diabetes review Flashcards
1
Q
what is the gold standard test for diagnosing diabetes ?
A
oral glucose tolerance test
- patient has to fast for at least 8 hours before test
- then given 150g of glucose and glucose levels measured 2 hours later
2
Q
what are normal fasting venous plasma glucose levels?
A
fasting < 6.1 mmol/L
3
Q
what are fasting glucose levels in someone with impaired fasting glycaemia?
A
6.1-6.9 mmol/L
4
Q
what are fasting glucose levels in someone with diabetes?
A
> _ 7mmol/L
5
Q
what are glucose levels of someone with impaired glucose tolerance 2 hours post prandial?
A
> _7.8-11mmol/L
6
Q
what are glucose levels of someone with diabetes 2 hours post prandial?
A
> 11mmol/L
7
Q
what is HbA1c?
A
glycated haemoglobin
8
Q
an HbA1c level above what reconfirms a T2D diagnosis?
A
> 48 mmol/mol
9
Q
what do pancreatic B-cells express, which permit rapid glucose uptake regardless of the extracellular sugar concentration?
A
GLUT2
10
Q
what cells produce insulin?
A
beta cells of Islets of Langerhans
11
Q
when is insulin released?
A
in the presence of excess glucose
12
Q
what are the Ca++ and K+ channels normally like in beta cells?
A
- Ca++ channels normally closed — keeps Ca++ out
- K+ channels normally open — -ve potential intracellularly
13
Q
what happens when glucose enters the beta cell through GLUT2?
A
- glucokinase breaks down the glucose
- ADP —> ATP using the energy from the breakdown of glucose
- ATP locks on to the K+ channels — closing them
- K+ accumulates in cell
- -ve potential inside the cell becomes +ve
- Ca++ channels open
- Ca++ enters
- degranulation
- insulin release
14
Q
what happens in type I diabetes?
A
beta cells get destroyed —> no or very little insulin produced
15
Q
what are the effects of insulin on the liver?
A
increased glucose uptake and glycogen synthesis
16
Q
what are the effects of insulin on the muscle?
A
increase glucose uptake and glycogen synthesis
17
Q
what are the effects of insulin on adipose?
A
- increased glucose uptake and storage as fat
- decreased breakdown to fatty acids (reserve energy)
18
Q
what are the effects of insulin on blood?
A
glucose levels fall
19
Q
what are the effects of a lack of insulin on the liver?
A
- decreased glucose uptake
- increased glycgoen breakdown and gluconeogenesis
- conversion of fatty acids to ketone bodies
20
Q
what are the effects of a lack of insulin on muscle?
A
decreased glucose uptake
21
Q
what are the effects of a lack of insulin on adipose?
A
- decreased glucose uptake and storage of fat
- increased breakdown of fat and release of fatty acids
22
Q
what are the effects of a lack of insulin on blood?
A
glucose levels rise
23
Q
what enzyme is used in the breakdown of fat and release of fatty acids?
A
lipoprotein lipase
24
Q
what happens when ketone bodies build up due to a lack of insulin?
A
H+ generated — there are initially buffered by as buffers are used up —> ACIDOSIS
25
how does low utilisation of glucose and increased endogenous production of glucose by the liver lead to dehydration and polypdipsia (increased thirst)?
- low utilisation of glucose and increased endogenous production of glucose by the liver
- hyperglycaemia
- loss of glucose in urine : osmotic drag of glucose on water, water and glucose lost in urine, electrolytes lost along with water
- increased urination (polyuria, nocturia)
- dehydration and polypdipsia
26
80% of people with T1D at diagnosis have what antibodies?
GAD65
27
69-90% of people with T1D at diagnosis have what antibodies?
islet cell antibodies
28
what are specific tests to help diagnose T1D?
- GAD65 antibodies
- Islet Cell antibodies
- ZnT8 antibodies
- insulin antibodies (IAA)
- C-peptide/insulin/glucose levels
29
as T1D progresses, what happens to C-peptide levels? what does this indicate?
levels fall — indicates lack of endogenous insulin production
30
___ blood glucose and low/absent _____ is very characteristic of T1D
- high
- C-peptide
31
describe T2D
- due to insulin resistance
- less acute onset compared to type 1
- progressive decline in beta cell function
- prediabetes : (at risk of diabetes/high risk for diabetes) — non-diabetic hyperglycaemia
32
in which diabetes is there a progressive decline in beta-cell function?
type 2
- may have up to 50% beta cell loss at time of diagnosis
- and 4-6% decline per year thereafter
33
what is the link between beta cell loss and medication?
as time goes by, previously effective medication becomes less effective a beta cells are no longer able to produce enough insulin
34
IGT vs IFT
IGT = impaired glucose tolerance
IFT = impaired fasting glucose
35
what are modifiable risk factors for T2D?
- overweight and obesity
- sedentary lifestyle
- previously identified glucose into leaven (IGT and/or IFG)
- metabolic syndrome — hypertension, decreased HDL cholesterol, increased triglycerides)
- dietary factors
- intrauterine environment
- inflammation
36
what are non-modifiable risk factors for T2D?
- ethnicity
- family history of T2D
- increasing age
- history of gestational diabetes (in mother)
- polycystic ovary syndrome (in mother)
37
what BMI is classified as underweight for white European and asian populations?
less than 18.5 kg/m2
38
what BMI is increasing but acceptable risk for ill health and premature death in white european and asian populations?
- white europeans = 18.5-24.9 kg/m2
- asian populations = 18.5-23 kg/m2
39
what BMI is increased risk for ill health and premature death in white european and asian populations?
- white europeans = 25-29.9 kg/m2
- asians = 23-27.5 kg/m2
40
what BMI is high risk for ill health and premature death in white european and asian populations?
