Automated insulin delivery system: Difference between revisions
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The '''artificial pancreas''' is a technology in development to help people with [[diabetes]], primarily type 1, automatically and continuously control their [[blood glucose level]] by providing the substitute [[endocrine]] functionality of a healthy [[pancreas]]. |
The '''artificial pancreas''' is a technology in development to help people with [[diabetes]], primarily type 1, automatically and continuously control their [[blood glucose level]] by providing the substitute [[endocrine]] functionality of a healthy [[pancreas]]. |
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The endocrine functionality of the pancreas is provided by [[Pancreatic islets|islet cells]] which produce the hormones [[insulin]] and [[glucagon]]. Artificial pancreatic technology must mimic the secretion of these hormones into the bloodstream in response to the body's changing blood glucose levels. Maintaining balanced blood sugar levels is crucial to the function of the brain, liver, and kidneys. Therefore, for type 1 patients it is necessary that the levels be kept balanced when the body cannot produce insulin itself. |
The endocrine functionality of the pancreas is provided by [[Pancreatic islets|islet cells]] which produce the hormones [[insulin]] and [[glucagon]]. Artificial pancreatic technology must mimic the secretion of these hormones into the bloodstream in response to the body's changing blood glucose levels. Maintaining balanced blood sugar levels is crucial to the function of the brain, liver, and kidneys.<ref>{{Cite web|url=http://columbiasurgery.org/pancreas/pancreas-and-its-functions|title=The Pancreas and Its Functions {{!}} Columbia University Department of Surgery|website=columbiasurgery.org|language=en|access-date=2018-11-07}}</ref> Therefore, for type 1 patients it is necessary that the levels be kept balanced when the body cannot produce insulin itself. |
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Artificial pancreas is a broad term for different [[Biological engineering|bio-engineering]] strategies currently in development to achieve these requirements. |
Artificial pancreas is a broad term for different [[Biological engineering|bio-engineering]] strategies currently in development to achieve these requirements. |
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==Approaches== |
==Approaches== |
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===Medical equipment=== |
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| ⚫ | [[Image:Bio-artificial pancreas with Islet Sheet technology.JPG|thumb|right|300px|'''The Bio-artificial pancreas''': this diagram shows a cross section of [[tissue engineering|bio-engineered tissue]] with encapsulated [[islets of Langerhans|islet cells]] which deliver [[endocrine]] [[pancreas#Function|hormones]] in response to [[glucose]].]] |
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==== Existing Technologies ==== |
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| ⚫ | A biological approach to the artificial pancreas is to implant [[tissue engineering|bioengineered tissue]] containing [[islets of Langerhans|islet cells]], or [[stem cells]] that could differentiate into such cells, which would secrete the amount of insulin, amylin, and glucagon needed in response to sensed glucose.<ref>{{cite journal|last1=Omami|first1=M|last2=McGarrigle|first2=JJ|last3=Reedy|first3=M|last4=Isa|first4=D|last5=Ghani|first5=S|last6=Marchese|first6=E|last7=Bochenek|first7=MA|last8=Longi|first8=M|last9=Xing|first9=Y|last10=Joshi|first10=I|last11=Wang|first11=Y|last12=Oberholzer|first12=J|title=Islet Microencapsulation: Strategies and Clinical Status in Diabetes.|journal=Current diabetes reports|date=July 2017|volume=17|issue=7|pages=47|doi=10.1007/s11892-017-0877-0|pmid=28523592}}</ref><ref>{{cite journal|last1=Desai|first1=T|last2=Shea|first2=LD|title=Advances in islet encapsulation technologies.|journal=Nature Reviews. Drug Discovery|date=May 2017|volume=16|issue=5|pages=338–350|doi=10.1038/nrd.2016.232|pmid=28008169}}</ref><ref>{{cite journal|last1=Sordi|first1=V|last2=Pellegrini|first2=S|last3=Krampera|first3=M|last4=Marchetti|first4=P|last5=Pessina|first5=A|last6=Ciardelli|first6=G|last7=Fadini|first7=G|last8=Pintus|first8=C|last9=Pantè|first9=G|last10=Piemonti|first10=L|title=Stem cells to restore insulin production and cure diabetes.|journal=Nutrition, metabolism, and cardiovascular diseases : NMCD|date=July 2017|volume=27|issue=7|pages=583–600|doi=10.1016/j.numecd.2017.02.004|pmid=28545927}}</ref> |
