Chem chapter 7

• Carbohydrates are organic compounds containing carbon, hydrogen, and oxygen, with a basic formula of (CH2O)n
• They are a primary source of energy for living organisms
• Carbohydrates play key structural roles in cells and tissues

Monosaccharides

• Monosaccharides are the simplest form of carbohydrates, often referred to as simple sugars
• They cannot be hydrolyzed into smaller carbohydrates
• They serve as the building blocks for more complex carbohydrates
• Classified by the number of carbon atoms they contain: trioses (3 carbons), tetroses (4 carbons), pentoses (5 carbons), hexoses (6 carbons), and heptoses (7 carbons)

Glucose

• A hexose sugar (6 carbons) with the formula C6H12O6
• Also known as dextrose or blood sugar
• Primary source of energy for cells in respiration
• Found in fruits, vegetables, and corn syrup

Fructose

• Another hexose sugar with the same formula as glucose (C6H12O6) but a different structure
• Also known as fruit sugar or levulose
• Found in fruits and honey
• Converted to glucose in the liver

Galactose

• A hexose sugar with the formula C6H12O6, an isomer of glucose and fructose
• Part of lactose (milk sugar)
• Converted to glucose in the liver

Ribose

• A pentose sugar (5 carbons) with the formula C5H10O5
• Component of RNA (ribonucleic acid)

Deoxyribose

• A modified pentose sugar with the formula C5H10O4
• Component of DNA (deoxyribonucleic acid); it lacks one oxygen atom compared to ribose

Disaccharides

• Disaccharides are composed of two monosaccharides joined by a glycosidic bond
• Formed when two monosaccharides undergo a dehydration reaction (removal of a water molecule)

Sucrose

• Composed of one glucose molecule and one fructose molecule
• Common table sugar
• Found in sugarcane and sugar beets

Lactose

• Composed of one glucose molecule and one galactose molecule
• Primary sugar found in milk
• Digested by the enzyme lactase

Maltose

• Composed of two glucose molecules
• Formed during the digestion of starch
• Found in germinating grains

Oligosaccharides

• Oligosaccharides contain a small number (typically 3-10) of monosaccharides linked together
• Often found attached to proteins or lipids on cell surfaces, where they play roles in cell recognition and signaling

Raffinose

• A trisaccharide composed of galactose, glucose, and fructose
• Found in beans, cabbage, and other vegetables

Stachyose

• A tetrasaccharide composed of two galactose molecules, one glucose molecule, and one fructose molecule
• Found in soybeans and other legumes

Polysaccharides

• Polysaccharides are complex carbohydrates composed of many monosaccharide units (hundreds to thousands) linked together by glycosidic bonds
• Serve as energy storage molecules or structural components in organisms
• Can be either homopolysaccharides (composed of the same type of monosaccharide) or heteropolysaccharides (composed of different types of monosaccharides)

Starch

• A homopolysaccharide composed of glucose units
• Primary energy storage form in plants
• Exists in two forms: amylose (linear) and amylopectin (branched)
• Found in potatoes, rice, wheat, and corn

Glycogen

• A homopolysaccharide composed of glucose units
• Primary energy storage form in animals and fungi
• Highly branched structure, similar to amylopectin but more extensively branched
• Stored in the liver and muscles

Cellulose

• A homopolysaccharide composed of glucose units
• Major structural component of plant cell walls
• Linear polymer with beta-1,4-glycosidic linkages
• Indigestible by humans due to the lack of an enzyme to break down beta-1,4-glycosidic bonds

Chitin

• A homopolysaccharide composed of N-acetylglucosamine units
• Major structural component of the exoskeletons of arthropods and the cell walls of fungi
• Similar to cellulose, but with an acetylamine group on each glucose unit

Pectin

• A heteropolysaccharide found in the cell walls of plants, particularly in fruits
• Composed of a complex mixture of polysaccharides, including galacturonic acid, rhamnose, galactose, and arabinose
• Used as a gelling agent in jams and jellies

Agar

• A heteropolysaccharide obtained from seaweed
• Consists of a mixture of agarose and agaropectin
• Used as a solidifying agent in microbiological culture media and in various other applications

