Diabetes Mellitus Flashcards
(90 cards)
1
Q
What are the fasting glucose ranges?
A
<=6: Normal
6.1 - 6.9: Impaired
>=7: Diabetic
2
Q
What are the OGTT 2hr glucose ranges?
A
<=7.7: Normal
7.7-11: Impaired
>=11: Diabetic
3
Q
What is the diagnostic criteria for DM?
A
2 abnormal tests or 1 abnormal test + symptoms
4
Q
What is HbA1c?
A
A form of haemoglobin that is measured primarily to identify the 3 month average of glucose plasma concentrations
Test is limited to 3month lifespan of RBCs
5
Q
How is HbA1c formed?
A
Non-enzymatic glycation pathway by Gb exposed to glucose forming glyco-haemoglobin
6
Q
What are the ranges of HbA1c?
A
42-47: Pre-diabetes
>46: Diabetic
Not yet in use in Glasgow
7
Q
List 5 types of diabetes
A
- T1D
- T2D
- Maturity onset diabetes of the young (MODY) - autosomal dominant
- Gestational D - 20% prevalence; 3rd trimester; increased BMI
- Secondary D: due to pancreatitis, CF, HHC (iron overload), steriod induced, acromegaly (increase GH from pituitary)
8
Q
What type of diabetes in insulin deficient?
A
T1DM
MODY
Also secondary:
Pancreatitis
CF
HHC
9
Q
What type of diabetes is insulin resistant?
A
T2DM
Gestational
Also secondary:
Steroid-induced
Acromegaly (GH)
10
Q
List the common antibodies in T1DM
A
ICA - Islet Cell Antibody
I-A2 - Insulinoma-Associated Antigen-2
GAD65 - Glutamic Acid Decarboxylase-65
Others:
IAA - Insulin Auto-Antibody
ZnT8 - Zinc Transporter
11
Q
List common symptoms of T1DM
A
Weight loss Polydipsia (thirst) Polyuria (excess urination) Nocturia (urinating at night) Cachexia
12
Q
What are common acute complications of T1DM?
A
Hypoglycaemia
- Iatrogenic (from medication)
Diabetic Ketoacidosis
- Suffers from biological stress e.g. infection, MI, trauma
- Fails to administer insulin = Hyperglycaemic ketoacidosis
High levels of ketone bodies in the blood lowers blood pH and triggers kidneys to excrete acidic urine
13
Q
What are the common T1DM susceptibility genes?
A
Polygenic
HLA DR3/4 and DR2/8 and DQ-A1
Located on chromosome 6 in the major histocompatibility complex (MHC)
Region is also associated with susceptibility genes associated with other autoimmune diseases; meaning that patients with T1DM are more susceptible to other autoimmune diseases such as Graves’ Disease, Addison’s Disease, and Coeliac Disease
14
Q
What is pernicious anaemia?
A
Body cannot make enought RBCs because of Vit. B12 deficiency
15
Q
What is the most common monogenic form of diabetes?
A
HNF alpha 1 MODY
Hepatic nuclear factor alpha-1
Changes in HNFa1 genes causes T1D by lowering the amount of insulin that is produced by the pancreas. It allows insulin to be normally produced in childhood but the amount of insulin reduces with age
16
Q
Define T1DM
A
T1DM is an autoimmune disease resulting in ABSOLUTE deficit of insulin and requires replacement therapy
Autoimmune destruction of pancreatic B-cells due to an abnormal T-cell response
17
Q
What age groups are most commonly effected by T1DM?
A
<35
Peak at 12
18
Q
List potential participating factors of T1DM
A
Viral infection
Environmental toxins
Autoimmune (hypersensitivity type 4) could be initiated by cytokine response to infection
19
Q
What is the pathophysiology of T1DM?
A
- Insulin deficit (due to lymphocytic infiltration and destruction of insulin-secreting b-cells in the pancreas)
- B-cell mass declines, insulin secretion decreases until the available insulin is no longer adequate to maintain normal blood glucose
- Hyperglycaemia
- Glucosuria
- Polyuria (osmotic diuresis)
20
Q
How does dehydration result in T1DM?
A
Fluid loss through the urine and high blood glucose concentrations (solution) in the blood (high osmolality) draws water from the cells, resulting in dehydration
21
Q
Why do T1DM have a strong appetite to eat?
A
Polyphagia
Lack of nutrients entering the cells stimulates appetite
No insulin to translocate GLUT4 onto membranes
22
Q
How does DKA result?
A
- Lack of glucose in cells results in catabolism of fats and proteins
- Excess amounts of FAs and their metabolites (ketones) in the blood
- Amount of lipids, FAs, and ketones in the blood exceeds capacity and rate at which the liver can process within a given time
- Excessive amounts of ketones decreases blood pH
- Ketoacids bind with HCO3- buffer in the blood, leading to reduced [HCO3-]serum
23
Q
What are the main themes of T1DM Tx?
