CARBOHYDRATES Flashcards
Aldoses
All except fructose (ketose)
Ketose
Fructose
Hexoses
D-glucose
D-galactose
D-fructose
Only L enantiomer CHO and a Pentose
L-Ribose
Tetrose
D-erythrose
Triose
D-glyceraldehyde
non reducing sugar (no hemiacetal group)
Sucrose
Order of Hormonal regulation of glucose metabolism
1) cellar uptake
2) glycolysis
3)glycogenesis
4) lipogenesis
5) glycogenolysis
6) gluconeogenesis
7) lipolysis
Product of aerobic glycolysis
Pyruvate
Product of anaerobic glycolysis
Lactate
Insulin promotes
Cellular uptake
Glycolysis
Glycogenesis
Lipogenesis
Insulin inhibits
Glycogenolysis
Gluconeogenesis
Lipolysis
Glucagon promotes
Glycogenolysis
Gluconeogenesis
TCA cycle happens in what intracellular organ
Mitochondria
Effect of insulin to plasma glucose level
Decreased
Effect of glucagon on plasma glucose
Increased
Main regulators of glucose metabolism
Insulin and glucagon
Source of insulin in the body
Beta cells of the islets of Langerhans in the PANCREAS
Source of glucagon in the body
Alpha cells of the islets of Langerhans in the PANCREAS
Source of somatostatin in the body
Delta cells of the islets of Langerhans in the PANCREAS
Source of cortisol
Adrenal cortex
Source of epinephrine
Adrenal medulla
Source of ACTH and Growth hormone
Anterior pituitary gland
Thyroxine source
Thyroid
Human plancetal lactogen source
Placenta
Effects of cortisol, epinephrine, ACTH, GH, Thyroxine, hPL on plasma glucose
Increased
Paracrine regulation of insulin and glucagon secretion
Somatostatin
Promotes gluconeogenesis and lipolysis
Cortisol
Promotes glycogenolysis and lipolysis
Epinephrine
Promotes cortisol secretion, gluconeogenesis, and glycogenolysis
ACTH
Inhibits cellular uptake and glycolysis ; insulin antagonist
Growth hormone
Promotes intestinal absorption of glucose, gluconeogenesis and glycogenolysis
Thyroxine
Homologous to growth hormone (insulin antagonist)
Human placental lactogen (hPL)
Hypoglycemic disorder that occurs after 10 hours without food ; secondary to hyperinsulinism (insulinoma), hormonal deficiencies, genetic disorders, autoimmunity or drug induced
Post-absorptive/fasting
Hypoglycemic disorder that occurs usually 4 hours after eating a meal
Post-prandial/alimentary/reactive
Hypoglycemia symptoms begin to appear at plasma glucose level between
50-55 mg/dL
Hypoglycemic symptoms that include tremulous, palpitations, anxiety, diaphoresis, hunger and paarasthesias ; related to autonomic nervous system ; predominates in reactive hypoglycemia
Neurogenic
Hypoglycemic symptoms that include dizziness, tingling, blurred vision, behavioral changes, seizure, and coma ; common in fasting ; decrease glucose in the brain
Neuroglycopenic
Panic value for hypoglycemia
40 and below mg/dL
A true manifestation of hypoglycemia presents with a triad of symptoms called
Whipple’s triad :
1) symptoms of hypoglycemia
2) low plasma glucose level (50 mg/dL and below)
3) relief of symptoms following glucose administration
Diagnostic criteria for insulinoma
Change in glucose level 25 mg/dL or below (degree of decrease from baseline) in coincident with INCREASED insulin, pro insulin, C-peptide, and DECREASED BHA (beta-hydroxy butyric acid)
Endogenous Hyperinsulinism - pancreatic tumor cells produce insulin
Insulinoma
Administration of excess dose of insulin
Exogenous hyperinsulinism
Insulin is increased together with proinsulin and C-peptide
Endogenous hyperinsulinism (insulinoma)
Increased insulin ; normal proinsulin and C-peptide
Exogenous hyperinsulinism (excess dose of insulin)
A marker of type I DM
C-peptide (decreased or negative)
Fragments released from the cleavage of proinsulin
C-peptide and Insulin
Fragments released from the cleavage of proinsulin (resembles letter C)
C-peptide
Most abundant ketone bodies (78%)
Beta-hydroxybutyrate / beta-hydroxybutyric acid
Decreased /negative insulin, proinsulin, c-peptide, and increased beta-hydroxybutyrate
Type I DM
Beta cell destruction leading to absolute insulin deficiency
Type I DM
Type I DM positive for autoantibodies
Immune-mediated Type I DM
Type I DM of unknown cause/etiology (negative for autoantibodies)
Idiopathic Type I DM
Approximately 99% of cases of type I DM are?
