If I Gave Regualr Insulin at 12:30 When Will I Administer Again
Am Fam Physician. 2011 Jul 15;84(2):183-190.
Article Sections
- Abstruse
- Concerns Well-nigh Insulin Therapy
- Initiating Advisable Insulin Therapy
- Counterpart Versus Human being Insulin
- Choosing the Correct Type of Insulin
- Initiation, Titration, and Follow-Up
- Insulin Injection Technique
- Using Insulin with Oral Medications
- References
Insulin therapy is recommended for patients with type ii diabetes mellitus and an initial A1C level greater than 9 percent, or if diabetes is uncontrolled despite optimal oral glycemic therapy. Insulin therapy may exist initiated as augmentation, starting at 0.three unit per kg, or equally replacement, starting at 0.six to one.0 unit per kg. When using replacement therapy, 50 percent of the total daily insulin dose is given as basal, and 50 percent equally bolus, divided up before breakfast, tiffin, and dinner. Augmentation therapy can include basal or bolus insulin. Replacement therapy includes basal-bolus insulin and correction or premixed insulin. Glucose command, adverse effects, cost, adherence, and quality of life need to be considered when choosing therapy. Metformin should be connected if possible because information technology is proven to reduce all-crusade mortality and cardiovascular events in overweight patients with diabetes. In a report 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 fourth dimension is critical to improving glycemic control and preventing diabetes-related complications.
Insulin is secreted continuously past beta cells in a glucose-dependent manner throughout the twenty-four hour period. It is also secreted in response to oral carbohydrate loads, including a large beginning-phase insulin release that suppresses hepatic glucose production followed by a slower second-phase insulin release that covers ingested carbohydrates 1 (Figure 1 2).
SORT: KEY RECOMMENDATIONS FOR Practice
| Clinical recommendation | Evidence rating | References |
|---|---|---|
| Analogue insulin is as effective as human being insulin but is associated with less postprandial hyperglycemia and delayed hypoglycemia. | A | 17–19 |
| Fasting glucose readings should be used to titrate basal insulin, whereas both preprandial and postprandial glucose readings should exist used to titrate mealtime insulin. | C | 1 |
| Lipohypertrophy due to repeated injections of insulin in the same surface area leads to poor insulin assimilation and may cause early postprandial hyperglycemia and/or delayed hypoglycemia. | C | 35 |
| Metformin (Glucophage) combined with insulin is associated with decreased weight gain, a lower insulin dose, and less hypoglycemia compared with insulin alone. | B | 38 |
| Oral medications should not be abruptly discontinued when starting insulin therapy because of the chance of rebound hyperglycemia. | C | 40 |
Figure one.
Insulin is secreted by the pancreas in a glucose-dependent manner continuously throughout the day, also as in response to oral carbohydrate loads.
Adjusted with permission from Diabetes Education Online. University of California, San Francisco. http://www.deo.ucsf.edu. Accessed December ten, 2010.
Blazon 2 diabetes mellitus is associated with insulin resistance and slowly progressive beta-prison cell failure. By the time type 2 diabetes is diagnosed in patients, upwards to half of their beta cells are not functioning properly. 3 Beta-cell failure continues at a rate of about 4 percentage each year. 4 Therefore, patients with blazon 2 diabetes often do good from insulin therapy at some indicate after diagnosis.
Concerns Nearly Insulin Therapy
- Abstract
- Concerns About Insulin Therapy
- Initiating Appropriate Insulin Therapy
- Counterpart Versus Human Insulin
- Choosing the Correct Type of Insulin
- Initiation, Titration, and Follow-Up
- Insulin Injection Technique
- Using Insulin with Oral Medications
- References
Pain, weight proceeds, and hypoglycemia may occur with insulin therapy. Pain is associated with injection therapy and glucose monitoring, although thinner and shorter needles are now bachelor to help decrease pain. Weight proceeds associated with insulin therapy is due to the anabolic furnishings of insulin, increased appetite, defensive eating from hypoglycemia, and increased caloric retention related to decreased glycosuria. In the U.K. Prospective Diabetes Written report, patients with type 2 diabetes who were taking insulin gained an average of 8 lb, 13 oz (4 kg), which was associated with a 0.9 percent decrease in A1C level compared with patients on conventional therapy.5
Hypoglycemia may occur from a mismatch betwixt insulin and sugar intake, exercise, or alcohol consumption. Hypoglycemia has been associated with an increased risk of dementia and may have implications in cardiac arrhythmia. 6,7 All patients should be instructed on the symptoms and treatment of hypoglycemia. 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 [three.89 mmol per L]), and so treated with a fast-acting carbohydrate, such as juice or glucose tablets. The blood glucose level should be rechecked after 15 minutes to make sure it has normalized.8
An epidemiologic study has raised concern about cancer run a risk with glargine (Lantus) and other insulin therapies. 9 Glargine is theoretically more likely to crusade cancer because of its high affinity for insulin-like growth factor I receptor. A consensus statement by the ADA indicates that this possible run a risk needs further inquiry but should not be a limiting cistron in handling selection.10 Finally, it is important to annotation that there have been no randomized controlled trials demonstrating reduced all-cause mortality or cardiovascular events with insulin augmentation in patients with type 2 diabetes.