A
- Diet and exercise
- Oral medication to increase insulin secretion or reduce insulin resistance
- Insulin replacement
24
Q
What dietary advice would you give to a T1DM patient?
A
- Maintain optimum body weight
- Eat more complex CHOs with a LOW glycaemic index
- Maintain a LOW cholesterol and LOW lipid profile
- Food intake must match available insulin and metabolic needs including activity level
25
What exercise advice would you give to a T1DM patient?
- Exercise can promote uptake of glucose by skeletal cells
- Weight control; reduce stress; improve CV fitness
RISK of hypoglycaemia with strenous and prolonged exercise - increased absorption of glucose by muscle and action of insulin
26
What insulin replacement therapy is available for T1DM patients?
Recombinant human insulin (Humulin)
3 forms:
1) Rapid-onset, short acting insulin
2) Intermediate-acting insulin
3) Slow-onset, long-acting insulin
27
Define hypoglycaemia and how might it occur in T1DM? And what it can lead to
<4mmol/L glucose
- Insulin shock
- Occur suddenly following exercise, insulin dosage error, vomiting, or skipping a meal
Lack of glucose quickly affects the nervous system because neurons cannot use AA/FAs as energy source
<2.5mmol/L = impaired neurological function (poor concentration, slurred speech, lack of coordination, staggering gait) and over stimulation of SNS (increase PP, moist skin, anxiety)
28
What could happen if hypoglycaemia is left untreated in T1DM?
Neuroglycopenia
- Loss of consciousness
- Seizures
- Death
29
How would you Tx hypoglycaemia in T1DM?
IV: 50% dextrose
Gel: 40% dextrose
Oral: High glycaemic index CHO
30
What processes are activated by insulin in the fed state?
1. Glucose uptake in muscle and adipose tissue
2. Glycolysis --> Energy
3. Glycogen synthesis --> Storage
4. Protein Synthesis
5. Uptake of ions (especially K+ and PO43-)
31
What processes are inhibited by insulin in the fed state?
1. Gluconeogenesis
2. Glycogenolysis
3. Lipolysis
4. Ketogenesis
5. Proteolysis
32
What are the insulin counter-regulatory hormones?
1. Glucagon - a-cells pancreas
2. Adrenaline - medulla of adrenal gland
3. glycocorticoids (cortisol) - adrenal cortex
4. Growth hormone - Anterior pituitary
33
List clinical symptoms of gyperglycaemia
1. Polyuria
2. Polydipsia (excessive thirst)
3. Lassitude (state of mental/physical weariness and lack of energy)
4. Pruritus Vulvae (itchy valva)
5. Balanitis - inflammation of the glans penis
34
Define DKA
DKA is characterised by uncontrolled catabolism
1. Metabolic acidosis
- pH <7.3
- HCO3- <15mmol/L (due to buffering)
2. Hyperglycaemia
- >13.9mmol/L (leads to osmotic diuresis, dehydration, and loss of electrolytes)
3. Ketosis
- increased ketone bodies
4. Ketouria and glucosuria
35
Characterise metabolic acidosis
Increased: H+
Decreased: HCO3- and CO2
36
List the counter-regulatory hormones
GH
Adrenaline
Cortisol
Glucagon
37
What hormones are increased during DKA?
Counter-regulatory hormones
| GH, adrenaline, glucagon, cortisol
38
DKA Tx
1. Hypovolaemia: IV fluids
- electrolyte + water loss = 0.9% saline
- only water loss = 5% dextrose
2. Insulin deficiency: IV insulin
- turns off ketogenesis and uncontrolled catabolism
- can cause hypokalaemic, as insulin causes K+ to move into cells
* resolution of acidosis requires insulin
3. Hypokalaemia
- IV insulin
- Total body K+ will require supplementation
39
What is a common patient with DKA?
T1DM
<65
Hyperglycaemia
Dehydrated
40
What does HONK stand for and what is it characterised by?
Hyperosmolar, hyperglycaemic, non-ketotic State
Characterised by:
- Hyperglycaemia,
- Hyperosmolality
- Dehydration
- ABSENCE of ketoacidosis
41
How does HONK occur?
A partial/relative insulin deficiency may initiate HONK by reducing glucose utilisation while inducing a glucagon-stimulated increase in hepatic glucose output
42
What are the cerebral risks of HONK
1. Central Pontine Myelinolysis
- due to hyponaturaemia (low Na+) causing water to move out of the cells (hyperosmolality)
2. Cerebral oedema
- due to rapid Tx for hyponaturaemia
- infusing rapidly with IV saline will cause a abrupt shift in fluids from extracellular compartment to intracellular compartment, which will cause oedema - treat slowly!!!
