What is insulin and how is it used to treat diabetes?

What is Insulin and How is it Used to Treat Diabetes

Insulin is a hormone essential for normal carbohydrate, protein, and fat metabolism that must be administered as exogenous therapy in type 1 diabetes for survival, and is frequently required in type 2 diabetes when oral medications fail to achieve glycemic control. 1

Physiological Role of Insulin

• Insulin regulates glucose metabolism by stimulating cells in liver, muscle, and fat tissues to take up glucose from blood and store it as glycogen, thereby controlling blood glucose levels and overall energy storage 2
• The hormone coordinates with glucagon to modulate blood glucose levels, with insulin acting via an anabolic pathway while glucagon performs catabolic functions 3
• Insulin modulates a wide range of physiological processes beyond glucose control, making its synthesis and levels critical in the onset and progression of several chronic diseases 3

Insulin Requirements by Diabetes Type

Type 1 Diabetes

• People with type 1 diabetes do not produce enough insulin to sustain life and therefore depend on exogenous insulin for survival 1
• Insulin treatment is essential and the primary therapy for all patients with type 1 diabetes mellitus 4
• Patients typically require initiation with multiple daily injections at the time of diagnosis, consisting of short-acting or rapid-acting insulin analogue given 0-15 minutes before meals together with one or more daily injections of intermediate or long-acting insulin 4

Type 2 Diabetes

• Individuals with type 2 diabetes are not dependent on exogenous insulin for survival initially, but over time many will show decreased insulin production, requiring supplemental insulin for adequate blood glucose control 1
• Insulin should be considered when HbA1c is ≥7.5% and is essential for treatment in those with HbA1c ≥10%, when diet, physical activity, and other antihyperglycemic agents have been optimally used 4
• For patients with severely elevated HbA1c (≥10-12%) with symptoms, ketosis, or unintentional weight loss, basal-bolus insulin should be started immediately, not just basal insulin alone 5

Other Diabetes Types

• An insulin regimen is often required in gestational diabetes and diabetes associated with pancreatic diseases, drug-induced diabetes, endocrinopathies, insulin-receptor disorders, and certain genetic syndromes 1

Types of Insulin Available

Classification by Duration of Action

• Insulin is available in rapid-acting, short-acting, intermediate-acting, and long-acting types that may be injected separately or mixed in the same syringe 1
• Rapid-acting insulin analogs include insulin lispro, insulin aspart, and insulin glulisine, which are dosed just before meals and result in better postprandial glucose control than regular insulin 1
• Long-acting basal insulins include NPH insulin and long-acting analogs (insulin glargine, insulin detemir, insulin degludec), with analogs causing less nocturnal hypoglycemia and having more predictable pharmacokinetics than NPH 5

Insulin Production Methods

• Insulin is obtained from pork pancreas or is made chemically identical to human insulin by recombinant DNA technology or chemical modification of pork insulin 1
• Insulin analogs have been developed by modifying the amino acid sequence of the insulin molecule to alter their time-action profiles 1

Initiating Insulin Therapy

Type 2 Diabetes Initial Regimen

• For type 2 diabetes patients not achieving glycemic goals on oral agents, start with basal insulin (glargine, detemir, degludec, or NPH) at 0.1-0.2 units/kg/day or 10 units once daily, combined with metformin 5
• The preferred method is to begin by adding a long-acting basal insulin or once-daily premixed insulin, alone or in combination with GLP-1 receptor agonist or other oral antidiabetic drugs 4
• For patients with severe hyperglycemia (HbA1c >10%), start basal-bolus insulin therapy at 0.3-0.4 units/kg/day, divided approximately half as basal insulin and half as prandial insulin 6

Type 1 Diabetes Initial Regimen

• Intensive therapy with multiple daily injections or continuous subcutaneous insulin infusion should be used, as this approach reduced A1C to 7% and led to 50% reductions in microvascular complications 1
• Insulin replacement plans typically consist of basal insulin, mealtime insulin, and correction insulin 1
• Automated insulin delivery systems should be considered for all adults with type 1 diabetes 1

