Diabetes Flashcards
1
Q
Quick recap glucose homeostasis
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2
Q
Aetiology of diabetes
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3
Q
Diagnosis
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- Usually based on clinical symptoms in combination with measured blood glucose levels
- Symptoms: Polydipsia, polyuria, infections, blurred vision, lethargy
- HbA1c reflects average glucose over 8-12 weeks
- Can be used as a diagnostic test
- HbA1C more than 48 mmol/mol
- Some factors affect accuracy of HbA1C and in these patient HbA1C should not be used for diagnosis
4
Q
Monitoring
Blood glucose targets
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- Pre-meal- 4-7 mmol/L
- Post-meal- <9mmol/L
- Not always possible. Hypoglycaemia may occur if too tight
- Self monitoring essential in type 1
- Type 2 only in some patients (due to cost/those on insulins)
5
Q
HbA1C
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- Refers to glycated Hb, which identifies average plasma glucose concentration over 2-3 months
- Long term control
- Need to be realistic
6
Q
Blood ketones (type 1 only)
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- Only required when experiencing hyperglycaemia to try to avoid DKA
- Blood ketones (not urine dipstick)
7
Q
Treatments- INSULIN
Rapid and short-acting
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- 5 main types of insulin
- RAPID ACTING
- Rapid onset and shorter duration. Taken just before with a meal
- Begins to work 15 minutes after injection, peaks approx. 1 hour, and continues to work for 2-4 hours
- Aim to provide a physiological bolus of insulin when used at mealtimes
- Types: Insulin glulisine (Apidra), Insulin lispro (Humalog) and Insulin Aspart (Novorapid)
- SHORT ACTING
- Not as quick to act as rapid. Usually taken before meals
- Begins to work 30 minutes after injection, peaks from 2 to 3 hours, and is effective for approximately 3-6 hours
- Used as part of a basal-bolus, to provide bolus at mealtimes
- Soluble insulin (Actrapid, Humulin S)
8
Q
Intermediate (NPH) (Isophane)
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- 24 hour duration
- Begins to work 2 to 4 hours after injection, peaks 4 to 12 hours later, and is effective for about 12-24 hours
- Used to cover blood sugar between meals, and to satisfy your overnight insulin requirement
- Can be OD or BD and can be used in combination with rapid or short-acting insulin
- Types: Insulatard
9
Q
Long acting
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- Slower onset, prolonged duration
- Peakless insulin levels, over 24 hours period (Note tresiba acts for 40 hours)
- Aim to mimic basal physiological insulin
- Used in type 2 diabetes OD or as part of basal-bolus in type 1 + 2
- Types: Insulin detemir (Levemir), Glargine (Lantus, Toujeo), Degludec (Tresiba)
10
Q
Pre-mixed
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- Combination of intermediate and rapid-acting
- Rapid element starts to act immediately, peak at 1 hour and last 4 hours; long acting element begins onset 2 hours, no peak activity, lasts upto 24 hours
- BD injections (Breakfast and evening)
- Biphasic aspart (Novomix 30), Biphasic lispro (Humalog mix 25, 50)
11
Q
Insulins release profile
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12
Q
Insulin regimens- which profiles which?
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13
Q
The insulins regimens- How do you decide
What factors do you think affect the regimen we choose a patient?
