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PH4703-Practical therapeutics > Diabetes > Flashcards

Diabetes Flashcards

1
Q

Quick recap glucose homeostasis

A
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2
Q

Aetiology of diabetes

A
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3
Q

Diagnosis

A
  • 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
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4
Q

Monitoring

Blood glucose targets

A
  • 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)
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5
Q

HbA1C

A
  • Refers to glycated Hb, which identifies average plasma glucose concentration over 2-3 months
  • Long term control
  • Need to be realistic
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6
Q

Blood ketones (type 1 only)

A
  • Only required when experiencing hyperglycaemia to try to avoid DKA
  • Blood ketones (not urine dipstick)
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7
Q

Treatments- INSULIN

Rapid and short-acting

A
  • 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)
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8
Q

Intermediate (NPH) (Isophane)

A
  • 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
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9
Q

Long acting

A
  • 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)
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10
Q

Pre-mixed

A
  • 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)
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11
Q

Insulins release profile

A
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12
Q

Insulin regimens- which profiles which?

A
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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?

A
  • 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
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14
Q

How do you decide

Once-daily regimens

A
  • 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
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15
Q

How do you decide

Twice daily mix

A
  • 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
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16
Q

How do you decide

Basal-Bolus

A
  • 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
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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
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18
Q

Summary of insulins- Mnemonic

A
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19
Q

General principles of insulin dose adjustment

A
  • 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
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20
Q

General principles of insulin dose adjustment

Basal-bolus regimens

A
  • 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%
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21
Q

Dose adjusting insulin

Once-daily regimen

A
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22
Q

Dose adjusting insulin

Mixed or intermediate insulin-twice daily

A
  • 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%
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23
Q

Basal-Bolus regimen

A
  • If type 2 diabetic and on larger doses of insulin only increase by 10%
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24
Q

Insulin titration summary

A
  • 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
Q

Type 2 diabetes management- oral therapies

A
  • 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
26
Q

NICE type 2 diabetes

27
Q

Initial treatment

A
  • 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
28
Q

Old dependables: SU and Pioglitazone

A
  • 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
29
Q

Thiazolidinediones

A
  • 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
Q

a-glucosidase Inhibitors

A
  • 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
Q

The Meglitinides

A
  • 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
Q

DPP4- Inhibitors

(Dipeptidyl Peptidase 4 inhibitor)

A
  • 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
33
Q

DPP4- Inhibitors

A
  • Increased insulin secretion
  • Rarely cause hypos
  • Weight neutral
  • Dose adjustment needed in renal impairment except LINAGLIPTIN
  • Sitagliptin, alogliptin
34
Q

SGLT2 inhibitors

A
  • 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
Q

GLP-1 agonist

A
  • 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
36
Q

GLP-1 modes of action

37
Q

NICE insulin in type 2 diabetes

A
  • 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
38
Q

Diabetic emergencies

A
  • Hypoglycaemia
  • DKA (Diabetic KetoAcidosis)
  • HHS (Hyperosmolar Hyperglycaemic State)
39
Q

Hypoglycaemia

A
  • 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
40
Q

Do they cause hypoglycaemia

41
Q

Causes of hypo’s

A
  • 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
Q

Treatment of hypo’s

A
  • 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
Q

Pharmacist role

A
  • 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
Q

DKA

A
  • 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
Q

Pathogenesis of DKA

A
  • 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
Q

Treatment of DKA

A
  • 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
47
Q

DKA role of pharmacist

A
  • 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
Q

DKA role of the pharmacist- sick day rules

49
Q

HHS

A
  • 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
Q

HHS

Aim and treatment

A
  • 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
Q

HHS

Pharmacist role

A
  • Compliance with medicines
  • Infection
  • Steroids
  • High carb intake
  • VTE prevention
  • Monitoring
52
Q

Variable Rate Insulin Infusion (VRII)

A
  • 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
53
Q

Complications of diabetes

Short term complications

A
  • Hypoglycaemia
  • DKA
  • HHS
54
Q

Complications of diabetes

Long term

A
  • Retinopathy
  • CVD
  • Neuropathy
  • Nerves and feet (neuropathy)
  • Diabetic foot ulcers
  • Amputations
  • Infectionw
55
Q

Reducing CV risk- primary prevention

Lifestyle advice

A
  • 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
Q

Reducing CV risk- primary prevention

Lipid modification

A
  • 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
Q

Reducing CV risk- primary prevention

BP management

A
  • 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
Q

BG monitoring in diabetes

A
  • 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
Q

Freestyle libre testing

A
  • Glucose monitoring system
  • Test interstitial fluid
  • As of Nov 2017, the freestyle libre is available on the NHS in some areas

PH4703-Practical therapeutics (36 decks)

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