Diabetes And Hypoglycaemia Flashcards
1
Q
What are blood glucose levels maintained by?
A
- Dietary carbohydrate
- Glycogenolysis
- Gluconeogenesis
2
Q
Name the 4 broad effects of insulin (on the liver and on the periphery)
A
- Decreased liver glucose production (so less glycogenolysis and gluconeogenesis)
- Increased movement of glucose into the liver for storage
- Increased peripheral uptake of glucose
- Decreased peripheral catabolism
3
Q
What is the FED state?
A
- FED = catabolism
- After eating when your body is digesting food and absorbing nutrients
4
Q
What happens to metabolism in the fed state?
A
- Glucose increases → insulin release
- Increase of liver nutrient uptake
- Increase in peripheral uptake
- Decrease in peripheral catabolism
- Decrease in liver glucose production
5
Q
In the fasting state, describe the effects of low insulin
A
- Increased glucose production via gluconeogenesis and glycogenolysis in the liver
- Increased lipolysis and proteolysis
- Decreased peripheral glucose uptake
6
Q
When and where is glucagon secreted?
A
- Alpha cells of the pancreas secrete glucagon when there is low blood sugar
7
Q
When and where is insulin secreted?
A
- Beta cells of the pancreas secrete insulin when there is high blood sugar
8
Q
What is the effect of insulin on adipose tissue?
A
- increased glucose uptake
- increased lipogenesis
- decreased lipolysis
9
Q
What is the effect of insulin on Striated muscle?
A
- increased glucose uptake
- increase glycogenolysis
- increased protein synthesis
10
Q
What is the effect of insulin on the Liver?
A
- decreased gluconeogenesis
- increased glycogenolysis
- increased lipolysis
11
Q
What are the 4 counter-regulatory hormones to insulin?
A
- Glucagon - Maintains blood glucose in fasting
- Adrenaline - Mobilises fuels in acute stress
- Cortisol - Changing long term
- Growth hormone - Inhibits insulin action
12
Q
How does glucagon counter regulate insulin?
A
Glucagon maintains blood glucose in fasting
13
Q
How does adrenaline counter regulate insulin?
A
Adrenaline mobilises fuels in acute stress
14
Q
How does cortisol counter regulate insulin?
A
cortisol changes long term?
15
Q
How does Growth hormone counter regulate insulin?
A
Growth hormone inhibits insulin action
16
Q
What is the function of insulin?
A
Promotes storage and growth
17
Q
What are the major metabolic pathways involving insulin?
A
- Glucose storage in muscle and liver
- Protein and fatty acid synthesis
18
Q
What are the major metabolic pathways involving glucagon?
A
- Activates gluconeogenesis
- glycogenolysis
- fatty acid release
19
Q
What are the major metabolic pathways involving epinephrine (adrenaline)?
A
- Stimulates glycogenolysis and fatty acid release
20
Q
What are the major metabolic pathways involving cortisol?
A
- Amino acid mobilisation
- gluconeogenesis
21
Q
What are the major metabolic pathways involving growth hormone?
A
Stimulates lipolysis
22
Q
Define diabetes mellitus
A
“a metabolic disorder characterised by chronic hyperglycaemia, glycosuria and associated abnormalities of lipid and protein metabolism”
- increased hepatic glucose production AND decreased cellular (peripheral) glucose uptake
23
Q
Why does DM cause glycosuria?
A
High blood glucose of excess of 10mmol/l causes glycosuria as this is above the renal threshold
24
Q
What are the classifications of diabetes mellitus?
A
- Type 1
- Type 2
- Secondary
- Gestational
25
What is type 1 diabetes?
Deficiency in insulin secretion (autoimmune destruction of Beta cells by T cells)
26
Explain how in type 1 DM, insulin deficiency leads to ketoacidosis and then diabetic coma
* Insulin deficiency causes increased lipolysis so increased FFAs (free fatty acids) so increased FFA oxidation in the liver which causes ketoacidosis which causes diabetic coma.
* Also, insulin deficiency causes hyperglycaemia, glycosuria, polyuria, volume depletion and this can cause diabetic coma also.
27
What is polyphagia?
Polyphagia is increased appetite, can be caused by hyperglycaemia
28
What is Polydipsia?
Polydipsia is increased thirst which can be caused by the volume depletion (due to the glycosuria so polyuria so volume depletion)
29
What is type 2 diabetes?
insulin secretion retained but target organ is resistant to its actions
30
Describe the onset of type 2 DM and if it has a strong familiar incidence or not
* Slow onset (months to years)
* Middle aged or elderly - prevalence increases with age
* Strong familiar incidence
31
Describe the pathophysiology of Type 2 DM
* Genetic predisposition + environmental factors (like obesity) will lead to **insulin resistance**
* Beta cell hyperplasia to compensate = normoglycemia
* Beta cell failure (early) = impaired glucose tolerance
* Beta cell failure (late) = diabetes
32
What is the HONK state?
