Anti-Diabetic Agents
The target capillary blood glucose levels
recommended by the California Sweet Success Program [13,19,20] during
pregnancy are:
| Time |
Glucose Value |
| Fasting |
60
- 89 mg/dl |
| 1 hour after meals |
100 -129 mg/dl |
If diet and exercise therapy fail to maintain blood glucose
levels in the recommended ranges insulin therapy is generally recommended [1]. However,
treatment with glyburide appears to be gaining approval as an acceptable
alternative to insulin therapy in some women [16].
Patients with diabetes prior to pregnancy, a history of diabetic ketoacidosis,
liver disease, or a fasting blood sugar greater than or equal to 140 mg/dL at
diagnosis are treated appropriately with insulin [1-4].
The commonly used types of insulin are regular insulin and NPH. Regular insulin
has a duration of action of 5 to 8 hours. Neutral Protamine Hagedorn , NPH, is named after one of its developers the physician Hans Christian Hagedorn who
discovered that combining a suspension of crystalline zinc insulin with protamine could prolong
the duration of action of the insulin.
Insulin aspart , insulin lispro, insulin detemir, and insulin glargine are human insulin that
have had their chemical composition slightly altered to influence their onset
and duration of action.
The American Diabetes Association (ADA) recommends that patients with preexisting diabetes who are taking detemir or glargine should be transitioned to NPH insulin
twice or three times daily until clinical trials have
proven the efficacy and safety of these analogs [32].
For patients who insist on continuing detemir or glargine throughout
pregnancy clinicians will have to rely on their knowledge of the
pharmacology of the treatments, sporadic case reports, and their own judgment
regarding the risks and benefits of continuing to use these analogs in a
particular patient [21].
The American Association of Clinical Endocrinologists, (AACE) Diabetes Mellitus
Clinical Practice Guidelines Task Force has recommended that continuous
subcutaneous insulin infusion (CSII) (insulin pump) therapy is indicated for
patients with type 1 diabetes mellitus who are pregnant [22]. However, a
systematic review did not show any advantage or disadvantage of using continuous
subcutaneous insulin infusion (CSII)
over multiple-dose insulin (MDI) in pregnant diabetic women [23] . The authors
of the review suggested CSII should perhaps be reserved for special
circumstances such as instances in which normoglycemia is not achieved by
conventional means.
The AACE Diabetes Mellitus Clinical Practice Guidelines Task Force
suggested CSII therapy is also indicated for:
- Patients who are unable to achieve acceptable control using a regimen of multiple daily injections
- Patients with histories of frequent hypoglycemia and/or hypoglycemia unawareness
- Patients with extreme insulin sensitivity (pump therapy facilitates better precision than subcutaneous injections)
- Patients with a history of dawn phenomenon (these patients can program a higher basal rate for the early morning hours to counteract the rise in blood glucose concentration)
- Patients who require more intensive diabetes management because of complications including neuropathy, nephropathy, and retinopathy
- Patients taking multiple daily injections who have demonstrated willingness and ability to comply with prescribed diabetes self-care behavior including frequent glucose monitoring, carbohydrate counting, and insulin adjustment
Glyburide appears to
be a safe and effective alternative to insulin in the treatment of gestational
diabetes for some women. Women with a 1 hour OGTT less than 200 mg/dL, a fasting
blood sugar less than 110 mg/dL, or who fail dietary
therapy after 30 weeks gestation appear to be good candidates for treatment with
glyburide therapy [5-9] if diet fails to control their blood sugar.
Although metformin also appears be a useful adjunct or alternative to insulin
during pregnancy [14,15] some authors caution that data are needed on the long-term safety of metformin
before it can be considered as first-line therapy for women with gestational diabetes [16,17].
Insulin
Insulin is a peptide hormone with a molecular weight of 5808 Da. It is
produced in the islets of Langerhans in the pancreas. Synthetic "human" insulin
is manufactured using recombinant DNA technology.
Doses of insulin are measured in units. U-100 insulin contains 100 units/mL.
Initial doses for insulin will vary according to trimester and weight.
See
Initial Insulin Calculator
and
Insulin Sensitivity
Calculator
For DKA see Diabetic
Ketoacidosis Order Set
In general, when a longer-acting insulin (e.g. NPH insulin
isophane suspensions) is mixed with short-acting or rapid acting-soluble insulin
(e.g., regular), the short-acting or rapid acting insulin should be drawn into
the syringe first. Insulin glargine must NOT be diluted or mixed with any other insulin or
solution
The subcutaneous tissue of the abdomen is preferred site for injection because absorption of the
insulin is more consistent from this location than subcutaneous tissues in other
locations.
Among the potential clinical adverse effects
associated with the use of all insulins are hypoglycemia and hypokalemia.
Storage
Unopened insulin should be stored in a refrigerator between 2 and 8°C (36 and
46°F); it should not be placed in a freezer. After initial use a vial may be kept at temperatures below 30°C (86°F) for up
to 28 days, but should not be exposed to excessive heat or sunlight.
Unused insulin should be thrown away after the expiration date. Insulin in a pump reservoir should be discarded after
at least every 48 hours of use or after exposure to temperatures that exceed
37°C (98.6°F).
Syringes
Insulin syringes are available in three barrel sizes 1mL (100 units), ½ mL (50 units) and 3/10 mL (30 units).
BD Micro-Fine™ IV Needle is a 28-gauge,
12.7mm (1/2")
BD Ultra-Fine™ Needle is a 30-gauge, 12.7mm (1/2")
BD Ultra-Fine™ Short Needle 31-gauge, 8mm (5/16")/p>
For information on safe disposal of needles, syringes, and other sharps in the community contact:
Rapid-acting Insulins- Onset 15 minutes
[21]
Insulin aspart [rDNA origin] injection (NovoLog®
)
Insulin lispro, [rDNA origin] injection (Humalog®)
Insulin analogs. Onset 15 minutes , peak of action 30 to 90 minutes, duration
of action less than 5 hours [22].
