1
Q
maintaining balance of insulin and glucagon
A
- always have each - depending on which is predominate will dictate what happens
- trying to prevent glucotoxicity (damage to arteries, Beta cells, eyes, nerves and kidneys)
2
Q
insulin/ key analogy
A
-dominates in fed state and opens up storage organs for glucose
3
Q
when does glucagon start to predominate?
A
-in fasting state, about 8 hours after you eat
4
Q
fed state
A
- insulin is predominate
- insulin is like a key that unlocks the storage organs
- insulin promotes the storage organs
- insulin promotes storage of glucose
- liver and muscle tissue: glucose-> glycogen: glycogenesis
- adipose tissue: glucose-> glycerol (+ FFA)-> TGA: fat synthesis
- net effect: decrease blood glucose
5
Q
fasting state
A
- glucagon is predominant
- liver and muscle: glycogenolysis (glycogen-> glucose)
- after 8 to 12 hours: muscle breakdown releases aa and glycogen
- fat tissue breaks down FFA and glycerol-> glucose
liver: gluconeogeneis (fats and proteins-> glucose) - net effect: increase blood glucose
6
Q
bolus insulin
A
-the additional insulin that has been secreted to deal with the carb load that has come form your meal
7
Q
incretin effect
A
-once in the small intestine, the GLP-1 causes an increase in the release of insulin; this is why there is a little jump of insulin right after the decrease of insulin after bolus insulin
8
Q
what is the purpose of maintaining the balance between insulin and glucagon
A
-prevent glucotoxicity
9
Q
24 hour blood sugar regulation
A
-the increase in insulin level will differ depending how large the meal and how many carbs
10
Q
DAWN phenomenon
A
- surge of growth hormone and cortisol (aka counter regulatory hormones) in the early hours of the morning to presumably prepare the body for daytime activities after a period of fasting.
- this is accomplished by the brain to prepare for the beginning of your day-> gives you energy when you wake up
11
Q
diagrams on slide 11
common effects of insulin and amylin and GLP1;
common effects of glucagon
A
- insulin and amylin effects
- glucagon effect
- -> insulin, amylin, GLP1 lower blood sugar (fat tissue increases uptake of excess glc; fat synthesis, muscle tissue increases uptake of glc; protein synthesis, liver begins glycogenesis); then glucagon is stimulated to be released and this increases blood sugar (fat tissue decreases uptake of glc; fat is broken down (FA + glycerol), muscle tissue decreases uptake of glc: protein breakdown (aa + glycogen), liver begins glycogenolysis, gluconeogenesis, and increases hepatic output of glc) … and so on…
12
Q
type 1 diabetes
A
- beta cell destruction with absolute insulin deficiency
- autoimmune
- iodopathic
13
Q
type 2 diabetes
A
-insulin resistance or relative insulin deficieny or combo; metabolic syndrome
14
Q
other specific types of diabetes
A
- genetic defects in beta cel auction (mature onset diabetes in the young)
- genetic defects in insulin sensitivity
- diseases of the exocrine pancreas
- endocrinopathies
- drug or chemical induced
- infections
- uncommon forms of immune mediated
- other genetic syndromes associated with diabetes
15
Q
what kind of diabetes may occur with pregnancy
A
gestational diabetes
16
Q
etiology of T2D
A
- beta cell destruction/ dysfunction with relative insulin deficiency and insulin resistance (IR)
- beta cell destruction: 5 to 8 years prior to symptoms: CANRISK assessment tool
- lack of insulin sensitivity (IR) linked to: hyperglycaemia (over 7mmol/L), central obesity, hereditary, ?aging, ?inactivity, ?high fate diet, and physiological state
- pre-diabetes
- metabolic syndrome
- gestational diabetes
- others
17
Q
what are the risk factors to develop T2D
A
- medical and family history (i.e. first degree relative with T2D, presence of vascular risk factors, presence of other diseases) - slide 16 fore more
