mg/kg) preserves C-peptide and reduces HbA1c in new-onset stage 3 type 1 diabetes, yet efficacy in delaying progression from stage 2 to stage 3 has not been evaluated. RESEARCH DESIGN AND METHODS: Children (n = 6) aged 5-14 years with stage 2 type 1 diabetes received off-label, low-dose ATG. HbA1c, C-peptide, continuous glucose monitoring, insulin requirements, and side effects were followed for 18-48 months. RESULTS: Three subjects (50%) remained diabetes free after 1.5, 3, and 4 years of follow-up, while three developed stage 3 within 1-2 months after therapy. Eighteen months posttreatment, even disease progressors demonstrated near-normal HbA1c (5.1% [32 mmol/mol], 5.6% [38 mmol/mol], and 5.3% [34 mmol/mol]), time in range (93%, 88%, and 98%), low insulin requirements (0.17, 0.18, and 0.34 units/kg/day), and robust C-peptide 90 min after mixed meal (1.3 ng/dL, 2.3 ng/dL, and 1.4 ng/dL). CONCLUSIONS: These observations support additional prospective studies evaluating ATG in stage 2 type 1 diabetes.
Subject(s)
Antilymphocyte Serum , Diabetes Mellitus, Type 1 , Child , Humans , Antilymphocyte Serum/therapeutic use , Blood Glucose , Blood Glucose Self-Monitoring , C-Peptide , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/chemically induced , Glycated Hemoglobin , Hypoglycemic Agents , Insulin , Prospective StudiesABSTRACT
We sought to determine if autologous umbilical cord blood (UCB) infusion followed by 1 year of supplementation with vitamin D and docosahexaenoic acid (DHA) can preserve C-peptide in children with type 1 diabetes. We conducted an open-label, 2:1 randomized study in which 15 type 1 diabetes subjects with stimulated C-peptide > .2 pmol/mL received either (1) autologous UCB infusion, 1 year of daily oral vitamin D (2000 IU), and DHA (38 mg/kg) and intensive diabetes management or (2) intensive diabetes management alone. Primary analyses were performed 1 year after UCB infusion. Treated (N = 10) and control (N = 5) subjects had median ages of 7.2 and 6.6 years, respectively. No severe adverse events were observed. Although the absolute rate of C-peptide decline was slower in treated versus control subjects, intergroup comparisons failed to reach significance (P = .29). Area under the curve C-peptide declined and insulin use increased in both groups (P < .01). Vitamin D levels remained stable in treated subjects but declined in control subjects (P = .01). DHA levels rose in treated subjects versus control subjects (P = .003). CD4/CD8 ratio remained stable in treated subjects but declined in control subjects (P = .03). No changes were seen in regulatory T cell frequency, total CD4 counts, or autoantibody titers. Autologous UCB infusion followed by daily supplementation with vitamin D and DHA was safe but failed to preserve C-peptide. Lack of significance may reflect small sample size. Future efforts will require expansion of specific immunoregulatory cell subsets, optimization of combined immunoregulatory and anti-inflammatory agents, and larger study cohorts.
Subject(s)
C-Peptide/blood , Cord Blood Stem Cell Transplantation , Diabetes Mellitus, Type 1/therapy , Docosahexaenoic Acids/administration & dosage , Vitamin D/administration & dosage , Administration, Oral , Area Under Curve , CD4 Lymphocyte Count , Case-Control Studies , Child , Child, Preschool , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/pathology , Female , Humans , Infant , Infusions, Intravenous , Male , T-Lymphocyte Subsets , Transplantation, AutologousABSTRACT
CONTEXT: Chronic abdominal pain is the most difficult management issue in patients with chronic pancreatitis. Recently, a long-acting depo-formulated version of octreotide has been developed that can be given as a once monthly intramuscular injection, Octreotide LAR(R) (O-LAR) rather than as a thrice daily subcutaneous injection (octreotide short-acting, O-SA). OBJECTIVE: To see if O-LAR is similar in efficacy to O-SA in the treatment of painful chronic pancreatitis in a small open-label, unblinded pilot study. PATIENTS: Seven advanced chronic pancreatitis patients with daily, severe abdominal pain who had previously responded to O-SA were recruited from the pancreas clinics of the University of Florida and monitored for one month on O-SA and for four months while on O-LAR. Each patient served as his/her own control as this was a paired data set. MAIN OUTCOME MEASURES: 1) Daily VAS scores; 2) daily morphine equivalents; 3) monthly health related quality of life chronic pancreatitis surveys; 4) daily diaries of work/pleasurable activities missed or hospitalization/Emergency Department visits. RESULTS: Average daily VAS scores for patients during O-SA therapy were 4.50+/-2.28 and during the fourth month of O-LAR therapy, 3.86+/-2.11, difference -0.64+/-0.80 (P=0.078). Average daily morphine equivalents were not dissimilar at 124.3+/-177.3 mg during O-SA therapy and 131.6+/-194.3 mg during O-LAR therapy; difference 7.3+/-17.5 mg P=0.310. Health related quality of life chronic pancreatitis scores were not significantly changed when moving from O-SA to O-LAR. Adverse events were rare. CONCLUSIONS: Octreotide LAR(R) may be a reasonable substitute for tid octreotide in treating chronic pancreatitis pain. Further, larger studies would be useful to better characterize the role of Octreotide LAR(R) in the management of chronic pancreatitis pain.
