المؤلفون: Steven Russell, David M. Nathan, El-Khatib Firas H, Edward R. Damiano

مصطلحات موضوعية: Insulin pump, Counterregulatory hormone, Adult, Blood Glucose, Pancreas, Artificial, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Biomedical Engineering, Bioengineering, Hypoglycemia, Infusions, Subcutaneous, Glucagon, Models, Biological, Insulin Infusion Systems, Internal medicine, Internal Medicine, medicine, Insulin lispro, Humans, Hypoglycemic Agents, Insulin, Artificial endocrine pancreas, Monitoring, Physiologic, Type 1 diabetes, Symposium, Insulin Lispro, business.industry, medicine.disease, Endocrinology, Diabetes Mellitus, Type 1, business, Algorithms, Software, medicine.drug, Boston

الوصف: Background: During a previous clinical trial of a closed-loop blood glucose (BG) control system that administered insulin and microdose glucagon subcutaneously, glucagon was not uniformly effective in preventing hypoglycemia (BG Methods: We identified and analyzed 36 episodes during which glucagon was given and categorized them as either successful or unsuccessful in preventing hypoglycemia. Results: In 20 of the 36 episodes, glucagon administration prevented hypoglycemia. In the remaining 16, BG fell below 70 mg/dl (12 of the 16 occurred during experiments performed before PK parameters were adjusted). The (dimensionless) levels of plasma insulin (normalized relative to each subject's baseline insulin level) were significantly higher during episodes ending in hypoglycemia (5.2 versus 3.7 times the baseline insulin level, p = .01). The relative error in the control algorithm's online estimate of the instantaneous plasma insulin level was also higher during episodes ending in hypoglycemia (50 versus 30%, p = .003), as were the peak plasma glucagon levels (183 versus 116 pg/ml, p = .007, normal range 50–150 pg/ml) and mean plasma glucagon levels (142 versus 75 pg/ml, p = .02). Relative to mean plasma insulin levels, mean plasma glucagon levels tended to be 59% higher during episodes ending in hypoglycemia, although this result was not found to be statistically significant (p = .14). The rate of BG descent was also significantly greater during episodes ending in hypoglycemia (1.5 versus 1.0 mg/dl/min, p = .02). Conclusions: Microdose glucagon administration was relatively ineffective in preventing hypoglycemia when plasma insulin levels exceeded the controller's online estimate by >60%. After the algorithm PK parameters were globally adjusted, insulin dosing was more conservative and microdose glucagon administration was very effective in reducing hypoglycemia while maintaining normal plasma glucagon levels. Improvements in the accuracy of the controller's online estimate of plasma insulin levels could be achieved if ultrarapid-acting insulin formulations could be developed with faster absorption and less intra- and intersubject variability than the current insulin analogs available today.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e61b7410199685de24abdc8d37da332aTest
https://europepmc.org/articles/PMC3005038Test/

المؤلفون: El-Khatib, Firas H., Jiang, John, Gerrity, Ross G., Damiano, Edward R.

المصدر: Diabetes Technology & Therapeutics ; volume 9, issue 2, page 135-144 ; ISSN 1520-9156 1557-8593

الإتاحة: https://doi.org/10.1089/dia.2006.0006Test

المؤلفون: John Jiang, El-Khatib Firas H, Edward R. Damiano

المصدر: Journal of diabetes science and technology. 1(2)

مصطلحات موضوعية: Counterregulatory hormone, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030232 urology & nephrology, Biomedical Engineering, Bioengineering, 030204 cardiovascular system & hematology, Hypoglycemia, Glucagon, 03 medical and health sciences, Carbohydrate counting, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Internal Medicine, Medicine, business.industry, Insulin, Original Articles, medicine.disease, Streptozotocin, Endocrinology, Blood sugar regulation, business, medicine.drug

