Complete Nurse's Guide to Diabetes Care, 3rd Edition

Chapter 6:

Treatment Strategies for Type 1 Diabetes

Belinda P. Childs, ARNP, MN, CDE, BC-ADM,1 and Davida Kruger, BC-ANP, MSN, BC-ADM2

1Belinda Childs is a Diabetes Nurse Specialist and Director at Great Plains Diabetes, Wichita, KS. 2Davida Kruger is a Certified Nurse Practitioner at Henry Ford Health Systems, Detroit, MI.

Type 1 diabetes (T1D) is a complex, multihormonal disease. Insulin has been the primary treatment for T1D. To successfully manage T1D, however, individuals must integrate several diabetes treatment components into their lifestyle, including management of insulin administration, food intake, and physical activity. The individual with T1D and the health-care provider must share an understanding of the disease process and available treatment strategies and collaborate in determining the best treatment choices.

EPIDEMIOLOGY

The incidence of T1D in the U.S. in people <20 years of age is estimated at 19 in 100,000 per year. In adults, T1D accounts for 5% of all diagnosed cases of diabetes. It is estimated that around 1.25 million people have T1D. The risk for T1D is higher for whites than for African Americans or Hispanics/Latinos.1

Autoimmune T1D has multiple genetic predispositions and also is related to poorly defined environmental factors. People with T1D are at risk for other autoimmune disorders, such as Grave’s disease, Hashimoto’s thyroiditis, Addison’s disease, vitiligo, pernicious anemia, and celiac disease.

The human leukocyte antigen DR-DQ and other minor genes convey an increased risk in developing T1D. A family history of T1D also carries an increased risk. Autoimmune markers—including autoantibodies to islet cell autoantibodies, autoantibodies to insulin, glutamic acid decarboxylase (GAD), and the tyrosine phosphatases IA-2 and IA-2(β)—pose the greatest risk of developing T1D. T1D is defined by the presence of one or more of these autoimmune markers. The disease has strongest HLA associations, with linkage to the DQA and DQB genes. The HLA–DR-DQ alleles can be either predisposing or protective.2

Tests are available to identify those at risk, but lacking a way to prevent T1D, testing typically is not recommended. Many individuals were screened as part of the Diabetes Prevention Trial, Type 1. To date, no strategy for prevention has been identified. The follow-up screening and study is called the TrialNet Natural History Study. Information can be obtained online (www.diabetestrialnet.org). Relatives of those with T1D should be informed of the opportunity to be tested but should do so in a clinical research setting.

PATHOPHYSIOLOGY

T1D occurs most frequently in children and young adults but may be diagnosed at any age, even in the eighth and ninth decade of life. As stated in Chapter 2, the two types of T1D are immune-mediated and idiopathic diabetes, with the former being much more common. The etiology of T1D remains unclear, but the key is insulin deficiency resulting from a failure of the β-cell to produce adequate insulin to control blood glucose levels. T1D has been referred to as insulin-dependent diabetes and juvenile-onset diabetes.

Other hormones involved in glucose regulation include glucagon, somatostatin, and amylin (Figure 6.1). Glucagon, produced by the α-cells in the islets of Langerhans in the pancreas, plays a major role in sustaining plasma glucose production. Glucagon maintains the basal blood glucose within a normal range during fasting. In the nondiabetic milieu, if glucose levels fall below normal, glucagon is released; this, in turn, triggers the release of hepatic glucose from the liver (glycogenolysis). The blood glucose level returns to normal. This glucose release is not needed after a meal. Normally, glucagon is suppressed by the effect of insulin on the liver, and glucagon is almost totally suppressed after a meal. In diabetes, the suppression of postprandial glucagon (hyperglucagonemia) is inadequate, resulting in increased hepatic glucose production (gluconeogenesis). Exogenous insulin is unable to restore normal postprandial insulin concentrations in the portal vein or to suppress the postprandial glucagon secretion. This results in an abnormal glucagon-to-insulin ratio; the release of hepatic glucose; and, ultimately, hyperglycemia.3 Somatostatin, which is produced by the δ-cells in the islets of Langerhans, also plays a role in the regulation of insulin and glucagon release.

Figure 6.1—Glucose homeostasis: role of insulin and glucagon

Figure 6.1—Glucose homeostasis: role of insulin and glucagon. A: For individuals without diabetes in the fasting state, plasma glucose is derived from glycogenolysis under the direction of glucagon (1). Basal levels of insulin control glucose disposal (2). Insulin’s role in suppressing gluconeogenesis and glycogenolysis is minimal because of low insulin secretion in the fasting state (3). B: For individuals with diabetes in the fasting state, plasma glucose is derived from glycogenolysis and gluconeogenesis (1) under the direction of glucagon (2). Exogenous insulin (3) influences the rate of peripheral glucose disappearance (4) and, because of its deficiency in the portal circulation, does not properly regulate the degree to which hepatic gluconeogenesis and glycogenolysis occur.

Source: Reprinted from Aronoff et al.3

Amylin, a regulatory hormone discovered in 1987, is cosecreted by the β-cells with insulin. It appears to play a role in postprandial glucose regulation by reducing excess glucagon in the postprandial period and regulating gastric emptying from the stomach to the small intestines. Amylin also appears to have an effect on satiety.