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- Type 1 or 2
- Who will administer the insulin
- Dexterity of patient
- Patient compliance
- Diet
- What is their blood glucose control
- Do they have post-prandial high blood glucose
14
Q
How do you decide
Once-daily regimens
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- Suitable for type 2
- Long-acting or intermediate insulin
- People with hyperglycemia through the day and night
- Require assistance injecting
- NG feeds/insulin infusions
- Intermediate insulin for people who high blood glucose overnight and in the morning but better during the day. Give at night
15
Q
How do you decide
Twice daily mix
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- Type 1 or 2
- Keep a consistent daily routine that includes 3 meals a day
- Some flexibility for adjusting doses, not as much as a basal-bolus regimen
- Type 2 diabetes, useful for high blood glucose levels after meals
- Easy for patients to understand
- Fewer injections than basal-bolus
- More effective at reducing HbA1C than basal alone
16
Q
How do you decide
Basal-Bolus
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- Type 1 and 2
- At least 4 injections per day
- A long-acting or intermediate-acting dose and separate injections of short or rapid-acting insulin at each meal
- Advantage flexibility over when meals are taken and allows doses to be varied in response to different carbohydrate quantities in meals
- Better potential for metabolic control if used optimally
- Potential for better lifestyle choices in terms of adjustment for diet and activity
17
Q
How do you decide
Continuous subcutaneous insulin infusion
A
- Type 1 diabetes
- Rapid-acting insulin
- Insulin pump connected to your body
- Delivers a constant feed of insulin into the body via an s/c cannula
- At meals times, an increased burst (bolus) of insulin can be delivered to keep blood glucose levels under control
- Predictable insulin release
- Reduced episodes of severe hypo’s
18
Q
Summary of insulins- Mnemonic
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19
Q
General principles of insulin dose adjustment
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- Do not adjust based on a one-off reading
- After an adjustment of long-acting insulin wait 3-4 days before the further adjustment (5 days with degludec)
- Once-daily insulin regimen
- Hyperglycaemia, increase by 10% in increments of 2,4,6 units
- If Hypoglycaemia, reduce by 2-4 units or 20% whichever is greater
- Mix insulin regimen
- Morning dose titrated against pre-launch and pre-evening meal BG
- Evening dose titrated against pre-bed and pre-breakfast BG
- Hyperglycaemia increase by 10%
- Hypoglycaemia reduce by 20% or 2-4 units whichever is greater
20
Q
General principles of insulin dose adjustment
Basal-bolus regimens
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- Adjust long-acting to control pre-breakfast blood glucose
- Reduce if BG low overnight or pre-breakfast
- Adjust rapid-acting to control BG pre-lunch and tea
- Increase or decrease quick-acting insulin by 0.5 units to 10g carbohydrate (or 2-5g carbohydrate per unit of insulin)
- Hyperglycaemia and trend increases overnight increase basal by 10-20%
- If type 2 and on larger doses than 10%
- If hypo overnight or pre-breakfast reduce basal by 20%
21
Q
Dose adjusting insulin
Once-daily regimen
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22
Q
Dose adjusting insulin
Mixed or intermediate insulin-twice daily
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- As a general rule if a 2-3 mmol/L improvement needed increase dose by 5% initially and for greater than a 5mmol/L improvement increase by 10%
23
Q
Basal-Bolus regimen
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- If type 2 diabetic and on larger doses of insulin only increase by 10%
24
Q
Insulin titration summary
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- Same principles apply, taking patterns of hypo- and hyperglycaemia separately
- If no patterns and high/low readings appear to be happening randomly
- Check insulin is in date, stored properly, being mixed appropriately (i.e. cloud insulin being rolled and dispersed before injection)
- Check injection sites (Lipohypertrophy) which may cause erratic absorption
25
Type 2 diabetes management- oral therapies
* Spectrum of agents
* Old dependables (metformin, sulfonylureas (SU) and pioglitazone)
* New kids on the block: SGLT2-I, GLP-1, DPP4-I
* Efficacy, safety, co-morbidities, individual patients needs and choice, licensing, cost
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NICE type 2 diabetes
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Initial treatment
* Metformin
* Titrate dose
* Caution renal impairment (renally cleared)
* GI side effects
* Stop immediately in AKI, Sepsis, Acute HF (Lactic acidosis)
* If not tolerated
* Sulfonylurea
* DPP4-I
* Pioglitazone
* Metaglinides
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Old dependables: SU and Pioglitazone
* Thiazolidinedione (Pioglitazone)
* Insulin sensitizer
* Contraindicated
* HF, Hepatic, DKA, Bladder Ca, Bone fracture
* Sulfonylureas
* Increased risk of hypos
* Accumulate in renal impairment
* Long-acting SU = long-acting hypos
* Inappropriate if a person at risk of hypo's or their consequences e.g. lorry driver
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Thiazolidinediones
* Mode of action: Bind and activate PPARy transcription factor =\> increase adipose and muscle insulin sensitivity
* Glycaemic impact: HbA1c down 0.7-1.4%
* Add on therapy
* Side effects: Fluid retention/ weight gain; Osteoporosis; Risk of bladder Ca
30
a-glucosidase Inhibitors
* These agents slow the digestion of starch in the small intestine
* Glucose from the starch enters the bloodstream more slowly
* Can be matched more effectively by an impaired insulin response or sensitivity
* Must be taken with a meal to prevent post-prandial glucose rise
* Side effects: Primarily GI dysmotility; Weight loss due to less glucose absorption
31
The Meglitinides
* Chemically related to the SUs, but far shorter-acting (t 1/2)
* Mode of action: Bind SUR1 sites of the ATP-dependent K+ channel =\> insulin secretion
* Glycaemic impact: HbA1c down 0.5-1.3%
* Weight gain
* Hypoglycaemia
32
DPP4- Inhibitors
| (Dipeptidyl Peptidase 4 inhibitor)
* Inhibits the degradation of GLP-1
* MOA: reduce incretin turnover =\> increase 1st phase insulin response, suppress glucagon
* Glycaemic impact: HbA1c decreased 0.5-0.8%.
