Examining the Relationship Between Pre- and Postprandial Glucose Levels and Insulin Bolus Timing Using Bluetooth-Enabled Insulin Pen Cap Technology and Continuous Glucose Monitoring.

Background: Timing of insulin administration in persons using multiple daily injections (MDI) is self-reported. New technology enabling tracking and logging of insulin doses, combined with continuous glucose monitoring (CGM), may provide insight into the relationship between insulin administration and glucose levels. Methods: We performed a prospective observational study using Bluetooth-enabled pen caps, along with CGM, in participants with type 1 diabetes (T1D) on MDI to objectively assess the relationship between the timing of insulin administration and its impact on pre- and postprandial glucose levels for a 2-week period. Results: We evaluated 50 participants (age 40.3 ± 19 years; A1c 8.2% ± 1.5%, duration of T1D 20 ± 15 years). Thirty-seven percent of total boluses resulted in persistent hyperglycemia (glucose >180 mg/dL 3 h postprandially), while 10% resulted in clinically significant hypoglycemia (glucose <55 mg/dL 3 h postprandially) on CGM. Preprandial glucose levels at the time of the bolus did not correlate with postprandial glucose levels. Late boluses, defined as a rise in glucose of ≥50 mg/dL before a bolus, were seen two times/patient/week. Missed boluses, defined as a rise in glucose of ≥50 mg/dL without a bolus within 2 h, occurred 17 times/patient/week. Late and missed boluses were associated with worse glycemic control (A1c; R2 = 0.1, P = 0.02; R2 = 0.1, P = 0.02). Conclusions: The use of Bluetooth-enabled pen caps, with CGM, in persons with T1D on MDI can illustrate the relationship between insulin bolus timing and postprandial glucose. These data may help clinicians and patients understand the impact of timing of insulin doses on glucose levels and glycemic control.

Nonadherence to Insulin Therapy Detected by Bluetooth-Enabled Pen Cap Is Associated With Poor Glycemic Control.

OBJECTIVE: To objectively evaluate adherence to timing and dosing of insulin by using Bluetooth pen caps and examine factors related to adherence. RESEARCH DESIGN AND METHODS: Bluetooth-enabled insulin pen caps were used in younger (ages 18-35 years) and older (ages ≥65 years) adults on two or more insulin injections per day. RESULTS: We evaluated 75 participants with diabetes, 42 younger (29 ± 4 years) and 33 older (73 ± 7 years). Nonadherence was found in 24% of bolus (Apidra) doses and 36% of basal (Lantus) doses. We divided participants into tertiles on the basis of overall adherence, with the most adherent tertile having 85% dose adherence compared with 49% in the least adherent tertile (P < 0.001). Participants in the most adherent tertile had better glycemic control than those in the least adherent tertile (7.7 ± 1.1% [61 ± 12 mmol/mol] vs. 8.6 ± 1.5% [70 ± 16.4 mmol/mol], P < 0.03). CONCLUSIONS: Nonadherence to insulin dosing and timing can be objectively assessed by Bluetooth pen caps and is associated with poor glycemic control.

MicroRNA-132 directs human periodontal ligament-derived neural crest stem cell neural differentiation.

Neurogenesis is the basis of stem cell tissue engineering and regenerative medicine for central nervous system (CNS) disorders. We have established differentiation protocols to direct human periodontal ligament-derived stem cells (PDLSCs) into neuronal lineage, and we recently isolated the neural crest subpopulation from PDLSCs, which are pluripotent in nature. Here, we report the neural differentiation potential of these periodontal ligament-derived neural crest stem cells (NCSCs) as well as its microRNA (miRNA) regulatory mechanism and function in NCSC neural differentiation. NCSCs, treated with basic fibroblast growth factor and epidermal growth factor-based differentiation medium for 24 days, expressed neuronal and glial markers (ßIII-tubulin, neurofilament, NeuN, neuron-specific enolase, GFAP, and S100) and exhibited glutamate-induced calcium responses. The global miRNA expression profiling identified 60 upregulated and 19 downregulated human miRNAs after neural differentiation, and the gene ontology analysis of the miRNA target genes confirmed the neuronal differentiation-related biological functions. In addition, overexpression of miR-132 in NCSCs promoted the expression of neuronal markers and downregulated ZEB2 protein expression. Our results suggested that the pluripotent NCSCs from human periodontal ligament can be directed into neural lineage, which demonstrate its potential in tissue engineering and regenerative medicine for CNS disorders.

