INTRODUCTION — Type 1 diabetes is characterized by destruction of the pancreatic beta cells, leading to insulin deficiency. It accounts for approximately 5 to 10 percent of cases of diabetes in the United States, Canada, and Europe (whereas type 2 diabetes accounts for over 90 percent). It is one of the most common chronic diseases of childhood, although type 1 diabetes may present in adulthood. In general, the younger the age of diagnosis and the longer the duration of type 1 diabetes, the greater the likelihood that the individual will have absolute insulin deficiency with undetectable C-peptide levels.
This topic will review the management of blood glucose in nonpregnant adults with type 1 diabetes. Management of type 1 diabetes in children, adolescents, and during pregnancy is reviewed separately. A general discussion of the classification of diabetes, clinical presentation and diagnosis of diabetes, and evaluation for diabetes-related complications is reviewed separately.
●(See "Overview of the management of type 1 diabetes mellitus in children and adolescents".)
●(See "Pregestational (preexisting) diabetes mellitus: Antenatal glycemic control".)
●(See "Classification of diabetes mellitus and genetic diabetic syndromes".)
●(See "Clinical presentation, diagnosis, and initial evaluation of diabetes mellitus in adults".)
●(See "Overview of general medical care in nonpregnant adults with diabetes mellitus".)
INTENSIVE DIABETES THERAPY — Intensive diabetes therapy includes the coordination of meals/diet and activity with insulin replacement as physiologically as possible, which involves the frequent monitoring of glucose levels and frequent insulin administration to match needs. It is the standard of care for patients with type 1 diabetes.
Glycemic targets — Glycated hemoglobin (A1C) and glucose monitoring are critical for directing therapy. For some populations, for example African Americans, the relationship between A1C and mean glucose derived from continuous glucose monitoring (CGM) may be different than that in White Americans. However, there is even greater variation in this relationship within races than between them [1]. (See "Measurements of glycemia in diabetes mellitus", section on 'Racial/ethnic differences'.)
●Glycated hemoglobin – A1C goals in people with diabetes should be tailored to the individual, balancing the demonstrated benefits with regard to prevention and delay in micro- and macrovascular complications with the risk of hypoglycemia. For most adults with type 1 diabetes, we aim for an A1C value of ≤7 percent (using an assay aligned to the Diabetes Control and Complications Trial [DCCT] in which the upper limit of normal is 6 percent). A1C goals may be higher in people in whom the risks of tighter control outweigh benefits. Data from the T1D Exchange Clinic Registry and from a United States electronic health record database suggest that the majority of adults with type 1 diabetes do not achieve an A1C goal of <7 percent, with the highest mean A1C levels observed in adolescents and young adults (figure 1) [2,3].
●Blood glucose – In general, for healthy, young and middle-aged adults, the target glucose range is 70 to 180 mg/dL (3.9 to 10 mmol/L), while minimizing time in hypoglycemia (<70 mg/dL [3.9 mmol/L]) and hyperglycemia (>180 mg/dL [10 mmol/L]) and avoiding glucose readings of <54 mg/dL (3 mmol/L) and >250 mg/dL (13.9 mmol/L) [4]. The actual mean blood glucose levels associated with A1C levels 6.50 to 6.99 percent in type 1 diabetes are 144, 140, and 154 mg/dL fasting, pre-meals, and pre-bed, respectively [5].
●Interstitial glucose – CGMs measure interstitial glucose levels every one to five minutes. Interstitial glucose concentrations correlate well with blood glucose results. CGM metrics are being increasingly used to assess glycemic control. Having a time in range [70 to 180 mg/dL (3.9 to 10 mmol/L)] of 70 percent has been associated with an estimated A1C of approximately 7 percent [6]. Additional important metrics include percent time in hypoglycemia, coefficient of variation (CV; measure of glucose variability), and the "glucose management indicator" (GMI), which is based on mean CGM glucose [6-8]. (See 'Monitoring blood glucose' below.)
Glycemic targets (A1C goals) are generally set higher (eg, <7.5 or <8 percent, or higher) for older adults and those with a history of severe hypoglycemia, hypoglycemia unawareness, comorbidities, or a limited life expectancy [9,10]. More stringent control may be indicated for selected motivated patients with type 1 diabetes and during pregnancy. (See "Pregestational (preexisting) diabetes mellitus: Antenatal glycemic control" and "Glycemic control and vascular complications in type 1 diabetes mellitus", section on 'Glycemic targets'.)
Insulin replacement — For people with type 1 diabetes, the goal of insulin therapy is to provide a physiologic profile of insulin by administration of a basal insulin (delivered by daily or twice-daily injections of an intermediate-acting or long-acting insulin preparation or continuous subcutaneous delivery of a rapid-acting insulin preparation via a pump) plus mealtime (prandial) boluses of a rapid-acting or short-acting insulin (table 1). The dose of the pre-meal bolus is determined by the ambient blood glucose level before the meal, the size and composition of the meal, anticipated activity levels, and trending glucose levels (when available) from CGM. (See 'Insulin regimens' below.)
This physiologic replacement of insulin with "basal-bolus" insulin therapy should be started as early as possible following the diagnosis of type 1 diabetes. Simpler regimens (eg, twice-daily injections of short-acting [regular] and intermediate-acting [NPH] insulin mixed together in the same syringe and given in fixed amounts before breakfast and dinner) are not recommended unless the patient cannot or will not adhere to multiple injections or an insulin pump. (See 'Choice of insulin delivery' below and "General principles of insulin therapy in diabetes mellitus", section on 'Insulin preparations'.)
The DCCT and its long-term Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study showed that, compared with a simple insulin regimen, early aggressive insulin therapy substantially and uniformly decreased the complications that accompany type 1 diabetes:
●The DCCT and other smaller studies demonstrated that improved glycemic control with intensive insulin therapy in patients with type 1 diabetes mellitus led to reductions in relatively early stages of retinopathy, nephropathy, and neuropathy by 35 to 76 percent (figure 2 and figure 3) [11,12].
●The EDIC follow-up study from the DCCT demonstrated that improved glycemic control with intensive insulin therapy also reduces more advanced stages of microvascular disease, as well as cardiovascular disease and mortality [13-17].
