Systematic Review on Overview of The Closed-Loop Vs Open-Loop Insulin Pump System

Abstract

Management of diabetes mellitus, especially Type 1 diabetes, requires precise regulation of blood glucose levels through insulin therapy. Traditionally, insulin delivery systems include open-loop and closed-loop technologies. Open-loop systems, which necessitate manual insulin dose adjustments by patients, offer greater flexibility and lower costs but pose challenges such as variability in glycemic control and increased user dependence. Conversely, closed-loop systems, often termed artificial pancreas systems, incorporate continuous glucose monitoring (CGM) with automated insulin regulation driven by advanced algorithms. These systems have demonstrated significant clinical benefits, such as increased time in the target glycemic range, reductions in HbA1c levels, and decreased incidence of hypoglycemia, particularly during sleep. Several randomized controlled trials have consistently shown that closed-loop systems improve glycemic outcomes by providing real-time, automated insulin adjustments, thereby minimizing fluctuations and enhancing overall glucose management. Additionally, they reduce the mental and physical burden associated with diabetes care, improving patient quality of life and adherence. However, the higher costs, technological complexities, and limited accessibility restrict their widespread adoption, especially in resource-constrained settings. Furthermore, despite advancements, the delayed action of subcutaneously delivered insulin and the reliance on sensor accuracy remain challenges. As research progresses, efforts are focused on developing more affordable, user-friendly, and reliable systems that can be broadly implemented across diverse patient populations. This review underscores the superior clinical efficacy, safety, and patient satisfaction associated with closed-loop insulin delivery systems compared to open-loop counterparts, emphasizing the need for continued innovation to overcome existing barriers and expand access for individuals living with diabetes.

Keywords

Introduction

Diabetes mellitus, particularly Type 1 diabetes, requires precise insulin administration to maintain glucose homeostasis. Insulin pumps were developed to provide continuous subcutaneous insulin infusion, reducing the need for multiple daily injections. Two major categories exist: open-loop and closed-loop systems. Open-loop pumps require patients to calculate and deliver doses manually, while closed-loop systems also referred to as "artificial pancreas systems" or automate insulin delivery based on real-time glucose levels.

In Open loop insulin delivery system mainly controlled by patient. In closed-loop systems, the system automatically adjusts insulin, reducing the need for constant manual intervention.¹

Glucose Metabolism

Glucose metabolism is critical for maintaining cellular energy production, primarily through the synthesis of adenosine triphosphate (ATP), with glucose serving as the body's main metabolic fuel. In healthy individuals, fasting blood glucose levels typically range from 80 to 90 mg/dL. Although blood glucose rises sharply after carbohydrate-rich meals, it seldom exceeds 120 to 140 mg/dL under normal conditions. When glucose levels surpass this homeostatic range, excess glucose is stored as glycogen in the liver and muscle tissues. However, because glycogen storage capacity is limited, the surplus glucose is converted into fat.

During periods when plasma glucose falls below basal levels—such as fasting or physical exertion—the liver compensates by producing glucose internally. This process occurs via glycogenolysis, where stored glycogen is broken down into glucose, and gluconeogenesis, where amino acids and fatty acids undergo conversion to form glucose. The regulation of these glucose metabolism pathways is tightly controlled by several key hormones. Insulin, glucagon, epinephrine, and gastrointestinal hormones, particularly glucagon-like peptide-1 (GLP-1), act in concert to maintain glucose levels within a healthy range.

Insulin, synthesized by pancreatic beta cells, plays a dual role: it accelerates glucose uptake into muscle and liver cells, increasing cellular glucose consumption by an order of magnitude, and facilitates the conversion of glucose beyond glycogen storage capacity into fat. Insulin also promotes the uptake of amino acids and fatty acids into hepatic cells, providing substrates necessary for gluconeogenesis. Baseline insulin secretion averages approximately 25 ng/min per kg of body weight but can increase rapidly within minutes of a rise in plasma glucose, often by tenfold.

Conversely, glucagon, produced by pancreatic alpha cells, primarily opposes insulin’s effects by stimulating hepatic glucose production when blood glucose drops below basal levels. It activates both glycogenolysis and gluconeogenesis and enhances the liver’s uptake of amino acids and fatty acids to support glucose synthesis. Glucagon additionally promotes the mobilization of fatty acids from adipose tissue, ensuring substrate availability for hepatic gluconeogenesis. Its release is triggered during fasting, exercise, and hypoglycemic episodes.

Epinephrine and norepinephrine share the function of promoting gluconeogenesis and fatty acid mobilization but also induce vasoconstriction, reducing blood flow to peripheral tissues and thereby decreasing their glucose uptake. These catecholamines are secreted during physical exercise, stress, and when glucose falls well below glucagon-release thresholds.

