Diabetes Flashcards
(83 cards)
1
Q
What is glucose?
A
monosaccharide used for ATP cycle for energy
2
Q
What is glycogen?
A
a polysaccharide of glucose that serves as a form of energy storage
3
Q
What is glucagon?
A
a peptide hormone produced by alpha cells of pancreas that raises the concentration of glucose and fatty acids in the bloodstream; is the main catabolic hormone of the body.
4
Q
What is somatostatin?
A
a hormone that many different tissues produce, but it is found primarily in the nervous and digestive systems. The primary function of somatostatin is to prevent the production of other hormones and also stop the unnatural rapid reproduction of cells — such as those that may occur in tumours. The hormone also acts as a neurotransmitter and has a role in the GI tract.
5
Q
What 2 features characterise diabetes?
A
- Hyperglycaemia = high blood glucose
- Caused by lack of insulin or reduced action of insulin
6
Q
The pancreas has both endocrine and exocrine functions. Briefly describe the function of each
A
- Exocrine; related to digestion
- Endocrine; related to insulin
7
Q
What is the pancreas composed of?
A
Islets of Langerhans –> endocrine cells that secrete hormones
8
Q
What 4 groups of cells make up the Islets of Langerhans? What does each group secrete?
A
- Alpha cells –> glucagon (25% of total hormone produce)
- Beta cells –> insulin (75%)
- Delta cells –> somatostatin (5%)
- F cells –> pancreatic polypeptide (involved in satiety)
9
Q
How is insulin formed?
A
- Production of pro insulin (insulin in yellow and c peptide in red) –> Proinsulin is the prohormone precursor to insulin made in the beta cells of the islets of Langerhans
- Cleavage at two sites: The cleavage sites are each located after a pair of basic residues (lysine-64 and arginine-65, and arginine-31 and −32).
- Equal amounts of insulin and c peptide produced
10
Q
Why would a c peptide test be carried out?
A
A c peptide test can be carried out to determine how much insulin the body is producing.
11
Q
What are the effects of insulin on the liver?
A
- Stimulates liver to store glucose in from of glycogen inhibits glycogenolysis (inhibits glycogen metabolism)
- Inhibits gluconeogenesis (inhibits generation of glucose)
12
Q
Effects of insulin on muscle and adipose tissue regarding carbohydrates?
A
- Increases rate of glucose transport across cell membrane
- Increases rate of glycolysis
- Stimulates glycogenesis (glycogen synthesis)
13
Q
Effects of insulin on muscle and adipose tissue regarding lipids?
A
- Decreases rate of lipolysis (lowers fatty acids)
- Stimulates fatty acid and triacyglycerol synthesis in tissues
- It increases the uptake of triglycerides from the blood into adipose tissue and muscle
14
Q
Effects of insulin on muscle and adipose tissue regarding proteins??
A
- It increases the rate of transport of some amino acids into tissues
- It increases the rate of protein synthesis in muscle, adipose tissue, liver, and other tissues
- It decreases the rate of protein degradation in muscle (and perhaps other tissues).
15
Q
Effects of insulin on the pancreas?
A
High insulin levels reduce the glucagon secretion from alpha cells of pancreas (to decrease levels of blood glucose)
16
Q
How can diabetes be a risk factor for atherosclerosis?
A
High glucose levels leads to formation of pro-inflammatory molecules
17
Q
Insulin effects on cancer growth?
A
- Insulin is a growth factor and effectively stimulates cancer cell growth
- Insulin excess is assumed to be a cancer-promoting factor
18
Q
What are the 4 ways to diagnose diabetes?
A
- Fasting glucose
- Random glucose
- Two hours reading post OGTT
- HbA1c
19
Q
What fasting glucose result is said to be diabetes?
A
≥ 7mmol/litre
20
Q
What is important to note about random glucose tests in asymptomatic patients?
A
Must be repeated twice
21
Q
What is an OGTT?