Initiating Appropriate Insulin Therapy
- Abstract
- Concerns About Insulin Therapy
- Initiating Appropriate Insulin Therapy
- Analogue Versus Human Insulin
- Choosing the Correct Type of Insulin
- Initiation, Titration, and Follow-Upwardly
- Insulin Injection Technique
- Using Insulin with Oral Medications
- References
The American College of Endocrinology and the American Association of Clinical Endocrinologists recommend initiation of insulin therapy in patients with blazon 2 diabetes and an initial A1C level greater than nine percent, or if the diabetes is uncontrolled despite optimal oral glycemic therapy. 11 Insulin may exist used alone or in combination with oral medications, such equally metformin (Glucophage). This recommendation is based on adept stance, and not on the results of randomized controlled trials comparison different approaches in patients with an initial A1C level greater than 9 per centum.
In the U.K. Prospective Diabetes Study, early intensive glucose control starting with a sulfonylurea, and then metformin, then insulin was associated with a 25 per centum reduction in microvascular complications and a 12 pct risk reduction in any diabetes-related stop bespeak, but was not associated with a reduction in all-cause mortality. 5 A subgroup of patients randomized to intensive therapy with metformin alone had a 36 per centum reduction in all-crusade mortality. 12 This supports electric current ADA guidelines that recommend using metformin as first-line pharmacologic therapy; however, boosted therapies need to exist added if diabetes is not controlled with metformin alone.
Recent trials have shown that intensive glucose control (i.due east., an A1C target of less than 6.0 or 6.5 percent) does not improve, and may worsen, clinical outcomes. 13–xv Older patients with a limited life expectancy and patients with a loftier risk of hypoglycemia, previous cardiovascular disease or advanced microvascular affliction, longer diabetes elapsing, or multiple comorbid conditions may benefit from less stringent glucose command.sixteen
Analogue Versus Human Insulin
- Abstruse
- Concerns About Insulin Therapy
- Initiating Advisable Insulin Therapy
- Analogue Versus Human Insulin
- Choosing the Correct Type of Insulin
- Initiation, Titration, and Follow-Up
- Insulin Injection Technique
- Using Insulin with Oral Medications
- References
Glucose command, adverse effects, cost, adherence, and quality of life need to exist considered when choosing a blazon of insulin. In general, analogue insulin is like to human insulin in controlling diabetes, although some trials have institute higher mean A1C levels in patients taking analogue insulin compared with human insulin. 17 Analogue insulin commonly causes less postprandial hyperglycemia and delayed hypoglycemia. xviii,19 In a recent meta-analysis, glycemic command was not improved with analogue insulin compared with human insulin, but nocturnal hypoglycemia was reduced.17
An manufacture-funded cost-effectiveness analysis found that the increased cost of medication is more than off prepare by the reduction in hypoglycemic events. 20 However, the assay assumed a cost differential of 14 percent, which is inconsistent with current pricing ($119 for a 10-mL vial of glargine insulin compared with $73 for a 10-mL vial of NPH insulin [Humulin N], a 63 percent divergence). 20,21 Cost-effectiveness analyses have differed regarding the long-term cost savings of using analogue insulin in patients with blazon 2 diabetes, with industry-sponsored studies finding reduced cost22 and government-sponsored studies finding no toll reduction. 23 Measures of adherence and quality of life have been improved with analogue insulin compared with human insulin. 24,25
Choosing the Correct Type of Insulin
- Abstruse
- Concerns Nigh Insulin Therapy
- Initiating Appropriate Insulin Therapy
- Analogue Versus Human Insulin
- Choosing the Correct Type of Insulin
- Initiation, Titration, and Follow-Up
- Insulin Injection Technique
- Using Insulin with Oral Medications
- References
Insulin regimens should exist tailored to the patient's needs and lifestyle. One of the near of import considerations is the pharmacokinetics of different insulin preparations 26 (Table 1 26 and Effigy ii 27 ). Table ii defines commonly used terms in insulin therapy.
