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glucose disorders Flashcards

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1
Q

disorders of glucose metabolism

A

hyperglycaemia - increased blood sugar

hypoglycaemia - decreased blood sugar

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2
Q

hyperglycaemia causes

A

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
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3
Q

diabetes mellitus

A 
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
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4
Q

complications if uncontrolled diabetes mellitus

A

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

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5
Q

glucose metabolism in a healthy person

A

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

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6
Q

glucose metabolism in the diabetic

A

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

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7
Q

if you find ketones un serum or urine

A

fat metabolism is higher than normal

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8
Q

types of diabetes mellitus

A

Type l diabetes mellitus (IDDM)
Type II diabetes mellitus (NIDDM) - non insulin dependent
Other specific types of diabetes
Gestational debates mellitus (GDM)

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9
Q

Type I diabetes

A

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

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10
Q

pathogenesis of type 1 diabetes

A

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
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11
Q

type 1 diabetes autoimmune antibodies

A

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

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12
Q

types of antibodies in type 1 diabetic

A
  1. 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
  2. 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
  3. 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
  4. insulinoma -asssocated antigens ( IA-2A & IA-2BA)
    found in > 50 % if newly diagnosed type 1 patients
  5. Zinc transport ZnT8
    found in 60-80% if newly diagnosed type 1 patients
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13
Q

type 1 diabetes - genetics

A

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

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14
Q

Initiation of type 1 diabetes

A

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

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15
Q

Tpe 2 diabetes

A

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
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16
Q

type 2 diabetes pathogenesis

A

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

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17
Q

type 2 diabetes - loss of Beta cell function

A

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

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18
Q

type 2 diabets -insulin resistance

A

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

19
Q

type 2 diabetes -Euglycemic insulin clamp

A

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

20
Q

rare insulin reistant syndomes - type 2 diabetes

A

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
21
Q

type 2 diabetes - diet & exercise

A

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

22
Q

type 2 diabetes - genetic factors

A

genetic factors contribute to development of type 2 but the mode of inheritance is unknown

23
Q

testing criteria for asymptomatic adults for type 2 diabetes mellitus

A 
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
24
Q

impaired glucose tolerance test

A

glucose levels aren’t normal but not abnormal enough to be considered diabetes mellitus

greater chance of developing diabetes mellitus as they age

25
Q

categories of impaired glucose tolerance and defence ranges

A

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

26
Q

other specific types of diabetes mellitus

A

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
27
Q

Cushing disease signs & lab findings

A

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+
28
Q

Gestational Diabetes

A

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

29
Q

gestational diabetes mellitus- Risk factors

A

first degree relative with diabetes

obesity

advance maternal age

glycosuria

previous pregnancy with adverse outcomes

30
Q

how Gestation diabetes mellitus affects fetus

A

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)

31
Q

gestational diabetes mellitus complications - baby & mother

A

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
32
Q

renal threshold of glucose

A

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

33
Q

tests used to diagnose diabetes mellitus

A

fasting plasma glucose (FPG)( fasting blood glucose)

oral glucose tolerance test ( OGTT)

HBa1c

symptoms & family history

34
Q

fasting plasma glucose

A

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

35
Q

Oral Glucose Tolerance Test ( OGTT) requirements

A

omit medications that affect glucose tolerance

test in the morning following 3 days of unrestricted diet /activity

fast 10-16 hrs

36
Q

2hr OGTT procedure & references ranges

A
  1. measure fasting glucose
    _>7.0 mmol/L STOP
    if < 7.0 mmol/L proceed
  2. give patient a 75g dose of glucose or ( 1.75g/kg body weight for a child )
  3. 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 )

37
Q

factors affecting OGTT prior to testing

A

carbohydrate intake

time of previous food consumed

absorption issues ( previous surgeries)

medications ( thiazides, estrogens, etc. ca increase glucose )

age

inactivity

stress

weight

38
Q

factors affecting OGTT during testing

A

posture

anxiety

coffee

tobacco

time of day ( do in morning )

activity

amount of glucose given

39
Q

intravenous tolerance test

A

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
40
Q

postprandial blood glucose

A

performed 2 hours after a mixed meal

references ranges the same as 2 hr glucose tolerance test

41
Q

screening tests for Gestational Diabetes Mellitus (GDM)

1 step approach

A

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

42
Q

screening test for GDM 2 step approach

A
  1. 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
43
Q

3 hr OGTT results

A

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

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