الوصف: Background: In order to stave off deleterious complications of the disease, the ultimate task for people with diabetes is to maintain their blood glucose in euglycemic range. Despite technological advancements, conventional open-loop therapy often results in prolonged hyperglycemia and episodic hypoglycemia, in addition to necessitating carbohydrate counting, frequent glucose monitoring, and drug administration. The logical conclusion in the evolution of exogenous insulin therapy is to develop an automated closed-loop control system. Methods: Eleven closed-loop control experiments were conducted in four anesthetized diabetic pigs, with carbohydrate loads simulated by intravenous glucose administration through ear-vein catheters. Type 1 diabetes-like pathology was induced using intravenous administration of cytotoxin streptozotocin. The augmented model-predictive control algorithm accounts for the accumulation of subcutaneous insulin, which is critical in avoiding excessive insulin dosing. Results: Control results consistently showed successful blood-glucose regulation to euglycemic range within 80–120 minutes after intravenous glucose loads, with no incidence of hypoglycemia. This is consistent with a negative oral glucose tolerance test for diabetes and is the optimal postprandial regulation that can be achieved with subcutaneous insulin administration. Results also demonstrated the potency of subcutaneous glucagon in staving off episodic hypoglycemia and revealed efficacy of the control algorithm in coping with a twofold variation in subject weights, while simultaneously overlooking erratic blood-glucose fluctuations. Conclusions: Using an automated adaptive glucose-control system, we show successful blood-glucose regulation in vivo and establish, definitively, the plausibility and practicality of closed-loop blood-glucose control using subcutaneous insulin and glucagon infusion in type 1 diabetes. The control system strikes an intricate balance between tight blood-glucose control and optimal drug consumption, while simultaneously maintaining emphasis on simplicity and reliability.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6bacc84abb0fb4ed05e5876f0f5fc675Test
https://pubmed.ncbi.nlm.nih.gov/19888405Test

المؤلفون: El-Khatib Firas H, John Jiang, Edward R. Damiano

مصطلحات موضوعية: Counterregulatory hormone, Blood Glucose, medicine.medical_specialty, Swine, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Biomedical Engineering, Monitoring, Ambulatory, Bioengineering, Hypoglycemia, Infusions, Subcutaneous, Glucagon, Diabetes Mellitus, Experimental, Bolus (medicine), Internal medicine, Blood Glucose Self-Monitoring, Internal Medicine, medicine, Infusion pump, Animals, Hypoglycemic Agents, Insulin, business.industry, Original Articles, medicine.disease, Endocrinology, Ambulatory, Feasibility Studies, business, Algorithms

الوصف: We sought to test the feasibility and efficacy of bihormonal closed-loop blood glucose (BG) control that utilizes subcutaneous (SC) infusion of insulin and glucagon, a model-predictive control algorithm for determining insulin dosing, and a proportional-derivative control algorithm for determining glucagon dosing.Thirteen closed-loop experiments (approximately 7-27 h in length) were conducted in six ambulatory diabetic pigs weighing 26-50 kg. In all experiments, venous BG was sampled through a central line in the vena cava. Efficacy was evaluated in terms of the controller's ability to regulate BG in response to large meal disturbances ( approximately 5 g of carbohydrate per kilogram of body mass per meal) based only on regular frequent venous BG sampling and requiring only the subject's weight for initialization.Closed-loop results demonstrated successful BG regulation to normoglycemic range, with average insulin-to-carbohydrate ratios between approximately 1:20 and 1:40 U/g. The total insulin bolus doses averaged approximately 6 U for a meal containing approximately 6 g per kilogram body mass. Mean BG values in two 24 h experiments were approximately 142 and approximately 155 mg/dl, with the total daily dose (TDD) of insulin being approximately 0.8-1.0 U per kilogram of body mass and the TDD of glucagon being approximately 0.02-0.05 mg. Results also affirmed the efficacy of SC doses of glucagon in staving off episodic hypoglycemia.We demonstrate the feasibility of bihormonal closed-loop BG regulation using a control system that employs SC infusion of insulin and glucagon as governed by an algorithm that reacts only to BG without any feed-forward information regarding carbohydrate consumption or physical activity. As such, this study can reasonably be regarded as the first practical implementation of an artificial endocrine pancreas that has a hormonally derived counterregulatory capability.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::188b3287b0b4b558ad4612bdd350ec6eTest
https://europepmc.org/articles/PMC2769971Test/

المؤلفون: Russell, Steven J.¹, El-Khatib, Firas H.², Sinha, Manasi¹, Magyar, Kendra L.¹, McKeon, Katherine², Goergen, Laura G.¹, Balliro, Courtney¹, Hillard, Mallory A.¹, Nathan, David M.¹, Damiano, Edward R.² edamiano@bu.edu

المصدر: New England Journal of Medicine. 7/24/2014, Vol. 371 Issue 4, p313-325. 13p.

