Insuline et son action dans le diabète

Introduction to Diabetes Medications

• The goals of diabetes treatment include:

  • Reducing short-term hyperglycemia complications (thirst, frequent urination, weight loss, increased hunger, and diabetic ketoacidosis).
  • Preventing long-term complications (cardiovascular, neurological, eye, kidney, and digestive problems).

• Diabetes treatment is a chronic condition.

• Several classes of antidiabetic medications exist.

• Insulin was discovered approximately 30 years ago.

• Sulfonylureas, biguanides, and newer antidiabetic molecules are other types of medications.

• The role of new antidiabetic molecules in type II diabetes treatment is still under discussion.

Physiology of Diabetes

• Hyperglycemia is always linked to a defect in insulin function:
  • Insufficient insulin secretion.
  • Impaired insulin action (insulin resistance).
  • Abnormal insulin quality.

Type 1 Diabetes (Insulin-Dependent Diabetes)

• Type 1 diabetes (DID) involves genetic predisposition and auto-immune phenomena.
• This condition is also associated with certain viruses.
• Diabetes develops when 80-90% of the beta cells are destroyed.
• Treatment focuses on insulin replacement therapy to mimic normal insulin secretion.

Type 2 Diabetes (Non-Insulin-Dependent Diabetes)

• Type 2 diabetes (DNID) is a multifaceted condition influenced by:
  • Genetic factors
  • Environmental factors
  • Obesity
• Hyperglycemia in type 2 diabetes is a result of:
  • Impaired insulin secretion
  • Reduced insulin effectiveness on target tissues (insulin resistance)
  • Increased hepatic glucose production.

Insulin

• Insulin is the body's only hypoglycemic hormone.
• It's produced by beta cells in the islets of Langerhans in the pancreas.
• Insulin is a polypeptide (molecular weight: 60,000) with two chains (α and β) connected by disulfide bonds.
• Proinsulin, an inactive precursor, is secreted by beta cells and subsequently processed to form active insulin.
• Insulin can be polymerized with zinc and proteins (protamine), extracted from animal pancreases (potential impurities and allergies), or produced using genetic engineering.
• Insulin is broken down by digestive enzymes, hence its requirement for parenteral administration (subcutaneous, intramuscular, or intravenous).

Insulin: Pharmacological Properties

• Insulin affects carbohydrate, fat, and protein metabolism.
  • Carbohydrates: Hypoglycemia by combined hepatic and peripheral action (liver and peripheral cells like muscle and adipose tissues).
  • Fats: Increased endogenous triglyceride synthesis.
  • Proteins: Increased amino acid uptake and protein synthesis.
  • Potassium: Increased potassium uptake into the cells (used to treat hyperkalemia).

Insulin: Pharmacokinetics

• IV administration leads to immediate hypoglycemic effects lasting only a short period (less than one hour).
• Subcutaneous administration has delayed onset (30 minutes), but the duration of action is longer (around 6-8 hours).
• Insulin degradation occurs primarily in the liver (40%) and kidneys, with increased hypoglycemic effects in cases of liver or kidney impairment.
• Certain factors like pregnancy (placental destruction), and medications like aspirin, MAOIs, and beta-blockers can impact insulin pharmacokinetics, reducing or changing its action.
• Alcohol can reduce glycogenolysis and affect insulin clearance.

Insulin: Forms and Types

• Insulin is categorized by its duration of action: rapid-acting, intermediate-acting (or semi-long-acting), and long-acting.
• Different forms arise from differing purification levels. Traditional forms (bovine or porcine) are less pure than newer forms (human or more highly purified animal forms). More recently, insulins identical to human insulin are available, made by either semisynthesis or genetic engineering.

Insulin: Side Effects

• Hypoglycemia : linked to poor blood sugar control (risk of severe hypoglycemia).
• Hypokalemia:
• Lipodystrophy : abnormal fat tissue deposits at injection sites.
• Allergic reactions (less common for human-identical insulins).
• Insulin therapy needs careful consideration.

Insulin: Indications

• Absolute insulin deficiency (Type 1 diabetes) .
• Pregnancy.
• Certain situations in type 2 diabetes, like infections, surgery, or retinopathy or neuropathy complications.

Sulfonylureas (SH)

• Chemicals: specific types (e.g. glibenclamide, carbutamide).
• Mechanism of action: stimulate the release of endogenous insulin from beta cells.
• Effects: increase in appetite
• Pharmacokinetics: Oral absorption, hepatic metabolism, renal elimination. They bind to plasma proteins.
• Side effects: Risk of hypoglycemia, specific side effects (e.g., pruritus, urticaria, jaundice, agranulocytosis, Lyell syndrome) in some cases. Can be teratogenic.
• Contraindications: include cases with insulin-dependent diabetes, diabetic ketoacidosis, pregnancy, and renal failure.

Biguanides

• Biguanides are often used in diabetes.
• Example: Metformin (Glucophage).
• Metformin is a strong base, leading to gastrointestinal issues.
• Mechanism of action: It does not influence insulin secretion but instead primarily affects hepatic glucose production (inhibiting glycogenolysis and gluconeogenesis) and intestinal glucose absorption. It often increases glucose uptake in peripheral tissues.
• Pharmacokinetics: Oral absorption (slow), minimal plasma protein binding, and predominantly renal elimination.
• Side effects: nausea, vomiting, diarrhea, and lactic acidosis (especially in patients with compromised kidney function or other risk factors).
• Contraindications: Those with renal impairment, alcoholism, pregnancy, or conditions that increase the risk of lactic acidosis (such as fasting, ketoacidosis, or hypoxia). Usage should be stopped around surgery with contrast agents for 3 days.

Testez vos connaissances sur les différents types d'insulines, leur durée d'action et leurs mécanismes liés au diabète. Ce quiz couvre également les effets indésirables de certains médicaments et des indications pour l'utilisation de l'insuline. Prêt à relever le défi ?