- however history of pre-diabetes is a strong indicator because if they do not live a healthier lifestyle to keep blood sugars low they could keep destroying beta cells
- chronic medications (drugs from some of the related diseases: HIV-> HAART, psych disorder-> atypical antipychotics)
- other secondary causes (down syndrome, huntingtons)
18
Q
diagnostic criteria for T2D
A
classic clinical features (overweight, 40+, polydipsia, polyuria, blurred vision, fatigue)
- family, medical, and medication history
- diagnostic testing (same as type 1- FPG, A1C, ZhPG in 75g OGTT, random PG)
19
Q
what did T1D and T2D use to be referred to
A
1- IDDM (insulin dependent diabetes mellitus)
2- NIDDM
-but now we know that patients can be allow the entire spectrum regardless- therefore we treat them based on their symptoms
20
Q
which of the diagnostic tests are more common for T2D over type 1
A
- A1C (because it looks over past 3 months, whereas in type 1 we need to look at right now)
- A1C just got validation to be diagnostic (and not confirmation)
21
Q
ZhPH test
A
give patient CHO load- test-> this is more of a confirmation test (if not 100% sure from another test)
22
Q
true or false: pre-diabetes is reversible
A
true
23
Q
pre-diabetes
A
- increased risk of developing T2D and complications
- impaired fasting glucose but normal post-prandial OR impaired glucose tolerance 2 hours after 75g OGTT OR BUT BUT NOT diagnostic for diabetes OR HbA1c 6-6.4%
24
Q
classic presentation of pre-diabetes
A
1) postprandial glucose levels deteriorate first- B cell dysfunction (this deteriorates first because of the beta cell dysfunction)
2) then pre- and post breakfast levels- IR and B cell dysfunction
3) Followed by nocturnal hyperglycaemia and increased fasting glucose
25
nocturnal hyperglycemia
-high bp glucose after a person wakes up- no longer a balance in the insulin and glucagon
26
How can you reduce the progression of pre-diabetes by 58%
-5-10% weight loss and frequent moderate intensity physical activity (i.e. walking)
27
metabolic syndrome
-metabolic disorder linked to T2D, HTN, Dyslipidemia, Atherosclerosis, Obesity, certain Cancers
28
what is the main feature of metabolic syndrome?
insulin resistance
29
true or false: there is now a harmonized definition of metabolic syndrome
true- different organizations through the world that uses slightly different definitions -> therefore have taken all the info and combined into one
30
what are some of the measures of metabolic syndrome? (need 3 or more)
- waist circumference- measure with tape measure around where hip bone is (different criterion numbers because people around the world have genetically different body types
- elevated TGA (because excess glucose is stored as TGA
- reduced HDL
- elevated BP
- elevated FPG
* the physiological blood sugar level (5.6) plus 2 other factors= metabolic syndrome
31
which body type leads to more of a problem: apple or pear?
apple
32
true or false: waist circumference is related to many medical problems
true-> lots of inflammation (high was it circumference causes more mediators of inflammation to be released (TNF-a, IL-6)
-leptin, FFA, angiotensin, PAI-1, Resistin, Visfatin, Glucocorticoids, Adiponectin, and sex steroids are all also released
33
Gestational diabetes
- physiological state of insulin resistance requiring a higher level of insulin (because of the fetus)
- usually detected week 24 to 28 of gestation
- often asymptomatic
- resolves after pregnancy termination
- significant risk of developing T2D later (30-60% over 10 year)
- different diagnostic criteria
- incidence varies among populations: Aboriginal populations 8-18%
34
true or false: gestational diabetes leads to a smaller baby
false- since the mom has excess sugar lots goes to the baby causing it to be bigger
35
pathophysiology diagram of ketoacidosis- what type of diabetes does this refer to?
