A more recent article on type 2 diabetes mellitus is available. Insulin therapy may be initiated as augmentation, starting at 0. When using replacement therapy, 50 percent of the total daily insulin dose is given as basal, and 50 percent as bolus, divided up before breakfast, lunch, and dinner. Augmentation therapy can include basal or bolus insulin.

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A more recent article on type 2 diabetes mellitus is available. Insulin therapy may be initiated as augmentation, starting at 0. When using replacement therapy, 50 percent of the total daily insulin dose is given as basal, and 50 percent as bolus, divided up before breakfast, lunch, and dinner. Augmentation therapy can include basal or bolus insulin. Replacement therapy includes basal-bolus insulin and correction or premixed insulin.

Glucose control, adverse effects, cost, adherence, and quality of life need to be considered when choosing therapy. Metformin should be continued if possible because it is proven to reduce all-cause mortality and cardiovascular events in overweight patients with diabetes. In a study comparing premixed, bolus, and basal insulin, hypoglycemia was more common with premixed and bolus insulin, and weight gain was more common with bolus insulin.

Titration of insulin over time is critical to improving glycemic control and preventing diabetes-related complications. Insulin is secreted continuously by beta cells in a glucose-dependent manner throughout the day.

It is also secreted in response to oral carbohydrate loads, including a large first-phase insulin release that suppresses hepatic glucose production followed by a slower second-phase insulin release that covers ingested carbohydrates 1 Figure 1 2. Analogue insulin is as effective as human insulin but is associated with less postprandial hyperglycemia and delayed hypoglycemia. Fasting glucose readings should be used to titrate basal insulin, whereas both preprandial and postprandial glucose readings should be used to titrate mealtime insulin.

Metformin Glucophage combined with insulin is associated with decreased weight gain, a lower insulin dose, and less hypoglycemia compared with insulin alone.

Oral medications should not be abruptly discontinued when starting insulin therapy because of the risk of rebound hyperglycemia. Insulin is secreted by the pancreas in a glucose-dependent manner continuously throughout the day, as well as in response to oral carbohydrate loads. Adapted with permission from Diabetes Education Online.

University of California, San Francisco. Accessed December 10, Type 2 diabetes mellitus is associated with insulin resistance and slowly progressive beta-cell failure. By the time type 2 diabetes is diagnosed in patients, up to one-half of their beta cells are not functioning properly. Pain, weight gain, and hypoglycemia may occur with insulin therapy. Pain is associated with injection therapy and glucose monitoring, although thinner and shorter needles are now available to help decrease pain.

Weight gain associated with insulin therapy is due to the anabolic effects of insulin, increased appetite, defensive eating from hypoglycemia, and increased caloric retention related to decreased glycosuria. In the U. Prospective Diabetes Study, patients with type 2 diabetes who were taking insulin gained an average of 8 lb, 13 oz 4 kg , which was associated with a 0. Hypoglycemia may occur from a mismatch between insulin and carbohydrate intake, exercise, or alcohol consumption.

Hypoglycemia has been associated with an increased risk of dementia and may have implications in cardiac arrhythmia. American Diabetes Association ADA guidelines recommend that the blood glucose level be checked if hypoglycemia is suspected glucose level lower than 70 mg per dL [3. The blood glucose level should be rechecked after 15 minutes to make sure it has normalized.

An epidemiologic study has raised concern about cancer risk with glargine Lantus and other insulin therapies. A consensus statement by the ADA indicates that this possible risk needs further research but should not be a limiting factor in treatment choice. The American College of Endocrinology and the American Association of Clinical Endocrinologists recommend initiation of insulin therapy in patients with type 2 diabetes and an initial A1C level greater than 9 percent, or if the diabetes is uncontrolled despite optimal oral glycemic therapy.

This recommendation is based on expert opinion, and not on the results of randomized controlled trials comparing different approaches in patients with an initial A1C level greater than 9 percent. Prospective Diabetes Study, early intensive glucose control starting with a sulfonylurea, then metformin, then insulin was associated with a 25 percent reduction in microvascular complications and a 12 percent risk reduction in any diabetes-related end point, but was not associated with a reduction in all-cause mortality.

Recent trials have shown that intensive glucose control i. Glucose control, adverse effects, cost, adherence, and quality of life need to be considered when choosing a type of insulin. In general, analogue insulin is similar to human insulin in controlling diabetes, although some trials have found higher mean A1C levels in patients taking analogue insulin compared with human insulin. An industry-funded cost-effectiveness analysis found that the increased cost of medication is more than off set by the reduction in hypoglycemic events.

Insulin regimens should be tailored to the patient's needs and lifestyle. Table 2 defines commonly used terms in insulin therapy. Adapted with permission from Endotext. Insulin pharmacology, types of regimens and adjustments. Accessed December 6, Adapted from Hirsch IB.

Insulin analogues. N Engl J Med. Use of either basal or bolus insulin to help improve glucose control in patients with partial beta-cell failure.

