Pathogenesis of Diabetes Mellitus (DM) Types 1 and 2 and Diabetic Ketoacidosis (DKA)

Type 1 Diabetes Mellitus (T1DM)

Pathogenesis: T1DM is an autoimmune disease characterized by the destruction of insulin-producing beta cells in the pancreatic islets. Here’s a breakdown of the process:

1. Genetic Predisposition: Certain genes increase susceptibility to T1DM. These genes don’t directly cause the disease, but create an environment where other factors can trigger an autoimmune response.
2. Environmental Triggers: Viruses, dietary factors, or other environmental exposures might act as triggers.
3. Immune System Activation: The immune system mistakenly attacks and destroys beta cells, leading to insulin deficiency.
4. Hyperglycemia: Without enough insulin, the body cannot take up glucose from the bloodstream, resulting in high blood sugar levels (hyperglycemia).

Type 2 Diabetes Mellitus (T2DM)

Pathogenesis: T2DM is a complex interplay of insulin resistance and impaired insulin secretion. Here’s a breakdown:

1. Insulin Resistance: Cells become resistant to the effects of insulin, leading to difficulty in taking up glucose from the bloodstream.
2. Compensatory Insulin Secretion: Initially, the pancreas tries to compensate by producing more insulin.
3. Insulin Deficiency: Over time, the pancreas may not be able to keep up with the increased demand for insulin, leading to insulin deficiency.
4. Hyperglycemia: Similar to T1DM, insufficient insulin action leads to hyperglycemia.

Factors Contributing to T2DM:

• Genetics: A family history of T2DM increases the risk.
• Lifestyle: Obesity, physical inactivity, unhealthy diet, and smoking contribute to insulin resistance.
• Ethnicity: Certain ethnic groups have a higher risk for T2DM.

Diabetic Ketoacidosis (DKA)

Pathogenesis: DKA is a life-threatening complication that can occur in both T1DM and T2DM, usually due to severe insulin deficiency. Here’s how it develops:

1. Insulin Deficiency: Without enough insulin, the body cannot use glucose for energy and turns to fat breakdown.
2. Fatty Acid Breakdown: This process produces ketone bodies (acetoacetate, beta-hydroxybutyrate, and acetone) as a substitute fuel source.
3. Metabolic Acidosis: Ketone bodies accumulate in the blood, leading to metabolic acidosis (increased blood acidity).
4. Electrolyte Imbalances: Acidosis and breakdown of tissues cause electrolyte imbalances (e.g., potassium loss).
5. Symptoms: Dehydration, nausea, vomiting, coma can occur if DKA isn’t treated promptly.

Key Points:

• T1DM is an autoimmune disease destroying insulin-producing cells.
• T2DM involves insulin resistance and impaired insulin secretion.
• Both T1DM and T2DM can lead to DKA due to severe insulin deficiency.
• DKA is a life-threatening complication requiring immediate medical attention.

Additional Notes:

• While the pathogenesis differs, both T1DM and T2DM lead to chronic hyperglycemia, which can damage various organs over time if not properly managed.