In addition, in the DCCT, early aggressive insulin therapy helped to sustain endogenous insulin secretion, which was associated with a lower A1C and a lower risk for severe hypoglycemia, defined as an episode of biochemical hypoglycemia that required assistance from another to treat [12].
What was considered "intensive therapy" in the DCCT is now considered to be standard therapy for management of type 1 diabetes. (See "Glycemic control and vascular complications in type 1 diabetes mellitus".)
Optimal insulin therapy requires an understanding of insulin pharmacokinetics (table 1). A number of factors influence the pharmacokinetics of insulin, including the insulin preparation, size of subcutaneous depot, injection technique, site of injection, alterations in subcutaneous blood flow, and, potentially, the presence and titer of anti-insulin antibodies. These issues are reviewed in detail elsewhere. (See "General principles of insulin therapy in diabetes mellitus".)
Monitoring blood glucose — Monitoring blood glucose is an integral part of intensive insulin therapy in type 1 diabetes as it is necessary to direct insulin dosing.
●Blood glucose monitoring (BGM) – BGM, often called self-monitoring of blood glucose (SMBG) requires intermittent capillary blood sampling and the use of a glucose meter. Ideally, for individuals using SMBG, testing at home should be done at least four times daily, before meals and at bedtime. Additional testing, two to three hours after meals and occasionally at 3 AM (for safety), as well as before and after exercise, before driving, and when hypoglycemia is suspected, may be indicated. (See "Glucose monitoring in the ambulatory management of nonpregnant adults with diabetes mellitus", section on 'BGM systems'.)
●Continuous glucose monitoring – CGM is useful for adults with type 1 diabetes, especially for those who are having frequent or severe hypoglycemia and who have developed hypoglycemic unawareness. Several generations of devices to sample glucose continuously from interstitial fluid are available, with ongoing development in progress.
Real-time CGM devices measure and transmit glucose values automatically every five minutes to a receiver and can alert (alarm) for hypoglycemia and hyperglycemia. There are CGM systems that transmit glucose data to mobile phones and allow users to "share" their data with family members, friends, and caregivers; others require the use of device-specific receivers. The immediate feedback of glucose results allows timely intervention for high, low, or trending glucose levels to aid management and avert serious hypoglycemic events. CGM devices increasingly provide feedback to insulin pumps, allowing automatic adjustments of basal rate infusions for low glucose values or trends (low glucose suspend) and high or rising glucose levels (automated increases in basal infusion). (See "Continuous subcutaneous insulin infusion (insulin pump)", section on 'Types of insulin pumps'.)
In addition to the real-time CGM devices, there is a commercially available "flash" or "intermittent scanning" CGM device. This device does not require calibration. It requires the user to pass the reader (or their smartphone) over the sensor/transmitter to visualize the glucose readings, which are measured every minute and recorded every 15 minutes. The first model of this device does not alarm, but the most recent model can provide real-time alarms.
Because of reliability issues and the need for calibration for some of the devices, CGM does not eliminate the need for at least occasional fingersticks (SMBG). (See "Glucose monitoring in the ambulatory management of nonpregnant adults with diabetes mellitus", section on 'CGM systems'.)
●Glycated hemoglobin – A1C should be tested approximately every three to six months to assess chronic glucose control.
Diabetes education — Type 1 diabetes treatment regimens are complex and are primarily dependent on self-care. All people with type 1 diabetes require intensive initial as well as ongoing self-management education and support in order to manage their diabetes safely and improve clinical outcomes and quality of life [18]. It is important to understand the effects of diet, physical activity, and stress on blood glucose; proper use of glucose and ketone monitoring; proper insulin injection techniques and use of insulin pump (when applicable); sick day rules; recognition, treatment, and prevention of hypoglycemia; foot care; and strategies for the prevention and management of complications. (See 'Follow-up' below and "Hypoglycemia in adults with diabetes mellitus", section on 'General approach to reduce risk' and "Overview of general medical care in nonpregnant adults with diabetes mellitus", section on 'Diabetes-related complications'.)
Diabetes therapy will have the greatest chance for success if the person is motivated, has a good understanding of the regimen, and is supported by family, friends, and a health care team with sufficient enthusiasm and expertise to guide therapy, educate the patient, and to monitor progress continuously.
Nutrition — One of the most important and difficult components of nutrition education is for patients to learn to estimate how much carbohydrate they are about to consume at any meal or snack. Matching insulin delivery to insulin requirements is based upon the patient understanding the anticipated glucose excursion with meals and selecting a dose of rapid-acting or short-acting insulin that will control postprandial blood glucose excursions. Use of insulin-to-carbohydrate ratios can free patients from having to eat a fixed amount of carbohydrate at particular meals. If they plan to eat less carbohydrate at a meal, they simply decrease the dose of prandial insulin. Mobile apps are available to help individuals estimate the carbohydrate content of their meals.
Patients vary considerably in how much insulin they need to cover a set amount of carbohydrate. Some patients need a different "insulin-to-carbohydrate ratio" at different meals. In addition, meals containing higher fat and protein may require different insulin delivery profiles to prevent late postprandial hyperglycemia [19-21]. (See "Nutritional considerations in type 1 diabetes mellitus", section on 'Advanced carbohydrate counting'.)
Physical activity — Incorporating regular physical activity into the diabetes treatment plan is helpful to avoid or limit weight gain frequently associated with intensive insulin administration [22]. It also has cardiovascular and other benefits. We encourage healthy adults with diabetes to perform at least 30 minutes of moderate-intensity aerobic activity on most days of the week. To increase adherence, the clinician should advise choosing a type of activity or exercise they will enjoy and offer regular encouragement and suggestions for overcoming barriers to exercise.
There are four aspects of exercise that are important to consider:
●The effect of exercise on blood glucose varies with the time of day and whether the person is relatively hypoinsulinemic or hyperinsulinemic at that time.
●Late hypoglycemia can occur several hours after vigorous aerobic exercise, due to repletion of muscle glycogen stores.
●The type (aerobic versus weightbearing), intensity, and duration of the exercise can affect glycemia.
●Exercise may change the profile of insulin absorption with more rapid absorption from an exercising limb.
Adjustments to the insulin regimen before, during, and after exercise are reviewed separately. (See "Exercise guidance in adults with diabetes mellitus", section on 'Glycemic management during exercise' and "Cases illustrating the effects of exercise in intensive insulin therapy for type 1 diabetes mellitus".)
