Carter, Rickey E

Abstract Context: Early postprandial hyperglycemia and delayed hypoglycemia remain major problems in current management of type 1 diabetes (T1D). Objective: Our objective was to investigate the effects of pramlintide, known to suppress glucagon and delay gastric emptying, on postprandial glucose fluxes in T1D. Design: This was a single-center, inpatient, randomized, crossover study. Patients: Twelve patients with T1D who completed the study were analyzed. Interventions: Subjects were studied on two occasions with or without pramlintide. Triple tracer mixed-meal method and oral minimal model were used to estimate postprandial glucose turnover and insulin sensitivity (SI). Integrated liver insulin sensitivity was calculated based on glucose turnover. Plasma glucagon and insulin were measured. Main Outcome Measure: Glucose turnover and SI were the main outcome measures. Results: With pramlintide, 2-hour postprandial glucose, insulin, glucagon, glucose turnover, and SI indices showed: plasma glucose excursions were reduced (difference in incremental area under the curve [iAUC], 444.0 mMmin, P = .0003); plasma insulin concentrations were lower (difference in iAUC, 7642.0 pMmin; P = .0099); plasma glucagon excursions were lower (difference in iAUC, 1730.6 pg/mlmin; P = .0147); meal rate of glucose appearance was lower (difference in iAUC: 1196.2 μM/kg fat free mass [FFM]; P = .0316), endogenous glucose production was not different (difference in iAUC: −105.5 μM/kg FFM; P = .5842), rate of glucose disappearance was lower (difference in iAUC: 1494.2 μM/kg FFM; P = .0083). SI and liver insulin sensitivity were not different between study visits (P > .05). Conclusions: Inhibition of glucagon and gastric emptying delaying reduced 2-hour prandial glucose excursions in T1D by delaying meal rate of glucose appearance.

Background: Understanding the effect size, variability, and underlying physiology of the dawn phenomenon is important for next-generation closed-loop control algorithms for type 1 diabetes (T1D). Subjects and Methods: We used an iterative protocol design to study 16 subjects with T1D on individualized insulin pump therapy for two successive nights. Endogenous glucose production (EGP) rates at 3 a.m. and 7 a.m. were measured with [6,6- 2 H 2 ]glucose as a single tracer, infused from midnight to 7 a.m. in all subjects. To explore possibility of tracer recycling due to prolonged [6,6- 2 H 2 ]glucose infusion, which was highly probable after preplanned interim data analyses, we infused a second tracer, [6- 3 H]glucose, from 4 a.m. to 7 a.m. in the last seven subjects to measure EGP at 7 a.m. Results: Cortisol concentrations increased during both nights, but changes in glucagon and insulin concentration were inconsistent. Although the plasma glucose concentrations rose from midnight to 7 a.m. during both nights, EGP measured with [6,6- 2 H 2 ]glucose between 3 a.m. and 7 a.m. did not differ during Night 1 but fell in Night 2. However, EGP measured with [6- 3 H]glucose at 7 a.m. was higher than that measured with [6,6- 2 H 2 ]glucose during both nights, thereby suggesting tracer recycling probably underestimating EGP calculated at 7 a.m. with [6,6- 2 H 2 ]glucose. Likewise, EGP was higher at 7 a.m. with [6- 3 H]glucose than at 3 a.m. with [6,6- 2 H 2 ]glucose during both nights. Conclusions: The data demonstrate a consistent overnight rise in glucose concentrations through increased EGP, mediated likely by rising cortisol concentrations. The observations with the dual tracer approach imply significant tracer recycling leading to underestimation of EGP measured by longer-duration tracer infusion.

ABSTRACTPURPOSETo determine interobserver spatial variability in language area localization using three commonly employed language tasks.MATERIALS AND METHODSWith institutional review board approval, 125 fMRI time series from 50 different clinical language cases were retrospectively reviewed by three blinded readers who selected 3‐dimensional points representing the perceived center of Wernicke's and Broca's areas using three language tasks (semantic decision, SD; sentence comprehension, SC; and silent word generation, WG). Point dispersion values were then calculated using the perimeter of the 3‐dimensional triangle defined by the three readers’ selections.RESULTSAfter resolving interobserver laterality disagreements, there was no difference in spatial variability between the three tasks (P = .069). The SD task had the fewest interobserver laterality disagreements (P = .028) and the SC task had fewer failed localizations for Broca's area (P = .050) and Wernicke's area (P = .013).CONCLUSIONWhile there were no differences between interobserver spatial variability in language area localization between the three tasks, language task choice impacts the accuracy of fMRI language area identification because tasks vary in their rates of interobserver laterality disagreements and failed localizations. A combination of tasks including one with low laterality disagreements (eg, SD) and one with few failed localizations (eg, SC) may offer the best combination.