Table 1.
Pharmacokinetic Profiles of Insulin Therapies
| Insulin type | Onset | Pinnacle | Duration |
|---|---|---|---|
| Long-interim | |||
| Detemir (Levemir) | iii to iv hours | six to 8 hours | 6 to 23 hours |
| Glargine (Lantus) | 90 minutes | None | 24 hours |
| Intermediate-acting | |||
| NPH (Humulin N) | 1 to 2 hours | iv to 10 hours | fourteen or more than hours |
| Short-acting | |||
| Aspart (Novolog) | xv minutes | 1 to 3 hours | 3 to 5 hours |
| Glulisine (Apidra) | xv to xxx minutes | 30 to 60 minutes | iv hours |
| Lispro (Humalog) | 15 minutes | 30 to 90 minutes | iii to 5 hours |
| Regular | 30 to sixty minutes | 2 to 4 hours | 5 to 8 hours |
| Mixed* | |||
| NPH/lispro or aspart | 15 to 30 minutes | Dual | 14 to 24 hours |
| NPH/regular | thirty to 60 minutes | Dual | 14 to 24 hours |
Effigy 2.
Onset of action, height, and duration of exogenous insulin preparations.
Adapted from Hirsch IB. Insulin analogues. N Engl J Med. 2005;352(2):177.
Tabular array two.
Commonly Used Terms in Insulin Therapy
| Term | Definition | Adding |
|---|---|---|
| Augmentation | Use of either basal or bolus insulin to help amend glucose control in patients with partial beta-jail cell failure | 0.3 unit per kg |
| Replacement | Utilise of basal and bolus insulin to control blood glucose when endogenous insulin product is minimal or absent | 0.six to i.0 unit per kg |
| Carbohydrate ratio | The number of units of insulin needed to cover for a certain number of grams of carbohydrates ingested | 500 divided by full daily insulin (usually about 1 unit per 10 g) |
| Correction (sensitivity) | How much 1 unit of insulin is expected to decrease the patient's blood glucose level; when the blood glucose level is to a higher place predefined targets, curt-acting insulin may be added to the bolus dose or given separately between meals | i,500 divided by total daily insulin (unremarkably well-nigh 1 unit per 25 g) |
AUGMENTATION ONLY
In one written report, patients who had uncontrolled type two diabetes and were taking a sulfonylurea and metformin were randomized to receive premixed, bolus, or basal counterpart insulin. Median A1C levels were similar amid the groups, merely hypoglycemia was more common in the premixed and bolus groups, and weight gain was more common in the bolus group. 28 The results of this study suggest that adding basal insulin to oral antihyperglycemics is similarly effective just has fewer adverse effects compared with adding premixed or bolus insulin
The goal of basal insulin is to suppress hepatic glucose production and meliorate fasting hyperglycemia (Figure iii ii). If basal insulin is titrated besides high, it will also partially comprehend meals and pb to hypoglycemia during the night or if a meal is missed. Long-interim analogue insulin may be administered once or twice daily, depending on the dose. Lower doses may non last 24 hours, whereas college doses may impede insulin absorption. NPH may exist administered 1 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.
Figure 3.
Augmentation therapy with basal insulin. Pharmacokinetic profile of using once-daily glargine, detemir, or NPH therapy.
Adapted with permission from Diabetes Education Online. University of California, San Francisco. http://www.deo.ucsf.edu. Accessed December x, 2010.
Bolus insulin may besides be used for augmentation (Effigy 4 2). Curt-acting insulin is administered before meals to cover the carbohydrate load. Short-interim analogue insulin is given up to xv minutes before a meal to maintain two-hour postprandial glucose levels. Taking insulin after meals increases the run a risk of early on postprandial hyperglycemia followed past delayed hypoglycemia. 29 Regular insulin may be used instead and is given xxx to 45 minutes before meals.
Figure 4.
Replacement therapy with basal-bolus insulin. Pharmacokinetic contour of using once-daily glargine, twice-daily detemir, or twice-daily NPH along with a short-acting analogue insulin earlier each meal.
Adapted with permission from Diabetes Instruction Online. University of California, San Francisco. http://www.deo.ucsf.edu. Accessed December 10, 2010.
