Diabetes Mellitus Flashcards
1
Q
this defines a group of metabolic disorders that share the phenotype of hyperglycaemia that affects multiple organ systems.
A
diabetes mellitus
2
Q
what are the 3 factors that contribute to hyperglycaemia
A
- reduced insulin secretion
- decreased glucose utilization
- increased glucose production
3
Q
what are some consequences of DM
A
- end stage renal disease
- non traumatic lower extremity amputations
- adult blindness
- CVD
4
Q
what are the two types of DM
A
Type 1 -> autoimmune
type 2 -> insulin resistant/insulin secretion impaired
5
Q
true or false: type 1 DM is “reversible”
A
false
6
Q
true or false: type 2 DM is “reversible”
A
true
7
Q
true or false: gestational DM is “reversible”
A
true
8
Q
what is a normal fasting plasma glucose level
A
<5.6 mmol/L
9
Q
what is a fasting plasma glucose level in someone who has DM
A
> 7.0 mol/L
10
Q
what is considered an impaired plasma glucose level
A
6.1-6.9mmol/L
11
Q
what is a normal hemoglobin A1C
A
<5.7%
12
Q
what is an impaired hemoglobin A1C
A
5.7-6.4%
13
Q
what is a hemoglobin A1C in someone with DM
A
> 6.5%
14
Q
widespread use of FPG or HbA1c is recommended due to asymptomatic cases, complications etc. what characteristics of an individual would lead to testing
A
recommended for all individuals age > 45 every three years or earlier if a BMI >25 or ethnically relevant definition for overweight
15
Q
what is the function of the LIVER in glucose homeostasis
A
glucose production and storage
16
Q
what is the function of the MUSCLE and FAT tissue in glucose homeostasis
A
glucose utilization
17
Q
what is the function of the PANCREATIC ISLET in glucose homeostasis
A
releases hormones that helps with utilization and production of glucose
18
Q
ingestion of nutrients stimulates cells in the gut to release these two incretins
A
glucose-dependant insulinotropic peptide (GIP) and glucagon-like peptide (GLP-1)
19
Q
what are the functions of GIP and GLP-1
A
- stimulate the production of insulin and inhibit glucagon
- promote proliferation of beta-cells and inhibit apoptosis
- GLP-1 delays gastric emptying and increases satiety
20
Q
what happens when the pancreas becomes aware that blood glucose levels are decreased
A
- pancreas decreases insulin and increases glucagon
- the liver and the kidney contribute to increased glucose production
21
Q
what happens when the brain becomes aware that blood glucose levels are decreased
A
- increased sympathoadrenal outflow which increases release of catecholamines (epi, NE, acetylcholine)
- this can either cause symptoms which in turn results in ingestion or
- signals to the kidneys and liver to make more glucose
22
Q
what are some clinical manifestations of hyPOglycemia
A
- confusion, fatigue, loss of conciousness
- palpitations, tremor
- sweating, hunger, pallor
- BP usually elevated
23
Q
this activates pro-inflammatory, pro-coagulant and pro-atherothrombotic responses in T1DM, T2DM and non-diabetic individuals. results in:
- increased platelet aggregation
- increased intravascular coagulation
- decreases arterial vasodilator mechanisms
A
hypoglycaemia
24
Q
this has an attenuated sympathoadrenal response, impaired counter regulatory effect, six times the risk of severe iatrogenic hypoglycaemia and it is reversible
A
hypoglycaemia unawareness HAAF (hypoglycaemia associated autonomic failure)
25
____ is secreted in the pancreas by the beta cells of the islets of langerhans
insulin
26
the two insulin chains are synthesized as a single high moclular weight precursor called _________
preproinsulin
27
proinsulin is cleaved to form _______ and _______ in the secretory granule cells of there beta-cell
insulin and C-peptide
28
how is insulin secreted from the beta cells
glucose enters the beta cells by GLUT -> glucose in transformed into glucose-6-phospohate but glucokinase and then into pyruvate -> ATP/ADP is produced from the mitochondria -> ATP sensitive K+ channel is activated and K+ is released -> depolarization occurs and Ca2+ enters the beta cell -> increase cAMP levels -> stimulates exocytosis of secretory granules from the beta cell -> insulin is released
29
mutations in what proteins may cause monogenic forms of diabetes (e.g. neonatal DM, maturity-onset diabetes of the young)
- GLUT
- Mitochondria
- ATP sensitive K+ channel
- Islet transcription factors
- Glucokinase
30
explain the insulin receptor and its action
- alpha subunit (hormone binding domains) are located extracellular
- beta subunit is intracellular
- when insulin binds to the receptor it stimulates intrinsic tyrosine kinase activity
- receptor autophosphorylation occurs
- activation of PI-3 kinase
- translocation of GLUT-4 to the cell surface
- glucose uptake ip skeletal muscle and fat
31
true or false: insulin promotes catabolic effects
false - anabolic
32
what effects does insulin have regarding carbohydrates (in muscles, adipose tissue and liver)
- increases glucose uptake, oxidation and storage (increased glycogen synthesis, decreased glycogenolysis)
- decreased gluconeogenesis
33
what effects does insulin have regarding AAs and proteins (in muscles)
- increase amino acid uptake and protein synthesis
- decrease amino acid release
34
what effects does insulin have regarding lipids (adipose tissue and liver)
- increased triglyceride synthesis
- decreased free fatty acids and glycerol
- decreased oxidation of FFA to ketoacids (liver)
35
this is the result of autoimmunity against the pancreatic beta cells; consequence is complete or near-total insulin deficiency
type 1 DM
36
are islet cell autoantibodies more present in type 1 or type 2 DM
type 1
37
what are some causes of type 1 DM
- genetics: class II MHC genes involved (e.g. DQA1*0301, DWB1*0302 and DQB1*0201 have a strong risk)
- environmental: molecular mimicry, vitamin D def., microbiome
38
interactions of genetic, environmental and immunologic factors lead to immune-mediated destruction of the pancreatic beta cells and insulin ________
deficiency
39
type 1 DM can develop at any age but most commonly before the ago of __
20
40
there are 3 stages to developing type 1 DM. this stage is characterized by the development of two or more islet cell autoantibodies but the maintenance of normoglycemia
stage 1
41
there are 3 stages to developing type 1 DM. this stage is defined by continued autoimmunity and the development of dysglycemia
stage 2
42
there are 3 stages to developing type 1 DM. this stage is defined by the development of hyperglycaemia that exceeds the diagnostic criteria for the diagnosis of diabetes
stage 3
43
type 1 DM is _________ (selective/nonselective) autoimmune destruction of beta cells
selective
44
_________, which is inflammation of the islets of langerhans occurs after beta cells are destroyed in type 1 DM
insulitis
45
what is the current theory regarding the mechanism of beta cell destruction
- begins with one beta cell molecule then spreads to other islet molecules
- neoantigens (foreign proteins absent in normal tissues) occur which is a result go excessive cells killed
46
why does an individual with diabetes have hyperglycaemia?
