Version May 2024
INTRODUCTION — The basic requirements of an optimal insulin regimen include administration of a basal insulin plus mealtime boluses of a rapid-acting, faster rapid-acting, or short-acting insulin. Basal insulin can be delivered by daily or twice-daily injections of an intermediate-acting (neutral protamine Hagedorn [NPH]) or long-acting (glargine, detemir, degludec) insulin preparation or by continuous subcutaneous insulin infusion (CSII) via a pump using a rapid-acting or faster rapid-acting insulin preparation (lispro, aspart, glulisine). Providing physiologic insulin replacement requires adjustment of doses to match requirements and relies on glucose monitoring and lifestyle modifications.
This topic will review CSII (insulin pump) therapy. Physiologic insulin replacement, choice of insulin delivery (multiple daily injection [MDI] insulin regimens versus CSII), and designing an MDI regimen are reviewed separately.
●(See "Management of blood glucose in adults with type 1 diabetes mellitus".)
●(See "Overview of the management of type 1 diabetes mellitus in children and adolescents".)
●(See "Insulin therapy for children and adolescents with type 1 diabetes mellitus".)
GENERAL PRINCIPLES
●Continuous insulin infusion – Continuous subcutaneous insulin infusion (CSII; insulin pump therapy) provides subcutaneous infusion of insulin, usually a rapid-acting or faster rapid-acting insulin analog. Basal insulin requirements are supplied in the form of mini-boluses delivered every five minutes. This "continuous" infusion generally constitutes 40 to 50 percent of the total daily insulin dose. In addition to basal insulin delivery, mealtime insulin bolus doses are given to minimize postprandial glucose excursions. (See 'Dosing' below.)
•Rapid-acting insulin analogs – We suggest rapid-acting insulin analogs (most commonly lispro and aspart) rather than regular insulin for CSII. In a meta-analysis of trials comparing rapid-acting insulin analogs with regular insulin for use in CSII, there was a small but significant reduction in glycated hemoglobin (A1C) with use of insulin analogs (mean difference -0.26 percent, 95% CI -0.47 to -0.06 percent) [1]. It was difficult to analyze hypoglycemia as it was defined differently in the various trials, and continuous glucose monitoring (CGM) was not available. The convenience of being able to administer a rapid-acting insulin immediately before the meal (compared with needing to administer preprandial boluses of regular insulin 30 to 45 minutes before meals), as well as the ability to more quickly correct hyperglycemia, also favor rapid-acting formulations.
•Faster rapid-acting insulin analogs – Limited clinical trial data support comparable efficacy of rapid-acting and faster rapid-acting insulin analogs when used for CSII [2-4]. In one 16-week trial, adults with type 1 diabetes on insulin pump therapy who were randomly assigned to faster-acting aspart exhibited a similar change in A1C to those who used insulin aspart but had a smaller increment in one-hour postprandial glucose (-16.4 mg/dL, 95% CI -25.7 to -7) [2]. Similar findings were reported in a 16-week trial that compared lispro and faster-acting lispro use in CSII [4].
In the aspart trial, time in hypoglycemia (≤70 mg/dL [3.9 mmol/L]) did not differ between the aspart and faster-acting aspart groups [2]. In the lispro trial, time in hypoglycemia (<70 mg/dL and <54 mg/dL (3.9 mmol/L) was lower with faster-acting lispro than with lispro, but faster-acting lispro conferred a higher rate of adverse events (60.5 versus 44.7 percent), primarily infusion site reactions, and infusion-related pain [4].
●Insulin pump components – A variety of insulin pumps are available, and the choice among pumps is largely a matter of individual preference, cost, lifestyle, and compatibility with CGM devices. (See 'Types of insulin pumps' below.)
In a traditional pump, insulin is infused from a reservoir/cartridge within the pump through tubing to a cannula or needle that is inserted subcutaneously (figure 1). The infusion set and site of infusion are changed by the person with diabetes (or their caregiver) every two to three days. The tubing, which connects the infusion set to the insulin cartridge/reservoir in the pump, can be connected to and disconnected from the infusion site without removing the cannula. Some traditional insulin pumps can be used with a CGM device as part of a hybrid closed-loop system. (See 'Insulin only, partially automated system' below.)