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[[Image:Artificial Pancreas.jpg|thumb|Artificial pancreas feedback system |alt=]] |
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| ⚫ | The medical equipment approach involves combining a [[continuous glucose monitor]] with an implanted [[insulin pump]] that can function together to replace the normal function of the pancreas.<ref name="Gingras2017">{{cite journal|last1=Gingras|first1=V|last2=Taleb|first2=N|last3=Roy-Fleming|first3=A|last4=Legault|first4=L|last5=Rabasa-Lhoret|first5=R|date=4 July 2017|title=The challenges of achieving postprandial glucose control using closed-loop systems in patients with type 1 diabetes.|journal=Diabetes, obesity & metabolism|doi=10.1111/dom.13052|pmid=28675686}}</ref><ref>{{cite journal|last1=Uduku|first1=C|last2=Oliver|first2=N|date=October 2017|title=Pharmacological aspects of closed loop insulin delivery for type 1 diabetes.|journal=Current Opinion in Pharmacology|volume=36|pages=29–33|doi=10.1016/j.coph.2017.07.006|pmid=28802779}}</ref><ref>{{cite journal|last1=Graf|first1=A|last2=McAuley|first2=SA|last3=Sims|first3=C|last4=Ulloa|first4=J|last5=Jenkins|first5=AJ|last6=Voskanyan|first6=G|last7=O'Neal|first7=DN|date=March 2017|title=Moving Toward a Unified Platform for Insulin Delivery and Sensing of Inputs Relevant to an Artificial Pancreas.|journal=Journal of diabetes science and technology|volume=11|issue=2|pages=308–314|doi=10.1177/1932296816682762|pmc=5478040|pmid=28264192}}</ref> |
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===Gene therapy=== |
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[[Image:Gene therapy.jpg|thumb|[[Gene therapy]]: Designing a [[viral vector]] to deliberately infect cells with [[DNA]] to carry on the viral production of [[insulin]] in response to the blood sugar level.]] |
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The original devices for use in type 1 diabetes were [[Glucose meter|blood glucose meters]]. Continuous blood glucose monitors are a more recent breakthrough and have begun to hit the markets for patient use after approval from the FDA. Both of these types of monitors require manual insulin delivery or carbohydrate intake depending on the reading from these devices. While the traditional blood glucose meters require the user to prick their finger every few hours to obtain data, continuous monitors use sensors placed just under the skin on the arm or abdomen to deliver blood sugar level data to receivers or smartphone apps as often as every few minutes. The sensors can be used for up to ten days. Four different continuous monitors are currently approved by the FDA.<ref name=":0">{{Cite news|url=https://www.managedcaremag.com/archives/2018/7/first-four-continuous-glucose-monitors|title=The First Four Continuous Glucose Monitors|date=2018-07-04|work=Managed Care magazine|access-date=2018-11-07|language=en}}</ref> |
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[[Gene therapy]] approaches have been used in research, either ''[[ex vivo]]'' to drive stem cells to become beta cells, or used directly to cause cells that do not normally produce insulin to produce it.<ref>{{cite journal|last1=Kuroda|first1=M|last2=Bujo|first2=H|last3=Aso|first3=M|last4=Saito|first4=Y|last5=Yokote|first5=K|title=Gene-manipulated Adipocytes for the Treatment of Various Intractable Diseases.|journal=Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan|date=2016|volume=136|issue=5|pages=705–9|doi=10.1248/yakushi.15-00262-4|pmid=27150923}}</ref><ref>{{cite journal|last1=Handorf|first1=AM|last2=Sollinger|first2=HW|last3=Alam|first3=T|title=Insulin gene therapy for type 1 diabetes mellitus.|journal=Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation|date=April 2015|volume=13 Suppl 1|pages=37–45|pmid=25894126}}</ref> |
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==== '''Existing Continuous Glucose Monitors''' ==== |
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===Medical equipment=== |
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The first continuous glucose monitor (CGM) was approved in December 2016. Developed by [[Dexcom]], the G5 Mobile Continuous Monitoring System requires users to prick their fingers twice a day (as opposed to the typical average 8 times daily with the traditional meters) in order to calibrate the device. The sensors used last seven days. The device uses Bluetooth technology to warn the user either through a handheld receiver or app on a smartphone if blood glucose levels reach below a certain point. The cost for this device excluding any coinsurance is an estimated $4,800 a year.<ref name=":0" /> |
