somogyi phenomenon and t1dm - what - why

- Rebound hyperglycaemia from late night/ early AM hypoglycaemia, - Due to exaggerated counter regulatory response-

Diabetes Flashcards by Grace W

List the insulin dependent vs insulin independent glucose transporters

i. Insulin independent
1. Brain = GLUT1
2. B islet cells, liver, kidney + small intestine (basolateral) = GLUT2
3. Neurons = GLUT3
4. GI tract (apical – fructose transport) + spermatocytes = GLUT5

ii. Insulin dependent
1. Skeletal muscle + adipocytes = GLUT4

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What is the pattern of insulin secretion? Loss of this =?

i. Pulsatile (periodicity of 9-14 minutes)

ii. Loss of pulsatility = one of the earliest signs of basal cell dysfunction

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Physiology of insulin secretion in pancreatic beta cells

i. Glucose enters B cell of pancreas via GLUT-2 transporter
ii. Glucose is phosphorylated to glucose-6-phosphate by glucokinase
iii. Glucose-6-phosphate can then be metabolised to generate ATP
iv. ↑ ATP leads to closure of ATP-sensitive K channel (K-ATP)
1. K-ATP is made up of two subunits:
a. SUR gene – chromosome 11 p
b. KIR 6.2 gene – chromosome 11 p
v. Closure of channel = intracellular accumulation of potassium = depolarisation of membrane
vi. Calcium channels open
vii. Influx of calcium leads to secretion of insulin

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Pathophysiology of neonatal diabetes

Activating mutation = ↑ number of open KATP channels at the plasma cell
Hyperpolarization of the beta cells
Decreased release of insulin

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Pathophysiology of hyperinsulinism of infancy

Inactivating mutations in either gene reduce the number of KATP channels
Depolarisation of beta cells
Increased/hypersecretion of insulin

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which hormones counteract insulin (4)?

glucagon, GH, adrenaline, cortisol

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which is the only organ glucagon clinically acts on?

liver

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sources of blood glucose (hormones, timing, and how we get the glucose)
what is the order in which these hormones are released?

Glucose Diet 2-4 hours
Glycogenolysis Glucagon 10-12 hours
Gluconeogenesis Cortisol 12-24 hours
Lipolysis GH 17-36 hours

adrenaline > glucagon > cortisol > GH

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name the three ketone types

B-hydroxybutyrate, acetoacetic acid, acetone

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3 processes we get glucose from

glycolysis
glycogenolysis
gluconeogenesis

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physiology of glycolysis (aerobic vs anaerobic)

Anaerobic fermentation
glycogen -> x2pyruvate and 2ATP
pyruvate -> lactic acid -> to liver
usually just muscle

AAerobic respiratory
pyruvate oxidation -> acetyl coA
-> krebs -> ETC -> CO2 + H2O + 38ATP
in mitochondria

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What infections can induce diabetes (name 3)

CMV, HUS, rubella

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how many % of new T1DM have FHx?

85% have no FHx

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what is peak age of t1dm dx?

bimodal peak at 4-6 years of age, and another at 10-14 years of age

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what genes are associated with t1dm (most common)?

HLADR3/DR4

DQ2/8

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how much of beta cell is destroyed before you get clinical signs in t1dm

90%

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dawn phenomenon and t1dm:

what is it
what causes it
when
how to fix

i. Early morning (2-8am) hyperglycaemia due to overnight GH secretion + ↑ insulin clearance
ii. Occurs in peri-pubertal + pubertal years
iii. Manage with ↑ evening protophane dose

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somogyi phenomenon and t1dm

what
why

Rebound hyperglycaemia from late night/ early AM hypoglycaemia,
Due to exaggerated counter regulatory response-

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classic t1dm triad of symptoms

polydipsia - from inc serum osm
polyuria - glycosuria + osmotic diuresis
weight loss - hypovolaemia + inc catabolism, insulin def

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diagnostic criteria t1dm

one of:

Fasting (>8 hours) BSL >7 mmol/L on more than one occasion
Random BSL >11.1 mmol/L on more than one occasion in a patient with symptoms of hyperglycaemia
BSL >11.1 two hours after oral glucose load of 1.75 g/kg (max 75g) in OGTT (rarely done)

nb HbA1c >6.5 – not established as diagnostic for diabetes in children

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the 5 t1dm autoantibodies - which is best predictor, and which is most present at dx? progression of autoabs?

Insular at first, GAD its mentioned most, but NOMA is the best. Issa Zingga!:

Anti-insulin antibodies (IAA) - first
Anti-glutamic acid decarboxylase (anti-GAD) - second, best
Anti-insulinoma protein 2 (anti-IA2) - third, best
Islet cell cytoplasmic antibodies (ICA) - 70%
Anti-zinc transporter (anti-ZNT8)

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which t1dm-associated gene is more associated with AI conditions?

HLA DR3 - note longer dm dormancy period, a/w ICA autoabs.

Note HLADR4 - a/w anti-IAA

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what % of t1dm will developed coeliac within first 6 yrs of dx?

Study These Flashcards

7-15% of children with T1DM develop celiac disease within the first 6 years of diagnosis

what % of t1dm will develop hyper vs hypothyroidism?

