Carbohydrate Metabolism

Classification of Carbohydrates:

1. Size of base carbon chain: triose (3 carbons), tetrose (4), pentose (5), hexose (6)

2. Location of CO Function group

   1. Aldose: terminal carbonyl group (aldehyde group)

   2. Ketose: Carbonyl group in the middle, linked to 2 other carbon atoms (ketone group)

3. Stereochemistry of compound

   1. Different spacial arrangements around each asymmetric

      carbon, forming stereoisomerscarbon, forming stereoisomers

   2. Two different series are possible: D and L.

4. Number of sugar units in chain

   1. Monosaccharides: 1 unit (glucose, fructose, galactose)

   2. Disaccharides: 2 units (maltose, lactose, sucrose)

   3. Polysaccharides: >10 units (starch [glucose], glycogen)

Stereochemistry of compound:

• Different spatial arrangements around each asymmetric carbon, forming steroisomers

• Two different series are possible: D and L

Number of sugar units in chain:

• Monosaccharides: 1 unit (glucose, fructose, galactose)

• Disaccharides: 2 units (maltose, lactose, sucrose)

• Polysaccharides: >10 units (starch [glucose], glycogen)

Size of base carbon chain:

• Triose (3 carbons), Tetrose (4), Pentose (5), hexose (6)

Location of CO function group:

• Aldose

  • Terminal carbonyl group (aldehyde group)

• Ketose

  • Carbonyl group in middle, linked to 2 other carbon atoms (ketone group)

• Aldose

• Ketose

• Two forms of carbohydrates

Chemical properties of Carbohydrates: Reducing carbohydrates:

• Carbohydrate must have ketone or aldehyde group

• All monosaccharide & disaccharides = reducing agents

• Examples: glucose, maltose, fructose, lactose, galactose

Chemical properties of Carbohydrates: Nonreducing carbohydrates:

• Do not have ketone or aldehyde group & will not reduce

Glucose metabolism:

• Primary source of energy for humans; nervous system totally depends on glucose from extracellular fluid

Fate of glucose:

• Most ingested carbohydrates are polymers (starch, glycogen)

• These are converted to disaccharides, & disaccharides are converted to monosaccharides by enzymes

• Monosaccharides are absorbed by the gut & transported to liver

• THE ONLY CARBOHYDRATE DIRECTLY USED FOR ENERGY OR STORED AS GLYCOGEN;GALACTOSE & FRUCTOSE MUST BE CONVERTED TO GLUCOSE

• Once glucose enters cell, it is shunted into 1 of 3 metabolic pathways

• ULTIMATE GOAL OF THE CELL IS TO CONVERT GLUCOSE TO CARBON DIOXIDE AND WATER

Regulation of Carbohydrate Metabolism:

• Liver, pancreas & other endocrine glands control blood glucose concentrations within a narrow range

Hormones that control glucose levels (gl):

• Insulin: from pancreas; decreases glucose

• Glucagon: from pancreas: increases glucose

• Epinephrine & glucocorticoids: from adrenal gland: increases glucose

• Growth hormone & ACTH: from anterior pituitary: increases glucose

• Thyroxine (thyroid gland) & somatostatin (pancreas): increases glucose

• Will be question asking which one is NOT one that increases glucose levels

Hyperglycemia:

• An increase plasma glucose levels caused by imbalance of hormones

Diabetes Mellitus:

• A group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both

Type 1 Diabetes Mellitus:

• Results from cellular-mediated autoimmune destruction of beta cells of pancreas, causing absolute deficiency of insulin

• Constitutes 10-20% of all diabetes cases; occurs in childhood & adolescence and is genetic/hereditary

Type 2 Diabetes Mellitus:

• Characterized by hyperglycemia caused by an individual’s resistance to insulin, resulting in a relative insulin deficiency

• Constitutes majority of diabetes cases & is adult onset

• Risk factors include age, obesity, lack of exercise, genetic predisposition

Other specific types of diabetes mellitus:

• Associated with genetic defects of beta cell function or insulin action, pancreatic/endocrine diseases, etc.

