Diabetes Mellitus: Definition and Pathogenesis

Diabetes Mellitus

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

Pathogenesis

• Type 1 diabetes is associated with an increased risk of other autoimmune diseases, including thyroid disease, celiac disease, and pernicious anemia.
• 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: family history of type 2 diabetes, 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 less adverse outcomes.
• Patient education should cover the disease, clinical manifestations of hypo/hyperglycemia, complications, medical treatment, insulin types, and injection techniques.
• Dietary recommendations should be provided, and SMBG should be performed for better optimization of BG.

Antidiabetic Drugs

• Metformin:
  • Considered the backbone of diabetes treatment, prescribed to every patient unless contraindicated or non-tolerated.
  • Forms: immediate release or extended-release.
  • Dose: starting dose 500 mg with main meals, optimal dose 1000 mg twice daily, maximum dose 2550 mg.
  • Practical issues: start with small doses and increase gradually to avoid GIT upset.
• Sulphonylurea:
  • Classified into 3 generations: glibenclamide (1st generation), gliclazide (2nd generation), and glimepiride (late 2nd generation).
  • Glibenclamide: should not be used during Ramadan fasting, in elderly patients above 60 years, or in stage 3 chronic kidney disease.
  • Gliclazide: can be used in patients with renal impairment without dose adjustment, but not preferred in patients with impaired liver functions.
  • Glimepiride: use with caution in patients with EGFR < 60 ml/min, and contraindicated in EGFR < 30 ml/min.
• Thiazolidinediones (TZDs):
  • One of the most potent insulin sensitizers, acting on PPAR gamma receptors in liver and adipose tissue.
  • Can be used in treatment of fatty liver and polycystic ovary.
  • Examples: Actos, Actozone, Diabetonorm.
• DPP-4 Inhibitors:
  • Leaders in management of type 2 diabetes.
  • Control blood glucose in a glucose-dependent manner with less incidence of hypoglycemia and weight neutral effect.
  • Examples: Sitagliptin, Vildagliptin, Linagliptin, Saxagliptin, Alogliptin.
• SGLT2 Inhibitors:
  • One of the promising groups in treatment of type 2 diabetes.
  • Act by inhibiting 90% of glucose reabsorption in the proximal convoluted tubule.
  • Examples: Dapagliflozin, Empagliflozin.
• GLP-1 Receptor Agonists:
  • One of the promising drugs in diabetes.
  • Control blood glucose in a glucose-dependent manner with less incidence of hypoglycemia and decreases satiety, resulting in weight loss.
  • Examples: Liraglutide, Dulaglutide, Semaglutide.

Insulin Therapy

• Indications:
  • Type 1 patients (IDDM).
  • Uncontrolled type 2 patients on two or more oral drugs at maximum dose, with HbA1c > 8.5%.
  • Recently diagnosed type 2 patients with HbA1c > 10% and blood glucose > 300 mg, especially with catabolic state or associated increased triglycerides level.
  • Hospital admission.
• Insulin types:
  • Premixed insulin.
  • Basal-bolus regimen (MDI).
• Starting insulin dose: 0.5 units/kg/day, divided into two-thirds as morning dose and one-third as night dose.
• Adjustment: starting dose can be increased to 0.7-1 unit/kg/day in prepubertal and adolescent patients.