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• Diabetes mellitus


  Not a single disease, but a heterogeneous group of syndromes characterized by an elevation of blood glucose caused by a relative or absolute deficiency of insulin
• Clinical classifications of diabetes


  • Type 1 diabetes
  • Type 2 diabetes
  • Gestational diabetes
  • Diabetes due to other causes
• Gestational diabetes


  Carbohydrate intolerance with onset or first recognition during pregnancy
• Gestational diabetes


  • Uncontrolled gestational diabetes can lead to fetal macrosomia and shoulder dystocia, as well as neonatal hypoglycemia
  • Diet, exercise, and/or insulin administration are effective in this condition
  • Glyburide and metformin may be reasonably safe alternatives to insulin therapy
• Type 1 diabetes


  Absolute deficiency of insulin caused by massive β-cell necrosis, usually ascribed to autoimmune-mediated processes directed against the β cell
• Type 1 diabetes


  • Requires exogenous insulin to avoid the catabolic state that results from and is characterized by hyperglycemia and life-threatening ketoacidosis
  • Cannot maintain a basal secretion level of insulin nor respond to variations in circulating fuels
• Hemoglobin A1c (HbA1c)


  Measure of how well treatment has normalized blood glucose in diabetic patients over the previous 3 months
• Goal of insulin administration in type 1 diabetes


  • Maintain blood glucose concentrations as close to normal as possible and avoid wide swings in glucose levels that may contribute to long-term complications
• Continuous subcutaneous insulin infusion (insulin pump)


  Method of insulin delivery that may be more convenient for some patients, eliminating the multiple daily injections of insulin
• Amylin


  Hormone that is cosecreted with insulin from pancreatic β cells following food intake
• Pramlintide


  Synthetic analog of amylin, may be used as an adjunct to insulin therapy
• Type 2 diabetes


  Influenced by genetic factors, aging, obesity, and peripheral insulin resistance, rather than by autoimmune processes or viruses
• Type 2 diabetes


  • Pancreas retains some β-cell function, but variable insulin secretion is insufficient to maintain glucose homeostasis
  • Often accompanied by the lack of sensitivity of target organs to either endogenous or exogenous insulin
• Insulin


  Polypeptide hormone consisting of two peptide chains that are connected by disulfide bonds, synthesized as a precursor (proinsulin) that undergoes proteolytic cleavage
• Insulin secretion


  • Regulated not only by blood glucose levels but also by certain amino acids, other hormones, and autonomic mediators
  • Most commonly triggered by high blood glucose, which is taken up by the glucose transporter into the β cells of the pancreas
• Human insulin


  Produced by recombinant DNA technology using special strains of Escherichia coli or yeast that have been genetically altered to contain the gene for human insulin
• Insulin lispro, insulin aspart, insulin glulisine


  Insulins with faster onset and shorter duration of action than regular insulin, because they do not aggregate or form complexes
• Insulin glargine, insulin detemir


  Long-acting insulins that show prolonged, flat levels of the hormone following injection
• Insulin-degrading enzyme (insulin protease)


  Enzyme that inactivates insulin, found mainly in the liver and kidney
• Rapid-acting and short-acting insulin preparations


  • Regular insulin
  • Insulin lispro
  • Insulin aspart
  • Insulin glulisine
• Regular insulin, insulin lispro, insulin aspart, insulin glulisine


  • Rapid-acting insulins that offer more flexible treatment regimens and may lower the risk of hypoglycemia
• Insulin lispro


  Differs from regular insulin in that lysine and proline at positions 28 and 29 in the B chain are reversed, resulting in more rapid absorption after subcutaneous injection
• Insulin aspart, insulin glulisine


  Have pharmacokinetic and pharmacodynamic properties similar to those of insulin lispro, administered to mimic the prandial (mealtime) release of insulin
• Diabetes mellitus
• At positions 28 and 29 in the B chain are reversed. This results in more rapid absorption after subcutaneous injection than is seen with regular insulin. Consequently, insulin lispro acts more rapidly. Peak levels of insulin lispro are seen at 30 to 90 minutes after injection, as compared with 50 to 120 minutes for regular insulin. Insulin lispro also has a shorter duration of activity. Insulin aspart and insulin glulisine have pharmacokinetic and pharmacodynamic properties similar to those of insulin lispro. They are administered to mimic the prandial (mealtime) release of insulin, and they are usually not used alone but with a longer-acting insulin to ensure proper glucose control. Like regular insulin, they are administered subcutaneously. Insulin lispro is usually administered 15 minutes prior to a meal or immediately following a meal, whereas glulisine can be taken either 15 minutes before a meal or within 20 minutes after starting a meal. Insulin aspart should be administered just prior to the meal or up to 15 minutes following the meal. All of the rapid-acting formulations are suitable for IV administration, although regular insulin is most commonly used when the IV route is needed. Insulin lispro, insulin aspart, and insulin glulisine may also be used in external insulin pumps.
• Neutral protamine Hagedorn (NPH) insulin


  A suspension of crystalline zinc insulin combined at neutral pH with the positively charged polypeptide protamine