Study These Flashcards

2-5% develop hypothyroidism

1% develop hyperthyroidism (much rarer, but more common than general population)

name 5 autoimmune conditiions associated with t1dm

1. thyroid disorder 2. coeliac disease 3. AI adrenalitis - 1 % 4. Gastric autoimmunity - anti-parietal cells, anti-IF 5. vitiligo - 6%

name two autoimmune syndromes associated with t1dm

APS-2 | IPEX

recommended diet stuff for t1dm

CHO 50% and low GI, fat 30% with saturated <10%, protein 20%

t1dm: target bsl, hba1c, what bsl to treat for hypo, and what ketones to treat

Target BSL = 4-8 Target HbA1C = <7.5% Treat: Hypoglycaemia = <4 Ketosis = >1

6 side effects of insulin Rx

1. Hypoglycaemia 2. Lipohypertophy at injection sites 3. insulin resistance 4. Insulin antibodies - nearly all develop antibodies after several moths 5. weight gain 6. local allergy

BD vs basal-bolus insulin regimens: - TDD - distribution

both TDD = 1UKD basal bolus: - usually nocte levemir (0.4UKD) + tds novo (each 0.2UKD) BD: usually levemir and novo BD - mane 2/3 TDD, evenine 1/3 TDD

2 molecules to assess mid-long term diabetes control

hba1c (2-3 month control) | fructosamine (glycated serum proteins) - 1-2 week control, useful in haemoglobinopathies (HbA1c spuriously ↓/↑)

pathogenesis of most of the macro/microvascular complications of t1dm

* Polyol pathway – metabolisms excess glucose to sorbitol then fructose = tissue damage * Glycosylation of proteins – glucose binds to proteins irreversibly and alteration leads to loss of function

types of diabetic retinopathy

- background - dilated vessels - non-proliferative - microinfarcts, cotton wool spots / soft exudate - proliferative - hard shit: ischaemia, haemorrhage, scarring, RD!

what is the earliest sign of diabetic nephropathy? define it.

albuminuria: albumin excretion between 30-300 mg/day (20-200 mcg/min)

what is necrobiosis lipoidica

inflammatory, granulomatous condition - oval/round plaques on shins. initially red/dusky -> yellow, central atrophy

mauriac syndrome: pathophys a/w signs

rare complication t1dm glycogen laden liver -> hepatomegaly + cushingoid facies a/w delayed puberty and DWARFISM catch up growth if diabetes fixed

what are normal ketone levels

<0.6

glucagon dosing in severe hypoglycaemia

1. 0.5ml = children <25 kg | 2. 1ml = children >25kg

definition of DKA

hyperglycaemia + metabolic acidosis + ketonaemia | venous gas <7.3 + blood or urinary ketones

hypo and hyperkalaemia on ECG

1. Hyperkalaemia = peaked T waves, widened QRS | 2. Hypokalaemia = flattened or inverted T waves, ST depression, widened PR interval

outline steps in DKA Mx

1. ABC 2. fluids 3. insulin infusion (0.1MKH if new Dx) 4. potassium - total body K deficit but apparent hyperK, risk of hypoK with insulin

when to switch to SC insulin from continuous in DKA? When to stop the infusion?

start SC just before meal. | stop continuous 30 mins after SC (for overlap)

when to give bicarb in DKA?

not recommended - causes paradoxical cerebral acidosis

what to do if still hypoglycaemic with DKA Mx?

inc to 10% dex - dont reduce insulin until 10% dex really not working

what is the rule for Na correcting during DKA?

Na should improve as glucose falls - hypoNa is dilutional effect of glucose

complications of DKA - and which is responsible for highest mortality

1. hypoNa 2. hypoglycaemia 3. cerebral oedema - causes 60% deaths 4. hypo/hyperK 5. renal failure 6. pancreatitis

cerebral oedema: - 3 at risk groups - warning signs related to Mx - how to treat

- first presentation, long history of poor control, young age (< 5 yr) - No sodium rise as glucose falls, hyponatraemia during therapy, initial adjusted hypernatraemia - mannitol

which other endocrine condition is a risk factor for DKA

hyPERthyroidism

best T2DM test for Dx?

fasting GTT

clinical signs of insulin resistance in T2DM, and which is the most common?

- cutaneous: acanthosis nigricans (best!), alopecia, skin tags - reproductive: amenorrhoea, hirsutism, virilisation - fat

treatment regimen of chocie in T2DM

metformin monotherapy

what is worse than DKA for T2DM?

hyperosmolar non-ketotic acidosis - insulin deficiency - extreme hyperglycaemia - extreme dehydration in cells - GNG without ketones bc there's still insulin - fluid resus +++

MODY inheritance pattern

MODY 2 - pathogenesis + gene - frequency - key clinical feature - risk of microvascular disease - optimal treatment

- Glucokinase gene GCK (glucose sensor) - Defective glucokinase -> increased plasma levels of glucose to elicit normal levels of insulin secretion - 15-30% - Mild, stable, fasting hyperglycemia, often diagnosed during routine screening. Not progressive. - generally no risk of microvascular disease - diet Mx

MODY 3 - pathogenesis + gene - frequency - key clinical feature - risk of microvascular disease - optimal treatment

- Hepatocyte nuclear factor-1-alpha HNF1alpha - Mechanism unclear, ?reduced insulin secretory response to glucose, low renal threshold for glucose (decreased renal absorption of glucose) - glycosuria key feature - yes to microvascular disease - sulfonylureas

Diabetes Flashcards

(55 cards)