Glucose homeostasis is complex. In addition to the hormones discussed thus far, several incretin hormones also play a role in postprandial glucagon and insulin secretion as well as in gastric emptying. Currently identified incretin hormones include glucagon-like peptide-1 and gastric inhibitory polypeptide.3

DIAGNOSIS

Although the symptoms of T1D (Table 6.1) can arise suddenly, the disease now is considered to have an insidious onset. In the past, most patients newly diagnosed with T1D were hospitalized with ketoacidosis. In the 21st century, however, most individuals are identified by symptoms and early glucose testing before becoming ill.

Table 6.1—Symptoms of Type 1 Diabetes

Polyuria—increased urination

Polyphagia—increased appetite

Polydipsia—increased thirst

Unexplained weight loss

In children, bedwetting

Yeast infections

Flushed skin

Fruity breath

Severe abdominal pain

Nausea and/or vomiting

Lethargy

THE IMPORTANCE OF OPTIMAL GLUCOSE CONTROL

The findings of the Diabetes Control and Complications Trial (DCCT) left no doubt that glucose control reduces the likelihood of developing the microvascular complications of diabetes.4 Data from the DCCT show that the risk of the development of microvascular complications decreases as hemoglobin A1c (A1C) nears the normal level. Any lowering of A1C and blood glucose level decreases the risk of developing microvascular complications.

A cohort of 1,349 patients who participated in the DCCT has been followed since the completion of the DCCT. The follow-up study, Epidemiology of Diabetes Interventions and Complications (EDIC), has demonstrated a beneficial effect of optimal glucose control as much as 18 years after the completion of DCCT. The risks of microvascular complications at years 4, 10, and 18 post-DCCT for retinopathy, nephropathy, and neuropathy are less prevalent in the intensive insulin group, even though these differences are diminishing over time. It is clear that the benefits of intensive insulin treatment early in the course of diabetes can have a long-term beneficial effect with fewer complication risks. This is now known as metabolic memory.5 Additionally, the intensive insulin group was found to have reduced rates of myocardial infarction, stroke, and cardiovascular death.5–8

Basal-Bolus Insulin Therapy

In individuals without diabetes or impaired glucose tolerance, nature carefully controls blood glucose levels within a narrow range. This is accomplished by the continuous secretion of a small amount of insulin, termed basal insulin, at a relatively constant level (i.e., it never “peaks”). Superimposed on the basal insulin is a bolus of insulin that the body secretes with each feeding. Figure 6.2 shows normal physiology.

Figure 6.2—Physiologic insulin secretion

Figure 6.2—Physiologic insulin secretion. B, breakfast; L, lunch; S, supper; HS, bedtime.

It is possible to closely mimic the pattern of basal and bolus insulin using exogenous insulin. One option is to use a continuous subcutaneous insulin infusion (CSII) pump, which can be programmed to release basal insulin at chosen rates, plus bolus insulin controlled by the pump wearer (for more information on CSII, see Chapter 26, Diabetes Technologies). Multiple daily injections using a long-acting (peakless or nearly peakless) insulin analog plus a rapid-acting insulin analog to cover meals also allow physiological basal-bolus insulin therapy. To maximize the advantages of these approaches, it is important that both the patient and provider understand not only the basal-bolus concept but also the action times of the various insulins (Table 6.2).

Table 6.2—Insulin Action Times

Table 6.2—Insulin Action Times

*Per manufacturers’ data; other data indicate equivalent pharmacodynamics.

For ongoing updates on insulin formulations, see Diabetes in Control. Available at www.diabetesincontrol.com. Accessed 30 January 2017

Insulin Timing and Action

The four general categories of insulin are based on their action times:

• Rapid acting: insulins lispro, aspart, and glulisine, which are genetically engineered insulin analogs

• Short acting: regular soluble insulin

• Intermediate acting: NPH, an isophane insulin

• Long acting: insulin glargine, insulin detemir, and insulin degludec, genetically engineered analogs

Table 6.2 summarizes the action profiles—that is, the time to onset, time to peak action, and duration of action—of these preparations. U-500 regular insulin is more similar to NPH than regular insulin. U-300 glargine and degludec have longer durations than insulin U-100 glargine and insulin detemir.

For most individuals with T1D, a basal-bolus approach to management is the best choice. Similar to normal physiology, the basal insulin reduces hepatic glucose production, keeping it in equilibrium with the use of basal glucose by the brain and other tissue. After meals, bolus (prandial) insulin secretion stimulates glucose use and storage while inhibiting hepatic glucose output, thereby limiting the meal-related glucose excursion. Individuals with T1D lack both basal and bolus insulin production. The basal-bolus therapeutic approach to managing diabetes allows for the most flexible lifestyle.

One basal-bolus strategy is to use glargine, detemir, or degludec as the basal insulin and insulin lispro, aspart, or glulisine as the bolus insulin (Figure 6.3). Usually, 40–60% of the total daily insulin dose is for basal needs, and the remaining insulin would be administered as bolus doses, divided based on meal content and composition. U-100 glargine or detemir can be given at any time of day but should be given at a consistent time of day (e.g., in the morning, at bedtime, or as a split dose given twice a day). Alternatively, NPH in two or three doses per day can be used to provide basal needs. The new U-300 lantus or degludec can be administered at any time once daily.

