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Year 3 - Met3b > Insulin, GLP-1 and oral hypoglycaemic agents > Flashcards

Insulin, GLP-1 and oral hypoglycaemic agents Flashcards

1
Q

What are the aims of treatment of diabetes

A

Maintenance of good health by
- giving education/information to enable patient to self manage
- focusing on dietary and lifestyle change
 Offering psychological and social support
 Controlling cardiovascular risk factors to reduce risk of complications
 Screening regularly for complications

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2
Q

What should all patients expect

A
  • Regular screening and review

- every diabetic should be seen at least twice per year

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3
Q

What does an annual review of diabetes include

A

▪ Review of symptoms
▪ Review clinical issues – glucose levels, BP, cholesterol, urine albumin creatinine ratio (ACR)
▪ Screen for complications – Eyes / Feet / Kidneys
▪ Issues identified can be addressed at subsequent visits
▪ An opportunity to develop targets over the next year

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4
Q

What treatment should be used to prevent complications

A

Smoking cessation

  • the biggest complication for diabetics
  • 1 cigarette in a diabetic is 5 cigarettes in a non diabetic
  • increases risk by 5 to 10 fold

Blood pressure

  • aim for 140/80 (130/80 mmHg if CVD or renal disease
  • first line treatment is ACE1 and then calcium channel blockers - often need greater than or equal to two blood pressure treatments

Cholesterol
 Diabetic > 40 years, or diabetic < 40years + 1 risk factor they have to be on a statin
 Aim for total cholesterol < 4.0 mmol/L, LDL < 2.0 mmol/L

Glycaemic control
- individualised to patient

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5
Q

What are diabetics screened for

A

 Eyes – digital retinal photography yearly
 Feet – yearly check for nerves and pulses
 Kidneys – yearly ACR and estimated GFR (ie serum creatinine)

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6
Q

What study shows the importance of glycemic control

A

United Kingdom Prospective Diabetes Study (1998)

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7
Q

What did the United Kingdom Prospective Diabetes Study (1998) show

A

Tight versus standard glycemic control had

  • little effect on macrovascular disease
  • but significantly reduced microvascular disease including nephropathy = reduced by 25-40%
  • even in the tightly control group there glycemic control got worse over time
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8
Q

What is the gold standard to assessing glycemic control in diabetic patients

A

Glycated haemoglobin (HbA1c)

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9
Q

what does the Glycated haemoglobin (HbA1c) depend on

A

the glycation of haemoglobin depends on prevailing glucose concentration. Higher glucose leads to more glycation of haemoglobin.

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10
Q

How long does the estimate for Glycated haemoglobin (HbA1c) last

A

Red cells survive around 3 months, so HbA1c tells you an approximate level of glucose control over preceding 3 months

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11
Q

What is a good Glycated haemoglobin (HbA1c) score

A

Good control less than 53 mmol/mol (old units = 7.0%)

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12
Q

Name the ways to assess glycemic control

A
  • Glycated haemoglobin (HbA1c)
  • Self monitoring of blood glucose (SMBG)
  • fructosamine
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13
Q

What is Glycated haemoglobin (HbA1c) affected by

A
  • conditions that increase you red blood cell turnover will falsely reduce the HbA1c
  • e.g. if you have blood loss and chronic anaemia as the red blood cells do have enough time to get glycolayted
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14
Q

How does self monitoring blood glucose (SMBG) act as a way to assess glycemic control

A
  • Patient can self test glucose levels using a meter
  • used in patients with insulin therapy
  • Pre-prandial (before meals) aim for around 4-7 mmol/L
  • Post prandial (After meals) - 2 hour glucose aim for around 5-9mmol/L
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15
Q

How do you use fructosamine to assess glycemic control

A
  • another glycated protein
  • lasts around two weeks
  • used in pregnancy
  • used in HbA1c invalid e.g. due to haemoglobinopathy
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16
Q

What should the diet be like of a diabetic

A

 Diet should be low in fat, sugar, salt,
- high in fibre, fruit, vegetables
 Carbohydrates should be low glycaemic index (GI)

