Diabetes Mellitus and Its Complications

Carbohydrate Metabolism Disorders & Diabetes

• Diabetes is a chronic metabolic disease marked by elevated blood glucose levels.
• Type 2 diabetes is common in adults, occurring when the body resists insulin or doesn't produce enough.
• Type 1 diabetes, also known as juvenile diabetes, is a condition where the pancreas makes little or no insulin.
• Access to affordable treatment, including insulin, is crucial for individuals with diabetes.
• Approximately 422 million people worldwide have diabetes, with the majority in low- and middle-income countries.
• The prevalence of diabetes has been steadily increasing over recent decades.

Health Implications of Diabetes

• Diabetes has direct effects and long-term complications, including coronary heart disease and cerebrovascular disease/stroke.
• People with diabetes have a greater risk (twice as high) of myocardial infarction compared to non-diabetics of the same age and sex.

Metabolic Syndrome

• Insulin resistance or glucose intolerance is a component of metabolic factors associated with cardiovascular disease, diabetes, and stroke.
• Metabolic syndrome also includes: obesity (particularly abdominal weight gain), atherogenic dyslipidemia, hypertension, thromboembolic state (elevated fibrinogen), and inflammatory state (indicated by elevated CRP).

Common Symptoms of Diabetes Mellitus (DM)

• Symptoms of diabetes include high blood and urine glucose levels (hyperglycemia and glucosuria), polyuria, polydipsia (excessive thirst), polyphagia (constant hunger), and sudden weight loss.
• During acute episodes, individuals may experience excessive blood and urinary ketones (ketonemia and ketonuria).

Glucose Metabolism Regulation

• The hormonal regulation of glucose metabolism aims to store glucose as glycogen and mobilize stored glucose to maintain stable blood glucose levels.
• The primary energy source for many tissues and organs is glucose.

Anabolic and Catabolic Hormones

• Important hyperglycemic agents include glucagon, epinephrine, cortisol, thyroxine, growth hormone, and certain intestinal hormones.
• Insulin promotes anabolic metabolism (macro-molecule synthesis), while these hormones induce catabolic metabolism (breaking down large molecules).

Insulin Signaling Pathways

• Insulin interacts with cell surface receptors initiating a cascade of phosphorylation/dephosphorylation events, second-messenger generation, and protein-protein interactions.
• These interactions affect various metabolic processes in nearly every tissue.
• Genetic variations and functional changes in insulin pathway proteins result in insulin resistance.

Insulin Signaling Defects

• Mutations in the INSR gene can result in Rabson-Mendenhall syndrome, reducing the number or diminishing the function of insulin receptors on cells.

Hormone Regulation of Glucose Metabolism

• The hormonal regulation of glucose metabolism is crucial for maintaining homeostasis in the body.

Glucose Metabolism in Diabetes

• In non-diabetic individuals, insulin-to-glucagon ratio is low while blood glucose is low.
• Muscle and hepatic glycogen stores are broken down to supply glucose during fasting.
• Further fasting can result in protein breakdown (into amino acids) in skeletal muscle, and triglyceride breakdown in adipose tissue.
• During these processes, amino acids and glycerol are converted to glucose via gluconeogenesis.
• Free fatty acids also fuel the heart, skeletal muscle, and liver.

Classification of Diabetes

• Type 1 diabetes accounts for 5-10% of diagnoses and is caused by insufficient insulin secretion.
• Insulin injection is necessary for type 1 diabetics. Type 1 individuals are prone to ketoacidosis.
• Type 2 diabetes is more common and typically occurs in individuals over 40 years old, but is increasingly prevalent among younger individuals.
• Type 2 diabetics generally aren't dependent on insulin injections, and are not prone to ketoacidosis.
• Secondary diabetes is a diabetes type caused by other underlying issues such as pancreatic disease, growth hormone excess, Cushing's syndrome, glucagonoma, somatostatinoma, severe liver disease, or drug administration.

Impaired Glucose Tolerance (IGT)

• Impaired glucose tolerance is an intermediate step in the development of type 2 diabetes.
• Individuals with IGT have abnormally high glucose tolerance but don't experience fasting hyperglycemia. IGT is a condition referred to as pre-diabetes.

