Carbohydrate Metabolism Flashcards
Carbohydrates Info
Major source of calories in diet
(CH2O)n = Hydrates of carbon
Aldehyde or ketone compounds with multiple hydroxyl groups
Aldose
Simple carbohydrate with 1 aldehyde
Ketose
Simple carbohydrate with 1 ketone group
Classification of Carbohydrates
Monosaccharides
Oligosaccharides/Disaccharides
Polysaccharides
Glycogen
Monosaccharides
Hexoses
Pentoses
Hexoses
6 carbon sugars
Glucose
Frustrose
Galactose
Pentoses
5 carbone sugars
Ribose
Deoxyribose
Oligosaccharides/Disaccharides
Sucrose
Lactose
Maltose
Sucrose
Glucose + Fructose
Lactose
Glucose + Galactose
Maltose
Glucose + Glucose
Polysaccharides
Long chain of branched carbohydrates
Contain 25-2500 glucose units
Starch
Starch
Plant carboyhydrate storage
Amylose and amylopectin subunits
Glycogen
Animal cell carbohydrate storage form
Digestion
Amylase
Disaccharidases
Amylase
Salivary Gland breaks polysaccharides into dextrins & maltose
Pancreatic amylase breaks polysaccharides into maltose
Disaccharidases
Brush border of intestine
Maltose, lactose, sucrose breaks into glucose, galactose, fructose
Monosaccharides Info
Enter GI circulation
Transported to liver
Glucose info
Sole source of body energy and only source of energy for some cells
Galactose, fructose go into liver and break down into glucose
Immediate energy needs of body
Met by aerobic and anaerobic glycolysis
Aerobic Glycolysis
Yields greatest amount of ATP
glucose converts into acetyl CoA and into Krebs (TCA) cycle
Clean metabolism: H2O + CO2
Anaerobic Glycolysis
Yields less ATP
Lactate must be cleared from the body
Glucose breaks down into pyruvate or lactate
Glucose storage
Liver glycogen: glycogenesis
Long term fasting: gluconeogenesis
Glycogenesis
Most immediate form of glucose in fasting state
Breakdown of glycogen
Gluconeogenesis
Formation of glucose from non-carbohydrate sources (amino acids, lactate, glycerol portion of lipids)
Hormonal Control of Circulating Glucose
Insulin
Glucagon
Growth Hormone
Glucocorticoids (Cortisol)
Adrenal/Epinephrine
Thyroxine (T4)
Insulin Info
Peptide hormone
Secreted by beta cells of islets of Langerhans
Turned on by elevated blood glucose
Binds to surface of body cells increasing membrane permeability to glucose
Stimulates synthesis of glycogen, lipids, and proteins
Body weight impacts the amount of insulin secreted
Hormones Antagonistic to Insulin
Glucagon
Adrenal/Epinephrine
Thyroxine (T4)
Growth Hormone
Glucocorticoids (Cortisol)
Glucagon
Polypeptide
Secreted by the alpha cells of the islets of Langerhans
Turned on by low blood glucose levels
Stimulates glycogenolysis and gluconeogenesis
Adrenal/Epinephrine
Adrenal medulla catecholamine
Stimulates glucogenolysis and lipolysis
Released in response to physical and emotional stress
Thyroxine (T4)
Thyroid amino acid hormone
Stimulates glycogeolysis and absorption of rate of glucose
Growth Hormone
Anterior pituitary polypeptide hormone
Stimulates glycogenolysis and inhibits glucose uptake by tissues
Glucocorticoids (Cortisol)
Adrenal cortex steroid hormone
Stimulates gluconeogensis
ADA Guidelines
Meet criteria on two subsequent days
- Symptoms of diabetes + random plasma glucose of >200 mg/dL
- A fasting plasma glucose >126 mg/dL
- During GGT, 2 hr after oral glucose, plasma glucose >200 mg/dL
- Glucose values between 105-125 mg/dL = impaired fasting glucose
Different Testing for Glucose
Random blood glucose
Fasting blood glucose
2-hours post prandial (after a meal)
Oral glucose tolerance test (GTT)
Serum and urine glucose and ketone bodies
Glycated Hemoglobin
Random Plasma Glucose
Collection not in relationship to time of last meal
>200 mg/dL = Presumptive Diabetes
Fasting Plasma Glucose
8 hour fast
Blood glucose level above reference range
- 105-125 mg/dL = Impaired fasting
- >126 mg/dL = Presumptive Diabetes
2 Hour Postprandial Glucose
Postprandial
Can give a standard glucose load of 75 g of glucose in solution or eat a carbohydrate rich meal
- >200 mg/dL = Diabetes mellitus
- <140 mg/dL = Normal
- 140-199 mg/dL = Impaired glucose tolerance
Oral Glucose Tolerance Testing (GTT)
Not the best test for diagnosing diabetes
May put undue stress on a diabetic
- Patient fasts for 8 hours
- Draw fasting blood glucose and collect fasting urine sample
- Ingest 75 g glucose load within 5 minutes
- Collect sampels at 30, 60, 120, and 180 minutes
- Time may be extended to 5 hours for hypoglycemia
Normal glucose response during GTT
30 min-1 hour: glucose elevates & insulin turned on