Peptidoglycan

• A heteropolysaccharide found in the cell walls of bacteria
• Composed of alternating N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) units, cross-linked by short peptides
• Provides structural support and protection to bacterial cells

Stereoisomers

• Stereoisomers have the same chemical formula and sequence of bonded atoms, but differ in the three-dimensional orientations of their atoms in space
• Stereoisomers are classified into enantiomers and diastereomers

Enantiomers

• Enantiomers are stereoisomers that are non-superimposable mirror images of each other
• Enantiomers have identical physical properties, such as melting point, boiling point, and refractive index, except for their interaction with plane-polarized light
• Enantiomers rotate plane-polarized light in equal but opposite directions
• A chiral molecule rotates plane-polarized light
• Achiral molecules do not rotate plane-polarized light
• A pair of enantiomers are designated as either dextrorotatory (d or +) or levorotatory (l or -), depending on whether they rotate plane-polarized light to the right or left, respectively
• The d and l prefixes are experimental determinations
• Most biological molecules are chiral, and living systems usually contain only one of the possible enantiomers of a particular compound

Chirality

• A chiral carbon atom is a carbon atom that is bonded to four different groups
• A molecule with one chiral carbon atom is always chiral
• A molecule with more than one chiral carbon atom is usually chiral, but there are exceptions
• Meso compounds are achiral molecules that contain chiral centers
• Meso compounds have an internal plane of symmetry
• The maximum number of stereoisomers for a molecule is 2^n, where n is the number of chiral carbon atoms
• Chirality is important in biological systems because many biological molecules are chiral, and enzymes are stereospecific

Diastereomers

• Diastereomers are stereoisomers that are not mirror images of each other
• Diastereomers have different physical properties, such as melting point, boiling point, and solubility
• Epimers and anomers are special types of diastereomers

Epimers

• Epimers are diastereomers that differ in the configuration at only one chiral center
• D-glucose and D-mannose are epimers at C-2
• D-glucose and D-galactose are epimers at C-4

Anomers

• Anomers are cyclic diastereomers that are formed when a sugar cyclizes
• The anomeric carbon is the carbon atom that is derived from the carbonyl carbon of the open-chain form of the sugar
• The α anomer has the OH group on the anomeric carbon on the opposite side of the ring from the CH2OH group that determines the D or L configuration
• The β anomer has the OH group on the anomeric carbon on the same side of the ring as the CH2OH group that determines the D or L configuration

D and L isomers

• The D and L isomers of a sugar are enantiomers
• The D or L configuration of a sugar is determined by the configuration of the chiral carbon atom that is farthest from the carbonyl group
• If the OH group on this carbon atom is on the right, the sugar is a D sugar
• If the OH group on this carbon atom is on the left, the sugar is an L sugar
• Most sugars in living organisms are D sugars

Aldoses

• Aldoses are carbohydrates that contain an aldehyde group
• Examples of aldoses encompass glucose, galactose, mannose, and ribose

Ketoses

• Ketoses are carbohydrates that contain a ketone group
• Examples of ketoses include fructose and ribulose

Haworth Projections

• Haworth projections represent the cyclic structure of sugars
• In a Haworth projection, the ring is drawn flat on the page
• The substituents on the ring are drawn either above or below the plane of the ring
• Groups on the right side of the Fischer projection are drawn below the plane of the ring in the Haworth projection
• Groups on the left side of the Fischer projection are drawn above the plane of the ring in the Haworth projection
• The position of the anomeric hydroxyl group determines whether the sugar is α or β

Chair Conformations

• Pyranose rings (six-membered rings) are not planar and adopt chair conformations
• In the chair conformation, substituents on the ring are either axial or equatorial
• Axial substituents are perpendicular to the plane of the ring
• Equatorial substituents are in the plane of the ring
• The chair conformation that minimizes steric hindrance is usually the more stable conformation
• Bulky substituents prefer to be equatorial

Common Monosaccharides

• Glucose is a common monosaccharide that is used as an energy source by many organisms
• Fructose is a common monosaccharide that is found in fruits and honey
• Galactose is a common monosaccharide that is found in milk
• Ribose is a common monosaccharide that is a component of RNA
• Deoxyribose is a common monosaccharide that is a component of DNA