43
HONK Tx
1. Hypovolaemia
- IV fluids
- SLOWLY to return to normal osmolality
2. Insulin deficiency
- IV insulin
3. Hypokalaemia
- IV K+
44
Which patients typically get HONK?
T2DM
| Incidious onset
45
What are the symptoms of hypoglycaemia?
1. Over activation of SNS
- Increased pulse rate
- Pale, moist skin
- Anxiety
- Tremors
If untreated: loss of consciousness, seizures, and death.
2. Neuroglycopaenic symptoms - Impaired neurological function
- Poor concentration
- Slurred Speech
- Lack of coordination
- Staggering gait
- Look DRUNK
46
Define hypoglycaemia
<4mmol/L
47
Tx of hypoglycaemia
Mild
- 15-20g of fast acting CHO (high-GI)
Severe
- 15-20g of fast acting CHO (high-GI)
- IM glucagon
- IV dextrose
- Longer acting CHO to prevent further episode
48
What is the most common metabolic complication of diabetes?
Hypoglycaemia
49
In T2DM what is the most common cause of insulin resistance?
Adipokines
50
List the adipokines involved in insulin resistance in T2DM
| And their functions
Leptin - Tells hypothalamus how much fat is stored
Adiponectin - reduces levels of FFAs
TNFa - inhibited by adiponectin; inflammatory cytokine
Resistin - enhances hypothalamic stimulation of glucose production
51
How do the adipokines change in T2DM
Increased:
- Letpin = increases resistance
- TNFa = increases inflammation
- Resistin = causes hyperglycaemia
Decreased:
- Adiponetin = Increased FFAs levels
52
Where are adipokines produce?
Adipocytes
53
What adipokine inhibits TNFa?
Adiponectin
54
How is insulin resistance caused?
Insulin receptor mutation
```
Results in:
- Severe hyperinsulinaemia
Associated with:
- Acanthosis Nigricans (darkened, thickened, patches of skin that usually develop in the armpit, and around the groin and neck)
- Hyperandrogenism
```
55
Define acanthosis nigricans
Acanthosis nigricans is a brown to black, poorly defined, velvety HYPERPIGMENTATION of the skin.
It is usually found in body folds, such as the posterior and lateral folds of the neck, the armpits, groin, navel, forehead, and other areas
56
What common symptoms would you find with insulin receptor mutation
Hyperinsulinaemia
- Acanthosis nigricans
- Hyperandrogenism
57
In normal renal glucose handling what happens?
90% SGLT2 in PCT
| 10% SGLT1 in descending loop of Henle
58
What are the effects of GLP1?
1. b-cells - release more insulin
2. a-cells - inhibit glucagon release
3. Stomach - slows gastric emptying
4. Liver- reduces hepatic glucose output
5. brain - promotes satiety (feeling full) and reduces appetite
59
What is the main factor in the development of T2DM?
Obesity
| Family history
60
Define T2DM
Impairment of pancreatic B-cell function (consequently insulin secretion) or peripheral insulin resistance
61
What does adiponectin do?
Decrease FFAs
62
What is the first presentation of insulin resistance?
Hyperinsulinaemia
63
What is the % of inheritability of T2DM from 1st degree relatives
40-50%
64
Tx for T2DM?
Hypoglycaemic drugs and insulin
65
List the main chronic microvascular complications of diabetes
Neuropathy
Nephropathy
Retinopathy
66
What are the acute complications of T1DM?
DKA
| Hypoglycaemia
67
What are the main landmark trials that changed diabetic glycaemic control? And what where their outcomes
DCCT (Diabetes Control and Complications Trial)
- T1DM
- 1993
- Conventional vs intensive treatment regimes
UKPDS (UK Prospective Diabetes Study)
- T2DM
- 1998
- Conventional vs intensive regimens
= both: clear evidence that intensive glycaemia control can help PREVENT micovascular disease
68
What's involved in the conventional vs intensive regimen
Conventional
- Mix
- 2 injections/day
Intensive (basal bolus)
- 4 injections/day
69
What is the pathophysiology of microvascular disease?
1. Capillary Damage
- Increased blood flow
- Increase capillary pressure
- Thickened and damaged blood vessels
- Endothelial damage - leakage of albumin and other proteins
2. Metabolic Damage
- Increase in glucose concentration, excess glucose enters the POLYOL PATHWAY (glucose --> Sorbitol --> Fructose)
- Glucose metabolises to sorbitol by aldose reductase
- Sorbitol accumulates
- Less NADPH available for cell metabolism
- Buildup of ROS and oxidative stress
= Oxidative stress activation
= Increased glycation = Advanced Glycation End-Products (AGEs)
70
What are the glucotoxic effects the lead to endothelial/metabolic dysfunction?
