Artificial Pancreas
Devices for simulating the activity of the pancreas. They can be either electromechanical, consisting of a glucose sensor, computer, and insulin pump or bioartificial, consisting of isolated islets of Langerhans in an artificial membrane.

Insulin Infusion Systems
Portable or implantable devices for infusion of insulin. Includes open-loop systems which may be patient-operated or controlled by a pre-set program and are designed for constant delivery of small quantities of insulin, increased during food ingestion, and closed-loop systems which deliver quantities of insulin automatically based on an electronic glucose sensor.

What is the pancreas?

The pancreas is an organ in the body that secretes several hormones, including insulin and glucagon, as well as digestive enzymes that help break down food. Insulin helps cells in the body take up glucose (sugar) from the blood to use for energy, which lowers blood glucose levels. Glucagon causes the liver to release stored glucose, which raises blood glucose levels.

Type 1 diabetes occurs when the pancreas produces little or none of the insulin needed to regulate blood glucose. Type 2 diabetes occurs when the pancreas does not produce enough insulin or the body becomes resistant to the insulin that is present. Patients with type 1 diabetes and some patients with type 2 diabetes inject insulin, and occasionally glucagon, to regulate their blood glucose, which is critical to lower their risk of long-term complications such as blindness, kidney failure and cardiovascular disease.

When managing diabetes, many patients must vigilantly test blood glucose with a glucose meter, calculate insulin doses, and administer necessary insulin doses with a needle or insulin infusion pump to lower blood glucose. Glucagon may be injected in an emergency to treat severe low blood glucose. Some patients benefit from additional monitoring with a continuous glucose monitoring system.

What is an artificial pancreas device system?

The Artificial Pancreas Device System is a system of devices that closely mimics the glucose regulating function of a healthy pancreas.

Most Artificial Pancreas Device Systems consists of three types of devices already familiar to many people with diabetes: a continuous glucose monitoring system (CGM) and an insulin infusion pump. A blood glucose device (such as a glucose meter) is used to calibrate the CGM.

A computer-controlled algorithm connects the CGM and insulin infusion pump to allow continuous communication between the two devices. Sometimes an artificial pancreas device system is referred to as a "closed-loop" system, an "automated insulin delivery" system, or an "autonomous system for glycemic control."

An Artificial Pancreas Device System will not only monitors glucose levels in the body but also automatically adjusts the delivery of insulin to reduce high blood glucose levels (hyperglycemia) and minimize the incidence of low blood glucose (hypoglycemia) with little or no input from the patient.

The FDA is collaborating with diabetes patient groups, diabetes care providers, medical device manufactures, researchers, and academic investigatorsto foster innovation by clarifying agency expectations for clinical studies and product approvals. These efforts have accelerated the development of the first hybrid closed loop system, the Medtronic's MiniMed 670G System

The FDA's guidance, The Content of Investigational Device Exemption (IDE) and Premarket Approval (PMA) Applications for Artificial Pancreas Device Systems, addresses requirements for clinical studies and premarket approval applications for and artificial pancreas device system, and provided a flexible regulatory approach to support the rapid, safe and effective development of artificial pancreas device systems. (See below).

The Artificial Pancreas System (An Autonomous System for Glycemic Control)

The illustration below describes the parts of a type of artificial pancreas device system and shows how they work together.

1. Continuous Glucose Monitor (CGM). A CGM provides a steady stream of information that reflects the patient’s blood glucose levels. A sensor placed under the patient's skin (subcutaneously) measures the glucose in the fluid around the cells (interstitial fluid) which is associated with blood glucose levels. A small transmitter sends information to a receiver. A CGM continuously displays both an estimate of blood glucose levels and their direction and rate of change of these estimates.
   • Blood Glucose Device (BGD). Currently, to get the most accurate estimates of blood glucose possible from a CGM, the patient needs to periodically calibrate the CGM using a blood glucose measurement from a BGD; therefore, the BGD still plays a critical role in the proper management of patients with an APDS. However, over time, we anticipate that improved CGM performance may do away with the need for periodic blood glucose checks with a BGD.
2. Control algorithm. A control algorithm is software embedded in an external processor (controller) that receives information from the CGM and performs a series of mathematical calculations. Based on these calculations, the controller sends dosing instructions to the infusion pump. The control algorithm can be run on any number of devices including an insulin pump, computer or cellular phone. The FDA does not require the control algorithm to reside on the insulin pump.
3. Insulin pump. Based on the instructions sent by the controller, an infusion pump adjusts the insulin delivery to the tissue under the skin.
4. The Patient. The patient is an important part of Artificial Pancreas Delivery System. The concentration of glucose circulating in the patient’s blood is constantly changing. It is affected by the patient’s diet, activity level, and how his or her body metabolizes insulin and other substances.

