BACKGROUND: The oral minimal model is a simple, useful tool for the assessment of β-cell function and insulin sensitivity across the spectrum of glucose tolerance, including normal glucose tolerance (NGT), prediabetes, and type 2 diabetes mellitus (T2DM) in humans. METHODS: Plasma glucose, insulin, and C-peptide levels were measured during a 180-minute, 75-g oral glucose tolerance test in 24 Korean subjects with NGT (n=10) and T2DM (n=14). The parameters in the computational model were estimated, and the indexes for insulin sensitivity and β-cell function were compared between the NGT and T2DM groups. RESULTS: The insulin sensitivity index was lower in the T2DM group than the NGT group. The basal index of β-cell responsivity, basal hepatic insulin extraction ratio, and post-glucose challenge hepatic insulin extraction ratio were not different between the NGT and T2DM groups. The dynamic, static, and total β-cell responsivity indexes were significantly lower in the T2DM group than the NGT group. The dynamic, static, and total disposition indexes were also significantly lower in the T2DM group than the NGT group. CONCLUSION: The oral minimal model can be reproducibly applied to evaluate β-cell function and insulin sensitivity in Koreans.
Blood Glucose ; C-Peptide ; Diabetes Mellitus, Type 2* ; Glucose Tolerance Test ; Glucose* ; Humans ; Insulin ; Insulin Resistance ; Prediabetic State

Although various basal-bolus insulin therapy (BBIT) protocols have been used in the clinical environment, safer and more effective BBIT protocols are required for glucose control in hospitalized patients with type 2 diabetes (T2D). Modeling approaches could provide an evaluation environment for developing the optimal BBIT protocol prior to clinical trials at low cost and without risk of danger. In this study, an in-silico model was proposed to evaluate subcutaneous BBIT protocols in hospitalized patients with T2D. The proposed model was validated by comparing the BBIT protocol and sliding-scale insulin therapy (SSIT) protocol. The model was utilized for in-silico trials to compare the protocols of adjusting basal-insulin dose (BBIT1) versus adjusting total-daily-insulin dose (BBIT2). The model was also used to evaluate two different initial total-daily-insulin doses for various levels of renal function. The BBIT outcomes were superior to those of SSIT, which is consistent with earlier studies. BBIT2 also outperformed BBIT1, producing a decreased daily mean glucose level and longer time-in-target-range. Moreover, with a standard dose, the overall daily mean glucose levels reached the target range faster than with a reduced-dose for all degrees of renal function. The in-silico studies demonstrated several significant findings, including that the adjustment of total-daily-insulin dose is more effective than changes to basal-insulin dose alone. This research represents a first step toward the eventual development of an advanced model for evaluating various BBIT protocols.
Blood Glucose/analysis ; Diabetes Mellitus, Type 2/*drug therapy ; Hospitalization ; Humans ; Hypoglycemic Agents/*therapeutic use ; Insulin/*therapeutic use ; Models, Theoretical

The incretin effect, which is a unique stimulus of insulin secretion in response to oral ingestion of nutrients, is calculated by the difference in insulin secretory responses from an oral glucose tolerance test (OGTT) and a corresponding isoglycemic intravenous glucose infusion (IIGI) study. The OGTT model of this study, which is individualized by fitting the glucose profiles during an OGTT, was developed to predict the glucose profile during an IIGI study in the same subject. Also, the model predicts the insulin and incretin profiles during both studies. The incretin effect, estimated by simulation, was compared with that measured by physiologic studies from eight human subjects with normal glucose tolerance, and the result exhibited a good correlation (r > 0.8); the incretin effect from the simulation was 56.5% +/- 10.6% while the one from the measured data was 52.5% +/- 19.6%. In conclusion, the parameters of the OGTT model have been successfully estimated to predict the profiles of both OGTTs and IIGI studies. Therefore, with glucose data from the OGTT alone, this model could control and predict the physiologic responses, including insulin secretion during OGTTs and IIGI studies, which could eventually eliminate the need for complex and cumbersome IIGI studies in incretin research.
Administration, Oral ; Adult ; Area Under Curve ; Blood Glucose/analysis ; *Computer Simulation ; Female ; Glucose/metabolism/pharmacology ; Glucose Tolerance Test ; Humans ; Incretins/*blood ; Insulin/blood ; Liver/drug effects ; Middle Aged ; *Models, Theoretical ; ROC Curve

