Insulin feedback can be implemented using a model estimate of concentration. Proportional integral derivative control with insulin feedback can achieve a desired breakfast response but still requires supplemental carbohydrate to be delivered in some instances. Studies assessing more optimal control configurations and safeguards need to be conducted.

Through the use of enzymatic sensors—inserted subcutaneously in the abdomen or ex vivo by means of microdialysis fluid extraction—real-time minimally invasive continuous glucose monitoring (CGM) devices estimate blood glucose by measuring a patient's interstitial fluid (ISF) glucose concentration. Signals acquired from the interstitial space are subsequently calibrated with capillary blood glucose samples, a method that has raised certain questions regarding the effects of physiological time lags and of the duration of processing delays built into these devices. The time delay between a blood glucose reading and the value displayed by a continuous glucose monitor consists of the sum of the time lag between ISF and plasma glucose, in addition to the inherent electrochemical sensor delay due to the reaction process and any front-end signal-processing delays required to produce smooth traces. Presented is a review of commercially available, minimally invasive continuous glucose monitors with manufacturer-reported device delays. The data acquisition process for the Medtronic MiniMed (Northridge, CA) continuous glucose monitoring system—CGMS® Gold—and the Guardian® RT monitor is described with associated delays incurred for each processing step. Filter responses for each algorithm are examined using in vitro hypoglycemic and hyperglycemic clamps, as well as with an analysis of fast glucose excursions from a typical meal response. Results demonstrate that the digital filters used by each algorithm do not cause adverse effects to fast physiologic glucose excursions, although nonphysiologic signal characteristics can produce greater delays.

Metabolic models used in developing and comparing closed-loop insulin delivery algorithms will need to explicitly describe intraday variation in metabolic parameters, but the model itself need not be comprised by a large number of compartments or differential equations.

OBJECTIVEEven under closed-loop (CL) conditions, meal-related blood glucose (BG) excursions frequently exceed target levels as a result of delays in absorption of insulin from the subcutaneous site of infusion. We hypothesized that delaying gastric emptying with preprandial injections of pramlintide would improve postprandial glycemia by allowing a better match between carbohydrate and insulin absorptions.RESEARCH DESIGN AND METHODSEight subjects (4 female; age, 15–28 years; A1C, 7.5 ± 0.7%) were studied for 48 h on a CL insulin-delivery system with a proportional integral derivative algorithm with insulin feedback: 24 h on CL control alone (CL) and 24 h on CL control plus 30-μg premeal injections of pramlintide (CLP). Target glucose was set at 120 mg/dL; timing and contents of meals were identical on both study days. No premeal manual boluses were given. Differences in reference BG excursions, defined as the incremental glucose rise from premeal to peak, were compared between conditions for each meal.RESULTSCLP was associated with overall delayed time to peak BG (2.5 ± 0.9 vs. 1.5 ± 0.5 h; P < 0.0001) and reduced magnitude of glycemic excursion (88 ± 42 vs. 113 ± 32 mg/dL; P = 0.006) compared with CL alone. Pramlintide effects on glycemic excursions were particularly evident at lunch and dinner, in association with higher premeal insulin concentrations at those mealtimes.CONCLUSIONSPramlintide delayed the time to peak postprandial BG and reduced the magnitude of prandial BG excursions. Beneficial effects of pramlintide on CL may in part be related to higher premeal insulin levels at lunch and dinner compared with breakfast.

OBJECTIVE -The purpose of this study was to examine the effect of type of insulin analog and age of insertion site on the pharmacodynamic characteristics of a standard insulin bolus in youth with type 1 diabetes receiving insulin pump therapy.RESEARCH DESIGN AND METHODS -Seventeen insulin pump-treated adolescents with type 1 diabetes underwent two euglycemic clamp procedures after a 0.2 unit/kg bolus of either insulin aspart or lispro on day 1 and day 4 of insulin pump site insertion. The glucose infusion rate (GIR) required to maintain euglycemia was the primary pharmacodynamic measure.RESULTS -There were no statistically significant differences in any of the pharmacodynamic parameters between aspart and lispro during day 1 and day 4. However, when the two groups were combined, time to discontinuation of exogenous glucose infusion, and time to halfmaximal onset and offset of insulin action were observed significantly earlier during day 4 compared with day 1 (P ϭ 0.03-0.0004), but the overall area under the GIR curve was similar on day 1 and day 4.CONCLUSIONS -With both insulin aspart and lispro, there is an earlier peak and shorter duration of action with increasing duration of infusion site use, but overall insulin action is not affected.