disease states in glucose metabolism

Hyperglycemia (in the blood) Increased: ○ glucose in plasma and urine ○ urine-specific gravity ○ serum and urine osmolality Ketones in serum and urine (ketonemia and ketonuria) Decreased blood and urine pH (acidosis) Electrolyte imbalance (from increased osmolality)

Diabetes Mellitus Types

• IDDM (Type 1) accounts for 5-10% of all diabetes cases and often presents with ketosis.
• IDDM typically has an early onset, often in juveniles, and is influenced by environmental, genetic, and viral factors.
• Insulin is still produced in IDDM, but its action or secretion is defective.

Characteristics of DM Type 1 vs. Type 2

• DM Type 1: often presents with ketosis due to the lack of insulin, which forces the body to use fat as a glucose source.
• DM Type 2: seldom presents with ketosis due to the hyperosmolar state of glucose, which inhibits glucagon's ability to stimulate lipolysis (glucagon attenuation).

Diabetes Mellitus Definition

• Diabetes mellitus is a metabolic disorder characterized by hyperglycemia resulting from a significant defect in either insulin action, insulin secretion, or both.

Diabetes Mellitus (DM)

• A metabolic disorder characterized by hyperglycemia due to a defect in insulin action and/or secretion.

Types of Diabetes Mellitus

• DM Type 1: IDDM, Juvenile Onset (5-10% of all cases)
  • Insulin is still produced, but in insufficient amounts.
  • Often associated with ketosis.
  • Caused by environmental factors, genetics, and previous viral encounters.
• DM Type 2: NIDDM, Adult Onset (90% of all cases)
  • Seldom associated with ketosis.
  • Caused by broken insulin receptors.

Ketosis in DM

• Ketosis is often seen in Type 1 DM due to the absence of insulin, leading to the use of fat as a glucose source.
• Ketosis is seldom seen in Type 2 DM due to the hyperosmolar state of glucose, which inhibits glucagon's ability to stimulate lipolysis (glucagon attenuation).

Characteristics of DM Type 1: IDDM

• Insulin-dependent diabetes mellitus, requiring exogenous insulin for life.
• Juvenile onset, which can be diagnosed early, often from birth.
• Caused by the presence of autoantibodies that destroy B-cells, leading to a deficiency in insulin secretion.
• Pancreas becomes dysfunctional over time, with complete destruction of B-cells by puberty.
• Symptoms include:
  • Tendency for ketosis.
  • 3 Ps: Polyuria (excessive urination), Polyphagia (excessive eating), Polydipsia (excessive thirst).
  • Microvascular problems.

Causes of DM Type 1: IDDM

• Pancreatic B-cell destruction.
• No or low insulin production.
• Presence of autoantibodies.
• Excess glucagon.

Diabetes Mellitus Symptoms

• Polyuria (excessive urination) occurs in patients with diabetes as the body tries to compensate for the hyperglycemic state by diluting or neutralizing it with high water consumption, often leading to frequent nighttime urination.

Diabetes Mellitus Symptoms (continued)

• Polydipsia (excessive thirst) is a consequence of the body's increased water usage, resulting in patients drinking large amounts of water to compensate.

Causes of Diabetes Mellitus Type 1

• Environmental factors contribute to the development of DM type 1, likely triggered by an individual's genetic predisposition.
• Viral infections can initiate DM type 1, with research suggesting a link to the presence of autoantibodies in the body.
• Genetic predisposition plays a role in the development of DM type 1, making individuals more susceptible to the disease.

Type 2 Diabetes (NIDDM)

• Accounts for 90% of all diabetes cases, also known as Adult Onset Diabetes.
• Characterized by insulin production, but cells are unable to recognize it.

Insulin Receptors and Glucose Uptake

• Insulin binds to receptors on the cell surface to allow glucose entry.
• When receptors are damaged, glucose cannot enter the cell.
• Insulin needs to bind to receptors to facilitate glucose uptake.

Causes of Type 2 Diabetes

• Defects in receptors that prevent insulin binding.
• Insulin resistance, where cells become less responsive to insulin.
• Presence of insulin, but cells are unable to utilize it.
• Glucagon attenuation, which disrupts glucose regulation.

Symptoms of Type 2 Diabetes

• Polyuria (excessive urination), polyphagia (excessive eating), and polydipsia (excessive thirst).
• Seldom ketosis tendency, and hyperosmolar states.
• Symptoms may be mild and often develop gradually.

Gestational Diabetes Mellitus (GDM)

• Occurs only in pregnant women, typically between 24-48 weeks of gestation.
• In most cases, GDM resolves on its own after delivery.
• If left untreated for at least 5 years, women with GDM are at risk of developing Type 2 Diabetes.
• Screening for GDM should begin between 24-28 weeks of gestation.
• The placenta produces substances that simulate insulin resistance during pregnancy, contributing to the development of GDM.