For the patch pump, the insulin reservoir, batteries, and cannula are in a wearable disposable device ("pod"), which delivers insulin subcutaneously (figure 2). The pod is changed every two to three days. Insulin delivery from the pod is controlled wirelessly by a handheld "controller," compatible smartphone, or personal diabetes manager (PDM). (See 'Types of insulin pumps' below.)
●Glucose monitoring – For most adults with type 1 diabetes, frequent testing of glucose levels is necessary to achieve A1C targets safely without frequent or severe hypoglycemia. Self-monitoring allows the user to adjust the doses and timing of insulin administration based on both immediate glucose data and the user's behaviors (eg, exercise and food intake). Many people with type 1 diabetes use a combination of blood glucose monitoring (BGM) by fingerstick with a glucose meter and, when available, CGM. Some insulin pumps can receive and display glucose data from CGM devices, and others use such data to automatically adjust basal rate delivery to address both low and high glucose levels. (See "Management of blood glucose in adults with type 1 diabetes mellitus", section on 'Intensive diabetes therapy' and "Glucose monitoring in the ambulatory management of nonpregnant adults with diabetes mellitus" and 'Types of insulin pumps' below.)
DOSING
Total daily dose — When converting a person with type 1 diabetes from a multiple daily injection (MDI) insulin regimen to continuous subcutaneous insulin infusion (CSII), the pre-pump level of chronic glycemia will help determine the initial pump basal rate and preprandial dosing. As an example, for a person who has met glycemic goals on the previous MDI regimen (eg, A1C <7 percent), the initial total daily dose (TDD) of insulin administered by pump may be 10 to 20 percent less than the TDD (both short-acting and long-acting insulin) of the previous regimen. Conversely, individuals who are above glycemic targets (high A1C with no hypoglycemia) may be started with the same TDD (both short-acting and long-acting insulin) as they had been using with their injection regimens.
Basal rate — In general, approximately 40 to 50 percent of the TDD is administered as the basal rate (divide by 24 to get units per hour). This proportion can be higher or lower depending on a number of factors, including if the individual consumes a low- or high-carbohydrate diet, respectively. For most adults, basal rates are in the range of 0.01 to 0.015 units per kg per hour (ie, for a 60 kg woman, approximately 0.6 to 0.9 units per hour).
The basal rates are adjusted empirically (eg, by approximately 10 percent) based on glucose monitoring results. The basal rate adjustment depends upon a number of factors, including the individual's glycemic goals, degree of hyperglycemia or hypoglycemia, fears of hypoglycemia or hyperglycemia, current use of continuous glucose monitoring (CGM) with alarms, age, and presence or absence of comorbidities (eg, more cautious adjustments in older adults with hypoglycemia unawareness or cardiovascular disease).
Certain time periods during the day may require higher or lower infusion rates depending on individual factors including lifestyle patterns and the "dawn phenomenon," which results in an increased need for insulin between 2:00 and 8:00 AM. Most pumps allow for preprogrammed changes in basal rate to accommodate these requirements. The "dawn phenomenon" is thought to result from diurnal secretion patterns of hormones, particularly increased growth hormone at midnight to 2:00 AM, that tend to antagonize the actions of insulin in the early morning hours and so raise blood glucose concentrations. The overnight basal rate(s) can be adjusted to maintain the pre-breakfast blood glucose in the target range [5,6], although this strategy is not always effective and may confer risk of hypoglycemia [7].
Temporary basal rates can also be programmed for defined periods of time. For example, a reduced temporary basal rate can be used to avoid hypoglycemia associated with aerobic activities.
When changing the subcutaneous basal insulin infusion rate, a delay in the actual increase or decrease in plasma insulin levels must be taken into account, based on the kinetics of absorption and time to reach a new steady state [8]. Therefore, basal rates of rapid-acting insulin should be changed approximately two hours before the change in plasma level is required.
Bolus dosing — The pre-meal bolus dose should be based primarily upon the carbohydrate content of the intended meal and the blood glucose level immediately before the meal. If CGM data are available, use of glucose trends (trend arrows) can help the person with diabetes fine-tune dosing [9]. High fat and protein meals (eg, steak and potatoes or pizza) can cause a prolonged rise in glucose and need for a higher insulin dose and longer duration of insulin action [10,11]. (See "Nutritional considerations in type 1 diabetes mellitus", section on 'Advanced carbohydrate counting'.)