Gestational diabetes mellitus:

• Glucose intolerance with onset during pregnancy

Pathophysiology of Diabetes Mellitus:

• Hyperglycemia, possibly severe

• Glucosuria can occur after renal tubular transporter system for glucose becomes saturated

Pathophysiology of Diabetes Mellitus: Type 1:

• Absence of insulin with excess of glucagon

• Greater tendency to produce ketones

Pathophysiology of Diabetes Mellitus: Type 2:

• Presence of insulin & hyperinsulinemia, attenuated glucagon

• Greater tendency to develop hyperosmolar nonketotic states

Criteria for Testing for Pre-Diabetes and Diabetes:

• All adults >45 years old should have fasting blood glucose measured every 3 years, unless already diagnosed with diabetes

Testing of glucose should be earlier or more frequent with these risk factors:

• Overweight tendencies (BMI greater than or equal to 25 kg/m²)

• Habitual physical inactivity

• Family history of diabetes in a first-degree relative

• High-risk populations

• History of gestational diabetes or delivering a baby >9lb

• Hypertension (>140/90)

Criteria for testing for pre-diabetes and diabetes: Type 2 diabetes

• Testing in children, beginning at age 10 or at onset of puberty & with follow-up testing every 2 years

  • Family history (first-or second degree) of type 2 diabetes

  • Race/ethnicity

  • Signs of insulin resistance

  • Maternal history of diabetes or gestational diabetes mellitus

Three methods of diagnosis:

• Must each be confirmed by one of the others on a subsequent day

1. HbA1c > or = 6.5% using a method that is NGSP certified

2. A fasting plasma glucose of > or = 126 mg/dL

3. An oral glucose tolerance test (OGTT) w/ 2-hour postload (75g- glucose level) > or = 200 mg/dL (mostly to confirm gestational diabetes)

4. Diabetes symptoms + random glucose level of > or = 200 mg/dL

Diabetes symptoms:

• Excessive urination

• Rapid weight loss

• Drinking a lot of water

Patients with following criteria have “pre-diabetes”:

• Fasting glucose of > or = 100 mg/dl but <126 mg/dL

• OGTT 2-hour level of > or = mg/dL but <200 mg/dL

Normal glucose level:

• ~99 mg/dL

When does a glucose level start to be concerning?:

• ~180 mg/dL

Criteria for Testing & Diagnosis of Gestational Diabetes:

• Age >25 years

• Overweight

• Strong family history of diabetes

• History of abnormal glucose metabolism

• History of poor obstetric outcome

• Presence of glycosuria

• Diagnosis of polycystic ovarian syndrome

Hypoglycemia:

• Decreased plasma glucose levels

• Can be transient & relatively insignificant or life-threatening

• Occurs in health-appearing and sick patients, as a result of reaction to medication or of illness

• Symptoms appear at glucose level of about 50-55mg/dL

Symptoms of hypoglycemia:

• Increased hunger

• Sweating

• Nausea

• Vomiting

• Dizziness

• Nervousness

• Shaking

• Blurred speech

• Blurred sight

• Mental confusion

Methods of Glucose Measurement:

• Can be measured from serum, plasma, or whole blood

• Serum or plasma must be refrigerated & separated from cells within 1 hour to prevent loss of glucose

• Fasting blood glucose should be obtained in morning after 8-10 hour fast

• Most common methods of glucose analysis use enzymes glucose oxidase or hexokinase

• Nonspecific methods are used in urinalysis section of lab to detect reducing substances other than glucose

Self-Monitoring of Blood Glucose:

• Those with type 1 diabetes should check levels 3 or 4 times/day

Glucose Tolerance and 2-Hour Postprandial Tests:

• Patient drinks standardized (75g) glucose load

• Glucose measurement is taken 2 hours later

What is used as a point of care method:

• Statstrip

• Results/Flowsheets Glucose Level

Glycosylated Hemoglobin/Hemoglobin A1C:

• Long-term blood glucose regulation can be followed by measurement of glycosylated hemoglobin

• Provides clinician with time-averaged picture of patient’s blood glucose concentration over past 3 months

• Glycosylated hemoglobin: Formation of a hemoglobin compound produced when glucose reacts with amino group of hemoglobin

• Hemoglobin A1C (HbA1C) is most commonly detected glycosylated hemoglobin

• Affinity chromatography is preferred method of measurement

Ketones:

• Produced by liver through metabolism of fatty acids

• Provide a ready energy source from stored lipids

• Increase with carbohydrate deprivation or decreased carbohydrate use (diabetes, starvation/fasting, high fat-diets)

• Specimen requirement is fresh serum or urine

Three ketone bodies:

• Acetone (2%)

• Acetoacetic acid (20%)

• 3 beta-hydroxybutyric acid (78%)

Acetone:

• 2%

Acetoacetic acid:

• 20%

2-beta-hydroxybutryric acid:

• 78%

• Three ketone bodies

Microalbuminuria:

• Increase in urinary albumin is an early sign of renal nephropathy, a complication of diabetes mellitus

• Annual assesment of kidney function by determination of urinary albumin excretion is recommended for diabetic patients

• Defined as persistent albuminuria in range of 30-299 mg/24 hr or albumin-creatinine ratio of 30-300 ug/mg

Islet Autoantibody and Insulin Testing:

• Presence of autoantibodies to beta-islet cells of pancreas is characteristic of type 1 diabetes

• Not currently recommended for diabetes diagnosis