Figure 6.3—Representation of idealized insulin effect provided by three daily injections of rapid-acting insulin with an evening injection of insulin glargine

Figure 6.3—Representation of idealized insulin effect provided by three daily injections of rapid-acting insulin with an evening injection of insulin glargine. B, breakfast; L, lunch; S, supper; HS, bedtime.

Insulin mixtures are also available. Premixed insulins do not allow as much flexibility in eating and physical activity times and usually are not the best choice in treating T1D. Carefully instruct patients about the onset of action of insulin and time of administration. Premixed 70/30 NPH/regular should be taken 30 min before eating, whereas a 70/30 NPA/aspart or 75/25 NPL/lispro dose should be administered 10 to 15 min before the meal.

Education and caution to ensure accurate dosing are needed when patients are asked to mix insulins themselves. The rule is to draw the clear insulin (e.g., regular) before the cloudy insulin (e.g., NPH). The dose should be given within 2–10 min of mixing. The exceptions are glargine and detemir, which cannot be mixed with any other insulin or drawn into a syringe that contained any other insulin. Also, glargine should be administered immediately after being drawn into a syringe,8 unlike NPH, which can be stored in syringes and refrigerated for up to 30 days.9 If glargine, detemir, degludec, or any other clear insulin has particles or has become cloudy, a new vial or pen should be used and the contaminated vial or pen should be discarded.

Practical Point

Although insulin that is being used does not have to be refrigerated, it generally should not exceed 86°F. See manufacturer package inserts for product-specific handling and storage information, including how long a vial or syringe can be used once opened. Extra insuln pens and vials that are not being used should be stored in the refrigerator.

NPH and regular insulin are being utilized with the increasing cost of analog insulins. Regular and NPH can be purchased by patients without a prescription. Some pharmacies sell human insulin at generic prices, and thus they offer a lower-cost option. It is not recommended, but historically, regular insulin was the first insulin used in insulin pumps. Generic insulin glargine was approved in December 2015 by the FDA and is a biosimilar glargine. Not all NPH and regular are sold at generic prices; only ReliOn®-brand NPH and regular are sold at generic prices. Others may cost as much as analogs.

Starting Insulin

Starting doses of insulin are best calculated based on body weight. The initial dose for adults is usually 0.5–1.5 units/kg body weight/day. The starting dose is determined within this range by the degree of ketosis with which the patient presents, not the blood glucose level. Most individuals with T1D have some level of ketosis and initially may have been treated with intravenous insulin and rehydrated (see Chapter 7). Others may be identified early in the disease process and simply need insulin replacement, which will mean a lower starting dose.

Children and adolescents with newly diagnosed T1D usually have some degree of ketosis or acidosis and thus are very insulin deficient and require high doses of insulin. Children also have a higher metabolic rate than adults and therefore have a higher clearance rate of drugs (e.g., insulin). Growth hormones can cause elevated blood glucose levels. Children require higher doses per kilogram of most insulins, as well as other medications, than do adults. Children and adolescents who develop diabetic ketoacidosis (DKA) usually are treated with low-dose intravenous insulin.

When a child is stable and ready for subcutaneous insulin, start with a dose of 1–2 units/kg body weight/day, reserving the lower doses for patients who have hyperglycemia and little or no ketosis and the highest dose for patients who have or have had DKA. Children should be fed to satiety (usually 40–60 kcal/kg body weight/day) to replenish their lost stores of body nutrients and should be given enough insulin to control blood glucose levels and restore anabolism to regain lost weight.

Insulin is divided between a rapid-acting insulin, which is administered with meals, and a longer-acting insulin, such as glargine or detemir, usually administered at bedtime. Glargine and detemir may be administered once or twice daily, if needed, as well as at any time of the day, as long as it is at consistent time(s), if this matches with patient/family needs to increase likelihood of consistent administration.The newer long-acting insulin U-300 glargine and degludec can be administered at any time of day. About 40–60% of the total daily insulin requirement should be given as basal and the remaining given as aspart, lispro, or glulisine. Mealtime aspart, lispro, or glulisine is dosed according to meal size, except that the largest dose per calorie or carbohydrate normally is given with breakfast because of the natural occurring hormones released during sleep that cause insulin resistance in the timeframe before dawn and are secreted especially in growing children. In children, especially toddlers, aspart, lispro, and glulisine can be given after the meal and the dose can be adjusted by how much the child actually has eaten. Once the child’s intake can be predicted with more certainty, the mealtime dosages are best given prior to the meal.