Positive for auto-antibodies (immune-mediated)
Insulin RESISTANCE with progressive insulin deficiency ; Initially, insulin production is normal, but the cells do not respond to it properly, which eventually leads the pancreas to stop secreting insulin ; chronic hyperglycemia is pancreatotoxic causing insulin deficiency
Type II DM
Other types of DM : Genetic defects of B cell function
Type IIIa
Other types of DM : Genetic defects in insulin action
Type IIIb
Other types of DM : diseases of the EXOCRINE PANCREAS (pancreatitis, pancreatomy, pancreatic cancer/neoplasia, CYSTIC FIBROSIS, hemochromatosis, fibrocalculous pancreatic atty
Type IIIc
Other types of DM : endocrinopathies / hormonal distortions
Type IIId
Other types of DM : drug- or chemical-induced
Type IIIe
Other types of DM : infections
Type IIIf
Other types of DM : uncommon forms of immune-mediated diabetes
Type IIIg
Other types of DM : other diabetes-related genetic syndromes
Type IIIh
Type of DM characterized by glucose intolerance during pregnancy ; major risk factor for type 2 DM
Gestational diabetes
Gestational diabetes may convert to type __ DM in 30-40% of cases within 10 years
Type 2 DM
DM type : Comprises less than 10% of cases
Type 1 DM
DM type : comprises more than 90% of cases; more common in women than in men
Type 2
DM type : childhood or juvenile onset
Type 1 DM
DM type : onset is during adulthood
Type 2 DM
DM type : autoimmunity (+ autoantibodies) and genetic predisposition/likelihood to inherit HLA-DR3/DR4
Type 1 DM
BMI of 25 kg/m^2 and above
Overweight / obese
BMI of 30 kg/m^2 and above
Obese
Hypertension blood pressure
140/90
Dyslipidemia (HDL____ ; TG____)
Less than or equal to 35 mg/dL ; greater than or equal to 250 mg/dL
Type 2 DM risk factors (3)
Genetic factors
Conditions characterized byInsulin resistance
Conditions related to metabolic syndrome or obesity
DM type : requires insulin injection
Type 1 DM
DM type : therapy involves lifestyle changes, oral hypoglycemic agents ; may require insulin
Type 2 DM
Acute complications among type 1 DM patients
Diabetic ketoacidosis (High BHA)
Acute complications in type 2 DM ; associated plasma glucose level exceeding 1000 mg/dL
Hyperglycemic hyperosomolar non-ketotic coma
Panic value for hyperglycemia
Greater than or equal to 500 mg/dL
Lab findings in both type 1 and 2 DM
Increased plasma glucose, plasma osmolarity, urine glucose, urine SG, anion gap, and osmolal gap
Low pH and sodium
DM symptoms (3Ps)
Polyuria, polydipsia, polyphagia ; pruritis, poor wound healing
Long term complications (Microvascular complications) :
Nephropathy, retinopathy, neuropathy,
Earliest indicator of nephropathy
Microalbuminuria
Long term complications (Macrovascular complications) :
Coronary artery diseases (MI)
Cerebral vascular accident (stroke)
Screening for DM: all adults 45 years old and above must be screened every _____
3 years
Screening for DM: individuals with 1 or more risk factors must be screened every ____ at a younger age
Year (annual screening)
Test and diagnostic criteria for DM:
Random plasma glucose must be in conjunction with _______
Symptoms of DM (3Ps) - polydipsia, polyphagia, polyuria
Test and diagnostic criteria for DM:
Requires fasting for at least 8 hours ; most preferred diagnostic test
Fasting plasma glucose
Test and diagnostic criteria for DM:
In 2h PG (OGTT), the patient must be on a normal to high carbohydrate intake of at least ____ grams per day for __ days prior to the test ; patient must fast ____ hours before the test
150 grams or more ; 3 days ; 8-14 hours
Test and diagnostic criteria for DM:
2h PG (OGTT) : the first component of routine OGTT for non pregnant adults ; second component of OGTT
Fasting plasma glucose ; administration of standard glucose load of 75 grams or 1.75 grams/kg Body weight
Test and diagnostic criteria for DM:
Not affected by fasting ; sample must be ___
HbA1C ; EDTA whole blood
NORMAL cut off value : RPG
<200 mg/dL
NORMAL cut off value : FPG
<100 mg/dL
NORMAL cut off value : 2h PG (OGTT)
<140 mg/dL
