Diabetes Mellitus

• Diabetes mellitus


  The most common of the endocrine disorders
• Hyperglycemia


  Clinical manifestation of diabetes mellitus
• Types of diabetes mellitus

  • Type 1 DM
  • Type 2 DM
• Type 1 DM


  Caused by an absolute deficiency of insulin
• Type 2 DM


  Defined by the presence of insulin resistance and β-cell dysfunction
• 1. cells


  • Destroyed in Type 1 DM
• Type 2 DM


  • Characterized by a combination of some degree of insulin resistance with a relative lack of insulin secretion that is insufficient to normalize plasma glucose levels, with a progressive loss of β-cell over time
• Abdominal obesity


  • Most individuals with type 2 diabetes exhibit this, which is the major contributor to insulin resistance
• Gestational diabetes mellitus


  Glucose intolerance which is first recognized during pregnancy
• Maturity onset diabetes of youth (MODY)

  Characterized by impaired insulin secretion in respond to a glucose stimulus with minimal or no insulin resistance. Patients typically exhibit mild hyperglycemia at an early age, but diagnosis may be delayed.
• Type A insulin resistance


  A clinical syndrome characterized by acanthosis nigricans, virilization in women, polycystic ovaries, and hyperinsulinemia. Antiinsulin receptor antibodies may block the binding of insulin.
• Type A insulin resistance was referred to in the past as type B insulin resistance
• Islets of Langerhans


  • Form the endocrine component of the pancreas, constituting 1% of the total pancreatic mass.
• β-cells


  Insulin is synthesized by these pancreatic cells
• Preproinsulin and Proinsulin


  Precursors of insulin
• Glucose


  The major stimulant to insulin release
• Insulin


  Lowers blood glucose by a variety of mechanisms, including stimulation of tissue glucose uptake, suppression of glucose production by the liver, and suppression of free fatty acid (FFA) release from fat cells.
• Amylin


  A hormone that is cosecreted from the pancreatic β-cell with insulin, which suppresses inappropriate glucagon secretion, slows gastric emptying, and causes central satiety.
• Honeymoon phase


  The phase that after the initial diagnosis of type 1DM, there is occasionally a period of transient remission called this phase before β-cell destruction requires lifelong insulin therapy.
• Amylin is also deficient in patients with Type 1 DM secondary to the destruction of β cells.
• Causes of Type 2 diabetes

  • Impaired insulin secretion
  • Insulin resistance (involving muscle, liver, and adipocytes)
  • Deficiency and resistance to incretin hormones
  • Excess glucagon secretion
  • Sodium-glucose cotransporter upregulation in the kidney
• Impaired insulin secretion


  A hallmark finding in type 2 DM.
• The incretin effect


  The increased insulin secretion in response to an oral glucose stimulus is referred to as this and is the result of gut hormones, stimulated by oral intake of nutrients (glucose, fat, or protein), that promote pancreatic insulin secretion.
• Peripheral skeletal muscle


  The major site of postprandial glucose disposal and approximately 80% of total body glucose uptake occurs in skeletal muscle.
• Hyperglucagonemia


  Excess glucagon secretion
• Metabolic syndrome


  A constellation of metabolic abnormalities that includes insulin resistance and confers a higher risk for cardiovascular disease (CVD).
• Most common initial symptoms of DM1

  • Polyuria
  • Polydipsia
  • Polyphagia
  • Weight loss
  • Lethargy accompanied by hyperglycemia
• Most common initial symptoms of DM2

  • Lethargy
  • Polyuria
  • Nocturia
  • Polydipsia
• Criteria for diagnosis of DM

  • A1C of 6.5% or more
  • Fasting (no caloric intake for at least 8 hours) plasma glucose of 126 mg/dL (7.0 mmol/L) or more
  • Two-hour plasma glucose of 200 mg/dL (11.1 mmol/L) or more during an oral glucose tolerance test (OGTT) using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water
  • Random plasma glucose concentration of 200 mg/dL (11.1 mmol/L) or more with classic symptoms of hyperglycemia or hyperglycemic crisis
• Glucose levels


  • Normal fasting plasma glucose (FPG) is less than 100 mg/dL (5.6 mmol/L)
  • Impaired fasting glucose (IFG) is FPG 100 to 125 mg/dL (5.6–6.9 mmol/L)
  • Impaired glucose tolerance (IGT) is diagnosed when the 2-hour postload sample of OGTT is 140 to 199 mg per dL (7.8–11.0 mmol/L)
• Regular insulin


  Has a relatively slow onset of action when given subcutaneously (SC), requiring injection 30 minutes prior to meals to achieve optimal postprandial glucose control and prevent delayed postmeal hypoglycemia.
• Lispro, aspart, and glulisine insulins


  Analogs that are more rapidly absorbed, peak faster, and have shorter durations of action than regular insulin. This permits more convenient dosing within 10 minutes of meals (rather than 30 min prior), produces better efficacy in lowering postprandial blood glucose than regular insulin in type 1 DM, and minimizes delayed postmeal hypoglycemia.
• Neutral protamine Hagedorn (NPH)


  Intermediate-acting. Variability in absorption, inconsistent preparation by the patient, and inherent pharmacokinetic differences may contribute to a labile glucose response, nocturnal hypoglycemia, and fasting hyperglycemia.
• Glargine and detemir


  Long-acting "peakless" human insulin analogs that result in less nocturnal hypoglycemia than NPH insulin when given at bedtime.