-
Indicated in the treatment of patients with diabetes mellitus for the control
of hyperglycemia.
Give calculated dose subcutaneously 15 minutes before a meal.
The algorithm below may used, but may need to be modified according to the
patient population. [25]
| Preprandial or Bedtime Blood Glucose
average for at least 3 consecutive days (mg/dl) |
Adjust dose of aspart (Novolog)
units |
|
>180 |
+3 |
|
160-180 |
+2 |
|
140-159 |
+2 |
|
120-139 |
+1 |
|
100-119 |
maintain dose |
|
80-99 |
-1 |
|
60-79 |
-2 |
|
<60 |
-4 |
See also: Insulin Sensitivity
Calculator
(100 Units per mL in 10 mL vials, 3 mL cartridges, or 3 mL Pens)
Pregnancy Category B
Short-acting Insulins- Onset 30 to 60 minutes
Regular insulin human injection, USP (rDNA origin)
(Humulin® -R,
Novolin®
-R)
Insulin. Onset 30 to 60 minutes , peak of action 2 to 3 hours, duration
of action 5 to 8 hours [22].
-
Indicated in the treatment of patients with diabetes mellitus for the control
of hyperglycemia.
Give calculated dose subcutaneously 30 minutes before a meal.
(100 Units per mL in 10 mL vials)
Pregnancy Category B
Regular insulin human injection, USP (rDNA origin)
( Humulin
R (U-500) ® ,Concentrated)
Insulin. Onset 30 to 60 minutes , peak of action 2 to 3 hours, duration
of action 5 to 8 hours [22].
-
Indicated in the treatment of diabetic patients with marked insulin
resistance (daily requirments more than 200 units)
Give calculated dose subcutaneously 30 minutes before a meal.
(500 Units per mL in 20 mL vials)
Pregnancy Category B
Intermediate-acting, Basal Insulin- Onset 2 to 4 hours
Neutral Protamine Hagedorn (NPH) Human Insulin (rDNA origin)
Isophane Suspension
(Humulin®
-N , Novolin® N)
Zinc insulin combined with the polypeptide protamine.
Onset 2 to 4 hours, peak of action 4 to 10 hours, duration of action 10
to 16 hours [22].
-
Indicated in the treatment of patients with diabetes mellitus for the control
of hyperglycemia.
Give calculated dose alone or mixed with short or
rapid acting insulin subcutaneously.
(100 Units per mL in 10 mL vials)
Pregnancy Category B
Long-acting, Basal Insulin - Onset 2 to 4 hours [21, 27-31]
Insulin glargine (Lantus® )
Insulin analog. Onset 2 to 4 hour, peak of action none, duration of action
20 to 24 hours [22]
-
Indicated in the treatment of patients with diabetes mellitus for the control
of hyperglycemia.
For patients on no basal insulin the starting dose for Lantus is 10 units alone
subcutaneously
once daily at the same time every day.
For patients already on once-daily NPH human insulin or ultralente human insulin
replace NPH or ultralente dose with Lantus 1:1 (unit for unit). Give dose
subcutaneously
once daily at the same time every day.
For patients already on twice-daily NPH human
insulin replace NPH with Lantus using 80% of the NPH dose. Give the dose subcutaneously
once daily at the same time every day.
Adjust dose by increasing dose by one unit daily until fasting glucose is less
than 100 mg/dL [24] OR use the algorithm below [25,26].
|
Fasting Blood Glucose average for at least 3 consecutive days (mg/dl) |
Adjust
dose of glargine (Lantus), units |
| >180 |
+8 |
| 160-180 |
+6 |
| 140-159 |
+4 |
| 120-139 |
+2 |
| 100-119 |
+1 |
| 80-99 |
maintain
dose |
| 60-79 |
-2 |
| <60 |
-4 |
Average dose of 10 IU once daily, and subsequently adjusted according to the patient's need to a
total daily dose ranging from 2 to 100 IU.
LANTUS must NOT be diluted or mixed with any other insulin or solution
(100 Units per mL in 10 mL vials, 3 mL cartridges, or 3 mL disposable
device)
Pregnancy
Category C
Insulin Pump
See Calculation of
Initial Insulin Pump Requirements
perinatology.com
Glyburide (Micronase® )
Oral blood-glucose-lowering drug of the sulfonyl- urea class [10].
- Used as an adjunct to diet to lower the blood glucose in patients
with non-insulin-dependent diabetes mellitus [11].
1.25 mg to 2.5 mg PO daily 60 minutes before meals to control postprandial
sugar.
May give at 10 to 11 PM to control fasting blood sugar.
May increase by 1.25 to 2.5 mg every 3 to 7days to a maximum
of 20 mg.
(1.25, 2.5, and 5 mg tablets)
Pregnancy Category B
Limited data indicate that the levels of glyburide in milk are negligible
[12].
SEE ALSO drugsafetysite.com/glyburide
Metformin (Glucophage®
)
Oral blood-glucose-lowering drug of the biguanide [18].
Lactic acidosis is a rare, but serious, metabolic complication that can
occur due to metformin accumulation during treatment; when it occurs, it is
fatal in approximately 50% of cases. Reported cases have occurred primarily in
diabetic patients with significant renal insufficiency.The onset of
lactic acidosis often is subtle, and accompanied only by nonspecific symptoms
such as malaise, myalgias, respiratory distress, increasing somnolence, and
nonspecific abdominal distress
(500, 850, and 1000 mg tablets)
Pregnancy Category B
SEE ALSO drugsafetysite.com/metformin
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Created 12/2/08
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