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ALLISON PETZNICK, DO, Northern Ohio Medical Specialists, Sandusky, Ohio

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Insulin therapy is recommended for patients with type 2 diabetes mellitus and an initial A1C level greater than 9 percent, or if diabetes is uncontrolled despite optimal oral glycemic therapy. Insulin therapy may be initiated as augmentation, starting at 0.3 unit per kg, or as replacement, starting at 0.6 to 1.0 unit per kg. 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 12 the 1 last update 05 Jun 2020 )).

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SORT: KEY RECOMMENDATIONS FOR PRACTICE

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Analogue insulin is as effective as human insulin but is associated with less postprandial hyperglycemia and delayed hypoglycemia.

A

1719

Fasting glucose readings should be used to titrate basal insulin, whereas both preprandial and postprandial glucose readings should be used to titrate mealtime insulin.

C

1

Lipohypertrophy due to repeated injections of insulin in the same area leads to poor insulin absorption 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 risk of rebound hyperglycemia.

C

40


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.xml.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence for 1 last update 05 Jun 2020 ratingEvidence ratingReferences

Analogue insulin is as effective as human insulin but is associated with less postprandial hyperglycemia and delayed hypoglycemia.

A

1719

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the 1 last update 05 Jun 2020 CC

1

Lipohypertrophy due to repeated injections of insulin in the same area leads to poor insulin absorption and may cause early postprandial hyperglycemia and/or delayed hypoglycemia.

the 1 last update 05 Jun 2020 CC

35

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B

38

Oral medications should not be abruptly discontinued when starting insulin therapy because of the risk of rebound hyperglycemia.

the 1 last update 05 Jun 2020 CC

40


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.xml.

  Enlarge     for 1 last update 05 Jun 2020    Print

Figure for 1 last update 05 Jun 2020 1.Figure 1.

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. http://www.deo.ucsf.edu. Accessed December 10, 2010.


Figure 1.

Insulin is secreted by the pancreas in a glucose-dependent manner for 1 last update 05 Jun 2020 continuously throughout the day, as well as in response to oral carbohydrate loads.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. http://www.deo.ucsf.edu. Accessed December the 1 last update 05 Jun 2020 10, 2010Adapted with permission from Diabetes Education Online. University of California, San Francisco. http://www.deo.ucsf.edu. Accessed December 10, 2010.

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. 3 Beta-cell failure continues at a rate of about 4 percent each year. 4 Therefore, patients with type 2 diabetes often benefit from insulin therapy at some point after diagnosis.

Concerns About Insulin Therapy

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.K. 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 0.9 percent decrease in A1C level compared with patients on conventional therapy.5

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. 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 [3.89 mmol per L]), then 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 risk with glargine (Lantus) and other insulin therapies. 9 Glargine is theoretically more likely to cause cancer because of its high affinity for insulin-like growth factor I receptor. A consensus statement by the ADA indicates that this possible risk needs further research but should not be a limiting factor in treatment choice.10 Finally, it is important to note 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

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. 11 Insulin may be used alone or in combination with oral medications, such as metformin (Glucophage). 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.

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Analogue Versus Human Insulin

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. 17 Analogue insulin usually causes less postprandial hyperglycemia and delayed hypoglycemia. 18reverses diabetes type 2 and obesity (☑ ribbon) | reverses diabetes type 2 glucagonhow to reverses diabetes type 2 for ,19 In a recent meta-analysis, glycemic control was not improved with analogue insulin compared with human insulin, but nocturnal hypoglycemia was reduced.17

An industry-funded cost-effectiveness analysis found that the increased cost of medication is more than off set by the reduction in hypoglycemic events. 20 However, the analysis 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 difference). 20,21 Cost-effectiveness analyses have differed regarding the long-term cost savings of using analogue insulin in patients with type 2 diabetes, with industry-sponsored studies finding reduced cost22 and government-sponsored studies finding no cost 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

Insulin regimens should be tailored to 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

1,500 divided by total daily insulin (usually about 1 unit per 25 g)

Table 2.

Commonly Used Terms in Insulin Therapy

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Augmentation

Use of either basal or bolus insulin to help improve glucose for 1 last update 05 Jun 2020 control in patients with partial beta-cell failureUse of either basal or bolus insulin to help improve glucose control in patients with partial beta-cell failure

0.3 unit per kg

Replacement

Use of basal and bolus insulin to control blood glucose when endogenous insulin production is minimal or absent

0.6 to 1.0 unit per kg

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500 divided by total daily insulin (usually about 1 unit per 10 g)

Correction (sensitivity)

How much 1 unit of insulin is expected to decrease 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 120-kg (265-lb) patient requiring basal-bolus and correction insulin would need 36 units of basal insulin (0.3 unit per kg); 12 units of short-acting insulin before each meal (0.3 unit per kg divided among three meals); and, for correction, 1 unit of a short-acting insulin for every 25 mg per dL (1.39 mmol per L) 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 by 10 percent based on the patient''s titration schedule for basal insulin (Table 4)(Table 4).31 It is also safe and effective to give patients autonomy to adjust insulin on their own. 32 Typically, insulin is increased or decreased by 2 to 3 units every three to seven days if the patient''s Titration Schedule for Basal Insulin in Patients with Diabetes Mellitus

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120 to 140 mg per dL (6.66 to 7.77 mmol per L)

2 units

141 to 160 mg per dL (7.83 to 8.88 mmol per L)

4 units

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6 the 1 last update 05 Jun 2020 units6 units

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8 units


Adapted with permission from Riddle MC, Rosenstock J, Gerich J; Insulin Glargine 4002 Study Investigators. The Treat-to-Target Trial: randomized addition of glargine or human NPH insulin to oral therapy of type the 1 last update 05 Jun 2020 2 diabetic patients. Diabetes Care. 2003;26(11):3081.Adapted with permission from Riddle MC, Rosenstock J, Gerich J; Insulin Glargine 4002 Study Investigators. The Treat-to-Target Trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care. 2003;26(11):3081.

