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PBL Y2 S4 > Case 6- Type 2 diabetes > Flashcards

Case 6- Type 2 diabetes Flashcards

1
Q

How is glucose regulated after eating?

A
  • Glucose acts on liver to release insulin
  • SI and LI endoendocrine cells release GLP-1 and GIP to increase insulin levels.
  • glucose used in the brain for energy
  • Insulin increases glucose uptake in fat and muscle tissues (brain is insulin-independent)
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2
Q

How does GLP-1 increase insulin levels? What is its other effects?

A

Acts on receptors on beta cells, increases cAMP = activation of PKA and Epac2 = exocytosis of insulin (release)

It also inhibits gastric emptying (more time for insulin to act), inhibits glucagon release and is appetite-suppressing

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3
Q

How does high blood glucose lead to release of insulin?

A
  • Glucose is taken up into the beta cell via GLUT2 (mainly) and GLUT1
  • Glucose metabolism (glycolysis) = ATP release, closes K+-ATP channels
  • Depolarisation of Beta cell = influx Na+ and Ca2+
  • Ca2+ leads to exocytosis of insulin
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4
Q

How is glucose managed when fasted?

A

= Blood glucose around 4 mmol/L
Glucagon released from alpha cells
- Increases endogenous glucose production at the liver
- Increases lipolysis of fat
- Decreases glucose uptake of muscles

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5
Q

How does glucagon lead to increased blood glucose? (pathway)

A
  • Triggers cAMP productoin = activates PKA
  • PKA phosphorylates glycogen synthase (directly) and glycogen phosphorylase (indirectly)
  • Increases glycogenolysis and inhibtis glycogenesis
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6
Q

When and how is somatostatin released from the pancreas? What is its effect?

A

Released from delta cells when glucose is high. By the same mechanism of insulin release (closure of K+-ATP channels etc.), glucose leads to release of somatostatin too. This inhibits glucagon and insulin release from a/b cells = lowers blood glucose

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7
Q

What is the primary ketone body in the blood and what is it formed from?

A

Excess acetyl CoA –> HMG CoA
–> B-hydroxybutyrate

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8
Q

What is the role of hormone sensitive lipase? How is it regulated?

A

Breaks down triglycerides into FA.
- Inhibited by insulin (lipogenesis)
- Stimulated by adrenaline/ noradrenalin (lipolysis)

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9
Q

What stimulates hunger?

A
  • Neuropeptide Y and AgRP - produced in the arcuate nucleus (in hypothalamus)
  • Ghrelin: increases NPY and AgRP, and antagonises leptin
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10
Q

What regulates neuropeptide Y production?

A

Inhibited by: leptin, insulin
Sitmulated by: glucocorticoids, ghrelin

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11
Q

What hormones are responsible for satiety?

A
  • CCK
  • Pancreatic polypeptide
  • GLP-1
  • Peptide YY : secreted from SI after eating
  • Leptin: produced by adipocytes
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12
Q

What stimulates/ inhibits thirst?

A

Osmoreceptors in hypothalamus control thirst
- Angiotensin II stimulates thirst centre
- increased plasma osmolality = increases ADH = increases thirst
- Atrial naturiertic peptide inhibits thirst

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13
Q

What tests can be used to identify pre-diabetics? Give their results

A
  • Impaired glucose tolerance test (OGTT): ingest 75g of glucose then measure blood glucose levels. Pre-diabetic= 7.8-11.1 mmol/L
  • Impaired fasting glucose: above normal blood glucose levels after fasting, i.e. 5.5-7 mmol/L
  • HbA1c: measure of glycated haemoglobin. Pre-diabetic= 42-47
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14
Q

How does diabetes lead to polyuria and polydipsia?

A

Hyperglycaemia = loss of glucose in the urine, has an osmotic drag so water is lost too (as well as electrolytes)
Increased urination
Dehydration = increased thirst

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15
Q

What ensures glycolysis doesn’t occur at low levels of glucose?