Incretin hormones, especially GLP-1, are released postprandially and enhance pancreatic insulin secretion even before blood glucose rises significantly. Furthermore, incretins contribute directly to glucose regulation independent of their insulinotropic effects, highlighting their importance in glucose homeostasis.

Together, these metabolic and hormonal mechanisms ensure the tight regulation of glucose levels essential for normal physiological functioning. Disruptions in this balance contribute to the pathophysiology of diabetes and underscore the importance of managing glucose metabolism effectively in diabetes care.^2-6

Diabetes mellitus

Diabetes mellitus is marked by a disruption in the glucose metabolism pathway. Type I diabetes is of greater relevance to this research, as the pancreas cannot produce enough insulin to regulate plasma glucose levels. Type I diabetes is an autoimmune condition where the body attacks its pancreatic beta cells. This autoimmune process typically takes place early in an individual's life, with later instances usually happening when one is in their early to mid-20s. For patients with Type I diabetes and many patients with Type II diabetes, insulin needs to be supplied from a source apart from the pancreas.

For a Type I diabetic individual, the insulin levels will depend solely on the effectiveness of the control being administered. Insufficient insulin supply leads to increased glucose production in the liver beyond the capacity for cellular uptake, causing hyperglycemia. When the hyperglycemic condition persists for a long duration, the diabetic individual will experience numerous repercussions. Initially, the elevated glucose levels in the bloodstream alter the body's osmotic equilibrium, leading to water loss and ultimately causing dehydration in numerous cells throughout the body. Secondly, when glucose levels in the body exceed a threshold of about 200 mg/dL, the kidneys can no longer reabsorb glucose, leading to its presence in urine. Elevated glucose levels in urine lead to alterations in the osmotic equilibrium of urinary fluid, causing the excretion of additional fluids and electrolytes that are not typically excreted. The existence of elevated glucose levels in the body can indeed damage tissue structures, including those of blood vessels, kidneys, eyes, and limbs.

Individuals with diabetes face an increased likelihood of heart failure and kidney failure. Furthermore, it is not unusual for individuals with diabetes to experience blindness, and they frequently require amputations due to gangrene's progression. As a final consequence of repeated hyperglycemia, the body's incapacity to utilize glucose for energy leads to a transition to fat and protein metabolism. This may lead to the body’s pH decreasing to perilous levels, potentially causing death due to acidosis, or the body may start using its tissue proteins, which can also lead to death.

Although hyperglycemia might be avoided by intentionally administering excess insulin for glucose use, hypoglycemia would occur from administering excessive insulin. The level of insulin present in the bloodstream directly influences the quantity of glucose entering the liver and muscle cells. With the increase in insulin availability, glucose absorption into liver and muscle cells also rises, irrespective of the demands of other cells. This poses an issue since glucose is the sole nutrient that some cells can utilize in adequate amounts to enable them to efficiently conduct their metabolic activities.

The brain and the retina are among the most significant of these. If the brain cannot obtain the essential glucose required for its metabolic processes, it will lead to death. Compounding the issue is that if the pancreas consistently ramps up its glucagon secretion to elevate glucose levels during hypoglycemia, it will ultimately lose sensitivity to low glucose levels, and eventually, hypoglycemia will fail to trigger glucagon production

Due to the central nervous system's role in epinephrine production, this minor hypoglycemia will trigger epinephrine secretion as well. Thus, to preserve healthy basal conditions, it is crucial for a diabetic individual to effectively manage glucose levels by utilizing meticulously calculated insulin doses.

The results for a diabetic patient after eating a meal heavily rely on the effectiveness of insulin treatment. In particular, the patient’s glucose levels will be influenced by both the dosage of insulin given and the timing of its administration. When insulin levels drop too low, two significant outcomes will lead to severe hyperglycemia. Initially, there will be insufficient insulin to facilitate the uptake of glucose into the liver and peripheral cells. Secondly, low insulin levels will lead to comparatively high glucagon levels, causing an increase in blood glucose levels.

Alongside the quantity of insulin given for a meal, the timing of its administration significantly affects the maintenance of normoglycemic levels. This period typically aligns with the release of GI hormones linked to the meal. If the administration occurs too soon, hypoglycemia will develop before the meal is absorbed and hyperglycemia will arise toward the end of the meal, since there won't be enough insulin available to process the glucose coming in from the meal's conclusion. Administering insulin too late will lead to hyperglycemia at the start of the meal and hypoglycemia towards the end of the meal or soon after.

