glucose disorders Flashcards
disorders of glucose metabolism
hyperglycaemia - increased blood sugar
hypoglycaemia - decreased blood sugar
hyperglycaemia causes
diabetes mellitus ***
excess growth hormone
- decreases entry of glucose into cells
excess glucocorticoids
- decreases entry of glucose into cells
- promotes gluconeogenesis
excess adrenocorticotropic hormone ( ACTH)
- increases secretion of cortisol
- promotes gluconeogenesis
diabetes mellitus
group of metabolic diseases categorized by hyperglycaemia from defects in insulin secretion, insulin action or both -hyperglycemia is main symptom * other symptoms: polyuria glucosuria polydipsia polyphagia ketonemia ketonuria sudden weight loss - glucsoenot getting to cells so fatty acids are broken down for energy
complications if uncontrolled diabetes mellitus
microvascular problems
- nephropathy
- neuropathy
- retinopathy
circulatory problems - can lead to amputation
- don’t take blood from feet of a diabetic, if you must a doctors permission is required
heart disease
glucose metabolism in a healthy person
brief fast
glucose is supplied to the extracellular fluid from the liver through the breakdown of glycogen
prolonged fast (>1 day)
glucose is synthesized though other sources ( lipids, proteins )
amino acids & fatty acids can be used ti produce glucose
after a meal
increased blood glucose & dietary amino acids stimulates the beta cells of pancreas to release insulin
this increase of insulin promotes the transport of glucose into cells
glucose metabolism in the diabetic
both production & metabolism of glucose are increased
release of insulin ( type l ) or cellular response to insulin ( type II) are decreased
decrease in insulin creates a semi- starvation state causing triglycerides & proteins to be use as a fuel source
- increases free fatty acids & ketones
a prolonged rise in blood glucose occurs after meals due to a decrease in insulin or insulin resistance
if you find ketones un serum or urine
fat metabolism is higher than normal
types of diabetes mellitus
Type l diabetes mellitus (IDDM)
Type II diabetes mellitus (NIDDM) - non insulin dependent
Other specific types of diabetes
Gestational debates mellitus (GDM)
Type I diabetes
10-20 % of diabetes mellitus cases
childhood or adolescence onset
absolute deficiency of insulin
- autoimmune destruction of beta-cells
- typically occurs after a viral infection
ketosis tendency - increase in ketone bodies ( not in type 2)
insulin dependent
pathogenesis of type 1 diabetes
autoimmune destruction of pancreatic beta cells by mononuclear cell infiltration ( called insulitis )
- this destruction is mediated by T cells
- begins months or years before clinical presentation
- 80-90% reduction in beta calls is required to induce symptoms
- rate of destruction is faster in children than in adults
type 1 diabetes autoimmune antibodies
antibodies can be detected in serum years before increase blood glucose levels are seen
screening for antibodies is controversial bc no treatment exists to prevent or delay the onset
types of antibodies in type 1 diabetic
- Islet cell cytoplasmic antibodies (ICAs) - *******2nd HIGHEST
found in 75-85% of newly diagnosed type 1 diabetics
detected by immunofluorescence microscopy on frozen section of pancreatic tail - Insulin autoantibodies ( IAAs) - HIGHEST ***
found in >90 % of children who develop type 1 before the age of 5; 40% of those after the age of 12 - Antibodies to the 65 kDa isoform of glutamic acid ( GAD65)
found in 60 % of newly diagnosed type 1 patients
found up to 10 years before onset - insulinoma -asssocated antigens ( IA-2A & IA-2BA)
found in > 50 % if newly diagnosed type 1 patients - Zinc transport ZnT8
found in 60-80% if newly diagnosed type 1 patients
type 1 diabetes - genetics
susceptibility to type 1 is inherited
- mode of inheritance is complex & not well defined
Multigenetic trait
- main locus is the major histocompatibility complex on chromosome6***
- 11 other loci on 9 chromosomes also contribute
Human leukocyte antigen ( HLA) -DQ & -DR genetic factors are the most important determinants for risk of type 1
