Diabetes Flashcards
MODY definition
Maturity onset diabetes of the young
monogenic defect in glucose sensing in the pancreas+/ loss of insulin secretion that causes familial form of early onset (<25yo) diabetes
MODY2 is caused by a gene defect for ____ which causes a ___ defect and the insulin threshold for a set blood glucose level ___
glucokinase
glucose sensing
increases
MODY1+3 are caused by gene defects in ___ they ____+___
HNF (hepatocyte nuclear factors)4alpha and 1 alpha respectively
regulate beta cell differentiation and function
MODY 4 is caused by a gene defect in ___
insulin promotor factor 1 (IPF1)
MODY 5 is caused by a gene defect in ___
HNF-1beta
MODY6 is caused by a gene defect in ___
NeuroD1/beta2 - neurogenic differentiation factor
there are __ different genes that can be affected to cause MODY
6
treatment for MODY is usually ___ because ___
sulfonylureas
beta cells still have some function
the pathogenesis of T2D is
initial hyperglycaemia with hyperinsulinism
the primary problem is decreased tissue insulin sensitivity
Main problem in T1D
AI loss of insulin secreting beta cells
2 processes that insulin switches off
lipolysis
livergluconeogenesis
5 processes insulin switches on
AA uptake in muscles
glycogen synth
DNA+protein synth
muscle and adipose glucose uptake and lipogenesis
definition of phosphorylation
+phosphate group (PO4-) to any hydroxyl group by kinases - causes large -ve charge in molecule
tyrosine kinase receptor for insulin is ___ = 2 ___ alpha subunits which ___
and 2 beta ___ subunits which
both linked by ___
dimeric extracellular bind to insulin transmembrane ATP binding and tyrosine kinase domain disulfide bonds
2 functions of phosphorylated IRS-1 after tyrosine kinase receptor for insulin is activated
activate Ras/MAPK pathway and gene expression
activate P13K, PKB (stims GLUT4 translocation to membrane and increases glucose uptake) and glycogen synth
Leprechaunism/Donohue syndrome :
mode of inheritance
mutations in which gene
features
auto dom (rare)
gene for insulin receptor
elfin face, growth retarded, abscence of S/C fat and decreased muscle mass
severe insulin resistance
Rabson Mendenhall syndrome:
mode of inheritance
mutations in which gene
features
auto recessive (rare)
insulin receptor
severe insulin resistance, dev. abnormalities, acanthosis nigricans, fasting hypoglycaemia, DKA
Ketone bodies for in ____ from ___ after ___
liver mitochondrion
acetyl-CoA
beta-oxidation
ketone bodies are important for energy for __+__
where they are converted to ___ for use in the ___
cardiac myocytes and renal cortex
acetyl CoA to enter the TCA
the entrance of acetyl CoA into the TCA is dependent on ___ for formation of ___
oxaloacetate
citrate
In starvation/diabetes ___ are oxidised for energy to ___ however ___ has been used for gluconeogenesis and so __ are formed
FAs
acetyl Co-A
oxaloacetate
ketone bodies
In T2D they dont usually suffer from DKA because
high insulin concn inhibits hormone sensitive lipase so there is no excessive breakdown of fat resources
Diabetes Insipidus is caused by a lack of __
ADH/vasopressin
diagnostic criteria for diabetes based on HbA1c
<=41mmol/mol = normal 42-47 = pre-diabetes >=48 = diabetes
diagnostic criteria for diabetes based on fasting glucose
<=6mmol/l = normal 6.1-6.9 = prediabetes >7 = diabetes
diagnostic criteria for diabetes based on 2hr glucose in OGTT
<=7.7mmol/l = normal 7.8-11 = pre-diabetes >=11.1 = diabetes
diagnostic criteria for diabetes based on random glucose
> 11.1mmol/l = diabetes
lipoatrophic diabetes =
genetic insulin action disorder
2 other endocrinopathies that can cause diabetes
