Type 1 Diabetes Mellitus

CHAPTER 3
TYPE 1 DIABETES MELLITUS

Jennifer M.Trujillo
1. What is the general approach to the treatment of type 1 diabetes mellitus?

Type 1 diabetes mellitus is caused by autoimmune destruction of the pancreatic beta cells, and this leads to an
absolute deficiency of insulin. Therefore, the mainstay of treatment of type 1 diabetes is insulin, administered in a
way that mimics normal physiologic insulin secretion. The goals of therapy are to prevent or delay the onset of
long-term complications of diabetes, including retinopathy, kidney disease, neuropathy, and cardiovascular disease;
to prevent treatment induced hypoglycemia; and to maintain quality of life. For most patients, the target hemoglobin
A1C (HbA1C) is , 7%, but this goal should be individualized on the basis of patient-specific factors. A fasting plasma
glucose (FPG) target of 80 to 130 mg/dL and a postprandial glucose (PPG) target of , 180 mg/dL correlate with
a target HbA1C of , 7%. The American Diabetes Association (ADA) recurrently recommends a PPG target of
, 180 mg/dL, whereas the American Association of Clinical Endocrinologists (AACE) recommends a PPG target
of , 140 mg/dL.
Achieving good glycemic control in type 1 diabetes usually requires intensive insulin therapy (IIT). IIT is the
use of multiple daily injections (MDIs) of insulin (both long-acting and rapid-acting formulations) or an insulin
pump in an effort to mimic the normal insulin secretion pattern by the pancreas. IIT may also be referred to as
physiologic, multiple-component, or basal-bolus insulin therapy. IIT is only one aspect of comprehensive, intensive
diabetes therapy to achieve tight glycemic control. IIT is complex because it requires multiple injections or pump
boluses each day in addition to basal insulin delivery, routine monitoring, and collaborative decision making. The
most successful IIT is delivered and adjusted on the basis of changes in nutritional intake, glucose levels,
stresses, and physical activity.
2. List the critical components of intensive insulin therapy.
• Frequent self-monitored blood glucose (SMBG) or a continuous glucose monitoring (CGM)
• Defined and individualized target blood glucose (BG) levels
• Use of SMBG data or sensor data and glucose patterns to meet treatment goals
• Dose modifications according to the individual’s response to therapy
• Understanding of diet composition, specifically carbohydrate content
• Careful balance of food intake, activity, and insulin dosage
• Use of accurate carbohydrate-to-insulin (C:I) ratios according to food intake
• Use of correction factors (CFs) for the adjustment of insulin according to glucose levels
• Patient education, motivation, and ongoing interaction between patient and health care team
3. Summarize the studies evaluating optimal glycemic control to decrease chronic diabetes complications
The Diabetes Control and Complications Trial (DCCT), evaluating patients with recent-onset type 1 diabetes,
showed that improved glycemic control (HbA1C , 7%) not only significantly reduced the rates of microvascular
complications, including progression of retinopathy, nephropathy, and neuropathy, but also increased the rates of
hypoglycemia. IIT was a key part of achieving glycemic control in the DCCT. The Kumamoto Study and the United
Kingdom Prospective Diabetes Study (UKPDS) extended these findings to show that improved glycemic control
(HbA1C , 7%) was associated with significantly reduced rates of microvascular complications in patients with
recent-onset type 2 diabetes. The long-term extensions of the DCCT and the UKPDS showed significant reductions
in cardiovascular complications, as well as good glycemic control, and demonstrated that the microvascular bene-
fits of good glycemic control persisted for decades. Subsequent studies (Action to Control Cardiovascular Risk in
Diabetes [ACCORD], Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled
Evaluation [ADVANCE], and VADT) in patients with more advanced type 2 diabetes failed to show that more
aggressive glycemic targets (HbA1C , 6%–6.5%) reduced cardiovascular complications, and one study (ACCORD)
showed an increase in mortality. Rates of hypoglycemia with more aggressive glucose control were significant
in all three trials.
4. Which patients are candidates for IIT?
All people with type 1 diabetes should be considered potential candidates for IIT. However, the degree of intensification
must be based on each patient’s personal situation and abilities. Patient characteristics that predict greater success with
IIT include motivation, willingness to perform frequent SMBG and record results or use a continuous glucose monitor,
time available to spend with a diabetes educator, the ability to recognize and treat hypoglycemia, sick days, and a sup-
portive network of family or friends. In addition, implementation of IIT requires a cohesive diabetes team that is available
for frequent interaction and discussion about results from monitoring, insulin adjustments, and other issues.
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22 FUEL METABOLISM
75 Breakfast Lunch Dinner

Plasma insulin (µU/mL)
50
20
4:00 8:00 12:00 16:00 20:00 24:00 4:00

Time
Fig. 3.1. Intensive insulin therapy pattern with multiple daily injections (MDIs).
5. What are the risks of IIT?