A

Glucokinase has a low affinity (50% saturated at 8-10mM) for insulin to stop glycolysis occurring at too high a rate. In other words, glucose needs to be fairly high before metabolism of glucose should occur

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16
Q

How does insulin lower blood glucose?

A

Binds to alpha subunits of receptor which activates tyrosine kinase. Leads to PI3K/AKt pathway, and increases GLUT4 translocation to increase glucose uptake. The cell membrane is also more permeable to amino acids, K+ and phosphate ions

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17
Q

What enzyme is responsible for inactivation of incretin hormones (GIP and GLP-1)?

A

DPP4

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18
Q

What is the role of somatostatin in relation to food intake?

A

increase the time of food exposure to the GI tract allowing maximum absorption of nutrients , i.e. by inhibiting glucagon and insulin it prevents rapid exhastion of food = available for longer

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19
Q

What receptor does glucagon bind to?

A

GLUT1, but less tightly than insulin = less depolarisation

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20
Q

What is self-tolerance?

A

Destroys T cells that develop specificity towards self-antigens/ autoantigens

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21
Q

What is type 1 diabetes caused by? What type reaction is this?

A

Autoimmune disease, leading to a lack of insulin secretion and hyperglycaemia (reduced uptake of glucose by GLUT4). It is a type 4 hypersensitivity reaction = cell-mediated immune response

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22
Q

What is the genetic component of T1DM?

A

Susceptibility genes= HLA DR3, HLA DR4
Have a lack of self-tolerance, so T cells target Beta cells (and recruit other immune cells), overall leads to lack of insulin release

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23
Q

How does T1DM usually present? Give the common symptoms and why they occur

A

Typically younger (<30) and acute onset with severe symptoms:
- Polyuria: glucose leads to osmotic diuresis
- Glucouria: excess glucose spills into the urine
- Polydipsia: dehydration and thirst
- Polyphagia and unexplained weight loss: decreased ATP from glucose so lipolysis & proteolysis are stimulated, leads to weight loss and increased hunger
- Fatigue
- Visual disturbance

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24
Q

What are some signs and symptoms of diabetic ketoacidosis?

A

Signs:
- Kassmaul respiration: laboured breathing to reduce CO2, aim to increase pH
- Fruity breath (from acetone)
- Hyperkalaemia

Symptoms= nausea, vomiting, abdominal pain, mental status changes

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25
Q

Why does T1DM lead to hyperkalaemia?

A

Insulin normally stimulates the Na+/K+ ATPase to bring K+ into the cell, therefore excess is left in blood

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26
Q

What is T2DM?

A

Metabolic disorder characterised by reduced sensitivity of target organs to insulin, leading to insulin resistance. Also have reduced B cell function from amyloid deposition, glucotoxicity etc.

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27
Q

How is metabolic syndrome diagnosed?

A

3 or more of:
- Hyperglycaemia = >5.6mmol/L
- Triglycerides >1.7 mmol/L
- HDL <50mg/dl (F) or <40 (M)
- BP >130/85
- BMI >35 (F), >40 (M)

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28
Q

What is the pathogenesis of T2DM?

A

Thought to be genetic component where there’s less GLUT4 transporters on cell membranes so glucose increases. More glucose= beta cells release more insulin (=hyperinsulinaemia). Over time, beta cells fatigue so insulin falls and glucose increases.
Beta cells also produce amylin so leads to amyloid deposition = also damages B cells to reduce insulin

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29
Q

What is responsible for beta cells damage in T2DM?

A

Inflammation, glucotoxicity, lipotoxicity, amyloid deposition

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30
Q

What is the common presentation of T2DM?

A

Usually asymptomatic and diagnosed during screening. Candida infections of vagina/ penis are common.
Also may have polyuria, fatigue and weight loss due to hyperglycaemia (i.e. when blood glucose is 10-11 mmol/L) - but this is more common in T1DM.

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31
Q

What is the most common cause of death from T1DM and T2DM?