PRE-DM cut off value : FPG
100-125 mg/dL
PRE-DM cut off value : 2h PG (OGTT)
140-199 mg/dL
PRE-DM cut off value : HbA1c
5.7 - 6.4%
DM cut off value : RPG
200 mg/dL and above
DM cut off value : FPG
126 mg/dL and above
DM cut off value : 2h PG (OGTT)
200 mg/dL or greater
DM cut off value : HbA1c
6.5% or greater
Test and diagnostic criteria for GDM :
Test for high risk women ; glucose load of __
One step method or 2h OGTT ; 75 grams
Test and diagnostic criteria for GDM :
ONE STEP METHOD Cut off value :
FPG ___
1h PG ___
2h PG ___
92 mg/dL or greater
180 mg/dL or greater
153 mg/dL or greater
Test and diagnostic criteria for GDM :
Screening test ; fasting is not required ; glucose load of ___
Two-step method : 1h OGTT ; 50 grams
Test and diagnostic criteria for GDM :
TWO STEP METHOD (1h OGTT) Cut off value :
140 mg/dL and above
Test and diagnostic criteria for GDM :
TWO STEP METHOD : Requires fasting ; glucose load ____
3h OGTT ; 100 grams
Test and diagnostic criteria for GDM :
TWO STEP METHOD (3h OGTT) Cut off value :
FPG ___
1h PG ___
2h PG ___
3h PG ___
95 mg/dL or greater
180 mg/dL or greater
155 mg/dL or greater
140 mg/dL or greater
GDM is established in Two-step method, if any __ of the cut off values are met or exceeded
Any 2
TEST FOR MONITORING GLYCEMIC CONTROL :
______ is most commonly analyzed using POCT devices at home or at the patient’s bedside ; collected _ to __ times daily for type 1 DM patients according to ADA guidelines
About __ to __ % lower than plasma glucose
Whole blood ; 3-4 times daily ; 10-15%
WHOLE BLOOD ADA glycemic goal (Pre-prandial)
70-30 mg/dL
WHOLE BLOOD ADA glycemic goal (Post-prandial)
180 mg/dL or greater
TEST FOR MONITORING GLYCEMIC CONTROL :
Hb A with glucose IRREVERSIBLY attached to one or both N-terminal valines of the B-chains
Glycated hemoglobin / HbA1c
TEST FOR MONITORING GLYCEMIC CONTROL :
HbA1c provides an index of average blood glucose levels over the past __ to __ months
2 to 3 months
TEST FOR MONITORING GLYCEMIC CONTROL :
HbA1c is unreliable in patients with ______
Hemolytic disorders
HbA1c ADA glycemic goal
<7%
HbA1c poor control
> 12%
TEST FOR MONITORING GLYCEMIC CONTROL :
Glycosylated albumin ; used to assess glycemic control over the past __ to __ weeks in cases when HbA1c is unreliable
Fructosamine ; 2-3 weeks
TEST FOR MONITORING GLYCEMIC CONTROL :
Fructosamine has the advantage of using SERUM samples but is unreliable when serum albumin is _____ mg/dL
3 mg/dL or less
TEST FOR MONITORING GLYCEMIC CONTROL :
Fructosamine reference range
205-285 mg/dL
TEST FOR MONITORING GLYCEMIC CONTROL :
Early indicator of diabetic nephropathy
Microalbuminuria
TEST FOR MONITORING GLYCEMIC CONTROL :
Microalbuminuria is a persistent albuminuria in two out of three urine collections of _____ ug/min, _____ mg/24h, or an albumin-creatinine ratio of ______ ug/mg or 3.5-30 mg/mmol within a 3- to 6- month period
Albumin excretion rate:
20-200 ug/min
30-300 mg/24
Albumin-creatinine ratio:
30-300 ug/mg
For glucose measurement, use sodium fluoride or SST to prevent glycolysis. Otherwise, glycolysis will take place at a rate of
2 mg/dL / hour @ 4C
7 mg/dL / hour @ RT
Effect of 10% contamination with 5 dextrose in glucose measurement
Plasma glucose will increase by 500 mg/dL
Common initial reaction in copper reduction
BENEDICT’S RXN:
Cupric ions from copper sulfate are reduced to cuprous ions by glucose in the presence of heat and alkaline environment
A nonspecific test for glucose ; subject to falsely increased result due to the presence of other reducing agents
Copper reduction
Copper reduction methods : redox is observed
Folin-Wu and Nelson-Somogyi
Copper reduction method:
Cu+ + Phosphomolybdic acid —> phosphomolybdenum
Folin-Wu
Pho(s) = Fo
Copper reduction method:
Cu+ = arsenomolybdic acid —> arsenomolybdenum
Nelson-Somogyi
(Arse)N(o) = Nelson
Copper reduction method:
Color of phosphomolybdenum and arsenomoybdenum
Blue
Copper reduction method:
Color of free neocuproine and Cu-neocuproine
Colorless ; yellow-orange