- Sorbitol accumulation via aldose reductase
- Formation of advanced glycation end-products (AGEs)
- PKC activation
- Oxidative stress
- Angiogenic factors
71
What is the hallmark of diabetic complications? T1DM
Diabetic retinopathy
72
What is the leading case of impaired vision in ages 20-74?
Diabetic retinopathy
73
What did the DCCT show in respect to Diabetic retinopathy?
Reduction in Diabetic retinopathy complications in the intensive group compared to the conventional group
74
Pathophysiology of diabetic retinopathy
- High retinal blood flow called by hyperglycaemia causes capillary pericyte damage
1. Capillary endothelial damage
2. Vascular leak
3. Microaneurysms
4. Capillary occlusion - cotton wool stops (infarcts) +- dot haemorrhages
5. Local Ischaemia + ischaemia
6. Neovascularisation (VEGF) - proliferate, bleed, fibrose
```
____
1. Early stages (non-proliferative)
• Hyperglycaemia
– Damage to small vessel wall
– Microaneurysms (swelling blood vessels)
• When vessel wall is breached
– Dot haemorrhages
• Protein and fluid left behind
– Hard exudates
• Micro-infarcts
– Cotton wool spots
```
```
2. Later stages (proliferative)
• Damage to veins
– Venous budding
– Blockage of blood supply
• Ischaemia→ VEGF and other growth factors
– Neovascularisation
– Proliferative retinopathy
– Vitreous haemorrhage
• Fluid not cleared from macular area
– Macular oedema
```
75
What is the difference between transudate and exudate?
- Transudate is fluid pushed through the capillary due to high pressure within the capillary.
- Exudate is fluid that leaks around the cells of the capillaries caused by inflammation.
76
How could you prevent diabetic retinopathy?
- Good glycaemic control
- Stop smoking
- BP control
- Retinal Screening: annual from 12yo.
77
Tx diabetic retinopathy
- Address risk factors
- Ophthalmic review
Laser
VEGF inhibitors
Virectomy
78
What is the pathogenesis of nephropathy
- Increased sorbitol (polyol pathway)
- PKC activation
- Oxidative stress
- Advanced glycation End-Products (AGEs)
All result in: endothelial and metabolic dysfunction
79
What are the stages of nephropathy?
1. Renal enlargement and hyperfiltration
2. Microalbuminuria
3. Macroalbuminuria
4. End-stage renal failure
80
What is the physiology of nephropathy?
1. First steps
- renal hypertrophy
- increased GFR
- afferent arteriole dilates: increased glomerular pressure, thickened GBM capillary damage, and shear-stress on endothelial cells
- end result: leakages of protein into urine
2. Later steps
- progressive glomerularsclerosis: hardening of glomerulus/scarring
- glomeruli destroyed
- progressive proteinuria
- RENAL FAILURE
81
Diabetic nephropathy management
- Screening for micoalbuminuria - every year from Dx
- Improve glycaemic control
- Refer to renal clinic once developed CKD (GFR<30)
82
Tx diabetic nephropathy
- ACEi/AngII blocker (ARB) - if micoalbuminuria present
- Lower BP
- Statins
- STOP SMOKING
83
List the different types of diabetic neuropathy
- Peripherial (sensory) neuropathy
- Autonomic neuropathy
- Mononeuritis multiplex = damage to >=2 different nerve areas
- Diabetic amyotrophy = weakness followed by wasting of pelvifemoral muscles; uni/bilateral
84
Tx diabetic neuropathy
- Sertonin/nor-adrenaline reuptake inhibitors (Duloxetine)
| - Pain management clinic
85
What pathologies cause diabetic foot?
Neuopathy and peripheral vascular disease
86
What is charcot foot?
Diabetic foot
Numb foot - repetitive microtrauma/stress fractures
Dysregulated blood flow - increased bone turn over/fragile foot
87
What are the features of autonomic neuropathy?
- CV: postural hypotension
- GU: erectile dysfunction
- GI: gastatory sweating and gastroparesis (vagus nerve damage; delayed gastric emptying)
88
What is included on the annual review for screening for diabetic microvascular complications
```
• HbA1c
• Chol, HDL, TG
• Creatinine
• Microalbuminuria
• Visual acuity
• Retinal screening
• Pedal pulses
• Foot sensation
• Lifestyle
– Exercise, diet
– smoking
• Drug therapy
• Mental well-being
• Foot sensation
• BMI
• BP
• Erectile function
• Contraception
```
89
How are ROS made?
increased glucose + transition metal (e.g. copper) = ROS
90
How are advanced glycated end products (AGEs) made
glucose + protein (lysine or valine) = Schiff base = ketoamine (amadori product) = (oxidation etc,,,) AGEs