genetic markers are not routinely measured as they have little value for diagnosis or management
Initiation of type 1 diabetes
initiation can be caused by viruses
- Rubella
- Mumps
- Enterovirus
- Coxsackie B virus
some studies have implicated early exposure to cow’s milk
- this model has been debated
Tpe 2 diabetes
80-90% of diabetes mellitus
adult onset
relative deficiency of insulin
- resistance to insulin with an insulin decretory defect
strong genetic predisposition
- increase in age, obesity, lack of exercise
- weight loss can usually improve hyperglycaemia
milder symptoms than type 1
- more likely to go into hyperosmolar coma
- not prone to ketosis
- not insulin dependent
type 2 diabetes pathogenesis
insulin resistance
-decreased ability insulin to act on peripheral tissue
Beta cell dysfunction
- inability of the pancreas to produce enough insulin to compensate for insulin resistance
type 2 diabetes - loss of Beta cell function
loss of function can be caused by;
increased demand
- on beta cells caused by insulin resistance
selective glucose unresponsiveness
- loss of glucose-induced insulin release
- the increased concentration of glucose in the blood renders the beta cells unresponsive to glucose ( glucotoxicity) **
increased fatty acids ( lipotoxicity ) **
note:the number of beta cells in type 2 patients is also reduced
type 2 diabets -insulin resistance
defined as: a decreased biological response to normal concentrations of circulating insulin
found in:
- obese , non-diabetic individuals
- type 2 diabetes
attributed to a defect in insulin action
type 2 diabetes -Euglycemic insulin clamp
patient receives constant insulin IV infusion in one are while also receiving variable amounts of IV glucose in the other arm to maintain glucose at a normal fasting concentration
possible findings
**Euglycemia: normal blood glucose with a marked increase in indigenous insulin
**Hyperglycaemia: increased blood glucose despite large does of exogenous insulin
rare insulin reistant syndomes - type 2 diabetes
Type A insulin resistance syndrome
- hyperinsulinemia
- acanthosis nigricans ( areas of darkened skin particularly in body folds)
- ovarian hyperandrogenism ( acne, inflamed skin, hair loss from scalp, body hair growth, infrequent menstruation; polycystic ovarian syndrome is the main cause )
Insulin Resistance syndrome
- aka syndrome X or Metabolic syndrome
- insulin resistance
- hyperinsulinemia
- obesity
- dysplipidemia( high triglycerides, low HDL)
- hypertension
type 2 diabetes - diet & exercise
diet & exercise are important determinants
- 60-80% of type 2 individuals are obese
and inverse relationship exists between the degree of physical activity & the prevalence of type 2 diabetes
- this protective effect is thought to be due to sketeletal muscle &adipose tissue having an increased sensitivity to insulin
type 2 diabetes - genetic factors
genetic factors contribute to development of type 2 but the mode of inheritance is unknown
testing criteria for asymptomatic adults for type 2 diabetes mellitus
beginning at age 45- every 3 years more frequent testing if patient has additional risk factors : -overweight -physically inactive - family history in a 1st degree relative -high-risk minorities - history of GDM or having a baby >9lbs -hypertension -low HDL -elevated triglycerides - history of cardiovascular disease
impaired glucose tolerance test
glucose levels aren’t normal but not abnormal enough to be considered diabetes mellitus
greater chance of developing diabetes mellitus as they age
categories of impaired glucose tolerance and defence ranges
Impaired glucose tolerance ( IGT)
- 2 hrs postload plasma glucose of **(7-8 - 11. 1 mol/L)
impaired fasting glucose
- added in 1997 to avoid OGTT
- fasting glucose of **(6.1 - 6.9 mmol/L)
these patients are prediabetics and are at a risk for developing cardiovascular disease
other specific types of diabetes mellitus
associated with certain secondary conditions :
- genetic defects of beta cell function
- pancreatic disease ( decrease insulin production )
- endocrine diseases ( ex. cushing ; hyperadrenocorticism, too much adrenal hormones especially corticosteroids )
- drug or chemical induced insulin receptor abnormalities