Insulin Titration and Adjustment

Basal Insulin Titration

• Increase basal insulin by 2 units every 3 days until fasting glucose reaches target without hypoglycemia 5
• Fasting plasma glucose values should be used to titrate basal insulin, whereas both fasting and postprandial glucose values should be used to titrate mealtime insulin 4

Advancing Therapy

• If basal insulin is optimally titrated but HbA1c remains above goal, add either a GLP-1 receptor agonist (preferred if weight gain or hypoglycemia are concerns) or rapid-acting insulin before meals 5
• If the desired glucose targets are not met with basal insulin alone, rapid-acting or short-acting prandial insulin can be added at mealtime to control postprandial glucose rises 4

Administration and Storage Guidelines

Injection Technique

• Insulin should be injected subcutaneously in the upper legs (thighs), upper arms, or stomach area (abdomen), rotating injection sites within the chosen area with each dose to reduce risk of lipodystrophy 7
• The shortest needles (4-mm pen and 6-mm syringe needles) are safe, effective, less painful, and should be the first-line choice in all patient categories 4
• Intramuscular injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result 4

Storage Requirements

• Vials of insulin not in use should be refrigerated between 36°F and 46°F (2°C and 8°C), while insulin in use may be kept at room temperature to limit local irritation at the injection site 1
• Extreme temperatures (<36°F or >86°F) and excess agitation should be avoided to prevent loss of potency, clumping, frosting, or precipitation 1
• Unopened insulin vials can be used until the expiration date if stored in the refrigerator, but should be discarded after 28 days if stored at room temperature 7
• Opened insulin vials should be thrown away after 28 days, even if insulin remains 7

Combination Therapy Considerations

Metformin with Insulin

• Metformin combined with insulin is associated with decreased weight gain, lower insulin dose, and less hypoglycemia compared to insulin alone and should be continued if not contraindicated 4
• Oral medications should not be abruptly discontinued when starting insulin therapy because of the risk of rebound hyperglycemia 4

Discontinuing Other Medications

• Sulfonylureas should be discontinued when initiating multiple daily insulin injections to reduce hypoglycemia risk 6

Critical Safety Considerations

Hypoglycemia Management

• Hypoglycemia is the most common adverse reaction with insulin and may result from excess insulin, too little food, a delayed meal, or more than usual exercise 1
• All insulin-requiring individuals should carry at least 15 grams of carbohydrate to treat hypoglycemic reactions 1
• Glucagon should be prescribed for all individuals taking insulin, and family members, caregivers, and school personnel should know its location and be educated on administration 1

Monitoring Requirements

• Blood glucose monitoring is an integral part of effective insulin therapy and should not be omitted from the patient's care plan 4
• Patients should practice self-monitoring of blood glucose whenever possible, as insulin dosage adjustments should be based on blood glucose measurements 1
• Early use of continuous glucose monitoring is recommended for adults with type 1 diabetes to improve glycemic outcomes and quality of life and minimize hypoglycemia 1

Medication Errors

• Patients must always check the insulin label before each injection to reduce the risk of medication error 7
• Never share insulin pens or syringes between patients, even if the needle is changed, as this carries risk for transmission of blood-borne pathogens 7

Common Pitfalls to Avoid

• Do not delay insulin initiation in patients with glucose >300 mg/dL and A1C >10%, as oral agents alone will not achieve control 6
• Do not use sliding scale insulin alone as primary therapy, especially in type 1 diabetes 5
• Do not inject insulin into areas with lipohypertrophy (pits or thickened skin), as this distorts insulin absorption 4
• Do not mix insulin glargine with any other type of insulin or liquid medicine 7
• Do not use insulin in an insulin pump unless specifically designed for pump use, and do not inject insulin intravenously unless in a hospital setting 7

Patient Education Essentials

• Patients should receive education on matching mealtime insulin doses to carbohydrate intake, and additionally to fat and protein intake, as well as how to modify insulin doses based on concurrent glycemia and anticipated physical activity 1
• Proper education regarding glucose monitoring, insulin injection technique, insulin storage, recognition and treatment of hypoglycemia, and "sick day" rules is imperative 1
• During illness, insulin must be continued even if the patient is unable to eat or is vomiting 1
• Patients should always have a spare bottle of each type of insulin used, as loss in potency may occur after the bottle has been in use for more than 1 month 1