Diabetes

Question 1

where are GLUT 1 receptors located

Answer 1

CNS, BBB

Question 2

where are GLUT 2 receptors located

Answer 2

renal tubular cells
liver

Question 3

where are GLUT 3 receptors located

Answer 3

neurons, placenta

Question 4

where are GLUT 4 receptors located

Answer 4

muscle (glucose)
adipose (triglycerides metabolised to glucose)

Question 5

how does metformin work

Answer 5

phosphorylates GLUT4, increasing sensitivity to insulin

Question 6

How does GLUT 4 and insulin interact

Answer 6

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

Question 7

what is basal insulin

Answer 7

insulin is secreted continously
suppresses hepatic glucose production between meals and overnight
maintain blood sugars at constant level
50% daily insulin requirements

Question 8

Glucagon reminder

Answer 8

increases gluconeogenesis (liver and kidney)
glycogenolysis (liver)

TURNS OFF GLYCOLYSIS in liver, glycolytic intermediates shuttled off to gluconeogenesis

Question 9

drugs that can cause diabetes

Answer 9

PIs
glucocorticoids
thiazide diuretics
atypical antipsychotics

Question 10

how does insulin work

Answer 10

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

Question 11

diabetes diagnostic criteria

Answer 11

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

Question 12

impaired glucose tolerance

Answer 12

fasting glucose less than 7.0
2hr OGTT: 7.8-11.0

Question 13

impaired fasting glucose

Answer 13

6.1 to 6.9

Question 14

2 consequences of insulin resistance

Answer 14

hyperglycaemia
lipid excess due to lipolysis (NAFLD)

Question 15

2 consequences of insulin resistance

Answer 15

hyperglycaemia
lipid excess due to lipolysis (NAFLD)

Question 16

metabolic syndrome diagnosis

Answer 16

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

Question 17

how do you treat Type 1s

Answer 17

Insulin monotherapy

Question 18

Short acting insulin

Answer 18

Actrapid

Subcut

3/day

30min before meal, peak action 2-5 hrs

duration: 5-8 hrs

human insulin

Question 19

Intermediate acting insulin eg protophane?

Answer 19

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

Question 20

Biphasic insulin: Actraphane

Answer 20

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

Question 21

what is the preferred management of Type 1s

Answer 21

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

Question 22

what is the initial total daily insulin dose for basal bolus regimen

Answer 22

0.6 units/kg body weight

Question 23

What is lipohypertrophy

Answer 23

when you inject at 1 site instead of rotating

Question 24

Metformin MOA

Answer 24

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

Question 25

when is metformin contraindicated

Answer 25

eGFR below 30

Question 26

Side effects of metformin

Answer 26

GIT: nausea, vom, diarrhoea

lactic acidosis (inhibited conversion lactate to glucose)

reduced Bit B12 absorption

DOES NOT CAUSE Hypoglycaemia

Question 27

sulphonyl urea examples

Answer 27

glibenclamide
gliclazide (lowest risk hypoglycaemia)
gli……

Question 28

Sulphonylurea MOA

Answer 28

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

Question 29

contraindications to using sulphonylurea

Answer 29

avoid: renal impairment eGFR below 60
do not use if: severe hepatic impairment
pregnancy

Question 30

side effects sulphonylureas

Answer 30

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

Question 31

stepwise approach to diabetes type 2 management

Answer 31

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

Question 32

insulin regimens Type 2

Answer 32

1. Add on: intermediate to long-acting

10 units starting (increase in increments to 20 units)
evening, no later than 10pm

2. Substitution: biphasic
   twice dly
   total dly dose: 15 units divided as follows:
3. 2/3 total dly dose 20 min before bfast (10 units)
4. 1/3 total dly dose, 30 min before supper (5 units)

Question 33

which population groups have blunting of hypoglycaemic symptoms

Answer 33

Elderly patients with neuropathy, patients with long-standing diabetes (>10 years), and patients taking β blockers

Question 34

DKA diagnosis

Answer 34

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

Question 35

DKA diagnosis

Answer 35

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

Question 36

how are ketones produced in DKA

Answer 36

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

Question 37

DKA complications explained

Answer 37

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.

Question 38

causes of DKA

Answer 38

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

Question 39

investigations in DKA

Answer 39

blood K: NORMAL/ baseline

FBC: leukocytosis, even without infection

U and E: Urea and Creat elevated