- no beta cells
- no insulin available to cells
- no glucose entering cells, therefore it accumulates in the blood causing hyperglycaemia
- cells starve (decreased ATP production, decreased energy = tired)
47
what are some of the compensatory mechanisms of hyperglycaemia (no glucose going into cells - all accumulating in blood)
- catecholamines released (episode/NE): this increases glycogenolysis in the liver
- cortisol is released: promotes gluconeogenesis
- patient tends to eat more because cells are starving (still rapid weight loss)
- ketones from lipolysis produces halitosis
48
when an individual has hyperglycaemia, it causes an increase in intravascular osmotic pressure which causes ___________ (fluid retention/dehydration)
dehydration
49
what happens to the kidney in hyperglycaemia
kidney increases (GFR)
- polyuria (urinate more frequently)
- glucosuria (sweet tasting urine)
50
what happens to the thirst centre in hyperglycaemia
polydipsia (excessive thirst)
51
this is a complication of hyperglycaemia; commonly caused by alterations in nutrition, inactivity, or inadequate use of antidiabteic meds; more prone to infections
acute hyperglycaemia
52
this is a complication of hyperglycaemia; includes hypertension, CVD, ESRD, and stroke risk
chronic hyperglycaemia
53
what are some macrovascular complications of hyperglycaemia
CVD and stroke
54
what are some mcirovascular complications of hyperglycaemia
- retinopathy (damage to the blood vessels of the light sensitive tissue at the back of the eye (retina)
- neuropathy (deterioration of kidney function)
55
true or false: DM is an independant risk factor for coronary artery disease (CAD). CAD risk factors (dyslipidemia, hypertension) are present in uncontrolled DM and can improve with adequate blood glucose control
true
56
hyperglycaemia disrupts platelet function and growth of the basement membrane. __________ (thinning/thickening) of the basement membrane may improve with glycemic control
thickening
57
what are some automonomic disturbances in diabetic neuropathy
- GI disturbances
- bladder dysfunction
- tachycardia
- postural hypotension
- sexual dysfunction
58
what are some sensory disturbances of diabetic neuropathy
- carpal tunnel syndrome
- paresthesia (burning or prickling sensation in hands, feet, etc)
- dysesthesias (symptoms that disrupt how you experience touch-based sensations)
59
this occurs when your body doesn't have enough insulin to allow blood sugar into your cells for energy. therefore the liver breaks down fat for fuel, a process that produces acids called ketones. when too many ketones are produced quickly they can build up to a dangerous amount in your body
diabetic ketoacidosis
60
describe the steps of DKA
insulin deficiency -> altered fat metabolism -> increased lipolysis -> increased conc. of FFF -> FFA oxidation -> increased ketoacids -> ketosis (can lead to vomiting and dehydration then shock) -> ketoacidosis -> shock
61
are K+ levels normal in someone with ketoacidosis?
serum levels are normal but intracellular levels are decreased
62
this is a polygenetic multifactorial disease with a strong genetic component; it is the most common form of DM
type 2 DM
63
what is the main contributing environmental factor to type 2 DM
obesity
64
true or false: type 2 DM is defined as decreased insulin secretion
false: change in number or sensitivity of insulin receptors
65
this can be characterized by
- impaired insulin secretion and resistance
- excessive hepatic glucose production
- abnormal fat metabolism
- systemic low-grade inflammation
type 2 DM
66
true or false: 5-10% of weight loss can terminate type 2 DM
true
67
obesity (increased FFA) effects: ____________: decreases muscle responsiveness by interfering with IRS signalling, decreases adiponectin and leptin levels
lipotoxcity
68
obesity (increased FFA) effects __________: inhibition of PPAR gamma by TNF from hypertrophic adipocytes and macrophages
inflammation
69
obesity (increased FFA) effects _________ deposition from cell apoptosis combined with hyperglycaemia and FFA may cause impaired insulin secretion
amylin
70
what is the relationship between insulin secretion and insulin resistance in a normal individual
when an individual becomes more insulin resistant, insulin secretion increases
71
what is the relationship between insulin secretion and insulin resistance in an individual with impaired glucose tolerance
if insulin secretion increases and there is not more resistance