A

cardiovascular disease

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32
Q

Compare the prevalence of T1DM and T2DM

A

T1DM= 5-10%
T2DM= >90%

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33
Q

What are some modifiable risk factors for T2DM?

A
  • Overweight or obese = 80% of the risk for T2DM, mainly central adiposity (1cm increase in waist = 3.5% increased risk)
  • Sedentary lifestyle
  • Metabolic syndrome: HTN, high TG, low HDL
  • Diet of low fibre and high glycaemic index
  • Intrauterine environment
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34
Q

What are some non-modifiable risk factors for T2DM?

A
  • Ethnicity= Black, South Asian, Hispanic
  • Family history of T2DM
  • Age: at age 70, 20% have it
  • History of gestational diabetes (when your body cant make enough insulin during pregnancy)
  • Polycystic ovary syndrome (can= insulin resistance)
  • Low birth weight
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35
Q

What are the genetics of T2DM? I.e. first-degree relatives, twins

A

T2DM = polygenic condition
- Risk is 70% if both parents have it
- First degree relatives of an individual of T2DM are 3x more likely to develop it
- Monozygotic twins = 50-90% concordance
Overall shows it requires environment factors for it to manifest/progress

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36
Q

When does hypergycaemia develop in Type 1 diabetes?

A

When 80-90% of the beta cells have been destroyed

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37
Q

How would you treat hypoglycaemia and severe hypoglycaemia episodes?

A

Hypo = Rapid acting glucose and slow acting carbohydrates

Severe hypoglycaemia = IV dextrose and IM glucagon

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38
Q

What is a risk of patients developing with T2DM?

A

Hyperosmolar hyperglycaemic state (HSS): very high blood glucose (>40) or osmolality >320, so water leaves body cells and into blood vessels. Cells change shape, leads to total body dehydration.
Symptoms= seizures, confusion, polyuria

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39
Q

What test would be performed if a diabetic patient presented with oedema?

A

Proteinuria test

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40
Q

What test would be performed to diagnose intestinal malabsorption of a diabetic patient?

A

Hydrogen breath test - if increased then shows there is too much bacteria (overgrowth) in your small intestine

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41
Q

What is non-enzymatic glycation and what does it create?

A

When glucose conjugates with lipids and proteins (seen in diabetes) = pro-inflammatory cytokines

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42
Q

What is the implication of non-enzymatic glycation seen in diabetes?

A

Leads to inflammation of blood vessels, thus LDL deposition and atherosclerosis. Also causes protein deposition in the vessel and around the basement membrane = hyaline arteriosclerosis.
Overall = decreased blood flow and decreased gas exchange

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43
Q

What are macrovascular complications of diabetes?

A

stroke, cardiovascular disease and peripheral vascular disease

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44
Q

What are the microvascular complications of diabetes? Give what they can lead to

A
  • Diabetic retinopathy: leading cause of blindness
  • Diabetic nephropathy: leading cause of CKD
  • Diabetic neuropathy: leading cause of non-traumatic lower extremity amputations
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45
Q

What is diabetic retinopathy and how is it graded?

A

Swelling or thickening of the macula due to an accumulation of fluid. Graded by an RMP system:
- Retinopathy = R0-R3
- Maculopathy= M0-M1
- Photocoagulation= P0-P1 (are there any photoregulation scars)

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46
Q

What is the prevalence of diabetic retinopathy in T1 and T2 DM patients? What accounts for the difference?

A

T1DM = 77% have a form of retinopathy (32% proliferative)
T2DM= 25% have retinopathy (3% proliferative)

T1DM has higher incidence as it is a younger onset

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47
Q

What are the 2 types of diabetic retinopathy?

A

Proliferative and non-proliferative, depending on if there is regeneration of blood vessels (can lead to bleeding)

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48
Q

What is the annual NHS budget on diabetes? As a proportion, how much of this is spent on complications?

A

£10-12 billion a year
80% on complications

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49
Q

What are some complications of diabetic retinopathy?