A
Oral glucose tolerance test; patient asked to take a glucose drink and their blood glucose level is measured before and at intervals
22
Q
What is an HbA1c test?
A
Average blood glucose levels for last 2/3 months
23
Q
Both fasting glucose and two hours glucose reading results can be used to diagnose diabetes
A
24
Q
What can an impaired gasting glucose and impaired glucose tolerance indicate?
A
Prediabetes
25
What is prediabetes?
Characterised by the presence of blood glucose levels that are higher than normal but not yet high enough to be classed as diabetes. Depends on HbA1c criteria:
* Reflects average plasma glucose over the previous 8 to 12 weeks
* ≥ 48 mmol/mol = diabetes
* ≥41 and \<48 mmol/mol = pre-diabetes
LIFESTYLE CHANGES
26
Classification of diabetes
27
Type 1 vs type 2 diabetes cause?
Type 1: Autoimmune destruction of insulin producing **beta cells** in the Islet of Langerhan
Type 2: Body is unable to metabolise glucose which leads to high blood levels; body does not produce enough insulin OR the body’s cells do not react to insulin
28
When does T1D typically occur? Who does it typically affect?
* Occur any age (BUT peaks around puberty)
* Equal sex incidence but after 15 years if age two-fold increase risk in male
29
There is a strong genetic component behind T1D. Certain genotypes of which system are considered as the strongest genetic risk factors for T1D? What are these genotypes?
* HLA Class II genotypes
* DR4-DQ8
* DR3-DQ2
These genotypes can cause autoimmunity, often triggered by environmental factors (e.g. infections such as flu).
30
What is HLA?
The human leukocyte antigen (HLA) system or complex is a group of related proteins that are encoded by the **major histocompatibility complex (MHC)** gene complex in humans. These cell-surface proteins are responsible for the regulation of the **immune** **system**.
31
What 4 autoantibodies are markers of beta cell autoimmunity in T1D?
* Insulin autoantibodies
* Glutamic acid decarboxylase autoantibodies (GAD)
* Islet antigen-2 autoantibodies (IA-2)
* ZnT8 transporter autoantibodies
These autoantibodies can be measured to diagnose T1D
32
Risk factors for T1D?
* Family History (genetic susceptibility)
* Perinatal factors - Low birth weight
* Viral infections
* Diet – cow’s milk
33
How does T1D present?
* Rapid onset (often few weeks)
* Weight loss + osmotic symptoms (polydipsia, polyuria, nocturia) + low energy
* Abdominal pain
* Often slim (but N.B. overweight people can also develop T1D)
* Can present as diabetes ketoacidosis (DKA)
34
Management of T1D?
* Always need insulin at start of diagnosis
* **No role of oral agent** (as body unable to produce any insulin)
35
Presentation of T2D?
* Often overweight
* Symptoms present over few months
* Minimal weight loss (unless left for long period)
* Can present with complications such as vision loss or foot ulcers or fungal infection
* Can also present in state of Hyperosmolar Hyperglycaemia State (HHS) or HONK
36
What is HHS?
Hyperosmolar Hyperglycaemia State:
* Occurs in people with T2D who experience very high blood glucose levels
* Can develop over course of weeks through combination of illness and dehydration
* Can lead to disorientation or gradual loss of consciousness
37
How are T2D and prediabetes interconnected?
Those with IGT or IFG (prediabetes), the risk of developing T2D increases --\> lifestyle changes!
38
How is T2D managed?
* Lifestyle (can reverse diabetes):
* Exercise
* Change in diet and weight loss
* Oral therapy:
* Metformin (first line)
* DDP4 Inhibitor, SGLT-2 Inhibitor, GLP-1 Agonist, Sulphonylureas
* Up to three agent
* Insulin:
* Once a day insulin
* Multiple injection of insulin
39
What is Metformin?
