GENERALITIES IN CC & DM

I. CARBOHYDRATES

  • Composed primarily of Carbon, Hydrogen, and Oxygen.

  • Functions of carbohydrates include:

    • Providing energy.

    • Contributing to the structural components of organisms; serve as the framework of an organism.

  • Complex carbohydrates (CHO) are digested into simple sugars, predominantly glucose, utilized primarily as energy sources or stored as glycogen.

    • GLUCOSE is the principal sugar circulating in the bloodstream.

    • Important dietary hexoses include: D-glucose, D-galactose, and D-fructose.

    • D-glucose is especially critical for various biological functions.

  • Carbohydrates are measured in various bodily fluids: whole blood, serum, or plasma.

II. FUNCTION OF THE ENDOCRINE PANCREAS

  • The endocrine pancreas plays a crucial role in controlling carbohydrate metabolism through insulin and other hormones.

A. HORMONES AND FUNCTIONS OF THE ENDOCRINE PANCREAS

  • Most individuals with diabetes have either Type 1 or Type 2 diabetes:

    • Type 1 Diabetes: Characterized by beta cell destruction leading to absolute insulin deficiency.

    • Type 2 Diabetes: Characterized by insulin resistance and defective insulin secretion.

  • The pancreas functions as both an endocrine and exocrine organ:

    • As an exocrine gland, it produces and secretes amylase responsible for the breakdown of ingested complex carbohydrates into monosaccharides.

    • Monosaccharides trigger the release of various hormones by the endocrine pancreas.

  • Islets of Langerhans contain various cells that secrete hormones:

    • Alpha Cells: Produce Glucagon, which stimulates glucose production and ketogenesis.

    • Beta Cells: Produce Insulin and Amylin.

    • Delta Cells: Produce Somatostatin, which inhibits other hormones.

    • Epsilon Cells: Produce Ghrelin.

    • Gamma or F cells: Produce Pancreatic Polypeptide.

  • The ratio of insulin to glucagon is crucial for regulating carbohydrate metabolism and is influenced by multiple factors:

    • Somatostatin, neural input, intestinal peptides, and concentrations of glucose and other metabolites.

Table 1. Hormone & Function of the Endocrine Pancreas

  • Insulin:

    • An anabolic hormone from beta cells.

    • Stimulates glucose uptake and glycogen formation.

    • Converts Preproinsulin → Proinsulin → Insulin.

    • In Type 2 diabetes, the proinsulin:insulin ratio is increased, indicating decreased beta cell function.

    • C-peptide connects Insulin's A chain to B chain and can be measured after an 8-hour fast or stimulation by an oral mixed meal.

    • Serum insulin can be falsely low during hemolysis; C-peptide and proinsulin are less affected.

  • Amylin (Islet Amyloid Polypeptide):

    • Co-secreted with insulin.

    • Inhibits postprandial glucagon secretion and slows gastric emptying.

    • High levels found in hyperinsulinemic states; low levels in Type 1 diabetes.

  • Glucagon:

    • Produced in alpha cells; stimulates hepatic glucose production.

    • Regulates glycogenolysis, gluconeogenesis, and ketogenesis.

  • Somatostatin:

    • Inhibits several hormones, including insulin and glucagon.

    • Functions beyond the pancreas, such as inhibiting gastric acid secretion and motility.

  • Ghrelin:

    • Synthesized primarily in stomach, stimulates appetite, inhibits insulin, and stimulates glucagon secretion.

  • Pancreatic Polypeptide (PP):

    • Influenced by nutrient ingestion, increases satiety, and inhibits pancreatic enzyme release.

  • Incretins:

    • GLP-1 stimulates insulin secretion, inhibits glucagon, and postpones gastric emptying.

    • Ozempic: GLP-1 analog that aids in weight loss by promoting insulin secretion.

III. GLUCOSE MEASUREMENT METHODS

  • Glucose can be analyzed in various specimens: whole blood, plasma, serum, CSF, pleural fluid, and urine.

  • Glycolysis in unseparated blood can decrease glucose levels by approximately 5-10 mg/dl/hour.

  • Sodium fluoride (NaF) can yield lower glucose values compared to plasma glucose due to various factors.