During physical activity, having excessive insulin in the body before exercising will lead to a rise in glucose absorption in the liver and peripheral tissues, along with a suppression of glucose and fatty acid synthesis. Since fatty acid levels remain unchanged, the glucose uptake by the cells rises. The result of all these factors is the development of hypoglycemia, which frequently happens during physical activity for diabetic individuals.

When insufficient insulin is available during exercise, the outcome will be hyperglycemia. This is not an issue while exercising, as the elevated glucose levels offer extra energy that can be utilized. Nonetheless, after the exercise is finished, the patient exhibits elevated glucose levels compared to normal, and the body does not attempt to bring the levels back to normal.

As mentioned in the earlier paragraphs, diabetes can lead to severe outcomes for both hyperglycemia and hypoglycemia. The capacity to maintain a lifestyle nearly equivalent to that of a healthy individual largely hinges on the patient’s ability to administer the correct dosage of insulin at the appropriate moment. To attain this ideal form of management, various insulin delivery techniques have been suggested and created.⁶

Key Objective of Open Loop System

• Deliver insulin in a customized, programmable manner that matches individual basal and bolus needs, ensuring more physiological insulin replacement than injections.
• Allow patients to easily adjust insulin doses for meals, exercise, and unpredictable lifestyle changes, promoting flexibility and better glucose control.
• Minimize the frequency of injections and provide more consistent blood glucose management, reducing both hyperglycemia and hypoglycemia risk when used correctly. ^7-8

Key Objectives of Closed Loop System

• Minimize hypoglycemia and hyperglycemia events by automatically adjusting insulin doses in response to real-time glucose measurements from a continuous glucose monitor (CGM).
• Maximize "time in range"—the proportion of time spent with blood glucose within the recommended boundaries—leading to improved overall glycemic control and lower HbA1c.
• Reduce the daily burden and mental effort associated with diabetes management by decreasing the need for manual insulin dosing decisions and interventions.
• Enhance quality of life through fewer interruptions (alarms, injections), greater lifestyle flexibility, and reduced disease-related anxiety, especially for families and children.
• Collect, monitor, and share glucose data efficiently to support better self-management and informed healthcare decisions.
• Provide a safe, reliable solution that integrates technology (pump, CGM, algorithm) for consistent and precise insulin management, helping to prevent long-term complications of diabetes.⁹

Mechanism of action -

• Open loop insulin delivery -

An Open-Loop Insulin Delivery System is a traditional type of insulin pump used in diabetes management. Unlike closed-loop systems, it does not automatically adjust insulin based on glucose levels.

The “loop” is open, meaning the patient must decide and manage insulin dosing. Basal rates are fixed or manually adjusted by the patient or clinician. Bolus doses for meals or corrections require manual calculation based on carbohydrate intake and glucose readings.

Figure: Open Loop Insulin Pump

How it works:

1. Insulin Pump delivers a continuous preset basal insulin dose.
2. Patient manually administers bolus doses for meals or high glucose readings.
3. Optional Continuous Glucose Monitor (CGM) may display glucose trends, but the pump does not act automatically on this data.^10-11

• Close loop insulin delivery -

A Closed-Loop Insulin Pump System also called an Artificial Pancreas System or Automated Insulin Delivery system. It an advanced technology for managing diabetes.

Figure: Closed-Loop Insulin Pump

How it works:

1. Continuous Glucose Monitor (CGM) checks glucose levels in the body every few minutes.
2. Algorithm (computer program) analyses these readings in real time.
3. Insulin Pump automatically adjusts insulin delivery (basal rates and sometimes bolus doses) based on the algorithm’s instructions.
4. The cycle repeats, creating a closed feedback loop.¹²

Types of Closed-Loop Systems:

1. Hybrid Closed-Loop-

• Automatically adjusts basal insulin.
• User still enters carbohydrates for meals and may deliver bolus doses.¹³

2. Fully Closed-Loop-

• Automates both basal and bolus insulin delivery.
• User input is minimal (only device maintenance) Still under development and less widely available. ^14-15

Open Loop Insulin Delivery -

Advantages

1. User Control:

The patient has full control over insulin dosing — they can adjust doses based on meals, activity, or blood glucose readings.

2. Flexibility in Use:

Can be used with different insulin types and delivery methods (injection, pen, or pump).

3. Lower Cost:

Less expensive compared to closed-loop (automated) systems because it does not require continuous glucose monitoring (CGM) or advanced software.

4. Less Technology Dependence:

Does not rely on sensors or algorithms, so there’s no risk of system malfunction or calibration errors.