Involves inverse colorimetry (colored reactant becomes colorless when reduced by glucose) ; AKA Hagedorn-Jensen method
Ferric reduction
Ferric reduction :
Color ferricyanide and ferrocynide
Yellow-orange ; colorless
More specific than copper and ferric reduction ; AKA Dubowski method
Condensation
Glucose + o-Toluidine —> Schiff’s base
Condensation
Condensation :
Color of Schiff’s base
Green
Component of the reagent mixture that converts Alpha-D-glucose (35% in the plasma) to Beta-D-glucose (65%)
Mutarotase
Oxidizing agent used in Peroxidase-coupled/Trinder reaction
H2O2 - hydrogen peroxide
Oxidizing agent used in Peroxidase-coupled/Trinder reaction
H2O2 - hydrogen peroxide
Chromogen used in Peroxidase-coupled/Trinder reaction
4-aminophenazone / 4-aminoantipyrene
Peroxidase-coupled/Trinder reaction : oxidized chromogen
Quinoneimine
Peroxidase-coupled/Trinder reaction : color of quinoneimine
Red / red-purple
Glucose oxidase method : subject to many interferences
POD-coupled/Trinder reaction
Peroxidase-coupled/Trinder reaction :
effect of strong oxidizing agents
Falsely increased
Peroxidase-coupled/Trinder reaction :
Effect of reducing agents (ascorbic acid, keto acids, drug metabolites)
Falsely decreased
Peroxidase-coupled/Trinder reaction : major interferent
Ascorbic acid
Glucose oxidase method :
Measurement of the degree of oxygen consumption using a pO2 (Clark) electrode ; requires addition of molybdate and iodide or catalase and ethanol to prevent reformation of O2
Polarographic
Possible source of error in polarographic method
Reformation of oxygen
Reformation of oxygen in polagrophic method is prevented by the addition of?
Molybdate and iodide / catalase and ethanol
“MICE”
Enzymatic method :
A uv method (absorbance @____ nm ) ; reference method ; coupling reaction is highly specific
Hexokinase ; increased absorbance @340 nm
Hexokinase: effect of hemolyzed//icteric sample
Falsely decreased
Enzymatic method :
Uv or colorimetric/spectrophotometric ; highly specific for glucose, not subject to interference from substance normally found in the serum ; not commonly used except in glucose POCT
Glucose dehydrogenase
Glucose dehydrogenase : dye used to enable colorimetric-spectrophotometric measurement
Tetrazolium dye
Glucose dehydrogenase :
Formed by the reaction of NADH and Tetrazolium in the presence of diaphorase ; color
Formazan (blue)
Inborn of errors of carbohydrate metabolism :
Due to deficiency of one or three enzymes involved in galactose metabolism ; affected children present with mental retardation, failure to thrive, and galactosuria
Galactosemia
3 enzymes invovolved in galactose metabolism
Galactose-1-phosphate uridyl transferase (GALT)
Galactokinase (GALK)
Uridine diphosphate galactose-4-epimerase (GALE)
type of glycogen storage diseases the usually manifest with hepatomegaly, hypoglycemia, and growth retardation
Hepatic glycgenoses
Most common hepatic glycogenoses ; presents with hypoglycemia, lactic acidosis,and hyperuricemia
Von Gierke disease
type of glycogen storage disease that manifest with EXERCISE intolerance, MUSCLE cramps, fatigue, and weakness
Muscle glycogenoses
GSD TYPE
Enzyme deficient : glycogen synthase
0
GSD TYPE
Enzyme deficient : Glucose-6-phosphate
Type I (Von Gierke)
GSD TYPE
Enzyme deficient : lysosomal acid alpha granules
Type II (Pompe)
GSD TYPE
Enzyme deficient : glycogen debranching enzyme
Type 3 (Cori-Forbes)
GSD TYPE
Enzyme deficient : glycogen branching
Type 4 (Andersen)
GSD TYPE
Enzyme deficient : phosphorylase
Type V (Mc Ardle)
GSD TYPE
Enzyme deficient : glycogen phosphorylase
Type VI (Hers)
GSD TYPE
Enzyme deficient : phosphofructokinase
Type VII (Tarui)
GSD TYPE
Enzyme deficient : adenyl kinase, phosphorylase B kinase
Type VIII (Hug/Ohtani)
GSD TYPE
Enzyme deficient : phosphorylase kinase
Type 9 (Bresolin)
GSD TYPE
Enzyme deficient : cyclic AMP-dependent kinase, phosphoglycerate mutase
Type 10 (Tonin)
GSD TYPE
Enzyme deficient : glucose transporter-2
Type 11 (Fanconi-Bickel)
GSD TYPE
Enzyme deficient : aldolase
Type 12 (kreuder)