Hypoglycemia and weight gain are the most common adverse effects of insulin therapy. IIT in the DCCT resulted
in a threefold increased risk of severe hypoglycemia compared with conventional treatment (62 episodes per
100 patient-years of therapy). Since the completion of the DCCT, newer rapid-acting and long-acting insulin
analogues have been developed and are associated with less hypoglycemia compared with the short-acting and
intermediate-acting human insulin products used in the DCCT. Frequent episodes of hypoglycemia can lead to
loss of clinical warning symptoms (e.g., palpitations, sweating, hunger) with hypoglycemia (known as hypoglyce-
mia unawareness). A unique risk of insulin pump therapy is diabetic ketoacidosis (DKA) as pump malfunctions or
infusion site problems can interrupt insulin delivery. Finally, IIT requires time and commitment from the patient
and may have negative psychosocial and economic implications.
6. What is the difference between basal insulin coverage and bolus insulin coverage?
IIT is designed to mimic the normal insulin secretion pattern, which includes continuous basal coverage in
addition to bursts of insulin to regulate the rise in glucose after food intake (Fig. 3.1). Basal insulin secretion
suppresses hepatic glucose production to control blood glucose levels in the fasting state and premeal periods.
Normal basal insulin secretion from the pancreas varies slightly throughout the day, responding to changes in
activity, blood glucose levels, and regulatory hormones. Basal insulin coverage in IIT is usually accomplished with
injections of long-acting insulin analogues or with the basal infusion function on the insulin pump. Bolus insulin
doses consist of two components, the nutritional dose, which is the amount of insulin required to manage glucose
excursions after meals, and the correction dose, which is the amount of insulin required to reduce a high glucose
level detected before a meal. Bolus coverage is accomplished by administration of rapid-acting or short-acting
insulin preparations or using the bolus function on the insulin pump. Physiologic insulin secretion requirements
are approximately 50% basal and 50% bolus.
7. How are basal and bolus insulins used with an MDI regimen?
A long-acting insulin is injected either once or twice daily to provide the basal insulin portion of an MDI regimen,
which is approximately 50% of a patient’s total daily dose. Ideally, basal insulin should cover background insulin
needs only, independent of food intake. A rapid-acting or short-acting insulin is injected before meals to provide
the bolus insulin portion of an MDI regimen (see Fig. 3.1). Rapid-acting insulin is preferred because of the rapid
onset and short duration of action. A patient can adjust each bolus dose to match the carbohydrate intake and
to correct for high glucose levels before the meal, whereas the basal dose remains constant from day to day.
Premixed “biphasic” insulin preparations combine either a rapid-acting insulin analogue or regular human insulin
with a crystalline protaminated form of the analogue or regular human insulin in an attempt to imitate basal or
bolus therapy with fewer injections.
8. What are the currently available bolus insulin preparations?
Bolus insulin options include rapid-acting analogues (aspart, glulisine, and lispro), short-acting regular human
insulin, and ultrarapid-acting agents (faster-acting insulin aspart and inhaled insulin). See Table 3.1 for a complete
list of products and their pharmacodynamic profiles. All bolus insulin agents are effective at lowering PPG levels
and HbA1C. Rapid-acting agents have a faster onset of action and shorter duration of action compared with short-
acting insulin. Because of this, current guidelines recommend the use of rapid-acting agents over short-acting
agents in patients with type 1 diabetes to reduce the risk of hypoglycemia; however, cost may necessitate the
use of regular insulin in some patients. Ultrarapid-acting agents may be an option for patients who have rapid rises
TYPE 1 DIABETES MELLITUS 23
Table 3.1. The Pharmacodynamics of Insulin Preparations.