Carbohydrate Metabolism

• Carbohydrate metabolism encompasses all biochemical processes involved in the synthesis and breakdown of carbohydrates
• It is a crucial aspect of energy production and storage in living organisms
• Three major pathways: glycolysis, glycogenesis/glycogenolysis, and gluconeogenesis

Glycolysis

• Glycolysis is the breakdown of glucose into pyruvate, releasing energy in the form of ATP and NADH
• It occurs in the cytoplasm of cells
• Consists of ten enzymatic steps, divided into an energy-investment phase and an energy-payoff phase
• Glycolysis is the sequence of reactions that metabolizes one molecule of glucose to two molecules of pyruvate with the concomitant net production of two molecules of ATP and two molecules of NADH.
• Glycolysis can occur aerobically or anaerobically, depending on the availability of oxygen and the electron transport chain.
• The end products are pyruvate, ATP, and NADH
• Under anaerobic conditions, pyruvate is converted to lactate (lactic acid fermentation) or ethanol and CO2 (alcoholic fermentation).

Glycogenesis/Glycogenolysis

• Glycogenesis is the synthesis of glycogen from glucose
• Glycogenolysis is the breakdown of glycogen into glucose
• These processes regulate blood glucose levels
• Glycogenesis occurs when glucose levels are high, while glycogenolysis occurs when glucose levels are low
• Primarily occurs in the liver and muscle cells

Gluconeogenesis

• Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursors, such as pyruvate, lactate, glycerol, and amino acids
• Occurs primarily in the liver and kidneys
• Important for maintaining blood glucose levels during fasting or starvation
• Some steps are the reverse of glycolysis, but several key steps are bypassed by different enzymes
• Gluconeogenesis is the metabolic process by which glucose is synthesized from non-carbohydrate precursors.
• Important precursors include pyruvate, lactate, glycerol, and certain amino acids.
• Gluconeogenesis bypasses the irreversible steps of glycolysis using different enzymes.
• Key enzymes include pyruvate carboxylase, phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-bisphosphatase, and glucose-6-phosphatase.

Glycogenesis

• Glycogenesis is the process of synthesizing glycogen from glucose.
• It primarily occurs in the liver and muscle tissues.
• Glycogen is a branched polymer of glucose used for glucose storage.
• The key enzyme is glycogen synthase, which adds glucose molecules to the growing glycogen chain using UDP-glucose as a substrate.
• Glycogenesis is stimulated by insulin in response to high blood glucose levels.

Glycogenolysis

• Glycogenolysis is the breakdown of glycogen to release glucose.
• It occurs primarily in the liver and muscle tissues.
• The key enzyme is glycogen phosphorylase, which cleaves glucose residues from the glycogen chain by adding a phosphate.
• Glycogenolysis is stimulated by glucagon and epinephrine in response to low blood glucose levels or energy demands.
• Debranching enzyme is also required to break the α-1,6-glycosidic bonds at branch points in glycogen.

Pentose Phosphate Pathway (PPP)

• The pentose phosphate pathway (also called the hexose monophosphate shunt) is a metabolic pathway parallel to glycolysis.
• It produces NADPH and pentoses (5-carbon sugars).
• It occurs in the cytoplasm.
• It has two phases: an oxidative phase that generates NADPH, and a non-oxidative phase that synthesizes pentoses and other sugars.
• NADPH is essential for reducing power in anabolic reactions and protecting against oxidative stress.
• Pentoses, such as ribose-5-phosphate, are crucial for nucleotide synthesis.

Citric Acid Cycle (TCA Cycle)

• The citric acid cycle (also known as the Krebs cycle or tricarboxylic acid cycle) is a series of chemical reactions that extract energy from acetyl-CoA.
• It occurs in the mitochondrial matrix.
• Acetyl-CoA is derived from pyruvate (from glycolysis), fatty acids, and amino acids.
• The cycle involves eight enzymatic steps that oxidize acetyl-CoA, releasing CO2, ATP, NADH, and FADH2.
• It is a central metabolic hub, linking carbohydrate, fat, and protein metabolism.

