An Adaptive Nonlinear Basal-Bolus Calculator for Patients With Type 1 Diabetes

Background: Bolus calculators help patients with type 1 diabetes to mitigate the effect of meals on their blood glucose by administering a large amount of insulin at mealtime. Intraindividual changes in patients physiology and nonlinearity in insulin-glucose dynamics pose a challenge to the accuracy of such calculators. Method: We propose a method based on a continuous-discrete unscented Kalman filter to continuously track the postprandial glucose dynamics and the insulin sensitivity. We augment the Medtronic Virtual Patient (MVP) model to simulate noise-corrupted data from a continuous glucose monitor (CGM). The basal rate is determined by calculating the steady state of the model and is adjusted once a day before breakfast. The bolus size is determined by optimizing the postprandial glucose values based on an estimate of the insulin sensitivity and states, as well as the announced meal size. Following meal announcements, the meal compartment and the meal time constant are estimated, otherwise insulin sensitivity is estimated. Results: We compare the performance of a conventional linear bolus calculator with the proposed bolus calculator. The proposed basal-bolus calculator significantly improves the time spent in glucose target ( P < .01) compared to the conventional bolus calculator. Conclusion: An adaptive nonlinear basal-bolus calculator can efficiently compensate for physiological changes. Further clinical studies will be needed to validate the results.

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Short‐term effects of dapagliflozin on insulin sensitivity, postprandial glucose excursion and ketogenesis in type 1 diabetes mellitus: A randomized, placebo‐controlled, double blind, cross‐over pilot study

Diabetes Obesity and Metabolism ◽

10.1111/dom.13439 ◽

2018 ◽

Vol 20 (11) ◽

pp. 2685-2689

Author(s):

Andreas Melmer ◽

Patrick Kempf ◽

Lukas Lunger ◽

Thomas R. Pieber ◽

Julia K. Mader ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Insulin Sensitivity ◽

Pilot Study ◽

Type 1 Diabetes Mellitus ◽

Postprandial Glucose ◽

Short Term ◽

Double Blind ◽

Postprandial Glucose Excursion

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Effects of delayed gastric emptying on postprandial glucose kinetics, insulin sensitivity, and β-cell function

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00199.2014 ◽

2014 ◽

Vol 307 (6) ◽

pp. E494-E502 ◽

Cited By ~ 17

Author(s):

Ling Hinshaw ◽

Michele Schiavon ◽

Ashwini Mallad ◽

Chiara Dalla Man ◽

Rita Basu ◽

...

Keyword(s):

Type 1 Diabetes ◽

Gastric Emptying ◽

Insulin Sensitivity ◽

Delayed Gastric Emptying ◽

Cell Function ◽

Postprandial Glucose ◽

Β Cell ◽

C Peptide ◽

Β Cell Function

Controlling meal-related glucose excursions continues to be a therapeutic challenge in diabetes mellitus. Mechanistic reasons for this need to be understood better to develop appropriate therapies. To investigate delayed gastric emptying effects on postprandial glucose turnover, insulin sensitivity, and β-cell responsivity and function, as a feasibility study prior to studying patients with type 1 diabetes, we used the triple tracer technique C-peptide and oral minimal model approach in healthy subjects. A single dose of 30 μg of pramlintide administered at the start of a mixed meal was used to delay gastric emptying rates. With delayed gastric emptying rates, peak rate of meal glucose appearance was delayed, and rate of endogenous glucose production (EGP) was lower. C-peptide and oral minimal models enabled the assessments of β-cell function, insulin sensitivity, and β-cell responsivity simultaneously. Delayed gastric emptying induced by pramlintide improved total insulin sensitivity and decreased total β-cell responsivity. However, β-cell function as measured by total disposition index did not change. The improved whole body insulin sensitivity coupled with lower rate of appearance of EGP with delayed gastric emptying provides experimental proof of the importance of evaluating pramlintide in artificial endocrine pancreas approaches to reduce postprandial blood glucose variability in patients with type 1 diabetes.

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Effect of Pramlintide on Postprandial Glucose Fluxes in Type 1 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2015-3952 ◽

2016 ◽

Vol 101 (5) ◽

pp. 1954-1962 ◽

Cited By ~ 17

Author(s):

Ling Hinshaw ◽

Michele Schiavon ◽

Vikash Dadlani ◽

Ashwini Mallad ◽

Chiara Dalla Man ◽

...

Keyword(s):

Type 1 Diabetes ◽

Gastric Emptying ◽

Insulin Sensitivity ◽

Area Under The Curve ◽

Postprandial Glucose ◽

Endogenous Glucose Production ◽

Fat Free Mass ◽

Glucose Turnover ◽

Plasma Glucagon

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.

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