glucose disorders

Question 1

disorders of glucose metabolism

Answer 1

hyperglycaemia - increased blood sugar

hypoglycaemia - decreased blood sugar

Question 2

hyperglycaemia causes

Answer 2

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

Question 3

diabetes mellitus

Answer 3

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

Question 4

complications if uncontrolled diabetes mellitus

Answer 4

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

Question 5

glucose metabolism in a healthy person

Answer 5

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

Question 6

glucose metabolism in the diabetic

Answer 6

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

Question 7

if you find ketones un serum or urine

Answer 7

fat metabolism is higher than normal

Question 8

types of diabetes mellitus

Answer 8

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

Question 9

Type I diabetes

Answer 9

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

Question 10

pathogenesis of type 1 diabetes

Answer 10

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

Question 11

type 1 diabetes autoimmune antibodies

Answer 11

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

Question 12

types of antibodies in type 1 diabetic

Answer 12

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

Question 13

type 1 diabetes - genetics

Answer 13

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

Question 14

Initiation of type 1 diabetes

Answer 14

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

Question 15

Tpe 2 diabetes

Answer 15

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

Question 16

type 2 diabetes pathogenesis

Answer 16

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

Question 17

type 2 diabetes - loss of Beta cell function

Answer 17

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

Question 18

type 2 diabets -insulin resistance

Answer 18

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

Question 19

type 2 diabetes -Euglycemic insulin clamp

Answer 19

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

Question 20

rare insulin reistant syndomes - type 2 diabetes

Answer 20

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

Question 21

type 2 diabetes - diet & exercise

Answer 21

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

Question 22

type 2 diabetes - genetic factors

Answer 22

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

Question 23

testing criteria for asymptomatic adults for type 2 diabetes mellitus

Answer 23

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

Question 24

impaired glucose tolerance test

Answer 24

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

greater chance of developing diabetes mellitus as they age

Question 25

categories of impaired glucose tolerance and defence ranges

Answer 25

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

Question 26

other specific types of diabetes mellitus

Answer 26

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

Question 27

Cushing disease signs & lab findings

Answer 27

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+ ```

Question 28

Gestational Diabetes

Answer 28

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

Question 29

gestational diabetes mellitus- Risk factors

Answer 29

first degree relative with diabetes obesity advance maternal age glycosuria previous pregnancy with adverse outcomes

Question 30

how Gestation diabetes mellitus affects fetus

Answer 30

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)

Question 31

gestational diabetes mellitus complications - baby & mother

Answer 31

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

Question 32

renal threshold of glucose

Answer 32

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

Question 33

tests used to diagnose diabetes mellitus

Answer 33

fasting plasma glucose (FPG)( fasting blood glucose) oral glucose tolerance test ( OGTT) HBa1c symptoms & family history

Question 34

fasting plasma glucose

Answer 34

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

Question 35

Oral Glucose Tolerance Test ( OGTT) requirements

Answer 35

omit medications that affect glucose tolerance test in the morning following 3 days of unrestricted diet /activity fast 10-16 hrs

Question 36

2hr OGTT procedure & references ranges

Answer 36

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 )

Question 37

factors affecting OGTT prior to testing

Answer 37

carbohydrate intake time of previous food consumed absorption issues ( previous surgeries) medications ( thiazides, estrogens, etc. ca increase glucose ) age inactivity stress weight

Question 38

factors affecting OGTT during testing

Answer 38

posture anxiety coffee tobacco time of day ( do in morning ) activity amount of glucose given

Question 39

intravenous tolerance test

Answer 39

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

Question 40

postprandial blood glucose

Answer 40

performed 2 hours after a mixed meal references ranges the same as 2 hr glucose tolerance test

Question 41

screening tests for Gestational Diabetes Mellitus (GDM) | 1 step approach

Answer 41

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

Question 42

screening test for GDM 2 step approach

Answer 42

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 ```

Question 43

3 hr OGTT results

Answer 43

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