Psychosocial issues — Patients with type 1 diabetes often experience significant stress related to the many self-care responsibilities to optimize glycemic control. Assessment and management of psychosocial issues are an important component of care in patients with type 1 diabetes. Depression, anxiety (fear of hypoglycemia and hyperglycemia), and eating disorders may develop and are associated with poor glycemic control [18,23] (see "Nutritional considerations in type 1 diabetes mellitus", section on 'Eating disorders'). In adolescents and young adults, comprehensive management of diabetes that addresses these psychosocial issues can improve glycemic control and reduce hospitalization [24,25]. In adults, food insecurity has been associated with worse glycemic control [26]. Financial difficulties, including the inability to purchase sufficient insulin or adequate self-monitoring equipment or supplies, can also contribute to poor glycemic control.
Challenges — Although intensive diabetes therapy (coordination of meals/diet, activity, frequent monitoring of blood glucose, and physiologic insulin therapy replacement) has clear benefits in adults with type 1 diabetes, it is important to consider the potential challenges associated with this regimen:
●Great effort is required by the patient to manage and coordinate diet, activity, insulin administration, and blood glucose monitoring. (See "Glucose monitoring in the ambulatory management of nonpregnant adults with diabetes mellitus".)
●There is a heightened risk of hypoglycemia with intensive insulin therapy. (See "Hypoglycemia in adults with diabetes mellitus", section on 'Risk factors for hypoglycemia'.)
●The cost of intensive diabetes therapy is greater than that of conventional treatment. Based upon an analysis of the DCCT and costs from the early 1990s, the cost of intensive diabetes therapy as performed in the DCCT (USD $4000 to $6000/year) was approximately three times that of conventional treatment (one or two injections per day with minimal SMBG) [27]. The overall cost of intensive diabetes management today varies enormously depending on which insulin is used, whether an insulin pump is involved, frequency of SMBG, use of CGM, and other factors. Cost remains an important barrier that may limit use of insulin analogs, insulin pens, SMBG, CGM, and insulin pumps.
●Weight gain may occur after initiation of intensive insulin therapy, which can affect patient compliance. (See 'Follow-up' below.)
In spite of these challenges, intensive insulin therapy is recommended for the majority of adults with type 1 diabetes.
INSULIN REGIMENS — The basic requirements of an optimal insulin regimen include administration of a basal insulin plus mealtime boluses of a rapid-acting or short-acting insulin. Basal insulin can be delivered by daily or twice-daily injections of an intermediate-acting or long-acting insulin preparation or continuous subcutaneous insulin infusion (CSII) via a pump using a rapid-acting insulin preparation. Mealtime boluses plus additional insulin used to correct hyperglycemia are provided by a rapid-acting or short-acting insulin (table 1). (See "General principles of insulin therapy in diabetes mellitus", section on 'Insulin preparations'.)
Choice of insulin delivery — The choice between multiple daily insulin (MDI) injections and continuous subcutaneous delivery of a rapid-acting insulin preparation via a pump (CSII) is largely a matter of patient preference, lifestyle, and cost. It should be made after both regimens are carefully explained to the patient. CSII can be of particular benefit in adults with variable basal requirements, unpredictable or varying schedules requiring flexible insulin dosing, and sometimes in those who have not been able to achieve their glycemic goals on MDI.
Glycemic outcomes — Glycemic control is generally similar with MDI and CSII when using self-monitoring of blood glucose (SMBG). The impact on hypoglycemia is less certain, with most trials showing no difference in severe hypoglycemic events. Regardless of the mode of insulin delivery (MDI versus CSII), clinical trials have reported improved glycemic outcomes with the use of continuous glucose monitoring (CGM) in adults with type 1 diabetes, with similar or lower A1C levels but less frequent hypoglycemia. Newer insulin pumps, which are integrated with CGM systems, have features that can reduce hypoglycemia by temporarily suspending insulin infusion ("low glucose suspend" feature). (See "Continuous subcutaneous insulin infusion (insulin pump)", section on 'Sensor-augmented insulin pump'.)
●In the Diabetes Control and Complications Trial (DCCT), in which all supplies were free, patients in the intensive therapy group were allowed to choose between MDI or CSII [11]. Glycemic control, frequency of severe hypoglycemia, and progression of microvascular disease were similar with either type of insulin therapy. It should be noted that pumps have become smaller, more reliable, and more sophisticated since the DCCT ended in 1993.
●In meta-analyses of randomized controlled trials that compared CSII with MDI, continuous therapy resulted in slightly better glycemic control (weighted mean difference -0.2 to -0.4 percentage points), with little difference between the two groups in the rate of hypoglycemia [28-31]. Many of the trials included in the meta-analyses used rapid-acting insulin analogs instead of regular insulin for CSII and rapid-acting and long-acting insulin analogs for MDI. In the 2017 and 2019 meta-analyses, which included a trial using CSII with CGM (sensor-augmented insulin pump), there was no difference in minor or severe hypoglycemic events; however, there was a reduction in the incidence of nocturnal hypoglycemia with CSII [30]. Small trials comparing intensive insulin therapy using MDI versus CSII reported no difference in quality-of-life measures between treatment groups [32,33]. Sensor-augmented pump therapy with a suspend feature was not used in these older studies. (See "Continuous subcutaneous insulin infusion (insulin pump)", section on 'Sensor-augmented insulin pump'.)
Risk of DKA — In some trials comparing MDI and CSII, the risk of diabetic ketoacidosis (DKA) was higher with CSII [31]. DKA in patients using CSII is usually due to detachment or blockage or leakage in the syringe or the infusion set or connectors, causing an interruption of insulin infusion [34,35]. Since the subcutaneous depot is very small, any interruption in continuous flow leads very quickly to hypoinsulinemia, hyperglycemia, and, possibly, DKA. DKA occurs more rapidly (four versus six hours) in patients with pump malfunction who are using insulin lispro rather than regular insulin [36]. (See "Continuous subcutaneous insulin infusion (insulin pump)", section on 'Troubleshooting'.)
