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The Family Practice Newsletter
The Ohio University College of Osteopathic Medicine
The Ohio Northern University Raabe College of Pharmacy
Doctors Hospital Family Practice
Volume 6, Issue 2
September, 2006
Initiating and Managing Insulin Therapy in Type I and Type II Diabetes Mellitus
Michael Moranville, Ohio Northern University Doctor of Pharmacy Candidate
Diabetes mellitus (DM) affects about 190 million people worldwide, and is predicted to rise to 330 million by 2025.
However, about 50 percent of diabetics remain undiagnosed and untreated. The United Kingdom Prospectieve Diabetes Study
(UKPDS)2 and the Diabetes Control and Complications Trial (DCCT)3 have proven that microvascular and macrovascular
complications of type 1 DM and type 2 DM, respectively, can be minimized with intensive treatment of blood glucose. 1 Type
1 DM is caused by destruction of pancreatic beta-cells due to autoantibodies. Type 2 DM is the result of insulin resistance due
to lack of muscle, liver, and adipose cell response to insulin followed by impaired insulin secretion. 1,4
Treatment with Insulin
Historically, insulin was reserved for type 1 patients and type 2 patients unresponsive to oral medications. However,
recent literature supports initiation of insulin much earlier after the diagnosis of type 2 DM and sometimes as first line therapy.
If severe hyperglycemia with catabolism is present, insulin should be implemented immediately. This situation is defined as
fasting plasma glucose >250mg/dL, random glucose levels consistently >300mg/dL, Hgb A1c > 10%, the presence of
ketonuria, or symptomatic diabetes with polyuria, polydypsia, polyphagia, and weight loss. 7
When using insulin in the management of diabetes mellitus, the goal is to mimic physiologic release of this hormone.
Therefore, a combination of products that provide bolus and basal coverage must be used. Long acting insulin products are
referred to as basal insulin and provide management of hyperglycemia when the patient is in the fasting state. Basal insulin
products are dosed one or two times daily in order to mimic basal insulin requirements. Commonly used basal insulin
products are glargine (Lantus) and NPH (Humulin N, Novolin N). Short and rapid-acting insulin products are referred to as
bolus insulin and are used to manage post-prandial hyperglycemia. Short acting insulin products, regular insulin
(Humulin R, Novolin R), are dosed 30 minutes before each meal. Rapid acting insulin products, aspart (NovoLog), and
lispro (Humalog) are injected 5-15 minutes before meals. When comparing rapid acting insulin with short acting insulin, the
former has a faster onset and peak, as well as a shorter duration. The major advantage with rapid acting is the increased
flexibility in dosing, such that the patient can use it immediately before starting a meal, which is convenient in those patients
with unpredictable mealtimes.
Dosing regular insulin can be especially difficult when used with NPH as a basal source of insulin due to crossover of
pharmacokinetic parameters. NPH is intermediate acting and has an onset of about two to four hours, peak of six to seven
hours, and lasts up to 20 hours. It usually requires two daily doses to maintain basal levels. When given with regular insulin,
the peak effects of the 2 products can overlap, causing the patient to experience hypoglycemia during that time. Long acting
insulin, insulin glargine, has a 2 hour onset before reaching its plateau. It has no peak and lasts up to 24 hours. Lantus is ideal
for supplying basal insulin and should be administered at the same time every day, ususually at bedtime. 5,8 There is less
nighttime hypoglycemia associated with Lantus, but it can also be given in the morning if hypoglycemia occurs while sleeping
or if patients have a difficult time remembering to take it at bedtime. 5,8-13
Implementing and maintaining a plan
Basal control with Lantus9-13 and prandial doses of rapid-acting insulin14 is a good choice for first line therapy because the
regimen provides similar effect to physiologic secretion of insulin, ease of dosing, and increased flexibility. NPH and regular
are appropriate substitutes, but they are not as easy to dose, and NPH is associated with more hypoglycemia. Hemoglobin A1c
tends to be maintained better with Lantus and rapid-acting combinations.9-15
Below, you will find a brief outline to assist in the initiation and continuation of insulin combinations in patients with
type 1 and type 2 diabetes mellitus. Keep in mind onset of action, peak activity, and duration of action when dosing the
various types of insulin. As with all medication regimens, insulin doses will need titrated based upon patient response,
including A1c and self monitoring blood glucose levels.
Insulin in Type 1 DM:

Normal required dose: 0.2 to 0.6 units/kg/day

Some obese patients will need more insulin: up to 1.2 units/kg/day.

Basal requirement - 50-75% of the total daily dose.5,15

Divide remainder between pre-meal doses with regular or rapid-acting insulin.

Honeymoon phase – rejuvenated function of preserved beta-cells
o may require a decreased insulin requirement for days, weeks, or months after initiation

monitor blood glucose closely16

Decreased renal function requires smaller doses – monitor blood glucose closely
Insulin in Type 2 DM

Lantus has the best results in clinical trials in terms of effectiveness and adverse events. 11-14

Insulin and oral medication combination:
o Sulfonylurea in the morning with evening insulin is common practice.