Regimens using a split mix of NPH and lispro or aspart can be used in patients with T1D (Figure 6.4). Approximately 50–60% would be given as a breakfast dose of mixed insulin NPH/lispro; 15–20% would be given as a supper dose of regular, lispro, aspart, or glulisine at the evening meal; and 15–20% as NPH at 10:00 p.m. As noted, it is important to eat meals as the insulin is peaking. Snacks are likely necessary during midmorning and midafternoon and at bedtime to prevent hypoglycemia It will be important during the adjustment phase to monitor a 3:00 a.m. blood glucose level to assess for nocturnal hypoglycemia. An acceptable 3:00 am blood glucose will vary based on the individual’s age, history of hypoglycemia, and comorbidities.

Figure 6.4—Representation of a split mix of NPH and rapid-acting insulin at breakfast, rapid-acting insulin at the evening meal, and NPH at bedtime

Figure 6.4—Representation of a split mix of NPH and rapid-acting insulin at breakfast, rapid-acting insulin at the evening meal, and NPH at bedtime. B, breakfast; L, lunch; S, supper; HS, bedtime.

Introduction of Analog Amylin

If an individual is insulin deficient, he or she is amylin deficient. The purpose of pramlintide, the synthetic form of amylin, is to reduce postprandial hyperglycemia. Pramlintide also has been shown to enhance satiety, which leads to the potential for weight loss. Pramlintide can be administered to those with T1D and insulin-requiring T1D. The primary side effects are nausea and hypoglycemia. Nausea is the most common side effect with the use of pramlintide. Starting pramlintide at a low dose and gradually increasing the dose helps to minimize nausea. Nausea is typically transient and goes away over time.

Pramlintide is used with insulin and has been associated with insulin-induced hypoglycemia. Lowering the insulin dose when pramlintide is initiated has been shown to minimize hypoglycemia.

Individuals must be willing to test their blood glucose levels frequently as they begin pramlintide to minimize the risk of insulin-induced hypoglycemia. Because of the action of pramlintide, the prandial insulin dose needs to be reduced by 30–50%. Some practitioners begin therapy by advising patients to take the pramlintide immediately before the meal and the insulin at the end of the meal so that the individual can adjust the rapid-acting insulin dose if he or she achieves satiety early in the meal. Nausea is minimized if the individual stops eating when satiety is achieved.

Pramlintide is given as an injection using a SymlinPen®, which is available in two sizes, either 60 µg or 120 µg. The 60-µg pen has four doses available: 15 µg, 30 µg, 45 µg, and 60 µg. The 120-µg pen has two doses available: 60 µg and 120 µg. The 60-µg pen is used when initiating Symlin® for those with T1D.

SELF-MONITORING OF BLOOD GLUCOSE

Self-monitoring of blood glucose (SMBG) is essential to diabetes control, regardless of the treatment strategies. Pattern management is the method of choice for making any insulin dose adjustments but is essential when using basal-bolus insulin therapy with rapid- and long-acting insulin.

Use of a sliding scale is not an effective way to adjust insulin doses. In the past, patients commonly were told to monitor their blood glucose levels before meals and at bedtime. This was done so that insulin could be adjusted on a sliding scale or algorithm according to the blood glucose level at the time. Regardless of the insulin tactics used, this method is retrospective. The calculated change corrects a previous error, which then may overlap another insulin dose and cause hypoglycemia later. This is particularly true when long-acting insulins are used. Many sliding scales are based on a set of standing orders for all patients regardless of weight or insulin sensitivity.

For example, using a sliding scale with a patient taking mixed regular and NPH insulins potentially could cause significant afternoon hypoglycemia. The morning NPH insulin may be working well, but adding extra regular or even rapid-acting insulin at noon because the prelunch blood glucose level is high will result in an overlap with the duration of the NPH and may cause afternoon hypoglycemia. The next logical action would be to decrease the evening insulin dose because the presupper blood glucose level is low, which will result in a high bedtime blood glucose level. As is evident, this becomes a vicious cycle. In contrast, the pattern management approach is a proactive approach rather than reactive.

Using SMBG for Pattern Management

With pattern management, the blood glucose level is checked fasting and 2 h postprandially. If the values are >200 mg/dL (11.1 mmol/L) or if ketones are present in the urine, supplements or a correction dose can be given immediately. Unless the blood glucose is very high, it is better to observe a 2- to 3-day pattern and then make a change based on that pattern. Correction doses may be given based on the premeal blood glucose, as long as it is noted.

Changes in insulin doses then are made according to the type of insulin involved. The fasting blood glucose level is a reflection of the U-300 glargine or degludec or bedtime U-100 glargine, detemir, or NPH insulin, and if it is too high or too low over a 2- to 3-day period, the glargine, detemir, NPH, or degludec dose should be adjusted accordingly. Of note, the change should be within 10–20% of the existing dose. If a percentage of the existing dose is used as the adjustment guide, the individual’s insulin sensitivity and weight will have to be taken into consideration. One size does not fit all in insulin management or adjustment.

The blood glucose level after breakfast is used to adjust the prebreakfast rapid-acting insulin dose, the level after lunch is used to adjust the lunchtime insulin dose, and the level after the evening meal is used to adjust the premeal insulin dose. Again, changes are made every 2–3 days in 10–20% increments until the measured values are in the target range agreed to by the patient or family.