Table 2. Enzymatic Methods

  • Glucose dehydrogenase: Measures concentration via chromophore or electrical current.

  • Glucose oxidase: Involves a peroxidase reaction.

  • Hexokinase: Velocity of reaction proportional to glucose concentration.

IV. DIABETES MELLITUS

  • Classified into groups where blood glucose levels are elevated, leading to various complications:

    • Causes include end-stage renal disease, diabetic neuropathy, and increased atherosclerotic disease risk.

  • **American Diabetes Association Guidelines: ** Fasting plasma glucose of 126 mg/dl (7.0 mmol/L) or higher on two occasions is diagnostic for diabetes.

  • Fasting glucose level should be measured after an 8-hour fast.

  • Prediabetes indicates abnormal glucose homeostasis without reaching diabetes classification.

Table 4. Types of Diabetes Mellitus
Type 1 Diabetes

  • Autoimmune destruction of islet beta cells leading to insulin deficiency.

  • Usually diagnosed in childhood; insulin-dependent.

  • Associated autoantibodies include ICA, IAA, GAD, IA2.

  • Linked to HLA DR and DQ loci.

Type 2 Diabetes

  • Characterized by progressive insulin resistance; most common form.

  • Typically presents in adulthood; non-insulin dependent.

Gestational Diabetes Mellitus (GDM)

  • Diabetes onset during pregnancy, may persist post-pregnancy.

V. MEASUREMENT OF GLYCEMIC CONTROL

  • HbA1c reflects average glucose levels over the previous three months.

  • Normal HbA1c is < 6%; influenced by red blood cell lifespan.

  • Tests are standardized using High Performance Liquid Chromatography (HPLC).

  • Interference in measurements can occur in conditions such as uremia, hypertriglyceridemia, and hemoglobinopathies.

VI. HYPOGLYCEMIA

  • Caused by an imbalance between glucose utilization and production, results in low plasma glucose levels.

Table 5. Symptoms of Hypoglycemia

Neuroglycopenic Symptoms

  • Related to brain dependence on glucose, may lead to altered mental status or seizures.

  • Key because glucose is the only brain energy source.

Adrenergic Symptoms

  • Symptoms include sweating, palpitations, tachycardia, and nervousness.

Types of Hypoglycemia

  • Fasting Hypoglycemia: Gradually occurs post-prolonged fasting; linked to various medical conditions.

  • Reactive Hypoglycemia: Rapid onset following meals; may be triggered by dietary patterns or hormonal imbalances.

  • C-peptide can help identify endogenous versus exogenous insulin causes of hypoglycemia.

VII. DIABETIC KETOACIDOSIS (DKA)

  • Severe acute metabolic complication mostly seen in Type 1 diabetics.

  • Characterized by hyperglycemia, ketosis, and metabolic acidosis; failure to take insulin is a common cause.

Precipitating Factors for DKA

  • Include infections, stress, unconventional diet, and physical activity deviations leading to glucose regulation disruption.

Table 6. Clinical Manifestations of DKA

  • Symptoms: Fatigue, nausea, vomiting, abdominal pain, fruity/acetone odor on breath, Kussmaul breathing.

  • Progression: Dehydration, mental status changes can lead to coma if untreated.

VIII. HYPERGLYCEMIC HYPEROSMOLAR NONKETOTIC COMA (HHNC)

  • Occurs primarily in Type 2 Diabetes; characterized by altered mental status and extreme hyperglycemia.

  • Commonly presents with profound hyperglycemia (over 1000 mg/dL), dehydration, but normal pH.

Table 7: Key Laboratory Findings of DKA

  • Glucose: > 200 mg/dL (often 500-700 mg/dL).

  • Ketonuria: Both ketonemia and ketonuria present.

  • Venous pH: < 7.3, Bicarbonate: < 15 mmol/L, Anion Gap: Increased.

  • Potassium Levels: Initially high but severe hypokalemia may occur during treatment.

  • Neutrophils: Typically exhibits a left-shifted neutrophilia.

  • Amylase & Lipase: Elevations can indicate concurrent pancreatitis in diabetic patients.