Electron Transport Chain (ETC) and Oxidative Phosphorylation

• The electron transport chain is a series of protein complexes embedded in the inner mitochondrial membrane.
• It accepts electrons from NADH and FADH2, generated during glycolysis, the citric acid cycle, and fatty acid oxidation.
• Electrons are passed through the chain, releasing energy that is used to pump protons (H+) from the mitochondrial matrix to the intermembrane space, creating an electrochemical gradient.
• Oxidative phosphorylation is the process by which ATP is synthesized using the energy of the proton gradient.
• ATP synthase is the enzyme that catalyzes the synthesis of ATP as protons flow back into the mitochondrial matrix.
• The ETC and oxidative phosphorylation are the primary sources of ATP production in aerobic organisms.

Insulin

• Insulin is a hormone produced by the beta cells of the pancreas.
• It promotes glucose uptake by cells, glycogenesis in the liver and muscles, and glycolysis.
• Insulin secretion is stimulated by high blood glucose levels.
• It inhibits gluconeogenesis and glycogenolysis.
• Insulin plays a crucial role in maintaining glucose homeostasis.

Glucagon

• Glucagon is a hormone produced by the alpha cells of the pancreas.
• It stimulates glycogenolysis and gluconeogenesis in the liver to increase blood glucose levels.
• Glucagon secretion is stimulated by low blood glucose levels.
• It inhibits glycogenesis.

Epinephrine

• Epinephrine (also known as adrenaline) is a hormone produced by the adrenal medulla.
• It is released in response to stress or exercise.
• Epinephrine stimulates glycogenolysis in the liver and muscles.
• It also promotes gluconeogenesis to increase blood glucose levels.

Cori Cycle

• The Cori cycle is a metabolic pathway in which lactate produced by anaerobic glycolysis in muscles is transported to the liver and converted to glucose through gluconeogenesis.
• The glucose is then returned to the muscles, where it can be used for energy.
• This cycle helps to recycle lactate and maintain glucose homeostasis.

Regulation of Carbohydrate Metabolism

• Carbohydrate metabolism is tightly regulated by hormones, enzymes, and allosteric effectors.
• Hormonal regulation includes insulin, glucagon, and epinephrine.
• Enzyme regulation involves allosteric modulation and covalent modification (e.g., phosphorylation).
• Key regulatory enzymes include hexokinase/glucokinase, phosphofructokinase-1 (PFK-1), pyruvate kinase, pyruvate carboxylase, fructose-1,6-bisphosphatase, glycogen synthase, and glycogen phosphorylase.
• The balance between glycolysis, gluconeogenesis, glycogenesis, and glycogenolysis is crucial for maintaining blood glucose levels and energy balance.

Hormones affecting Carbohydrate Metabolism

• Insulin:
• Gland: Pancreas (beta cells)
• Action: Lowers blood glucose by promoting glucose uptake, glycogenesis, and glycolysis
• Glucagon:
• Gland: Pancreas (alpha cells)
• Action: Increases blood glucose by stimulating glycogenolysis and gluconeogenesis
• Epinephrine:
• Gland: Adrenal medulla
• Action: Increases blood glucose by stimulating glycogenolysis and gluconeogenesis

Diabetes Mellitus (DM)

• Diabetes Mellitus is a metabolic disorder characterized by chronic hyperglycemia (elevated blood glucose levels).
• Results from defects in insulin secretion, insulin action, or both.
• Two major types: Type 1 and Type 2.

American Diabetes Association (ADA) Criteria for Diagnosis

Diabetes Mellitus (DM)

• Hemoglobin A1C ≥ 6.5%.
• Or Fasting Plasma Glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 hours.
• Or 2-hour Plasma Glucose (2-h PG) ≥ 200 mg/dL (11.1 mmol/L) during an Oral Glucose Tolerance Test (OGTT). The test should use a glucose load containing 75g anhydrous glucose dissolved in water.
• Or in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥ 200 mg/dL (11.1 mmol/L).

Impaired Glucose Tolerance (IGT)

• 2-hour Plasma Glucose (2-h PG) in the OGTT is between 140 mg/dL (7.8 mmol/L) and 199 mg/dL (11.0 mmol/L).