PREPARATIONS (U-100 UNLESS
OTHERWISE NOTED) ONSET PEAKa DURATIONa
Bolus Insulin Products
Ultra-rapid acting
Insulin aspart (Fiasp) 15–20 min.b 90–120 min. 5–7 hours
Insulin human—inhaled (Afrezza) 12 min. 35–40 min. 90–180 mins.
Rapid-acting analog
Insulin aspart (NovoLog)
Insulin lispro U-100, U-200 (Humalog) 10–20 min. 30–90 min. 3–5 hours
Insulin glulisine (Apidra)
Short-acting
Regular (Humulin R, Novolin R) 30–60 min. 2–4 hours 5–8 hours
Basal Insulin Products
Intermediate-acting
NPH (Humulin N, Novolin N) 2–4 hours 4–10 hours 10–24 hours
Long-acting analog
Insulin detemir (Levemir) 1.5–4 hours 6–14 hoursc 16–20 hours
Insulin glargine U-100 (Lantus, Basaglar) 2–4 hours No peak 20–24 hours
Insulin glargine U-300 (Toujeo) 6 hours No peak 36 hours
Insulin degludec U-100, U-200 (Tresiba) 1 hour No peak 42 hours
Combination Products
70% NPH/30% regular (Humulin 70/30, Novolin 70/30) 30–60 min. Dual 10–16 hours
75% NPL, 25% lispro (Humalog 75/25) 5–15 min. Dual 10–16 hours
50% NPL, 50% lispro (Humalog 50/50) 5–15 min. Dual 10–16 hours
70% insulin aspart protamine, 30% insulin aspart 5–15 min. Dual 15–18 hours
(Novolog 70/30)
a
The peak and duration of insulin action are variable, depending on injection site, duration of diabetes, renal function, smoking status,
and other factors.
b
Onset of appearance is 2.5 minutes compared to 5.2 minutes for insulin aspart (NovoLog)
c
Long-acting insulins are considered “peakless” although they have exhibited peak effects during comparative testing.
NPH, neutral protamine Hagedorn; NPL, insulin lispro protamine suspension
in glucose after meals and desire a bolus insulin with a faster pharmacokinetic onset. Faster-acting insulin aspart
(Fiasp) is insulin aspart formulated with niacinamide, which aids in speeding the initial absorption of insulin.
9. What are the currently available basal insulin preparations?
Basal insulin options include long-acting analogues (detemir, glargine U-100, glargine U-300, degludec) and neutral
protamine Hagedorn (NPH) insulin. See Table 3.1 for a complete list of products and their pharmacodynamics pro-
files. All basal insulin agents are effective at lowering FPG levels and HbA1C. The pharmacodynamics of NPH insulin
make it a less ideal basal insulin because it has a distinct peak effect and does not last a full 24 hours. It must be
administered twice daily in patients with type 1 diabetes. Insulin detemir and glargine U-100 have improved phar-
macodynamic profiles compared with NPH, but they may still exhibit a peak effect and may not last a full 24 hours
in all patients. Insulin glargine U-300 and insulin degludec are newer basal insulins without peak effects and have
durations of action that exceed 24 hours. These pharmacodynamic benefits are appealing because they permit
once-daily dosing without the effect wearing off, allow for more dosing flexibility, and are less likely to cause
hypoglycemia. Studies have shown that these agents result in similar reductions in FPG and HbA1C but result in
less nocturnal hypoglycemia compared with insulin glargine U-100.
10. When should bolus insulin be taken?
• Rapid-acting insulin should be taken 5 to 10 minutes before meals and snacks.
• Rapid-acting insulin can be taken:
• 15 to 30 minutes before meals if the premeal BG is higher than 130 mg/dL
• Immediately after eating, if gastroparesis or a concurrent illness is present
• Upon arrival of food, if unfamiliar with meal size, content, or timing (i.e., in a restaurant or hospital)
• Fast-acting insulin aspart (Fiasp) should be taken at the beginning of the meal or within 20 minutes after start-
ing the meal.
24 FUEL METABOLISM
• Inhaled insulin should be taken at the beginning of the meal.