Insulin pumps have insulin calculators for bolus dosing for meals and for correction of hyperglycemia. The use of calculated "active insulin" or "insulin on board" helps prevent hypoglycemia that can occur from overcorrecting for hyperglycemia with multiple correction boluses administered close together in time ("stacking"). Insulin pumps also allow for delivery of extended or dual-wave boluses to help manage the prolonged or delayed rise in glucose concentrations that occur after ingesting higher fat and protein meals or in the presence of gastroparesis.
The timing of dosing preprandially will depend on the insulin used. The kinetics of regular insulin require administration approximately 30 to 45 minutes before eating so that the insulin peak matches the peak glucose after the meal. Rapid-acting insulin can be administered 10 to 15 minutes prior to eating; rapid-acting and faster rapid-acting insulins can also be given immediately before eating, or even during the meal in specific circumstances (eg, presence of gastroparesis or pre-meal hypoglycemia).
SAFETY CONSIDERATIONS
Pump failure
●Causes of apparent pump failure – Pump failure may occur due to mechanical failure or detachment, blockage-kinking, or leakage in the infusion set/cannula, syringe, or connectors, causing an interruption of insulin flow [12-14]. The pump may be in suspension mode or may need a battery change. Air in the infusion set may cause reduced insulin delivery in the absence of true pump failure. Use of expired or damaged insulin (exposure to high temperatures or freezing) will also present as pump failure. A poor infusion site can impede insulin delivery; infusion sites may not absorb insulin well due to overuse, scarring, or lipohypertrophy [15].
●Acute management – Since the subcutaneous depot is very small and only rapidly acting insulin is administered, any interruption in continuous flow can lead very quickly to hypoinsulinemia and potentially diabetic ketoacidosis. If there is no glucose response to insulin boluses, the infusion set should be immediately changed and a new insertion site chosen. Failure of insulin delivery despite these actions usually indicates pump failure.
If pump failure occurs, individuals can replace basal insulin with rapidly acting insulin injections every three to four hours (each dose equivalent to three to four times the hourly basal rate) with careful, frequent blood glucose monitoring (BGM) or continuous glucose monitoring (CGM). If the anticipated interruption in pump therapy is more than a few hours, individuals should transition to an intermediate-acting or long-acting basal insulin to replace the basal infusion. Using the total daily basal insulin dose as a guide, a similar dose can be given as one or two injections of glargine or detemir or divided into two injections of NPH daily. In this setting, we do not use basal insulin with a very long duration of action such as insulin degludec, as it takes approximately four days to reach steady state. When restarting pump therapy, if there is residual basal insulin on board, a lower temporary basal rate may be needed until the intermediate-acting or long-acting insulin effect has dissipated.
●Prevention and precautions – If problems with infusion sets recur, the individual's insertion technique should be reviewed. A different type of infusion set (eg, metal needle instead of Teflon catheter) can be considered. All pump users should know how to check for ketones (either blood or urine) and have a back-up plan for both basal and mealtime insulin (ie, insulin vials and syringes or insulin pens) to use in the event of pump failure.
Superficial infection — Adults who are treated with continuous subcutaneous insulin infusion (CSII) may rarely develop infections at the site of catheter insertion. This is more likely to occur if the infusion set has not been changed for >72 hours, if the site was not properly prepared, or if the infusion set was not properly inserted. If the infusion site is red, swollen, painful, draining purulent material, or has increased warmth, the infusion set should be immediately removed and discarded and a new set placed at another site. The old site should be cleaned and treated with warm soaks; occasionally, oral antibiotic therapy is needed.
NPO for procedures — If meeting their glycemic goals, people with type 1 diabetes who are using a nonautomated insulin delivery system (eg, sensor-augmented insulin pump) and are not eating (nil per os [NPO]) in preparation for a procedure may continue with their usual basal infusion rate. Depending on overall glycemia before the procedure, the length of the procedure, and degree of concern about hypoglycemia, the basal rate may be reduced by up to 20 percent for at least two to three hours pre-procedure or once the individual becomes NPO to minimize the risk of hypoglycemia. People using automated insulin delivery (AID) systems who are concerned about hypoglycemia while NPO may instead set a temporary, higher target glucose (or target glucose range) prior to a procedure; the methods for adjusting the target glucose vary across AID systems and can include the use of an "exercise" or "activity" mode. More information about device management can be found through the PANTHER program.