* Used to treat type 2 diabetes, and to help prevent type 2 diabetes if you're at high risk of developing it.
* Acts directly or indirectly on the liver to lower glucose production, and acts on the gut to increase glucose utilisation, increase GLP-1 and alter the microbiome.
40
What are the 3 criteria for gestational diabetes?
1. Diabetes in pregnancy
2. New diabetes not present prior pregnancy
3. Hyperglycaemia first detected in pregnancy
41
Diagnosis of gestational diabetes is different from normal diabetes. What are the results of fasting glucose and 2 hours plasma glucose for both?
Normal:
* Fasting glucose ≥ 7mmol/litre said to be diabetes
* 2 hours plasma glucose level of ≥ 11.1mmol/litre
Gestational:
* Fasting glucose above \> 5.6 mmol/litre
* 2 hours plasma glucose level of 7.8mmol/litre
42
What test can be done to diagnose gestational diabetes?
**Oral glucose tolerance test** (BUT criteria for diagnosis different from ’normal diabetes’
43
If you have had gestational diabetes, what can you do to self-monitor during pregnancy?
Capillary blood glucose
44
Why would you not use a Hb1Ac test during gestational diabetes?
Do NOT use Hb1Ac due to physiological changes that occur during pregnancy --\> Pregnancy can result in lower HbA1c levels
45
Risk factors for gestational diabetes?
* BMI \>30
* Previous macrosomic baby
* Previous gestational diabetes
* FH of diabetes
* Ethnic minority
46
What short term effects can gestational diabetes lead to?
* _Macrosomia_: a baby who is born much **larger than average** for their gestational age
* _Pre-eclampsia_: High blood pressure and signs of damage to other organs (liver and kidneys)
* _Stillbirth_
* _Neonatal morbidity_
47
What is macrosomia?
A baby who is born much larger than average for their gestational age
48
Long term effects of gestational diabetes?
* Obesity (child)
* Development of T2D (mother)
49
Management of gestational diabetes?
* Diet (if mild)
* Limited oral options
* Majority require insulin (ONLY during pregnancy)
50
What are the 3 main inherited/genetic types of diabetes?
1. Mature onset diabetes of the young (MODY)
2. Maternal inherited diabetes and deafness
3. Wolfram Syndrome (DIDMOAD
51
What is mature onset diabetes of the young (MODY)?
* A rare form of diabetes that runs strongly in the family (inherited)
* Most common form of **monogenic diabetes** (results from mutations in a single gene)
52
What is maternal inherited diabetes and deafness?
a form of diabetes often accompanied by hearing loss, especially of high tones
53
What is Wolfram Syndrome (DIDMOAD)?
combination of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DIDMOAD)
54
What is secondary diabetes?
Secondary diabetes is diabetes that results as a consequence of another medical condition.
55
What are common causes of 2ary diabetes?
* Diseases of the pancreas that destroy beta cells e.g. pancreatic cancer, CF, pancreatitis (gallstones, alcohol)
* Hormonal syndromes that interfere with insulin secretion (e.g. pheochromocytoma)
* Drugs (e.g. glucocorticoids)
* Haemochromatosis
56
What is haemochromatosis?
Genetic disorder characterised by excessive intestinal absorption of dietary iron results in damage to pancreas (and other organs)
57
Diabetes can also be drug-induced. What are the causes of this?
* Steroid
* Usually high dose and prolonged
* Atypical anti-psychotics
* Immunotherapy (e.g. Nivolumab used in melanoma treatment)
* Protease Inhibitor (used in HIV treatment)
58
How can Cushing's syndrome induce diabetes?
* Presence of glucocorticoids, such as cortisol, increase the availability of blood glucose to the brain
* Cortisol act son the liver, muscle, adipose tissue and pancreas
* In the liver, high cortisol levels increase gluconeogenesis and decrease glycogen synthesis
59
How can excess GH (acromegaly) lead to diabetes?