Impaired Fasting Glucose (IFG)

• Fasting Plasma Glucose (FPG) is between 100 mg/dL (5.6 mmol/L) and 125 mg/dL (6.9 mmol/L).

Type 1 Diabetes Mellitus

• Also known as insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes.
• Characterized by the autoimmune destruction of the insulin-producing beta cells in the pancreas.
• Leads to absolute insulin deficiency.
• Typically has a rapid onset and often diagnosed in childhood or adolescence.
• Patients require exogenous insulin for survival.
• Genetic predisposition and environmental factors play a role in its development.
• Patients are prone to ketoacidosis due to the lack of insulin, leading to uncontrolled lipolysis and ketone body formation.

Type 2 Diabetes Mellitus

• Also known as non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes.
• Characterized by insulin resistance, where cells fail to respond properly to insulin.
• Often associated with obesity, physical inactivity, and a family history of diabetes.
• Pancreas may initially produce normal or even elevated levels of insulin, but eventually, beta-cell dysfunction can lead to relative insulin deficiency.
• Has a gradual onset, often diagnosed in adulthood.
• Management involves lifestyle modifications (diet, exercise), oral hypoglycemic agents, and sometimes insulin.
• Patients are at risk for hyperosmolar hyperglycemic state (HHS), a condition of severe hyperglycemia and dehydration, but are less prone to ketoacidosis than those with type 1.

Comparison of Type 1 and Type 2 Diabetes Mellitus

• Type 1:
• Cause: Autoimmune destruction of pancreatic beta cells
• Insulin: Absolute deficiency
• Onset: Rapid, usually in childhood or adolescence
• Body weight: Normal or underweight
• Ketoacidosis: Common
• Treatment: Insulin injections or pump
• Genetic Predisposition: Moderate
• Environmental Factors: Significant role in triggering autoimmune response
• Type 2:
• Cause: Insulin resistance and progressive beta-cell dysfunction
• Insulin: Relative deficiency or insulin resistance
• Onset: Gradual, usually in adulthood
• Body weight: Often overweight or obese
• Ketoacidosis: Rare, but hyperosmolar hyperglycemic state (HHS) is possible
• Treatment: Lifestyle modifications, oral medications, sometimes insulin
• Genetic Predisposition: Strong
• Environmental Factors: Obesity, inactivity are major contributors

Gestational Diabetes

• Gestational diabetes develops during pregnancy in women who did not have diabetes before.
• It's characterized by high blood sugar levels that can affect both the mother and the baby.
• Typically diagnosed during the second or third trimester.
• Caused by hormonal changes during pregnancy, which can lead to insulin resistance.
• Women with gestational diabetes are at an increased risk of developing type 2 diabetes later in life.
• Management includes dietary changes, exercise, and sometimes insulin therapy.
• Monitoring blood glucose levels is essential to ensure a healthy pregnancy.

Other Types of Diabetes (Secondary Diabetes Mellitus)

• This category includes types of diabetes caused by specific underlying conditions or factors.
• Examples include diabetes due to genetic defects, endocrine disorders (e.g., Cushing's syndrome, acromegaly), diseases of the pancreas (e.g., pancreatitis, cystic fibrosis), drug-induced diabetes (e.g., glucocorticoids), and infections (e.g., congenital rubella).
• Treatment focuses on managing the underlying cause and controlling blood sugar levels.

Impaired Glucose Tolerance (IGT)

• IGT is a pre-diabetic state where blood glucose levels are higher than normal but not high enough to be classified as diabetes.
• It indicates a higher risk of developing type 2 diabetes, cardiovascular disease, and other complications.
• Diagnosed through an oral glucose tolerance test (OGTT).
• Characterized by normal fasting glucose but elevated glucose levels 2 hours after consuming a glucose load.
• Lifestyle modifications, such as diet and exercise, are crucial in preventing progression to type 2 diabetes.