No routine insulin boluses should be administered until the individual can eat. The management of insulin therapy (including use of insulin delivery systems) during and after surgical procedures is reviewed separately. (See "Management of diabetes mellitus in hospitalized patients", section on 'Patients with type 1 diabetes' and "Perioperative management of blood glucose in adults with diabetes mellitus", section on 'Glucose management'.)
Privacy and cybersecurity — The wireless communication between glucose monitoring devices and insulin pumps allows for the possible interception of data and control of insulin delivery by unauthorized individuals [14,16]. People with diabetes who use these devices should be cautioned about these risks. They further should be counseled to avoid linking their devices in public settings and to disable the remote bolus feature of the insulin pump if present [16].
TYPES OF INSULIN PUMPS — A variety of insulin pumps are available, some of which communicate with specific continuous glucose monitoring (CGM) devices. Others use CGM feedback information to automatically adjust basal rate delivery and mitigate both low and high glucose levels. The choice among pumps is largely a matter of individual preference, cost, and lifestyle.
Insulin pumps can be used alone or in conjunction with a CGM device to give the person with diabetes more information about their blood glucose levels and allow them to make better informed decisions about insulin dosing. This approach is known as sensor-augmented insulin pump therapy. When the insulin pump uses an algorithm (based on parameters including CGM results and target glucose) to control basal insulin infusion, the system is termed a partially automated (hybrid) closed-loop system (artificial pancreas or automated insulin delivery [AID]). Some advanced automated (hybrid) closed-loop systems administer automatic insulin correction doses as well. The user must still determine and administer pre-meal bolus insulin (hence the term "hybrid"), with dose selection based on insulin-to-carbohydrate ratios and "correction" factors to address ambient glucose levels at the time of the meal. Use of sensor-augmented insulin pump therapy and the hybrid closed-loop system can reduce time in hypoglycemia.
Sensor-augmented insulin pump — Sensor-augmented insulin pump therapy involves the use of an insulin pump and a CGM device that function independently. Insulin delivery is not automatically adjusted based on CGM readings. A randomized trial compared sensor-augmented insulin pump therapy with multiple daily injection (MDI) insulin therapy using standard blood glucose monitoring (BGM) without use of CGM in 329 adults [17]. After one year, the reduction in mean A1C was significantly greater in the pump and CGM therapy group (between-group difference -0.6 percentage points). Of note, the design of the study (sensor-augmented pump therapy versus MDI without CGM) could not distinguish between the effects of pump therapy and CGM. (See "Glucose monitoring in the ambulatory management of nonpregnant adults with diabetes mellitus", section on 'CGM systems'.)
Low glucose threshold suspend or predictive low glucose suspend systems — Some insulin pumps can suspend insulin delivery when glucose readings reach a prespecified low glucose threshold or are predicted to reach that threshold.
●Low glucose threshold suspend – These insulin pumps can be programmed to interrupt insulin delivery (for up to two hours) at a preset sensor glucose value (low glucose threshold suspend). The threshold suspend feature reduces the frequency and duration of nocturnal hypoglycemia, as illustrated by the findings from randomized trials [18-20]:
•In one trial, 247 people with type 1 diabetes and nocturnal hypoglycemia (mean age approximately 43 years) were randomly assigned to sensor-augmented insulin pump therapy with or without a threshold suspend feature [18]. After three months, nocturnal hypoglycemia (measured as area under the curve) was significantly lower in the group with the threshold suspend feature (1.5 versus 2.2 events per person per week). Severe hypoglycemia was rare (four episodes), but all events were in the control group.
•In another trial, 95 people with type 1 diabetes and well-documented hypoglycemia unawareness (mean age 18.6 years) were randomly assigned to standard insulin pump (without CGM) or to sensor-augmented insulin pump therapy with a threshold suspend feature [19]. After six months, the rate of severe and moderate hypoglycemic events was significantly lower in the group using the threshold suspend feature (9.5 versus 34.2 events per 100 patient-months). Of note, despite randomization, the baseline frequency of moderate and severe hypoglycemia was substantially greater in the threshold suspend group than the control group, which limits interpretation of the results.