Dose adjustments and absorption — One advantage of CSII is that it allows for flexibility of insulin dosing and adjustments. As an example, a temporary basal rate can be programmed, such that basal rates can be reduced for aerobic activities. In addition, CSII may allow more flexibility in the timing of meals (a relative advantage that may also pertain to MDI regimens that use insulin analogs instead of NPH).
CSII can deliver insulin accurately in fractions of units, which can be a benefit for adults who are very insulin sensitive. Doses as low as 0.05 units can be accurately delivered with CSII. While these extremely small doses of insulin may not be clinically important for some adults, nonpump insulin delivery can only provide insulin at 0.5- to 1-unit increments, which for some patients, especially children, may not be optimal.
For adults who have gastroparesis or eat high fat and protein meals, advanced bolus features (extended or dual-wave bolus) may help to better control the delayed or prolonged hyperglycemia observed after meals.
In addition, insulin absorption with pump therapy appears to be less variable from day to day [37], and therefore, blood glucose profiles may be more predictable, particularly compared with NPH and glargine-based MDI regimens. Both the small subcutaneous depot and the constancy of the injection site and depth for the two to three days with each catheter contribute to the relative consistency of absorption.
Lifestyle considerations — There are patients who prefer not to wear a CSII device. Some patients who use pumps complain that the treatment is awkward, embarrassing, or unpleasant, particularly when sleeping or having sexual intercourse. Pump-treated patients can take off the pump for brief periods. Doing so for one hour or less does not usually lead to loss of blood glucose control. For longer periods (such as overnight), the patient should transition to an intermediate-acting or long-acting basal insulin.
Although the available hybrid closed-loop devices may lower A1C modestly without an increase (and even a decrease) in hypoglycemia, the interface between patient management of boluses and automated basal rate control may be troublesome with numerous alarms. For some adults, however, use of hybrid closed-loop devices may reduce fear of nocturnal hypoglycemia, thereby decreasing anxiety and improving duration of sleep. The next generation of fully automated, closed-loop insulin delivery devices are being designed to reduce the burden of self-care associated with type 1 diabetes.
Cost — The costs of the pump and supplies are higher than those of insulin injection therapy (MDI).
Multiple daily injections — Many different insulin regimens may be used in an MDI regimen. Some of the more common ones are shown in the table (table 2). Regardless of the type of insulin chosen, these insulin regimens should be monitored with SMBG or use of CGM. (See 'Monitoring blood glucose' above.)
Choosing basal/prandial insulin — The choice of basal (NPH, U-100 or U-300 glargine, detemir, or degludec) and prandial (lispro, aspart, glulisine, regular) insulin for an MDI regimen depends upon patient preference, lifestyle, and cost concerns with variable insurance coverage of different insulins. Owing to the convenience for patients regarding timing of prandial rapid-acting insulin and the reduced risk of hypoglycemia, most patients use insulin analogs. Since regular and NPH insulins are less expensive than analog insulins, some patients need to use them for cost reasons. (See "General principles of insulin therapy in diabetes mellitus", section on 'Insulin preparations'.)
In short-term trials, there may be a modest benefit of insulin analogs over non-analog insulin on A1C levels. As an example, in an 18-week trial in 595 adults with type 1 diabetes randomly assigned to NPH/regular versus detemir/aspart, there was a small but significant difference in A1C values (mean difference -0.22 percentage points) favoring the insulin analogs [38]. Although the patients in the analog group received a slightly higher daily dose (by 4 units) of basal insulin, the risk of overall and nocturnal, but not severe, hypoglycemia was lower in the analog group. Whether the basal, bolus, or both analogs were responsible for the improvement compared with non-analog treatment is not clear. Long-term trials with diabetic complications as endpoints are lacking.
Basal insulin options — The choice of basal insulin depends upon patient preference, lifestyle, and cost concerns.
●Insulin glargine – In patients with type 1 diabetes, glycemic control is similar if once-daily glargine is given before breakfast, before dinner, or at bedtime, but there is less nocturnal hypoglycemia with breakfast administration [39].
Although many patients can achieve stable basal serum insulin concentrations with a single daily injection of U-100 insulin glargine given in the morning or evening (regimens 3 and 4) (table 2), this is not always the case. Some patients with type 1 diabetes achieve better glycemic control with U-100 glargine given twice per day (regimen 5) (table 2). U-100 insulin glargine has a half-live of 12 hours.
Insulin glargine is also available in a more concentrated formulation (U-300 glargine), which prolongs its duration of action and further smooths its profile. This insulin is given once daily and can be of benefit for some adults with type 1 diabetes. Similar to insulin degludec, U-300 insulin glargine has little peak effect and may reduce hypoglycemia in individual patients. (See "General principles of insulin therapy in diabetes mellitus", section on 'Basal insulin analogs'.)
●Insulin detemir – The duration of action of insulin detemir is shorter than that of insulin glargine [40], though still somewhat longer than NPH (table 1). In one study, a detemir dose of 0.29 units/kg provided the same effect as 0.3 units/kg NPH but with a longer duration of action (16.9 versus 12.7 hours, respectively) [41]. Like NPH, twice-daily injections appear to be necessary in most patients with type 1 diabetes. Duration of action is shorter when lower doses are used.
●Insulin degludec – Insulin degludec is a very long-acting basal insulin available in U-100 and U-200 formulations (table 1) [42]. It is administered once daily at any time of day. In contrast to U-100 glargine and detemir insulins, degludec may be mixed with rapid-acting insulins without appreciably altering the kinetics of the degludec or the rapid-acting insulin. The long-term safety profile of insulin degludec is unknown.
In meta-analyses of short-term trials comparing long-acting (glargine or detemir) with intermediate-acting (NPH) insulin in adults with type 1 diabetes, there was little glycemic advantage to the long-acting insulin analogs (mean difference in A1C -0.06 to -0.39 percentage points) [43-45]. In one analysis, detemir once or twice daily and glargine once daily caused less weight gain than NPH once daily [43]. In addition, there was a slightly lower risk of severe hypoglycemia and nocturnal hypoglycemia with detemir once or twice daily compared with NPH once or twice daily [45]. However, in most of the older studies, CGM data were not available, so ascertainment of hypoglycemia was incomplete. In addition, the majority of the studies in the meta-analysis used NPH once daily as the comparator, which is not standard therapy for NPH considering its duration of action [43]. Therefore, the design of the studies in the meta-analysis favored glargine.