An artificial pancreas is a system made of three parts that work together to mimic how a healthy pancreas controls blood glucose, also called blood sugar, in the body. An artificial pancreas is mainly used to help people with type 1 diabetes.

In type 1 diabetes, the pancreas does not produce insulin. People with type 1 diabetes control their blood glucose level by checking it and taking insulin, either by injection or through an insulin infusion pump, several times a day. An artificial pancreas automatically monitors your blood glucose level, calculates the amount of insulin you need at different points during the day, and delivers it.

Most artificial pancreas systems require you to count and enter the amount of carbohydrates you consume at mealtime. These are called “hybrid” artificial pancreas systems, because some of the insulin is given automatically and some is given based on the information you enter. These systems help control blood glucose levels throughout the day and night, making it easier for people with type 1 diabetes to keep their blood glucose level in range. Keeping blood glucose levels in range will prevent other health problems from developing and may improve daily life for people with type 1 diabetes.

Other names for the artificial pancreas include

• automated insulin-delivery system

• closed-loop system

• bionic pancreas

Three devices make up an artificial pancreas system.

• A continuous glucose monitor (CGM) tracks blood glucose levels every few minutes using a tiny sensor that is inserted under the skin. The sensor wirelessly sends the information to a program stored on a smartphone or on an insulin infusion pump.

• The program calculates how much insulin is needed and signals the insulin infusion pump when insulin needs to be delivered.

• The insulin infusion pump will deliver small doses of insulin throughout the day when blood glucose levels are not in your target range. There are different types of insulin pumps.
  • One type of pump is worn outside the body on a belt or in a pocket or pouch. Insulin flows from the pump through a plastic tube that connects to a smaller tube, called a catheter, which has a needle that is inserted under the skin and stays in place for several days.
  • Another type of pump attaches directly to the skin with an adhesive pad and gives insulin through a catheter inserted under the skin. This kind of pump is replaced every few days.

Next-generation technology maintains blood glucose levels by automatically delivering insulin.

A device known as a bionic pancreas, which uses next-generation technology to automatically deliver insulin, was more effective at maintaining blood glucose (sugar) levels within normal range than standard-of-care management among people with type 1 diabetes, a new multicenter clinical trial has found. The trial was primarily funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health, and published in the New England Journal of Medicine (link is external) .

Automated insulin delivery systems, also called artificial pancreas or closed-loop control systems, track a person’s blood glucose levels using a continuous glucose monitor and automatically deliver the hormone insulin when needed using an insulin pump. These systems replace reliance on testing glucose level by fingerstick, continuous glucose monitor with separate insulin delivery through multiple daily injections, or a pump without automation.

Compared to other available artificial pancreas technologies, the bionic pancreas requires less user input and provides more automation because the device’s algorithms continually adjust insulin doses automatically based on users’ needs. Users initialize the bionic pancreas by entering their body weight into the device’s dosing software at the time of first use.

Users of the bionic pancreas also do not have to count carbohydrates, nor initiate doses of insulin to correct for high blood glucose. In addition, health care providers do not need to make periodic adjustments to the settings of the device.

“Keeping tight control over blood glucose is important in managing diabetes and is the best way to prevent complications like eye, nerve, kidney, and cardiovascular disease down the road," said Dr. Guillermo Arreaza-Rubín, director of NIDDK’s diabetes technology program. “The bionic pancreas technology introduces a new level of ease to the day-to-day management of type 1 diabetes, which may contribute to improved quality of life.”

The 13-week trial, conducted at 16 clinical sites across the United States, enrolled 326 participants ages 6 to 79 years who had type 1 diabetes and had been using insulin for at least one year. Participants were randomly assigned to either a treatment group using the bionic pancreas device or a standard-of-care control group using their personal pre-study insulin delivery method. All participants in the control group were provided with a continuous glucose monitor, and nearly one-third of the control group were using commercially available artificial pancreas technology during the study.

In participants using the bionic pancreas, glycated hemoglobin, a measure of a person’s long-term blood glucose control, improved from 7.9% to 7.3%, yet remained unchanged among the standard-of-care control group. The bionic pancreas group participants spent 11% more time, approximately 2.5 hours per day, within the targeted blood glucose range compared to the control group. These results were similar in youth and adult participants, and improvements in blood glucose control were greatest among participants who had higher blood glucose levels at the beginning of the study.

