L19 - Diabetes and Hypoglycaemia Flashcards

1
Q

How are blood glucose levels maintained?

A
  • through dietary carbohydrates
  • glycogenolysis
  • gluconeogenesis
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2
Q

Describe blood glucose homeostasis?

A

FED STATE:
after a meal is eaten, the plasma glucose rises and so does insulin.
A rise in insulin causes the liver to stop breaking down glycogen into glucose. The uptake of glucose in the liver to be converted increases. Periperral catabolism decreases (break down of lipids and protein)

FASTING STATE:
decrease in plasma glucose leads to decrease of insulin levels. This in turn causes an increase in liver glucuneogenesis and an increase in lipolysis and proteolysis. There is also a decrease in peripheral uptake of glucose in muscle.

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3
Q

What is the function of Glucagon?

A

mobilises fuel and maintains the blood glucose during fasting state.
It activates gluconeogenesis and glycogenolysis
It activates fatty acid release

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4
Q

What is the function of Epinephrine?

A

Mobilises fuels in acute stress

stimulates glycogenolysis and fatty acid release

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5
Q

What is the function of cortisol?

A

amino acid mobilisation and gluconeogenesis

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6
Q

What is the function of growth hormone?

A

inhibits insulin action and stimulates lipolysis

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7
Q

What is Diabetes Mellitus?

A

A metabolic disorder characterised by chronic hyperglycaemia, glycosuria and associated abnormalities of lipid and protein metabolism.

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8
Q

What are the classes of diabetes?

A

type 1 - deficiency in insulin secretion

type 2 - target organs have resistance to insulin

secondary - chronic pancreatitis or surgery.

gestational - occurs for the first time in pregnancy

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9
Q

What is type 1 diabetes?

A

predominantly in young children and young adults

sudden onset (days or weeks)

most common cause is autoimmune destruction of Beta cells in the pancreas. May be due to interaction between genetic and environmental factors.

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10
Q

Describe the pathogenesis of type 1 diabetes?

A

destruction of Beta cells starts with autoantigen formation. Autoantigens are presented to T lymphocytes to initiate autoimmune response. Activated T lymohocytes with secrete IL-2 and Interferon, which will then go onto activate auto-antigens that are specific to T-lymphocytes. They then destroy the Islet cells and produce IL-4 which stimulates the proliferation of islet cell auto-antibodies.
There will also be circulating auto-antibodies to various cell antigens against glutamic acid decarboxylase, tyrosine phosphatase-like molecule as well as islet auto-antigen

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11
Q

How does destruction of B-cells in pancreas lead to hyperglycaemia?

A

It leads to a deficiency in insulin which lowers plasma glucose levels.
It also leads to a decrease in amylin, which is a glucoregulatory peptide that is co secreted with insulin. Amylin lowers blood glucose by slowing gastric emptying and suppressing glucagon output from pancreatic cells.

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12
Q

Describe Glycosuria as a metabolic complication of type 1 diabetes?

A

as a result of hyperglycaemia, the kidney threshold is exceeded and it cannot reabsorb all the glucose from the blood so a lot of it excreted in the urine. Urine contains too much glucose

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13
Q

Describe Polysuria as a metabolic complication of type 1 diabetes?

A

polysuria is excessive urination. This occurs as a result of high blood suagr levels and glycosuria. When excess glucose ends up in the urine, it pulls more water, and therefore results in more urine.

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14
Q

Describe volume depletion and polydipsia as a metabolic complication of type 1 diabetes?

A

When polyuria occurs, more water leaves the body, known as volume depletion.
To compensate, the body’s thirst increases and more water is drunk. This is called polydipsia

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15
Q

How does type 1 diabetes cause ketoacidosis?

A

insulin deficiency results in increased lipolysis and an increase in free fatty acids in circulation. This leads to increased FFA oxidation in the liver and the production of ketone bodies. This is known as ketoacidosis

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16
Q

Describe the presentation of diabetes type 2?

A

there is a slow onset in patients (months/years)
patients are usually middle aged or elderly - prevalence increases with age.
strong familiar incidence.

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17
Q

Describe the pathophysiology of type 2 diabetes?

A

Genetic predisposition and obesity lifestyle factors together lead to insulin resistance. In compensation, beta cell hyperplasia will occur which will make more insulin. However this will eventually lead to Beta cell failure and impaired glucose tolerance
As more and more beta cells fail, this leads to diabetes.

18
Q

Describe some metabolic complications of type 2 diabetes

A

low insulin leads an incfrease in both gluconeogenesis and glycogenolysis. These in turn lead to hyperglycaemia and glycosuria.
Osmotic diuresis and loss of water/electrolytes from the body, increases blood viscosity and increases the risk of thrombosis. It also leads to dehydration.
Hyperglycaemia itself also increases plasma osmolarity and this may lead to cerebral dehydration

19
Q

What is Impaired Glucose Tolerance?

