PBL 3 - Diabetes T1

Question 1

) (i) What are the main plasma unmeasured anions responsible for the anion gap
in this scenario? (1/2 mark) (ii) What other metabolite could contribute as well?

Answer 1

Ketoacids

ii) Lactic acid (from dancing

Question 2

Billy is in hyperglycemia. What are the two main hormones involved and how
does their respective levels affect the various pathways of glucose metabolism? [2
marks]

Answer 2

Lack of insulin: inhibits glycolysis, stimulate glycogenolysis and gluconeogenesis
[1]
Excess glucagon (insulin normally restrains glucagon secretion): inhibits
glycolysis. [1]
* Glucagon inhibits formation of fructose2,6biphosphate, an extremely potent
allosteric regulator of phosphofructokinase1: a controlling step in glycolys

Question 3

3) What is the effect of lack of insulin on lipid metabolism? How does it contribute
to ketogenesis? [2

Answer 3

Lack of insulin: stimulates lipolysis [1] that delivers Free Fatty Acids used for
ketogenesis

Question 4

What is the effect of alcohol on the NAD/NADH ratio in the liver and how does
this affect glucose metabolism? [

Answer 4

Alcohol is broken down by alcohol dehydrogenase, which also catalyses the
reduction of NAD+ to NADH. NAD/NADH are cofactors used in hepatic
gluconeogenesis. This change the ratio inhibits hepatic gluconeogenesis.

Question 5

Briefly explain the mechanism that normally prevents appearance of
glucose in the urine and how it is affected in patients with Type 1 diabetes. [3
marks]

Answer 5

Glucose is freely filtered by the glomerulus and normally reabsorbed in the
proximal tubule [1 mark]
In hyperglycemia patients have high plasma concentrations of glucose. [1 mark] so
there is saturation of glucose transporters in the proximal tubule and some glucose
end up in urine.
OR renal threshold for total glucose reabsorption is exceeded. [1 mark]

Question 6

What is type 1 diabetes

Answer 6

auto-immune T-cell mediated disruption of pancreatic B cells resulting in decreased insulin production within islets of Langerhans

Question 7

When does T1D develop

Answer 7

5-14 years old

Question 8

Normal action of insulin

Answer 8

o Stimulates uptake via GLUT 4
o Increased glycolysis
o Increased glycogenesis
o Stimulates adipogenesis
o Stimulates protein synthesis and uptake of a.a. into cells
o Promotes uptake of K+ into cells
o Increase translation of MRNA –> new proteins

Question 9

Normal function of glucagon

Answer 9

o Increased glycogenolysis
o Increased gluconeogenesis
o Lipolysis via HSL

Question 10

What usually inhibits glucagon

Answer 10

Insulin

Somatostatin

Question 11

What occurs in hyperglycaemia

Answer 11

More glycogenolysis, gluconeogenesis than needed due to excess glucagon
Less glycolysis as high glucagon –> Inhibits F2,6,BP –> PFK-1 not activated

Question 12

How does high blood sugar levels cause osmotic diuresis

Answer 12

 Normally all glucose reabsorbed after ultrafiltration, but above 11mmol/L, glucose transporters become saturated and cannot reabsorb glucose
 Hyperosmolality of ECF occurs, shift of fluid from inside –> outside –> hyponatremia (diluted) –> excess water excreted in urine

Question 13

What causes diabetic ketoacidosis

Answer 13

o Lack of insulin and inability to use carbohydrate –> mimics starvation state –>body switches to metabolising lipids.
o Lipolysis occurs –> glycerol + FFA –> FFA–> ketogenesis
 FFA also used for Beta oxidation –> acetyl coA
 Glycerol –> glucose

Question 14

What is kussmaul breathing

Answer 14

Deep laboured breathing

Question 15

Ketones!!

Answer 15

Ketones are acidic and will dissociate to form H+ and anions
 Acidosis will pull Na+ and K+ out of the cell via H+/K+ ATPase (cell exchanges H+ for K+ to try and reduce acidity) –> elevated serum K+ when total K+ is lower due to loss through urine.
 Acidity –> Kussmaul breathing (deep laboured breathing)- body tries to compensate for acidity by getting rid of CO2. Compensatory respiratory alkalosis
 Acidity –> denatures enzymes –> slows down metabolism even more –>more ketones accumulate

Question 16

What is the anion gap

Answer 16

Difference in measured cations – measured anions = unmeasured (Na+ +K+) – (Cl- +HCO3-)
o Used to find out cause of metabolic acidosis

Question 17

Normal anion gap

Answer 17

<12

or <16 if include K

Question 18

Why is there a high anion gap in scenario

Answer 18

• This is because there is an increase in unmeasured anions due to the ketone bodies dissociating. The H+ is removed by the bicarbonate (hence why it’s low).
• Other examples of high anion gap acidosis- methanol, lactate

Question 19

Effect of alcohol on T1D

Answer 19

• Sweetened wine/beer can cause temporary glucose levels
• Excess alcohol –> hypoglycaemia next morning
• Alcohol –> acetaldehyde using NAD+ –> NADH, increase in NADH:NAD ration inhibit malate dehydrogenase which converts malate –> oxaloacetate used in gluconeogenesis. (inhibits gluconeogenesis)
• Especially true in diabetics as body has less glycogen stores to rely on
• Dancing –>lactate. Lactate –> pyruvate via pyruvate dehydrogenase requires NAD+ which is inhibited  lactate acidosis.

Question 20

Acute tx

Answer 20

Replace fluid and electrolytes lost (Saline infusion)
Bolus of insulin of 0.1 unit per kg
Pottasium supplements as insulin decreases potassium levels in blood –> cardiac complications

Question 21

Management of T1D

Answer 21

Humalog

Glargine lifestyle factors

Question 22

What is humalog

Answer 22

Fast acting insulin (lispro)

Taken before and after eating (more flexible)

Question 23

What is glargine

Answer 23

Long-acting basal insulin analogue given once daily at night
Resembles basal insulin secretion in non-diabetics

Question 24

Lifestyle factors in T1D

Answer 24

 Low carbohydrate diet/GI diet
 Avoid sugary drinks/soda
 Plenty of fluid to avoid dehydration
 Exercise