5. Useful for Educated/Experienced Patients:

Suitable for individuals who are knowledgeable about their insulin needs and capable of self-managing their diabetes.^16-18

Disadvantages

1. Manual Adjustment Required:

The patient must calculate and inject insulin doses based on blood glucose and meal intake manually — increases the chance of human error.

2. Inconsistent Glucose Control:

Since insulin delivery isn’t automatically adjusted, it can lead to fluctuations in blood glucose levels (hyperglycemia or hypoglycemia).

3. Higher Burden on Patient:

Requires frequent blood glucose monitoring, meal planning, and dose calculation, leading to mental and physical fatigue.

4. Delayed Response:

Insulin delivery cannot automatically respond to rapid changes in blood sugar levels.

5. Less Suitable for Children or Elderly:

Manual management can be difficult for people with limited understanding or dexterity.^19-20

Close Loop Insulin Delivery -

Advantages

1. Automated Glucose Control:

Continuously monitors blood glucose and automatically adjusts insulin levels, reducing fluctuations and maintaining glucose within target range.

2. Reduced Hypoglycemia Risk:

The system can predict and prevent low blood sugar by suspending or reducing insulin delivery.

3. Improved HbA1c Levels:

Provides tighter glycemic control compared to open-loop systems, as proven in multiple clinical studies.

4. Less Patient Burden:

Reduces the need for frequent manual blood glucose checks and insulin dose calculations.

5. Better Overnight Control:

Automatically adjusts insulin during sleep, minimizing nighttime hypoglycemia.

6. Improved Quality of Life:

Offers greater convenience, flexibility, and peace of mind for patients, especially active individuals or children.

7. Data Recording and Alerts:

Provides continuous data, trend analysis, and alerts for abnormal glucose levels, improving disease management.^24-25

Disadvantages

1. High Cost:

Significantly more expensive than open-loop systems due to advanced sensors, pumps, and software.

2. Technical Complexity:

Requires calibration, software updates, and maintenance; sensor or pump malfunction can disrupt control.

3. Limited Accessibility:

Not all patients can afford or have access to closed-loop systems, especially in low-resource settings.

4. Delayed Insulin Action:

Subcutaneous insulin delivery still has a delay between sensing and action, so rapid glucose changes (e.g., after meals) may not be fully prevented.

5. Dependence on Technology:

Requires reliable CGM sensors and pump function — any sensor error or signal loss can affect insulin delivery accuracy.

6. User Training Required:

Patients must be trained to understand system operation, alerts, and troubleshooting.^26-27

Clinical Effectiveness of Closed-Loop vs Open-Loop Insulin Pump Systems

Recent studies have demonstrated that closed-loop insulin delivery systems (also referred to as automated insulin delivery or artificial pancreas systems) significantly improve glycemic outcomes compared to open-loop systems such as conventional continuous subcutaneous insulin infusion (CSII) or sensor-augmented pump (SAP) therapy. Randomized controlled trials have consistently shown that closed-loop systems increase the percentage of time in range (TIR; blood glucose 70–180 mg/dL) by approximately 10–15 percentage points compared to open-loop therapy, equivalent to an additional 2–3 hours per day within the target glycemic range. Reductions in glycated hemoglobin (HbA1c), though modest, are statistically significant, typically ranging from 0.3% to 0.5% beyond those observed with standard pump therapy. Closed-loop systems also decrease time spent in hypoglycemia and hyperglycemia, with particular benefits observed overnight, and without a corresponding increase in severe hypoglycemia or diabetic ketoacidosis events. Improvements in glycemic variability and patient-reported outcomes, such as sleep quality and diabetes-related distress, have also been reported. These findings collectively highlight closed-loop insulin delivery as a clinically effective advancement over open-loop systems, particularly in individuals with type 1 diabetes, while ongoing considerations related to cost, patient education, and long-term adherence remain important for broader implementation. ^28-29

CONCLUSION

Open-loop and closed-loop insulin delivery systems represent two different stages in the evolution of diabetes management technologies. Open-loop systems, while offering improved flexibility compared to multiple daily injections, still rely heavily on patient input, leading to variability in glycemic outcomes and increased risk of human error. In contrast, closed-loop systems (also called “artificial pancreas”) integrate continuous glucose monitoring with automated insulin delivery, providing tighter glycemic control, reduced incidence of hypoglycemia, and improved quality of life. Despite their higher cost and need for advanced infrastructure, closed-loop systems demonstrate a clear advantage in terms of safety, efficacy, and patient satisfaction. Future research and technological advancements should focus on enhancing accessibility, affordability, and ease of use of closed-loop systems, ensuring that more individuals with diabetes can benefit from these innovations.   

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