REPLACEMENT
Replacement therapy includes basal-bolus insulin and correction or premixed insulin; an insulin pump may exist used, but is beyond the scope of this article. Replacement should exist considered for patients with type ii 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 exist added to basal insulin if fasting glucose goals are met just postprandial goals are not. When blood glucose levels are in a higher place predefined targets, additional short-interim insulin may be added to the bolus dose earlier meals. For example, a patient takes 40 units of glargine daily and 12 units of lispro (Humalog) earlier each meal, and has a correction cistron of ane unit for every twenty mg per dL (1.eleven mmol per L) above 120 mg per dL (half-dozen.66 mmol per 50). If the claret glucose level at breakfast is 160 mg per dL (8.88 mmol per L), the patient would accept 12 units of lispro for the meal plus an additional 2 units for correction before eating.
Premixed insulin similarly reduces A1C compared with basal-bolus insulin.30 NPH is combined with regular insulin or brusque-acting analogue insulin and is administered ii or iii times daily. Fewer injections are needed, but patients are more restricted in their eating habits and schedule. Patients must consume breakfast, lunch, dinner, and possibly midmorning and bedtime snacks to foreclose hypoglycemia. If used, correction insulin must exist administered separately with a short-acting insulin. This may increment the number of injections compared with basal-bolus therapy (Figure five two).
Figure 5.
Premixed insulin therapy. Pharmacokinetic contour of using a short-acting analogue insulin or regular insulin along with NPH in a premixed insulin regimen.
Adapted with permission from Diabetes Teaching Online. University of California, San Francisco. http://www.deo.ucsf.edu. Accessed December 10, 2010.
Initiation, Titration, and Follow-Upward
- Abstract
- Concerns About Insulin Therapy
- Initiating Appropriate Insulin Therapy
- Analogue Versus Homo Insulin
- Choosing the Correct Type of Insulin
- Initiation, Titration, and Follow-Upward
- Insulin Injection Technique
- Using Insulin with Oral Medications
- References
The initial dosage of insulin is individualized based on the patient's insulin sensitivity. Insulin therapy may be started with a set dosage, such every bit ten units of glargine daily, or by using weight-based equations. Equations to estimate augmentation, replacement, sugar ratio, and correction therapy are listed in Table 2. When using replacement therapy, 50 percentage of the full daily insulin dose is given as basal and 50 percent every bit bolus, divided upwards before breakfast, lunch, and dinner. For example, a 120-kg (265-lb) patient requiring basal-bolus and correction insulin would need 36 units of basal insulin (0.three unit per kg); 12 units of short-acting insulin before each repast (0.3 unit per kg divided amidst three meals); and, for correction, one unit of a short-interim insulin for every 25 mg per dL (1.39 mmol per Fifty) above the set glucose target.
Titration of insulin over time is critical to improving glycemic control and preventing diabetes-related complications. 5,31 Current ADA goals for glucose control are outlined in Table 3.16 Fasting glucose readings are used to titrate basal insulin, whereas both preprandial and postprandial glucose readings are used to titrate mealtime insulin. 1 Physicians may increase or decrease basal and/or bolus insulin past ten percent based on the patient's home glucose readings. Some physicians have adopted the Treat-to-Target Trial'due south titration schedule for basal insulin (Tabular array 4).31 It is also safe and effective to requite patients autonomy to adjust insulin on their own. 32 Typically, insulin is increased or decreased past 2 to three units every three to seven days if the patient'south blood glucose level is not within set targets.
Table 3.
American Diabetes Association Blood Glucose and A1C Goals for Patients with Diabetes Mellitus
| Measurement | General population | Pregnant women |
|---|---|---|
| Fasting blood glucose | 90 to 130 mg per dL (5 to 7.21 mmol per Fifty) | 60 to 100 mg per dL (three.33 to 5.55 mmol per L) |
| Postprandial blood glucose | < 180 mg per dL (9.99 mmol per Fifty) | 100 to 130 mg per dL (5.55 to vii.21 mmol per Fifty) |
| A1C | < 7.0 percent | < 6.0 percentage |
Tabular array 4.
