Glucose Metabolism and Abnormalities

Glucose Metabolism

• Glucose is a major food source, primary energy source, and calories provider.
• It is used as energy (ATP) and stored as liver and muscle glycogen, fat.
• There are three types of carbohydrates: monosaccharides (e.g., glucose), disaccharides (e.g., sucrose), and polysaccharides (e.g., starch).

CHO Metabolism

• Glycolysis: metabolism of glucose to pyruvate or lactate.
• Glycogenesis: synthesis of glycogen from glucose.
• Glycogenolysis: breakdown of glycogen to glucose for energy.
• Gluconeogenesis: formation of glucose-6-phosphate (G6P) from a non-carbohydrate source.
• Lipogenesis: conversion of carbohydrates to fatty acids and adipose tissue.
• Lipolysis: breakdown of fats.

Plasma Glucose Regulation

• Plasma glucose levels are maintained within a narrow range by hormones that modulate the movement of glucose into and out of circulation.
• Primary regulators: insulin and glucagon.
• Other hormones also play a role in regulating plasma glucose levels, including epinephrine, growth hormone, cortisol, thyroxine, and somatostatin.

Insulin and Glucagon

• Insulin:
  • Released when fasting plasma glucose > 126 mg/dL.
  • Lowers plasma glucose levels.
  • Promotes glycogenesis and glycolysis.
  • Inhibits glycogenolysis and gluconeogenesis.
• Glucagon:
  • Released when fasting plasma glucose < 45-50 mg/dL.
  • Raises plasma glucose levels.
  • Inhibits glycogenesis and glycolysis.
  • Promotes glycogenolysis and gluconeogenesis.

Hypoglycemia

• Low plasma glucose levels (< 45-50 mg/dL).
• Symptoms: non-specific, including increased hunger, sweating, nausea, vomiting, dizziness, nervousness, blurring of speech and sight, and mental confusion.

Galactosemia

• Deficiency of galactose-1-phosphate uridyl transferase enzyme.
• Galactose or lactose cannot be metabolized to glucose.
• Galactose accumulates in blood (galactosemia) and urine.
• Can lead to mental retardation, cataracts, and death.

Specimen Collection and Handling

• Fasting specimen for FBS/FPG (8-10 hour fast/overnight).
• Collect in sodium fluoride tube (grey top).
• Must separate viable cells within 1 hour of collection.
• Preferred specimens: plasma, serum, whole blood, CSF, and urine.

Expected Values

• FPG: 70-99 mg/dL.
• Random (non-fasting): 70-125 mg/dL.
• 2-hour postprandial: 126 mg/dL usually indicates a problem.
• FBS should be repeated on another day to confirm diagnosis.

Lab Tests

• 2-hour Post Prandial:
  • Patient has FBS drawn.
  • Ingests 75 gram high carbo breakfast/drinks glucola.
  • Has repeated glucose test at 2 hours.
• Oral Glucose Tolerance Test:
  • Patient directions: eat an adequate carbohydrate diet at least three days prior to test.
  • Obtain fasting specimen.
  • Test is begun in early a.m.
  • Test dose (glucose load): 75 gm for adults and 1.75 gm/kg for children.
  • Patient is to remain resting, no smoking or eating during test period.
  • Blood is collected at timed intervals and measured.

Clinical Application

Hyperglycemia

• Plasma glucose > 110 mg/dL.
• Generally referred to as Diabetes Mellitus.
• Immediate effects: increased ECF osmotic pressure, acidosis.

Diabetes Mellitus

• Hyperglycemia.
• Ketosis: ketonemia, ketonuria.
• Hyperlipidemia.
• Decreased blood pH.
• Glycosuria.
• Loss of electrolytes: Na+.

WHO and ADA Classification

• Type 1 diabetes mellitus:
  • Less common: 10-20% of cases.
  • Cause: lack of insulin secretion due to destruction of pancreatic beta cells.
  • Juvenile onset diabetes.
  • Most severe form of DM.
  • Ketosis prone.
  • Insulin dependent.
• Type 2 diabetes mellitus:
  • Most common: 90% of cases.
  • Causes: peripheral tissues are not able to respond to insulin, insulin secretion is delayed.
  • Adult onset diabetes.
  • Less severe form of DM.
  • Not ketosis prone.
  • Non-insulin dependent.
• Gestational diabetes mellitus:
  • Diabetes mellitus that develops during pregnancy (and resolves after pregnancy).
  • GDM associated with increased infant morbidity and mortality.
  • GDM mothers are at increased risk of developing diabetes mellitus.
• Secondary diabetes:
  • Pancreatic disease.
  • Endocrine disease: excess GH, cortisol, epinephrine.
  • Severe liver disease.
  • Drug or chemical induced.