Complications of Hyperglycemia (DM)

• Hyperglycemia leads to several changes and complications in the body affecting both microvascular and macrovascular systems:

Microvascular Complications

• Diabetic Retinopathy:
• High blood sugar damages blood vessels in the retina
• Can lead to blurred vision, floaters, and even blindness
• Diabetic Nephropathy:
• Damages the blood vessels (glomeruli) in the kidneys
• Impairs kidney function, possibly leading to kidney failure
• Diabetic Neuropathy:
• Nerve damage due to prolonged exposure to high blood sugar
• Peripheral neuropathy: affects the extremities, causing numbness, tingling, pain, and foot ulcers
• Autonomic neuropathy: affects the autonomic nervous system (digestion, heart rate, bladder control)
• Increased Risk of Infection:
• Hyperglycemia impairs the function of immune cells
• Increases susceptibility to bacterial and fungal infections
• Wound healing is slowed

Macrovascular Complications:

• Cardiovascular Disease:
• High blood sugar accelerates atherosclerosis (plaque buildup) in arteries
  • Increases the risk of coronary artery disease, heart attack, and stroke
• Peripheral Artery Disease (PAD):
• Reduced blood flow to the limbs due to atherosclerosis
• Causes pain, numbness, and increased risk of infections and amputations
• Cerebrovascular Disease:
• Increases the risk of stroke (blood clot or bleeding in the brain) due to damaged blood vessels

Other Complications:

• Skin Conditions:
• Increased risk of bacterial and fungal infections, dry and itchy skin
• Delayed Wound Healing:
• High glucose impairs white blood cell function
• Affects the body's ability to repair wounds
• Ketoacidosis (DKA):
• Primarily in type 1 diabetes due to insulin deficiency
• Body produces excess ketones (acidic byproducts of fat metabolism) due to lack of glucose for energy
• Can lead to a life-threatening condition
• Hyperosmolar Hyperglycemic State (HHS):
• Primarily in type 2 diabetes with severe hyperglycemia, dehydration, and altered mental status
• Gastroparesis:
• Occurs due to autonomic neuropathy that affects the stomach
• Delayed stomach emptying leading to nausea, vomiting, and erratic blood sugar control
• Increased Risk of Cognitive Impairment and Alzheimer's Disease.
• Non-alcoholic fatty liver disease (NAFLD)
• An accumulation of fat in the liver of people who drink little or no alcohol
• Over time, NAFLD can lead to liver damage, cirrhosis, and liver failure.

Mechanisms Contributing to Hyperglycemic Complications

• Polyol Pathway:
• Excess glucose is converted to sorbitol and fructose, leading to osmotic stress and cellular damage, particularly in the eyes, kidneys, and nerves
• Advanced Glycation End Products (AGEs):
• Glucose reacts with proteins and lipids to form AGEs
• AGEs accumulate in tissues, causing inflammation and damage
• Protein Kinase C (PKC) Activation:
• Hyperglycemia activates PKC, leading to altered gene expression, endothelial dysfunction, and vascular damage
• Oxidative Stress:
• High glucose levels increase the production of reactive oxygen species (ROS)
• ROS cause cellular damage and contribute to the progression of diabetes complications.

Hypoglycemia

• Hypoglycemia is defined as abnormally low blood glucose levels.
• Generally, a blood glucose level below 70 mg/dL (3.9 mmol/L) is considered hypoglycemia, but symptoms can vary.

