T2DM

Question 1

Aetiology

Answer 1

Relative insulin insensitivity. Reduced insulin secretion, with or w/o resistance.
Usually in old, obese, sedentary, alcohol.
Other causes- steroids, pancreatic, cushings etc.

Question 2

Symptoms

Answer 2

Polyuria
Polydipsia
Glycosuria
Fatigue

Question 3

Complications

Answer 3

Progression to insulin dependance.
Vascular as for T1
Pregnancy risk- miscarriage, pre term, pre eclampsia, congential maloframtion, macrosomia, worse macrovascular complications.
Metformin safe in pregnancy.

Question 4

Treatment

Answer 4

Diet and lifestyle.
Exercise increase insulin release.
Metformin insulin sensitiser, reduced gluconeogenesis.
Thiazalidadiones insulin sensitiser.
Sulphonylureas inhibit K/ATP channel to increase insulin release.
Meglitidines increase insulin release. 
Others
Insulin.

Question 5

Dipeptyl peptidase 4/gliptins eg sitagliptin.

Answer 5

Inhibits DPP4 degradation of native GLP1.
2nd line behind metformin.
Add to metformin/sulphonylureas with HbA1c over 6.5% IF:
-significant risk hypo
-sulphonylurea not tolerated or CI
-can use as triple therapy
-continue if Hba1c falls over 0.5% maintained over 6 months.
AE- GI, pancreatitis. Weight neutral or loss!

Question 6

Glucagon like peptide 1 analogues eg exenatide

Answer 6

Mimic GLP1 from intestinal L cells= stimulates insulin synthesis and secretion. Reduces glucagon secretion.
Widely used.
AE- GI including GORD, pain injection, weight LOSS!

Question 7

Alpha glucosidase inhibitors eg acarbose

Answer 7

Delay glucose load to blood by blocking breakdown in SI.
Rarely used now.
AE- flatulence, diarrhoea, high ALT.

Question 8

Thiazolidinediones/glitazones eg pioglitazone

Answer 8

Stimulates nuclear peroxisome proliferator= gene upregulation= increase insulin sensitivity, reduce gluconeogenesis, reduce Hba1c.
Rarely used now. Can combine.
AE- weight gain, fluid retention, HF, OP, bladder CA.

Question 9

Biguanides eg metformin

Answer 9

Reduce insulin resistance, reduce gluconeogenesis, reduce gut glucose absorption.
1st line for T2DM. Can combine.
AE- sometimes slight weight gain. GI. Lactic acidosis rare. Decrease vitB12 rare.
Contra indicated if reduced HRH function, and respiratory disease.
Not metabolised.
Not act on beta cells so no beta function required.

Question 10

Sulphonylurea eg gliclazide

Answer 10

Close ATP K channels= depolarisation= open VGCa= pro insulin release.
Can use in renal impairment.
AE- weight gain, hypoglycaemia.

Question 11

Anti obesity eg orlistat

Answer 11

Reduce diet fat conversion to FA and glycerol. Inhibit pancreatic and gastric lipase.
Part of overall plan if BMI over 28.
AE- GI, faecal incontinence.

Question 12

Meglitinides eg repaglinide

Answer 12

Antagonise K ATP channel.
ST control post prandial glucose, take immediately before eat.
No weight gain, low risk hypoglycaemia, fast acting.

Question 13

sodium glucose cotransport 2 inhibitors eg dapagliflozin

Answer 13

Inhibit SGLT2 in PCT, prevent glucose reabsorption.
Add on for T1 and T2DM.
AE- lack LT studies. UTIs, polyuria.

Question 14

Explanation

Answer 14

• when we eat our gut breaks down the food into sugar which is absorbed into the blood. It is then taken up into cells to be used for energy to make our bodies work. In order to be taken up, the hormone insulin is required. In type 2 diabetes which you have, usually some insulin is being produced but the body is not responding to it in the normal way. So sugar is staying in the blood causing the symptoms you probably had.
• it is commonly due to bad diet and lack of exercise. So the first treament we try is to lose weight, eat healthy, exercise more and stop smoking and drinking. If this doesnt work then we can try tablets to help the insulin work better at letting the sugar be used, and this is normally enough to manage the condition in the long term. But Eventually the pancreas can get tired and can stop producing any, so at that point, which is unlikely you can need insulin injections. Also we need you to be good at monitoring your blood sugar levels. And it is important to notice the signs of low blood sugar.
• as is said, these treatments are usually very effective and mean you can live a normal life. But if your blood sugar is not well controlled this can in the long term damage your blood vessels and nerves, which can put you at risk of things like heart attacks, numbness and eye problems.

Question 15

HONK

Hyperosmolar nonketotic coma

Answer 15

Glucose often over 28 M
Usually no ketones or sev acidosis
Hyperosmolarity
Often hyperNa
Mx- K, insulin, fluid, airway, heparin, monit UE, stop metformin