other forms of diabetes Flashcards
4 other types of diabetes
Monogenic Causes
Diseases of the exocrine pancreas
Endocrine causes
Drug-induced diabetes
what is the commonest type of monogenic diabetes
maturity onset diabetes of the young - MODY
when is MODY diagnosed
less than 25 years
characteristics of MODY
Autosomal dominant
Non-insulin dependent
Single gene defect altering beta cell function
Tend to be non-obese
what is transcription factor MODY
Hepatic nuclear factor (HNF) mutations alter insulin secretion, reduce beta cell proliferation
what is HNF1A mutation (MODY3)
Very sensitive to sulphonylurea treatment (tablet), so often do not need insulin (~80%)
what is HNF4A mutation (MODY 1)
FH, young age of onset, non-obese, Sus, AND
Macrosomia (>4.4kg at birth)
Neonatal hypoglycaemia
what is glucokinase (GCK) mutation (MODY 2)
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
what is MODY typically misdiagnosed as
type 1 or young onset type 2
which patients might be MODY
- Parent affected with diabetes
- Absence of islet autoantibodies
- Evidence of non-insulin dependence?
- Good control on low dose insulin
-No ketosis
-Measurable C-peptide
- Good control on low dose insulin
- Sensitive to sulphonylurea
is C peptide present in synthetic insulin
no
what happens to C peptide in t1 diabetes
C-peptide is negative within 5 years (due to complete autoimmune beta cell destruction)
what happens to C peptide in type 2 and mODY
it persists
when is permanenet neonatal diabetes diagnosed
less than 6 months
signs of permanent neonatal diabets
Small babies, epilepsy, muscle weakness
what happens in permanent neonatal diabetes
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
describe maternally inherited diabetes and deafness (MIDD)
Mutation in mitochondrial DNA
Loss of beta cell mass
Similar presentation to Type 2
Wide phenotype
describe lipodystrophy
Selective loss of adipose tissue
Associated with insulin resistance, dyslipidaemia, hepatatic steatosis, hyperandrogenism, PCOS
describe acute inflammatory disease of exocrine pancreas
usually transient hyperglycaemia, due to increased glucagon secretion
describe chronic pancreatitis
Alcohol
Alters secretions, formation
of proteinaceous plugs that
block ducts and act as a foci
for calculi formation
Stop alcohol, treat with insulin
describe hereditray haemochromatosis
Autosomal recessive – triad of cirrhosis, diabetes and bronzed hyperpigmentation
Excess iron deposited in liver, pancreas, pituitary, heart and parathyroids
Most need insulin
describe deposition
Amyloidosis / cystinosis
describe pancreatic neoplasia
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
describe cystic fibrosis
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
what does insulin improve in cystic fibrosis
Body weight
Reduces infections
Lung function
Improves quality of life, and survival
endocrine causes of diabetes
- acromegaly
- cushings syndrome
- pheocromocytoma
4.
describe acromegaly
Excessive secretion of growth hormone
Similar to Type 2
Insulin resistance rises, impairing insulin action in liver and peripheral tissues
describe cushings syndrome
Increased insulin resistance, reduced glucose uptake into peripheral tissues
Hepatic glucose production increased through stimulation of gluconeogenesis via increased substrates (proteolysis and lipolysis)
describe pheochromocytoma
Catecholamine, predominately epinephrine excess
Increased gluconeogenesis
Decreased glucose uptake
describe drug induced diabetes
Glucocorticoids increase insulin resistance
Thiazides / protease inhibitors (HIV) / antipsychotics – mechanisms not clearly understood