• Human regular insulin should be taken 15 to 30 minutes before meals.
11. When should basal insulin be taken?
• Insulin glargine U-100, detemir, glargine U-300, and degludec should be taken once a day at the same time
each day.
• Insulin glargine U-100 or detemir may be taken at bedtime if the “dawn phenomenon” is present.
• Basal insulin analogues (glargine, detemir, or degludec) cannot be mixed with other insulins.
• If nocturnal hypoglycemia results from taking a full dose of glargine or detemir at bedtime, an option would be
to split the dose so that 50% is taken in the morning and the other 50% is taken in the evening, approximately
12 hours apart.
• NPH insulin is taken in the morning and at bedtime to avoid nocturnal hypoglycemia.
• Doses of insulin glargine U-300 and insulin degludec should not be adjusted more frequently than every 3 to
4 days because of their longer half-lives.
12. What is the role of SMBG?
Optimal diabetes control requires frequent SMBG (or CGM) to permit well-informed adjustments in insulin doses.
Patients on IIT, who do not use CGM, should perform SMBG at least four times daily, before meals, and at bedtime.
Patients should also test if symptoms of hypoglycemia occur and should always test before driving if frequent
hypoglycemia or hypoglycemia unawareness is present. SMBG is crucial during times of intercurrent illness or
stresses for early detection and potential prevention of hyperglycemic emergencies, such as DKA. Patients may
also benefit from occasional testing 1 to 2 hours after meals. Patients using CGM may perform SMBG with less
frequent use of the glucometer, but the glucometer should still be easily accessible in case of emergencies or
device failure. The role of CGM is described below.
13. What is an insulin pump?
An insulin pump is a small, lightweight, portable, battery-operated device, which is either attached directly to the
body (patch pump) or worn on clothing or a belt similar to a pager (traditional pump). A traditional pump is com-
posed of a pump reservoir (which holds a 2- to 3-day supply of rapid-acting or short-acting insulin), connected to
an infusion set, which ends in a cannula that is inserted into the skin and changed every 2 to 3 days. A patch pump
is tubing free and consists of a disposable reservoir that attaches directly to the body with self-adhesive backing
and a built-in infusion set in the device for insertion into the subcutaneous tissue. The patch pump is controlled by
a handheld personal digital assistant (PDA). Insulin is delivered through either system in microliter amounts continu-
ously over 24 hours. The user is responsible for setting the basal rates and determining the bolus doses, depending
on the meal ingested and the results of SMBG. Currently, three companies offer insulin pumps in the United States.
Each pump has special features and functions that are unique and help with the flexibility of pump use. To learn
more about each of these pumps, contact the companies listed in Table 3.2.
14. What are the patient’s responsibilities before insulin pump therapy can be initiated?
• Commit at least 2 to 3 months to pump initiation and training, including multiple meetings with the diabetes
team before, during, and after the pump is initiated.
• Demonstrate the ability to monitor BG values at least 4 to 10 times per day, keep logs of BG readings, insulin
doses and food consumed, and communicate information to the team.
Table 3.2. Currently Available Insulin Pumps and Continuous Glucose Monitors.
PRODUCT COMPANY AND WEBSITE
Insulin pumps MiniMed Paradigm Revel Medtronic Diabetes (www.medtronicdiabetes.com)
Omnipod Insulet Corporation (www.myomnipod.com)
t:slim X2 Tandem Diabetes Care (www.tandemdiabetes.com)
Continuous glucose G4 Platinum Dexcom (www.dexcom.com)
monitors G5
G6
Guardian Connect Medtronic Diabetes (www.medtronicdiabetes.com)
FreeStyle Libre Flash system Abbott (www.freestylelibre.us)
Combination insulin MiniMed 530G with Enlite Medtronic Diabetes (www.medtronicdiabetes.com)
pump/continuous sensor
glucose monitor MiniMed 630G with Enlite
sensor
MiniMed 670G with Guardian
Sensor
6 Basal infusion
Bolus doses
5
Combination
bolus for high-fat
Insulin infusion rate
4 restaurant meal
3
Basal rate increased Basal rate
to prevent dawn decreased
2 phenomenon during Lower basal rate to
exercise prevent overnight
hypoglycemia
1
0
12:00 2:00 4:00 6:00 8:00 10:00 12:00 2:00 4:00 6:00 8:00 10:00 12:00
AM AM AM AM AM AM PM PM PM PM PM PM PM
Time of day
Fig. 3.2. Insulin delivery pattern with pump therapy.
• Review pump training materials and practice pump functions at least two to three times before wearing the
pump.
• Be willing to test basal rates or agree to wear a CGM system to ensure that the basal rates are set appropriately.
15. What are the benefits of insulin pump therapy?
Currently, insulin pump therapy is the dosing strategy that most closely mimics physiologic insulin secretion.
Benefits include better, more precise glucose control with less glycemic variability, a reduction in frequency and
severity of hypoglycemia, ability to adjust basal rates throughout the day (Fig. 3.2), ability to extend bolus dose
durations to better cover high-fat meals (see Fig. 3.2), improved flexibility of lifestyle, ability to administer small
amounts of insulin (as little as 0.025 units), protection from overcorrection by tracking active insulin, and ability
to integrate with CGM technology.
16. What are the limitations of insulin pump therapy?
The cost of an insulin pump and supplies is higher compared with that of an MDI regimen. The device must be
worn 24 hours a day, and optimal use requires highly motivated, competent patients and a higher level of training.
A strong support system from a diabetes team is beneficial. Other limitations include infusion site infections and
risks of DKA if insulin delivery is interrupted.
17. What is CGM?
Currently, three companies offer CGM devices in the United States. To learn more about CGM products, contact
the companies listed in Table 3.2. CGM devices report interstitial glucose levels in real time and provide an in-
sight into glucose trends. Traditional systems consist of a sensor, which is placed just under the skin and senses
the glucose level in interstitial fluid; a transmitter, which is attached to the sensor and collects the glucose data;
