Diabetes Flashcards
where are GLUT 1 receptors located
CNS, BBB
where are GLUT 2 receptors located
renal tubular cells
liver
where are GLUT 3 receptors located
neurons, placenta
where are GLUT 4 receptors located
muscle (glucose)
adipose (triglycerides metabolised to glucose)
how does metformin work
phosphorylates GLUT4, increasing sensitivity to insulin
How does GLUT 4 and insulin interact
insulin signals cell to insert GLUT4 transporters into membrane, allowing glucose entry, stored for later use
in absence of insulin, glucose can not enter cell
what is basal insulin
insulin is secreted continously
suppresses hepatic glucose production between meals and overnight
maintain blood sugars at constant level
50% daily insulin requirements
Glucagon reminder
increases gluconeogenesis (liver and kidney)
glycogenolysis (liver)
TURNS OFF GLYCOLYSIS in liver, glycolytic intermediates shuttled off to gluconeogenesis
drugs that can cause diabetes
PIs
glucocorticoids
thiazide diuretics
atypical antipsychotics
how does insulin work
decreases plasma glucose levels through suppression of hepatic glucose production
stimulates glucose use in skeletal muscle and adipose tissue (instead of stimulating fat lipolysis for energy so that glucose blood levels may decrease)
converts glucose to glycogen (stored form)
lipogenesis
protein synthesis
reduces K and Mg
diabetes diagnostic criteria
Fasting plasma glucose _ 7.0 mmol/L or
2 hr OGTT _ 11.1 mmol/L or
HbA1c_ 6.5% or
Random plasma glucose _ 11.1 mmol/L AND symptomatic
impaired glucose tolerance
fasting glucose less than 7.0
2hr OGTT: 7.8-11.0
impaired fasting glucose
6.1 to 6.9
2 consequences of insulin resistance
hyperglycaemia
lipid excess due to lipolysis (NAFLD)
2 consequences of insulin resistance
hyperglycaemia
lipid excess due to lipolysis (NAFLD)
metabolic syndrome diagnosis
3 of following:
central obesity
high blood pressure
high blood sugar
high serum triglycerides
low serum HDL
assoc. with: increased risk Type 2 D, CVD
how do you treat Type 1s
Insulin monotherapy
Short acting insulin
Actrapid
Subcut
3/day
30min before meal, peak action 2-5 hrs
duration: 5-8 hrs
human insulin
Intermediate acting insulin eg protophane?
subcut
1/2 times dly, usually at night but no later than 10pm
Neutral Protamine Hagedorn (NPH) insulin
onset: 1-3 hrs
peak: 6-12 hrs
duration: 16-24 hrs
Biphasic insulin: Actraphane
Subcut
2 per day
Regular human insulin plus NPH in diff proportions
premixed insulin (intermediate or short acting mixture)
onset: 30 min
peak: 2-12 hrs
duration 16-24 hrs
what is the preferred management of Type 1s
basal bolus
premeal short acting insulin (bolus) PLUS bedtime (not later than 10) intermediate acting insulin (Protophane/Humulin N)
total dose divided into: 40-50 % basal insulin and rest as bolus, split equally before each meal
what is the initial total daily insulin dose for basal bolus regimen
0.6 units/kg body weight
What is lipohypertrophy
when you inject at 1 site instead of rotating
Metformin MOA
Reduces hepatic gluconeogenesis and glycogen metabolism
Improves insulin resistance via enhancing insulin-mediated glucose uptake by skeletal muscle
Decrease carbohydrate absorption from GIT
Lowers triglyceride and total cholesterol levels, raises HDL
Indicated alone in obese, mild diabetics as it does not enhance lipogenesis (unlike insulin)
taken with meals
500mg once/twice dly or 850mg once/twice dly
after 5-7 days, uptitrate to 2000mg/day (depends on GIT SEs)
if severe GIT SEs, extended-release formulation preferred
when is metformin contraindicated
eGFR below 30
Side effects of metformin
GIT: nausea, vom, diarrhoea
lactic acidosis (inhibited conversion lactate to glucose)
reduced Bit B12 absorption
DOES NOT CAUSE Hypoglycaemia
sulphonyl urea examples
glibenclamide
gliclazide (lowest risk hypoglycaemia)
gli……
Sulphonylurea MOA
requires residual beta cell functioning: NB