Hyperglycaemic, hyperosmolar non-ketotic state
33
Describe the effects that low insulin levels has on the metabolic processes of the body
* Low insulin causes increased gluconeogenesis and increased glycogenolysis = hyperglycaemia
* Hyperglycaemia will then cause glycosuria ... leading to dehydration, thrombosis and cerebral dehydration
34
Name the 3 ways (tests) that we can diagnose DM type 2 (in the presence of symptoms)
* Random plasma glucose greater than 11.1 mmol/l
* Fasting plasma glucose greater than 7.0 mmol/l
* Oral glucose tolerance test (OGTT) plasma glucose greater than 11.1 mmol/l
35
How do you diagnose DM in the absence of symptoms?
In the absence of symptoms you need to take 2 blood samples on 2 separate days
36
Explain what is meant by impaired glucose tolerance (IGT)
This is a pre-diabetic state, person is at risk of diabetes and CVS disease
* fasting plasma glucose is greater than 7mmol/l and OGTT is between 7.8 and 11.1
37
Explain what is meant by impaired fasting glycaemia (IFG)
This is a pre-diabetic state, person is at risk of diabetes and CVS disease. Blood glucose levels are raised but not high enough for diabetes yet.
* fasting plasma glucose 6.1 to 6.9 mmol/l and OGTT value of less than 7.8mmol/L
38
What is the first step in DM type 2 treatment?
Diet and exercise (lifestyle changes)
39
What is secondary diabetes?
chronic pancreatitis, pancreatic surgery → causes secretion of insulin antagonists
40
What differentiates gestational diabetes?
It occurs for the first time in pregnancy
41
Describe the common ages and onset of DM Type 1
* children and young adults mostly
* sudden onset (days or weeks), symptoms may be preceded by a prediabetic period
42
Describe the most common cause of DM type 1
* Most common cause is autoimmune destruction of beta cells of pancreas (due to genetic and environmental factors)
43
What genes are strongly linked with type 1 DM?
* There is a strong link in the HLA genes (HLADR and HLADQ) in MHC region of chromosome 6
* these increase susceptibility to the disease - so people with these genes may be more prone to the environment triggering the autoimmune destruction of the beta cells
44
Describe the pathogenesis of DM type 1 (role of TH1, TH2, autoantibodies ...)
* Autoantigens are presented to T lymphocytes (T helper 1 and T helper 2) to initiate an autoimmune response.
* T helper 1 will secrete IL2 and IF
* IL2 will activate autoantigens specific to T cytotoxic lymphocytes which destroy the beta islet cells through secretion of toxins
* T helper 2 will secrete IL4 which stimulates lymphocytes to proliferate and produce autoantibodies
* These autoantibodies are specific to various beta cell antigens such as glutamic acid decarboxylase, islet auto-antigen and tyrosine-phosphatase-like molecule - most common antibody is is the islet cell antibody
45
What is the most commonly detected antibody associated with type 1 diabetes?
Islet cell antibody
46
What does the destruction of pancreatic beta cells cause?
Hyperglycaemia
47
Why does the destruction of pancreatic beta cells cause hyperglycaemia?
Absolute deficiency of insulin and amylin
48
What is amylin?
Glucoregulatory peptide hormone co-secreted with insulin
49
What does amylin do?
Lowers blood glucose by slowing down gastric emptying and supressing glucagon output from pancreatic beta cells
50
What does an increased plasma osmolarity lead to?
Cerebral dehydration and impaired consciousness
51
What does hyperglycaemia cause?
Glycosuria
52
What does glycosuria cause?
Osmotic diuresis and loss of water and electrolytes
53
What does loss of water and electrolytes cause?
* Dehydration
* Increased blood viscosity
* Thrombosis
54
What are the symptoms that would cause you to test for diabetes?
* Polyuria
* Polydipsia
* Weight loss (type 1 only)
55
What does fasting mean when testing for diabetes?
No caloric intake for at least 8 hrs
56
When do you do an oral glucose tolerance test?
In patients with:
* impaired fasting glycaemia
* Unexplained glycosuria
* Clinical features of diabetes with normal plasma glucose values
57
Why do you carry out an oral glucose tolerance test?
To check the bodys ability to metabolise glucose
58
How do you do an oral glucose tolerance test?
75g oral glucose tolerance and blood tests at 0 and 120 mins after glucose
59
How do you treat type two diabetes?
Diet and exercise → oral monotherapy → combination of drugs → insulin with insulin + combinations of drugs
60
What drug is used in oral monotherapy for type 2 diabetes?
Metformin
61
What is the function of metformin?
Decreases gluconeogenesis and increases utilisation of glucose in the periphery
62
Name some different drugs used in treatment of DM type 2
* Metformin
* Suflonylureas
* Thiazolinediones
* SGLT2 inhibitors
* Incretin-targeting drugs (DPP-4 inhibitors and synthetic GLP-1 analogues)
63
How do sulfonylureas work?
Depolarise beta cells to release insulin, can cause hypoglycaemia.