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17
Q

How much exercise should a diabetic do

A

 Physical activity – at least 30 minutes vigorous exercise 3x per week

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18
Q

How much weight reduction improves glycemic control

A

 3-5% weight reduction improves glycaemic control

 This is effective in 50% of patients initially

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19
Q

what should you use if treatment via diet and lifestyle strategy fails

A

 Subsequent failure to control diabetes is frequent after a year or so
 Early use of oral hypoglycaemic agents recommended if diet and lifestyle strategy fails

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20
Q

List the treatment for hypoglycaemia

A 
 Sulfonylureas / Prandial glucose regulators (PGRs)
 Biguanides
 Alpha glucosidase inhibitors
 Thiazolidinediones (glitazones)
 DPP-4 inhibitors
 GLP-1 analogues
 Insulin
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21
Q

What do insulin secretagogues do

A
  • they stimulate insulin release from B cells into the blood stream
  • open up potassium channels in the beta cells
  • cause insulin to be released
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22
Q

What is the mechanism of action of insulin secretagogues

A

Increase pancreatic insulin secretion by opening potassium channels in beta cells which increase insulin release

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23
Q

Name an insulin secretagogues

A

Sulfonylureas / Prandial glucose regulators (PGRs

- meglitinides

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24
Q

Name an example of a biguanide

A

Metformin

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25
Q

How do biguanides work

A

Muscle and adipose tissue - increase glucose utilisation

improves insulin sensitivity in the liver and muscle

reduce hepatic glucose output

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26
Q

What is the first line drug in the vast majority of type 2 diabetes

A

Metformin

  • reduce weight
  • reduces mortality in T2D
  • suggestion that it reduces cancer
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27
Q

What case would you not use metformin

A

Severe hepatic disease

Renal disease

  • CKD - stage for
  • EGFR - less than 30
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28
Q

What do alpha glucosidase inhibitors do

A
  • reduce intestinal absorption of glucose

- block the disaccharide into monosaccharides to stop the glucose from being absorbed

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29
Q

What is the problem with alpha glucosidase inhibitors

A

It will deliver glucose into the lower bowel

- bacteria ferments the glucose and causes flatuculance which is a big problem with this drug

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30
Q

Name the side effects of alpha glucosidase inhibitors

A
  • flatulance
  • diarrhoea
  • abdominal pain
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31
Q

What do thaiazolidinediones do (glitazones)

A
  • PPARP agonists
  • improve insulin sensitivity

Muscle and adipose tissue

  • decrease insulin resistnace
  • increase glucose uptake

Pancreas

  • decrease demand for insulin secretion
  • increase beta cell insulin content

Liver

  • decrease insulin resistance
  • decrease hepatic glucose production
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32
Q

what is the structure of glucagon like peptide 1 (GLP1)

A

31 amino acid peptide

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33
Q

Where is GLP-1 produced

A

Cleaved from proglucoagon in L cells in the GI tract

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34
Q

What family is GLP-1 part of

A

Incretins

35
Q

what is GLP-1 secreted in response to

A

Secreted in response to meal ingestion

36
Q

What affects does GLP-1 have

A

 Glucose-dependently stimulates insulin secretion and decreases glucagon secretion
 Delays gastric emptying
 Decreases food intake and induces satiety
 Stimulates beta-cell function and preserves or increases beta-cell mass in animal models

37
Q

what stimulates insulin more - oral or IV glucose

A

oral glucose

  • get more insulin stimulation due to stimulation of hormones called GLP-1 (and other incretins)
  • these stimulate insulin and decrease glucagon concentration
  • they suppress the appetite
38
Q

Why does oral glucose stimulate insulin more

A
  • with oral insulin you get more insulin stimulation due to stimulation of hormones called GLP-1 (and other incretins)
  • these stimulate insulin and decrease glucagon concentration
  • they suppress the appetite
39
Q

Who would you use GLP-1 in

A
  • BMI of our 35 kg/m2

- poor glucose control

40
Q

What format does a GLP-1 analogue have to be given in

A
  • Injection as it is a peptide
41
Q

What does a GLP-1 analogue do

A
  • suppresses appetite

- stimulates insulin release

42
Q

What do DPP-IV inhibitors do

A
  • inhibit breakdown of GLP-1
43
Q

how should you take DPP-IV inhibitors

A 
These are called “Gliptins”
 Oral
 Once daily
 Well tolerated
 Third line therapy
44
Q