1-2 hours: glucose begins to fall under action of insulin
At 2 hours glucose has returned to normal reference range
3-5 hours: glucose remains in fasting range under action of antagonistic hormones
Abnormal glucose response during GTT
Fasting Blood Glucose: above reference range
30 min-1 hour: glucose elevates, insulin not secreted or not secreted in adequate amount
1-2 hours: Blood glucose level continues to rise
2 hours: glucose well above the reference range, glucosuria often present
3-5 hours: unregulated glucose remains high
Specimen Preparation
Separate sample from cells (lose 7% of glucose/hr)
Once separated, sample is stable 1 day at RT and several days if refrigerated
Gray Top tube: contains sodium fluoride which inhibits glycolysis
Methodology Serum or Plasma
Hexokinase
Glucose Oxidase
CSF Glucose
Concentration of glucose in CSF is about 2/3 of serum glucose level
Urine glucose
Blood glucose > renal threshold (180 mg/dL) = glucosuria
Associated with diabetes mellitus
Pregnant women may have lowered renal thresholds
- if glucose + on UA: test for diabetes
Benedict’s test: Alkaline CuSO4 measures reducing substances
Strip method: glucose oxidase
False Positive with Benedict’s test
Vitamin C
Uric Acid
Creatinine
Other Reducing sugars
False positive with oxidizing agents
Bleach
H2O2
Ketone Bodies
Formed when fat used as sole energy source
Assay for ketone bodies in serum and urine of Type 1 diabetics
Provide an indicator of the degree of ketosis
Methodology for Ketone
Sodium nitroprusside (purple +)
Reference range: Negative
Glycated Hemoglobins
Hgb A1a, Hgb A1b, Agb A1c (80% og Hb A1)
AKA glycosylated hemoglobin, glycohemoglobin
Formation of Glycated Hgb
When glucose reacts with amino group on hemoglobin to form ketoamine
Hgb A1C
Formation is increased if the blood glucose is elevated
Provides an indicator of control over past 2-3 months
ADA guidelines Hgb A1C
Test 2x/year if under good control
Test quarterly if therapy changes
Hgb A1C reference ranges
3-6%
Control over past 2 months = Gly Hgb <7%
Glycosylated Hemoglobin Methodology
Test performed on EDTA whole blood
Methods based on charge difference
Methods based on structural difference
Hgb A1C Charge Difference Methods
Ion exchange column separates Hgb A1C from other forms of Hgb
Electrophoresis and isoelectric focusing
Hgb A1C Structural Difference Methods
Immunoassay methods
Point of Care Devices
High performance liquid chromatography
Urine Microalbumin Info
Diabetes associated renal disease
Loss of albumin into urine
Urine Microalbumin ADA recommends
Annual screening
- Random urinary albumin/creatinine ratio
- 24 hour urine albumin
- 4 hour urine albumin
Urine Microalbumin Test Results
30-300 mg/day = reversible
>550 mg/day = not reversible
Primary Diabetes mellitus Info
Disorder of insulin production (absolute or relative)
Beta cells of the islets of Langerhans
Glucosuria
Glucose in urine
Polyuria
Large urine volume
Polydipsia
Large water intake from excessive thirst
Clinical Outcomes of Long-Term Out of Control Diabetes
Circulatory problems causing ulcers leading to amputation
Diabetic neuropathy
Atherosclerosis
Heart attack
Stroke
Nephrosclerosis
Kidney transplants
Retinopathy
Lead to blindness
Diabetic ketoacidosis
Sweet smelling breath
Rapid breathing
Lowered blood pH
Other complications
Diabetic diuresis (increase osmolality)
Diabetic coma
Type 1 Diabetes
Juvenile onset or absolute (IDDM)
High fasting glucose
NO insulin production
Autoimmune in nature
Type 1 Diabetes Testing
GTT does not return to normal 1-3 hours
Glucose remains high in absence of insulin
Urine = Positive for glucose
Ketone bodies produced if patient is burning fat and glucagon levels are high
Type 2 Diabetes
Mature onset or relative (NIDDM)
Familial association
Type 2 Diabetes Testing
Glucose above normal at 2 hr postprandial
Urine = Positive for glucose if >RT
May develop ketosis
Familial association
Secondary Causes of Hyperglycemia
Hormonally related
Acromegaly (elevated cortisol)
Cushing’s syndrome (rare - elevated thyroxine)
Hyperthyroidism
Gestational Diabetes mellitus
Diabetes expressed during pregnancy
Family history
Babies are large (4000 grams)
Mother may return to normal after pregnancy (could develop DM later in life)
Hypoglycemia
Blood glucose <50 mg/dL
Associated with coma because of cerebral dependence on glucose
Patient may present with lethargy and confusion
Causes of Hypoglycemia
Insulin or drug induced
Fasting hypoglycemia
Insulinoma
Reactive hypoglycemia
Insulin over production