In both trials, there was no significant difference in change in A1C, and there were no episodes of diabetic ketoacidosis (ie, no deterioration of glycemia with brief suspension of insulin delivery). These findings suggest that the threshold suspend feature is useful, and the first trial shows that it can improve the ability of sensor-augmented insulin pump therapy to reduce nocturnal hypoglycemia [18]. The design of the second trial (augmented pump with threshold suspend feature versus standard pump therapy without CGM) could not distinguish between the effects of CGM and a CGM/pump system with threshold suspend feature [19].
●Predictive low glucose suspend – Some insulin pumps are available with a "predictive low glucose suspend" feature. In contrast to low glucose threshold suspend, in which insulin delivery is suspended when the glucose reading reaches the threshold value (eg, 70 mg/dL [3.9 mmol/L]), predictive low glucose threshold suspend reduces or suspends insulin infusion when the trend in CGM results predicts that hypoglycemia will occur. In randomized trials of predicative low glucose suspend in children and adults, using different devices, there was a reduction of hypoglycemia without an increase in hyperglycemia [21-23].
Automated insulin delivery systems — Automated insulin delivery (AID) systems comprise an insulin pump and a CGM device with integrated function, enabling automatic adjustment of insulin delivery based in part on CGM data. Partially automated systems and a more fully automated system for insulin delivery are available for clinical use. More fully automated systems that deliver dual hormone therapy are in development.
Insulin only, partially automated system — Three partially automated (hybrid) insulin delivery systems are commercially available in the United States [24-26]. In addition, do-it-yourself (DIY) hybrid systems are also in use and are discussed below. (See 'Do-it-yourself automated insulin delivery systems' below.)
Principles of use — When using these insulin pump/CGM systems in the "auto" or "automatic" mode, instead of infusing basal insulin in mini-boluses every five minutes according to the programmed basal rates ("manual" mode), the system automatically gives a mini-bolus (or no bolus) of rapidly acting insulin every five minutes determined by an algorithm that uses parameters including CGM results and target glucose (figure 1). Automatic correction insulin doses are also provided in advanced hybrid closed-loop systems.
With these "hybrid" closed-loop devices, the user still needs to determine and administer pre-meal insulin boluses, which is facilitated with an individualized insulin-to-carbohydrate ratio set in the pump's bolus calculator. Some systems require periodic fingerstick capillary glucose measurements for calibration and to address high or low values, and some have limited choices for the target glucose. Each of the available devices can transmit insulin dosing data (display of basal and bolus insulin delivery), CGM and BGM data, as well as pump and CGM settings to cloud-based systems. These data can be retrieved and reviewed on demand (figure 3A-B and figure 4A-B).
Time in target range and hypoglycemia — Partially AID (hybrid closed-loop) systems increase time spent in target glucose range (70 to 180 mg/dL [3.9 to 10 mmol/L]) and reduce A1C compared with sensor-augmented pump therapy without increasing risk of hypoglycemia [27]. As an example, in a meta-analysis of trials comparing the use of any hybrid closed-loop system with any insulin-based treatment in nonpregnant adults with type 1 diabetes, the proportion of time spent near normoglycemia (70 to 180 mg/dL [3.9 to 10 mmol/L]) over 24 hours was modestly, albeit significantly, higher with the hybrid closed-loop system (weighted mean difference 9.62 percent, 95% CI 7.54-11 percent) [27]. Overall, the incidence of severe hypoglycemia was low in both groups. Many trials have examined the utility of these devices in the outpatient setting, during eating and usual daily activities, over an extended period of use [24,28-35]. As examples:
●In a crossover, random-order trial, 33 adults (mean A1C 8.5 percent [69.4 mmol/mol]) were assigned to either 12 weeks of partially automated (hybrid), closed-loop insulin delivery (intervention) followed by 12 weeks of sensor-augmented pump therapy (control), or to the opposite order (sensor-augmented pump therapy followed by hybrid, closed-loop insulin delivery) [29]. Participants performed their usual daily activities and were not monitored remotely by study staff.
Compared with the sensor-augmented pump, use of the hybrid closed-loop system resulted in a greater proportion of time spent in the target range of 70 to 180 mg/dL (3.9 to 10 mmol/L; 67.7 versus 56.8 percent, mean difference 11 percentage points, 95% CI 8.1-13.8). The mean glucose level (157 versus 168 mg/dL) and the mean A1C level (7.3 versus 7.6 percent) were also lower during the closed-loop phase of insulin delivery. Hypoglycemia, as measured by the area under the curve when glucose was <63 mg/dL (3.5 mmol/L), was lower during the closed-loop system than during the control period (169 versus 198 [mg/dL x min]).