GH is one of the glucose counter-regulatory hormones, rising in response to hypoglycaemia, it has both intrinsic hyperglycaemic actions and causes insulin resistance.
60
How can a somatostatin secreting tumour (somatostatinoma) lead to diabetes?
The location of somatostatin in pancreatic islet D cells suggests that it may act as a local regulator of insulin and glucagon secretion. Changes in islet D-cell function in experimentally-induced and spontaneous diabetes in animals suggest that the peptide may be involved in the pathogenesis of diabetes.
61
How can a glucagon secreting tumours (Glucagonoma) lead to diabetes?
Excess glucagon causes blood glucose levels to rise
62
What are counter regulatory hormones for insulin? What are the 4 main ones?
* Hormones that usually oppose the action of insulin
* Glucagon
* Adrenaline/noradrenaline
* Glucocorticoid
* Growth hormone
63
When are counter regulatory hormones for insulin released?
Secreted as a result of **stress response**
64
What are common stimuli for insulin release?
* Glucose
* Fatty acids and ketones
* Vagal nerve stimulation
* Gut hormones
* Drugs (diabetes medication)
* Prostaglandins
65
What are common stimuli for inhibition of insulin release?
* Sympathetic stimulation
* Alpha adrenergic agents (adrenaline)
* Beta blockers
* Dopamine
* Serotonin
* Somatostatin
66
What is glucagon produced by?
Produced by alpha cells of pancreas
67
Where is glucagon rapidly degraded?
Liver and kidney
68
What are the stimuli for glucagon release?
* Amino acids
* Beta adrenergic stimulation
* Fasting, hypoglycaemia
* Exercise
* Cortisol
69
What are the stimuli for inhibition of glucagon release?
* Glucose
* Somatostatin
* Free fatty acids
* Ketones
* Insulin
70
What are the actions of glucagon?
Aims to increase blood glucose by:
* Glycogenolysis (liver)
* Gluconeogenesis (liver)
* Lipolysis
Also reduces intestinal motility and gastric acid secretion
71
Effects of insulin on:
* glucose production
* glucose utilisation
* lipolysis?
* decrease
* increase
* decrease
72
Effects of glucagon on:
* glucose production
* glucose utilisation
* lipolysis?
* increase
* N/A
* N/A
73
Effects of adrenaline on:
* glucose production
* glucose utilisation
* lipolysis?
* increase
* decrease
* increase
74
Effects of cortisol on:
* glucose production
* glucose utilisation
* lipolysis?
* increase
* decrease
* increase
75
Effects of GH on:
* glucose production
* glucose utilisation
* lipolysis?
* increase
* decrease
* increase
76
Effects of free fatty acids on:
* glucose production
* glucose utilisation
* lipolysis?
* increase
* decrease
* N/A
77
Summary of glucagon vs insulin
78
Glucose homeostasis
79
How does diabetes lead to glucose in urine?
1. Hyperglycaemia
2. Kidney tubules can't deal with large volume of glucose; ability to reabsorb as much as possible is lost
3. Leads to glucose in urine --\> glycosuria
80
When glucose is lost in the urine, it is **osmotically active**. What does this result in?
* Pulls water with it
* Glucose in urine = water in urine
* This leads to **polyuria**
81
What is the blood called when it has a **low water** but **high glucose** composition?
Hyperosmolar blood
82
What is the effect of a hyperosmolar state on the hypothalamus? Which symptom of diabetes does this lead to?
* Stimulates osmo receptors on hypothalamus
* This triggers **increase in thirst** (polydipsia)
83
Mechanism behind T1D leading to weight loss?
1. Decrease in glucose utilisation results in decreased ATP production
2. Body starts using other metabolic sources of fuel:
1. Lipolysis; breaking down triglycerides into FFAs and glycerol
2. Proteolysis; breaking down proteins and muscles to release amino acids
(also due to dehydration)