Common Causes of Hypoglycemia

• Drug-Induced Hypoglycemia
• Often caused by medications used to treat diabetes
  • Insulin: Excessive insulin dosage or improper timing of insulin injections
  • Sulfonylureas (e.g., glipizide, glyburide): Stimulate insulin release from the pancreas, which can cause hypoglycemia, particularly if meals are skipped or delayed
  • Meglitinides (e.g., repaglinide, nateglinide): Similar to sulfonylureas but with a shorter duration of action, also posing a risk for hypoglycemia
• Other medications may also cause hypoglycemia, although less commonly
  • Quinine
  • Pentamidine
  • Salicylates
• Management involves adjusting medication dosages, monitoring blood glucose levels, and educating patients (especially those on insulin) about the signs and symptoms of hypoglycemia
• Reactive Hypoglycemia (Postprandial Hypoglycemia)
• Occurs within a few hours after eating a meal
• The body releases too much insulin in response to carbohydrate intake, causing a rapid drop in blood glucose levels
• Often seen in individuals who have had gastric surgery (e.g., gastrectomy, gastric bypass) or those with early-stage diabetes
• Symptoms include sweating, shakiness, anxiety, rapid heartbeat, and confusion
• Management involves eating smaller, more frequent meals; limiting simple carbohydrates; and increasing protein and fiber intake
• Fasting Hypoglycemia
• Occurs after prolonged periods without food (8 hours or more)
• Can be caused by various underlying medical conditions, including
  • Liver disease: Impaired glycogen storage and glucose production
  • Kidney disease: Impaired insulin clearance and glucose regulation
  • Hormone deficiencies: Deficiencies in cortisol (Addison's disease) or growth hormone, which play a role in glucose regulation
  • Tumors: Insulinomas (insulin-secreting tumors of the pancreas) or other tumors that consume glucose
  • Alcohol consumption: Inhibits gluconeogenesis
• Management involves identifying and treating the underlying cause
  • In the case of tumors, surgical removal may be necessary
  • Hormonal deficiencies may require hormone replacement therapy
  • Regular meals and snacks can help prevent fasting hypoglycemia in some cases

Enzymatic Glucose Methodologies

Glucose Oxidase Method

• Glucose oxidase catalyzes the oxidation of glucose to gluconic acid and hydrogen peroxide.
• Hydrogen peroxide is then reacted with a chromogen in the presence of peroxidase to produce a colored compound.
• The intensity of the color produced is proportional to the glucose concentration, typically measured spectrophotometrically.
• Commonly used in point-of-care glucose meters.
• Susceptible to interference from substances that can be oxidized by peroxidase or react with hydrogen peroxide.

Hexokinase Method

• Hexokinase catalyzes the phosphorylation of glucose by ATP to form glucose-6-phosphate (G-6-P) and ADP.
• Glucose-6-phosphate dehydrogenase (G-6-PD) then oxidizes G-6-P to 6-phosphogluconate, reducing NAD+ or NADP+ to NADH or NADPH.
• The increase in NADH or NADPH is measured spectrophotometrically at 340 nm, which is proportional to the glucose concentration.
• Considered a reference method for glucose measurement due to its high accuracy and minimal interference.
• Less susceptible to interferences compared to the glucose oxidase method.

Laboratory Diagnosis of Glucose-Related Disorders

Glucose Testing

• Fasting Plasma Glucose (FPG):
• Measurement of blood glucose after an overnight fast (typically 8-12 hours).
• Used to screen for and diagnose diabetes mellitus and pre-diabetes
• Oral Glucose Tolerance Test (OGTT):
• Measures blood glucose levels at specific intervals (e.g., 2 hours) after the patient consumes a standard glucose load (typically 75 grams).
• Used to diagnose gestational diabetes and assess insulin resistance.
• Random Plasma Glucose:
• Blood glucose measurement taken at any time of day, without regard to the last meal.
• Used for diagnosing diabetes in patients with classic symptoms of hyperglycemia.
• Hemoglobin A1c (HbA1c):
• Measures the average blood glucose level over the past 2-3 months.
• Reflects the percentage of hemoglobin that is glycated (glucose attached).
• Used for diagnosing and monitoring diabetes mellitus.
• Not affected by short-term fluctuations in glucose levels
• Continuous Glucose Monitoring (CGM):
• Tracks glucose levels in real-time throughout the day and night, using a sensor inserted under the skin.
• Provides a detailed picture of glucose trends and patterns
• Allows for better management of diabetes, particularly in type 1 diabetes.
• Self-Monitoring of Blood Glucose (SMBG):
• Patient uses a glucose meter to check blood glucose levels at home
• Used to adjust insulin dosages, diet, and exercise.

