Type 1 Diabetes Pathophysiology and Clinical Features

Question 1

type 1 histology?

Answer 1

lymphocyte infiltration in islet cells

Question 2

type 2 histology?

Answer 2

amyloid deposition in islets

Question 3

which type has a stronger genetic link?

Answer 3

type 2

higher incidence seen in monozygotic twins

Question 4

what genes are responsible for the familial link in diabetes?

Answer 4

mostly HLA genes

• DR3 DQ2 genotype
• DR4 DG8 genotype

Question 5

environmental factors in T1DM development?

Answer 5

seasonality (winter)
timing of birth
viral infection trigger
maternal factors trigger
weight gain trigger

Question 6

what are the autoantibodies in T1DM?

Answer 6

IA2 = islet antigen
IAA = insulin
GAD = glutamic acid decarboxylase
ZnT8 = zinc transporter

Question 7

what factors/markers in a newborn increase risk of diabetes?

Answer 7

infection
age of mother
ABO mismatch
birth order
stress
HLA gene

Question 8

name 4 auto-immune trigger factors which may trigger the onset of type 1 diabetes in a predisposed individual

Answer 8

viral infection
vit D deficiency
diet
environmental factors

Question 9

what factors may accelerate disease progression in diagnosed type 1 diabetes?

Answer 9

infection
insulin resistance
puberty
diet/weight
stress

Question 10

what is the classic triad of T1DM presenting symptoms?

Answer 10

polyuria
polydipsia
weight loss

Question 11

what other symptoms may occur in T1DM?

Answer 11

fatigue and somnolence
blurred vision
candidial infection
DKA

Question 12

how might polyuria present in children?

Answer 12

enuresis (bed wetting)

Question 13

what candidial infections commonly occur in diabetes?

Answer 13

pruritic vulvae

balanitis

Question 14

management of newly diagnosed T1DM?

Answer 14

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

Question 15

what is included in an annual review assessment?

Answer 15

weight
BP
bloods: HbA1c, renal function, lipids
retinal screening
foot risk assessment

Question 16

children are more likely to get T1DM if what parent is affected?

Answer 16

father

Question 17

what autoimmune condition is most commonly associated with T1DM?

Answer 17

CF

Question 18

how is insulin normally secreted?

Answer 18

biphasic secretion in response to meal
- rapid, pre formed insulin = 5-10 mins
- slow phase over 1-2 hrs
secreted into portal vein

Question 19

is insulin secreted when fasting?

Answer 19

yes

at rate of 0.25-1.5 units/hr

Question 20

do all types of diabetes need insulin right away?

Answer 20

no
type 1 needs insulin almost immediately
LADA after a few years
Type 2 after many years, sometimes not at all

Question 21

which forms of diabetes are ketones usually found in?

Answer 21

type 1
secondary
not usually in type 2 or monogenic

Question 22

how do type 1 and type 2 differ in terms of glucose levels, complications and C-peptide at diagnosis?

Answer 22

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

Question 23

what type of diabetes is usually the cause in children diagnosed under 6 months?

Answer 23

monogenic rather than type 1

Question 24

what is LADA and how is it diagnosed?

Answer 24

Latent Onset Diabetes of Adulthood

presence of elevated autoantibodies in patients with recently diagnosed diabetes who don’t immediately require insulin

Question 25

when is LADA suspected?

Answer 25

``` adults 25-40 often male non-obese autoantibody positive associated autoimmune conditions non-insulin requiring at diagnosis sub-optimal control on oral agents ```

Question 26

how is CF associated diabetes screened for and managed?

Answer 26

OGTT screening in all CF patients over 10 | insulin therapy preferred

Question 27

what is DIDMOAD syndrome/Wolfram syndrome?

Answer 27

``` diabetes insipidus diabetes mellitus optic atrophy deafness (neurological anomalies) ```

Question 28

what are the features of bardet-biedl syndrome?

Answer 28

``` often very obese polydactyly hypogonadal visual impairement hearing impairement mental retardation diabetes consanguineous parents ```

Question 29

what features indicate that it is not type 1 diabetes?

Answer 29

diagnosed <6 months detectable insulin production 3 years after diagnosis C-peptide positive

Question 30

name 5 auto-immune conditions which are commonly associated with type 1 diabetes

Answer 30

``` thyroid disease coeliac disease pernicious anaemia addisons disease IgA deficiency ```

Question 31

what are the symptoms and signs of coeliac disease?

Answer 31

``` can be asymptomaic bloating/diarrhoea malabsorption anaemia low albumin low calcium ```

Question 32

how is coeliac disease diagnosed?

Answer 32

``` anti TTG antibodies IgA deficiency common duodenal biopsy (villous atrophy) ```

Question 33

what is type 1 polyglandular endocrinopathy associated with?

Answer 33

mild immune deficiency primary hypoparathyroidism/pernicious anaemia/alopecia same diseases as type 2

Question 34

what diseases is type 2 polyglandular endocrinopathy associated with?

Answer 34

``` any or all of addisons disease vitiligo primary hypogonadism primary hypothyroidism coeliac disease ```

Question 35

how is type 1 polyglandular endocrinopathy inherited?

Answer 35

autosomal recessive