“Our observation that this system can safely improve glucose control to the degree we found, and do so despite requiring much less input from users and their health care providers, has important implications for children and adults living with diabetes,” said Dr. Steven Russell, study chair, associate professor of medicine at Harvard Medical School, and staff physician at the Massachusetts General Hospital in Boston.

Hyperglycemia, or high blood glucose, caused by problems with insulin pump equipment, was the most frequently reported adverse event in the bionic pancreas group. The number of mild hypoglycemia events, or low blood glucose, was low and was not different between the groups. The frequency of severe hypoglycemia was not statistically different between the standard of care and bionic pancreas groups.

Four companion papers were also published in Diabetes Technology and Therapeutics, two of which provided more detailed results among the adult and youth participants. The third paper reported results from an extension study in which the participants from the standard-of-care control group switched to using the bionic pancreas for 13 weeks and experienced improvements in glucose control similar to the bionic pancreas group in the randomized trial. In the fourth paper, results showed that using the bionic pancreas with a faster-acting insulin in 114 adult participants improved glucose control as effectively as using the device with standard insulin.

“NIDDK’s decades-long investment in developing advanced technologies for diabetes management has reached another promising milestone and continues to provide significant return,” said NIDDK Director Dr. Griffin P. Rodgers. “While we continue to search for a cure for type 1 diabetes, devices like the bionic pancreas can allow people to worry less about their blood-glucose levels and focus more on living their fullest, healthiest lives.”

Dr. Edward Damiano, project principal investigator, professor of biomedical engineering at Boston University, and founder and executive chair of Beta Bionics, Inc., concurs. “The completion of this study represents a major milestone for the bionic pancreas initiative, which simply would not have been possible had it not been for the support provided by the NIDDK over the years.”

The study is one of several pivotal trials funded by NIDDK to advance artificial pancreas technology and look at factors including safety, efficacy, user-friendliness, physical and emotional health of participants, and cost. To date, these trials have provided the important safety and efficacy data needed for regulatory review and licensure to make the technology commercially available. The Jaeb Center for Health Research in Tampa, Florida, served as coordinating center.

Funding for the study was provided by NIDDK grant 1UC4DK108612 to Boston University, by an Investigator-Initiated Study award from Novo Nordisk, and by Beta Bionics, Inc., which also provided the experimental bionic pancreas devices used in the study. Insulin and some supplies were donated by Novo Nordisk, Eli Lilly, Dexcom, and Ascensia Diabetes Care. Partial support for the development of the experimental bionic pancreas device was provided by NIDDK Small Business Innovation Research (SBIR) grant 1R44DK120234 to Beta Bionics, Inc.

The NIDDK, a component of the NIH, conducts and supports research on diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition, and obesity; and kidney, urologic, and hematologic diseases. Spanning the full spectrum of medicine and afflicting people of all ages and ethnic groups, these diseases encompass some of the most common, severe and disabling conditions affecting Americans.

• threshold suspend and predictive suspend systems

• insulin-only systems

• dual hormone systems

Threshold suspend and predictive suspend systems

The threshold suspend and predictive suspend systems can temporarily stop or “suspend” delivering insulin if your blood glucose level gets low.

The threshold suspend system stops delivering insulin when your blood glucose level drops to a pre-set level. The predictive suspend system calculates your blood glucose level and will stop delivering insulin before your blood glucose level gets too low. Neither system automatically increases insulin doses.

Stopping insulin delivery at the right moment can help a person with type 1 diabetes avoid low blood sugar, or hypoglycemia, a condition when a person’s blood glucose level is lower than their target range. These systems may help people with type 1 diabetes who develop hypoglycemia overnight, particularly children.

Insulin-only systems

Insulin-only systems keep your blood glucose level within your target range by automatically increasing or decreasing the amount of insulin delivered to your body based on your CGM values. Insulin-only systems can increase insulin doses if your blood glucose level is higher than your target range.

One type of insulin-only system is the hybrid system. The hybrid insulin-only system automatically adjusts insulin doses in response to your CGM values. But you must still count carbohydrate levels and calculate insulin doses for all meals and snacks.

Dual hormone systems

Researchers are currently developing and testing systems that use two hormones—insulin to lower glucose levels and glucagon to raise blood glucose levels. Using two hormones to control blood glucose is similar to the way the pancreas works in people who do not have diabetes. These systems may be able to tightly control glucose levels without causing hypoglycemia. Researchers are also testing how well other combinations, such rapid-acting insulin and pramlintide, can control blood glucose levels.