Describe the NICE guidelines for glucose lowering

A
  1. Lifestyle changes
  • ↓ HbA1c ≥48mmol/L
    2. Metformin standard release – modified release if not tolerated
  • Slow titration, take after meals
  • Care with dose of metformin if eGFR<45, stop if <30
  • Consider sulfonylurea if not overweight, metformin CI or not tolerated↓ HbA1c ≥58mmol/L
    3. Dual therapy (aim = 53mmol/L)
  • Metformin + Sulfonylurea (if hypoglycaemia a problem or metformin not tolerated:
    DPP-4 inhibitor/Pioglitazone)
  • Once daily if concordance is problematic
    Consider PGRs if erratic lifestyle↓ HbA1c ≥58mmol/L
  1. Triple therapy
    - Metformin + SU + DPP-4 inhibitor/Pioglitazone/Insulin
    - Consider GLP-1 analogue if: BMI>35, problems from weight gain
    - Continue >6 months if HbA1c drop >1% and weight loss >5%
  2. Intensify insulin or add Pioglitazone
    - Warn re oedema
45
Q

What are the side effects of biguinides - metformin

A

nausea
diarrhoea
lactic acidosis in patients with renal failure - stop at EGFR of 30

46
Q

What are the side effects of Sulfonylureais e.g. gliclazide and prandial glucose regulators e.g. Repaglinide

A

Hypoglycaemia

Weight gain

47
Q

What are the side effects of glitazones e.g. pioglitazone

A 
Weight gain 
oedema 
heart failure contradicted
post menopausal fractures
bladder cancer
(giving less now)
48
Q

What are the side effects of alpha glucosdiase inhibitors such as acarbose

A

flatulence

diarrhoea

49
Q

What are the side effects of DPP-IV inhibitors such as sitagliptin

A

Nasopharyngitis

pancreatitis

50
Q

What are the side effects of GLP-1 agonists such as exenatide

A

Nausea
diarrhoea
pancreatitis and pancreatic cancer (evidence is minimal)

51
Q

Describe normal glucose metabolism

A
  1. Glucose is ingested
  2. Digested and broken
    down by gut enzymes
  3. Incretins released by gut
    lead to stimulation of insulin release from the pancreas
  4. Glucose is absorbed in the small intestine
  5. Insulin acts on the liver, muscle and adipose tissue to stimulate glucose uptake
52
Q

what goes wrong in type 2 diabetes

A
  • Insulin resistance
  • insulin deficiency
    or a combination of both
53
Q

What goes wrong in type 1 diabetes

A

Insulin deficiency

54
Q

describe what normal insulin secretion looks like

A
  • two phases of insulin with each meal - tends to be biphasic
  • see a short lived rapid generated meal related and then a low steady basal insulin profile
  • always a bit of insulin even at night
55
Q

What are the indications of insulin in type 1 diabetes

A
  • essential for life
56
Q

What do you give insulin for in type 2 diabetes

A 
 inadequate glycaemic control on tablets
 contraindications to tablets
 symptomatic hyperglycaemia
 pregnancy
 infection / foot ulcers
57
Q

What are the types of insulin

A

Human insulin - produced from E coli and manufactured - tend to be in T2D

analogue inulin - genetically modified and used in T1D

58
Q

What are the types of human insulin

A

 Short acting–eg Humulin S

 Intermediate acting–eg Humulin I

 Biphasic - mixture of short and intermediate – eg Humulin M3

59
Q

What are the types of analogue insulin

A

 Rapid acting – eg Novorapid, Lispro

 Long acting (basal insulin) – eg Lantus, Levmir

 Biphasic - mixture of rapid and intermediate eg Novomix 30

60
Q

How is insulin given

A
  • by a pen device - simplify administration
61
Q

Where should insulin be injected into

A
  • Subcutaneous fat
62
Q

What injection sites should be used for injecting insulin

A
  • Abdomen - fastest absorption
  • thighs
  • buttocks - slowest absorption
63
Q

