Integrated Pathophysiologic Concepts: Diabetes Mellitus

Chapter 20: Integrated Pathophysiologic Concepts: Diabetes Mellitus

• Diabetes mellitus is a disease where the body's ability to produce or respond to insulin is impaired, leading to abnormal carbohydrate metabolism and elevated blood/urine glucose levels.
• Glucose is the primary energy source for all cells. Insulin facilitates glucose uptake into cells.

Glucose Metabolism Review

• Glucose is used by cells for energy production.
• Stored glucose is called glycogen.
• Glycogen is stored primarily in the liver and muscles.
• Hormones involved in glucose metabolism include insulin and glucagon.
• Insulin promotes glucose uptake by cells, promoting protein synthesis and fat storage, and also potassium, phosphate, and magnesium transport into cells.
• Glucagon, on the other hand, breaks down glycogen in the liver to raise blood glucose.

Pancreas Review

• The pancreas has both endocrine and exocrine functions.
• Endocrine function: produces hormones like insulin and glucagon.
• Exocrine function: secretes digestive enzymes and bicarbonate-rich fluids.
• Islets of Langerhans are clusters of cells in the pancreas, including alpha cells (produce glucagon), beta cells (produce insulin), and delta cells (produce somatostatin).

Function of Insulin

• Insulin is an anabolic hormone promoting glucose uptake into cells, protein synthesis, and lipid storage (preventing fat breakdown).
• Insulin binds to insulin receptors on cells, opening glucose channels to let glucose enter cells.
• Insulin also facilitates the transport of potassium, phosphate, and magnesium into cells.

Feedback Mechanisms—Glucose Homeostasis

• Insulin secretion increases in response to elevated blood glucose, amino acids, potassium, phosphate, magnesium, glucagon, and gastrin.
• Insulin decreases when blood glucose is low, insulin levels are high, or alpha cell function is stimulated (resulting in glucagon production).
• Glucagon is released when glucose levels are low, causing the breakdown of glycogen in the liver to raise blood glucose.

Diabetes Mellitus Types

• Type 1 Diabetes: Characterized by the destruction of beta cells in the pancreas, leading to a lack of insulin production. This is often an autoimmune response; often presenting in childhood or young adulthood.
• Type 2 Diabetes: Characterized by insulin resistance, where the body does not respond effectively to insulin, and/or a decline in insulin production. It is usually a gradual onset condition, sometimes presenting in younger age groups now, and increasing in prevalence.
• Gestational Diabetes: A form of diabetes that develops during pregnancy due to the body's impaired response to insulin.

Diabetes Mellitus Type 1 Pathophysiology

• Beta cells are destroyed.
• Insulin production is reduced or absent.
• This leads to elevated blood and insulin levels, eventually leading to pancreatic exhaustion.

Diabetes Mellitus Type 2 Pathophysiology

• Insulin resistance, where cells don't respond properly to insulin, decreases glucose uptake.
• Decreased insulin production by beta cells.
• Increased glucose production by the liver.
• These factors lead to elevated blood glucose.

Diabetes Mellitus Type II Diagnosis

• Fasting blood sugar (FBS) greater than 126 mg/dL.
• Random blood sugar (RBS) greater than 200 mg/dL.
• Hemoglobin A1c (HbA1c) is a gold standard blood test; indicates average blood glucose levels over several months (typically three months, due to the lifespan of Red Blood Cells).
  • An A1C of 6.5% or greater is diagnosed as diabetes.
  • Values between 5.7%-6.4% indicate prediabetes.

Clinical Manifestations of Diabetes Mellitus

• Polydipsia: excessive thirst (caused by osmotic diuresis, trying to get rid of excess sugar in the blood via urine).
• Polyuria: excessive urination (caused by osmotic diuresis).
• Polyphagia: excessive hunger (caused by cells unable to access glucose).
• Glycosuria: sugar in the urine.
• Unintentional weight loss (when glucose isn't accessible, the body breaks down protein and fats for energy).