and a separate receiver, which collects the data from the transmitter and displays current and stored glucose
readings. The receiver updates the user’s glucose levels in real time, providing values every 5 minutes, and dis-
plays glucose trends with a graph and arrows. With some CGM devices, a smartphone or an insulin pump can be
used as the receiver. Some newer CGM devices have received approval from the U.S. Food and Drug Administra-
tion (FDA) for the data to be used for treatment decision making without verification by SMBG. Some CGM de-
vices require routine calibration with SMBG to maintain accuracy; some newer systems do not. Traditional CGM
devices also provide alerts to the patient when glucose levels are too high or too low or are falling or rising rap-
idly. A new intermittent or “flash” CGM system differs from the traditional CGM devices in that it only communi-
cates readings on demand (not continuously), does not have alarms, and does not require calibration with SMBG.
Some CGM devices are integrated with an insulin pump in one system. To date, we do not yet have an inte-
grated insulin pump/CGM system that truly functions as an artificial pancreas (a system that reads glucose levels
and automatically delivers the right amount of basal and bolus insulin doses to maintain glycemic control), but the
technology is getting closer. The MiniMed 530G and 630G systems include the Enlite CGM device with a low glu-
cose threshold suspend feature, which automatically stops insulin delivery for up to 2 hours when glucose levels
fall below a predetermined threshold and the user does not respond to the alert. The MiniMed 670G system is the
26 FUEL METABOLISM
first hybrid closed-loop system. The system provides automated insulin delivery by automatically adjusting basal
insulin delivery every 5 minutes on the basis of CGM data. It can also suspend insulin delivery up to 30 minutes
before low glucose levels are predicted to occur. Integrated systems with either a t:slim X2 (Tandem) or Omnipod
insulin pump combined with a Dexcom CGM are expected in the near future as well.
CGM use with IIT can reduce HbA1C, hypoglycemia, and glucose variability in patients with type 1 diabetes.
Current guidelines recommend CGM when patients with type 1 diabetes are not meeting glycemic targets. Tradi-
tional CGM may also be useful for patients with hypoglycemia unawareness and/or frequent hypoglycemic events.
18. What is carbohydrate counting, and how is it used with IIT?
Currently, carbohydrate counting is considered the “gold standard” for estimation of meal-time insulin doses.
Carbohydrate counting is a tool used to match bolus insulin doses to food intake because carbohydrates have
the greatest effect on BG levels. The peak of bolus insulin analogues should match the peak of BG following
carbohydrate digestion and absorption ( 1–3 hours, depending on the fat and fiber content of the meal).
19. List the common foods that contain dietary carbohydrates.
• Starch: cereals, grains, beans, bread, rice, pasta, and starchy vegetables
• Sugar: lactose (milk and yogurt), fructose (fruit, juice, and honey), and sucrose (table sugar and desserts)
• Fiber: cellulose and hemicellulose, lignins, gums, or pectins found in fruits, vegetables, legumes, and whole grains
20. How are carbohydrates counted?
Calculating the number of carbohydrates may initially require measuring and weighing commonly eaten foods. Nu-
trition labels on the package state the number of grams of carbohydrates based on the serving size. Carbohydrate
reference books are available at bookstores or through the American Dietetic Association (http://www.eatright.org)
or the American Diabetes Association (ADA; http://www.diabetes.org). Software programs are available for PDAs or
online. Many restaurant chains provide nutrition brochures. See Chapter 6 for practical exercises in carbohydrate
counting and insulin dosing.
21. What is the C:I ratio?
The C:I ratio is used to estimate how many grams of carbohydrate each unit of rapid-acting insulin will cover
(e.g., 20:1 5 20 g of carbohydrate consumed requires 1 unit of bolus insulin).
22. How do you determine an initial C:I ratio?
Ratios are based on a patient’s weight and the total daily dose (TDD) of insulin, which usually indicates the patient’s
sensitivity to insulin. An MDI regimen of basal insulin and premeal injections of rapid-acting insulin must be previ-
ously (or concurrently) implemented before establishing a C:I ratio. A person must be taught to count carbohydrates
before using a C:I ratio safely.
1. Add up the patient’s TDD of insulin on current therapy.
2. Consider the HbA1C value (ADA target is , 7%), frequency of hypoglycemia, and comorbidities.
3. The initial C:I ratio is estimated in our practice by dividing 550 by the TDD. Example: 550 divided by 30 units 5
18:1 C:I ratio.
In clinical practice, the constant in the C:I formula may range from 350 to 550. The initial calculated C:I must
then be adjusted on the basis of each patient’s records and is, therefore, only a starting point.
23. What is an example of an initial C:I ratio when changing to basal and bolus insulins?
• 40 units of Humulin 70/30 premixed insulin in the morning
• 17 units of Humulin 70/30 premixed insulin before the evening meal
• TDD 5 57 units (HbA1C of 8.5% with 2–3 nocturnal hypoglycemic episodes per week)
• 550 4 57 5 9.6
• Begin with a C:I 5 10:1
In this example, 1 unit of rapid-acting insulin will be given for every 10 g of carbohydrate eaten.
24. How do you adjust the C:I ratio once the initial ratio has been established?
Fine-tuning of a C:I ratio is based on BG records before meals and 2 hours after meals. The desired premeal BG is
typically 80 to 130 mg/dL for most patients using IIT. A C:I ratio is correct if the BG increases by approximately 30 to
50 mg/dL over the premeal value at the 2-hour postprandial reading and returns to the range of 80 to 130 mg/dL by
about 4 to 5 hours after the bolus insulin is given (Fig. 3.3). If 2-hour PPG level increments exceed 50 mg/dL, the C:I
ratio should be adjusted and testing repeated with further adjustments until the desired excursion is consistently
achieved.
25. What are the common causes of high BG?
• Missing an injection or bolus dose of insulin
• Menstrual cycle
• Decreased activity
• Stress, illness, or infection
• Underestimating carbohydrates
• Steroids or other medications
2 hours after a meal