You need a prescription from your doctor to get an artificial pancreas. Together, you and your doctor will consider which system can best control your blood glucose levels and fit your lifestyle. Other factors to consider are

• age—some models are approved for children as young as 2 years old, while others are approved for people ages 6 years and older

• whether you can place the devices in the correct position without help, check that they are working properly, and adjust them or enter carbohydrate data as needed

• whether you prefer an insulin pump with tubing or one that attaches directly to your skin

• whether you have access to a Wi-Fi network so that information can flow between the parts of the system

Parents or guardians of children with type 1 diabetes should talk about appropriate artificial pancreas systems with the child’s doctor.

Researchers continue to develop new and different types of artificial pancreas systems that will meet the needs of people with type 1 diabetes and other types of diabetes.

How much an artificial pancreas will cost you depends on your health insurance provider. Private insurance plans or government plans may not cover all artificial pancreas systems available for people with type 1 diabetes. More information on how to pay for type 1 diabetes devices and medicines is found in Financial Help for Diabetes Care.

Diabetes is a disease that happens when your blood glucose, or blood sugar, is too high. Glucose is the body’s main source of energy. Insulin, a hormone made by the pancreas, tells the body’s cells to take in glucose. If you have type 1 diabetes, your body doesn’t make insulin, and glucose builds up in your blood. Over time, high levels of blood glucose can cause serious health problems.

People with diabetes must test their blood glucose regularly with a fingerstick or use a continuous glucose monitor. They take insulin when needed by giving themselves injections or using an insulin pump. Researchers have developed all-in-one diabetes management systems. These “artificial pancreas” systems track blood glucose levels using a continuous glucose monitor, calculate when insulin is needed, and automatically deliver it using an insulin pump. Artificial pancreas systems don’t entirely eliminate the need for patient input, but substantially reduce the level of effort.

To test the efficacy and safety of an artificial pancreas, a team led by Drs. Sue A. Brown and Boris Kovatchev at the University of Virginia and Dr. Roy W. Beck at the Jaeb Center for Health Research carried out a six-month study of the Control-IQ technology system from Tandem Diabetes Care. They enrolled 168 people with type 1 diabetes. The study was funded by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Results were published online on October 16, 2019, in the New England Journal of Medicine.

Participants were randomly assigned to use either the Control-IQ artificial pancreas or sensor-augmented pump (SAP) therapy. SAP uses a continuous glucose monitor and insulin pump, but still requires frequent input and decisions from the user about when and how much insulin to administer. The Control-IQ system uses advanced computer algorithms to automatically adjust insulin doses based on glucose levels.

People who used the artificial pancreas system showed a significant increase in the amount of time their blood glucose levels stayed in the target range of 70 to 180 mg/dL—from 61% at start of the study to 71%. This translated to an additional 2.6 hours per day in range. In contrast, the control group remained unchanged at 59%. Artificial pancreas users also showed improvements in time spent with high and low blood glucose and other measurements related to diabetes control.

No severe low blood sugar (hypoglycemia) events occurred in either group. Diabetic ketoacidosis—a life-threatening complication—occurred in one participant in the artificial pancreas group due to an issue with the insulin pump setup called pump infusion set failure.

“This artificial pancreas system has several unique features that improve glucose control beyond what is achievable using traditional methods,” says Kovatchev. “In particular, there is a special safety module dedicated to prevention of hypoglycemia, and there is gradually intensified control overnight to achieve near-normal blood sugar levels every morning.”

“Artificial pancreas technology has tremendous potential to improve the day-to-day lives of people with type 1 diabetes,” says NIDDK Director Dr. Griffin P. Rodgers. “By making management of type 1 diabetes easier and more precise, this technology could reduce the daily burden of this disease, while also potentially reducing diabetes complications including eye, nerve, and kidney diseases.”

An artificial pancreas may help people with type 1 diabetes reach their target blood glucose levels and improve their quality of life.

With an artificial pancreas system, your glucose levels will be monitored continuously. The computer program improves blood glucose control by automatically adjusting the amount of insulin it delivers to keep your blood glucose levels in range. The system helps you avoid hypoglycemia and hyperglycemia.

Doctors can monitor insulin doses remotely and recommend dosage adjustments for people who need closer supervision. Also, parents or guardians can monitor blood glucose levels from their own smartphones throughout the day and night.