Complications of Diabetes During Pregnancy

• Glucose intolerance can occur during pregnancy due to metabolic and hormonal changes
• Babies born to diabetic mothers are at risk of respiratory distress, hypocalcemia, and hyperbilirubinemia

Neuropathy

• Neuropathy is a complication of diabetes that commonly affects the nerves of the hands and feet
• It can also affect nerves controlling autonomic functions of the body, such as digestion
• Additionally, it can affect nerves in the hips and thighs

Nephropathy

• Nephropathy is a complication of diabetes that causes damage to the kidneys
• In severe cases, it can lead to kidney failure
• Not everyone with diabetes develops kidney damage

Retinopathy

• Retinopathy is a complication of diabetes that causes disease of the retina
• It can result in impairment or loss of vision

Kidney Damage and Dialysis

• High glucose levels can damage the kidneys
• Those who have kidney failure may undergo dialysis
• Dialysis is a process of filtering blood through a machine, which is then returned to the body of the patient

Impaired Fasting Glucose

• Fasting glucose level of ≥ 100 mg/dL but ≤ 126 mg/dL
• Not considered diabetes, but borderline between diabetes and impaired fasting glucose
• Indicates problems with glucose metabolism

Impaired Glucose Tolerance

• 2-hr OGTT ≥ 140 mg/dL but ≤ 200 mg/dL
• Discovered through a 2-hour Oral Glucose Tolerance Test (OGTT)
• Worse than impaired fasting glucose

Pre-diabetes

• HbA1c of 5.7% - 6.4%
• Indicates progression to pre-diabetes stage
• Glycated hemoglobin (HbA1c) represents average glucose levels over 90-120 days

Glycated Hemoglobin (HbA1c)

• Glucose attaches to hemoglobin (Hb) in RBCs
• Primarily bonds with HbA1
• High sugar levels in the blood detected through HbA1c
• Used as a screening test for diabetes

Impaired Fasting Glucose

• Fasting glucose level of ≥ 100 mg/dL but ≤ 126 mg/dL
• Not considered diabetes, but borderline between diabetes and impaired fasting glucose
• Indicates problems with glucose metabolism

Impaired Glucose Tolerance

• 2-hr OGTT ≥ 140 mg/dL but ≤ 200 mg/dL
• Discovered through a 2-hour Oral Glucose Tolerance Test (OGTT)
• Worse than impaired fasting glucose

Pre-diabetes

• HbA1c of 5.7% - 6.4%
• Indicates progression to pre-diabetes stage
• Glycated hemoglobin (HbA1c) represents average glucose levels over 90-120 days

Glycated Hemoglobin (HbA1c)

• Glucose attaches to hemoglobin (Hb) in RBCs
• Primarily bonds with HbA1
• High sugar levels in the blood detected through HbA1c
• Used as a screening test for diabetes

Diagnosis of Diabetes Mellitus

• Symptoms of DM require 3Ps: polyuria, polydipsia, and polyphagia
• Random plasma glucose level ≥200 mg/dL at any time of day without fasting, which needs to be confirmed by one of the tests below

Diagnostic Tests for Diabetes Mellitus

• HbA1c (NGSP-certified method) ≥6.5%
• FPG (Fasting Plasma Glucose) ≥126 mg/dL
• OGTT (Oral Glucose Tolerance Test) ≥200 mg/dL (2-hour post load 75g)

Categories for Oral Glucose Tolerance

• Normal glucose tolerance: 2-hour PG ≤140 mg/dL (≤7.8 mmol/L)
• Impaired glucose tolerance: 2-hour PG 140-199 mg/dL (7.8-11.1 mmol/L)
• Provisional diabetes diagnosis (must be confirmed): 2-hour PG ≥200 mg/dL (≥11.1 mmol/L)

Standard Glucose Solutions for OGCT and OGTT

• OGCT (Oral Glucose Challenge Test) for gestational diabetes: 50g
• Standard OGTT: 75g
• 3-hour OGTT: 100g

Glucose Solutions for OGCT (Oral Glucose Challenge Test)

• Standard glucose solution for OGCT to diagnose gestational diabetes: 50g
• Standard glucose solution for 2-hour OGTT (Oral Glucose Tolerance Test): 75g
• Standard glucose solution for 3-hour OGTT: 100g

Interpretation of OGTT Results

• Normal glucose tolerance: 2-hour plasma glucose (PG) ≤140 mg/dL or ≤7.8 mmol/L
• Diagnosis of gestational diabetes: 2-hour PG ≥200 mg/dL after a 75g OGTT

Categories of Fasting Plasma Glucose

• Normal fasting glucose: FPG 70-99 mg/dL (3.9-5.5 mmol/L)
• Impaired fasting glucose: FPG 100-125 mg/dL (5.6-6.9 mmol/L)
• Provisional fasting glucose: FPG ≥126 mg/dL (≥7.0 mmol/L)

Diagnostic Criteria for Gestational Diabetes

• Fasting plasma glucose: ≥92 mg/dL (5.1 mmol/L)
• 1-hour plasma glucose: ≥180 mg/dL (10 mmol/L)
• 2-hour plasma glucose: ≥153 mg/dL (8.5 mmol/L)

Hypoglycemia

• Hypoglycemia: decreased plasma glucose
• Glucagon: released when there is low glucose level in the blood, inhibits insulin and releases epinephrine

Von Gierke Disease (G-6-Phos Deficiency Type 1)

• Autosomal recessive inheritance pattern
• Characterized by severe hypoglycemia, metabolic acidosis, ketonemia, elevated lactate and alanine levels
• Associated with hyperlipidemia, uricemia, and growth retardation
• Impaired glycogenolysis in the liver, preventing glycogen conversion back to glucose
• Resulting glycogen accumulation in the liver causes hepatomegaly (enlarged liver)

Galactosemia

• Congenital deficiency of one of three enzymes involved in galactose metabolism, leading to increased plasma galactose levels
• Diagnosed by measuring erythrocyte Galactose 1-phosphate-uridyltransferase activity
• Failure to metabolize galactose leads to hypoglycemia
• Characterized by hypoglycemia, hyperbilirubinemia, and elevated galactose levels in the blood

Inborn Errors of Metabolism

• Includes galactosemia, inborn errors of amino acid metabolism, alimentary hypoglycemia, and idiopathic hypoglycemia
• Caused by genetic defects