↑ 30 – 50 mg/dL above
premeal glucose
(i.e., 110–170 mg/dL)

↑ 20– 40 mg/dL above
premeal glucose
(i.e., 100–160 mg/dL)

↑ 10 –30 mg/dL above
premeal glucose
(i.e., 90–150 mg/dL)
Goal glucose 5 hours after a meal or

before a meal before the next meal
is 80 –120 mg/dL goal glucose
(for most pts.) 80 –120 mg/dL
Fig. 3.3. Expected postprandial blood glucose (BG) range with rapid-acting bolus insulin.
26. What are other factors to consider when troubleshooting high BG readings?
• Dawn phenomenon: a rise in BG occurs in predawn hours because of increased growth hormone and cortisol
production.
• Bad insulin: high BG occurs when insulin denatures if exposed to moderate-to-extreme temperatures or agitation,
is beyond expiration date, or vial or pen device has been used for longer than the manufacturer’s storage recom-
mendations.
• Insulin pump or infusion set technical problems: settings programmed incorrectly; battery depleted; pump mal-
functions; tubing incorrectly primed; air bubbles in the tubing; dislodged, bent or kinked cannula; occlusion at
infusion site; infusion set in place . 72 hours.
27. What causes high postprandial BG readings that are difficult to explain?
• Coffee (caffeine): a rise in BG after drinking coffee (including drinking it black, without cream or sugar) is seen
in many patients’ records and likely results from increases in epinephrine or free fatty acid mobilization and
subsequent worsening insulin resistance.
• Cereal: a rise in BG is seen by patients consuming cereal, often requiring a lower C:I ratio (more insulin) and
may be related to the glycemic index of most cereals combined with greater insulin resistance in the morning.
• Food-on-the-fingers: high BG readings occur from residual food or dextrose on fingers when testing (patients
must wash hands or wipe off first drop of blood).
• Restaurant meals: Chinese food, Mexican food, pizza, and fried foods are high in fat and may require more
insulin because of insulin resistance. A delay in digestion following a high-fat meal may require a split or
extended bolus dose.
28. How is correctional insulin added for high BG before meals?

Correctional or supplemental insulin (high BG CF) is used to reduce high BG detected before meals. A high BG CF
is the expected amount that one unit of insulin will decrease the BG under normal circumstances. It is determined
by using a formula based on the person’s insulin sensitivity. The initial CF is estimated in our practice by dividing
1650 by the TDD. In clinical practice, the constant in the CF formula may range from 1500 to 1800. The initial
calculated CF must then be adjusted on the basis of each patient’s records and is, therefore, only a starting point.
29. What is an example of determining an initial CF?

• 17 units of insulin glargine at noon and 5 units insulin lispro before each meal
• TDD 5 32 units (HbA1C of 7.2% with 1–2 hypoglycemic episodes per week)
• 1650 4 32 5 52
• Begin with a CF of 50:1
In this example, 1 unit of rapid-acting insulin will lower the BG about 50 mg/dL; therefore, 1 extra unit will
be taken (in addition to the meal insulin dose) for each 50 mg/dL that the premeal BG is over the premeal goal of
100 mg/dL.
28 FUEL METABOLISM
30. What is an example of C:I and CF usage?

To determine the amount of insulin needed before a meal, start with calculating the amount of bolus insulin needed
to cover the meal. Example:
• C:I ratio is 20:1
• Meal consists of 80 g of carbohydrates
• Calculation: 80 4 20 5 4 units of insulin to cover the meal
Next, determine the amount of correctional insulin needed. If the BG is out of the target range before a meal,
subtract the goal BG (100 mg/dL) from the actual BG and divide by the CF. Example:
• CF is 60:1
• Preprandial BG is 220 mg/dL
• Calculation: 220 2 100 mg/dL 5 120 mg/dL above target
• Calculation: 120 (mg/dL) 4 60 5 2 units of insulin
In this example, the patient should take 6 units of bolus insulin before the meal—4 units to cover the
carbohydrates in the meal and 2 units to return the premeal high BG to the target range.
31. When is a CF used?