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[[Image:Artificial Pancreas.jpg|thumb|The [[medical equipment]] approach to an artificial pancreas: automatic control of an [[insulin pump]] with [[control theory|feedback]] from a [[continuous glucose monitor|continuous blood glucose sensor]]]] |
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[[Abbott Laboratories|Abbott Laboratories']] FreeStyle Libre CGM was approved in September 2017. It does not support smartphone use. This device does not require finger pricks at all, and the sensor, placed on the upper arm, lasts 10 days. The estimated cost for this monitor is $1,300 a year.<ref name=":0" /> |
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| ⚫ | The medical equipment approach involves combining a [[continuous glucose monitor]] with an implanted [[insulin pump]] that can function together to replace the normal function of the pancreas.<ref name=Gingras2017/><ref>{{cite journal|last1=Uduku|first1=C|last2=Oliver|first2=N|title=Pharmacological aspects of closed loop insulin delivery for type 1 diabetes.|journal=Current Opinion in Pharmacology |
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In March 2018, the FDA approved the Guardian Connect, a CGM by [[Medtronic]], their first monitor independent from any linked insulin pumps. The device requires two finger pricks per day to be calibrated, and sensors can be worn on the upper arm or abdomen for seven days. Their system can be accessed by smartphone, and is able to predict the future glucose levels of the patient and can warn the user anywhere form 10 minutes to an hour before the level becomes too high or low. The estimated total cost is $3355.50 a year.<ref name=":0" /> |
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In September 2016 the FDA approved the Medtronic MiniMed 670G, which was the first approved hybrid [[closed-loop transfer function|closed loop system]] which senses a [[Type 1 diabetes|diabetic]] person's [[Basal (medicine)|basal]] insulin requirement and automatically adjusts its delivery to the body.<ref>{{cite web|title=Recently approved devices: The 670G System - P160017|url=http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm522764.htm|publisher=FDA|date=September 28, 2016}}</ref> |
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Dexcom's next G6 model CGM was approved in March 2018, which can last up to ten days and does not need finger prick calibration. Like Medtronic's monitor, it can predict glucose level trends. It is compatible for integration into insulin pumps. <ref name=":0" /> |
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As of 2017 dealing with blood sugar levels following a meal remained a challenge for the field.<ref name=Gingras2017>{{cite journal|last1=Gingras|first1=V|last2=Taleb|first2=N|last3=Roy-Fleming|first3=A|last4=Legault|first4=L|last5=Rabasa-Lhoret|first5=R|title=The challenges of achieving postprandial glucose control using closed-loop systems in patients with type 1 diabetes.|journal=Diabetes, obesity & metabolism|date=4 July 2017|doi=10.1111/dom.13052|pmid=28675686}}</ref> |
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==== Closed-Loop Systems ==== |
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Unlike the continuous sensor alone, the closed-loop system requires no user input in response to reading from the monitor; the monitor and insulin pump system automatically delivers the correct amount of hormone calculated from the readings transmitted.<ref>{{Cite journal|last=Elleri|first=Daniela|last2=Dunger|first2=David B|last3=Hovorka|first3=Roman|date=2011-11-09|title=Closed-loop insulin delivery for treatment of type 1 diabetes|url=https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-120|journal=BMC Medicine|language=En|volume=9|issue=1|doi=10.1186/1741-7015-9-120|issn=1741-7015}}</ref> |
