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Insulin

Insulin is a peptide hormone that is produced by the beta cells of the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy. Insulin plays a role in metabolic functions such as glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance uptake, glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis, glycogenesis Glycogenesis Glycogen Metabolism, lipogenesis Lipogenesis De novo fat synthesis in the body. This includes the synthetic processes of fatty acids and subsequent triglycerides in the liver and the adipose tissue. Lipogenesis is regulated by numerous factors, including nutritional, hormonal, and genetic elements. Nonalcoholic Fatty Liver Disease, and protein synthesis Synthesis Polymerase Chain Reaction (PCR). Exogenous insulin may be needed for individuals with diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing. There are several forms of insulin, and they differ in their time of onset, peak effect, and duration. Insulin can be classified as fast acting, short acting, intermediate acting, or long acting. A combination of classes can be used to maintain glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance control throughout the day. Common adverse effects include hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia, weight gain after initiation of an insulin regimen, and local injection site changes.

Last updated: Sep 1, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Pharmacodynamics

Chemistry

  • Insulin is a small protein normally created and released by pancreatic beta cells. 
  • Available formulations can be:
    • Human insulin: identical to endogenously produced insulin
    • Analog insulin: altered to create pharmacokinetic advantages

Mechanism of action

  • Insulin acts on cells to ↑ glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance uptake in all tissues, including the: 
    • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
    • Skeletal muscle
    • Adipose tissue Adipose tissue Adipose tissue is a specialized type of connective tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or “brite” adipose tissue, which is a transitional form. Adipose Tissue: Histology
  • This occurs via glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance transporters (GLUTs): 
    • GLUT4 → muscle and adipose
    • GLUT2 GLUT2 A glucose transport facilitator that is expressed primarily in pancreatic beta cells; liver; and kidneys. It may function as a glucose sensor to regulate insulin release and glucose homeostasis. Digestion and Absorption liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
  • Exogenous insulin is often used to overcome hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus caused by:
    • Insulin deficiency ( type 1 Type 1 Spinal Muscular Atrophy diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus)
    • Insulin resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing ( type 2 Type 2 Spinal Muscular Atrophy diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus)

Physiologic effect

  • In the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy:
    • ↑ Glycogen synthesis Synthesis Polymerase Chain Reaction (PCR)
    • Glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis
    • Lipogenesis Lipogenesis De novo fat synthesis in the body. This includes the synthetic processes of fatty acids and subsequent triglycerides in the liver and the adipose tissue. Lipogenesis is regulated by numerous factors, including nutritional, hormonal, and genetic elements. Nonalcoholic Fatty Liver Disease
    • ↑ Protein synthesis Synthesis Polymerase Chain Reaction (PCR)
    • Glycogenolysis Glycogenolysis The release of glucose from glycogen by glycogen phosphorylase (phosphorolysis). The released glucose-1-phosphate is then converted to glucose-6-phosphate by phosphoglucomutase before entering glycolysis. Glycogenolysis is stimulated by glucagon or epinephrine via the activation of phosphorylase kinase. Glycogen Metabolism and gluconeogenesis Gluconeogenesis Gluconeogenesis is the process of making glucose from noncarbohydrate precursors. This metabolic pathway is more than just a reversal of glycolysis. Gluconeogenesis provides the body with glucose not obtained from food, such as during a fasting period. The production of glucose is critical for organs and cells that cannot use fat for fuel. Gluconeogenesis
    • ↓ Conversion of fatty and amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance to ketones Ketones Organic compounds containing a carbonyl group =C=O bonded to two hydrocarbon groups. Basics of Carbohydrates
  • In muscle:
    • Glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis
    • ↑ Protein synthesis Synthesis Polymerase Chain Reaction (PCR)
    • Lipogenesis Lipogenesis De novo fat synthesis in the body. This includes the synthetic processes of fatty acids and subsequent triglycerides in the liver and the adipose tissue. Lipogenesis is regulated by numerous factors, including nutritional, hormonal, and genetic elements. Nonalcoholic Fatty Liver Disease
    • ↑ Glycogen synthesis Synthesis Polymerase Chain Reaction (PCR)
  • In adipose tissue Adipose tissue Adipose tissue is a specialized type of connective tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or “brite” adipose tissue, which is a transitional form. Adipose Tissue: Histology:
    • ↑ Triglyceride storage
    • Lipolysis Lipolysis The metabolic process of breaking down lipids to release free fatty acids, the major oxidative fuel for the body. Lipolysis may involve dietary lipids in the digestive tract, circulating lipids in the blood, and stored lipids in the adipose tissue or the liver. A number of enzymes are involved in such lipid hydrolysis, such as lipase and lipoprotein lipase from various tissues. Nonalcoholic Fatty Liver Disease
  • On blood levels:
    • Glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance
    • Fatty acids Fatty acids Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated. Fatty Acids and Lipids
    • ↓ Keto acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance
    • ↓ Amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance

Pharmacokinetics

Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption

  • Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption and onset of action depend on:
    • Mode of administration
    • Site of administration
  • Fastest to slowest: 
    • IV > IM > SC
    • Abdomen > arms > buttocks > thigh Thigh The thigh is the region of the lower limb found between the hip and the knee joint. There is a single bone in the thigh called the femur, which is surrounded by large muscles grouped into 3 fascial compartments. Thigh: Anatomy
  • Other factors that may have an effect:
    • Exercise
    • Temperature
    • Local blood supply

Excretion

  • Insulin is cleared through the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy.
  • Dosing may need to be adjusted in individuals with renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome.

Classification

Insulin types can be classified based on their pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics:

  • Fast acting: 
    • Absorbed quickly
    • Quick peak effect
    • Examples:
      • Lispro
      • Aspart
      • Glulisine
  • Short acting: 
    • Still absorbed rapidly
    • Slightly longer peak effect
    • Example: regular
  • Intermediate acting: 
    • Absorbed more slowly
    • Lasts longer
    • Example: neutral protamine Hagedorn ( NPH NPH Normal pressure hydrocephalus (NPH) is a neurodegenerative disorder characterized by the triad of gait abnormalities, dementia, and urinary urgency or incontinence. Normal pressure hydrocephalus can be either idiopathic or secondary to intraventricular or subarachnoid hemorrhage. Normal Pressure Hydrocephalus)
  • Long acting:
    • Absorbed slowly
    • Minimal peak effect (provides a stable plateau Plateau Cardiac Physiology effect)
    • Lasts most of the day
    • Examples: 
      • Detemir
      • Glargine
      • Degludec
A comparison of the onset, peak effect, and duration of different insulin subtypes

A comparison of the onset, peak effect, and duration of different insulin subtypes

Image: “Insulin is categorized by how fast it works in the body, how soon it peaks and then how long it lasts. Notice how rapid acting insulins have a rapid rise and fall while longer acting insulin builds more slowly to a stable baseline before declining.” by A. Peters, M. Komorniczak. License: CC BY 3.0

Indications

Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus

Subcutaneous insulin:

  • Type 1 Type 1 Spinal Muscular Atrophy diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus:
    • Individuals with type 1 Type 1 Spinal Muscular Atrophy diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus require insulin replacement at all times.
    • Multiple daily injections can be used to simulate physiologic insulin release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology:
      • Basal (long-acting) insulin is given once or twice daily.
      • Boluses of rapid-acting insulin are given with meals.
    • A continuous insulin infusion (via insulin pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols) with meal-time boluses is also an option.
  • Type 2 Type 2 Spinal Muscular Atrophy diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus:
    • Added when oral therapy has failed to provide adequate glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance control
    • Usually used in addition to other oral antidiabetic medications (e.g., metformin Metformin A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. Non-insulinotropic Diabetes Drugs)
    • Indicated for initial therapy when severe hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus is noted upon diagnosis
  • Gestational diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus: preferred therapy for uncontrolled hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus despite diet and activity modifications

IV insulin:

