Type 1 Diabetes

Question 1

How would diabetes be diagnosed?

Answer 1

Symptoms: Thirsty, passing lots of urine, blurred vision, fatigue, thrush.
Fasting blood glucose: >7
OGTT: >11
HbA1c: >48 (not used in glasgow yet).

2 abnormal tests or 1 test + symptoms.

Question 2

List the types of diabetes?

Answer 2

Type 1 (insulin deficient)
Type 2 (insulin resistant)
MODY (maturity onset diabetes of the young - autosomal dominant).
Gestational
Secondary (pancreatits, cystic fibrosis, haemachromatosis, steroid induced, acromegaly).

Question 3

What auto-antibodies are usually found in Type 1 DM?

Answer 3

ICA (islet cell antibody)
I-A2 (Insulinoma-associated antigen-2).
IAA (insulin auto-antibody)
GAD65 (Glutamic acid decarboxylase 65)
ZnT8 (zinc transporter).

Question 4

What ways are there to predict type 1 diabetes?

Answer 4

HLA 
Auto-antibodies
First-phase insulin response to glucose
Tcell function
Elevated lysophosphatidylchloine
Reduced B-cell mass by PET scan.

Question 5

What other autoimmune diseases is Type 1 DM usually associated with?

Answer 5

Thyroid disease (hypo/hyper)
Coeliac 
Addisons disease
Pernicious anaemia
Inflammatory bowel disease
Premature ovarian failure.

Question 6

How do pancreatic B cells release insulin?

Answer 6

GLUT2 receptors sense blood glucose levels.
Glucose is taken up and converted to G6P (glucokinase) then pyruvate which is turned into ATP in mitochondria.
B-cells have a K+ channel and K+ moves out of the cell.
The cell depolarises and Ca2+ enters via a voltage-gated calcium channel.
This determines how many secretory granules of insulin are released.

Lots of glucose = lots of ATP = lots of K+ going out = lots of calcium going in = lots of insulin released.

Question 7

What causes MODY in B-cells?

Answer 7

Islet transcription factors modulate processes in the cell. If a transcription factor is wiped out then a ‘breaking mechanism’ is put on the cell giving insufficient insulin release.

Question 8

What are the 2 most common types of MODY and their prevalence?

Answer 8

HNF-1alpha: 60%

Glucokinase: 20%

Question 9

List the main hypoglycaemic drugs?

Answer 9

Sulphonylureas
Biguanides
Thiazolidinediones
Incretin minics & DPP-4 inhibitors
SGLT2 inhibitors.

Question 10

How do sulphonylureas work?

Answer 10

Inhibit ATP-sensitve K+ channels.

therefor cell doesnt depolarise, no insulin released

Question 11

How do Biguanides (metformin) work?

Answer 11

Mimicsinsulin by inhibiting hepatic gluconeogenesis.

Thought to be by inhibiting mitochondrial ATP synthesis - gluconeogenesis stops at it is very energy consuming.

Question 12

How do Thiazolidinediones work?

Answer 12

Stops inappropriate deposition of lipid in non-adipose tissue (which leads to insulin resistance) - therefore improves insulin sensitivity.
Pioglitazone still used.

Question 13

How do Incretins work?

Answer 13

GI hormones that potentiate insulin secretion.

Glucogon-like peptide-1 (GLP-1).
Gastric Inhibitory peptide (GIP).

Question 14

Which drug degrades Incretins?

Answer 14

DPP-4 Inhibitors.

Question 15

How do SGLT2 Inhibitors work?

Give examples of drugs.

Answer 15

Inhibit renal re-uptake of glucose from filtrate by SGLT2.
Produce lots of sweet urine - also have an effect on BP as water is lost.

Canagliflozin, Dapagliflozin.

Question 16

Why are SGLT1 inhibitors not used?

Answer 16

As these receptors are found in the gut for uptake of glucose transport after a meal, so would cause you to by hypoglycaemic.