In trials comparing insulins degludec and glargine in patients with type 1 diabetes (each in combination with pre-meal aspart), there was similar glycemic efficacy (-0.4 percentage point reduction in A1C), with less overall and/or nocturnal hypoglycemia with degludec, but no significant difference in rates of severe hypoglycemia [46,47].
In a crossover trial including 501 adults with type 1 diabetes and at least one risk factor for hypoglycemia who were randomly assigned to insulin degludec or glargine for 32 weeks and then crossed over to the alternate regimen for an additional 32 weeks, there was a reduced rate of overall symptomatic hypoglycemia with degludec (2200 versus 2463 episodes per 100 patient-years' exposure in the degludec and glargine groups, respectively; rate ratio [RR] 0.89, 95% CI 0.85-0.94) [48]. The rate of nocturnal symptomatic hypoglycemia was also reduced with degludec (277 and 429 episodes per 100 patient-years' exposure, RR 0.64, 95% CI 0.56-0.73). The absolute rate of severe hypoglycemia was only a small fraction of total episodes, but the proportion of patients affected was approximately 7 percent lower with degludec (10.3 percent) compared with glargine (17.1 percent). The loss-to-follow-up in this brief study was greater than 20 percent, making the results somewhat unreliable. Whether the results would apply to patients at lower risk for hypoglycemia is not known.
Prandial insulin options — For patients with type 1 diabetes, basal insulin alone is inadequate for good glycemic control. Prandial (pre-meal or preprandial) boluses are necessary. Either rapid-acting insulin (lispro, aspart, glulisine) or short-acting (regular) can be given pre-meal. Although rapid-acting insulins are more expensive than regular insulin, the convenience for patients regarding timing of pre-meal administration and reduction in hypoglycemia reported in some studies represent distinct advantages for patients [49-52]. Rapid-acting insulins:
●Can be injected 10 to 15 minutes before or up to immediately after meals, whereas regular insulin should be given 30 to 45 minutes or more before meals to optimally match the glycemic excursions after a meal.
●Have a shorter duration of action, reducing hypoglycemia several hours after the dose is given.
●Are particularly useful in addressing unexpectedly high blood glucose levels (eg, between meals or in the setting of stress) because they will lower glucose levels more rapidly and without the prolonged effect of regular insulin.
In a meta-analysis of randomized trials comparing rapid-acting insulin analogs with regular insulin, there was only a minor benefit of insulin analogs in terms of A1C values (mean difference approximately -0.15 percent) and no significant difference in risk of severe hypoglycemia [53]. In two of the trials, there was a significant reduction in nocturnal hypoglycemia with insulin analogs. CGM was not used in most of these studies, so reliable data on reduction of severe and nocturnal hypoglycemia were not available. There are no data examining the relative effects of insulin analogs on long-term diabetic complications. The convenience of rapid-acting insulin compared with regular insulin should not be underestimated.
An even faster-acting insulin aspart (with added niacinamide) has more rapid initial absorption than insulin aspart, with a similar time to peak concentration. There is also a faster insulin lispro. Insulin lispro as well as the faster-acting insulin lispro are available in pens in more concentrated formulations (U-200). Regular insulin is available in a very concentrated (U-500) formulation for injection using U-500 syringes or a U-500 regular insulin pen. U-500 regular has a delayed peak action and a more prolonged duration of action compared with U-100 regular insulin, and it is generally not used in type 1 diabetes. (See "General principles of insulin therapy in diabetes mellitus".)
One inhaled insulin preparation is available, but it is rarely used [54]. Studies have shown that inhaled insulin causes a very rapid rise in serum insulin concentration (similar to that after subcutaneous insulin lispro and aspart, and faster than that after subcutaneous regular insulin). However, there are dosing constraints (only available in 4-unit increments), and the basal insulin must still be administered by injection. Inhaled insulin is contraindicated in the presence of chronic lung disease. No study has demonstrated whether inhaled insulin can achieve A1C levels as low as 7 percent in type 1 diabetes. Inhaled insulin is reviewed in more detail elsewhere. (See "Inhaled insulin therapy in diabetes mellitus".)
Designing an MDI insulin regimen
●Initial total daily dose (TDD) – Most newly diagnosed patients with type 1 diabetes can be started on a TDD of 0.2 to 0.5 units of insulin per kg per day, although many will ultimately require 0.6 to 0.7 units per kg per day. Adolescents, especially during puberty, as well as adults with infections or other acute medical conditions or stresses often need more. The starting dose can be adjusted upward (or downward) every few days based upon symptoms and blood glucose measurements.
●Basal bolus composition and timing – In designing an MDI injection regimen, approximately 40 to 50 percent of the TDD should be given as a basal insulin, either as once-daily degludec or U-300 glargine, once- or twice-daily U-100 glargine or detemir, or as twice-daily intermediate-acting insulin NPH. The long-acting insulin can be given either at bedtime or in the morning; the NPH is usually given as approximately two-thirds of the dose in the morning and one-third at bedtime.
The remainder of the TDD is given as short-acting or rapid-acting insulin, divided before meals. The pre-meal dosing is determined by the pre-meal glucose level, meal size and content, glucose trends (when available from CGM), as well as activity and exercise pattern (see "Nutritional considerations in type 1 diabetes mellitus"). Regimens that use NPH in the morning may not require a pre-lunch dose of short-acting (regular) or rapid-acting insulin because the peak of NPH action is occurring at that time, potentially reducing the frequency of injections.
●Injection sites – The abdomen is the preferred site for pre-meal injections of regular insulin because absorption is quicker from this site [55]. In comparison, the thigh or buttock is a good site for the evening intermediate-acting insulin (NPH) dose; the slower rate of absorption enhances the likelihood that the insulin will last through the night. The site of injection is less important for rapid-acting or long-acting insulin analogs, and therefore, they may be administered in the abdomen, thighs, buttock, or upper arms. However, insulin absorption may be faster in an exercising limb. (See "General principles of insulin therapy in diabetes mellitus".)
