CARBOHYDRATES

- source of energy for human body

- aldehyde/ ketone w/ 2+ hydroxyl groups
- mono, di, polysaccharide
- D-glucose
D-glucose
- principal & almost exclusive CHO circulating in blood
- blood glucose from hydrolysis of dietary starch, conversion of other
dietary hexose into glucose by liver, & from synthesis of glucose from
AA, FA & lactate
- principal fuel for peripheral tissues
- maintained by metabolic processes & hormonal control
Hormonal Regulation
1. Insulin
- small peptide (-cells of Islets of Langerhans of pancreas): high
BG
- ONLY hormone that lowers blood glucose
- Inc membrane permeability: bind to receptors on cell surface
entry to liver, muscle & adipose tissue
- Enhance synthesis of glycogen, lipid & CHON
- Inc BG: secreted; dec BG: inhibited
2. Glucagon
- polypeptide (-cells of Islets of Langerhan of pancreas): low BG
- principal hormone: RAPID increase of BG in blood
- stimulates hepatic glycogenolysis & gluconeogenesis
3. Epinephrine
- adrenaline
- inc glucose by:
stimulating glycogenolysis & lipolysis while
inhibiting release of insulin
4. Thyroxine
- thyroid gland
- promotes glycogenolysis deplete glycogen stores in liver
5. Growth Hormone
- somatotropin (anterior pituitary)
- inhibits glucose uptake by tissues
- stimulates liver glycogenolysis raise glucose conc
6. Adrenocotricotropin (ACTH)
- stimulates release of cortisol (adrenal gland) inc glucose
7. Cortisol
- stimulates gluconeogenesis
8. Somatostatin
9. Somatomedins
Disorders of CHO
1. Hyperglycemia
2. Hypoglycemia
3. Inborn errors of CHO metabolism
- normal or dec plasma glucose, excretion of a nonglucose
reducing sugar in urine
HYPERGLYCEMIA: Diabetes Mellitus
- MOST IMPT--hyperglycemia
- Deficiency of insulin secretion, complications overtime
TYPE 1 DM
- severe DM
- absolute deficiency of insulin (autoimmune destruction of -cells)
- viral or chemical, genetic
- islet cell, insulin autoantibodies
- abrupt onset of symptoms following viral infection, ketosis
- REQUIRE
insulin treatment: prevent ketosis & sustain life
- History of rapid weight loss, polyphagia, polydipsia & polyuria
- Neurologic: confusion, disorientation & loss of consciousness
- Any age, frequently juvenile
- 10% of all DM; Asian/ African descent
Lab findings
- hyperglycemia
- polyuria, inc urine & serum osmolarity, inc specific gravity,
ketonemia, ketonuria, acidosis, electrolyte imbalance
Pathophysiology
Low insulin: impaired entry of glucose HIGH BG
High BG exceed renal reabsorptive capacity Glycosuria/
Glucosuria

Water is excreted w/ glucose Thirsty & hungry Polydipsia (H2O)

& Polyphagia (desire for eating)
Increase glucagons
a. Inhibited: Glycolysis
b. Stimulated: Glycogenolysis, lipolysis & gluconeogenesis
Catabolism of AA & FA-> inc acetyl CoA (cholesterol or ketoacid.
Acetoacetic acid. -hydroxybutyric acid & acetione) KETOSIS
a. ketonemia (blood)
b. ketonuria
c. sweet organic odor (acetone)
Overproduction of ketoacids acidosis/ low blood pH dec HCO3
[CO2 & H2O]
Depletion of HCO3 metabolic acidosis
Respiratory center stimulated rapid, deep breathing & increased
excretion of CO2 by lungs coma
TYPE 2 DM
- milder DM
- relative deficiency of insulin activity due to insulin resistance (normal
BUT insufficient peripheral response) & secretory defect
- inc amyloid deposition in tissue (starchlike-CHONS-CHO complex)
- env factors: excessive calories, lack exercise
- no relationship to viruses
- not prone to ketosis; doesnt require insulin
- inc risk of developing vascular complications & hyperosmolar coma
- obese, 40+, progess slowly
- most common DM: 80-90%
Pathophysiology
Hyperglycemic hyperosmolar nonketotic coma
- urinary losses of H2O, glucose & electrolytes (osmotic diuresis) w/o
sufficient fluid replacement DEHYDRATION high BG coma
Elderly patients
Treatment
Dietary measures
Insulin/ oral hypoglycemic agents
Complications (w/in 10-15 yrs)
Retinopathy (blindness)
Nephropathy
Neuropathy
Microvascular/ macrovascular disease
Heart attack & strokes (vascular complications)
Arteriosclerosis diminished BF to legs gangrene
Susceptibility to infection
Lab Dx
3 criteria:
Symptoms of DM + RPG >200mg/dL (11.1 mmol/L)
FPG >126mg/L (7mmol/L)
OGTT: 2 hours after oral glucose load >200mg/L
1.Casual (Random) Plasma Glucose (RPG)
- irrespective of last meal/ time of day
- presumptive DM: >200mg/L
2.Fasting Plasma Glucose (FPG)
- 8hr+ fasting
- DM: >126mg/L
3.Urine Glucose
- screening test
- 160-180mg/dL (8.9-80mmol/L)
4.Two-hour postprandial plasma glucose
- 2 hours after Px consumes std load of glucose (75g)
- DM: >200mg/dL
5.Oral Glucose Tolerance Test (OGTT)
- unlimited physical activity & unrestricted diet (150g CHO) for 3
days
- test: morning after fasting 10-16 hrs (H2O is permitted)
- fasting glucose