  • Diabetic ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis ( DKA DKA Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus. Diabetic ketoacidosis is characterized by hyperglycemia and ketoacidosis due to an absolute insulin deficiency. Hyperglycemic Crises)
  • Hyperosmolar hyperglycemic state Hyperosmolar hyperglycemic state A serious complication of type 2 diabetes mellitus. It is characterized by extreme hyperglycemia; dehydration; serum hyperosmolarity; and depressed consciousness leading to coma in the absence of ketosis and acidosis. Hyperglycemic Crises
Glycemic excursions and insulin action

Glycemic excursions and insulin action:
This graph depicts the use of basal and bolus (meal-time) insulin to cover variations in blood glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance levels throughout the day.

Image by Lecturio.

Other indications

Besides diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus, IV insulin can be used in several other conditions (often in conjunction with dextrose Dextrose Intravenous Fluids to maintain euglycemia).

  • Hyperkalemia Hyperkalemia Hyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs. Hyperkalemia:
    • Shifts K into cells
    • Temporary treatment used to acutely ↓ K levels
  • Hypertriglyceridemia-induced acute pancreatitis Acute pancreatitis Acute pancreatitis is an inflammatory disease of the pancreas due to autodigestion. Common etiologies include gallstones and excessive alcohol use. Patients typically present with epigastric pain radiating to the back. Acute Pancreatitis:
    • ↓ Fatty acid release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology from adipocytes Adipocytes Cells in the body that store fats, usually in the form of triglycerides. White adipocytes are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. Brown adipocytes are thermogenic cells that can be found in newborns of some species and hibernating mammals. Adipose Tissue: Histology
    • ↑ Triglyceride storage
    • ↓ Triglyceride levels
  • Beta-blocker and calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blocker (CCB) toxicity Toxicity Dosage Calculation:
    • Indicated in hemodynamically unstable individuals refractory to other treatments
    • ↑ Inotropy in myocytes Myocytes Mature contractile cells, commonly known as myocytes, that form one of three kinds of muscle. The three types of muscle cells are skeletal, cardiac, and smooth. They are derived from embryonic (precursor) muscle cells called myoblasts. Muscle Tissue: Histology (affected by CCB toxicity Toxicity Dosage Calculation) by ↑ glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance uptake needed for aerobic metabolism
    • Overcomes insulin deficiency caused by beta-blocker’s effect on the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy

Adverse Effects and Contraindications

Adverse effects

  • Hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia
    • Confusion
    • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
    • Palpitations Palpitations Ebstein’s Anomaly
    • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
    • Diaphoresis
  • Weight gain after initiation
  • Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • Anaphylaxis Anaphylaxis An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. Type I Hypersensitivity Reaction
  • Injection site:
    • Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion
    • Swelling Swelling Inflammation
    • Lipoatrophy

Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation

  • Hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia (insulin drives K+ into cells)
  • Hypersensitivity
  • Hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia

Precautions

Dosing adjustments and close monitoring may be necessary for individuals with:

  • Hepatic impairment
  • Renal impairment

Drug interactions

  • ↑ Hypoglycemic effect with:
    • Other antidiabetic agents
    • Alcohol
    • Androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens
    • Beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers)
    • Direct-acting antiviral Antiviral Antivirals for Hepatitis B agents for hepatitis C Hepatitis C Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C virus can cause both acute and chronic hepatitis, ranging from a mild to a serious, lifelong illness including liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis C Virus
    • Monoamine oxidase inhibitors Monoamine oxidase inhibitors Monoamine oxidase inhibitors are a class of antidepressants that inhibit the activity of monoamine oxidase (MAO), thereby increasing the amount of monoamine neurotransmitters (particularly serotonin, norepinephrine, and dopamine). The increase of these neurotransmitters can help in alleviating the symptoms of depression. Monoamine Oxidase Inhibitors ( MAOIs MAOIs Monoamine oxidase inhibitors are a class of antidepressants that inhibit the activity of monoamine oxidase (MAO), thereby increasing the amount of monoamine neurotransmitters (particularly serotonin, norepinephrine, and dopamine). The increase of these neurotransmitters can help in alleviating the symptoms of depression. Monoamine Oxidase Inhibitors)
    • Salicylates
    • Sulfa antibiotics
  • ↑ Insulin dosing may be needed with:
    • Corticosteroids Corticosteroids Chorioretinitis
    • Estrogens/oral contraceptives
    • Thiazide diuretics Thiazide diuretics Thiazide and thiazide-like diuretics make up a group of highly important antihypertensive agents, with some drugs being 1st-line agents. The class includes hydrochlorothiazide, chlorothiazide, chlorthalidone, indapamide, and metolazone. Thiazide Diuretics
    • Antipsychotics
    • Niacin Niacin A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and NADP. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs

Comparison of Insulins

Table: Different types of available insulins
Insulin effect Type of Insulin Classification Onset of action Peak of action Duration of action
Fast acting Lispro Analog 15–30 minutes 1–3 hours 4–6 hours
Aspart
Glulisine
Short acting Regular Human 30 minutes 1.5–3.5 hours 8 hours
Intermediate acting NPH NPH Normal pressure hydrocephalus (NPH) is a neurodegenerative disorder characterized by the triad of gait abnormalities, dementia, and urinary urgency or incontinence. Normal pressure hydrocephalus can be either idiopathic or secondary to intraventricular or subarachnoid hemorrhage. Normal Pressure Hydrocephalus Human 1–2 hours 4–6 hours > 12 hours
Long acting Detemir Analog 1–2 hours 3–9 hours 14–24 hours
Glargine 3–4 hours No peak Approximately 24 hours
Degludec Approximately 1 hour No peak > 40 hours
Note: The pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics are based on SC administration.
NHP: neutral protamine Hagedorn

References

  1. Donner, T. (2019). Insulin: Pharmacology, therapeutic regimens, and principles of intensive insulin therapy. Endotext. NCBI Bookshelf. NCBI. Retrieved August 22, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK278938/
  2. Weinstock, R. S. (n.d.). General principles of insulin therapy in diabetes mellitus. Uptodate. Retrieved August 2, 2021, from https://www.uptodate.com/contents/general-principles-of-insulin-therapy-in-diabetes-mellitus
  3. Durnwald, C. (n.d.). Gestation diabetes mellitus: Glycemic control and maternal prognosis. Uptodate. Retrieved August 2, 2021, from https://www.uptodate.com/contents/gestational-diabetes-mellitus-glycemic-control-and-maternal-prognosis
  4. Insulin Regular Drug Information (n.d.). Uptodate. Retrieved August 3, 2021, from https://www.uptodate.com/contents/insulin-regular-drug-information
  5. Insulin glargine (n.d.). Medscape. Retrieved July 28, 2021, from https://reference.medscape.com/drug/lantus-toujeo-insulin-glargine-999003#4
  6. Types of Insulin (n.d.). UCSF Diabetes Education Online. Retrieved August 2, 2021, from https://dtc.ucsf.edu/types-of-diabetes/type2/treatment-of-type-2-diabetes/medications-and-therapies/type-2-insulin-rx/types-of-insulin/#intacting
  7. American Diabetes Association (2020). Management of diabetes in pregnancy. Standards of Medical Care in Diabetes. 43(1): S183–S192. Retrieved August 22, 2021, from https://care.diabetesjournals.org/content/43/Supplement_1/S183
  8. Brutsaert, E. F. (2020). Drug treatment of diabetes mellitus. MSD Manual Professional Version. Retrieved August 22, 2021, from https://www.msdmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/drug-treatment-of-diabetes-mellitus
  9. Nolte Kennedy, M. S. (2012). Pancreatic hormones and antidiabetic drugs. In Katzung, B. G., Masters, S. B., & Trevor, A. J. (Eds.), Basic & Clinical Pharmacology (12th ed., pp. 743–765). Retrieved August 22, 2021, from https://pharmacomedicale.org/images/cnpm/CNPM_2016/katzung-pharmacology.pdf

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