acromegaly
Cushing’s
drug induced diabetes (2)
steroids
thiazides
3 congenital conditions that can cause diabetes
Downs
Turners
Prader Willi
antibodies present in T1D
produce __ with ___ in the pancreas (histology)
anti-GAD
anti-islet cell Igs
insulinitis with lymphocyte infiltrate
T1D and T2D probability of microvasc complications at diagnosis
T1D = no signs usually T2D = 20% have them
T1D/T2D onset of symptoms at diagnosis is severe/insidious
T1D = severe T2D = insidious
discriminatory tests (3) for T1+2D
GAD/anti-islet cell Igs
ketones
C-peptides in the plasma
LADA = late onset ___
often misdiagnosed as __ but will have __+__
T1D
T2D but will have ketones and GAD Ig
MODY is GAD IG __ and C peptide __
GAD -ve
C +ve
HbA1c =
measures
glycated Hb
glucose control over past 2-3 months
3 microvascular complications of diabetes
neuropathy
nephropathy
retinopathy
cause of 75% of diabetic mortality
cardiac and renal causes
in T2D histology =
amyloid in pancreas
2 HLA genotypes that most increase risk of T1D
DR3-DQ2
DR4-DQ8
autoantibodies in T1D (4)
They are all though to differentiate from __
GAD 65 Ig (against glutamic acid decarboxylase
IA-2 Ig (Islet antigen 2)
ZnT8 Ig (ZnT8 transporter
IAA (insulin)
ICA - islet cell cytoplasmic Ig
ideal HbA1c for a T1D
48-58mmol/mol
if only have 50% of beta cell mass =>
hypergylcaemia
if only have __% of beta cell mass then need insulin
10%
blood glucose at presentation of T1/2D =
1 = >25 2 = 10-25
increased pancreatic auto-Igs in patients with recently diagnosed diabetes who dont initially require insulin =
LADA
___% of CF patients have diabetes at 20yo
25%
screen for diabetes in CF with ___ from age ___
OGTT from age 10
DIDMOAD/Wolfram syndrome features:
mode of inheritance =
Diabetes insipidus and mellitus, optic atropy, deaf, neuro abnormality
mitochondrial
Bardet-Biedl syndrome features:
more likely if ___ parents
v obese, polydactyly, hypogonadal, visual and hearing impairment, mental retardation, diabetes
consanguinous
Type 2 polyglandular endocrinopathy = T1D associated with any/all of: (5)
coeliacs addisons vitiligo primary hypogonadism primary hypothyroidism
Type 1 polyglandular endocrinopathy = T1D associated with any of: (9)
mild immune deficiency, primary hypoPT, pernicious anaemia, alopecia coeliacs addisons vitiligo primary hypogonadism primary hypothyroidism
tense tiredness is used to describe
hypoglycaemic symptoms
3 aims of insulin therapy
avoid hyperglycaemia +DKA
reduce chronic complications
acoid hypoglycaemia
rapid acting insulin analogues duration of action
5hrs
short acting - soluble/regular insulins duration of action
8hrs
intermediate acting insulins - isophane duration of action
20hrs
long acting insulin analogues duration of action
24hrs
basal bolus regime = ___ prandially and ___ before bed
rapid acting
long acting
analogues increase or decrease the risk of hypos?
decrease
bg target for a diabetic pre meal =
1-2hrs after start of meal =
4-7mmol/l
<10
analogue prandial insulin examples (3)
novorapid (insulin aspart)
lispro (humalog)
glulisine (apidra)
soluble prandial insulins examples (2)
actrapid
humulin S
isophane basal insulin egs (2)
insulatard
humulin I
basal analogue insulin egs (2)
lantus (glargine)
levemir (determir)
DAFNE =
dose adjustment for normal eating
in diabetics on insulin
1 unit insulin : ___ carbs
10g
if postprandial bg is __ mmol/l > pre meal = increase insulin dose
2
use of insulin in a hypo?
DON’T OMIT it
treat hypo then give insulin as normal
if on IV insulin then bg aim is __mmol/l
5-12
if on IV insulin and bg >12mmol/l = check __
ketones