• It is recommended that high BG corrections be taken before meals or at least 5 hours after the last bolus
because of the duration of action of the bolus insulin analogues.
• Hypoglycemia may occur from the accumulation of active insulin if BG corrections are performed too frequently
(stacking).
32. What can be done for a high postprandial BG reading?

• If a postprandial BG is dangerously high (i.e., . 300 mg/dL) or a patient insists on making high BG corrections
, 5 hours since the last bolus or during the night, he or she should be instructed in how to take a partial
correction for safety.
• Using one half of the usual premeal CF to lower the BG to the target level is safest between meals.
• A target level of 150 mg/dL (expected BG level 2 hours postprandial) rather than a target BG of 100 mg/dL is
used as the correction target between meals.
33. What is an example of using a half CF?

• BG before dinner 5 100 mg/dL
• BG 2 hours after dinner 5 300 mg/dL
• “Expected” BG 2 hours after dinner 5 130 to 150 mg/dL
• Calculation: 300 minus 150 mg/dL 5 150 mg/dL above target
• CF is 60:1
• Calculation: 150/60 5 2.5 units (full CF)
• The premeal insulin is still active for about 3 more hours; therefore, use a half CF
• Calculation of half CF: 2.5 (units) 4 2 5 1.3 units
In this example, 1.3 units with an insulin pump or 1 unit with a syringe or insulin pen should be given 2 hours
after the meal to bring the postprandial BG into the target range. BG should be rechecked within 2 hours to avoid
a severe low glucose.
34. How do you calculate an initial basal rate for insulin pump therapy?
• An established C:I ratio and CF on MDI are critical for a smooth transition to pump therapy.
• To calculate an initial basal rate, take the current TDD of insulin on MDI, and reduce it by 25% (or other
appropriate reduction, depending on current HbA1C and number of hypoglycemic episodes).
• Use 50% of this reduced dose as the new total basal dose to be given over 24 hours.
• Start with one basal rate for 24 hours (divide the total basal dose by 24). [Initial basal rate per hour 5
(TDD 3 0.75) 4 (2 3 24).]
• The remaining 50% will be used as bolus doses for meals on the basis of carbohydrate counting.
3 5. Calculate an example of an initial basal rate for insulin pump therapy

1. Current TDD of insulin is 50 units. 25% reduction of TDD 5 37.5 units
2. 50% of reduced dose 5 37.5 4 2 5 18.75 units as total basal
3. Total basal insulin 5 18.75 4 24 5 0.78 U/hr
In this example, the initial basal rate will be 0.8 U/hr. Basal rate adjustments will then be made on the basis
of testing and recording BG profiles throughout the day.
36. When are nighttime basal rate adjustments made?

Nighttime basal rates should be adjusted before the daytime basal rates are verified. Testing is typically performed
during the first week of insulin pump therapy. Be aware that patients transitioning from injected long acting
insulins (glargine, detemir, or degludec) may have overlapping insulin activity, which may cause hypoglycemia
during the first week. Testing is then repeated if a significant weight change occurs, if an exercise routine is
begun or altered, following hormonal changes (e.g., puberty, menopause), or as needed.
37. List the recommendations to follow during the nighttime basal rate verification process
Here are the instructions for the patient to use when verifying overnight basal rates:
• Assess basal rate accuracy on three nights.
• Eat the evening meal early, preferably before 5 pm (or begin the test period  5 hours after eating), and take
the usual insulin bolus for dinner and correction, if needed.
• Choose a meal that you frequently eat or one for which you are confident of the carbohydrate amount.
• Avoid meals with . 15 to 20 g of fat, 10 g of fiber, and alcohol on testing nights.
• Avoid any food or insulin bolus after the evening meal.
• Avoid exercise other than typical activity.
• Monitor BG before and 2 hours after the evening meal, at 9 pm, 12 midnight, 3 am, 6 am, and before breakfast
(or use CGM during this time).
• Stop the test if BG is , 70 mg/dL or . 250 mg/dL during the basal test and treat the abnormal BG.
38. How are nighttime basal rate adjustments made?