- other genetic syndromes
Cushing disease signs & lab findings
caused by Excessive Cortisol
signs :
- truncal obesity
- moon-shaped face
- hump back on upper back
- hypertension
- hirsutism
- carbohydrate intolerance ( diabetes )
lab findings INCREASED -cortisol -glucose -aldosterone -Na+
Gestational Diabetes
inset during Pregnancy
due to metabolic hormonal changes
- normally insulin resistance is increased during pregnancy, a normal glucose concentration is maintained by increasing insulin secretion
- if a woman cannot supplement insulin sufficiently, GDM will develop
return to normal after delivery
higher risk of developing diabetes mellitus later
screening is doen 24-28 weeks gestation
gestational diabetes mellitus- Risk factors
first degree relative with diabetes
obesity
advance maternal age
glycosuria
previous pregnancy with adverse outcomes
how Gestation diabetes mellitus affects fetus
fetus will have increase glucose circulating from mom
increased glucose causes an increase insulin secretion
Once baby is born & umbilical cord is cut, the increased glucose from the mother is abruptly terminated
there is still residual increased in insulin which causes a severe drop in glucose ( hypoglycaemia in baby)
gestational diabetes mellitus complications - baby & mother
baby
- hypocalcemia
- hypoglycemia
- increased birth weight ( macrosomia )
- hyperbilirubinemia
- respiratory distress syndrome
mother
- high rate of cesarean delivery
- hypertension
- increased risk of developing type 2 diabetes
renal threshold of glucose
no glucose in urine of healthy individuals
renal threshold of glucose = the level of glucose in the blood above which glucose is excreted in the urine: 8.8-9.9 mmol/L
tests used to diagnose diabetes mellitus
fasting plasma glucose (FPG)( fasting blood glucose)
oral glucose tolerance test ( OGTT)
HBa1c
symptoms & family history
fasting plasma glucose
performed after 10-16 hr fast
normal: 3.9- 6.0 mmol/L
impaired : 6.1-6.9 mmol/L
diabetes : _>7.0 mmol/L on 2 or more occasions
critical values : < 2.5 mmol/L or > 25 mmol/L
Oral Glucose Tolerance Test ( OGTT) requirements
omit medications that affect glucose tolerance
test in the morning following 3 days of unrestricted diet /activity
fast 10-16 hrs
2hr OGTT procedure & references ranges
- measure fasting glucose
_>7.0 mmol/L STOP
if < 7.0 mmol/L proceed - give patient a 75g dose of glucose or ( 1.75g/kg body weight for a child )
- measure glucose 2 hrs after glucose was fully consumed ( consume within 5 mins)
normal <7.8 mmol/L
impaired 7.8-11.1 mmol/L
diabetes mellitus _> 11.1 mmol/ L ( confirm on another day )
factors affecting OGTT prior to testing
carbohydrate intake
time of previous food consumed
absorption issues ( previous surgeries)
medications ( thiazides, estrogens, etc. ca increase glucose )
age
inactivity
stress
weight
factors affecting OGTT during testing
posture
anxiety
coffee
tobacco
time of day ( do in morning )
activity
amount of glucose given
intravenous tolerance test
recommended for people with
- malabsorption disorders
- previous gastric or intestinal surgeries
2 methods:
- both administer glucose intravenously
- differ in concentration of glucose ( g/kg)
- differ in measurement time
postprandial blood glucose
performed 2 hours after a mixed meal
references ranges the same as 2 hr glucose tolerance test
screening tests for Gestational Diabetes Mellitus (GDM)
1 step approach
recommended that all non diabetic pregnant woman be screened at 24-28 weeks gestation
perform after an overnight fast
( at least 8 hrs)
measure FPG
give 75 g of oral glucose
measure plasma glucose at 1 & 2 hrs after drink
one value must meet or exceed:
fasting 5.1mmol/L
1hr 10.0mmol/L
2hr 8.5mmol/L
screening test for GDM 2 step approach
- screening test
give 50 g glucose
measure after 1 hr
if _>7.8 mmol/L perform 3 hr glucose OGTT
2. diagnosis ( 3hr OGTT) perform afte an overnight fast measure FPG give 100g oral glucose load values are measured every hour over the 3 hours
3 hr OGTT results
if 2 of 4 values are met or exceeded GDM is confirmed
fasting plasma glucose 5.3 mmol/L
1 hr 10.0 mmol/L
2hr 8.6mmol/L
3 hr 7.8 mmol/L