مصطلحات موضوعية: *ARTIFICIAL pancreases, *TREATMENT of diabetes, *BLOOD sugar monitors, *INSULIN therapy, *HYPOGLYCEMIA, *DISEASE risk factors

مستخلص: The article discusses clinical trials that tested an autonomous, wearable, bihormonal, bionic pancreas in diabetic adults and adolescents in separate outpatient settings. Topics addressed include the use of bionic endocrine pancreatic systems to improve glycemic control, the administration of insulin and glucagon using control algorithms, and absence of severe hypoglycemic events. Also mentioned are the bionic pancreas' limitations such as a risk of hypoglycemia and poor stability of glucagon.

المؤلفون: El-Khatib, Firas H, Russell, Steven J, Magyar, Kendra L, Sinha, Manasi, McKeon, Katherine, Nathan, David M, Damiano, Edward R

المصدر: Journal of Clinical Endocrinology & Metabolism; 2014 May, Vol. 99 Issue 5, p1701-1711, 11p

المؤلفون: RUSSELL, STEVEN J.¹, EL.-KHATIB, FIRAS H.², NATHAN, DAVID M.¹, MAGYAR, KENDRA L.¹, JIANG, JOHN², DAMIANO, EDWARD R.² edamiano@bu.edu

المصدر: Diabetes Care. Nov2012, Vol. 35 Issue 11, p2148-2155. 8p. 1 Chart, 3 Graphs.

مصطلحات موضوعية: *BLOOD sugar analysis, *BLOOD sugar monitoring, *DIABETES, *HYPOGLYCEMIA, *VENOUS pressure

مستخلص: OBJECTIVE--To test whether safe and effective glycemic control could be achieved in type 1 diabetes using a bihormonal bionic endocrine pancreas driven by a continuous glucose monitor in experiments lasting more than two days and including six high-carbohydrate meals and exercise as challenges to glycemic control. RESEARCH DESIGN AND METHODS--Six subjects with type 1 diabetes and no endogenous insulin secretion participated in two 51-h experiments. Blood glucose was managed with a bionic endocrine pancreas controlling subcutaneous delivery of insulin and glucagon with insulin pumps. A partialmeal-priming bolus of insulin (0.035 units/kg/meal, then 0.05 units/kg/meal in repeat experiments) was administered at the beginning of each meal (on average 78 ± 12 g of carbohydrates per meal were consumed). Plasma glucose (PG) control was evaluated with a reference quality measurement on venous blood every 15 min. RESULTS--The overall mean PG was 158 mg/dL, with 68% of PG values in the range of 70-180 mg/dL. There were no significant differences in mean PG between larger and smaller meal-priming bolus experiments. Hypoglycemia (PG ,70 mg/dL) was rare, with eight incidents during 576 h of closed-loop control (0.7% of total time). During 192 h of nighttime control, mean PG was 123 mg/dL, with 93% of PG values in the range of 70-180 mg/dL and only one episode of mild hypoglycemia (minimum PG 62 mg/dL). CONCLUSIONS--A bihormonal bionic endocrine pancreas achieved excellent glycemic control with minimal hypoglycemia over the course of two days of continuous use despite highcarbohydrate meals and exercise. A trial testing a wearable version of the system under free-living conditions is justified. [ABSTRACT FROM AUTHOR]

المؤلفون: Bionic Pancreas Research Group, Russell, Steven J¹, Beck, Roy W¹, Damiano, Edward R¹, El-Khatib, Firas H¹, Ruedy, Katrina J¹, Balliro, Courtney A¹, Li, Zoey¹, Calhoun, Peter¹, Wadwa, R Paul¹, Buckingham, Bruce¹, Zhou, Keren¹, Daniels, Mark¹, Raskin, Philip¹, White, Perrin C¹, Lynch, Jane¹, Pettus, Jeremy¹, Hirsch, Irl B¹, Goland, Robin¹, Buse, John B¹

المصدر: New England Journal of Medicine. 9/29/2022, Vol. 387 Issue 13, p1161-1172. 12p.

مستخلص: Background: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting.Methods: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed.Results: A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P<0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, -0.1 to 0.04; P<0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P = 0.39). No episodes of diabetic ketoacidosis occurred in either group.Conclusions: In this 13-week, randomized trial involving adults and children with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction than standard care in the glycated hemoglobin level. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT04200313.). [ABSTRACT FROM AUTHOR]