Artificial pancreas systems are not completely “hands off.” You have to regularly maintain the devices to be sure they are working properly and enter meal sizes into the system every time you eat. You will also need to

• check the CGM and infusion pump catheter to be sure they are in place and change them when needed

• check the CGM for accuracy and replace the CGM sensor from time to time

• count the amount of mealtime carbohydrates and enter them into the system

• adjust the computer program settings to make sure you get the right amount of insulin to keep your blood glucose level in your target range

• reboot or reconnect the CGM, infusion pump, and computer program if there are problems

• manage high or low blood glucose levels if the system is not able to keep your blood glucose in range

The adhesive patches used with these systems may cause skin redness or irritation. Some medicines you take might also interfere with the glucose monitor.

For more than 20 years, the NIDDK has funded technology to improve the lives of people with type 1 diabetes. Together with other federal government agencies and partner organizations, the NIDDK works to advance blood glucose monitoring, automate insulin delivery, and decrease complications of living with type 1 diabetes.

The NIDDK supports clinical trials to test artificial pancreas systems for children, adolescents, and adults with type 1 diabetes. New trials will test artificial pancreas systems in larger groups of people over longer periods of time.

Recent clinical trials funded by the NIDDK have shown that artificial pancreas systems control blood glucose levels better than other methods, especially through the night—a challenge for many people with type 1 diabetes—and in children as young as 6 years old. Researchers continue to improve the design and components of artificial pancreas systems and to expand their use in different age groups and in real-life situations, such as during exercise.

An insulin pump is a treatment option for people who live with diabetes and need to take insulin. Wearing an insulin pump helps you or your loved one stay on top of your insulin needs every day. But there are important things to know and learn.

New to using an insulin pump? Find out tips to help manage daily activities.

What’s an Insulin Pump, and How Does It Work?

If you have type 1 diabetes, you’ll need to take insulin shots or wear an insulin pump to replace the insulin your body needs but doesn’t make. If you have type 2 diabetes, you may need to take insulin if other treatments are not able to keep your blood sugar within your target range.

An insulin pump is about the size of a small smartphone. It usually has a display screen, a place for an insulin container, and a thin tube with a needle that attaches to your body (the infusion set). The needle goes into the fatty layer under your skin, usually in the stomach area.

This device delivers insulin to manage blood sugar almost the way your body would: a steady flow and an extra dose. The steady flow is your insulin pump regularly giving you short-acting or rapid-acting insulin, called basal insulin. To keep your blood sugar from spiking after eating, you can program the pump to deliver an extra dose, called bolus insulin.

How to Use an Insulin Pump When You’re Physically Active

With an insulin pump, you can adjust insulin doses and durations, reducing the risk of exercise-related low blood sugar. However, wearing an insulin pump during physical activity has its own challenges.

The type, intensity, and duration of physical activity can affect your blood sugar levels. It’s important to keep track of your blood sugar before, during, and after you’re active and share the results with your health care team. They can help you to set insulin doses on your pump if needed.

If you have trouble keeping your pump in place, you may:

• Apply medical tape around the edges of your infusion set.
• Ask your doctor if you can disconnect the pump and for how long during physical activity.
• Ask your doctor if you can place your infusion set in a part of your body that moves less when you’re active.

How to Shower or Swim With an Insulin Pump

Insulin pumps can handle some moisture, but not all are waterproof. If you can’t or don’t want to disconnect your pump, you may:

• Ask your health care team for a longer set of tubing that won’t limit your movement. That way you can put your pump on a shelf or place it on the floor beside the bathtub. Or put the pump inside a waterproof pouch and hang it on a shower curtain hook.
• Put the pump in a waterproof case before swimming and place it securely under a lightweight wetsuit, scuba top, or T-shirt.

It’s important to make sure that your pump doesn’t get too warm or too cold when you’re in the shower or bath or while swimming. Insulin is sensitive to temperature. Exposure to heat or cold can reduce the quality of the insulin. The ideal temperature for your insulin pump may vary by brand. You can check the user guide or the label on your pump.

How to Wear an Insulin Pump in Bed

You may have some questions about wearing an insulin pump in bed. What if you roll onto the pump, get tangled up in the tube, or press a button while sleeping?

Rolling onto your insulin pump won’t damage it — it’s designed to be worn when you’re awake or asleep. And the tube is thick enough not to get too tangled. If the tangling still bothers you, try using less tubing when you change your infusion set next time.

It’s also unlikely to press any buttons on the pump to deliver a bolus in your sleep. The buttons are designed not to be pressed by accident, and setting a bolus needs more than one press of a button. But if sleeping on the pump makes you uncomfortable, try to clip the pump to your pajamas, put it inside a pocket, or place it under the pillow to keep it in a fixed position.