- nonpregnant: 75g flavored sol

- pedia: 0.75g/kg body weight
- pregnant: 100g
- drink ingested 15 minutes
- plasma glucose measured every 30 mins (2 hrs)
- Px seated throughout test
- Samples collected in NaF; w.in 4 hrs
- Factors that affect: illness, trauma, stress, some drugs
- Normal: rise 150mg/L or higher w.in 30-60 mins normal in
3 hrs
- Diabetic: higher for a longer period of time
- Gestational Diabetic:
a. fasting: >105mg/L
b. 1 hr glucose: >190mg/L
c. 2 hr: >165mg/L
d. 3 hr: >145mg/L
6.Glycated Hb
- glycosylated Hb; Hb A1c
- determine compliance w/ therapy; extent to w/c diabetic ctrl
has been achieved
- more convenient than OGTT
- only 1 blood sample
7.Self-monitoring of BG
- capillary whole blood
- serum/ plasma higher than WB
GESTATIONAL
- pregnancy: hormonal & metabolic changes
- family history of diabetes, recurrent monilial infection/ large
babies (>4K g), infants w/ congenital anomalies
- maternal symptoms mild; fetus: devastating (congenital
malformation & perinatal mortality)
- after delivery: normal or DM in later life
IGT (Impaired glucose tolerance)
- plasma glucose level following oral glucose load: not normal
but not sufficiently abnormal to be DM
IFG (impaired fasting glucose)
- plasma glucose level following an 8-hour fast: greater than
normal but not sufficiently high to be DM
HYPOCGLYCEMIA
- low glucose: <50mg/L
- reactive hypo: excessive administration of insulin
- factitious hypo: other hypoglycemic agent
- ethanol ingestion: reduction of gluconeogenesis
- fasting/ spontaneous hypo: uncommin
- rapid fall in plasma glucose release of epinephrine & symptoms
caused by epinephrine:
a. weakness, sweat, shakiness, trembling, nausea,
lightheadedness, rapid pulse
b. adregenergic symptoms
- gradual fall in plasma glucose: <20 or 30 mg/L:
a. impairement of CNS function
b. neuroglycopenia: headache, confusion, lethargy,
unconsciousness
Lab: samples drawn every 4 hrs
INBORN ERRORS OF CARBOHYDRATES METABOLISM
1. Glycogen Storage Disease
- inheritable disorders: deficiency of 1 or more enzymes involved
in metabolism of glycogen
- liver, heart or musculoskeletal system
2. Type I (Von Gierkes)
- more common type
- short stature & huge abdomen (massive enlargement of liver)
- severe hypoglycemia, inc plasma lactic acid, hyperlipidemia
- caused by deficiency or absence of enzyme glucose 6phosphate in liver (needed for final step in formation of glucose
from hepatic glycogen)
3. Galactosemia
- rare genetic disorder
- inability to metabolize galactose
- develop vomiting, diarrhea, cirrhosis of liver, cataracts & mental
retardation
4. Hereditary Fructose Intolerance
- deficiency of fructose-1-phosphate aldolase

- vomiting, hypoglycemia, hepatomegaly, failure to thrive

5. Mucopolysaccharide storage disease
- structural components of cartilage, bone, skin & other CT
- mucopolysaccharidoses
- hereditary disorders
- glycosaminoglycans: accumulate in various tissues & excreted in
urine
- dermatan sulfate, heparin sulfate & keratin sulfate
6. Hurlers syndrome
- severe progressive disorder characterized by corneal clouding &
death (before age 10)
- coarse facies, skeletal abnormalities, developmental delay.
hepatosplenomegaly