Because of the difference in pharmacokinetics of regular insulin (duration of action, five to eight hours) versus rapid-acting insulin analogs (two to four hours), an increase in the dose of intermediate-acting or long-acting insulin may be required when a patient is switched from regular insulin to an insulin analog for the pre-meal bolus dose (table 1). In a randomized clinical trial of 56 patients with type 1 diabetes using variable-dose lispro or regular insulin before meals along with twice-daily NPH insulin, A1C values were lower after 12 months (6.3 versus 6.7 percent) and hypoglycemia was less frequent (7.4 versus 11.5 episodes per month, defined as blood glucose concentrations less than 70 mg/dL [3.8 mmol/L]) in the insulin lispro group, but 30 percent more NPH insulin was required [56].
Continuous subcutaneous insulin infusion (insulin pump) — A variety of insulin pumps are available, some of which "communicate" with specific CGM devices. The choice among pumps is largely a matter of patient preference, cost, and lifestyle. Initiating insulin pump therapy is reviewed in detail separately. (See "Continuous subcutaneous insulin infusion (insulin pump)".)
ADJUNCTIVE THERAPY NOT RECOMMENDED — Although other diabetes agents are being tested (or have been tested) in patients with type 1 diabetes, we do not recommend the use of these adjunctive therapies, owing to the absence of long-term efficacy and safety data [57]:
●Amylin analogs – Amylin analogs, such as pramlintide, influence blood glucose levels by slowing gastric emptying, promoting satiety, and suppressing the abnormal postprandial rise of glucagon in patients with diabetes. Pramlintide is the only adjunctive therapy that is US Food and Drug Administration (FDA) approved for type 1 diabetes. However, many questions remain unanswered regarding clinical use and long-term outcomes with this class of drug.
Pramlintide reduces A1C slightly (approximately 0.3 percentage points) with a lower insulin dose [58,59]. It does not cause weight gain and may be associated with a modest weight loss. Whether the putative clinical benefit balances the inconvenience of taking more injections, the frequent gastrointestinal side effects (mild to moderate nausea and occasional vomiting), and the substantial added expense is unclear. (See "Amylin analogs for the treatment of diabetes mellitus".)
●Glucagon-like peptide 1 (GLP-1) receptor agonists – GLP-1 receptor agonists are not approved by the FDA for use in type 1 diabetes. In randomized trials comparing the addition of liraglutide or placebo to insulin therapy in patients with type 1 diabetes, the addition of liraglutide resulted in trivially lower A1C levels (placebo-corrected reductions in A1C of approximately 0.1 to 0.2 percentage points), lower insulin doses, and lower body weight; however, there was an increase in symptomatic hypoglycemia and hyperglycemia with ketosis in the liraglutide groups [60,61]. (See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus".)
●Sodium-glucose co-transporter (SGLT) inhibitors – The SGLTs are a family of proteins involved in glucose transport [62]. SGLT2 is expressed in the proximal tubule of the kidney and mediates reabsorption of approximately 90 percent of the filtered glucose load. SGLT2 inhibitors promote the renal excretion of glucose and thereby modestly lower elevated blood glucose levels. SGLT1 is predominantly expressed in the small intestine and mediates the absorption of glucose; SGLT1 inhibition reduces intestinal glucose absorption.
SGLT2 inhibitors are available for the treatment of type 2 diabetes. (See "Sodium-glucose co-transporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Glycemic efficacy'.)
Although SGLT2 inhibitors have been studied as add-on therapy to insulin in patients with type 1 diabetes, any small benefit in reducing A1C and body weight is offset by the increased risk for adverse effects, including diabetic ketoacidosis (DKA) [63-67]. SGLT2 inhibitors are not approved by the FDA for use in type 1 diabetes. (See "Sodium-glucose co-transporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Adverse effects' and "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis" and "Sodium-glucose co-transporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Contraindications and precautions'.)
Sotagliflozin is a dual SGLT1 and SGLT2 inhibitor that is under investigation as adjunctive therapy in type 1 diabetes [68]. In a phase III trial, 1402 patients with type 1 diabetes selected to be at low risk for DKA were randomly assigned to sotagliflozin or placebo in addition to insulin therapy. After 24 weeks, the proportion of patients who achieved an A1C <7 percent and no severe hypoglycemia or DKA was greater in the sotagliflozin group (28.6 versus 15.2 percent) [69]. However, the rate of DKA was higher in the sotagliflozin group (3 versus 0.6 percent), as was the frequency of dehydration and genital infections. Of note, participants were instructed in how to mitigate the risk of ketoacidosis and were provided with ketone testing strips and meters to measure beta-hydroxybutyrate in addition to regular measurements during study visits. There was no difference in severe hypoglycemia. The increased risk for treatment-related complications, especially DKA and added expense, is not balanced by the modest lowering of A1C.
●Metformin – Metformin is a biguanide that decreases hepatic glucose output and increases insulin-mediated glucose utilization in peripheral tissues (such as muscle and liver). In the absence of contraindications, metformin is considered the first choice for oral treatment in type 2 diabetes. It has been evaluated as an adjunct to insulin therapy in type 1 diabetes. In a meta-analysis of five trials comparing the addition of metformin versus placebo or comparator in patients with type 1 diabetes, there was a significant reduction in insulin dose but not in A1C [70]. There are no data on microvascular or macrovascular outcomes, although a trial is underway [71]. (See "Metformin in the treatment of adults with type 2 diabetes mellitus".)
FOLLOW-UP
●Frequency – The frequency of clinic visits and adjustments to the insulin regimen vary based on the needs of the patient and patient/health care team preference. In general, nonpregnant patients with type 1 diabetes are seen every three months, although stable patients who are safely meeting their glycemic goals can be seen less frequently. During adjustments of therapy and if patients are not meeting goals, they may need to be seen more frequently. For some individuals, many day-to-day problems can be solved over the telephone or via televisits or email (especially if data from devices [glucose meter, insulin pump, continuous glucose monitors (CGM)] have been uploaded and/or blood glucose levels have been faxed in or emailed prior to the conversation).
●Assessment of glucose patterns and insulin adjustment – At clinic visits, all devices (glucose meters, CGM, pumps) should be downloaded and the glucose and insulin data reviewed. The insulin regimen is adjusted based on glucose patterns, with an eye to reducing hypoglycemia, while at the same time achieving target glucose and A1C levels. There should be ongoing discussion and agreement on target glucose and A1C levels, determined by the patient's age, comorbidities, history of hypoglycemia, and preference.