- white europeans = 30 kg/m2 or higher
- asians = 27.5 kg/m2 or higher
41
for every 1cm increase in waist, by what % does the risk of developing t2d and risk of IFG increase?
risk of t2d = 3.5%
risk of IFG = 3.2%
42
for every 1 kg/m2 increase in BMI, how much does the risk of developing t2d and risk of IFG increase?
risk of t2d = 8.4%
risk of IFG = 9.5%
43
on average, a 50 year old individual with diabetes and no history of vascular disease will die how many years earlier compared to someone without diabetes?
6
44
what are the effects of decreasing HbA1c by 1%?
45
what are the different treatment options for controlling hyperglycaemia in type 2 diabetes?
1. lifestyle intervention = where we start
2. insulin sensitisation eg. metformin, pioglitazone (thiazolidinedione)
3. insulin secretion — DPP-4 inhibitors, GLP-1 receptor agonists, meglitinides, SUs
4. glucose excretion = insulin independent — SGLT2 inhibitors
5. insulin replacement — injected insulin
46
look at power point for big treatment tables
ugh
47
what is 1st line diabetes pharm treatment?
metforin
48
metformin dose?
start at 500mg once daily, can increase up to 2g (can increase more up to 3g but not acutually very useful)
49
when should metformin be used in caution?
- chronic kidney disease : GFR <45 — decrease dose to 500mg. GFR <30 — stop metformin as it can increase the risk of lactic acidosis when GFR drops
- illness — may need to stop to prevent lactic acidosis
50
what is 2nd line drug treatment for diabetes?
SU = sulphonylurea ….. but can use other drugs
51
how do sulphonylureas work?
bind to and close ATP sensitive K+ channels in pancreatic beta cells
52
name a sulphonylurea
glicazide
53
what is 3rd line therapy for diabetes?
in obese/overweight, if HA1c 64 (8%) eg. SGLT2i/DPP4-inhibitors/GLP1-receptor agonists
if HbA1c > 80 — will likely need insulin
54
when should metformin be avoided?
- eGFR <30
- severe hepatic impairment
- stop with intercurrent illness
55
when is metformin MR (modified release) used?
if GI intolerance
56
metformin onset?
slow onset — if need rapid control consider SU therapy
57
what is a complication of metformin?
vitamin B12 deficiency — peripheral neuropathy
58
what does metformin do?
- decreases hepatic glucose production
- decreases intestinal glucose absorption
- improves insulin sensitivity in peripheral tissues
59
in metformin there is a very low risk of what?
hypoglycaemia - because it works by increasing insulin sensitivity and if glucose levels are low it will not work
60
what benefits can metformin have?
reduce CV mortality
mortality and cancer benefit
weight neutral - may even help lose a bit of weight
61
alcohol and metformin?
alcohol can be used in moderation but it increases the risk effect of lactic acidosis
62
when can hypoglycaemia occur with metformin?
RARE but can occur in:
- starvation
- excessive exercise when fasting
- alcohol intoxication
63
what are the primary physiological actions of insulins (treatment)?
- increases glucose disposal
- decreases hepatic glucose production
64
disadvantages of treatment with insulin?
hypoglycaemia
weight gain
injectable
training requirements
65
what do meglitinides (glinides) do?
increase insulin secretion by acting on KATP channels
66
what are the advantages of glinides?
- shorter acting so can be used to decrease postprandial glucose excursions
- dosing flexibility
- can be used in those at risk of hypoglycaemia
67
what do alfa-glucosidase inhibitors do?
slows intestinal carb digestion/absorption
68
advantages of alfa-glycosidase inhibitors?
- no hypoglycaemia
- decrease post prandial glucose excursions
- poss decrease CVD events
69
what do SGLT2 inhibitors do?
increase glucose excretion from kidneys by blocking reabsorption
70
advantages of SGLT2 inhibitors?
insulin independent mechanism
71
disadvantages of SGLT2 inhibitors?
diuretic effect, thrush (due to glucose in urine)
72
describe GLP-1 receptor agonists
- injectable SC therapy and costs ££££
- generally used as ‘add on’ therapy — 3rd line, earlier if weight loss desirable
- weight loss, reduction in SBP
- GI side effects
- weekly, daily or BD
- licence with insulin
- weight loss benefit
- need to stop if HbA1c <1% and 3% loss of weight not achieved at 6 months
73
what are sympathetic signs of hypos?
sweating, tremulousness, palpitations, blurring, hunger, pins and needles
74
what are neuroglycopenic signs of hypos?
confusion, incoordination, drowsiness, seizures, coma
75
what is DKA?
diabetic ketoacidosis
76
who is DKA seen in?
type 1 DM, new diagnosis, long standing type 2 rarely
77
what levels are seen in DKA?
- hyperglycaemia >11mol/L (may be normoglycaemic)
- ketones >_3mmol/L, urine >2+ ketones
- acidosis: bicarbonate <15, ph <7.3
78
DKA treatment
- IV fluids
- K+ replacement
- insulin replacement
- replacement of electrolytes
- LMWH, antibiotics
79
what is HHS?
hyperosmolar hyperglycaemic state
80
who is HHS seen in?
poorly controlled t2d
81
what are osmolality levels in HHS?
>320
82
HHS treatment
- IV fluids, IV fluids, IV fluids
- replace electrolytes
- IV insulin may be needed (only if glucose not dropping despite iv fluids)
- LMWH (DVT prophylaxis)
83
The progressive decline in beta-cell function during the natural history of type 2 diabetes might be expected to lead to what?
a gradual loss of effectiveness for antihyperglycaemic therapies that lower blood glucose levels via the action of endogenous insulin
84
what agents might be expected to be effective at all stages of the natural history of t2d?
insulin independent therapies - they are combinable with insulin-dependent therapies