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In September 2016 the FDA approved the [[Medtronic MiniMed 670G]], which was the first approved hybrid [[Closed-loop transfer function|closed loop system]] which senses a [[Type 1 diabetes|diabetic]] person's [[Basal (medicine)|basal]] insulin requirement and automatically adjusts its delivery to the body.<ref name=":1">{{Cite web|url=http://wayback.archive-it.org/7993/20170111141252/http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm522764.htm|title=Recently-Approved Devices - The 670G System - P160017|last=Health|first=Center for Devices and Radiological|website=wayback.archive-it.org|language=en|access-date=2018-11-07}}</ref> It is made up of a continuous glucose monitor, an insulin pump, and a glucose meter for calibration. It automatically functions to modify the level of insulin delivery based off the detection of blood glucose levels by continuous monitor. It does this by sending the blood glucose data through an algorithm that analyzes and makes the subsequent adjustments.<ref name=":1" /> The system has two modes. Manual mode lets the user chose the rate at which basal insulin is delivered. Auto mode regulates basal insulin levels from the continuous monitor's readings every five minutes.<ref>{{Cite web|url=https://www.medtronicdiabetes.com/products/minimed-670g-insulin-pump-system|title=MiniMed 670G Insulin Pump System {{!}} World's First Hybrid Closed Loop System|website=www.medtronicdiabetes.com|language=en|access-date=2018-11-07}}</ref> |
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The device was originally available only to those aged 14 or older, and in June 2018 was approved by the FDA for use in children aged 7-14. Families have reported better sleep quality from use of the new system, as they do not have to worry about manually checking blood glucose levels in during the night.<ref>{{Cite web|url=https://www.medtronicdiabetes.com/loop-blog/fda-approves-minimed-670g-system-children-7-13/|title=FDA Approves the MiniMed 670G System for Children 7-13 - The LOOP Blog|website=www.medtronicdiabetes.com|language=en-US|access-date=2018-11-07}}</ref> The full cost of the system is $3700, but patients have the opportunity to get it for less.<ref>{{Cite web|url=https://www.medtronicdiabetes.com/loop-blog/update-minimed-670g-availability/|title=Update on MiniMed 670G Availability|website=www.medtronicdiabetes.com|language=en-US|access-date=2018-11-07}}</ref> |
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===Bioengineering=== |
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| ⚫ | [[Image:Bio-artificial pancreas with Islet Sheet technology.JPG|thumb|right|300px|'''The Bio-artificial pancreas''': this diagram shows a cross section of [[tissue engineering|bio-engineered tissue]] with encapsulated [[islets of Langerhans|islet cells]] which deliver [[endocrine]] [[pancreas#Function|hormones]] in response to [[glucose]].]] |
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| ⚫ | A biological approach to the artificial pancreas is to implant [[tissue engineering|bioengineered tissue]] containing [[islets of Langerhans|islet cells]], or [[stem cells]] that could differentiate into such cells, which would secrete the amount of insulin, amylin, and glucagon needed in response to sensed glucose.<ref>{{cite journal|last1=Omami|first1=M|last2=McGarrigle|first2=JJ|last3=Reedy|first3=M|last4=Isa|first4=D|last5=Ghani|first5=S|last6=Marchese|first6=E|last7=Bochenek|first7=MA|last8=Longi|first8=M|last9=Xing|first9=Y|last10=Joshi|first10=I|last11=Wang|first11=Y|last12=Oberholzer|first12=J|title=Islet Microencapsulation: Strategies and Clinical Status in Diabetes.|journal=Current diabetes reports|date=July 2017|volume=17|issue=7|pages=47|doi=10.1007/s11892-017-0877-0|pmid=28523592}}</ref><ref>{{cite journal|last1=Desai|first1=T|last2=Shea|first2=LD|title=Advances in islet encapsulation technologies.|journal=Nature Reviews. Drug Discovery|date=May 2017|volume=16|issue=5|pages=338–350|doi=10.1038/nrd.2016.232|pmid=28008169}}</ref><ref>{{cite journal|last1=Sordi|first1=V|last2=Pellegrini|first2=S|last3=Krampera|first3=M|last4=Marchetti|first4=P|last5=Pessina|first5=A|last6=Ciardelli|first6=G|last7=Fadini|first7=G|last8=Pintus|first8=C|last9=Pantè|first9=G|last10=Piemonti|first10=L|title=Stem cells to restore insulin production and cure diabetes.|journal=Nutrition, metabolism, and cardiovascular diseases : NMCD|date=July 2017|volume=27|issue=7|pages=583–600|doi=10.1016/j.numecd.2017.02.004|pmid=28545927}}</ref> |
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==Initiatives around the globe== |
==Initiatives around the globe== |
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Revision as of 05:41, 7 November 2018
The artificial pancreas is a technology in development to help people with diabetes, primarily type 1, automatically and continuously control their blood glucose level by providing the substitute endocrine functionality of a healthy pancreas.