Bedtime NPH plus morning sulfonylurea – decrease dose of sulfonylurea by one-half

Bedtime Lantus plus morning sulfonylurea – decrease dose of sulfonylurea by one-fourth.
o Meformin is also effective as an insulin sensitizer
o
Thiazolidinediones (Actos and Avandia) are sensitizers also, but take a long time to start working and may have a
poor side effect profile, depending on the patient.
o
Insulin Dose: 0.15 units/kg/day to 0.2 units/kg/day of Lantus is needed when adding to oral agents5,15

Adjust dose every no more frequently than every 3 days

Insulin Monotherapy in Type 2 DM:

Weight based dosing:

0.4 to 0.6 units/kg of total daily insulin5,8,15
o Half of this dose is given as a long acting or intermediate insulin and the rest is divided between
preprandial doses.
o Smaller doses of insulin are required for highly active patients. 17
Special Circumstances:
Converting Lantus to NPH:

Once daily NPH - ratio is 1:1 (Lantus:NPH)

Twice daily NPH – ratio is 0.8:1 (Lantus:NPH)4,5,8,17

Carbohydrate counting:18
o
Insulin to carbohydrate ratio - calculates the number of consumed carbohydrates covered by one unit of insulin

For regular insulin: 500 ÷ total daily dose of insulin

For rapid-acting insulin: 450 ÷ total daily dose of insulin

Correction factor5 – adjusts for pre-meal hyperglycemia by indicating how much the blood glucose will decrease (in mg/dL)
per one unit of insulin given.
o
For regular insulin: 1500 ÷ total daily dose of insulin required
o
For rapid-acting insulin: 1800 ÷ total daily dose of insulin required

Fasting hyperglycemia (morning readings)
o reduce snacking after evening meal
o preprandial rapid acting insulin if blood glucose at bedtime is > 140mg/dL.
o
If bedtime blood glucose is not elevated, extra nightly injections of intermediate acting insulin may be used.
Patients receiving this treatment should check their blood glucose in the middle of the night to be sure hypoglycemia while
sleeping is not the cause of rebound fasting hyperglycemia in the morning.

Daytime hyperglycemia and normal fasting levels
o lower carbohydrate intake and insulin in the morning.5,17
When initiating insulin, patients should check their blood glucose before meals and at bedtime. If multiple daily injections or pumps are
used, they should continue to monitor their blood glucose at least three times a day. Less complicated regimens require less monitoring, and
patients should alternate between bedtime and morning fast readings. Testing should increase during pregnancy and acute illness. Testing at
2 a.m. may be needed to avoid overnight hypoglycemia. HgbA1c tests should be performed every 3 months until patients are stable on
therapy and then every 6 months.1-5,17
For a complete list of all the references used for this article, please view our online archive at www.doctorsfp.com. Click on
pharmacy and then Newsletters.
The Family Practice Newsletter is edited by Stephanie Gibson, Pharm.D., Director of Clinical Pharmacy Services at Doctors Hospital
Family Practice and Assistant Clinical Professor, ONU Raabe College of Pharmacy. Address questions and/or comments to
[email protected].
References:
1. Del Prato S, Felton AM, Munro N, Nesto R, Zimmet P, et. al. Improving glucose management: Ten steps to get more patients
with
type 2 diabetes to glycaemic goal. Int J Clin Pract 2005; 59(11): 1345-1355.
2. Turner RC, Holman RR, Cull CA, Stratton IM, Matthews DR, et. al. Intensive blood-glucose control with sulfonylureas or
insulin
compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;
352:
837-853.
3. Shamoon H, Duffy H, Fleischer N, Engel S, Saenger P, et. al. The effect of intensive treatment of diabetes on the development
and
progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977-816.
4. DeWitt DE, Hirsch IB. Outpatient insulin therapy in type 1 and type 2 diabetes mellitus. JAMA 2003; 289: 2254-2264.
5. Mooradian AD, Bernbaum M, Albert SG. Narrative review: A rational approach to starting insulin therapy. Ann Intern Med
2006;
145: 125-134.
6. American Diabetes Association. Insulin Administration. Diabetes Care 2004; 27(1): S106-S109.
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diabetes:
a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2006; 29(8): 1963-1972.
8. Campbell RK, White JR, Levien T, Baker D. Insulin glargine. Clin Ther 2001; 23(12): 1938-1957.
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protamine
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randomized, parallel group study. Am J Med Sci 2004; 328(5): 274-280.
12. Hamann A, Matthaei S, Rosak C, Silvestre L. A randomized clinical trial comparing breakfast, dinner, or bedtime
administration
of insulin glargine in patients with type I diabetes. Diabetes Care 2003; 26: 1738-1744.
13. Kennedy L, Herman WH, Strange P, Harris A, et. al. Impact of active versus usual algorithmic titration of basal insulin and
pointof-care versus laboratory measurement of HbA1c on glycemic control in patients with type 2 diabetes. Diabetes Care 2006;
29:1-8.
14. Holleman F, Van den Brand J, Hoven R, Van der Linden JM, Van der Tweel I, et. al. Comparison of LysB28, ProB29-human
insulin
analog and regular human insulin in the correction of incidental hyperglycemia. Diabetes Care 1996; 19(12): 1426-1429.
15. Lexi-Comp (Lexi-Drugs, comp + specialties) [computer program]. Lexi-Comp, Skyscape.Ver: 4.0.46/2003.8.31.
16. American Diabetes Organization. Diabetes Dictionary. 2006 [cited 11 September 2006]. Available from: URL:
http://www.diabetes.org/aboutus.jsp?WTLPromo=HEADER_aboutus&vms=211611502513.
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September 2006]. Available from: http://www.diabetesnet.com/diabetes_control_tips/carb_factor.php.