insulin

• Diabetes mellitus


  A chronic metabolic disorder characterised by a high blood glucose concentration-hyperglycaemia (fasting plasma glucose >7.0 mmol/L, or plasma glucose >11.1 mmol/L, 2 h after a meal) -caused by a deficiency of insulin production or effectiveness

  
• Diabetes must be accompanied by hyperglycemia, but hyperglycemia is not necessarily diabetes
• Type 1 diabetes


  Insulin-dependent and is caused by a loss or decrease in insulin production. It is an absolute lack of insulin, caused by autoimmune damage to the pancreatic B cells. The pathogenesis of type 1 diabetes is closely related to genetic factors

  
• Type 2 diabetes


  Non-insulin-dependent and accompanied by insulin resistance closely related to obesity. It is a relative lack of insulin, mainly due to impairment of insulin secretion and function. The pathogenesis of type 2 diabetes is closely related to environmental factors, such as age, lifestyle, and overnutrition

  
• Other forms of diabetes


  • Syndromes associated with autoantibodies directed against insulin receptors which cause severe insulin resistance
  • Functional A-cell tumours
  • 'Glucagonomas'
  • Hyperglycaemia can also be a clinically important adverse effect of several drugs, including glucocorticoids, high doses of thiazide diuretics and several of the protease inhibitors used to treat HIV infection

  
• After continuous glucose infusion, insulin secretion in normal human body can be divided into two stages (1st phase and 2nd phase). However, there was no significant change in insulin secretion in type 1 diabetes. In type 2 diabetes, there is a stage 1 loss of insulin production

  
• Insulin preparations


  • Ultra short acting insulin (analogue)
  • Short-acting insulin
  • Mid-acting insulin
  • Long-acting insulin
  • Ultra long acting insulin (analogue)
  • Premixed insulin (analogue)
  • Compound preparation

  
• Oral hypoglycemic agents


  • Biguanides: metformin, phenformin, etc
  • Sulfonylureas: tolbutamide, glibenclamide, etc
  • Other drugs: thiazolidinediones (rosiglitazone, etc); acarbose, etc
• Insulin


  • Acts mainly on the liver, fat and muscle tissue
  • Promotes glucose uptake, glycogen synthesis and glycolysis, and inhibits gluconeogenesis and glycogenolysis
  • Promotes the synthesis of fatty acids and triglycerides, and inhibits lipolysis
  • Promotes amino acid uptake and protein synthesis, and inhibits protein degradation

  
• Insulin secretion


  1. Amino acids, glucose and fatty acids in food stimulate B cells to secrete insulin

  2. Glucagon, secreted by the islet A cells, promotes insulin release, but it raises blood glucose levels

  3. Somatostatin, secreted by the D cells of the islets, inhibits release of insulin and of glucagon

  4. Amylin is stored with insulin in secretory granules in B cells and is co-secreted with insulin, inhibiting insulin secretion

  5. Incretins (GLP-1 and GIP) are secreted by the small intestine and promote insulin production

  
• Insulin is essential for the treatment of type 1 diabetes and a valuable component of the treatment of many patients with type 2 disease

  
• Type 1 diabetes must be treated with insulin

  
• Commonly used insulin preparations


  • Ultra short acting insulin (analogue)
  • Short-acting insulin
  • Mid-acting insulin
  • Long-acting insulin
  • Ultra long acting insulin (analogue)
  • Premixed insulin (analogue)
  • Compound preparation

  
• Ultra short acting insulin (analogue)

  • Insulin lispro
  • Insulin glulisine
  • Insulin aspart

  
• Mid-acting insulin


  • Isophane insulin
  • Insulin zinc supension
  • Protamine zinc insulin

  
• Long-acting insulin


  Extra slow insulin zinc suspension
• Ultra long acting insulin (analogue)

  • Insulin detemir
  • Glargine insulin
  • Insulin degludec

  
• Premixed insulin (analogue)


  • Biphasic hypoprotamine zinc
  • Biphasic insulin glulisine
  • Biphasic insulin aspart

  
• Compound preparation


  • Insulin Degludec and Insulin Aspart Injection
  • Liraglutide Injection
  • Insulin Glargine and Lixisenatide Injection
• Patients with type 2 diabetes who require insulin treatment


  • Patients unable to control type 2 diabetes through diet control or oral hypoglycemic drugs
  • Patients with various acute or serious complications, such as ketoacidosis and non ketotic hypertonic coma
  • Patients with severe infections, consumptive diseases, high fever, pregnancy, trauma, and surgery; other patients

  
• Hypoglycaemia


  The main undesirable effect of insulin, which is common and, if very severe, can cause brain damage or sudden cardiac death

  
• Classification of oral hypoglycemic agents


  • Biguanides
  • Sulfonylureas
  • Other drugs (thiazolidinediones, acarbose, etc.)
• Biguanides


  Reduced hepatic glucose production, increased glucose uptake and utilisation in skeletal muscle, reduced carbohydrate absorption from the intestine, increased fatty acid oxidation, reduced circulating low-density and very-low-density lipoprotein

  
• Clinical use of biguanides

  Patients with type 2 diabetes, especially those with obesity; other syndromes with accompanying insulin resistance including polycystic ovary syndrome, non-alcoholic fatty liver disease, gestational diabetes and some forms of premature puberty

  
• Unwanted effects of biguanides


  • Dose-related gastrointestinal disturbances (e.g. anorexia, diarrhoea, nausea), which are usually but not always transient
  • Lactic acidosis (rare but potentially fatal toxic effect)
  • Long-term use may interfere with absorption of vitamin B
• Sulfonylureas


  The principal action is on B cells, stimulating insulin secretion and thus reducing plasma glucose

  
• Clinical use of sulfonylureas


  Used to treat early type 2 diabetes, can be combined with metformin or thiazolidinediones
• Unwanted effects of sulfonylureas


  • Hypoglycaemia
  • Stimulate appetite and often cause weight gain
  • Gastrointestinal upsets, allergic skin rashes, bone marrow toxicity, etc.
• Thiazolidinediones


  Bind to the peroxisome proliferator-activated receptor-y (PPARy) which is complexed with retinoid X receptor (RXR), causing differentiation of adipocytes, increases lipogenesis and enhances uptake of fatty acids and glucose, promotes sodium ion reabsorption in renal collecting ducts
• Mechanism of rosiglitazone


  Enhances insulin sensitivity in skeletal muscle, liver, and adipose tissue, thereby enhancing tissue glucose utilization and thus hypoglycemic effects

  
• α-Glucosidase inhibitors (Acarbose)


  Delay carbohydrate absorption, reducing the postprandial increase in blood glucose

  
• Clinical use of α-Glucosidase inhibitors


  Used in type 2 diabetes inadequately controlled by diet with or without other agents
• Unwanted effects of α-Glucosidase inhibitors


  • Flatulence, loose stools or diarrhoea
• Hyperglycemia is an important pathogenesis and risk factor of metabolic diseases such as diabetes
• The core therapeutic goal of drugs such as insulin preparations, biguanides, bulfonylureas, thiazolidinediones, and acarbose is to reduce blood glucose