It is useful to review the patient's blood glucose monitoring technique, insulin injection timing and technique, and food records. The results obtained should be discussed so that the patient can learn how to interpret the findings and how to make appropriate adjustments in dietary intake and insulin dose. Maintaining improved glycemic control over the long term requires a major effort to prevent complacency and to avoid burnout.
A number of different patterns and problems can be identified during this initial period. (See "Cases illustrating problems with insulin therapy for type 1 diabetes mellitus".)
As examples:
•Postprandial hyperglycemia – If postprandial rises in blood glucose are too high, options include modifying the content of the diet (including more high fiber, slowly absorbed carbohydrate, and/or reducing the amount of carbohydrate), altering the time between when the insulin is given and the meal is started, and/or adjusting the preprandial insulin dose. Alternatively, if it is not already being used, try replacing the regular insulin with a rapid-acting insulin, which is absorbed and therefore acts more rapidly than regular insulin, resulting in lower postprandial blood glucose values [72]. (See "Nutritional considerations in type 1 diabetes mellitus", section on 'Carbohydrate consistency' and 'Prandial insulin options' above.)
•Fasting hyperglycemia – The "dawn phenomenon" is thought to result from diurnal secretion patterns of hormones, particularly increased growth hormone at midnight to 2 AM, that tend to antagonize the actions of insulin in the early morning hours and so raise fasting blood glucose concentrations. Basal insulin should keep glucose readings at target when the individual is not eating, exercising, or under stress. To determine if basal insulin dosing needs to be adjusted requires examining glucose profiles beginning at least three to four hours after the last meal or snack and insulin bolus and occasionally at 3 AM.
However, overnight glycemic patterns may not solely reflect basal insulin dosing. When addressing nocturnal and fasting hyperglycemia, question the patient concerning evening snacking and bedtime insulin bolusing for food and/or correction of hyperglycemia. Evening or night-time snacking with insufficient coverage with rapid-acting insulin can cause fasting hyperglycemia.
•No discernible pattern – If the blood glucose records show no consistent pattern, the problem may be an erratic lifestyle and eating pattern. If the patient is disciplined and consistent in the content and timing of meals, the site and timing of insulin injections, and the timing and frequency of exercise, it is easier to interpret blood glucose patterns and make appropriate alterations to the regimen. Compared with previous nonphysiologic, fixed-dose regimens, current regimens provide somewhat more flexibility in timing of meals, meal size, and composition since timing and size of doses can be varied.
Some women need to alter the insulin dosing a few days prior to menses. Episodes of hyperglycemia can also be caused by stress, pain, steroid medications, and acute illnesses such as infections. Injection technique and site of insulin administration should also be assessed.
●Managing hypoglycemia – Episodes of severe hypoglycemia (and any glucose <54 mg/dL [3 mmol/L]) should be reviewed in detail to determine their cause and means of prevention. Poor hypoglycemia awareness becomes more prevalent with longer duration of type 1 diabetes and in adults with recurrent hypoglycemia [73]. It is important to screen for and address hypoglycemia unawareness and to ensure that the patient's family or partner is well equipped to deal with hypoglycemia. Glucagon (nasal, intramuscular, or subcutaneous) should be available for emergency use. Education and medical interventions, as well as the use of CGM, can help prevent life-threatening severe hypoglycemia. (See "Hypoglycemia in adults with diabetes mellitus" and "Interactive diabetes case 3: Hypoglycemia in a patient with type 1 diabetes".)
●Preventing weight gain – Weight gain is a common problem with insulin replacement, especially when A1C levels are reduced substantially. Poor adherence may subsequently be a problem in patients who intentionally omit insulin injections to lose weight or avoid weight gain. The use of newer insulin analogs and CGM, as well as careful attention to insulin dosing (avoiding giving too much basal insulin) may help prevent excessive weight gain [43,74,75]. Attention should also be paid to caloric content and exercise to avoid or limit the weight gain that commonly accompanies intensive insulin administration. (See 'Diabetes education' above.)
Patients randomly assigned to intensive insulin therapy in the Diabetes Control and Complications Trial (DCCT) gained significantly more weight than those who received conventional therapy (5.1 versus 2.4 kg) [22]. Higher baseline A1C values and greater decrements in A1C during intensive therapy were both associated with greater weight gain.
The potential importance of these findings is illustrated in a subsequent analysis of the DCCT, in which patients were divided into quartiles based upon weight gain, from no weight gain (first quartile) to maximal weight gain (fourth quartile) [76]. The mean body mass index (BMI) in the fourth quartile was 31 kg/m2, placing these patients in the obesity range. The following results were observed:
•Intensive insulin therapy resulted in similar glycemic control at follow-up (mean 6.1 years) in all the weight gain quartiles.
•Patients in the first quartile (no weight gain) had decreases in serum triglyceride, total cholesterol, and low-density lipoprotein (LDL) cholesterol concentrations compared with baseline, reflecting the benefits of improved glycemic control on serum lipid concentrations in the absence of weight gain.
•Patients in the fourth quartile had a significant elevation in serum concentrations of these lipids and in blood pressure compared with baseline. They also had higher waist-to-hip ratios (abdominal obesity) than patients in other quartiles.
The constellation of lipid abnormalities, abdominal obesity, and hypertension is similar to that in the central obesity-insulin resistance syndrome that is characteristic of many patients with type 2 diabetes (see "Metabolic syndrome (insulin resistance syndrome or syndrome X)"). Such patients are predisposed to develop coronary atherosclerosis, although it is unproven whether control of weight gain could be important in decreasing the risk of macrovascular complications in patients receiving intensive insulin therapy. Excessive weight gain might detract from the demonstrated large benefit of insulin therapy on macrovascular complications demonstrated by the DCCT/Epidemiology of Diabetes Interventions and Complications (EDIC) study [13].
●Sick-day rules – Sick-day management is directed towards preventing hypoglycemia, significant hyperglycemia, and diabetic ketoacidosis (DKA).
During an illness, blood glucose monitoring should be performed more frequently, eg, every two to three hours including during the night; this may be increased to every one to two hours if necessary. Alternatively, use of a CGM, if available, can be particularly helpful for sick-day management.