64
What are some examples of Sulfonylureas?
* Glipizide
* Glimepiride
* Glyburide
65
How do SGLT2 inhibitors work?
Prevent glucose reabsorption in the kidney
- so glucose is excreted
66
What are some examples of SGLT2 inhibitors?
* Canagliflozin
* Empagliflozin
67
What drug is used in oral combination therapy for type 2 diabetes?
* Sulphonylureas
* Gliptins
* GLP-1 analogues
68
What do thiazolidinediones do?
* Reduced insulin resistance
69
What are some examples of DPP-4 inhibitors?
* Sitagliptin
* Saxagliptin
* Linagliptin
* Alogliptin
70
What are some examples of GLP-1 agonists?
* Liraglutide
* Exenatide
* Lixisenatide
* Semaglutide
* Dulaglutide
71
How do incretin targeting drugs work?
Help the body to increase glucose when needed
72
What is the aim of monitoring glycaemic control?
To prevent complications or avoid hypoglycaemia
73
How can we monitor glycaemic control?
* Capillary blood measurement
* urine analysis
* Blood HbA1c
* Urinary albumin
74
What does glucose in urine give an indication of?
Blood glucose concentration above renal threshold
75
What is blood HbA1c?
Glycated Hb; covalent linkage of glucose to residue in Hb
76
What are the long term complications of (badly managed) diabetes?
Micro and macro vascular disease
77
What are the examples of microvascular disease?
Retinopathy, nephropathy, neuropathy
78
What are some examples of macrovascular disease?
Atherosclerosis heart attack/ stroke
79
What is hypoglycaemia defined as (in numbers)?
Plasma glucose \<2.5 mmol/L
80
What are the causes of hypoglycaemia?
* Drugs
* More common in type 2 diabetes (when taking insulin and inslin secretagogues)
81
What is the treatment for hypoglycaemia?
Exogenous insulin and insulin secretagogues
82
Describe what sulfonylureas actually are - name 3
They are insulin analogues and insulin secretagogues (mimic insulin or increase secretion of insulin from beta cells)
* glyburide
* glipizide
* glimepiride
83
What is a risk of any type 2 DM drugs when used together with insulin secretagogues?
Hypoglycaemia
84
What can cause hypoglycaemia in patients without diabetes?
* Alcohol and pharma drugs (Beta blockers, ACE inhibitors, IGF-1 etc)
* Endocrine disease
* Insulinoma
* Inherited metabolic disorders
* Sepsis
* Chronic kidney disease
85
Explain how ethanol (alcohol) can cause hypoglycaemia
Ethanol inhibits gluconeogenesis BUT NOT glycogenolysis
* hypoglycaemia may occur after several days of alcohol binge with limited food intake resulting in hepatic depletion of glycogen
86
What happens if you have a several day long alcohol binge with limited food intake?
Hepatic depletion of glycogen
87
Explain how sepsis can cause hypoglycaemia
* Is a common cause of hypoglycaemia.
* Cytokines can **accelerate utilization of glucose** and **inhibit gluconeogenesis**
88
Why does chronic kidney disease cause hypoglycaemia?
Involve impaired gluconeogenesis, reduced renal clearance of insulin and reduced renal glucose production
89
What is another name for reactive hypoglycaemia?
Postprandial hypoglycaemia
90
What is reactive hypoglycaemia?
Drops in blood sugar are usually recurrent and occur within four hours of eating
91
What causes reactive hypoglycaemia?
* Possibly a benign tumour in the pancreas overproducing insulin
* Too much glucose used up by the tumour itself
* Deficiencies in the counter-regulatory hormones
92
What are the categories for signs of hypoglycaemia?
* Neurogenic
* Neuroglycopaenic
93
Describe the counter-regulatory response to hypoglycaemia
Brain needs glucose.
* Inhibition of insulin release is the first defence to hypoglycaemia
* Second response is stimulation of alpha cells to produce glucagon
* Also stimulates release of cortisol and Adrenaline
94
In the counter-regulatory response to hypoglycaemia, what is the function of adrenaline?
* Stimulates hepatic glycogenolysis and also gluconeogenesis
* Also decreases use of glucose in the periphery
95
What are the neurogenic symptoms of hypoglycaemia triggered by?
Falling glucose levels
96
What are the neurogenic symptoms of hypoglycaemia activated by?
Autonomic nervous system
97
What are the neurogenic symptoms of hypoglycaemia mediated by?
Sympathoadrenal release of catecholamines and ACh
98
What are the neurogenic symptoms of hypoglycaemia?
* Mood changes
* Trembling
* Paleness
* Sweating
* Dizziness
* Blurred vision
* Hunger
* Headaches
* Extreme tiredness
99
What is neuroglycopaenia caused by?
* Neuronal glucose deprivation
100
What are the symptoms of neuroglycopaenia?
* Confusion
* Difficulty speaking
* Ataxia
* Paresthesia
* Seizures
* Coma
* Death