type 1
- slide 25
- brain communicates with the adrenal glands to secrete the counter-regulatory hormones/ pancreas for insulin
- kidney function will eventually suffer because you need to have volume for proper function
36
pathophysiology diagram of hyperglycaemic hyperosmolar state
-same process occurs but there is no lipolysis in T2 therefore no ketoacidois
slide 26
37
main features of T2D
- cellular energy starvation
- insulin resistance
- hyperinsulinemia (cells are still starving, but insulin stays in the blood and is unable to do anything= hyperinsulemic)
- hyperglycemic hyperosmolar state (= glycosuria and dehydration)
38
what does HHS lead to in T2D
- polyuria
- polydipsia
- blurred vision
- muscle cramps
- headache
- anxiety and irritability
- confusion
- slow healing wounds
- prone to fungal and and bacterial infections
39
what does energy starvation lead to in T2D
- fatigue
| - weight loss
40
what are some chronic complications of T2D
- retinopathy
- nephropathy
- neuropathy
- loss of functionality and QoL
41
true or false: when diagnosing diabetes, you need to look at all diagnostic numbers (no just those related to DM, but also bp, BMI, etc)
true
42
true or false: if you are hyperinsulemic you cannot also be hyperglycemic
false, it is possible to be both (i.e. in type2, it is insulin doesn't work therefore could have high levels of sugar and insulin at the same time)
43
what are some good treatment suggestions of people with type 2 diabetes
- nutrition therapy (diet, reduce CHO load-> can reduce A1C by 2%- this is more than any drug)
- drugs also important to-> to try to reduce insulin sensitivity, work on gut (on GLP-1), try to utilize kidney (block some of the transporters that block glucose)
44
pathogenesis: T1 vs T2
1- genetic, enviro, autoimmune, idiopathic
| 2- genetic, lifestyle, secondary causes, med induced, idiopathic
45
insulin production: T1 vs T2
1- absent or relative
2- relative insulin deficiency (most puts have lost 50% beta cell function by time of diagnosis
-hyperinsulemia and HHS
46
age of onset: T1 vs T2
1- usually younger than 20, insidious up to 8th decade
| 2- usually after 45, but increasing incidence amongst younger people
47
symptoms T1 vs T2
```
1- quick onset and classic criteria; 3 poly's
-minimal or gradual in adults
-slow healing wounds
-prone to fungal infections
2- absent or mild- asymptomatic for 5-8 years
-slow onset
-slow healing wounds
-prone to fungal infections
(2 poly's)
```
48
body type: T1 vs T2
1-usually lean
| 2- 70-80% are obese
49
family history: T1 vs T2
1- some genetic markers
| 2- marked but not fully understood
50
DKA/HHS
1- DKA is hallmark feature in patients with absolute insulin deficiency
2- seldom DKA except with major stress/ illness
-HHA is hallmark feature
51
chronic complications T1 vs T2
1- microvascular
-macrovascuar
-depends on degree of hyperglycaemia
2- same as type 1; 50% have 1 complication at time of diagnosis
52
good video on slide 35
watch if confused on anything
53
what percentage of CHO are broken down?
90%
54
which CHO cannot be broken down?
Fibre
55
can proteins and fats raise blood sugar level right after a meal?
no
56
3 types of secreting cells in pancreas
alpha, beta, delta
57
what do delta cells secrete
somatostatin
58
net effect of glucagon
blood glucose increases
59
what is it called wen glucose-> glycogen
glycogenesis
60
what process forms glucose from other sources?
gluconeogenesis
61
what is the form in which glucose is stored in fat tissue
TGA
62
where is glucagon like peptide 1 secreted
small intestine
63
what is the level of sugar that we describe glucotoxicity (aka hyperglycemia)
equal or greater than 7
64
what initiates the DAWN effect
brain
65
is the DAWN effect related to the level of sugar on the body
no
66
what is the threshold for blood sugar absorption
10mmol/L
67
what is never in the urine if kidneys are working well
glucose and aa
68
what are the clinical features in type 1 that start with P and which is not found in T2
polydipsia, polyuria, polyphagia (polyphagia not found in T2)
69
what is the physiological blood glucose level
5.6mmol/L
70
complications from T2D
- nerve damage
- kidney damage
- eye damage
- blood vessel damage
- heart disease
- foot damage
71
hypoglycemia
- blood sugar under 4mmol
- tremor
- tachycardia
- sweaty palms
- hungry
- nausea
- headache
- irritable
- confusion