The American Diabetes Association (the Association) goals of therapy are fasting plasma glucose 80–130 mg/dL (4.4–7.2 mmol/L), postprandial plasma glucose at the highest peak <180 mg/dL (<10.0 mmol/L), and A1C <7%). For frail older adults, those with a history of severe hypoglycemia, and people facing other special situations, these targets should be individualized. The recommended A1C for children and adolescents is ≤7.5%.10

Glucose monitoring is an important tool for the individual with diabetes to use for daily adjustment, pattern management, and review with the provider during office visits. Optimal pattern management uses several days of SMBG records, whether handwritten or downloaded from the meter. (Cables and software for downloading meter data are available for most glucose meters.) The ability to download meter data offers the individual the opportunity to self-manage blood glucose levels without keeping a logbook. The health-care provider also may appreciate downloaded records. Written records with detailed journaling of factors, such as specific food, emotions, and physical activity, help the individual with diabetes learn problem-solving skills. Downloaded meter information will require supplemental information about the individual’s food plan, medication, activity, and treatment of hypoglycemia so that adjustments in medication, meals, or activity can be made based on accurate information. Also, for downloaded information to be useful, it should be downloaded regularly (e.g., weekly). If the meter is only downloaded at the health-care provider’s office, the individual with diabetes is missing the opportunity to make regular adjustments to his or her meal plan, exercise, and medication.

For more information regarding the use of the continuous glucose sensor adjustments for continuous insulin infusion pumps, see Chapter 26, Diabetes Technologies. Technologies are changing rapidly. Recently some continuous sensors have been approved by the FDA for insulin dosing; others have not received FDA approval. Individuals should be counseled to verify the accuracy of their device prior to administering extra insulin.

Correcting Hyperglycemia

Correction doses of insulin can be given, but care should be taken to avoid overtreating with insulin. If individuals overtreat hyperglycemia with too much or too frequent insulin, they increase the risk of hypoglycemia. The resultant hypoglycemia then may be overtreated with food, which could result in hyperglycemia and insulin being supplemented again. This is referred to as the sliding-scale effect. The level of hyperglycemia at which a patient corrects may vary among individuals and should be decided by the patient and provider. Extreme caution should be used if using a correction bolus with split-mixed insulin.

For patients who take intermediate- or long-acting insulin, no single value can be used to correct for a high premeal glucose level. In this case, 10% of the total insulin dose may be supplemented as rapid-acting insulin. Another method is to use the rule of 1,700 (Table 6.3). This method involves dividing the total daily dose of insulin, including rapid- and long-acting insulins, into 1,700.11,12 Some practitioners choose to use 1,800 to 2,000 as the denominator. In this way, the patient with diabetes can determine by approximately how many milligrams 1 unit of rapid-acting insulin will lower the blood glucose. A safe target should be identified, e.g., 100–150, to prevent overcorrection. It is best to give a correction dose premeal to prevent stacking of the insuln and increasing the risk of hypoglycemia. If the dose is given at the 2- or 3-hour postprandial glucose reading, the individual still has insulin on board from the previous meal dose. Correction doses should be used cautiously. An upper limit correction dose should be identified. Food and activity also can be adjusted to alter blood glucose.

Table 6.3—Calculating Correction or Insulin Sensitivity Factors

1,700 Rule

Determine total daily dose of insulin: Insulin dose is 11 units of aspart before each meal and 35 units of NPH at bedtime. Total daily dose = 68 units.

Divide daily dose into 1,700: Total daily dose = 68 units divided into 1,700 = 25. Thus, 1 unit of aspart will drop blood glucose about 25 mg/dL.

If blood glucose is 200 mg/dL (11.1 mmol/L) before the evening meal, and target blood glucose is 100 mg/dL, 200 − 100 = correction needed for 100 mg/dL.

Using the correction factor, give an extra 4 units aspart to decrease blood glucose to 100 mg/dL (55.6 mmol/L).

Correcting Hypoglycemia

With basal-bolus insulin therapy, the 15 g/15 min rule becomes important. This rule suggests that to treat hypoglycemia, the individual with diabetes should take 15 g glucose, wait 15 min, recheck, and if necessary, administer an additional 15 g glucose. In the past, we often taught individuals with diabetes to follow up treatment with a complex carbohydrate–protein snack. This, however, may not be necessary. Treatment will depend on the time of day in which the hypoglycemia occurs. If the hypoglycemia occurs during the peak of the NPH action or after exercise, an additional snack may be required to prevent recurrent hypoglycemia In addition, the NPH dose may need to be decreased.

Patients converting from an insulin regimen of NPH and/or regular in which frequent or prolonged hypoglycemia may have existed, may find that elevated blood glucose levels will occur after treatment if low blood glucose levels are treated the same way as in their previous regimen. This will be particularly true if these patients eat a high-calorie, high-carb, high-fat food, such as chocolate or peanut butter, in which case they might experience unexpected prolonged hyperglycemia. The insulins have a longer peak action and thus the hypoglycemia may have lasted longer than with the more rapid acting insulin or newer basal insulin that are peakless. See Chapter 8 for additional information regarding hypoglycemia.