Care for-to-Target Trial's Titration Schedule for Basal Insulin in Patients with Diabetes Mellitus
| Fasting glucose level | Increase in basal insulin |
|---|---|
| 120 to 140 mg per dL (6.66 to vii.77 mmol per L) | 2 units |
| 141 to 160 mg per dL (seven.83 to 8.88 mmol per L) | iv units |
| 161 to 180 mg per dL (eight.94 to 9.99 mmol per L) | six units |
| > 180 mg per dL (9.99 mmol per L) | eight units |
Patients should go to the physician's office for follow-up at least every 3 to four months. The frequency of communicating insulin titration via clinical contact, telephone, e-mail, or fax is highly correlated with comeback of A1C levels.33,34
Insulin Injection Technique
- Abstruse
- Concerns About Insulin Therapy
- Initiating Appropriate Insulin Therapy
- Analogue Versus Human being Insulin
- Choosing the Correct Type of Insulin
- Initiation, Titration, and Follow-Up
- Insulin Injection Technique
- Using Insulin with Oral Medications
- References
Insulin is effective only if administered accordingly. Injections may be given in the abdomen, outer thigh, back of the arm, and flank/buttocks region. The needle should be placed at a 90-degree angle to the skin and held in place for five to 10 seconds after injection to prevent insulin leakage. viii
Rotation of injection sites is important to preclude lipohypertrophy (i.eastward., scar tissue from repeated injections in the aforementioned area). Lipohypertrophy leads to poor insulin assimilation and depot formation, which may randomly release insulin, causing early on postprandial hyperglycemia and/or delayed hypoglycemia. 35
Insulin is available in pens and vials. Benefits of insulin pens include the convenience of storing at room temperature for 28 days afterward opening and ease of utilise for patients with visual or dexterity problems. Patients with visual difficulties may mind to the "clicks" of the insulin pen to count the number of units. Patients should be instructed to prime the insulin pen earlier every use. Priming consists of cartoon up 1 or ii units of insulin and injecting into the air to allow the insulin to fill the needle.
Using Insulin with Oral Medications
- Abstruse
- Concerns Almost Insulin Therapy
- Initiating Advisable Insulin Therapy
- Analogue Versus Human being Insulin
- Choosing the Correct Type of Insulin
- Initiation, Titration, and Follow-Upward
- Insulin Injection Technique
- Using Insulin with Oral Medications
- References
Many oral medications are safe and effective when combined with insulin therapy. To maximize benefit without causing significant adverse effects, it is important to consider the mechanism of action for different therapies.
Insulin sensitizers take been proven safe and effective when combined with insulin therapy. 36,37 Metformin is usually continued indefinitely after the patient starts insulin therapy because it reduces cardiovascular risk in overweight patients with type 2 diabetes.12 Metformin combined with insulin is also associated with decreased weight proceeds, a lower insulin dosage, and less hypoglycemia compared with insulin alone. 38 Thiazolidinediones improve insulin sensitivity but may increase weight gain, fluid retentivity, and run a risk of congestive heart failure when combined with insulin.36 Thiazolidinediones as well have not been shown to reduce macrovascular complications or all-cause mortality.
Alpha-glucosidase inhibitors filibuster absorption of carbohydrates in the gastrointestinal tract to subtract postprandial hyperglycemia. These medications are safety and constructive when combined with insulin.39
Insulin secretagogues (sulfonylureas and glitinides) can be combined with insulin, especially when only basal augmentation is being used. Yet, there is a possible increased adventure of hypoglycemia that needs to exist monitored closely. Usually by the time insulin is required for meals, insulin secretagogues are not effective or necessary. However, it is recommended to go along oral medications while starting insulin to foreclose rebound hyperglycemia.40 After the diabetes is controlled, the patient may exist weaned off of oral medications.
Incretin therapies include dipeptidyl-peptidase Four inhibitors (sitagliptin [Januvia] and saxagliptin [Onglyza]) and glucagon-like peptide-1 agonists (exenatide [Byetta] and liraglutide [Victoza]). Sitagliptin is currently the but one of these medications that is approved by the U.S. Food and Drug Administration for combination therapy with insulin. This combination is associated with improved fasting and postprandial glucose control.41 Exenatide combined with insulin has been associated with improved glycemic command, weight loss, and no increased gamble of hyperglycemia.42 As with thiazolidinediones, glucagon-like peptide-1 agonists and saxagliptin take not been shown to reduce macrovascular events or all-cause mortality.
Data Sources: A PubMed search was completed in Clinical Queries using the cardinal terms intensive insulin therapy, insulin and cancer, insulin and weight gain, UKPDS, self-titration insulin, human and analog insulin, metformin and insulin, sulfonylurea and insulin, and incretin and insulin. The search included meta-analyses, randomized controlled trials, clinical trials, and reviews. Search dates: Baronial 24, 2010, and November 29, 2010.
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