Use of basal and bolus insulin to control blood glucose when endogenous insulin production is minimal or absent. The number of units of insulin needed to cover for a certain number of grams of carbohydrates ingested. How much 1 unit of insulin is expected to decrease the patient's blood glucose level; when the blood glucose level is above predefined targets, short-acting insulin may be added to the bolus dose or given separately between meals.

In one study, patients who had uncontrolled type 2 diabetes and were taking a sulfonylurea and metformin were randomized to receive premixed, bolus, or basal analogue insulin. Median A1C levels were similar among the groups, but hypoglycemia was more common in the premixed and bolus groups, and weight gain was more common in the bolus group. The goal of basal insulin is to suppress hepatic glucose production and improve fasting hyperglycemia Figure 3 2. If basal insulin is titrated too high, it will also partially cover meals and lead to hypoglycemia during the night or if a meal is missed.

Long-acting analogue insulin may be administered once or twice daily, depending on the dose. Lower doses may not last 24 hours, whereas higher doses may impede insulin absorption.

NPH may be administered one to three times daily. NPH is often used during pregnancy and in patients who are unable to afford the up-front cost of analogue insulin. Augmentation therapy with basal insulin. Pharmacokinetic profile of using once-daily glargine, detemir, or NPH therapy.

Bolus insulin may also be used for augmentation Figure 4 2. Short-acting insulin is administered before meals to cover the carbohydrate load. Short-acting analogue insulin is given up to 15 minutes before a meal to maintain two-hour postprandial glucose levels. Taking insulin after meals increases the risk of early postprandial hyperglycemia followed by delayed hypoglycemia.

Replacement therapy with basal-bolus insulin. Pharmacokinetic profile of using once-daily glargine, twice-daily detemir, or twice-daily NPH along with a short-acting analogue insulin before each meal. Replacement therapy includes basal-bolus insulin and correction or premixed insulin; an insulin pump may be used, but is beyond the scope of this article.

Replacement should be considered for patients with type 2 diabetes that is uncontrolled with augmentation therapy and who are able to comply with such a regimen or who desire tighter control.

Bolus insulin should be added to basal insulin if fasting glucose goals are met but postprandial goals are not. When blood glucose levels are above predefined targets, additional short-acting insulin may be added to the bolus dose before meals.

For example, a patient takes 40 units of glargine daily and 12 units of lispro Humalog before each meal, and has a correction factor of 1 unit for every 20 mg per dL 1.

If the blood glucose level at breakfast is mg per dL 8. Premixed insulin similarly reduces A1C compared with basal-bolus insulin. Fewer injections are needed, but patients are more restricted in their eating habits and schedule. Patients must eat breakfast, lunch, dinner, and possibly midmorning and bedtime snacks to prevent hypoglycemia. If used, correction insulin must be administered separately with a short-acting insulin.

This may increase the number of injections compared with basal-bolus therapy Figure 5 2. Premixed insulin therapy. Pharmacokinetic profile of using a short-acting analogue insulin or regular insulin along with NPH in a premixed insulin regimen. The initial dosage of insulin is individualized based on the patient's insulin sensitivity. Insulin therapy may be started with a set dosage, such as 10 units of glargine daily, or by using weight-based equations. Equations to estimate augmentation, replacement, carbohydrate ratio, and correction therapy are listed in Table 2.

When using replacement therapy, 50 percent of the total daily insulin dose is given as basal and 50 percent as bolus, divided up before breakfast, lunch, and dinner.

For example, a kg lb patient requiring basal-bolus and correction insulin would need 36 units of basal insulin 0. Some physicians have adopted the Treat-to-Target Trial's titration schedule for basal insulin Table 4.

Some microvascular benefit has been associated with A1C targets of 6. Adapted with permission from American Diabetes Association.

Standards of medical care in diabetes— [published correction appears in Diabetes Care. Diabetes Care. The Treat-to-Target Trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Patients should go to the physician's office for follow-up at least every three to four months. The frequency of communicating insulin titration via clinical contact, telephone, e-mail, or fax is highly correlated with improvement of A1C levels.

Insulin is effective only if administered appropriately. The needle should be placed at a degree angle to the skin and held in place for five to 10 seconds after injection to prevent insulin leakage. Rotation of injection sites is important to prevent lipohypertrophy i. Insulin is available in pens and vials. Benefits of insulin pens include the convenience of storing at room temperature for 28 days after opening and ease of use for patients with visual or dexterity problems.

Patients should be instructed to prime the insulin pen before every use.


Insulin Management of Type 2 Diabetes Mellitus

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Dosing of Insulin Glargine in the Treatment of Type 2 Diabetes

Sharing poses a risk of transmission of blood borne pathogens. BASAGLAR is indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. BASAGLAR is contraindicated during episodes of hypoglycemia, and in patients with hypersensitivity to insulin glargine or one of its excipients. Changes in insulin strength, manufacturer, type, injection site, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Any changes in insulin regimen should be made cautiously and only under close medical supervision, and the frequency of blood glucose monitoring should be increased. Due to reports of hypoglycemia and hyperglycemia, advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor blood glucose.

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