T2 diabetes

Question 1

What is type II diabetes? What is it associated with? What can it be managed with initially and at later stages?

Answer 1

• Type II diabetes is a combination of insulin resistance and defect in insulin production by β cells.
• Associated with obesity but not always.
• Initially resultant hyperglycaemia can be managed by lifestyle changes/medications but later on may need insulin.

Question 2

What is the initiating factor of T2D?

Answer 2

insulin resistance

Question 3

What happens during the intermediate phase before T2D and at T2D stage?

Answer 3

During the intermediate phase there is an increase in insulin production by β cells in order to compensate for the insulin resistance but by T2D insulin production has wained/decreased.

Question 4

What is needed for T2D diagnosis?

Answer 4

Can be made on random blood glucose above 11.1 if associated with symptoms. Can be made with fasting glucose or 2-hour glucose test.

Question 5

Why doesn’t the hyperglycaemia here usually not cause ketosis?

Answer 5

Because ketosis usually happens when there is no insulin production at all, here there is just enough to prevent ketosis. They can still get ketoacidosis if unwell.

Question 6

What is long duration type II diabetes?

Answer 6

When β cell failure can progress to complete insulin deficiency

Question 7

What is the pathophysiology behind insulin resistance?

Answer 7

Increase in adipocytokines (pro-inflammatory cytokines) increase insulin resistance. Fatty acids play a major role

Question 8

What are the responses normally and in type II diabetes when exposed to glucose?

Answer 8

Normally when exposed to glucose they should have a very fast peak of insulin production (first phase insulin production). In intermediate state this is blunted. In T2D this is absent. Loss of 1st phase insulin production

Question 9

What does the reduced action of insulin do to the liver?

Answer 9

Increases hepatic glucose output. Impaired insulin mediated glucose disposal.

Question 10

What do GWAS show in T2D?

Answer 10

GWAS show that SNPs alone have mild effect on T2D but cumulative effect of all SNPs is significant

Question 11

What is the role of obesity in T2D?

Answer 11

Big association. Fatty acids and adipocytokines important and drive insulin resistance. Central obesity.

Question 12

What are other things that contribute to T2D?

Answer 12

Intrauterine environment and gut microbiota

Question 13

What is the presentation of T2D?

Answer 13

Less osmotic symptoms, hyperglycaemia, obesity, dyslipidaemia, hypertension

Question 14

What are risk factors for T2D?

Answer 14

Age, high BMI, ethnicity, PCOS, inactivity, family history

Question 15

What is needed for diagnosis in terms of HbA1C?

Answer 15

1 x HbA1C > 48 mmol/l if symptomatic. 2x if asymptomatic

Question 16

What is a hyperosmolar hyperglycaemic state?

Answer 16

Hyperosmolar hyperglycaemic state is when they usually present with renal failure. They are both hyperglycaemic and very hyperosmolar (dehydrated) - get osmotic diuresis to get rid of the glucose

Question 17

What is management for T2D?

Answer 17

Lifestyle changes/diet modification, medications, insulin later on, education

Question 18

What does a consultation of T2D usually include?

Answer 18

Check glucose levels, HbA1C, weight, medication review, blood pressure, dyslipidaemia, complication asessemnt

Question 19

What are dietary reccomendations for T2D?

Answer 19

Total calorie control, reduce calories as simple carbs increase as complex carbs, reduce sodium intake

Question 20

What drugs are used to reduce hepatic glucose production?

Answer 20

metformin

Question 21

What drugs are used to improve insulin sensitivity?

Answer 21

Metformin, thiazolidinenones

Question 22

What drugs are used to boost insulin secretion?

Answer 22

Sulphonylureas, DPP4 inhibitors, GLP -1 agonists

Question 23

What drugs are used to inhibit carb gut absorption & renal glucose reabsorption?

Answer 23

Alpha gluconidase inhibitors, SGLT2 inhibitors

Question 24

What does metformin do? What are side effects? When is it contraindicated?

Answer 24

Metformin reduces insulin resistance and decreases hepatic glucose output and increases glucose disposal. GI side effects. Contraindicated in liver disease, moderate renal failure, heart failure

Question 25

What are sulphonylureas? What is their mechanism of action?

Answer 25

Usually closure of ATP sensitivie potassium channels causes insulin production. Sulphonylureas bypass normal mechanism to get closure of these potassium channels and therefore insulin production

Question 26

What is pioglitazone? What does it do? Side effects?

Answer 26

Pioglitazone is a peripheral insulin sensitizer. Improved outcomes. Side effects are heart failure, hepatitis, peripheral weight gain.

Question 27

In which drugs does weight gain happen as side effect?

Answer 27

All except metformin (mild weight gain)

Question 28

What is glucagon like peptide 1 (GLP1)? What is it degraded by?

Answer 28

Glucagon like peptide 1 is produced by the gut (L cells) In response to food and boosts insulin production and increases satiety. It has a short half life because degraded by DPP4.

Question 29

What are some GLP-1 agonists and what do they do? And why?

Answer 29

They increase the actions of GLP1, increasing insulin production, decreasing glucagon and glucose, and mediate incretin effect contributing to weight loss and satiety.

Question 30

What are DPP4 inhibitors?

Answer 30

DPP4 inhibitors increase the effect of GLP1 (exogenous) to boost insulin. neutral on weight

Question 31

What are SGLT-2 inhibitors and what do they do? What are the outcomes?

Answer 31

inhibit the sodium/glucose transporter, increasing glucose loss in urine (glycosuria).

Question 32

What can gastric bypass do?

Answer 32

Gastric bypass can potentially reverse T2D

Question 33

What are other drugs used to manage symptoms of T2D?

Answer 33

For hypertension ACE inhibitors. For dyslipidaemia statins.