other forms of diabetes

Question 1

4 other types of diabetes

Answer 1

Monogenic Causes
Diseases of the exocrine pancreas
Endocrine causes
Drug-induced diabetes

Question 2

what is the commonest type of monogenic diabetes

Answer 2

maturity onset diabetes of the young - MODY

Question 3

when is MODY diagnosed

Answer 3

less than 25 years

Question 4

characteristics of MODY

Answer 4

Autosomal dominant
Non-insulin dependent
Single gene defect altering beta cell function
Tend to be non-obese

Question 5

what is transcription factor MODY

Answer 5

Hepatic nuclear factor (HNF) mutations alter insulin secretion, reduce beta cell proliferation

Question 6

what is HNF1A mutation (MODY3)

Answer 6

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

Question 7

what is HNF4A mutation (MODY 1)

Answer 7

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

Question 8

what is glucokinase (GCK) mutation (MODY 2)

Answer 8

GCK is the glucose-sensor of beta cells, rate determining step in glucose metabolism, controlling the release of insulin
Higher set point, but still tight glycaemic control
Mild diabetes, no treatment required

Question 9

what is MODY typically misdiagnosed as

Answer 9

type 1 or young onset type 2

Question 10

which patients might be MODY

Answer 10

• Parent affected with diabetes
• Absence of islet autoantibodies
• Evidence of non-insulin dependence?
  
  • Good control on low dose insulin
    -No ketosis
    -Measurable C-peptide
• Sensitive to sulphonylurea

Question 11

is C peptide present in synthetic insulin

Answer 11

no

Question 12

what happens to C peptide in t1 diabetes

Answer 12

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

Question 13

what happens to C peptide in type 2 and mODY

Answer 13

it persists

Question 14

when is permanenet neonatal diabetes diagnosed

Answer 14

less than 6 months

Question 15

signs of permanent neonatal diabets

Answer 15

Small babies, epilepsy, muscle weakness

Question 16

what happens in permanent neonatal diabetes

Answer 16

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 17

describe maternally inherited diabetes and deafness (MIDD)

Answer 17

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

Question 18

describe lipodystrophy

Answer 18

Selective loss of adipose tissue

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

Question 19

describe acute inflammatory disease of exocrine pancreas

Answer 19

usually transient hyperglycaemia, due to increased glucagon secretion

Question 20

describe chronic pancreatitis

Answer 20

Alcohol
Alters secretions, formation
of proteinaceous plugs that
block ducts and act as a foci
for calculi formation
Stop alcohol, treat with insulin

Question 21

describe hereditray haemochromatosis

Answer 21

Autosomal recessive – triad of cirrhosis, diabetes and bronzed hyperpigmentation
Excess iron deposited in liver, pancreas, pituitary, heart and parathyroids
Most need insulin

Question 22

describe deposition

Answer 22

Amyloidosis / cystinosis

Question 23

describe pancreatic neoplasia

Answer 23

Common cause of cancer death
4-5 resections per week at STH
Require sc insulin
Prone to hypoglycaemia due to loss of glucagon function
Frequent small meals, enzyme replacement
Insulin pumps

Question 24

describe cystic fibrosis

Answer 24

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

Regulates chloride secretion

Viscous secretions lead to duct obstruction, and fibrosis

Incidence is 25 to 50% in adults

Ketoacidosis rare

Insulin treatment required

CF survival better, so microvascular complications increasing

Question 25

what does insulin improve in cystic fibrosis

Answer 25

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

Question 26

endocrine causes of diabetes

Answer 26

1. acromegaly
2. cushings syndrome
3. pheocromocytoma
   4.

Question 27

describe acromegaly

Answer 27

Excessive secretion of growth hormone
Similar to Type 2
Insulin resistance rises, impairing insulin action in liver and peripheral tissues

Question 28

describe cushings syndrome

Answer 28

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

Question 29

describe pheochromocytoma

Answer 29

Catecholamine, predominately epinephrine excess
Increased gluconeogenesis
Decreased glucose uptake

Question 30

describe drug induced diabetes

Answer 30

Glucocorticoids increase insulin resistance
Thiazides / protease inhibitors (HIV) / antipsychotics – mechanisms not clearly understood