Diabetes

Question 1

MODY1

Answer 1

Gene mutation: HNF4alpha
Reduced TGs
May respond to sulphonyureas

Question 2

MODY2

Answer 2

GCK (glycokinase)
Hyperglycaemia of early mild onset nonprogressive

2nd most common. Heterozygotes lead to mild reductions in beta cell response to glucose (higher threshold for insulin release, HbA1c less than 7%, mild fasting hypoglycaemia), maybe misdiagnosed as GDM or well controlled type 2 adults.

Homozygous are unable to secret insulin = severe neonatal diabetes

Oral agents or small doses of insulin may be useful.

Question 3

MODY3

Answer 3

HNF1alpha (hepatocyte nuclear factor 1alpha)
Reduced renal abs of glucose
Most common (65% of cases), abnorms of CHO metabolism: from IGT to severe diabetes, often progressing from mild to severe over time.
Very sensitive to sulphonyureas.

Question 4

MODY4

Answer 4

IPF-1
Homozygous mutation causes pancreatic agenesis
May respond to sulphonyureas

Question 5

MODY 5

Answer 5

HNF1beta
Nonhuperglycaemic renal disease (renal cysts and renal dysfunction) ass with renal abnorms, hypospadius, joint laxity, learning problems

Does NOT respond to oral agents, requires INSULIN

Question 6

MODY 6

Answer 6

NEUROD1 - development of pancreatic islets

Extremely rare

Question 7

Features of Wolfram syndrome

Answer 7

Diabetes insipidus, DM, optic atrophy and deafness (DIDMOAD). Sometimes ass with mitochondrial mutations.

Question 8

Define MODY
Types?
Most common?

Answer 8

Group of Heterogenous clinical entities characterised by onset between 9y and 25y, AD inheritance and a primary in insulin secretion (defects in beta cell function).

6 Types, 80% of cases are type 2 and 3 in European populations.

Type 2 = glycokinase enzyme mutation
The rest are problems with various transcription factors