What about sex? It’s a good idea to ask your doctor if you can take your pump off during intimate moments and for how long. Sex is a form of exercise, so keep in mind that blood sugar may drop while you’re sexually active.

How to Hide an Insulin Pump

While insulin pumps keep getting smaller, fitting a device into your day-to-day clothing choices can be a challenge. If you prefer not showing your insulin pump, you may:

• Choose underwear with pockets and put your pump into a pocket.
• Use a bra pouch that is available for insulin pumps.
• Clip the pump to a belt, armband, or leg strap.
• Tape your pump to your skin where it will be covered by your clothing.

Have a Backup Plan

Using an insulin pump doesn’t take away the need to check your blood sugar. Checking blood sugar regularly is important because it will warn you if your pump stops working right. And if it breaks or falls off, you need to be ready to give yourself insulin by injection. To get prepared:

• Ask your doctor about creating a backup kit.
• Update your insulin backup plan at every routine visit.
• Have your pump’s customer service number in hand so that you can get help to reset the device if needed.

Using an insulin pump may make you or your loved one’s diabetes management easier. It’s not permanent; you can change your mind and return to injections at any time. Talk with your health care team to find which method best fits your needs.

You may also want to ask your doctor for a referral for diabetes self-management education and support (DSMES) for hands-on help with your device.

Definition/Introduction

The prevalence of diabetes has increased fourfold in the last three to four decades. It currently affects more than 500 million people in the world. Of these, 90% of this is type 2 diabetes. Although oral medications can also manage type 2 diabetes, a significant percentage of these people require insulin for proper glycemic control. Type 1 diabetes is solely insulin-dependent and involves a substantial portion of young kids 18 years of age, posing a considerable challenge to their management.

Insulin delivery has evolved remarkably over the last century. In the early 20th century, the first type 1 diabetic was treated with insulin, which served as a lifesaving measure for this patient. Later on, advancements in insulin production led to the development of human insulin by the end of the 20th century. Currently, we have many insulin preparations available, including short-acting, ultra short-acting, long-acting, ultra long-acting, intermediate-acting, and mixed preparations. The insulin analogs have been prepared through genetic engineering and are very similar to human insulin. The development of insulin pens has tremendously improved insulin delivery in terms of ease and accuracy.

Late in the 20th century, a continuous subcutaneous insulin infusion (CSII) delivery system was developed, which is currently commonly known as an insulin pump. The first insulin pump was about the size of an Army backpack. The closed-loop pumps were designed to deliver insulin and dextrose as needed as a computerized algorithm calculated the dosing through the real-time measurement of blood glucose since the blood glucose analyzer was inside the insulin pump. But the size and the complexity of those devices limited their use, and they were solely used for research purposes. The next generation devices had an open-loop insulin delivery, which was delivered intravenously at a preset rate and boluses at 15 times the set rate. But recurrent infections and phlebitis also limited the use of these sets of insulin pumps. In 1976 the first commercial insulin pump was developed that was called blue brick and was later termed the Auto Syringe. It was designed by Kamen. Complications, including hyperglycemia, diabetic ketoacidosis, and infection at the injection site, were common with early pumps causing the limited acceptance of this technology until the 1990s.

Newer and more refined technology has now revolutionized insulin pumps in terms of their ease of use and the quality of care, resulting in improved glycemic control. There has been growing popularity of these devices, and insulin pumps are now becoming the mainstay of treatment for insulin-dependent diabetes. Recent studies report population disparity in the access to insulin pumps even when medical insurance plans cover the cost.

Insulin pumps are devices that continuously deliver short-acting insulin at a predetermined or auto-adjusted rate per hour.

Insulin Pump Parts

1. The pump itself
2. Infusion set
3. Sensor and transmitter in sensor-augmented insulin pumps

For most devices, the pump and infusion set are separate, connected by thin plastic tubing, but some devices combine both into one called the tubeless pump. The infusion set is attached to the patient with a cannula placed in the subcutaneous tissue and secured with adhesive. Infusion sets are typically placed into the upper arm, abdomen, lower back, or upper thigh. The pump contains the reservoir and the battery. The reservoir is changed every two to three days. The reservoir typically holds a two to three-day supply of rapid-acting insulin analog depending on the patient's total daily insulin needs. It requires replacement after all the insulin is used up in the reservoir. Battery requirements vary from device to device; some contain a rechargeable lithium battery that uses a cable, whereas others require a standard alkaline battery. Pumps should always be on if there is a functioning battery. Often the pump will be in standby mode to conserve battery. From the home screen of the insulin pump, there will be options to review basal insulin settings and the history of delivered insulin boluses. Additionally, there will be settings for priming the device for changing infusion sets and insulin reservoirs. Returning to an active home screen requires a specific series of button presses that vary depending on the device.