Subject(s)
Abdominal Pain/drug therapy , Octreotide/administration & dosage , Pancreatitis, Chronic/drug therapy , Quality of Life , Abdominal Pain/etiology , Adult , Aged , Delayed-Action Preparations/administration & dosage , Drug Administration Schedule , Female , Gastrointestinal Agents/administration & dosage , Humans , Injections, Intramuscular , Injections, Subcutaneous , Male , Middle Aged , Pancreatitis, Chronic/complications , Pilot ProjectsABSTRACT
This cross-sectional study compares race and ethnicity reporting in 3 medical journals before and after implementation of updated guidance on the reporting of race and ethnicity in August 2021.
Subject(s)
Ethnicity , Periodicals as Topic , HumansABSTRACT
OBJECTIVE: We conducted an open-label, phase I study using autologous umbilical cord blood (UCB) infusion to ameliorate type 1 diabetes (T1D). Having previously reported on the first 15 patients reaching 1 year of follow-up, herein we report on the complete cohort after 2 years of follow-up. RESEARCH DESIGN AND METHODS: A total of 24 T1D patients (median age 5.1 years) received a single intravenous infusion of autologous UCB cells and underwent metabolic and immunologic assessments. RESULTS: No infusion-related adverse events were observed. ß-Cell function declined after UCB infusion. Area under the curve C-peptide was 24.3% of baseline 1 year postinfusion (P < 0.001) and 2% of baseline 2 years after infusion (P < 0.001). Flow cytometry revealed increased regulatory T cells (Tregs) (P = 0.04) and naive Tregs (P = 0.001) 6 and 9 months after infusion, respectively. CONCLUSIONS: Autologous UCB infusion in children with T1D is safe and induces changes in Treg frequency but fails to preserve C-peptide.
Subject(s)
Blood Transfusion, Autologous , Diabetes Mellitus, Type 1/therapy , Fetal Blood/transplantation , C-Peptide/blood , Child , Child, Preschool , Diabetes Mellitus, Type 1/immunology , Female , Follow-Up Studies , Humans , Infant , Male , Pilot Projects , T-Lymphocytes, Regulatory/immunologyABSTRACT
OBJECTIVE: Interest continues to grow regarding the therapeutic potential for umbilical cord blood therapies to modulate autoimmune disease. We conducted an open-label phase I study using autologous umbilical cord blood infusion to ameliorate type 1 diabetes. RESEARCH DESIGN AND METHODS: Fifteen patients diagnosed with type 1 diabetes and for whom autologous umbilical cord blood was stored underwent a single intravenous infusion of autologous cells and completed 1 year of postinfusion follow-up. Intensive insulin regimens were used to optimize glycemic control. Metabolic and immunologic assessments were performed before infusion and at established time periods thereafter. RESULTS: Median (interquartile range [IQR]) age at infusion was 5.25 (3.1-7.3) years, with a median postdiagnosis time to infusion of 17.7 (10.9-26.5) weeks. No infusion-related adverse events were observed. Metabolic indexes 1 year postinfusion were peak C-peptide median 0.50 ng/ml (IQR 0.26-1.30), P = 0.002; A1C 7.0% (IQR 6.5-7.7), P = 0.97; and insulin dose 0.67 units * kg(-1) * day(-1) (IQR 0.55-0.77), P = 0.009. One year postinfusion, no changes were observed in autoantibody titers, regulatory T-cell numbers, CD4-to-CD8 ratio, or other T-cell phenotypes. CONCLUSIONS: Autologous umbilical cord blood transfusion in children with type 1 diabetes is safe but has yet to demonstrate efficacy in preserving C-peptide. Larger randomized studies as well as 2-year postinfusion follow-up of this cohort are needed to determine whether autologous cord blood-based approaches can be used to slow the decline of endogenous insulin production in children with type 1 diabetes.
Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 1/therapy , Fetal Blood/transplantation , Blood Transfusion, Autologous/methods , C-Peptide/blood , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Child , Child, Preschool , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/immunology , Follow-Up Studies , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/therapeutic use , Infant , Infusions, Intravenous , Insulin/therapeutic use , Leukocyte Count , Time FactorsABSTRACT
BACKGROUND AND AIMS: Due to the unavailability of biologic porcine secretin (BPS), 2 synthetic forms of secretin were developed. Our aim is to determine the bioequivalency of the 3 forms of secretin in pancreatic function testing. METHODS: In a randomized, crossover design, synthetic porcine (SPS) and synthetic human secretin (SHS) were compared in a group of 12 subjects with chronic pancreatitis undergoing secretin stimulation test (SST). The 2 synthetic forms of secretin were then compared with BPS in 12 subjects utilizing a similar design. Finally, 18 healthy subjects underwent secretin stimulation testing with SHS. RESULTS: There was excellent correlation of peak bicarbonate measurements in the comparison of SPS to SHS (R = 0.967) as well as in the comparison of all 3 forms of secretin (P = 0.08, ANOVA for correlated samples). In the SST, each of the synthetic forms of secretin were 100% accurate in diagnosing chronic pancreatitis in disease subjects and in excluding chronic pancreatitis in normal controls. The synthetic forms of secretin were associated with fewer side effects when compared with BPS with the exception of transient tachycardia which occurred in up to 19% of subjects. CONCLUSIONS: The synthetic porcine and human forms of secretin are equivalent to one another and to biologic porcine secretin and can be used interchangeably in pancreatic function testing.