stimulates insulin secretion from beta cells
promotes beta cell growth
enhances beta cell sensitivity to glucose (glucose is most potent stimulus for release of insulin from b cells)
reduces glucagon release
in more detail: Beta cells possess K channels regulated by intracellular ATP. when blood glucose increases, more glucose enters beta cells, more ATP produced, closes K channels. depolarisation of beta cell initiates influx Ca through ca channels, triggers insulin release
contraindications to using sulphonylurea
avoid: renal impairment eGFR below 60
do not use if: severe hepatic impairment
pregnancy
side effects sulphonylureas
Hypoglycemia
0.2-0.4 severe cases in 1000 patient years
Risk factors: renal impairment, elderly patients, irregular meal schedule
Weight gain (5kg over first 6 years
stepwise approach to diabetes type 2 management
Non-drug first (diet and exercise)
+Metformin ?HbA1C target (go to Sulphonylurea if target not achieved)
+Sulphonylurea ? HbA1C target
-Sulphonylurea (withdraw) +Insulin **adherence NB
NO oral agents in type 1
insulin regimens Type 2
- Add on: intermediate to long-acting
10 units starting (increase in increments to 20 units)
evening, no later than 10pm
- Substitution: biphasic
twice dly
total dly dose: 15 units divided as follows: - 2/3 total dly dose 20 min before bfast (10 units)
- 1/3 total dly dose, 30 min before supper (5 units)
which population groups have blunting of hypoglycaemic symptoms
Elderly patients with neuropathy, patients with long-standing diabetes (>10 years), and patients taking β blockers
DKA diagnosis
keto: serum and urine ketone conc increases
diabetic: blood glucose > 13.8, less than 40
acidosis: blood pH < 7.2
bicarb level: <18
raised anion gap (met acidosis)
serum osmolality <350
DKA diagnosis
keto: serum and urine ketone conc increases
diabetic: blood glucose > 13.8, less than 40
acidosis: blood pH < 7.2
bicarb level: <18
raised anion gap (met acidosis): accumulation Beta hydroxybutyruate and acetoacetic acid
serum osmolality <350
how are ketones produced in DKA
In DKA, low levels of effective circulating insulin and an increase in glucagon, suppress glucose oxidation and increase lipolysis. Lipolysis leads to increased production of ketones, especially β-hydroxybutyrate. The ratio between acetoacetate and B-OHB increases from 1:1 to 1:10. While oxidation of fatty acyl CoA and acetoacetate provides an alternative source of energy, ensuing ketonemia contributes to metabolic acidosis.
essentially: lack of insulin means that there is no inhibition of fatty acid transport into matrix of mitochondria
DKA complications explained
Acidosis causes nausea and vomiting, a frequent presenting symptom of DKA. Loss of fluid in vomit exacerbates the water deficit and consequent dehydration induced by osmotic diuresis.
(osmotic diuresis: hyperglycaemia causes increase in urine output, glucose draws water across membrane)
Acidosis is a contributory factor in the development of the dangerously high plasma potassium (hyperkalemia) that is also a feature of untreated DKA, because acidosis induces an exchange of hydrogen ions for potassium ions across cell membranes with hydrogen ions passing into cells and potassium ions passing out of cells to the ECF (blood plasma).
insulin def: K doesnt enter cells (serum is normal or raised)
Hyperkalemia, however, masks the underlying whole-body potassium deficiency that occurs in DKA.
causes of DKA
Infections – pneumonia, UTI, sepsis, gastroenteritis etc.
Inadequate insulin treatment or non-compliance
New onset diabetes
Infarction - Myocardial infarction, cerebral, mesenteric, peripheral
Drugs – cocaine, atypical antipsychotics, corticosteroids, glucagon, interferon etc.,
Pregnancy
investigations in DKA
blood K: NORMAL/ baseline
FBC: leukocytosis, even without infection
U and E: Urea and Creat elevated