Patients should be instructed to measure capillary or urinary ketones if the blood glucose concentration is above 250 to 300 mg/dL (13.9 to 16.7 mmol/L) for unexplained reasons, especially if the person feels generally unwell at the time. Ketones should be monitored during periods of illness or stress or if there are symptoms compatible with ketoacidosis, such as nausea, vomiting, and abdominal pain. Home testing of blood for beta-hydroxybutyrate is available, but it is used infrequently in adults, at least in the United States. This method permits earlier and a more quantitative detection of ketosis compared with tests for urinary ketones, which measure acetone and acetoacetate.
The presence of ketones in the urine does not always mean that the person has impending ketoacidosis. Ketonuria indicates that the person is in a catabolic state and is breaking down fat, and it can occur in anyone who has a negative caloric balance while dieting. However, in type 1 diabetes, the presence of urine ketones along with hyperglycemia is presumptive evidence of a pathologic catabolic state more serious than hyperglycemia alone. Under these circumstances, the person should be advised to retest every two to three hours, take measures to keep well hydrated, and take extra insulin if indicated. Treatment of DKA is discussed separately. (See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment".)
●Diabetes-related complications – Patients with diabetes require ongoing evaluation for diabetes-related complications (table 3). This topic is reviewed in detail separately. (See "Overview of general medical care in nonpregnant adults with diabetes mellitus", section on 'Diabetes-related complications'.)
●Special situations – Lapses in dietary control during special occasions (such as eating at a restaurant or traveling) are to be expected. Religious fasting or major changes in activity levels will affect glucose control. Patients should be educated so that they can adjust their insulin regimens to prevent marked fluctuations in the plasma glucose concentration. (See "Cases illustrating intensive insulin therapy in special situations" and "Interactive diabetes case 9: Management of type 1 diabetes in a patient on glucocorticoid therapy".)
●Other – There are a number of other issues that should be reviewed in patients receiving multiple daily insulin (MDI) injections or continuous subcutaneous insulin infusion (CSII). It is often helpful to focus on one particular aspect (such as exercise, diet, or insulin-to-carbohydrate ratios) for a few weeks and then switch to another issue. Giving the patient written feedback on how they are doing (graphing out their changes in weight, A1C, etc) may also be useful.
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".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Type 1 diabetes (The Basics)" and "Patient education: Using insulin (The Basics)" and "Patient education: Should I switch to an insulin pump? (The Basics)")
●Beyond the Basics topics (see "Patient education: Type 1 diabetes: Overview (Beyond the Basics)" and "Patient education: Type 1 diabetes: Insulin treatment (Beyond the Basics)" and "Patient education: Blood glucose monitoring in diabetes (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●We recommend intensive diabetes therapy for most adults with type 1 diabetes with the goal of achieving glycemic control as close to the nondiabetic range as safely possible (Grade 1A). Intensive diabetes therapy includes the coordination of meals/diet and activity with physiologic insulin replacement, guided by frequent monitoring of blood glucose levels or use of continuous glucose monitoring (CGM). (See 'Intensive diabetes therapy' above and 'Insulin replacement' above.)
●Glycated hemoglobin (A1C) goals in patients with diabetes should be tailored to the individual, balancing the demonstrated benefits with regard to prevention and delay in microvascular complications with the risk of hypoglycemia. For adults with type 1 diabetes, we aim for an A1C value of ≤7 percent (using an assay aligned to the Diabetes Control and Complications Trial [DCCT] in which the upper limit of normal is 6 percent) in patients in whom the benefits outweigh the risks. Higher targets may be appropriate in certain adults such as those who are older, have a history of severe hypoglycemia, or with serious comorbidities. (See 'Glycemic targets' above and "Glycemic control and vascular complications in type 1 diabetes mellitus".)
●For patients with type 1 diabetes, the goal of insulin therapy is to provide a physiologic profile of insulin by administration of a basal level of insulin (delivered by daily or twice-daily injections of an intermediate-acting or long-acting insulin preparation, or continuous subcutaneous delivery of a rapid-acting insulin preparation via a pump [CSII]) and pre-meal boluses of a rapid-acting or short-acting insulin (table 1). The dose of the pre-meal bolus is determined by the ambient blood glucose level before the meal, the size and composition of the meal, anticipated activity levels, and glucose trends (if using CGM). (See 'Insulin replacement' above.)
●CGM is particularly useful for adults with type 1 diabetes who are having frequent or severe hypoglycemia and who have developed hypoglycemic unawareness. In the absence of CGM, blood glucose monitoring, using a glucose meter to read the test strips, should be performed at least four times daily before meals and bed. Additional testing, two to three hours after meals and occasionally at 3 AM, as well as before and after exercise, before driving, and when hypoglycemia is suspected, may be indicated. A1C should be tested regularly to assess chronic glucose control. (See 'Monitoring blood glucose' above and "Glucose monitoring in the ambulatory management of nonpregnant adults with diabetes mellitus".)
●The choice between multiple daily insulin injections (MDI) and continuous subcutaneous delivery of a rapid insulin preparation via a pump is largely a matter of patient preference, lifestyle, and cost. It should be made only after both regimens are carefully explained to the patient. (See 'Choice of insulin delivery' above.)
●There are several different MDI regimens (table 2). The choice of basal and pre-meal bolus insulin for an MDI regimen depends upon patient preference, lifestyle, and cost. There may be modest glycemic benefit (modest reduction in A1C and/or rate of severe hypoglycemia) of insulin analogs over conventional insulin; the long-term effects of the individual MDI regimens on diabetic complications are not yet known. (See 'Choosing basal/prandial insulin' above and "General principles of insulin therapy in diabetes mellitus", section on 'Human insulins'.)
●All patients with type 1 diabetes should receive ongoing self-management education and support in order to improve clinical outcomes and quality of life. Insulin adjustments are a lifelong exercise and must be made in response to glycemic (blood glucose and A1C) control that is not meeting individualized targets. Hypoglycemia is a constant theme and may require insulin adjustments. Changes in exercise pattern, dietary habits, weight loss, and travel plans require adjustments in the insulin plan coincident with and not after the changes. (See 'Diabetes education' above and 'Follow-up' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges David McCulloch, MD, who contributed to earlier versions of this topic review.