* Side-effects: GI dysmotility; Pancreatitis; bowel cancer
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DPP4- Inhibitors
* Increased insulin secretion
* Rarely cause hypos
* Weight neutral
* Dose adjustment needed in renal impairment except LINAGLIPTIN
* Sitagliptin, alogliptin
34
SGLT2 inhibitors
* Canagliflozin, dapagliflozin
* Inhibits glucose absorption in the renal tubules, leading glucosuria
* Can cause Euglycaemia DKA- **Stop treatment**
* Canagliflozin- the risk of lower limb amputation. If osteomyelitis and ulceration STOP treatment
* Perianal fasciitis
* Efficacy dependent on good renal function
* DON'T initiate if CrCl \<60ml/min all SGLT2i
* Canagliflozin and empagliflozin can be continued down to 45mL/min (CANVAS trial)
* Cause recurrent UTI due to mechanism of action- stop if the patient diagnosed with pyelonephritis or UTI
35
GLP-1 agonist
* Glucagon-like peptide- 1 (GLP-1) receptor agonist prescribed for patients who have not been able to control their condition with tablet medication
* For type 2 diabetes
* Sc injection
* Victoza (lariglutide)- OD, semaglutide- Once weekly
* NICE GLP-1 agonist
* If oral triple therapy not effective, not tolerated or contra-indicated consider in combination with metformin and SU
* If BMI \>35 or \<35 but insulin therapy would have a significant occupational implication or weight loss would benefit other co-morbidities
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GLP-1 modes of action
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NICE insulin in type 2 diabetes
* Continue metformin
* Review other anti-hyperglycemic
* NPH (Intermediate) OD or BD
* SGLT2i + iinsulinan option
* Long-acting insulin (Glargine or detemir) an option instead of NPH
* If assistance with injection needed and OD
* Lifestyle resticted by hypo's
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Diabetic emergencies
* Hypoglycaemia
* DKA (Diabetic KetoAcidosis)
* HHS (Hyperosmolar Hyperglycaemic State)
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Hypoglycaemia
* Glucose \<4mmol/L
* Mild if able to self treat
* Severe if needs intervention from another person to treat
* Most common emergency
* Commonest SE of diabetes treatment
* BG drops \<4mmol/L, get physiological response to counter regulate (adrenaline, NA, growth hormone, cortisol and glucagon)
* Hypo-unawareness- Do not counter regulate effectively
* Review injection site technique, activity patterns, gastroparesis, changes to insulin sensitivity
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Do they cause hypoglycaemia
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Causes of hypo's
* Reduced carbs in the diet
* Inappropriate stat doses of insulin
* Incorrect timing of insulin
* Advancing age
* AKI
* Stopping steroids
* Increased exercise
* Surgery
* Lack of monitoring/education
* Recovery from acute illness
* Not treating a hypo properly
* Drug-induced
42
Treatment of hypo's
* Mild: 10-20g glucose (Fast-acting carbohydrate)
* 5 dextrose tablets / glucogel
* Glass of lucozade
* 200mL fruit juice
* Can't swallow
* IM glucagon
* 10 min to reach full effect
* IV
* 25g IV glucose
* 10% or 20% glucose fluid
* For all repeat blood glucose every 15 minutes until in range \>4mol/L
43
Pharmacist role
* Renal deterioration
* Elderly on SU
* Suitability in different patient groups
* Co-morbidities
* Preventing disease burden
* Medicines Optimisation
* Repeat purchase of glucose tablets
* Tight HbA1c
* Education on hypo awareness and management
* Check timing of insulin
44
DKA
* Life threatening complication of type 1
* Insufficient insulin intake
* 10-30% cases first presentation of diabetes
* 50% precipitated by infection
* Clinical features: Polyuria, polydipsia, muscle crampls, ab pain, SOB, ketone smelling breath
* Definitions