OBJECTIVE: Pharyngoesophageal stricture formation and dysphagia following total laryngectomy negatively affect quality of life and result in nutritional compromise that can be successfully managed with various techniques. This study was conducted to describe our experiences of office-based balloon dilatation by transnasal endoscopy, which can be performed by an otolaryngologist. METHOD: The present study investigated three patients who underwent transnasal endoscopy guided balloon dilatation of pharyngoesophageal stricture. The assessment was performed based on the number of procedures and recurrences, final subjective outcomes, and complications. RESULT: There were no post-procedural complications. In one patient, a scarric band was found after the procedure; therefore, steroids were injected into the stricture site. There were 2–3 balloon dilatations and the interval between dilatations was 3–6 months. All patients were able to tolerate solid diet after 2 or 3 sessions. CONCLUSION: Transnasal endoscopic balloon dilatation, which can be easily performed by an otolaryngologist in an office setting without sedation or general anesthesia, can be a useful modality for treating pharyngoesophageal stricture after total laryngectomy.
Anesthesia, General ; Constriction, Pathologic ; Deglutition Disorders ; Diet ; Dilatation ; Endoscopy ; Humans ; Laryngectomy ; Methods ; Quality of Life ; Recurrence ; Steroids

Background: This study evaluated the difference in brain metabolite profiles between normothermia and hypothermia reaching 25°C in humans in vivo. Methods: Thirteen patients who underwent thoracic aorta surgery under moderate hypothermia were prospectively enrolled. Plasma samples were collected simultaneously from the arteries and veins to estimate metabolite uptake or release. Targeted metabolomics based on liquid chromatographic mass spectrometry and direct flow injection were performed, and changes in the profiles of respective metabolites from normothermia to hypothermia were compared. The ratios of metabolite concentrations in venous blood samples to those in arterial blood samples (V/A ratios) were calculated, and log 2 transformation of the ratios [log2 (V/A)] was performed for comparison between the temperature groups. Results: Targeted metabolomics were performed for 140 metabolites, including 20 amino acids, 13 biogenic amines, 10 acylcarnitines, 82 glycerophospholipids, 14 sphingomyelins, and 1 hexose. Of the 140 metabolites analyzed, 137 metabolites were released from the brain in normothermia, and the release of 132 of these 137 metabolites was decreased in hypothermia. Two metabolites (dopamine and hexose) showed constant release from the brain in hypothermia, and 3 metabolites (2 glycophospholipids and 1 sphingomyelin) showed conversion from release to uptake in hypothermia. Glutamic acid demonstrated a distinct brain metabolism in that it was taken up by the brain in normothermia, and the uptake was increased in hypothermia. Conclusion Targeted metabolomics demonstrated various degrees of changes in the release of metabolites by the hypothermic brain. The release of most metabolites was decreased in hypothermia, whereas glutamic acid showed a distinct brain metabolism.

BACKGROUND: Dihydrotestosterone (DHT) induces androgenic alopecia by shortening the hair follicle growth phase, resulting in hair loss. We previously demonstrated how changes in the microRNA (miRNA) expression profile influenced DHT-mediated cell death, cell cycle arrest, cell viability, the generation of reactive oxygen species (ROS), and senescence. Protective effects against DHT have not, however, been elucidated at the genome level. OBJECTIVE: We showed that epigallocatechin gallate (EGCG), a major component of green tea, protects DHT-induced cell death by regulating the cellular miRNA expression profile. METHODS: We used a miRNA microarray to identify miRNA expression levels in human dermal papilla cells (DPCs). We investigated whether the miRNA expression influenced the protective effects of EGCG against DHT-induced cell death, growth arrest, intracellular ROS levels, and senescence. RESULTS: EGCG protected against the effects of DHT by altering the miRNA expression profile in human DPCs. In addition, EGCG attenuated DHT-mediated cell death and growth arrest and decreased intracellular ROS levels and senescence. A bioinformatics analysis elucidated the relationship between the altered miRNA expression and EGCG-mediated protective effects against DHT. CONCLUSION: Overall, our results suggest that EGCG ameliorates the negative effects of DHT by altering the miRNA expression profile in human DPCs.
Aging ; Alopecia ; Cell Cycle Checkpoints ; Cell Death ; Cell Survival ; Computational Biology ; Dihydrotestosterone ; Genome ; Hair ; Hair Follicle ; Humans* ; MicroRNAs* ; Reactive Oxygen Species ; Tea