Diabetes Mellitus Pathogenesis

Diabetes Mellitus

• Diabetes mellitus is a metabolic disorder with multiple etiologies, characterized by chronic hyperglycemia due to defects in insulin action or insulin secretion.

Pathogenesis

• People with type 1 diabetes are at increased risk for other autoimmune diseases, such as thyroid disease, celiac disease, and pernicious anemia (vitamin B12 deficiency).
• Associated conditions include autoimmune hepatitis, primary adrenal insufficiency (Addison disease), dermatomyositis, and myasthenia gravis.

Type 1 Diabetes

• May also occur with other autoimmune diseases in the context of specific genetic disorders or polyglandular autoimmune syndromes.
• Routine screening for thyroid dysfunction is recommended for all patients with type 1 diabetes.
• Screening for celiac disease should be considered in adult patients with suggestive symptoms or signs.

Criteria for Testing for T2DM in Children & Adolescents

• Overweight plus any 2 of the following:
  • Family history of type 2 diabetes in 1st or 2nd degree relatives.
  • Race/ethnicity.
  • Signs of insulin resistance or conditions associated with insulin resistance.
  • Maternal history of diabetes or GDM.
• Age of initiation: 10 years or at onset of puberty.

Strategies of DM Management

• Health education is key for better compliance and fewer adverse outcomes.
• Patient needs to know about:
  • The disease.
  • Alarming clinical manifestations of hypo- or hyperglycemia.
  • Complications of the disease.
  • Medical treatment and types of insulin.
  • How to use insulin correctly and storage/injection instructions.
• Importance of:
  • Fixing times for insulin and meals.
  • Following dietary recommendations.
  • Asking a nutritionist for a diet plan.
  • Performing SMBG for better optimization of blood glucose.

Anti-Diabetic Drugs

• Metformin:
  • Considered the backbone of diabetes treatment.
  • Should be prescribed to every patient unless contraindicated or non-tolerated.
  • Forms: immediate release and extended-release.
  • Dose: starting dose 500 mg with main meals, optimal dose 1000 mg twice daily, maximum dose 2550 mg (up to 3000 mg in some guidelines).
  • Practical issues: start with a small dose and increase gradually to avoid GIT upset.
  • Complications: GIT disturbance, vit B12 malabsorption, and lactic acidosis (extremely rare).
• Sulphonylurea:
  • Take care of risk of hypoglycemia and weight gain.
  • Classified into 3 generations: Gibenclamide, Gliclazide, and Glimepride.
• TZDS (Thiazolidinediones):
  • One of the most potent insulin sensitizers.
  • Act on PPAR gamma receptors in liver and adipose tissue.
  • Can be used in treatment of fatty liver and polycystic ovary.
  • Take care of cardiovascular risk: avoid in heart failure, no renal dose adjustment, and avoid in renal impairment.
• DDP4 (Dipeptidyl Peptidase-4) Inhibitors:
  • Leader group in management of type 2 diabetes.
  • Control blood glucose in a glucose-dependent manner with less incidence of hypoglycemia and weight-neutral effect.
• SGLT2 (Sodium-Glucose Cotransporter 2) Inhibitors:
  • One of the promising groups in treatment of type 2 diabetes.
  • Act by inhibiting 90% of glucose reabsorption in the first segment of the proximal convoluted tubule.
  • Glucosuric and natriuretic effects.
  • Complications: urinary tract infection, mycotic vaginal infection, euglycemic ketoacidosis, and osteoporesis.
• GLP1 (Glucagon-Like Peptide-1) Receptor Agonists:
  • One of the promising drugs in diabetes.
  • Control blood glucose in a glucose-dependent manner with less incidence of hypoglycemia and decrease satiety, leading to weight loss.
  • May be the first line therapy in treatment of diabetic patients with cardiovascular risk factors.

Insulin Therapy

• Indications:
  • Type 1 patients (IDDM).
  • Uncontrolled type 2 patients on two or more oral drugs at maximum dose and HbA1c is still more than 8.5%.
  • Recently diagnosed type 2 patients with HbA1c 10% or more and blood glucose more than 300 mg, especially if there is a catabolic state (weight loss-ketones) or associated increased triglycerides level.
  • At hospital admission.
• Insulin types:
  • Premixed insulin.
  • Basal bolus regimen (MDI).
• Starting dose of insulin: 0.5 unit per kg per day, divided into two-thirds as morning dose and one-third as night dose.
• Example: 7-year-old child recently diagnosed with type 1 DM, weight 20 kg, insulin regimen suggested is basal bolus regimen including rapid-acting analogue and long-acting analogue.