●In a trial in children and adolescents with the same device, but delivering insulin only overnight, 25 patients (mean A1C 8.1 percent [65 mmol/mol]) used the hybrid closed-loop insulin delivery system overnight and discontinued it before breakfast [29]. Compared with the sensor-augmented insulin pump, use of the hybrid closed-loop system resulted in a greater proportion of nocturnal time spent with glucose levels in the target range of 70 to 145 mg/dL (3.9 to 8 mmol/L; 59.7 versus 34.4 percent, mean difference 24.7 percentage points, 95% CI 20.6-28.7). The mean overnight glucose level was lower with the closed-loop system (146 versus 176 mg/dL). The proportion of time spent with a blood glucose level <70 or <50 mg/dL (<3.9 or <2.8 mmol/L) was low and was not reduced during the closed-loop treatment arm (<4 and <1 percent, respectively).
●In a subsequent six-month trial comparing a hybrid closed-loop system with a sensor-augmented insulin pump in 168 patients ≥14 years of age, the percentage of time in target range (70 to 180 mg/dL [3.9 to 10 mmol/L]) as measured with CGM was higher in the closed-loop group (71 versus 59 percent, risk-adjusted difference 11 percent, 95% CI 9-14) [25]. A1C levels improved in patients using the closed-loop system (7.4 to 7.06 percent) but did not change in controls (7.4 to 7.39 percent). Although there were no serious hypoglycemic events in either group, the percentage of time spent in hypoglycemia was lower in patients assigned to the closed-loop system (eg, <54 mg/dL, 0.29 versus 0.35 percent, risk-adjusted difference -0.10, 95% CI -0.19 to -0.02). There were, however, more hyperglycemic adverse reactions, including one episode of ketoacidosis, in the closed-loop group (14 versus 2 patients), primarily due to infusion set failures. In a similarly designed 16-week trial in children 6 to 13 years of age, the percentage of time in target range was higher with the closed-loop system (67 versus 55 percent, mean adjusted difference 11 percentage points, 95% CI 7-14) [36].
Hybrid closed-loop systems also have been studied in young children (aged <6 years) with type 1 diabetes [37]. The use of AID therapy in children is discussed in detail separately. (See "Insulin therapy for children and adolescents with type 1 diabetes mellitus", section on 'Automated insulin delivery (hybrid closed-loop insulin pumps)'.)
Patient selection — All individuals with type 1 diabetes may be candidates for AID therapy if adequate infrastructure and resources are available to support its use. The strongest evidence supporting use of AID systems is in individuals with high risk of hypoglycemia or impaired awareness of hypoglycemia and individuals who have not achieved glycemic goals on current therapy [38-40]. AID therapy also may provide greater benefit when initiated closer to the time of type 1 diabetes diagnosis.
Structured and individualized training and support are essential prior to initiation of AID therapy [38]; rather than reducing demands of care, AID therapy requires that individuals have extensive knowledge of both general diabetes care and device management. After initiating AID therapy, close monitoring and support remain critical, particularly over the first three to six months of use when discontinuation rates are highest [38]. For the first commercial hybrid closed-loop system in the United States, the few available small reports indicate that discontinuation rates in the real world are high [41,42]. Improvements have been made in the newer, advanced hybrid closed-loop systems to reduce burden and improve effectiveness, with additional advancements anticipated in future models. Individuals receiving MDI insulin therapy may transition directly to hybrid AID systems without prior insulin pump experience [43], although short-term device training before initiation of AID therapy may be helpful for individuals who have not previously used an insulin pump and/or CGM [38].
Insulin only, fully automated system — In contrast to partially automated hybrid closed-loop systems, an insulin-only, more fully automated system enables initiation of insulin pump use solely on the basis of user body weight and without input of basal insulin doses or insulin dosing parameters. Once initiated, the system automatically calibrates and adjusts insulin delivery based on glycemia. This system also requires only qualitative descriptions of carbohydrate intake (eg, "usual for me," "more," or "less" for the specific meal type). As carbohydrate counting is not needed for pre-meal insulin dosing, the fully automated system eliminates a major challenge to more widespread use of insulin pump therapy. In the United States, this more automated system has regulatory approval for use in individuals with type 1 diabetes aged ≥6 years [44].
