Imagine for a moment that you are diagnosed with Type 1 Diabetes Mellitus (T1DM) and the insulin you take could jeopardise your health if you get the dose just a little bit wrong. Imagine that the dose you took in the morning which worked, doesn't work now and imagine that you have to worry about this every single moment of your life from the day you were diagnosed. You have to live with fear your entire life. Thanks to the advances in medical science it's no longer a death sentence like it used to be in the earlier days but it's still a life sentence which restricts the victims from having a normal life. People with Type 1 Diabetes Mellitus have to constantly check their glucose level 10 to 12 times a day and then inject a calculated dose of insulin manually. This constantly cuts in their daily chores and prevents them from having a normal carefree life.

In the history of diabetes technology, every tool that's ever developed for diabetes has improved health and medical control of the diabetes. This however comes at the expense of increased burden on patients. It constantly asks people with diabetes to do more, think more, test more, and wear more. The new technology called Hybrid closed loop insulin delivery system helps improve the lifestyle of T1DM patients as well as increase control over it.

In 2016, FDA approved its first hybrid closed loop delivery system. These are also called as artificial pancreas as they replicate the function of pancreas. These are wearable systems which constantly monitor the glucose level using Continuous Glucose Monitor (CGM) and send a signal to the insulin pump which injects insulin subcutaneously in the body accordingly. There is a direct communication between CGM system and the pump. As it happens automatically 'closed' term is used and because of the continuous cycle of feedback information the term 'loop' is used in the title of this system. This system uses a personalised model-predictive control algorithm to calculate the insulin dose. There are two types in which this device is attached to the body.

The first type has four components-CMG sensor, CGM receiver, CAD and insulin pump. The CGM sensor and the infusion site are inserted under the skin of the patient and the insulin pump is attached to the infusion site via a “tube”. The CGM receiver displays the updated readings as graphs minute-by-minute. The CAD (Control Algorithm device) e.g. - smartphones, tablets or personal computers receive these readings from CGM receiver and calculates the dose using an algorithm. The CAD communicates with insulin pump implanted in the body worn via Bluetooth and that automatically administers the correct insulin dose. The CAD tells the patient how much insulin is being injected and if the system is working or not.

The second type has two components- disposable insulin pump (POD) and personal diabetes manager (PDM). The PDM is a hand-held, battery-powered remote controller for the POD (insulin pump). It has seven functional buttons, a back-lit liquid-crystal coloured display, and a blood glucose (BG) meter. The PDM provides audio alarms, alerts, and reminders related to insulin delivery, reservoir level, POD functioning, and battery life. The POD is a microprocessor- controlled device worn directly on the body. It delivers insulin based on the user's custom-programmed basal rates and bolus doses for up to 3 days according to patient's individual insulin needs. The POD is activated and controlled exclusively through use of the PDM. The POD and PDM interact wirelessly using secure, bidirectional radio frequency. Wireless interaction is only required to set a bolus delivery, change system settings, perform BG measurements, or change the POD. In operation mode and during basal delivery, no wireless connection is needed, so the PDM does not need to be near the POD. The POD sounds an alarm if any attention is needed.

The problem with this type of technology is that the glucose level in tissue fluid which is monitored by CGM doesn't change as quickly as blood glucose level and it takes some time for insulin injected in the subcutaneous fat to take effect. Thus the insulin effect always lags somewhat compared to the insulin that is made by normal functioning pancreas where changes in blood glucose level are sensed instantly and insulin is directly released into blood. If wrong (excess) dose of insulin gets injected it may result in hypoglycaemia which is very dangerous.

The safety and performance of hybrid closed loop systems were tested on adults as well as children. It was found that children with type 1 diabetes mellitus have increased sensitivity as compared to adolescents and adults and are at a higher risk of severe hypoglycaemia overnight. On 21June 2018, FDA approved hybrid closed loop system for use in paediatric patients. There are few brands in market which sell hybrid closed loop insulin drug delivery system such as OmniPod, MiniMed 670G etc.

A newer approach to avoid hypoglycaemia caused due to this system is to control glucose level by releasing insulin as well as glucagon as the pancreas release insulin to lower glucose levels and release glucagon to raise glucose levels. This system has the potential to eliminate the need for carbohydrate counting before meals, which is required in hybrid closed loop drug delivery system.

This technology is new to the medical industry and more tests are being done to improve it. As of now this kind of system is available in the USA and to some extent in Canada and will take time to reach the underdeveloped and developing countries. One thing is for sure that this technology will create a paradigm shift in the way we think of Type 1 Diabetes Mellitus.

Maithili Pokle

T.Y.B.Pharm

Tags: MET Institute of Pharmacy