Effects of Acute and Chronic Hyperglycaemia

Question 1

Why do patients with diabetes mellitus have increased urination?

Answer 1

increased glucose - polyuria cuases net inflow of glucose into urine - brings water along by osmosis - increased urination and dehydration

Question 2

What differs Type 1 from Type 2 diabetes?

Answer 2

Type 1 - autoimmune attacks beta cells in pancrease - absolute lack of insulin

Type 2= resistance to insulin= ‘relative’ lack of insulin

Question 3

How do we diagnose diabetes?

Answer 3

• Fasting blood glucose > 6.9 mmol/l
• 2hr post glucose load/Random >11 mmol/l
• HBA1c (glycated haemoglobin)> 48 mmol/mol
• Confirm a single elevated reading..unless symptoms

Question 4

Why does polyuria happen in hyperglycaemia?

Answer 4

b/c the overlaod of glucose spills into the urine

Question 5

why does blurred vision occur in diabetes?

Answer 5

B/c glucose enters the eye bringing water with it -

Question 6

Why does weight loss occur in hyperglycaemia?

Answer 6

losing sugar - cannot absorb it

Question 7

what is the emergency situation of Type 2 diabetes?

Answer 7

not ketosis b/c they typically produce enough insulin to prevent ketosis- but could have HHS

Question 8

What is Diabetic ketoacidosis

Answer 8

•Is a serious acute complication of Type 1 Diabetes Mellitus

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•Remains an important cause of morbidity and mortality

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•Mortality < 5% but higher in elderly/other illnesses

Question 9

how do we diagnose DKA?

Answer 9

•Diabetic: hyperglycaemia

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•Keto: presence of ketones in the blood/urine

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•Acidosis: presence of acidic blood

Question 10

What is the action of insulin?

Answer 10

• Increased transport of glucose, K+ and amino acids into cells
• Stimulation of protein synthesis
• Activation of glycogen synthase
• Inhibition of gluconeogenesis

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•Storage of CHO, Protein, Fat

Question 11

insulin stimulates increased transport of what molecules into the cells?

Answer 11

glucose, K+ and amino acids into cells

Question 12

“Starvation in the midst of plenty” refers to what?

Answer 12

Diabetes mellitus - plenty of food/glucose, but your body behaves as if it is starving

Question 13

what are the effects of chronic hyperglycaemia?

Answer 13

• Chronic hyperglycaemia leads to diabetes-specific microvascular complications in the eyes, kidneys and nerves- Microvascular complications occur at levels of glycaemia below those at which the patient is symptomatic
• Leading cause of blindness in the working age population
• Leading cause of ESRD needing dialysis
• Leading cause of disabling neuropathies
• 50% of all non-traumatic amputations
• Continuous relationship between level of glycaemia and risk of complications (HBA1c)

Question 15

How does chronic hyperglycaemia cause complications?

Answer 15

• Alteration of cellular homeostasis by increased cellular glucose uptake and increased intracellular glucose concentration
• •Imbalance between reactive oxygen species and cellular antioxidant defense mechanisms: oxidative stress
• Cells unable to reduce glucose uptake more vulnerable e.g.endothelial cells v VSMCs
• Increased polyol pathway flux
• Increased formation of AGEs
• Activation of PKC
• Increased flux through hexosamine pathway

Question 16

What is diabetic retinopathy?

Answer 16

• Sight-threatening chronic ocular disorder
• Eventually develops to some extent in almost all patients with DM
• Processes incompletely understood, but hyperglycaemia itself is sufficient- don’t also need high blood pressure to develop
• Increased blood glucose causes structural, physiologic and hormonal changes that affect the retinal microvasculature
• Loss of pericytes
• Thickened basement membrane
• Increased vessel permeability
• Decreased retinal blood flow
• Capillary occlusion
• Retinal hypoxia leads to increased VEGF and Angiogenesis
• Haemorrhage
• Traction retinal detachment

Question 17

What is panretinal laser photocoagulation?

Answer 17

treatment for proliferative diabetic retinopathy - where the peripheral retina is damaged by a laser - making it dead tissue that can no longer revascularize - therefore we spare the retina from further damage

Question 18

What is diabetic nephropathy?

Answer 18

• Less straightforward relationship between glycaemia and nephropathy: hyperglycaemia necessary but not sufficient-you wouldn’t get this without hyperglycaemia - but you won’t necessarily get it with hyperglycaemia
• Only 30% of patients develop clinically overt nephropathy
• Hyperglycaemia, hypertension, proteinuria
• Thickened GBM
• Podocyte abnormalities
• Expansion of glomerular mesangium: increased production of extracellular matrix proteins (collagen, fibronectin, laminin)

Question 19

What stage of diabetic nephropathy is fht efirst reliable and detectable evidence of renal failure?

Answer 19

microabunimuria

Question 20

What is diabetic neuropathy?

Answer 20

• Distal sensory neuropathy commonest
• Distal small fibre neuropathy: pain and impaired pain/temp sensation- they have lost sensation but they have a lot of pain signals/burning pain in feet
• Autonomic neuropathy-
• Mononeuropathies- where diabetes just effects a single nerve

Question 21

What is the underlying pathology of diabetic neuropathy?

Answer 21

Pathology likely multifactorial:

• Genetic predisposition
• Nerve hypoxia/ischaemia
• Oxidative stress
• AGE’s
• Growth factor deficiency

Question 22

What is the leading cause of death in Diabetes?

Answer 22

macrovascular disease

Typ1 = CV mortality predominantly in nephropathy

Typ 2 = metabolic syndrome

Question 23

the cut off for diabetes has been decided by what?

Answer 23

sugar levels below that which would cuase macrovascular disease = not diabetes - however, above that levell = prediabetes