A

Intraretinal microvascular abnormalities = beading, looping, reduplication
Bleeding if proliferative

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50
Q

What should eGFR and ACR be? (normal)

A

eGFR > 90
ACR <3 (albumin-creatinine ratio)

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51
Q

What is diabetic nephropathy? What does it lead to?

A

Damage to blood vessels/ arterioles, possibly the glomeruli filtration barrier (i.e. basement membrane) in the kidney, leading to CKD and renal failure.

Leads to albuminuria, with increased ACR (start to leak proteins)

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52
Q

What is the prevalence of diabetic nephropathy in T1 and T2 DM?

A

T1DM = 30%
T2 = 40%

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53
Q

What is defined as moderately increased albuminuria?

A
  • ACR of 2.5mg/mmol + (men), 3.5 mg/mmol + (female)
    OR
  • urinary albumin >20 mg/L
  • postiive albumin test results from first 2 morning urine samples
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54
Q

How is diabetic nephropathy diagnosed?

A
  • Positive dipstick for proteinuria
  • OR ACR > 30 mg/mmol
  • OR urinary albumin concentration > 200mg/L
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55
Q

How is diabetic retinopathy treated?

A

Most important = glycaemic and BP control
- Photocoagulation = laser therapy to burn peripheral retina to preserve central retina
- Anti-VEGF, i.e. reduce blood vessel formation
- Surgery, if bleeding

56
Q

How is diabetic nephropathy treated?

A
  • BP control
  • RAAS blockade: ACE-i, ARB (i.e. ramipril)
  • Glycaemic control
  • CVD risk management
57
Q

What is diabetic neuropathy?

A

Damage to peripheral distal nerves; leads to lost sensation or pain to distal lower limbs and hands

58
Q

What are the types of diabetic neuropathy? Which is the most common?

A
  • Distal symmetrical sensorimotor polyneuropathy and small fibre neuropathy = lose sensation in distal limbs; below knees and hands
  • Radiculopathies
  • mononeuropathy (can affect CN nerves, i.e. leading to foot drop)
  • Autonomic neuropathy
59
Q

What are the 2 groups of symptoms that can be caused by peripheral neuropathy?

A
  • Neuropathic pain, i.e. burning, paraesthesia, increased sensitivity
  • Loss of sensation (important - as we use pain symptoms to avoid trauma)
60
Q

What can autonomic neuropathy lead to?

A
  • Postural hypotension
  • Small bowel bacterial overgrowth (SBBO) = diarrhoea
  • Gastroparesis = early satiety + vomiting
61
Q

What drugs might you give to treat pain from diabetic neuropathy?

A

Gabapentin
Duloxetine (SNRI)
Pregabalin
Amitryptilyline (TCA)

62
Q

What causes foot ulcers (diabetic foot)?

A

Neuropathy: deformity from increased pressure
Ischaemia: from peripheral vascular disease

63
Q

Why are foot ulcers common in diabetics?

A

Somatic sensory nerves supplying the distal extremities have paraesthesia which eventually leads to sensory deficits so the patient isnt aware of the wound. Hyperglycaemia leads to impaired wound healing, so can lead to foot ulcers. infection is common

64
Q

What is the most severe and common complication of diabetes? Why is it so dangerous?

A

Coronary heart disease- very dangerous as dont often get the classical symptoms seen in non-diabetic patients, i.e. only 50% get angina as a first manifestation of CHD

65
Q

How is diabetes diagnosed?

A

Symptomatic patients (i.e. polyuria, polydipsia present) with 1 of:
- HbA1c > 48 mmol/L
- Fasting blood glucose > 7 mmol/L
- Random glucose/ OGTT > 11.1 mmol/L

If asymptomatic, same cut off values as above but present on 2 different occasions

66
Q

What are some contraindications for using HbA1c for diabetes diagnosis? Give the alternative

A

Anyone with abnormal RBC life span, examples:
- Pregnancy= low HbA1c, use OGTT
- Renal dialysis= low, esp if given EPO
- Alcoholics
- Haemolytic anaemia, antiretroviral drugs etc. all lower RBC = low HbA1c
- Splenectomy = high Hb1Ac
ALL but pregnancy, use fasting blood glucose instead

67
Q

How is type 1 diabetes diagnosed?