Insulin should not be…

A

Injected through clothing

64
Q

Name the types of insulin regimens

A

 Once-daily / twice-daily intermediate- or long-acting (basal) insulin

 Once-/ twice-/ three-times daily premixed insulin

 Basal–bolus therapy

65
Q

Describe once daily basal insulin

A

 Once daily intermediate or long acting insulin, given in addition to tablets - still taking tablets
 Usually given before bed or first thing in the morning

66
Q

Describe premixed insulin - twice daily regime

A
  • 30% short acting - on breakfast and dinner (twice a day)
  • 70% long acting kicks in over the day and night

Contains

  • basal component
  • short acting component
  • Used in type 2 diabetes does not tend to be used in type 1
67
Q

Describe the basal bolus therapy

A
  • 3 injections of rapid acting at breakfast, lunch and dinner
  • 1 injection of long acting at night time
  • mimics normal physiology
  • used in type 1 diabetes or in type 2 diabetes with poor glucose control
68
Q

How do you prescribe insulin

A

Only write number
 Eg Novomix 30 – 10 and 8

 Never write “U”, “IU” or “UNITS”

Ensure insulin given at correct times
 Usually pre meal

Ensure correct type of insulin written up
 Care with novomix and novorapid

Ensure blood glucose monitoring undertaken appopriately
 Usually 2-4 times per day – fasting, pre meal and pre bed

69
Q

Case study

  • morning glucose is persistent 10-14mmol/L (high)
  • they are on twice daily insulin - so short and acting
  • what would you do to lower the morning glucose
A

Increase the night time insulin to lower the morning glucose

  • if the glucose was low you would reduce the night time insulin to raise the morning glucose
70
Q

What is the blood pressure control in management in diabetes

A
  • 140/80 or 130/80 in CVD or renal disease
71
Q

How should cholesterol be compared

A
  • diabetic >40 years or Diabetic <40 years + 1 risk factor = statin
  • aim: total cholesterol <4mmol/L, LDL <2mmol/L
72
Q

what screening takes place in diabetes

A

Eyes – digital retinal photography yearly

Feet – yearly check for nerves and pulses

Kidneys – yearly ACR and eGFR (ie serum creatinine)

73
Q

Name some sulfonylureas

A
  • Gliclazide
  • tolbutamide
  • Glibenclamide
  • glipizide
  • glimepiride
  • chlorpropamide
74
Q

name some meglitinides

A
  • repaglinide

- Nateglinide

75
Q

When should you stop giving biguanides (metformin)

A
  • Tissue hypoxia e.g. sepsis or MI
  • general anaesthesia (GA)
  • Before contrast medium containing iodine - risk of renal failure and subsequent lactic acidosis - restart no earlier than 48 hours after test of renal function which shows no deterioration
76
Q

name an example of alpha-glucosidase inhibitors

A

Acarbose

77
Q

Name an example of thiazolidinediones

A

pioglitazone

78
Q

Name examples of GLP-1 receptor analogues

A
  • exenatide
  • liraglutide
  • lixisenatide
79
Q

Name examples of DPP4 inhibitors

A
  • Sitagliptin
  • Vildagliptin
  • Alogliptin
  • Linagliptin
  • Saxagliptin
80
Q

What are thiazolidinediones contraindicated in

A
  • past/present heart failure

- osteoporosis

81
Q

What are the indications for insulin therapy

A
  • T1DM

T2DM

  • inadequate glycaemic control on tablets or CI to tablets
  • symptomatic hyperglycaemia
  • pregnancy
  • infection/foot ulcers
82
Q

What are the sick day rules of insulin

A
  • drink lots of fluid (3L)
  • If unable to eat - sugary fluids
  • monitor glucose regularly >4 times/day
  • never stop tablets or insulin (may increase insulin)
  • oral agent users may require insulin during course of illness
83
Q

When should you admit someone who is on insulin to hospital when they are ill

A
  • Vomiting
  • dehydrated
  • child
  • pregnant

Year 3 - Met3b (26 decks)

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