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Molecular Basis Of Disease > Diabetes And Hypoglycaemia > Flashcards

Diabetes And Hypoglycaemia Flashcards

1
Q

How are blood glucose levels maintained?

A

Dietary carbohydrates

Glycogenolysis

Gluconeogenesis

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2
Q

What is the effect of increased insulin?

A

Decreased liver production of glucose

Liver nutrients uptake

Increase peripheral uptake + decrease peripheral catabolism

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3
Q

What occurs to the insulin levels in the fasting state?

A

Insulin levels decrease to try increase glucose production

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4
Q

How does decreased insulin increase glucose production in the fasting state?

A

Increase liver gluconeogenesis

Decrease peripheral uptake

Increase proteolysis and lipolysis

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5
Q

Why is it important to maintain plasma glucose level?

A

Enough to fuel the body.

Brain and erythrocytes require a continuous supply of glucose

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6
Q

How is high plasma glucose level regulated in the body?

A
  1. High blood sugar levels are detected by beta cells in the pancreas
  2. Beta cells release insulin into the blood stream
  3. Insulin stimulates glucosereuptake from the blood into tissues
  4. Insulin also stimulates glycogen formation in the liver
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7
Q

How is low plasma glucose concerntration maintained?

A
  1. Low blood sugar is detected by alpha pancreatic cells
  2. Glucagon released from alpha cells
  3. Glucagon breaks down glycogen in the liver
  4. Increases blood glucose level
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8
Q

What is the role of insulin in the liver?

A

Decrease Gluconeogenesis

Increase glycogen synthesis

Increase lipogenesis

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9
Q

What is the role insulin the striated muscle?

A

Increase glucose uptake

Increase glycogen synthesis

Protein synthesis

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10
Q

What is the role of insulin in adipose tissue?

A

Increase glucose reputake

Increase lipogenesis

Decrease lipolysis

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11
Q

What is the role of epinephrine in controlling blood glucose concerntration?

A

Mobilises fuels in acute stress

Stimulates glycogenolysis

Stimulates fatty acid release

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12
Q

What is the role of cortisol in controlling plasma glucose concerntration?

A

Changes long term

Stimulates glyconeogenesis And amino acid mobilisation

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13
Q

What is the role of growth hormone in controlling plasma glucose concerntration?

A

Inhibits insulin action

Stimulates lipolysis

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14
Q

What is diabetes mellitus?

A

A metabolic disorder charecterised by chronic hypoglycemia

And often associated with abnormalities of lipid and protein metabolism

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15
Q

What are the 4 types of diabetes patients can be classified into?

A

Type 1

Type 2

Secondary

Gestational

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16
Q

What is type 1 diabetes?

A

Deficiency in insulin secretion

Sudden onset (days/weeks)

In young children or young adults.

Appearance of symptoms may be proceeded by a “pre diabetic” period of several months

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17
Q

What is type 2 diabetes?

A

Insulin secretion is retained but there is target organ resistance to its actions

Slow onset (months/years)

Patients middle aged/elderly

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18
Q

What is secondary diabetes?

A

Chronic pancreatitis

Pancreatic surgery

Secretion of antagonists

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19
Q

What is gestational diabetes?

A

Occurs for the first time in pregnancy

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20
Q

What causes type 1 diabetes?

A

Autoimmune destruction of B cells

Due to interaction between genetic and environmental factors

  • strong link with HLA genes on chromosome 6
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21
Q

What is the pathogenisis of type 1 diabetes?

A
  1. Auto antigens form on insulin producing beta cells and circulate in the blood stream and lymphatics
  2. Processing and presentation of auto antigens by antigen presenting cells (T lymphocytes)
  3. Activation of
    - macrophages
    - autoantigen specific cytotoxic T cells
    - B lymphocytes to product islet cell auto antibodies + antiGADs antibodies

Most commonly detected antibody associated with type 1 is islet cell antibody

  1. Destruction of beta cells with decreased insulin secretion
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22
Q

What is amylin?

A

A glucoregulatory peptide hormone co-secreted with insulin

Lowers blood glucose by slowing gastric emptying + suppressing glucagon output from pancreatic cells

23
Q

What causes hyperglycemia?

A

Deficiency in insulin and amylin

24
Q

What is polyphagia?

A

Excessive eating or appetite

Due to to hyperglycemia

25
Q

What is polydipsia?

A

Excessive thirst or drinking

Due to increased volume depletion in urine

26
Q

How can ketoacidosis occur as a result of insulting deficiency in type 1 DM?

A
  1. Increased lipolysis
  2. Increased fatty acids
  3. Increased fatty acid oxidation in the liver
  4. Ketoacidosis (DKA)
27
Q

What causes type 2 diabetes?

A

Genetic predisposition and obesity + lifestyle factors

Insulin resistance - Beta cell disfunction

28
Q

What is the pathophysiology of type 2 diabetes?

A
  1. Combination of genetic predisposition and obesity and lifestyle factors cause insulin resistance
  2. Compensatory beta cell hyperplasia (normoglycaemia)
  3. Early Beta cell failure (impaired glucose tolerance
  4. Late Beta cell failure (diabetes)
29
Q

What are the metabolic complications of type 2 diabetes?