A

When plasma glucose level is higher than normal (7 mmol/L) and the OGTT (oral glucose tolerance test) has a value of 7.8-11.1 mmol

20
Q

What is Impaired Fasting Glycaemia?

A

When fasting plasma glucose is between 6.1. to 6.9 mmol/L and the OGTT (oral glucose tolerance test) has a value less than 7.8 mmol

21
Q

What is an OGTT and when should it be carried out?

A

Oral Glucose Tolerance Test.
when 75g of oral glucose is goven and blood samples are taken at 0 and 120 mins after glucose
should be carried out to check body’s ability of metabolising glucose. Done on patients with IFG, unexplained Glycosuria and in clinical features of diabetes with normal plasma glucose

22
Q

State the stepwise treatment of type 2 diabetes?

A

1 - diet and excersise
2 - oral monotherapy
3 - oral combination
4 - insulin and oral agents

23
Q

How does Metformin treat type 2 diabetes?

A

it decreases gluconeogenesis and also increases the utilisation of glucose at the periphery

24
Q

How does Sulfonylureas treat type 2 diabetes?

A

Depolarises the beta cells of the pancreas to increase insulin release

25
Q

How does Thiazolidinediones treat type 2 diabetes?

A

activates the ppar gamma receptor which reduces insulin resistance

26
Q

How does SGLT2 Inhibitors treat type 2 diabetes?

A

promote glucose excretion via the kidney. Decreases the amount of glucose reabsorbed into the blood

27
Q

How do Incretin Targeting Drugs treat type 2 diabetes and give examples of them?

A

incretin allows the body to release insulin when needed:

  • DPP 4 Inhibitors prevent the natural breakdown of incretins
  • synthetic GLP 1 analouges
28
Q

Describe some ways in which glycaemia can be monitored?

A
  • capillary blood measurement
  • urine analysis
  • blood HbA1c
  • urinary albumin
29
Q

What are some long term complications of type 1 and 2 diabetes?

A

Microvascular disease (retinopathy, nephropathy, neuropathy)

Macro vascular disease (related to atherosclerosis, heart attack/stroke)

30
Q

What is Hypoglycaemia?

A

Defined as plasma glucose below 2.5 mmol/L

Can occur in patients with or without diabetes

31
Q

What are the causes of Hypoglycaemia?

A

Drugs are the most common cause

common in type 1 diabetes and less common in type 2 diabetes taking insulin and insulin secretagogues

32
Q

Give some examples of drugs that can cause hypoglycaemia in diabetes?

A

exogenous insulin and insulin secretagogues like glyburide, glipizide, and glimepiride are sulfonylureas that can cause hypoglycaemia

33
Q

Describe some causes of hypoglycaemia in pateints without diabetes?

A
  • alcohol
  • drugs including: quinolone, quinine, beta blockers, ACE inhibitors, IGF-1
  • endocrine diseases like cortisol disorders
  • inherited metabolic disorders like hereditary fructose intolerance
  • insulinoma
34
Q

How does alcohol cause hypoglycaemia?

A

it inhibits gluconeogenesis but not glycogenolysis. Usually occurs several days after alcohol binge with limited food intake - which results in a hepatic depletion of glycogen

35
Q

How does Sepsis cause hypoglycaemia?

A

Cytokine accelerated glucose utilisation and induced inhibition of gluconeogenesis in the presence of glycogen depletion.

36
Q

How may CKD cause hypoglycaemia?

A

chronic kidney disease

likely to involve impaired gluconeogenesis, reduced renal clearance of insulin and reduce renal glucose production

37
Q

What is postprandial hypoglycaemia and what are its causes?

A

A drop in blood sugar after eating.

May be caused by a benign tumour in pancreas, which may be causing an overproduction of insulin. Too much glucose may be used by the tumour itself. There may be deficiencies in counter-regulatory hormones like glucagon.

38
Q

Describe the counter-regulatory response to hypoglycaemia?

A

autonomic nervous system sends signal to pancreas to stop secreting insulin and to increase glucagon secretion. This causes the liver to increase its glucose output.
It also sends signals to adrenal glands to release cortisol and epinephrine. This stimulates hepatic glycogenolysis and gluconeogenesis. It also decreases the glucose utilisation

39
Q

Describe the Neurogenic (autonomic) signs of Hypoglycaemia?

A

triggered by falling glucose levels.
activated by ANS and mediated by sympathoadrenal release of catecholamines and Ach.

  • mood changes
  • blurred vision
  • paleness
  • extreme tiredness
  • headaches
  • sweating
  • trembling
  • dizziness
40
Q

Describe the Neuroglycopaenic signs of Hypoglycaemia?

A

due to neuronal glucose deprivation

  • confusion
  • difficulty speaking
  • ataxia
  • paresthesia
  • seizures
  • coma
  • death