* Acidaemia: Bicarbonate \<15mmol/L And/Or Venous blood gas pH \<7.3
* Hypreglycaemia: BG\> 11.1 mmol/L or known diabetic
* Ketones: Ketonaemia \>3mmol/L; Ketonuria (2++)
45
Pathogenesis of DKA
* In absolute absence of insulin
* Inappropriate glucose release
* Hepatic gluconeogenesis
* Hepatic Glycogenolysis
* Lipolysis- increase serum fatty acids- metabolised as alternate energy source
* Ketogenesis- production of ketones- metabolic acidosis
46
Treatment of DKA
* 0.1 unit/kg/hr IV insulin- fixed rate
* Continue long-acting insulin
* 0.9% NaCl with K (if needed 40mmol/L if K+ \<5.5mmol/L)
* 10% glucose when blood glucose \<14
* Rehydrate 1L 0.9% sodium chloride over 1hr, then 2 hrs
* Aim to reduce ketones by 0.5mmol/L/hr
* Reduce BG by 3mmol/L/hr
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DKA role of pharmacist
* Identification of patients
* MUR particularly those on SGLT2i (stop) report to MHRA
* Access to ketone strips and meters
* VTE prophylaxis
* Guideline adherence
* Education on sick day rules
* Assess compliance
48
DKA role of the pharmacist- sick day rules
49
HHS
* Severe metabolic disorder of type 2 diabetes
* Mortality rate 15-20%
* Diagnosis
* Extreme hyperglycaemia (\>30mmol/L)
* With the absence of ketones
* Hypovolaemia
* Osmolarity 320 mosmol/Kg or more
* (2NA + glucose + Urea)
* Typically occurs in elderly
* PC- several days of feeling unwell with profound dehydration (unlike DKA acute)
50
HHS
Aim and treatment
* Normalise osmolaity, replace fluid, normalise BG, prevent VTE, prevent fluid overload and cerebral oedema
* Reduce blood glucose by 5mmol/L/Hr
* Treatment
* Fluids (often 3-6 L in 12 hrs)
* Electrolytes
* IV insulin (0.05 units/Kg/Hr)
51
HHS
Pharmacist role
* Compliance with medicines
* Infection
* Steroids
* High carb intake
* VTE prevention
* Monitoring
52
Variable Rate Insulin Infusion (VRII)
* Also knows as sliding scale insulin
* Insulin rate adjusted according to BM
* Continue basal insulin
* Stop mealtime insulin or pre-mix regime
* Regulates patients BG
* Glycaemic control impacts on the risk of post-operative infective
* Post-operative glycaemic control influences wound healing
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Complications of diabetes
Short term complications
* Hypoglycaemia
* DKA
* HHS
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Complications of diabetes
Long term
* Retinopathy
* CVD
* Neuropathy
* Nerves and feet (neuropathy)
* Diabetic foot ulcers
* Amputations
* Infectionw
55
Reducing CV risk- primary prevention
Lifestyle advice
* Individualised
* Encourage high-fibre, low-glycaemic-index sources of carbohydrate in the diet, such as fruit vegetables, whole grains and pulses; include low-fat dairy products and oily fish; and control intake of foods containing saturated and trans fatty acids
56
Reducing CV risk- primary prevention
Lipid modification
* Stain for primary prevention type 1 diabetes
* Older than 40 years or
* Diabetes for more than 10 years or
* Established neuropathy or
* Have other CVD risk factors
* Atorvastatin 20mg OD
* Primary prevention type 2
* Atorvastatin 20mg OD if have a 10% or greater 10-year risk
57
Reducing CV risk- primary prevention
BP management
* First line ACEI
* Target BP less than 140/80mmHg (or \<130mmHg if there is the kidney, eye or cerebrovascular damage)
* Don't offer antiplatelet therapy for adults with type 2 diabetes without coronary or cerebrovascular disease
58
BG monitoring in diabetes
* Not routinely performed in patients who are on oral agents
* Consider for hypoglycaemia risk
* Recommended for insulin patients
* Additional ketone monitoring advised for Type 1 patients
59
Freestyle libre testing
* Glucose monitoring system
* Test interstitial fluid
* As of Nov 2017, the freestyle libre is available on the NHS in some areas