Concise Review: The Deleterious Effects of Cigarette Smoking and Nicotine Usage and Mesenchymal Stem Cell Function and Implications for Cell-Based Therapies.

Stem cell sources for cell-based therapeutics are often screened for infectious agents and genetic diseases prior to implantation; however, there are other risk factors that are often overlooked, which may ultimately lead to less efficacious clinical outcomes. One such risk factor is exposure of mesenchymal stem cells (MSCs) to cigarette smoke or nicotine. Recent data have shown that exposure to cigarette smoke or nicotine leads to decreased regenerative potential, namely decreased proliferation, decreased migration, and decreased differentiation potential of exposed MSCs. This review provides a brief introduction into MSCs and their respective niches and a summary regarding the interactions of cigarettes and nicotine with MSCs populations. Specifically, the effects of cigarette smoke and nicotine on the regenerative potential of MSCs (i.e., proliferation, migration, and differentiation) will be covered with an emphasis on considerations for the development of future cell-based clinical trials and therapies. Stem Cells Translational Medicine 2017;6:1815-1821.

Neural Crest Stem Cells Can Differentiate to a Cardiomyogenic Lineage with an Ability to Contract in Response to Pulsed Infrared Stimulation.

INTRODUCTION: Cellular cardiomyoplasty has rapidly risen to prominence in the clinic following a myocardial infarction; however, low engraftment of transplanted cells limits the therapeutic benefit to these procedures. Recently, lineage-specific stem cells differentiated into cardiomyocytes have gained much attention to assist in the repair of an injured heart tissue; however, questions regarding the ideal cell source remain. In the present study, we have identified a source that is easy to extract stem cells from and show that the cells present have a high plasticity toward the cardiomyogenic lineage. We focused on the recently discovered neural crest stem cells residing in the periodontal ligament that can be easily obtained through dental procedures. MATERIALS AND METHODS: Neural crest stem cells were obtained from human excised third molars and differentiated in culture using a protocol for directed differentiation into cardiomyocytes. Differentiation of cells was assessed through gene expression and immunostaining studies. Optical stimulation using pulsed infrared radiation (IR) (λ = 1863 nm) was delivered to cell aggregates to study their contractile ability. RESULTS: We show that neural crest stem cells can be differentiated to a cardiomyogenic lineage, which was verified through immunostaining and gene expression. We observed a significant increase in cardiomyocyte-specific markers, NK2 homeobox 5 (NKX2.5) and troponin T type 2 (TNNT2), with positive changes in tropomyosin I (TPM1), gap junction protein alpha 1/Cx43 (GJA1/Cx43), and myocyte enhancement factor 2C (MEF2C). Furthermore, we were able to elicit and maintain pulse-by-pulse contractile responses in the derived cells, including in cardiospheres, with pulsed IR delivered at various radiant energies. The contractility in responses to IR could be maintained at different frequencies (0.25-2 Hz) and up to 10-min durations. While these cells did not maintain their contractility following cessation of IR, these cells demonstrated responses to the optical stimuli that are consistent with previous reports. We also found no evidence for irreversible mitochondrial depolarization in these cells following the long duration of infrared stimulation, suggesting the robustness of these cells. CONCLUSIONS: Overall, these results suggest the merit of neural crest-derived stem cells for cardiomyogenic applications and a potential cell source for repair that should contribute to efforts to translate cell-based strategies to the clinic.