Other Carbohydrate-Related Analytes

• Fructosamine:
• Measures glycated serum proteins, reflecting average glucose levels over the past 2-3 weeks.
• Used as an alternative to HbA1c when HbA1c measurements are unreliable.
• Lactate:
• Measures the level of lactic acid in the blood.
• Elevated lactate levels can indicate anaerobic metabolism, hypoxia, or metabolic disorders.
• Used to diagnose and monitor conditions such as sepsis and shock
• Ketone Bodies:
• Measures the levels of beta-hydroxybutyrate, acetoacetate, and acetone in the blood or urine.
• Elevated ketone levels indicate increased fat metabolism and can be present in diabetic ketoacidosis (DKA) or starvation.
• Used to monitor patients with diabetes, particularly type 1.
• Insulin Level:
• Measures the amount of insulin in the blood.
• Helps to differentiate between type 1 and type 2 diabetes and diagnose insulinomas.
• C-Peptide:
• Measures the level of C-peptide in the blood, which is released when proinsulin is cleaved to form insulin.
• Indicates the amount of insulin being produced by the pancreas.
• Useful for assessing beta-cell function and diagnosing hypoglycemia.
• Glycogen:
• Glycogen storage diseases (GSDs) are a group of inherited metabolic disorders characterized by defects in enzymes controlling glycogen synthesis or breakdown.
• Analysis of glycogen structure may be involved GSD diagnosis.
• Galactose-1-Phosphate Uridyltransferase (GALT):
• Measurement to diagnose galactosemia
• Galactosemia is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galactose properly.
• Newborn screening programs often include testing for galactosemia to identify affected infants early, allowing for immediate dietary intervention to prevent severe complications.

Glucose in Urine and Cerebrospinal Fluid (CSF)

Urine Glucose

• Clinical Significance:
• Normally, glucose is not present in urine because it is completely reabsorbed by the renal tubules.
• Glucosuria (glucose in urine) typically occurs when the blood glucose level exceeds the renal threshold (approximately 180 mg/dL).
• Common causes of glucosuria include:
• Diabetes mellitus: Uncontrolled hyperglycemia exceeds the renal threshold.
• Renal glucosuria: A rare condition where the renal tubules are unable to reabsorb glucose effectively, even with normal blood glucose levels.
• Pregnancy: Increased glomerular filtration rates can sometimes exceed the tubular reabsorption capacity.
• Monitoring urine glucose can be used in management of diabetes, though blood glucose and HbA1c are preferred.
• Methodologies:
• Glucose oxidase method:
• A common enzymatic method used in urine dipsticks and automated analyzers.
• Glucose oxidase catalyzes the oxidation of glucose to gluconic acid and hydrogen peroxide.
• Hydrogen peroxide reacts with a chromogen in the presence of peroxidase to produce a colored compound, which is measured colorimetrically.
• Copper reduction test (Clinitest):
• A non-specific test that detects reducing substances, including glucose, in urine.
• Based on the reduction of cupric ions to cuprous oxide, resulting in a color change.
• Less specific than enzymatic methods and can be affected by other reducing agents in urine.

Cerebrospinal Fluid (CSF) Glucose

• Clinical Significance:
• CSF glucose levels provide information about glucose metabolism in the central nervous system.
• CSF glucose levels normally correlate with plasma glucose levels but are typically about 60-70% of the plasma glucose concentration.
• CSF glucose is decreased in conditions such as:
• Bacterial meningitis: Bacteria consume glucose in the CSF.
• Fungal meningitis: Fungi utilize glucose.
• Tuberculous meningitis: Mycobacterium tuberculosis consumes glucose.
• Hypoglycemia: Low plasma glucose levels result in decreased CSF glucose.
• CSF glucose is increased in:
• Hyperglycemia: Elevated plasma glucose levels result in increased CSF glucose.
• Traumatic tap: Contamination with blood.
• CSF glucose is evaluated along with protein levels, cell counts, and microbiological studies to diagnose central nervous system infections and other neurological disorders.
• CSF to serum glucose ratio less than 0.4 indicates abnormality.
• Methodologies:
• Glucose oxidase method:
• Enzymatic method commonly used to measure glucose in CSF due to its specificity and ease of use.
• Hexokinase method:
• A more accurate reference method used in clinical laboratories.
• Involves the phosphorylation of glucose by hexokinase, followed by spectrophotometric measurement.
• Collection and Handling:
• CSF glucose should be measured promptly after collection, as glycolysis can occur in the sample, leading to falsely low glucose readings.
• If immediate analysis is not possible, the sample should be refrigerated or preserved with a glycolysis inhibitor.
• A concurrent blood glucose measurement should performed when testing CSF glucose.