A

Hyperglycaemia with one or more of:
- Ketosis
- Rapid weight loss
- Aged <50
- Family or personal history of autoimmune disease
- BMI <25

68
Q

What are some markers of T1DM? (4 autoantibodies, 1 other)

A
  • GAD65: in 80% of patients
  • Islet cell antibodies: 69-90%
  • ZnT8 antibodies: pancreatic beta cell zinc transporter
  • Insulin autoantibodies
  • C peptide: byproduct of proinsulin -> insulin, so levels reflect insulin production. Half life = 3-4x insulins, so if low then indicates absense
69
Q

What test would be used to establish the patients current glycaemic control?

A

Blood glucose test

70
Q

Which test would establish the patient’s glycaemic control over the past 2-3 hours?

A

Glycosuria test

71
Q

Which test establishes the patient’s long-term glycaemic control?

A

Hb1Ac

72
Q

Which test would be most appropriate if the patient presents with oedema?

A

Proteinuria test

73
Q

Which test would be used to confirm diagnosis of acidosis?

A

Blood gases test

74
Q

What is the estimation of diabetes prevalence? Give % of T1 vs T2.
Why is it likely to be higher?

A

463 million; 90% T2D, 10% T1D
Estimated higher due to the ‘iceburg effect’, i.e. hidden (asymptomatic) disease

75
Q

How is diabetes affected by gender and age? (epidemiology)

A
  • More common in Men
  • Most common in 65+
  • Increasingly more diagnosed <40
76
Q

How is diabetes affected by ethnicity?

A
  • Ethnic minorities in UK have 3-5x increased prevalence than white
  • Indian, Carribean and Black subcontinents have highest prevalence
77
Q

Why is diabetes prevalence increased in South Asians and other ethnic groups?

A

Despite low BMI, they have;
- more abdominal (visceral fat)
- Higher insulin resistance and hyperinsulinaemia
- Increased inflammatory response
- Lower adiponectin; important for lowering glucose
- More dyslipidaemia

78
Q

Why is sudden death common in diabetic patients?

A

Autonomic neuropathy, altered pain perception, possibly increased positive arterial remodelling.

79
Q

What are the 3 insulin therapy regimes that can be used? What type insulin so they use (short/ intermediate etc.)?

A
  • Basal-bolus regime: rapid or short acting insulin before meals, and long-acting preparation for basal requirements (mimics the pancreas)
  • 1, 2 or 3 injections per day: biphasic with short and intermediate acting insulin
  • Continuous insulin infusion via pump: rapid- or short-acting insulin
80
Q

When would a continuous insulin infusion be used/ recommended?

A

In patients experiencing regular hypoglyaemic episodes that have to take multiple daily injections

81
Q

What is analogue insulin?

A

laboratory grown, genetically modified sequence = the rapid insulilns are analogues

82
Q

How many times should glucose be monitored in T1D per day§?

A

4 times a day, before meals and before sleeping
Should be checked more if ill, exercising or pregnant

83
Q

What is hypoglcyaemia classed as?

A

<4 mmol/L blood glucose

84
Q

What defences do we have against hypoglycaemia? (normal)

A
  • Inhibit insulin (4.5)
  • Secrete glucagon (4)
  • Secrete adrenaline (3.75)
  • Secrete growth hormone (3.5)
  • Secrete cortisol (3.25)
  • Symptoms (3)
  • Cognitive impairment (2.75)
85
Q

Why do T1D have ‘impaired awareness of hypoglycaemia’?