Glucose Metabolism

• Glucose is a major food source, primary energy source, and calories provider.
• It is used as energy (ATP) and stored as liver and muscle glycogen, fat.
• There are three types of carbohydrates: monosaccharides (e.g., glucose), disaccharides (e.g., sucrose), and polysaccharides (e.g., starch).

CHO Metabolism

• Glycolysis: metabolism of glucose to pyruvate or lactate.
• Glycogenesis: synthesis of glycogen from glucose.
• Glycogenolysis: breakdown of glycogen to glucose for energy.
• Gluconeogenesis: formation of glucose-6-phosphate (G6P) from a non-carbohydrate source.
• Lipogenesis: conversion of carbohydrates to fatty acids and adipose tissue.
• Lipolysis: breakdown of fats.

Plasma Glucose Regulation

• Plasma glucose levels are maintained within a narrow range by hormones that modulate the movement of glucose into and out of circulation.
• Primary regulators: insulin and glucagon.
• Other hormones also play a role in regulating plasma glucose levels, including epinephrine, growth hormone, cortisol, thyroxine, and somatostatin.

Insulin and Glucagon

• Insulin:
  • Released when fasting plasma glucose > 126 mg/dL.
  • Lowers plasma glucose levels.
  • Promotes glycogenesis and glycolysis.
  • Inhibits glycogenolysis and gluconeogenesis.
• Glucagon:
  • Released when fasting plasma glucose < 45-50 mg/dL.
  • Raises plasma glucose levels.
  • Inhibits glycogenesis and glycolysis.
  • Promotes glycogenolysis and gluconeogenesis.

Hypoglycemia

• Low plasma glucose levels (< 45-50 mg/dL).
• Symptoms: non-specific, including increased hunger, sweating, nausea, vomiting, dizziness, nervousness, blurring of speech and sight, and mental confusion.

Galactosemia

• Deficiency of galactose-1-phosphate uridyl transferase enzyme.
• Galactose or lactose cannot be metabolized to glucose.
• Galactose accumulates in blood (galactosemia) and urine.
• Can lead to mental retardation, cataracts, and death.

Specimen Collection and Handling

• Fasting specimen for FBS/FPG (8-10 hour fast/overnight).
• Collect in sodium fluoride tube (grey top).
• Must separate viable cells within 1 hour of collection.
• Preferred specimens: plasma, serum, whole blood, CSF, and urine.

Expected Values

• FPG: 70-99 mg/dL.
• Random (non-fasting): 70-125 mg/dL.
• 2-hour postprandial: 126 mg/dL usually indicates a problem.
• FBS should be repeated on another day to confirm diagnosis.

Lab Tests

• 2-hour Post Prandial:
  • Patient has FBS drawn.
  • Ingests 75 gram high carbo breakfast/drinks glucola.
  • Has repeated glucose test at 2 hours.
• Oral Glucose Tolerance Test:
  • Patient directions: eat an adequate carbohydrate diet at least three days prior to test.
  • Obtain fasting specimen.
  • Test is begun in early a.m.
  • Test dose (glucose load): 75 gm for adults and 1.75 gm/kg for children.
  • Patient is to remain resting, no smoking or eating during test period.
  • Blood is collected at timed intervals and measured.

Clinical Application

Hyperglycemia

• Plasma glucose > 110 mg/dL.
• Generally referred to as Diabetes Mellitus.
• Immediate effects: increased ECF osmotic pressure, acidosis.

Diabetes Mellitus

• Hyperglycemia.
• Ketosis: ketonemia, ketonuria.
• Hyperlipidemia.
• Decreased blood pH.
• Glycosuria.
• Loss of electrolytes: Na+.

WHO and ADA Classification

• Type 1 diabetes mellitus:
  • Less common: 10-20% of cases.
  • Cause: lack of insulin secretion due to destruction of pancreatic beta cells.
  • Juvenile onset diabetes.
  • Most severe form of DM.
  • Ketosis prone.
  • Insulin dependent.
• Type 2 diabetes mellitus:
  • Most common: 90% of cases.
  • Causes: peripheral tissues are not able to respond to insulin, insulin secretion is delayed.
  • Adult onset diabetes.
  • Less severe form of DM.
  • Not ketosis prone.
  • Non-insulin dependent.
• Gestational diabetes mellitus:
  • Diabetes mellitus that develops during pregnancy (and resolves after pregnancy).
  • GDM associated with increased infant morbidity and mortality.
  • GDM mothers are at increased risk of developing diabetes mellitus.
• Secondary diabetes:
  • Pancreatic disease.
  • Endocrine disease: excess GH, cortisol, epinephrine.
  • Severe liver disease.
  • Drug or chemical induced.