The endocrine functionality of the pancreas is provided by islet cells which produce the hormones insulin and glucagon. Artificial pancreatic technology must mimic the secretion of these hormones into the bloodstream in response to the body's changing blood glucose levels. Maintaining balanced blood sugar levels is crucial to the function of the brain, liver, and kidneys.[1] Therefore, for type 1 patients it is necessary that the levels be kept balanced when the body cannot produce insulin itself.
Artificial pancreas is a broad term for different bio-engineering strategies currently in development to achieve these requirements.
Different bio-engineering approaches under consideration include:
- the medical equipment approach—using an insulin pump under closed loop control using real-time feedback data from a continuous blood glucose monitor.
- the biological approach—the development of a treatment with engineered stem cells which potentially could be integrated into the body to increase functional beta cell count.
Approaches
Medical equipment
Existing Technologies
The medical equipment approach involves combining a continuous glucose monitor with an implanted insulin pump that can function together to replace the normal function of the pancreas.[2][3][4]
The original devices for use in type 1 diabetes were blood glucose meters. Continuous blood glucose monitors are a more recent breakthrough and have begun to hit the markets for patient use after approval from the FDA. Both of these types of monitors require manual insulin delivery or carbohydrate intake depending on the reading from these devices. While the traditional blood glucose meters require the user to prick their finger every few hours to obtain data, continuous monitors use sensors placed just under the skin on the arm or abdomen to deliver blood sugar level data to receivers or smartphone apps as often as every few minutes. The sensors can be used for up to ten days. Four different continuous monitors are currently approved by the FDA.[5]
Existing Continuous Glucose Monitors
The first continuous glucose monitor (CGM) was approved in December 2016. Developed by Dexcom, the G5 Mobile Continuous Monitoring System requires users to prick their fingers twice a day (as opposed to the typical average 8 times daily with the traditional meters) in order to calibrate the device. The sensors used last seven days. The device uses Bluetooth technology to warn the user either through a handheld receiver or app on a smartphone if blood glucose levels reach below a certain point. The cost for this device excluding any coinsurance is an estimated $4,800 a year.[5]
Abbott Laboratories' FreeStyle Libre CGM was approved in September 2017. It does not support smartphone use. This device does not require finger pricks at all, and the sensor, placed on the upper arm, lasts 10 days. The estimated cost for this monitor is $1,300 a year.[5]
In March 2018, the FDA approved the Guardian Connect, a CGM by Medtronic, their first monitor independent from any linked insulin pumps. The device requires two finger pricks per day to be calibrated, and sensors can be worn on the upper arm or abdomen for seven days. Their system can be accessed by smartphone, and is able to predict the future glucose levels of the patient and can warn the user anywhere form 10 minutes to an hour before the level becomes too high or low. The estimated total cost is $3355.50 a year.[5]
Dexcom's next G6 model CGM was approved in March 2018, which can last up to ten days and does not need finger prick calibration. Like Medtronic's monitor, it can predict glucose level trends. It is compatible for integration into insulin pumps. [5]
Closed-Loop Systems
Unlike the continuous sensor alone, the closed-loop system requires no user input in response to reading from the monitor; the monitor and insulin pump system automatically delivers the correct amount of hormone calculated from the readings transmitted.[6]
In September 2016 the FDA approved the Medtronic MiniMed 670G, which was the first approved hybrid closed loop system which senses a diabetic person's basal insulin requirement and automatically adjusts its delivery to the body.[7] It is made up of a continuous glucose monitor, an insulin pump, and a glucose meter for calibration. It automatically functions to modify the level of insulin delivery based off the detection of blood glucose levels by continuous monitor. It does this by sending the blood glucose data through an algorithm that analyzes and makes the subsequent adjustments.[7] The system has two modes. Manual mode lets the user chose the rate at which basal insulin is delivered. Auto mode regulates basal insulin levels from the continuous monitor's readings every five minutes.[8]
The device was originally available only to those aged 14 or older, and in June 2018 was approved by the FDA for use in children aged 7-14. Families have reported better sleep quality from use of the new system, as they do not have to worry about manually checking blood glucose levels in during the night.[9] The full cost of the system is $3700, but patients have the opportunity to get it for less.[10]
Bioengineering
A biological approach to the artificial pancreas is to implant bioengineered tissue containing islet cells, or stem cells that could differentiate into such cells, which would secrete the amount of insulin, amylin, and glucagon needed in response to sensed glucose.[11][12][13]
Initiatives around the globe
In the United States in 2006, JDRF (formerly the Juvenile Diabetes Research Foundation) launched a multi-year initiative to help accelerate the development, regulatory approval, and acceptance of continuous glucose monitoring and artificial pancreas technology.[14][15]
Grassroots efforts to create and commercialize a fully automated artificial pancreas system have also arisen directly from patient advocates and the diabetes community.[16] Bigfoot Biomedical, a company founded by parents of children with T1D have created algorithms and are developing a closed loop device that monitor blood sugar and appropriately provide insulin.[17]
References
- ^ "The Pancreas and Its Functions | Columbia University Department of Surgery". columbiasurgery.org. Retrieved 2018-11-07.