A

Lose their defences against hypoglcyaemia, as they cannot:
- Inhibit insulin (4.5)
- Secrete glucagon (4)

If severe/ advanced T1D, they also:
- Don’t secrete adrenaline (3.75)
- Don’t develop symptoms, i.e. hunger or sweating

Means they only notice hypoglycaemia when there is cognitive impairment

86
Q

What are the acute implications of hypoglcyaemia?

A

Symptoms = hunger, sweating, shaking
- negative effect on mood and emotion
- Impairs cognitive function
- irritability
- Impairs cognitive function and performance of activities
- Interferes with balance, coordination, vision, loss of consciousness

Severe episodes= coma, seizures, strokes

87
Q

What are some causes of hypoglycaemia? (diabetic and non-diabetic)

A

Diabetic= insulin/ sulfonylurea, increased activity, overdose
Non-diabetic= alcohol, pituitary insufficiency, Addison’s disease

88
Q

What is a smart insulin pen?

A

Automatically records when you inject insulin, including how much and when. Connects to smart phone app

89
Q

What is a smart glucose meter (bolus calculator)?

A

Programmed with insulin:carb ratio and correction factor

90
Q

What are sensor augmented pumps?

A

Displays continuous glucose monitoring (CGM) data on the screen and stops insulin automatically when glucose falls (‘predictive low glucose suspend technology’)

91
Q

Compare a closed loop and hybrid closed loop system

A

Closed loop = autonomous, graduated modulation of insulin delivery to achieve target glucose.
‘Hybrid closed-loop’ = meal bolus still required.

92
Q

What is the first line of management of T2D?

A

Lifestyle changes: NHS diabetes prevention programme, exercise, diet

93
Q

What is the second line for managing T2D? What is its aim?

A

Metformin: start on 500mg OD, can increase up to 2g (max 3g). If GI upset = give modified-release metformin.
Aim= HbA1c <48 mmol/L

94
Q

What is the third line for managing T2D? What is its aim?

A

Add sulphonylurea (SU), DPP-4, SGLT2-inhibitor, GLP-1 receptor agonist, pioglitazone .
Aim= HbA1c <53

95
Q

What is the forth line for managing T2D? What is its aim?

A

Triple therapy: metformin and 2 of the drugs above, or metformin and insulin (i.e. NPH or longer-acting insulin)
Aim = HbA1c <53

96
Q

If a patient had CVD or CKD, how would the treatment plan for T2D change?

A

If CVD or CKD, start with a GLP-1 receptor agonist or SGLT2 inhibitor

97
Q

What is metformin contraindicated in? When might you reduce the dose or stop the medication?

A

CKD
If GFR <45= reduce dose. If GFR <30, then stop medication due to the risk of lactic acidosis

98
Q

For T2D, how regularly is HbA1c checked?

A

Every 3-6 months, with treatment escalation if it exceeds 58

99
Q

How does metformin work? What are some side effects?

A

Increases insulin sensitivity (so reduces resistance) and lowers hepatic production of glucose. May also reduce appetite and = weight loss

Side effects: diarrhoea, abdominal pain, lactic acidosis, vitamin B12 deficiency

100
Q

What is the MOA of SGLT2 inhibitors?

A

Inhibits glucose reabsorption in the PCT via inhibiting sodium-glucose transporters. More glucose lost in the urine and has slight diuretic effect.
Also may lead to weight loss, BP lowering and CVD protection

101
Q

Who may benefit from SGLT2 inhibitors the most?

A

Patients with high CVD risk

102
Q

What are some side effects of SGLT2 inhibitors?

A

Increased risk of UTI, diabetic ketoacidosis, diuresis

103
Q

What do SGLT2 inhibtor drug names end in?

A

‘flozin’, i.e. empagliflozin

104
Q

What is the MOA of sulphonylurea? What are its side effects?

A

Binds to sulphonylurea receptor (SUR-1) which leads to closure of K+ ATP sensitive channels = depolarisation = increases insulin release
Side effects= weight gain and hypoglycaemia

105
Q

How do DPP-4 inhibitors work? What does the drug name usually end in?