A

Dehydration

Thrombosis

Cerebral dehydration

30
Q

Explain how type 2 diabetes can cause dehydration.

A
  1. Glycosuria due to hyperglycemia
  2. Osmotic diuresis
  3. Loss of water and electrolytes
31
Q

Explain how type 2 diabetes can cause thrombosis

A

Increased blood viscosity due to the increased plasma osmolarity

32
Q

Explain how type 2 diabetes causes cerebral dehydration.

A

Increased plasma osmarity due to hyperglycemia

33
Q

How diabetes diagnosed?

A

When symptoms are present:

Random plasma glucose > 11.1 mmol/l

Fasting plasma glucose > 7.0 mmol/l

Oral glucose tolerance test (OGTT) - plasma Glu > 11.1 mmol/l

In abscense of symptoms:

Test blood samples on 2 separate days

34
Q

How can glycated Haemoglobin (HbA1c) be used to detect diabetes?

A

Reflects the average plasma glucose over 8 to 12 weeks

Performed any time of the day

Initially used as glycaemic control, but now used for diagnosis

> 6.5% is diabetic

HOWEVER, may be effected by a variety of genetic, haematologic disorders

35
Q

How is impaired glucose tolerance (IGT) diagnosed in pre-diabetes?

A

Fasting plasma glucose > 7 mmol/L

OGTT value of 7.8 - 11.1 mmol

36
Q

How is impaired fasting Glycaemia (IFG)?

A

Fasting plasma glucose 6.1 to 6.9 mmol/L

OGTT value of < 7.8 mmol/L

37
Q

What is the use of the oral glucose tolerance test?

A

To check the body’s ability of metabolising glucose

  • in patients with IFG
  • in unexplained glycosuria
  • in clinical features of diabetes with normal plasma glucose values
38
Q

How is the oral glucose tolerance test carried out?

A

75g oral glucose and test after 2 hour

Blood samples collection at 0 and 120 mins after glucose

39
Q

What are the treatments of type 2 diabetes?

A
  • Diet and exercise
  • Oral monotherapy (metformin)
  • Oral combination
  • insulin injection and oral agents
40
Q

What drugs are used to treat type 2 diabetes?

A

Metformin

Sulfonylureas

Thiazolifinediones

SGLT2 inhibitors

Incretin targeting drugs:
- DPP-4 inhibitors (prevent breakdown of natural incretins)
- GLP-1 agonist

41
Q

What is the aim of monitoring glycaemic control?

A

To prevent complications or avoid hypoglycaemia

42
Q

What are ways to monitor glycaemic control?

A

Self monitoring to be encouraged: using analysis and capillary blood measurement

2-3 months: blood HbA1c

Others: urinary albumin

43
Q

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

A

Micro vascular disease
- retinopathy, neuropathy, nephhropathy

Macro vascular disease
- related to atherosclerosis heart attack/stroke

MECHANISMS OF COMPLICATIONS UNCLEAR

44
Q

What is hypoglycaemia?

A

Plasma glucose level < 2.5 mmol

45
Q

What are the causes of hypoglycaemia?

A

Drugs are the most common cause

  • common in type 1 diabetes
  • less common in type 2 diabetes taking insulin

Tumour in the pancrease

46
Q

What are some sulfonylureas that cause hypoglycaemia?

A

Glyburide

Glipzide

Glimepiride

47
Q

How can hypoglycaemia occur in patients without diabetes?

A

Drugs such as alcohol

Endocrine diseases eg. Cortisol disorder

Inherited metabolic disorders eg. Hereditary fructose intolerance

Insulinoma - tumour in beta cells

48
Q

What is the role of ethanol in hypoglycaemia?

A

Inhibit Gluconeogenesis but not glycogeolysis

Hypoglycaemia will typically follow several days alcohol binge with limited food intake

49
Q

What is the role of sepsis in hypoglycaemia?

A

Cytokines acceleration glucose utilisation

nduced inhibition of gluconeogenesis in the setting of glycogen depletion.

50
Q

What is the role of CDK in hypoglycaemia?

A

Mechanism not clear - impared Gluconeogenesis

Reduced renal clearance of insulin

Reduce renal glucose production

51
Q

What is reactive hypoglycaemia (hypo after eating)?

A

Drop sin blood sugar level usually reccurant and occur within four hours after eating

52
Q

What is the cause of reactive hypoglycaemia?

A

CAUSE UNCLEAR

Possibly a benign tumour in the pancreas may cause overproduction of insulin

Too much glucose may be used by the tumour itself

Deficiency’s in counter regulatory hormones eg. Glucagon

53
Q

What are the NEUROGENIC (autonomic) signs and symptoms of hypoglycaemia?

A

Mediated by sympathoadrenal release of catecholamines and ACh

Mood changes
Paleness
Trembling
Sweating
Dizziness
Blurred vision
Headache
Extreme tiredness
Hunger

54
Q

What are the NEUROGLYCOPAENIA signs and symptoms of hypoglycaemia?

A

Due to neuronal glucose deprivation

Confusion
Difficulty speaking
Ataxia
Parenthesia
Seizures
Coma
Death

Molecular Basis Of Disease (32 decks)

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