PANCE - Diabetes Mellitus Pathophysiology

Here are key facts for PANCE from the Diabetes Mellitus - Pathophysiology tutorial, as well as points of interest at the end of this document that are not directly addressed in this tutorial but should help you prepare for the boards. See the tutorial notes for further details and relevant links.

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1. Diagnostic criteria: Random plasma glucose level of 200+ mg/dL or a fasting plasma glucose level of 126+ mg/dL. 2. Pathophysiologic impact: Chronic hyperglycemia produces dysfunction and damage of multiple organs, including the heart, kidneys, eyes, and peripheral nervous system. 3. Classic clinical presentation: The "3 P's" - polyuria, polydipsia, and polyphagia. 4. Classification: Type 1, Type 2, Monogenic diabetes (including MODY), Secondary diabetes, and Gestational diabetes. 1. Epidemiology: Accounts for 5-10% of all diabetes mellitus cases. 2. Pathophysiology: Caused by autoimmune destruction of pancreatic beta cells; insulitis often visible in pancreatic tissue samples. 3. Immunologic markers: Islet autoantibodies including those targeting insulin, GAD65, ZnT8, and IA2. 4. Genetic factors: Associated with variations in HLA alleles, particularly class II DR and DQ cell-surface proteins. 5. Management principle: Requires exogenous insulin administration due to absolute insulin deficiency. 1. Epidemiology: Represents 90-95% of all diabetes cases. 2. Pathophysiology: Characterized by peripheral tissue insulin resistance and relative insulin deficiency due to mild beta cell destruction. 3. Histopathology: Amyloid deposits visible in pancreatic tissue. 4. Risk factors: Associated with obesity, central fat distribution, sedentarism, stress, and inflammation. 5. Treatment approach: May include diet and exercise, Metformin, insulin, GLP-1 receptor agonists, or SGLT2-inhibitors. 1. Diabetic Ketoacidosis (DKA):

• Population: More common in under-treated Type 1 diabetes
• Clinical presentation: Nausea and vomiting, fatigue, "fruity" odor, and Kussmal breathing
• Management: Fluids, electrolytes, and insulin to normalize blood glucose

2. Hyperosmolar Hyperglycemic Syndrome (HHS):

• Population: More common in Type 2 diabetes
• Pathophysiology: Occurs when a patient with polyuria has deficient water intake leading to severe dehydration
• Mortality: Has a mortality rate of up to 20% - much higher than diabetic ketoacidosis
• Treatment: Requires saline, insulin, and electrolytes

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1. Hyperglycemia mechanism (the "3 P's"):

• Glycosuria: Hyperglycemia surpasses renal glucose reabsorption threshold
• Polyuria: Glycosuria induces osmotic diuresis
• Polydipsia: Results from depleted water and electrolyte stores
• Polyphagia: Caused by chronic catabolic state despite increased food intake

2. Type 1 Diabetes - Clinical Pearls:

• Environmental triggers: Potential role of viral infections (particularly enterovirus) and diet during infancy and childhood
• Clinical course: Often has progressive reduction in insulin levels as more cells are destroyed
• Diagnostic consideration: No longer referred to as "juvenile diabetes" as some adults diagnosed with Type 2 may be misclassified based on age
• Clinical variant: Idiopathic Type 1 diabetes exists without autoimmune involvement, though very rare

3. Type 2 Diabetes - Clinical Insights:

• Pathophysiologic basis: Loss of Glut-4 receptors in peripheral tissues
• Exercise benefit: Exercise increases Glut-4 receptors in skeletal muscle, improving insulin sensitivity
• Clinical course: Initially may have elevated insulin levels in response to resistance; levels eventually fall
• Presentation pattern: Many patients are asymptomatic with diagnosis occurring after routine blood testing
• Age consideration: Historically adult-onset but increasingly common in children due to obesity and inactivity

1. Vascular disease:

• Pathogenesis: Results from chronic hyperglycemia
• Manifestations: Can lead to heart failure and atherosclerosis (causing myocardial infarction or stroke), kidney damage, visual impairment, and peripheral nerve dysfunction

2. Special population considerations:

• Pediatric impact: Impaired growth in children
• Infection risk: Increased susceptibility due to immune suppression
• Hypoglycemia: Look for dizziness, sweating, palpitations, and tachycardia; treat with glucose

1. Definition: Condition where glucose levels are elevated but not high enough to be classified as diabetes 2. Epidemiology: The CDC reports that 1 in 3 Americans is pre-diabetic 3. Risk assessment: Pre-diabetic patients are at high risk for Type 2 diabetes and cardiovascular complications 4. Management approach: Advise patients to take preventive steps such as increasing physical activity and losing weight

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Below is information not explicitly contained within the tutorial but important for PANCE. 1. Laboratory testing: Role of HbA1c, fasting plasma glucose, oral glucose tolerance test, and urinalysis in diagnosis and monitoring. 2. Physical examination: Important findings and screening for complications during the focused diabetes examination. 3. Risk assessment tools: Validated instruments for identifying patients at risk for diabetes complications. 1. Medication selection: Evidence-based algorithms for initiating and intensifying pharmacologic therapy. 2. Insulin regimens: Types, timing, dosage adjustment, and patient education considerations. 3. Technology integration: Role of continuous glucose monitoring and insulin pumps in modern diabetes management. 1. Acute illness management: Adjusting diabetes medications during intercurrent illness. 2. Perioperative considerations: Guidelines for managing diabetes medications during the perioperative period. 3. Exercise prescription: Specific recommendations for exercise type, duration, and intensity in patients with diabetes. 1. Complication screening protocols: Evidence-based schedules for retinopathy, nephropathy, and neuropathy screening. 2. Cardiovascular risk reduction: Comprehensive approach to modifiable risk factors in patients with diabetes. 3. Immunization recommendations: Important vaccines for patients with diabetes and their administration schedule.