A

DPP-4 breaks down GLP-1, so preserves the incretin effect = increasing insulin and inhibiting glucagon release

Ends in ‘liptin’

106
Q

What is the MOA of orlistat?

A

Binds to gastric and pancreatic lipases, so when administered with fat-containing food, it reduces lipolysis of TG so there is less absorption of FA and MG.

107
Q

When would orlistat be given?

A
  • Obesity = BMI >30
  • BMI >27 with diabetes, HTN or dyslipidaemia
  • Reduce weight gain after weight loss
    BUT take with diet and exercise
108
Q

What drug may be given for Candida infections with T2DM?

A

Clotimazole

109
Q

What is the role of AMPK?

A

It inhibits ACC (phosphorylates it) = reduces amount of Malonyl CoA = less inhibition on Beta-oxidation = promotes breakdown of FA (lipolysis)

110
Q

How can obesity be caused?

A
  • Single gene mutation (monogenic obesity): MCR4, leptin
  • Polygenic disorders: majority, multiple genes promoting energy storage, so accompanied with low PA = obesity
  • Gene-environment interactions
111
Q

How come some people are morbidly obese (BMI >50), but don’t develop T2D?

A

The individual’s genetic makeup may mean they’re not susceptible to T2D.

112
Q

How can obesity lead to T2D?

A
  • Inherited genes making you hungry
  • Inherited genes leading to higher insulin resistance
  • Too much food intake and low PA (environment)
    = overweight, body becomes resistant
    = Fatty deposits in pancreas cause more damage
    gene may be present where beta cells fatigue quickly = body needs more insulin but can’t produce it
113
Q

Which type diabetes has a larger genetic link?

A

type 2: identical twins have 90% increased risk, compared to type 1 where they have 40% increased risk

114
Q

How is obesity diagnosed in adults and children?

A

BMI: obesity is BMI > 35, and morbidly obese BMI 40+
Waist circumference: consider in adults with BMI <35
- Men > 102cm= v high risk
- Women > 88cm = v high risk

In children= CENTILE charts

115
Q

Why may you see variability in T2D incidence with age, ethnicity and sex?

A

Distribution of fat varies, and visceral (abdominal) fat has higher risk of T2D than cutaneous fat

116
Q

What is the relationship between T2D and obesity?

A

Linear relationship: increased fat mass = insulin resistance and T2D progression.
Obesity = 80% of the risk for T2D

117
Q

How is beta cell dysfunction affected by T2D? At time of diagnosis & after

A

At diagnosis, B cells function may have already declined by 50%
Thereafter, may be 4-6% decline per year

118
Q

What is neuroglycopenia? How is it treated?

A

Occurs with hypoglycaemia = confusion, incoordination, drowsiness, seizures, coma
Give 15g-20g glucose, wait 15 minutes and repeat bloods. Keep repeating until normal

119
Q

How is diabetic ketoacidosis diagnosed?

A
  • Hyperglycaemia > 11 mmol/L (but may be normoglycaemic)
  • Ketones 3+ mmol/L, or urine >2+
  • Acidosis: bicarbonate <15, pH <7.3, (required for diagnosis!)
120
Q

How would you treat DKA?

A
  • IV fluids – as they are significantly dehydrated and will have lost electrolytes, need to replace these (can use LMWH)
  • Potassium replacement
  • Insulin replacement: need to check potassium levels before treatment, as if a patient is hypokalaemic then there is a risk of cardiac arrest
121
Q

What bariatric surgery options may be considered for obese patients?

A
  • Gastric balloon: temporary, insert balloon for 6-12 months
  • Gastric band: inflatable device, sits on stomach to reduce food that passes into stomach
  • Gastric sleeve: removes greater curvature of the stomach (most popular)
  • Gastric bypass: creating a pouch at the top of stomach then reattaching the bowel so it bypasses the rest of the stomach. Need to take B12 llifelong
122
Q

How is the success of bariatric surgery measured?