Food Plan Considerations

Using a basal-bolus regimen provides greater flexibility in lifestyle and schedule for patients with diabetes. Rapid-acting insulin can be adjusted based on the carbohydrate–calorie consumption at any given time. Snacks, often required with split-mix regimens, may not be required with basal-bolus regimens. Snacks, however, may be eaten, if desired, without compromising glucose control if carbohydrates are counted and supplemented with insulin. This is a benefit for many children and adults who have been frustrated by a strict eating schedule that required that they eat even when they were not hungry, such as at bedtime.

The key to achieving the greater flexibility in meal timing and portions afforded by basal-bolus therapy is learning to count carbohydrate intake and match insulin doses appropriately. This can be taught in the course of medical nutrition therapy delivered by a registered dietitian or diabetes educator (see Chapter 4, Nutrition Therapy). Often, the first step in learning carbohydrate counting is to eat consistent amounts of carbohydrates and calories. Advanced carbohydrate counting includes determining the individual’s insulin-to-carbohydrate ratios and insulin sensitivity factor and learning how to appropriately use these factors. Patients who wear continuous glucose sensors have recognized the effect of protein and fat on the postprandial blood glucose, and additional bolus insulin may be required to cover the high-fat, high-protein meal. Total calories should be counted or portions monitored to prevent weight gain, especially after puberty. The ability to be flexible with the timing and quantity of meals has had a major impact on glucose control as well as the ability to control weight.

Practical Point

Reviewing a patient’s food history in correlation to the blood glucose values is critical to the success of any glucose management strategy, but it becomes essential in basal-bolus therapy.

Exercise Considerations

Overall, exercise tends to have a blood glucose–lowering effect. However, depending on the type, duration, intensity, fitness of the individual, and other factors, the response varies widely from person to person. The individual with diabetes will need to either increase caloric intake or decrease insulin with additional physical activity. With a basal-bolus regimen, the patient may lower either the basal or the bolus insulin. If the exercise is anticipated and occurs within 3 h of the rapid-acting dose, the patient can decrease the premeal dose or ingest more calories or carbohydrates. SMBG to detect postexercise hypoglycemia is needed for up to 36 h after the activity.10,13 The intermediate- or long-acting dose can be decreased if a prolonged activity, such as an active vacation, or intense physical activity, such as skiing or yard work, is planned. The keys are to individualize the plan and to carefully monitor blood glucose.

INSULIN/PRAMLINTIDE STORAGE AND ADMINISTRATION

Typically, insulins and pramlintide do not need to be refrigerated when opened, but they should not be exposed to extremes in temperature. These products have varying durations of stability once opened and used unrefrigerated. The stability varies from 14 to 56 days depending on the product and whether it is in a vial or pen. Marking the vial, syringe, or pen with the date it should be discarded ensures use before expiration. Unopened vials and syringes should be refrigerated until used.

Patients should be alert to unexpected changes in blood glucose levels. Unexplained increases should prompt a patient to verify that the insulin is not outdated, has not been exposed to direct sunlight or excessive heat (≥86°F for most, ≥96°F for aspart), and has not been frozen.8 Refer to the package insert for specific handling and storage instructions.

Insulins that are in suspension (cloudy) should be rolled gently a minimum of 20 times before use, whether in a vial or pen. This should be done with consistency because some of the variable absorption of the suspended insulin is related to inconsistent mixing of the suspension. If the dose is drawn up and then the syringe is laid down before injection, then the filled syringe must be remixed by gentle rolling before administration.

Manufacturers of disposable syringes and pen needles recommend that these devices only be used once. The small-gauge needles do not withstand multiple uses without “fraying.” Viewed under the microscope, a needle used just two or three times begins to look like a rope unraveling. Another potential issue, which arises with reuse of syringes or needles, is the inability to guarantee sterility. Most insulin preparations have bacteriostatic additives that inhibit the growth of bacteria commonly found on the skin. Nevertheless, syringe or needle reuse may carry an increased risk of infection for some individuals. Patients with poor personal hygiene, acute concurrent illness, open wounds on the hands, or decreased resistance to infection for any reason should not reuse a syringe or pen needle.

Appropriate Candidates for Pramlintide Therapy

Candidates for pramlintide therapy should meet the following criteria:

• Adherent to current insulin regimen

• Consistent SMBG

• Elevated postprandial glucose levels

• A1C <9%

• No recent history of recurrent severe hypoglycemia requiring assistance

• No hypoglycemia unawareness

• No current diagnosis of gastroparesis

• Not a pediatric patient

• Not pregnant or planning a pregnancy

• Has a diabetes team or provider familiar with intensive insulin management

Pramlintide (Symlin) Initiation Guidelines for Type 1 Diabetes

• Start with 15 µg

—Administer immediately before a major meal or snack

—Reduce mealtime insulin by 30–50%

—Self-monitor blood glucose

* Anticipate higher values during initiation period

* Evaluate long-acting insulin and insulin timing

• If no significant nausea for 3–7 days, advance Symlin

—Advance in 15-µg increments every 3–7 days as tolerated to maximum of 60 µg (10 units)

—If nausea occurs and persists, reduce to previous dose

—Adjust insulin doses to optimize control

* Consider insulin action, timing, and amount

Source: From Childs et al. Considering pramlintide therapy for postprandial blood glucose control. Diabetes Spectr 2007;20:108–114; Kruger et al. New insights into glucose regulation. Diabetes Educ 2006;32:221–228; and Kruger et al. Pramlintide for the treatment of insulin-requiring diabetes mellitus: rationale and review of clinical data. Drugs 2004;64:1419–1432.