Insulin type used: This is usually rapid-acting insulin-like lispro, aspart, or glulisine, but also any kind of rapid-acting insulin can be used in an insulin pump. In some cases with uncontrolled diabetes and a total daily dose (TDD) of over 100 Units of insulin, U-500 concentrated regular insulin can also be used in the insulin pump. This reduces the frequency at which the reservoir has to be changed.

Insulin Delivery

Basal: Insulin is continuously delivered at a preset rate or an auto-adjusted rate for a basal supply lasting 24 hours.

Mealtime Bolus: Insulin is also delivered at the time of meals as a mealtime bolus. Bolus is calculated based on the number of carbs entered by the patient. The insulin to carb ratio (ICR) has to be entered into the pump beforehand by the patient or their clinician and is calculated by the formula: ICR: 450/TDD. ICR reflects the number of grams of carbs covered by one unit of insulin. With insulin pumps, there is the option for different bolus profiles, including dual wave, short extended, and long extended boluses, which will be discussed below.

The patient also gets a correction bolus along with the mealtime bolus insulin, and the correction is calculated based on the insulin sensitivity factor (ISF). ISF shows how much the blood glucose is lowered by 1 unit of insulin. ISF is calculated by the formula: 1700/TDD.

There are currently two different modes in which the insulin pumps can be used:

1. Auto mode: In this mode, the pump is usually connected to or communicates to a continuous glucose monitoring device (CGM). Preset algorithms will change the basal rate of insulin delivery and adjust it based on blood glucose. There is a basal IQ and also a control IQ as some examples of the auto mode. There are also temporary basal rates in situations with higher or lower insulin requirements. The rate is adjusted based on the ISF.
2. Manual Mode: In this mode, the user, or the physician, can set a predetermined basal rate based on the total daily dose of insulin needed by that patient. The rates can be adjusted and have to be entered manually.

The hybrid closed-loop system is the first generation of automated insulin delivery, which dynamically modulates basal insulin delivery but still requires the users to administer boluses.

Some newer modalities will come to market, like fully automated multi-hormonal closed-loop systems.

Automated adjustment of bolus calculators is available to improve glycemic control and postprandial spikes.

Insulin pump treatment is associated with improved glycemic control and decreased number of daily injections. Although the data does not document a clear difference in glycemic control in young children, there is increased user satisfaction among the parents of the kids with the use of insulin pumps.

There is also a feature that allows for a dual wave bolus, which involves a usual pre-meal insulin bolus followed by an extended bolus delivered evenly over many hours as programmed by the patient. The study comparing the normal bolus delivery with the dual wave bolus showed improved glycemic control in patients receiving the dual wave bolus, and it prevented prolonged postprandial hyperglycemic excursions.

Duration of insulin action: This is the time rapid-acting insulin will take to control blood glucose. Duration of insulin action is a decline in bolus activity by 20 to 25% each hour. As a result, a certain percentage of insulin is still available at the end of 3 to 4 hours. In general, the greater the bolus amount of insulin is, the higher the amount of insulin is available at the end of that time. Insulin on board is a term used to describe the amount of insulin available after a bolus is delivered for the next 3 to 5 hours as determined by the preset insulin action time in the insulin pump.

There are also features associated with hypoglycemia suspension of the pumps used in auto mode with the sensor-augmented version. This function is referred to as threshold suspend (TS), or low glucose suspends (LGS). There is a 40 to 50% decrease in the rate of hypoglycemia without any significant increase in HbA1c. Another technology known as predictive low glucose suspend (PLGS) will suspend the insulin delivery almost 30 minutes before hypoglycemia is expected to occur.

Issues of Concern

Infusion site infection, erythema, induration, tenderness to palpation, or signs of fluid leakage from the infusion site are some of the commonest problems that can arise. They are all indications for removal and the need for a new site to be chosen at a different location.

Hyperglycemia: Insulin analogs are rapid-acting, with the onset of action within 15 minutes, peaking in approximately 60 minutes, and lasting less than five hours after injection. In patients on a continuous subcutaneous insulin infusion, hyperglycemia secondary to disruption in insulin delivery must be on the differential.

The clinician should always check the infusion site during the physical exam. The easiest way to evaluate is to deliver an insulin bolus via the pump and recheck blood glucose. If blood glucose remains elevated despite insulin bolus, the tubing or infusion set is likely compromised and requires replacement. If the patient is unable to replace the unit, then restarting multiple daily injections with long and short-acting insulins should be considered. The daily requirement of long-acting insulin can be calculated from the patient's total daily needs of their basal rate.