• If BG levels change by . 20 to 30 mg/dL during overnight monitoring, adjust the basal rate for the next night
by 0.1 U/hr, starting 1 to 3 hours before the BG change was seen.
• Changes are made until the FBG level in the morning is within the target range (80–130 mg/dL).
• Daytime basal rates are verified next, usually 1 to 2 weeks after pump initiation or as necessary.
39. Describe the procedure for making daytime basal rate adjustments
• Have patients skip breakfast and check their BG levels every hour from 7 am to 12 noon (or use a CGM) to
verify the morning basal rate.
• If BG levels change by . 20 to 30 mg/dL during this time, adjust the basal rate for the next day by 0.1 U/hr,
starting 1 to 3 hours before the glucose change was seen.
• After the morning basal rate is set, have patients skip their other meals (on separate days), and follow the
same monitoring and adjustment procedures to confirm the afternoon and evening basal rate(s).
40. What is the role of noninsulin medications in the treatment of type 1 diabetes?
Pramlintide, an amylin analogue, delays gastric emptying, decreases inappropriate glucagon secretion from the
pancreas after a meal, and increases satiety. It is approved for use as an adjunct to insulin therapy in patients
with type 1 diabetes who have failed to achieve desired glycemic control despite optimal insulin therapy. Pramlint-
ide has been shown to induce weight loss and lower insulin doses. It is administered before meals and concurrent
reduction of meal-time bolus insulin dosing is required to reduce the risk of hypoglycemia.
Metformin, glucagon-like protein-1 (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 (SGLT-2)
inhibitors may reduce insulin requirements and improve metabolic control in patients with type 1 diabetes. Several
medications in these classes have been or are being studied in patients with type 1 diabetes, but none has been
approved by the FDA for use in type 1 diabetes.
41. What is the recommended treatment of hypoglycemia?

Dextrose should be taken for a BG of , 70 mg/dL. The patient should take 15 g of a quick-acting carbohydrate:
fruit juice, glucose tablets or gel, or dextrose-based candy (SweetTARTS, Smarties, Spree). Pure glucose (without
added fat or protein) is preferred. The patient should wait 15 minutes and test the BG again. If the repeat BG is
, 70 mg/dL, additional dextrose should be taken. Once glucose returns to normal, the patient should eat a meal
or snack to prevent recurrent hypoglycemia.
42. Why does rebound hyperglycemia occur after hypoglycemia?

• Overtreatment with an inappropriate amount of carbohydrate may occur.
• No treatment (i.e., sleeping through a low glucose episode) may result in counterregulatory hormone release
and increased hepatic glycogenolysis.
• Treatment with a food that contains fat will delay digestion and absorption, thereby prolonging hypoglycemia
and causing counterregulatory hormone release with subsequent hepatic glycogenolysis.
43. Discuss the use of glucagon to treat severe hypoglycemia

All patients using MDI or pump therapy should be given a glucagon emergency kit prescription and a demonstration.
Glucagon is used to raise BG when a person is unable to swallow. This may occur either as a result of a seizure or
unconsciousness. Family members should receive instruction, and the patient should be able to demonstrate the
procedure to a third party (coworker or neighbor).
30 FUEL METABOLISM
KEY PO I N T S
Intensive Insulin Therapy
1. Studies have demonstrated that optimal diabetes management decreases chronic complications.
2. Intensive insulin therapy, or basal-bolus therapy, is required to mimic normal pancreatic insulin secretion.
3. Basal insulin is physiologic insulin required to manage blood glucose (BG) fluctuations due to hepatic glucose
production.
4. Bolus insulin is matched to carbohydrate intake using a carbohydrate-to-insulin ratio.
5. Correctional bolus insulin reduces the BG to within normal limits when a high glucose correction factor is used.
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Type 1 Diabetes Mellitus

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Type 1 Diabetes Mellitus

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CHAPTER 3

TYPE 1 DIABETES MELLITUS

1. What is the general approach to the treatment of type 1 diabetes mellitus?

75 Breakfast Lunch Dinner

4:00 8:00 12:00 16:00 20:00 24:00 4:00

5. What are the risks of IIT?

Table 3.1. The Pharmacodynamics of Insulin Preparations.

• Inhaled insulin should be taken at the beginning of the meal.

2 hours after a meal

3 hours after a meal

4 hours after a meal

Goal glucose 5 hours after a meal or

28. How is correctional insulin added for high BG before meals?

29. What is an example of determining an initial CF?

30. What is an example of C:I and CF usage?

31. When is a CF used?

32. What can be done for a high postprandial BG reading?

33. What is an example of using a half CF?

3 5. Calculate an example of an initial basal rate for insulin pump therapy

36. When are nighttime basal rate adjustments made?

38. How are nighttime basal rate adjustments made?

41. What is the recommended treatment of hypoglycemia?

42. Why does rebound hyperglycemia occur after hypoglycemia?

43. Discuss the use of glucagon to treat severe hypoglycemia

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