Diabetes Mellitus: Definition and Pathogenesis

Study Notes

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.