Type 1 Diabetes Pathophysiology and Clinical Features Flashcards
type 1 histology?
lymphocyte infiltration in islet cells
type 2 histology?
amyloid deposition in islets
which type has a stronger genetic link?
type 2
higher incidence seen in monozygotic twins
what genes are responsible for the familial link in diabetes?
mostly HLA genes
- DR3 DQ2 genotype
- DR4 DG8 genotype
environmental factors in T1DM development?
seasonality (winter) timing of birth viral infection trigger maternal factors trigger weight gain trigger
what are the autoantibodies in T1DM?
IA2 = islet antigen IAA = insulin GAD = glutamic acid decarboxylase ZnT8 = zinc transporter
what factors/markers in a newborn increase risk of diabetes?
infection age of mother ABO mismatch birth order stress HLA gene
name 4 auto-immune trigger factors which may trigger the onset of type 1 diabetes in a predisposed individual
viral infection
vit D deficiency
diet
environmental factors
what factors may accelerate disease progression in diagnosed type 1 diabetes?
infection insulin resistance puberty diet/weight stress
what is the classic triad of T1DM presenting symptoms?
polyuria
polydipsia
weight loss
what other symptoms may occur in T1DM?
fatigue and somnolence
blurred vision
candidial infection
DKA
how might polyuria present in children?
enuresis (bed wetting)
what candidial infections commonly occur in diabetes?
pruritic vulvae
balanitis
management of newly diagnosed T1DM?
blood glucose and ketone monitoring (at home) insulin treatment - usually basal (once daily) with bolus (with meals) regimen estimate carbohydrates regular DSN and dietitian contact appropriate medical clinic review regularly check control via HbA1c annual review assessment record any severe episodes
what is included in an annual review assessment?
weight BP bloods: HbA1c, renal function, lipids retinal screening foot risk assessment
children are more likely to get T1DM if what parent is affected?
father
what autoimmune condition is most commonly associated with T1DM?
CF
how is insulin normally secreted?
biphasic secretion in response to meal
- rapid, pre formed insulin = 5-10 mins
- slow phase over 1-2 hrs
secreted into portal vein
is insulin secreted when fasting?
yes
at rate of 0.25-1.5 units/hr
do all types of diabetes need insulin right away?
no
type 1 needs insulin almost immediately
LADA after a few years
Type 2 after many years, sometimes not at all
which forms of diabetes are ketones usually found in?
type 1
secondary
not usually in type 2 or monogenic
how do type 1 and type 2 differ in terms of glucose levels, complications and C-peptide at diagnosis?
type 1 glucose usually slightly higher
type 1 rarely has complication at diagnosis, type 2 often does
C-peptide low at diagnosis in type 1 and eventually absent after a few years
C-peptide normal/raised at diagnosis in type 2 and still present after a few years
what type of diabetes is usually the cause in children diagnosed under 6 months?
monogenic rather than type 1
what is LADA and how is it diagnosed?
Latent Onset Diabetes of Adulthood
presence of elevated autoantibodies in patients with recently diagnosed diabetes who don’t immediately require insulin
when is LADA suspected?
adults 25-40 often male non-obese autoantibody positive associated autoimmune conditions non-insulin requiring at diagnosis sub-optimal control on oral agents
how is CF associated diabetes screened for and managed?
OGTT screening in all CF patients over 10
insulin therapy preferred
what is DIDMOAD syndrome/Wolfram syndrome?
diabetes insipidus diabetes mellitus optic atrophy deafness (neurological anomalies)
what are the features of bardet-biedl syndrome?
often very obese polydactyly hypogonadal visual impairement hearing impairement mental retardation diabetes consanguineous parents
what features indicate that it is not type 1 diabetes?
diagnosed <6 months
detectable insulin production 3 years after diagnosis
C-peptide positive
name 5 auto-immune conditions which are commonly associated with type 1 diabetes
thyroid disease coeliac disease pernicious anaemia addisons disease IgA deficiency
what are the symptoms and signs of coeliac disease?
can be asymptomaic bloating/diarrhoea malabsorption anaemia low albumin low calcium
how is coeliac disease diagnosed?
anti TTG antibodies IgA deficiency common duodenal biopsy (villous atrophy)
what is type 1 polyglandular endocrinopathy associated with?
mild immune deficiency
primary hypoparathyroidism/pernicious anaemia/alopecia
same diseases as type 2
what diseases is type 2 polyglandular endocrinopathy associated with?
any or all of addisons disease vitiligo primary hypogonadism primary hypothyroidism coeliac disease
how is type 1 polyglandular endocrinopathy inherited?
autosomal recessive