Type 1 Diabetes Complications

• Diabetic ketoacidosis (DKA): A serious complication characterized by ketone accumulation in the blood due to insufficient insulin and an increased rate of fat breakdown, leading to acidosis.
  • Symptoms include fruity breath (ketones), Kussmaul respirations (deep and rapid breathing to compensate for acidosis), dehydration, and possibly coma.

Type 1 Diabetes Treatment

• Daily insulin injections are needed because insulin is not produced naturally, often with various types of insulin (rapid acting, short acting, intermediate acting).
• Careful carbohydrate counting is critical to determine the correct insulin dosage based on the amount of carbohydrates consumed.
• Regular exercise is very important and critical in diabetes management.

Insulin Pumps and CGMs

• Insulin pumps deliver insulin continuously, improving blood glucose control.
• Continuous glucose monitors (CGMs) measure glucose levels continuously and signal insulin pumps to adjust insulin delivery.

Diabetes Type 2 Treatment Approaches

• Medications improve insulin sensitivity, insulin secretion, and glucose excretion to maintain optimal blood glucose levels.
• Diet and exercise are important components in managing type 2 diabetes.

Hypoglycemia

• Abnormally low blood sugar (<70 mg/dL).
• Symptoms include light-headedness, palpitations, excessive perspiration, and (more severely) confusion, trembling, seizures, and coma.
• Treatment involves quickly raising blood glucose with quick-acting carbohydrates.

Insulin Shock

• A rapid onset of hypoglycemia often due to excessive insulin or insufficient carbohydrate intake.
• Symptoms: diaphoresis, light-headedness, tremor, confusion; can progress to coma.
• Treated with quick-acting glucose.

How Hyperglycemia Damages Blood Vessels

• Hyperglycemia leads to vessel wall thickening, damage, inflammation, and plaque buildup (atherosclerosis), affecting vessels throughout the body. This reduces blood flow, leading to tissue damage.

Diabetic Macrovascular Complications

• Increased risk of cardiovascular issues, stroke, peripheral artery disease, leading to foot complications, and heart attack.
• Cardiovascular issues, including clogged arteries, stroke high blood pressures, increase in risk of heart attack and other issues stemming form poor blood flow.

Diabetic Microvascular Complications

• Retinopathy (eye damage, blindness).
• Nephropathy (kidney damage, kidney failure).
• Neuropathy (nerve damage, numbness, tingling, pain, possible muscle wasting).

Chronic Complications Summary

• Diabetes can cause a range of chronic complications, including various types of neuropathy, retinopathy, nephropathy and atherosclerosis.

Wound Healing in Diabetes

• Poor wound healing in patients with diabetes is linked to elevated glucose levels, which impair the blood supply and nerve function vital to healing. These factors can also lead to bacterial infection, further delaying or impeding healing.

Gestational Diabetes

• Happens only during pregnancy, caused by insulin resistance.
• Often leads to larger babies.
• Routine prenatal glucose tolerance tests (GTTs) are critical for diagnosis and monitoring.
• Usually resolves after delivery, but carries increased risk of developing Type 2 DM later in life.
• Prevention involves balanced nutrition (protein, carbs, and fats).

Somogyi Effect

• Temporary overcompensation by the body; Hypoglycemia during the night is corrected during the morning, leading to a rebound of hyperglycemia.

Dawn Phenomenon

• The natural hormone secretion of the body (such as GH, cortisol, glucagon, catecholamines) that occurs in the early morning hours result in an increase of blood glucose levels, especially in the pre-dawn hours, leading to higher levels of blood glucose in the morning.

Miscellaneous: Orthostatic Hypotension

• A sudden drop in blood pressure when standing up due to insufficient compensatory mechanisms to maintain blood pressure.
• Causes include autonomic issues, insufficient norepinephrine response, poor blood pressure response.

Explore the essential concepts of diabetes mellitus, including its effects on glucose metabolism and the role of insulin and glucagon. This quiz covers key physiological aspects, the function of the pancreas, and how these elements contribute to the management of diabetes. Test your understanding of how glucose and hormones interact in the body.