●In a 13-week, unblinded trial in which 219 participants (ages 6 to 79 years, mean age 28 years) with type 1 diabetes (mean A1C approximately 7.8 percent) were randomly assigned to a fully automated insulin system or standard care (any mode of insulin delivery coupled with CGM), the fully automated system conferred a greater reduction in A1C (mean adjusted difference in A1C -0.5 percent, 95% CI -0.6 to -0.3 percent) [45]. The percentage of time spent in target glucose range (≥70 mg/dL and ≤180 mg/dL [3.9 to 10 mmol/L]) was higher with the fully automated insulin system than standard care (mean adjusted difference 11 percent, 95% CI 9-13 percent). Frequency of hypoglycemia was similar between groups.
Bihormonal, fully automated system (bionic pancreas) — Studies have evaluated the efficacy of a bihormonal, more automated closed-loop system of insulin delivery based upon continuous glucose sensing (bionic pancreas). This system, which can deliver insulin and glucagon, is not commercially available.
●In a crossover trial, 43 adults received therapy with automated, bihormonal (insulin and glucagon), closed-loop system for 11 days and therapy with their own insulin pump for 11 days [33]. The bihormonal pump therapy only requires input of the person's body mass index (BMI) to initiate therapy. The delivery of the insulin and glucagon during the closed-loop arm was determined completely automatically by an algorithm that was, in turn, dependent on CGM results. During the closed-loop system part of the trial, patients could electively "announce" meals, allowing a "priming" dose to be administered. Participants continued all normal activities, including exercise and driving. Fingerstick plasma glucoses were checked at least four times daily; however, the closed-loop system was driven entirely by the CGM using commercially available devices.
The mean CGM glucose concentration was lower during the closed-loop system, as compared with the comparator period (140.4 versus 162 mg/dL [7.8 versus 9.0 mmol/L]), and the percentage time with a glucose level <60 mg/dL (3.3 mmol/L) was lower (0.6 versus 1.9 percent, respectively). There were no severe hypoglycemic events during the closed-loop period.
●In a similarly designed, five-day crossover trial, 32 adolescents participated in the same activities, ate the same meals, and stayed in the same cabins as nonparticipants at a diabetes camp [28]. On days 2 through 5 of the closed-loop system, as compared with the control period, the mean glucose level was lower (142 versus 158 mg/dL [7.0 versus 8.8 mmol/L]) and the percentage time with a glucose level <70 mg/dL (3.9 mmol/L) or <60 mg/dL (3.3 mmol/L) was similar (3.1 and 4.9 percent and 1.3 and 2.2 percent, respectively). There were no severe hypoglycemic events during the closed-loop period.
Do-it-yourself automated insulin delivery systems — The use of do-it-yourself automated insulin delivery (DIY AID) systems or "looping" by individuals with type 1 diabetes to automatically infuse insulin has increased in the United States and globally. The systems use commercially available insulin pumps and CGM devices, smartphones, and experimental applications that control insulin infusion. Additional hardware and communication devices may be needed. Free open-source resources for each of the available DIY looping systems are offered on their websites. None of these systems are US Food and Drug Administration (FDA) approved, all are considered experimental, and all involve a high degree of involvement by the person with diabetes.
Limited clinical trial data support the utility of open-source AID systems for selected individuals willing to learn these systems. As an example, in a 24-week trial comparing an open-source DIY AID system with sensor-augmented insulin pump therapy in 97 people with type 1 diabetes (48 children [median age 13 years] and 49 adults [median age 40 years]), the improvement in percentage of time spent in target glucose range was greater in participants using the open-source AID system (adjusted difference 14 percent, 95% CI 9.2-18.8 percent) [46]. All participants underwent a four-week run-in period before randomization to gain experience with the study devices, and all had at least six months' prior experience using an insulin pump. Since the design of this study did not incorporate a comparison of the open-source non-FDA approved DIY AID system with a currently commercially available FDA-approved AID (hybrid closed-loop) system, it could not compare their safety or effectiveness.