- ^ Gingras, V; Taleb, N; Roy-Fleming, A; Legault, L; Rabasa-Lhoret, R (4 July 2017). "The challenges of achieving postprandial glucose control using closed-loop systems in patients with type 1 diabetes". Diabetes, obesity & metabolism. doi:10.1111/dom.13052. PMID 28675686.
- ^ Uduku, C; Oliver, N (October 2017). "Pharmacological aspects of closed loop insulin delivery for type 1 diabetes". Current Opinion in Pharmacology. 36: 29–33. doi:10.1016/j.coph.2017.07.006. PMID 28802779.
- ^ Graf, A; McAuley, SA; Sims, C; Ulloa, J; Jenkins, AJ; Voskanyan, G; O'Neal, DN (March 2017). "Moving Toward a Unified Platform for Insulin Delivery and Sensing of Inputs Relevant to an Artificial Pancreas". Journal of diabetes science and technology. 11 (2): 308–314. doi:10.1177/1932296816682762. PMC 5478040. PMID 28264192.
- ^ a b c d e "The First Four Continuous Glucose Monitors". Managed Care magazine. 2018-07-04. Retrieved 2018-11-07.
- ^ Elleri, Daniela; Dunger, David B; Hovorka, Roman (2011-11-09). "Closed-loop insulin delivery for treatment of type 1 diabetes". BMC Medicine. 9 (1). doi:10.1186/1741-7015-9-120. ISSN 1741-7015.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b Health, Center for Devices and Radiological. "Recently-Approved Devices - The 670G System - P160017". wayback.archive-it.org. Retrieved 2018-11-07.
- ^ "MiniMed 670G Insulin Pump System | World's First Hybrid Closed Loop System". www.medtronicdiabetes.com. Retrieved 2018-11-07.
- ^ "FDA Approves the MiniMed 670G System for Children 7-13 - The LOOP Blog". www.medtronicdiabetes.com. Retrieved 2018-11-07.
- ^ "Update on MiniMed 670G Availability". www.medtronicdiabetes.com. Retrieved 2018-11-07.
- ^ Omami, M; McGarrigle, JJ; Reedy, M; Isa, D; Ghani, S; Marchese, E; Bochenek, MA; Longi, M; Xing, Y; Joshi, I; Wang, Y; Oberholzer, J (July 2017). "Islet Microencapsulation: Strategies and Clinical Status in Diabetes". Current diabetes reports. 17 (7): 47. doi:10.1007/s11892-017-0877-0. PMID 28523592.
- ^ Desai, T; Shea, LD (May 2017). "Advances in islet encapsulation technologies". Nature Reviews. Drug Discovery. 16 (5): 338–350. doi:10.1038/nrd.2016.232. PMID 28008169.
- ^ Sordi, V; Pellegrini, S; Krampera, M; Marchetti, P; Pessina, A; Ciardelli, G; Fadini, G; Pintus, C; Pantè, G; Piemonti, L (July 2017). "Stem cells to restore insulin production and cure diabetes". Nutrition, metabolism, and cardiovascular diseases : NMCD. 27 (7): 583–600. doi:10.1016/j.numecd.2017.02.004. PMID 28545927.
- ^ Artificial Pancreas Project : JDRF
- ^ KMorandi says (2017-08-10). "Insurers can profit while improving the lives of people with type 1 diabetes". STAT. Retrieved 2017-08-10.
- ^ Hurley, Dan (24 December 2014) [1] WIRED Magazine, Diabetes Patients Are Hacking Their Way Toward a Bionic Pancreas
- ^ Knutson, Ryan (8 June 2015) [2] The Wall Street Journal, Computer Experts Deliver Insulin to Diabetic Kids