A

By how much excess weight a person is set to lose, i.e. any weight that takes you over BMI of 25

123
Q

What is the eligibility criteria for bariatric surgery?

A
  • BMI >40
  • BMI >35 and a comorbidity associated with your obesity, i.e. T2D
  • Ethnicity is taken into account, so South Asians can be considered with a BMI >30 as they have higher risk of T2D
124
Q

How many adults are obese or overweight in the UK?

A

28% = obese
Further 36.2% are overweight

125
Q

Why does visceral fat pose a larger risk for T2D than subcutaneous?

A

It is unstable - adipocytes are innervated by autonomic NS. There is a constant turnover of lipids, and the free FA from lipolysis can damage B cells and reduce insulin/ lead to insulin resistance.
Damage of B cells = inflammatory mediators released

Overall: greater adipose mass= high sympathetic NS activity= more lipolysis = free FA damaging etc.

126
Q

What type of drug is pioglitazone and what is its MOA?

A

Thiazolidinediones = agonist of the nuclear receptor PPARy, which is responsible for insulin-sensitive transcription

127
Q

When would diabetic patients need to inform the DVLA of their condition?

A

If the patient is on insulin treatment for >6 months

128
Q

For group 1 (car & motocycle), what is the DVLA guidance for diabetics to be allowed to drive?

A
  • Adequate awareness of hypoglycaemia
  • No more than 1 episode of severe hypoglycaemia in last 12 months, with the episode being >3 months ago
  • Has appropriate glucose monitoring
  • Has appropriate visual field acuity
129
Q

For group 2 (bus and lorry), what is the DVLA guidance for diabetics to be allowed to drive?

A
  • Full awareness of hypoglycaemia
  • No episode of severe hypoglycaemia in last 12 months
  • Regular glucose monitoring
  • must use a glucose meter with memory for last 3 months
130
Q

How does impaired awareness of hypoglycaemia affect a diabetic’s license to drive?

A

group 1 = can only drive once awareness has been regained (confirmed by GP or consultant)
Group 2 = license is revoked, inform DVLA

131
Q

What are disadvantages of using BMI?

A

o Muscular people: overestimates BMI
o South Asian populations: underestimated where there is a higher risk
o Older people: lower risk

132
Q

Compare gynacoid and android weight distributions, what stimulates these distributions?

A

Gynacoid= lower fat obesity: i.e. pear shaped, stimulated by estrogen and progesterone (after menopause women tend to have upper fat obesity)

Android = upper fat obesity, i.e. apple shaped, encouraged by testosterone and possibly alcohol

133
Q

Compare SGLT1 and SGLT2:
- Location
- Transport
- Km
- Affinity/ capacity

A

SGLT1= mainly in GI tract (some in kidney), co-transports 2 Na+ with 1 glucose. Has a Km of 2mM, thus has high affinity but low capacity for glucose

SGLT2= In PCT in kidney, co-transports Na+ with glucose (1:1). Has a Km of 5mM, thus has low affinity but high capacity for glucose

134
Q

Which GLUTs are insulin-sensitive?

A

GLUT4= insulin sensitive (in adipose, muscle, heart): kM =5
GLUT1 and GLUT2= insulin-insensitive (Gi tract, renal, hepatic, islet cells)
GLUT1 Km=5, GLUT2 Km= 17

135
Q

In the small intestine, how is glucose transported from the lumen to RBCs?

A
  • SGLT1 apical side: glucose gets into SI cell, with 2Na+
  • Leaves via GLUT2 (basolateral side): passively transported into blood
  • Enters RBC via GLUT1
136
Q

How is glucose absorbed in the renal tract?

A

around 90% absorbed in early PCT by SGLT2, then in the late PCT the rest is absorbed by SGLT1

137
Q

Why does oral administration lead to more insulin release than IV?

A

Due to the incretin effect; oral glucose goes via GI tract = GIP and GLP-1, but IV skips this

PBL Y2 S4 (9 decks)

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