Some patients find it practical to reuse syringes or needles. If needle reuse is planned, the needle must be recapped after each use. Certainly, a needle should be discarded if it is noticeably dull or deformed or if it has come into contact with any surface other than skin. With just one injection, tips of the newer, smaller (31- and 32-gauge) needles can bend into a hook form that can lacerate tissue or break off, leaving needle fragments in the skin. The medical consequences of this are unknown, but it may increase lipodystrophy or have other adverse effects. In addition to the dulling of the fine needle after puncturing the bottle and the skin, lubrication is lost and the next injection can be painful. Advise patients who are reusing needles to inspect injection sites for redness or swelling and to consult their health-care provider before initiating the practice or if they detect signs of skin inflammation.

Insulin may be injected into the subcutaneous tissue of the upper arm or the anterior and lateral aspects of the thigh, buttocks, and abdomen (with the exception of a circle within a 2-inch radius around the navel). Pramlintide may be injected into the abdomen or upper thigh in the same way insulin would be administered. Intramuscular injection is not recommended for routine insulin injections, although regular insulin may be given under some circumstances (e.g., DKA or dehydration) because the rate of absorption is faster. Exercise increases the rate of absorption from injection sites, particularly of NPH and regular formulations, probably by increasing blood flow to the skin and perhaps also by local actions.

Site selection should take into consideration the variable absorption among sites. Rotating within one area (e.g., rotating injections systematically around the abdomen), rather than rotating to a different area with each injection, decreases variability in insulin absorption from day to day. Glargine and detemir, however, are reported to have consistent absorption regardless of injection site.

Insulin Injection Tips

• Select a site that has no lipohypertrophy or scar tissue.

• Use the same anatomical region for selected injections (e.g., all morning shots in the abdomen, evening meal injection in the arm, bedtime injection in the thigh).

• Use insulin that is at room temperature.

• Ensure that no air bubbles remain in the syringe or pen before injection.

• Note that day-to-day use of topical alcohol is not required. If used, wait until alcohol has evaporated completely before injection.

• Keep muscles in the injection area relaxed, not tense, when injecting.

• Penetrate the skin quickly.

• Do not change the needle’s direction during insertion or withdrawal.

• Count to five to ensure that all insulin is delivered through a small-gauge needle.

• Do not wipe the needle with alcohol. Recap carefully.

Insulin Pen Tips

• Screw on the pen needle until it is snug, not tight.

• Prime the pen needle before every injection with 1–2 units to ensure that the pen needle is not clogged and insulin is coming out the tip of the pen needle. The pramlintide pen needle does not need to be primed.

• Select a pen needle from 4 mm to 8 mm. The 0.5-inch or 12-mm needle may actually lead to an intramuscular injection, which will alter the absorption.14

• Continue to hold down the dose knob while counting to 10 to ensure that all the insulin is delivered.

• Release the pinch before removing the needle to allow the insulin to “depot” and to reduce the likelihood of insulin coming back out on the skin.

• If bruising occurs or if a drop of blood is noted at the injection site, hold pressure over the injection site for about 10 sec to help clot the small blood vessel. Do not rub.

• Dispose of pen needles in sharps containers or according to local guidelines.

• Dispose of empty plastic pens in the trash.

Rotation of the injection site is also important to prevent lipohypertrophy or lipoatrophy. Lipohypertrophy is a buildup of fat at the injection site. Lipoatrophy is a loss of fat that causes dimpling of the tissue at the injection site. Hypertrophy and atrophy can occur with overuse of an injection site. Some patients are more prone to lipohypertrophy and lipoatrophy. Both of these reactions were more common when patients used insulins from animals and are less common with the use of new insulin preparations. Areas of hypertrophy usually lead to slower inconsistent absorption. Autoimmunity to the insulin may play a role in the development of lipohypertrophies and lipoatrophies. If a patient has hypertrophied injection sites, which could result in a dramatic decrease in insulin requirements, precautions should be taken to prevent hypoglycemia when insulin is injected into a new site. In addition, unexplained hypoglycemia may occur if insulin is injected consistently into a hypertrophied area.

Site inspection is an important part of a diabetes visit, especially if an individual is experiencing widely fluctuating blood glucose readings. It is important for the nurse to support the use of new injection sites to help reduce hypertrophies and improve glucose control.

INSULIN DELIVERY SYSTEMS

Insulin delivery methods include syringes, pens, and insulin pumps. It is vital that both health-care providers and individuals with diabetes understand the options available for achieving optimal glucose control.