FOLLOW-UP VISITS — As in adults with type 1 diabetes treated with multiple daily injection (MDI) insulin therapy, the frequency of clinic visits and adjustments to the insulin regimen vary based on individual needs. This information is reviewed in detail separately. (See "Management of blood glucose in adults with type 1 diabetes mellitus", section on 'Follow-up'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diabetes mellitus in adults" and "Society guideline links: Blood glucose monitoring".)
SUMMARY AND RECOMMENDATIONS
●General principles – With continuous subcutaneous insulin infusion (CSII; insulin pump therapy), basal insulin is supplied in the form of mini-boluses of insulin delivered every five minutes (usually constituting 40 to 50 percent of the total daily dose [TDD]) with pre-meal bolus doses given to minimize postprandial glucose excursions. We suggest rapid-acting insulin analogs (lispro, aspart, and glulisine) rather than regular insulin for insulin pump therapy (Grade 2C). (See 'General principles' above.)
●Dosing
•TDD – For individuals meeting glycemic goals who are transitioning from a multiple daily injection (MDI) insulin regimen to CSII, the initial TDD of insulin administered by pump may be 10 to 20 percent less than the TDD (both short-acting and long-acting insulin) of the previous regimen. Conversely, people who are above glycemic targets (high glycated hemoglobin [A1C] with no hypoglycemia) may be started with the same TDD (both short-acting and long-acting insulin) as they had been using with their injection regimens. (See 'Total daily dose' above.)
•Basal rate – Approximately 40 to 50 percent of the TDD is administered as the basal rate (divide by 24 to get units per hour). This proportion can be higher or lower depending on a number of factors, including if the individual consumes a low- or high-carbohydrate diet, respectively. For most individuals, basal rates are in the range of 0.01 to 0.015 units per kg per hour (ie, for a 60 kg woman approximately 0.6 to 0.9 units per hour). (See 'Basal rate' above.)
•Bolus dosing – The pre-meal bolus dose should be based primarily upon the carbohydrate content of the intended meal and the blood glucose level immediately before the meal. Many insulin pumps have insulin calculators for bolus dosing for meals and for correction of hyperglycemia. Extended or dual-wave boluses can be used to help manage the prolonged or delayed rise in glucose that is commonly observed after eating higher fat and protein meals or in the presence of gastroparesis. The use of calculated "active insulin" or "insulin on board" helps prevent hypoglycemia that can occur from overcorrecting for hyperglycemia with multiple correction boluses ("stacking"). (See 'Bolus dosing' above.)
●Types of insulin pumps – A variety of insulin pumps are available, and the choice among pumps is largely a matter of individual preference, cost, lifestyle, and compatibility with continuous glucose monitoring (CGM) devices (figure 1 and figure 2). Use of sensor-augmented insulin pump therapy and hybrid closed-loop systems can reduce time in hypoglycemia. (See 'Types of insulin pumps' above.)
•Sensor-augmented insulin pump – Sensor-augmented insulin pump therapy involves the use of an insulin pump and a CGM device that function independently. (See 'Sensor-augmented insulin pump' above.)
•Low glucose threshold suspend or predictive low glucose suspend systems – Some insulin pumps can suspend insulin delivery when glucose readings reach a prespecified low glucose threshold or are predicted to reach that threshold. (See 'Low glucose threshold suspend or predictive low glucose suspend systems' above.)
•Automated insulin delivery (AID) systems – These systems comprise an insulin pump and a CGM device with integrated function. When partially automated insulin delivery systems are in the "auto" or "automatic" mode, the system automatically gives a mini-bolus (or no bolus) of rapidly acting insulin every five minutes determined by an algorithm that uses parameters including CGM results and target glucose (figure 1). Automatic correction insulin doses are also provided in advanced hybrid closed-loop systems. With these "hybrid" closed-loop devices, the user still needs to determine and administer pre-meal insulin boluses. With more fully automated systems, insulin pump use can be initiated solely on the basis of user body weight. Once initiated, the system automatically calibrates and adjusts insulin delivery based on glycemia. (See 'Insulin only, partially automated system' above and 'Insulin only, fully automated system' above.)
●Follow-up visits – The frequency of clinic visits and adjustments to the insulin regimen vary based on the needs of the person with diabetes. (See "Management of blood glucose in adults with type 1 diabetes mellitus", section on 'Follow-up'.)
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