The management of type 1 diabetes mellitus entails replacing the actions of the beta cells of the pancreatic islet to detect the needs of insulin and to have insulin administered according to the needs of the patient's body. Insulin is a natural hormone, and it is an essential medication for a multitude of disease states. One of the most critical uses of insulin is in type 1 diabetes mellitus and type 2 diabetes mellitus.[1][2] Insulin is one of the few medications indicated for use in the management of gestational diabetes.[3] Due to its effects of driving potassium into the intracellular compartment, it has utility in the management of hyperkalemia.[4] Insulin is a component in the management of complications of diabetes mellitus, including diabetic ketoacidosis as well as the hyperosmolar hyperglycemic state.[5] There is a proven clinical benefit of using insulin in critical illnesses to prevent or treat hyperglycemia-related toxicity.[6] Commonly, treatment of hypertriglyceridemia includes dietary modifications and medical management with the use of fibrates, fish oil, and niacin, amongst others. One of the other very important applications of insulin is in the treatment of severe hypertriglyceridemia as well as hypertriglyceridemia-induced pancreatitis. Insulin lowers the triglycerides by upregulating the formation of lipoprotein lipase, which works by hydrolyzing the triglycerides. Insulin infusion can help patients with severe hypertriglyceridemia by quickly reducing the blood concentrations of triglycerides to less than 1000 mg/dl.[7]

Insulin’s significant actions focus on storing excess energy in a fed state. Insulin promotes glycogen synthesis, lipid synthesis, protein synthesis, DNA synthesis, as well as cellular growth and differentiation. Once glucose gets absorbed from a meal, it enters the blood, and then the pancreas releases insulin. Insulin synthesis occurs in the beta cells of the pancreas initially as preproinsulin. Preproinsulin then converts to proinsulin, which then transforms into a single peptide with A, B, and C peptide units. The A and B peptides are joined by disulfide bonds to make insulin and get secreted into the bloodstream. Insulin binds to its cellular receptor. The insulin receptor is composed of alpha subunits, beta subunits, and a tyrosine kinase enzyme. When insulin binds to the alpha subunit, this triggers phosphorylation and activation of the target proteins intracellularly by the tyrosine kinase leading to many effects on cellular metabolism. Activation of the insulin receptor also leads to increased expression of GLUT ( a glucose transporter) to the membrane surface and promotes the entry of glucose to the intracellular compartment and then undergoes cellular metabolism. Insulin signals glucose conversion to glycogen for storage as well as the formation of acetyl coenzyme A and triacylglycerol, which get stored in adipose tissue. Also, insulin directs amino acids for protein synthesis.[3]

In patients with diabetes mellitus, to reach the goal of normal 24-hour insulin activity like in healthy adults without diabetes mellitus, one single insulin formulation with a defined onset, peak, and duration of action is not helpful. Hence there is a need for different kinds of insulin that have different pharmacokinetics. Based on the mode of action, there are four different types of insulin analogs. The rapid-acting insulin has a rapid onset of action (about less than 30 minutes), peak action at about 1 hour, and short duration of action (up to 5 hours). Insulin Lispro and Insulin Aspart are the rapid-acting insulins. These insulins help achieve glycemic control, specifically in the postprandial state. The short-acting insulin analogs activity begins in about 30 to 60 minutes, peaks at 2 to 4 hours, and activity last for about 8 hours. These insulin analogs must be administered approximately 20 to 30 minutes before meals for effectiveness. The intermediate-acting insulin analogs have an onset of activity at around 1 to 2 hours, peak action at 6 to 10 hours, and a duration of action up-to about 16 hours. Neutral protamine Hagedorn (NPH) and Lente insulin are intermediate-acting insulin analogs. Some of the long-acting insulin analogs are insulin Detemir and insulin Glargine. Their activity begins at around 2 hours, peak effect from 6 to 20 hours, and lasts up to about 36 hours.[8]

There are multiple routes of administration of insulin. Administration can be as a bolus as an intravenous injection or as a continuous intravenous infusion. Typically, glycemic control is achieved by using basal and prandial insulin administration or by continuous subcutaneous insulin infusion. It can be given as a subcutaneous or intramuscular injection as well. Recently, the inhalational route for the administration of insulin is available for clinical use.[2][9] Transplantation of the islet cells of the pancreas or pancreatic transplantation is an investigational procedure that can mimic natural insulin synthesis and functionality.[10] Administration of insulin via oral and transdermal routes is being evaluated and may be available shortly for everyday use.[9]

Like any other medication, there are clinically significant side effects associated with the use of insulin. Insulin administration can lead to local hypersensitivity reactions such as erythema, pruritus, swelling, and pain at the site of injection. Local dermal lipo-dystrophic reactions can occur. An inappropriately excessive dose of insulin or incoordination with meals/missing meals, hypoglycemia can occur, which can be life-threatening. Untreated hypoglycemia can cause seizures, coma as well as death, which makes it especially important in elderly patients who are more susceptible. Long term use of insulin can lead to the production of antibodies against it with possible development of insulin resistance. As mentioned earlier, insulin can cause the potassium to shift to the intracellular compartment and lead to hypokalemia. Hypokalemia can manifest as cardiac arrhythmias, muscle cramping, gastrointestinal upset, confusion, weakness as well as lethargy.[9]

There are a few contraindications to the use of insulin. A patient history of allergic reactions to insulin, its reuse is contraindicated. In patients with insulinoma, where there is excessive endogenous production of insulin, the use of exogenous insulin is contraindicated. There is a relative contraindication to using insulin in the setting of hypokalemia. The potassium concentrations must be corrected before the administration of insulin, as insulin has a known effect of causing hypokalemia.