Insulin Pens

Not only are insulin pens convenient, but also individuals are more likely to deliver accurate doses with insulin pens. Patients may be able to see the numbers on the dial or screen better than on a syringe and may be able to manipulate a dialing mechanism more easily than with use of a syringe plunger. Also, when beginning insulin, anxious patients often are less threatened by an insulin pen than by a needle, syringe, and vial. The smaller volume of insulin that the patient needs to carry, compared with a vial and syringe, reduces the exposure of the insulin to the temperature fluctuations and elements of daily living. The cartridges and prefilled pens hold 300 to 600 units each. Insulin pens are available with replaceable cartridges or as disposable pens. Note the following three important patient education points:

• The needles should be removed after each use.

• The user should “prime every time” to ensure that insulin is at the tip of the needle and to ensure that air does not enter the cartridge.

• The needle should remain in the skin for the count of 10 to ensure that all the insulin has been delivered before the needle is removed.

• Regardless of the insulin concentration (i.e., U-200 insulin lispro, U-300 insulin glargine, U-200 degludec, or U-500 regular), the patient dials up the units on the disposable pen as directed. Ten units is 10 units. Patients should be cautioned that they should not try to save insulin out of a cartridge by drawing the last insulin into a syringe because this will change the dose administered and may lead to hypoglycemia.

The pen needle should be removed from the pen immediately after an injection is complete. The needle provides an opening into the sterile chamber, permitting an entry for bacteria, air, or leakage of insulin. In the case of cloudy suspension, the concentration may be altered by fluid leakage when insulin is not fully suspended.

Other Insulin Delivery Devices

Many people with T1D, from children to older adults, use continuous subcutaneous insulin infusion (CSII) with or without continuous glucose monitoring. Learning to use an insulin pump successfully requires a program of user education and frequent support from the health-care team (see Chapter 26, Diabetes Technologies). Patch pumps are also an option for basal and bolus delivery (V-Go®) or bolus delivery only (Calibra Finesse). Other systems are in development.

Another option is the use of an injection port, such as the I-Port Advance™, now marketed by Minimed. For individuals who are giving multiple injections, the port prevents the need to use multiple sites every day and reduces the number of injections per day. Like an insulin pump needle, the port site should be changed every 3 days.

Continued Research for T1D

Only continued research will reveal the prevention and cure for T1D. Although pancreas transplantations are sometimes an option, they usually are performed only if the individual with diabetes also needs a kidney, and the number of donor organs to treat everyone with T1D is insufficient. In addition, risks are associated with the need for antirejection medications.15

Islet transplantations are another potential cure under investigation. A multicenter clinical trial is finding that up to 50% of transplant recipients remain free of the need for exogenous insulin for 1 year after receiving islet cells. Major obstacles include islet cell rejection, a limited supply of islets, and the risk of long-term use of antirejection medications.16

Investigations of other new therapies center on the use of currently approved medications used to treat type 2 diabetes that also may benefit individuals with T1D, including incretin hormones from the gut that regulate glucose; use of glucagon; new insulin analogs; stem cell advances; and new insulin delivery systems, including the closed looped artificial pancreas.

SUMMARY

Near-physiological glucose control is achievable in T1D with a motivated individual and a knowledgeable health-care team. An insulin regimen can be crafted to match each individual’s lifestyle. The person with diabetes must understand insulin action times and his or her individual response to insulin. The effects of the food plan, physical activity, and emotions can be evaluated with regular monitoring of blood glucose levels, using a glucose monitor or using a continuous glucose sensor. To achieve optimal glucose control requires that the individual become active in self-managing his or her disease and that the health-care team, including the nurses in all settings, provide accurate information, coaching, and support.

REFERENCES

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8. Grajower MM, Fraser CG, Holcombe ML, Daugherty ML, Harris WC, et al. How long should insulin be used once a vial is opened? (Editorial). Diabetes Care 2003;26:2665–2669

9. American Diabetes Association. Insulin administration (position statement). Diabetes Care 2004;27:106–109

10. American Diabetes Association. Standards of medical care in diabetes—2016 (position statement). Diabetes Care 2016;39(Suppl. 1):S28–S93

11. Warshaw HS, Kulkarni K. Complete Guide to Carbohydrate Counting. 3rd ed. Alexandria, VA, American Diabetes Association, 2011

12. Davidson PC, Hebblewhite HR, Bode BW, Steed RD, Welch NS, Greenlee MC, Richardson PL, Johnson J. Statistically based CSII parameters: correction factor, CF (1700 rule), carbohydrate-to-insulin ratio, CIR (2.8 rule), and basal-to-total ratio. Diabetes Technol Ther 2003;3:237–242

13. Colberg SR. Exercise and Diabetes: A Clinician’s Guide to Prescribing Physical Activity. Alexandria, VA, American Diabetes Association, 2013

14. O’Neal KS, Johnson J, Swar S. Nontraditional considerations with insulin needle length selection. Diabetes Spect 2015;28:264–267. Available from http://dx.doi.org/10.2337/diaspect.28.4.264. Accessed 4 July 2016

15. National Institute of Diabetes and Digestive and Kidney Disease. Diabetes. Available from www.niddk.nih.gov/health-information/health-topics/Diabetes/pancreatic-islet-transplantation/Pages/index.aspx. Accessed 4 July 2016

16. Clinical Islet Transplant Consortium. What is islet transplantation? Available from www.citisletstudy.org/islet.html. Accessed 4 July 2016