Gestational Diabetes (GD)

• Gestational diabetes (GD) is a temporary form of diabetes that develops during pregnancy.
• GD often progresses to type 2 diabetes in the woman.
• Nutritional needs increase during pregnancy, and adipose cells increase, leading to a higher need for insulin secretion.

Complications of Diabetes

• Complications of diabetes include retinopathy (damage to the retina), neuropathy (nerve damage), angiopathy (vessel damage), nephropathy (kidney damage), susceptibility to infections, hyperlipidemia (high lipid levels), ketoacidosis (high ketone levels), HHNC (hyperglycemic hyperosmolar nonketotic coma).
• Complications occur more frequently in type 1 diabetes, except for HHNC (occurs in type 2).

Hyperlipidemia and Atherosclerosis

• Abnormal triglyceride, cholesterol, and very-low-density lipoprotein (VLDL) levels are often associated with type 2 diabetes.
• HDL levels tend to be lower in diabetics than non-diabetics.

Diabetic Ketoacidosis (DKA)

• Ketoacid production increases in diabetics due to insulin deficiency and triggered triglycerides mobilization in adipose tissues.
• Increased production of ketoacids reduces blood pH, leading to keto-acidosis.
• The mortality rate for diabetic keto-acidosis is between 1-8%.

Hyperglycemic Hyperosmolar Nonketotic Coma (HHNC)

• HHNC is an emergency medical condition triggered by very high blood glucose levels, serum osmolality, and intense thirst.
• People with HHNC have frequent urination and may experience lethargy and/ or coma.
• HHNC has a mortality rate of between 10-20%.

Hypoglycemia

• Hypoglycemia causes neurogenic problems ranging in severity from mild to severe coma, seizures, and death. Symptoms often manifest when blood glucose is around 50 mg/dL.
• Aggressive insulin use is a common cause of hypoglycemia in people who are maintaining normal blood sugar levels.

Function Tests

• Postprandial plasma glucose (PPPG) tests measure glucose clearance rates from the blood after a carbohydrate load (often 75g of glucose solution). This test is helpful in diagnosing diabetes. Two tests are recommended for accurate diagnosis.

• Oral glucose tolerance test (OGTT) evaluates glucose clearance under controlled conditions. It's standardized by the ADA to help diagnose people with diabetes. A minimum 8-hour fast before testing is crucial. The glucose load is usually 75g and levels are measured 2 hours after ingestion. Results are consistent with values above 200 after a 2hr measurement.

• A fasting blood glucose (FPG) test measures blood glucose after an 8-hour fast; this is now the preferred blood glucose test to diagnose people with diabetes, particularly when diagnosing diabetes in people who are over 40 years old.

• A random plasma glucose (RPG) test measures blood glucose at any time of day, helping diagnose severe diabetes symptoms. A blood glucose of 200 mg/dL or higher is suggestive of diabetes in this test.

Glycated Hemoglobin (HbA1c)

• HbA1c, formed by glucose binding to hemoglobin, reflects average plasma glucose levels for the preceding 120 days in red blood cells.
• Diagnostic criteria for diabetes using HbA1c are above 6.5%.

Urinary Glucose

• While sometimes helpful in screening, urinary glucose is a less reliable marker for diabetes diagnosis than other tests.

Urinary Protein

• Microalbuminuria, the presence of albumin in urine, is an early sign of glomerular nephropathy, frequently associated with diabetes. This measured is most helpful when monitoring in a patient population.
• Urine albumin/creatinine ratio is a useful screening test for microalbuminuria, an indicator for early kidney disease associated with diabetes.

Insulin Resistance (IR)

• Insulin resistance is a significant factor in diabetes mellitus, impacting the effectiveness of insulin to regulate blood sugar.
• Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) is a widely used estimation of insulin resistance, calculated as (fasting plasma insulin (FPI) multiplied by fasting plasma glucose (FPG)) divided by the constant 22.5.
• High HOMA-IR usually means greater insulin resistance.

This quiz tests your knowledge on the long-term complications associated with diabetes mellitus, particularly focusing on cardiovascular issues. It explores various aspects of metabolism, insulin signaling, and the hormonal regulation of glucose in the body. Enhance your understanding of how diabetes affects health and the body's response to glucose.