Table 4.

Treat-to-Target Trial''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.33,34

Insulin Injection Technique

Insulin is effective only if administered appropriately. 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. 8

Rotation of injection sites is important to prevent lipohypertrophy (i.e., scar tissue from repeated injections in the same area). Lipohypertrophy leads to poor insulin absorption and depot formation, which may randomly release insulin, causing early 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 after opening and ease of use for patients with visual or dexterity problems. Patients with visual difficulties may listen to the “clicks” of the insulin pen to count the number of units. Patients should be instructed to prime the insulin pen before every use. Priming consists of drawing up 1 or 2 units of insulin and injecting into the air to allow the insulin to fill the needle.

Using Insulin with Oral Medications

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 have 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 gain, a lower insulin dosage, and less hypoglycemia compared with insulin alone. 38 Thiazolidinediones improve insulin sensitivity but may increase weight gain, fluid retention, and risk of congestive heart failure when combined with insulin.36 Thiazolidinediones also have not been shown to reduce macrovascular complications or all-cause mortality.

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Insulin secretagogues (sulfonylureas and glitinides) can be combined with insulin, especially when only basal augmentation is being used. However, there is a possible increased risk of hypoglycemia that needs to be monitored closely. Usually by the time insulin is required for meals, insulin secretagogues are not effective or necessary. However, it is recommended to continue oral medications while starting insulin to prevent rebound hyperglycemia.40 After the diabetes is controlled, the patient may be weaned off of oral medications.

Incretin therapies include dipeptidyl-peptidase IV inhibitors (sitagliptin [Januvia] and saxagliptin [Onglyza]) and glucagon-like peptide-1 agonists (exenatide [Byetta] and liraglutide [Victoza]). Sitagliptin is currently the for 1 last update 05 Jun 2020 only 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 control, weight loss, and no increased risk of hyperglycemia.42 As with thiazolidinediones, glucagon-like peptide-1 agonists and saxagliptin have not been shown to reduce macrovascular events or all-cause mortality.Incretin therapies include dipeptidyl-peptidase IV inhibitors (sitagliptin [Januvia] and saxagliptin [Onglyza]) and glucagon-like peptide-1 agonists (exenatide [Byetta] and liraglutide [Victoza]). Sitagliptin is currently the only 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 control, weight loss, and no increased risk of hyperglycemia.42 As with thiazolidinediones, glucagon-like peptide-1 agonists and saxagliptin have not been shown to reduce macrovascular events or all-cause mortality.

reverses diabetes type 2 dinner menu (🔥 uncontrolled icd 10) | reverses diabetes type 2 chartshow to reverses diabetes type 2 for Data Sources: A PubMed search was completed in Clinical Queries using the key 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 for 1 last update 05 Jun 2020 meta-analyses, randomized controlled trials, clinical trials, and reviews. Search dates: August 24, 2010, and November 29, 2010.Data Sources: A PubMed search was completed in Clinical Queries using the key 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: August 24, 2010, and November 29, 2010.

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ALLISON PETZNICK, DO, is a family physician at Firelands Regional Medical Centers in Sandusky, Ohio. She is also a family physician and diabetologist with Northern Ohio Medical Specialists in Sandusky....

Address correspondence to Allison Petznick, DO, Northern Ohio Medical Specialists, 1200 W. Strub Rd., Ste. 230, Sandusky, OH 44870 (e-mail: [email protected]). Reprints are not available from the author.

Author disclosure: No relevant financial affiliations to disclose.

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1. Ritzel RA, Bulter PC. Physiology of glucose homeostasis and insulin secretion. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker; 2002:61–72....

2. reverses diabetes type 2 insulin resistance (⭐️ your guide to getting started) | reverses diabetes type 2 blood pressurehow to reverses diabetes type 2 for Diabetes Education Online. University of California, San Francisco. http://www.deo.ucsf.edu. Accessed December 10, 2010.

the 1 last update 05 Jun 2020 3. 3. Gastaldelli A, Ferrannini E, Miyazaki Y, Matsuda M, DeFronzo RA. Betacell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study. Diabetologia. 2004;47(1):31–39.

4. U.K. Prospective Diabetes Study 16. Overview of 6 years''div-gpt-ad-right''s Collections


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Home / Journals / afp / Vol. 84/No. 2(July 15, 2011) / Insulin Management of Type 2 Diabetes the 1 last update 05 Jun 2020 Mellitus Home / Journals / afp / Vol. 84/No. 2(July 15, 2011) / Insulin Management of Type 2 Diabetes Mellitus