other types of diabetes

Question 1

what is MODY?

Answer 1

maturity- onset diabetes of the young - MODY

Question 2

describe the genetic history of MODY

Answer 2

Autosomal dominant
Non-insulin dependent
Single gene defect altering beta cell function

Question 3

describe the physical history of MODY

Answer 3

Tend to be non-obese
Diagnosed <25y

Question 4

what is the transcription factor in MODY?

Answer 4

Hepatic nuclear factor and the mutations alter insulin secretion, reduce beta cell proliferation

Question 5

what treatment does HNF1A mutation (MODY 3) require?

Answer 5

Very sensitive to sulphonylurea treatment (tablet), so often do not need insulin (~80%)

Question 6

what treatment does HNF4A mutation (MODY 1) require?

Answer 6

-FH, young age of onset, non-obese, Sus, AND
-Macrosomia (>4.4kg at birth)
-Neonatal hypoglycaemia

Question 7

Glucokinase gene (GCK) mutation (MODY 2)- what does GCK do?

Answer 7

GCK is the glucose-sensor of beta cells, rate determining step in glucose metabolism, controlling the release of insulin

Question 8

what is treatment required forGlucokinase gene (GCK) mutation (MODY 2)

Answer 8

Higher set point, but still tight glycaemic control
Mild diabetes, no treatment required

Question 9

which patients might be MODY?

Answer 9

Parent affected with diabetes
Absence of islet autoantibodies
Evidence of non-insulin dependence
Sensitive to sulphonylurea

Question 10

describe evidence of non insulin dependence

Answer 10

Good control on low dose insulin
No ketosis
Measurable C-peptide

Question 11

is c peptide present in synthetic insulin?

Answer 11

no

Question 12

what is c peptide half life?

Answer 12

C-peptide longer half-life, 30 vs 3 mins

Question 13

describe c peptide in type 1 diabetes?

Answer 13

In Type 1 diabetes C-peptide is negative within 5 years (due to complete autoimmune beta cell destruction)

Question 14

describe c peptide in type 2 diabetes?

Answer 14

Type 2 and MODY C-peptide persists

Question 15

signs of Permanent Neonatal Diabetes- when is it diagnosed?

Answer 15

Diagnosed <6 months (usually de novo

Question 16

Signs of Permanent Neonatal Diabetes

Answer 16

Small babies, epilepsy, muscle weakness

Question 17

describe the physiology behind Permanent Neonatal Diabetes

Answer 17

Mutations encode Kir6.2 and SUR1 subunits of the beta cell ATP sensitive potassium channel
Rising ATP closes the channel as a result of hyperglycaemia, depolarising the membrane and insulin is secreted
Mutations prevent closure of the channel, and thus beta cells unable to secrete insulin
Sulphonylureas close the KATP channel

Question 18

where is the Maternally inherited diabetes and deafness (MIDD) mutation?

Answer 18

Mutation in mitochondrial DNA
Loss of beta cell mass
Similar presentation to Type 2
Wide phenotype

Question 19

describe Lipodystrophy

Answer 19

Selective loss of adipose tissue

Question 20

what is Lipodystrophy associated with?

Answer 20

Associated with insulin resistance, dyslipidaemia, hepatatic steatosis, hyperandrogenism, PCOS

Question 21

describe acute inflammation of exocrine pancreas

Answer 21

usually transient hyperglycaemia, due to increased glucagon secretion

Question 22

what causes chronic pancreatitis??

Answer 22

Alcohol

Question 23

what happens in chronic
pancreatitis?

Answer 23

Alters secretions, formation
of proteinaceous plugs that
block ducts and act as a foci
for calculi formation

Question 24

how to treat chronic pancreatitis?

Answer 24

Stop alcohol, treat with insulin

Question 25

describe the genetic makeup of hereditary haemochromatosis?

Answer 25

Autosomal recessive – triad of cirrhosis, diabetes and bronzed hyperpigmentation

Question 26

where is elves iron deposited in Hereditary Haemochromatosis?

Answer 26

Excess iron deposited in liver, pancreas, pituitary, heart and parathyroids

Question 27

what is deposition?

Answer 27

Amyloidosis / cystinosis

Question 28

what is pancreatic neoplasia a common cause of?

Answer 28

cause of cancer death

Question 29

what do people with pancreatic neoplasia require?

Answer 29

sc insulin

Question 30

what are people with pancreatic neoplasia prone to?

Answer 30

Prone to hypoglycaemia due to loss of glucagon function

Question 31

what is the treatment for people with Pancreatic Neoplasia?

Answer 31

Frequent small meals, enzyme replacement
Insulin pumps

Question 32

what is the gene causing cystic fibrosis? what does it regulate?

Answer 32

Cystic fibrosis transmembrane conductance regulator (CFTR) gene located on chromosome 7q22
Regulates chloride secretion

Question 33

what do viscous secretions from CFTR lead to ?

Answer 33

Viscous secretions lead to duct obstruction, and fibrosis

Question 34

what treatment is required in cystic fibrosis?

Answer 34

Insulin treatment required

Question 35

in cystic fibrosis, what does insulin improve?

Answer 35

Body weight
Reduces infections
Lung function
Improves quality of life, and ?survival

Question 36

describe insulin resistance in acromegaly

Answer 36

Insulin resistance rises, impairing insulin action in liver and peripheral tissues

Question 37

describe insulin resistance in Cushings syndrome

Answer 37

Increased insulin resistance, reduced glucose uptake into peripheral tissues
Hepatic glucose production increased through stimulation of gluconeogenesis via increased substrates (proteolysis and lipolysis)

Question 38

describe blood glucose levels in pheochromocytoma

Answer 38

Catecholamine, predominately epinephrine excess
Increased gluconeogenesis
Decreased glucose uptake

Question 39

what do glucocorticoids do?

Answer 39

increase insulin resistance

Question 40

what other drugs cause diabetes?

Answer 40

Thiazides / protease inhibitors (HIV) / antipsychotics