Diabetic ketoacidosis (DKA): Since insulin analogs remain active for a relatively short duration, the risk for diabetic ketoacidosis is a concern as these patients do not have long-acting insulin in their system. Studies comparing the incidence of DKA in patients treated with continuous subcutaneous insulin infusion versus multiple daily injections have demonstrated lower rates of DKA in patients on a continuous subcutaneous insulin infusion.

In rare case reports, the insulin pump site change has been associated with hypoglycemia after being injected with an unsolicited insulin bolus. In those reported cases, the events were preceded by the pump site change, and an alarm followed, indicating that a high dose of insulin bolus was delivered without the user's appropriate bolus instructions, resulting in hypoglycemia. It is essential to be aware of this possible complication when using insulin pumps.

Clinical Significance

An initial randomized study by DeVries compared the efficacy of continuous subcutaneous insulin infusion to multiple daily injections with NPH and regular insulin and demonstrated a reduction in the hemoglobin A1c of 0.84% at 16 weeks.

A larger clinical trial called the 5-Nations trial performed in 11 European centers reported a hemoglobin A1c decrease of 0.22% with a lower incidence of hypoglycemic events and higher user perception of satisfaction when comparing continuous subcutaneous insulin infusion to multiple daily injections using NPH.

Hypoglycemia: Continuous subcutaneous insulin infusion is associated with lower hemoglobin A1c levels, so there are concerns for an increased risk of hypoglycemia. Studies have shown that event rates of severe hypoglycemia and hypoglycemic coma were significantly lower with continuous subcutaneous insulin infusion versus multiple daily injections.

There has been a reported decrease in blood glucose variability in the users of insulin pumps, as described in various studies. Preliminary studies have suggested that blood glucose variability is the underlying pathophysiologic mechanism leading to diabetic complications, including nephropathy, retinopathy, coronary artery disease, and cognitive decline, although more research is needed to establish causation.

Clinical indications for insulin pump therapy:

1. All patients with type 1 diabetes.
2. Patients with type 1 diabetes are difficult to manage due to frequent hypoglycemia.
3. Patients with type 2 diabetes who do not meet glycemic targets despite multiple daily insulin injections (MDI) and extensive lifestyle changes.
4. Individuals suffering from gastroparesis will benefit from insulin pumps' extended bolus delivery feature.
5. Pregnancy
6. Variable schedule or shift workers.
7. Patients requiring small doses of insulin-like, for example, the pediatric diabetic population.

Ideal candidates for insulin pump therapy:

1. Willingness to wear the insulin pump and the sensor.
2. Motivation and interest in pump education.
3. Good vision and ability to operate the pump and make necessary adjustments.
4. Knowledge of carb counting.
5. Ability to calculate the insulin bolus from the device.

Insulin pump technology will continue to develop rapidly, improving the quality of life for patients with diabetes. It will be challenging for healthcare professionals to stay abreast of every advancement, but a basic understanding of insulin pump delivery can help avoid common complications and improve outcomes.

Nursing, Allied Health, and Interprofessional Team Interventions

The interprofessional team must maintain strong communication during the transition of care so that all involved in managing the patient's health problems are aware that the patient is on insulin pump therapy. The patient or a certified pump specialist should make adjustments to the pump settings, including but not limited to insulin boluses, temporary basal settings, and other changes to basal rates. Persistent hyperglycemia, problems with infusion sites, or removal of the device should be rapidly communicated with the physician.

In most hospitals, there is a system where the patients can continue to use their insulin pumps as inpatients. Still, the patients should be able to consent to and be willing and able to manage their insulin pump on their own as the hospital personnel is usually not trained in managing insulin pumps, so ultimately it would be the patient's responsibility to handle all pump's changes for optimal blood glucose control. In all settings, the healthcare staff has the right to suspend the pump and start the patient on a conventional regimen if they consider this to be in the best interest of the patient, such as in situations of anesthesia, any critical change in patient's mental and health status and when the patient is not fully awake to be able to manage the insulin pump independently.

Nursing, Allied Health, and Interprofessional Team Monitoring

The nursing staff must maintain a log of the blood glucose levels and basal rates on the insulin pump. That usually happens with the help of the patient reporting all glucose levels, especially if the patient is on CGM. The individual requirements may vary from hospital to hospital. Still, most of the time, there is a need to maintain some paperwork showing that the patient consented and can manage the pump independently.