Diabetes Mellitus Overview

Diabetes Mellitus: Overview

• Definition: A group of metabolic diseases characterized by chronic hyperglycemia.
• Epidemiology: Worldwide prevalence has dramatically increased in the past two decades, with an estimated 650 million cases projected by 2030. This rise is attributed to increased obesity, lack of physical activity, and more widespread diabetes testing (50% of diabetic patients are currently undiagnosed).

Causes of Diabetes

• Insulin Deficiency: Reduced insulin production/secretion.
  • Absolute: Complete destruction of pancreatic beta cells.
  • Relative: Insufficient secretion unable to compensate for increased insulin requirements due to insulin resistance.
• Insulin Resistance: Impaired insulin function.
  • Normal insulin levels cause insufficient biological responses.
  • Can affect pre-receptor, receptor, and post-receptor stages.

Normal Insulin Physiology

• Secretion: Insulin synthesized in beta cells; proinsulin cleavage produces C-peptide and insulin.
• Mechanism of Action: Lowers blood glucose, promotes protein synthesis and lipogenesis, and increases intracellular potassium accumulation.

Types of Diabetes

• 1. Type 1 Diabetes (Insulin-Dependent DM):*

• Cause: Autoimmune destruction of beta cells.

• Characteristics: Absolute insulin deficiency after approximately 90% of beta cells are destroyed. Typically diagnosed in childhood (<20 years old; with peaks at 4-6 and 10-14 years), often with sudden onset.

• Pathophysiology: Genetic predisposition and environmental triggers lead to an autoimmune response, progressive beta-cell destruction, and absolute insulin deficiency, resulting in reduced glucose uptake by tissues.

• Subdivision:

  • Autoimmune: Presence of antibodies against islet cell antigens (ICA), glutamic acid decarboxylase (GAD), tyrosine phosphatase (IA-2), and insulin (IAA).
  • Idiopathic: No detectable antibodies.
  • Latent Autoimmune Diabetes in Adults (LADA): A type 1-like disease with a later onset and milder course.

• 2. Type 2 Diabetes (Insulin-Independent DM):*

• Cause: Hereditary and environmental factors, often associated with metabolic syndrome (e.g., obesity).

• Characteristics: Characterized by reduced tissue sensitivity to insulin (insulin resistance) and decreased insulin secretion. Usually diagnosed in adults (age >40) with gradual onset.

• 3. Gestational Diabetes:*

• Definition: Glucose metabolism disorder arising during pregnancy, resolving after childbirth.

• Characteristics: Typical onset in the second and third trimesters.

• Pathophysiology: Hormonal changes trigger insulin resistance.

• Management: Primarily managed with a healthy diet and increased physical activity; insulin therapy may be necessary if lifestyle modifications are insufficient.

• Complications: Risk of preeclampsia, eclampsia, and urinary tract infections (UTIs).

• Resolution: Usually resolves post-pregnancy.

• 4. Other Specific Forms:*

• Maturity-Onset Diabetes of the Young (MODY): A specific form of diabetes related to pancreatic beta cells.

• Pancreatic Disease: Associated with conditions like chronic pancreatitis and cystic fibrosis.

• Drug/Chemical-Induced Diabetes: Examples include glucocorticoids and thiazides.

• 5. Prediabetes:*

• Definition: A state between normal glucose regulation and diabetes.

• Characteristics: Elevated blood glucose levels that are not high enough to classify as diabetes.

• Risk: Significant risk of developing type 2 diabetes without lifestyle changes.

Clinical Presentation

• Symptoms more pronounced in types 1 and 2.
• Some type 2 cases are asymptomatic.
• Common presentations include glycosuria (osmotic polyuria, nocturia, thirst, increased fluid intake), weight loss, fatigue, fluctuating vision, and hyperosmolar hyperglycemic syndrome (reduced glucose use, hyperglycemia, osmotic diuresis, water & electrolyte depletion and hyperosmolality), and increased vulnerability to infections (e.g., UTIs, skin infections).

Diagnosis

• Hyperglycemia Tests:
  • Fasting Plasma Glucose (FPG): Used for initial diagnosis; 7 mmol/L+ without other causes = type 2 diabetes. Prediabetes: 5.6-6.9 mmol/L.
  • Oral Glucose Tolerance Test (OGTT): Measures fasting and 2-hour post-glucose levels; helpful when FPG unclear.
  • Hemoglobin A1c (HbA1c): Measures average blood glucose over 8-12 weeks; used to monitor existing diabetes.
• Other Diagnostic Methods:
  • C-peptide: High levels suggest insulin resistance (type 2); low levels suggest absolute insulin deficiency (type 1).
  • Urinalysis: Looks for glycosuria, ketones, and microalbuminuria.
  • Specific Antibodies: Tests for antibodies associated with autoimmune type 1 diabetes.
• Type Classification: Confirm diagnosis, identify the type of diabetes and any potential complications.