Type 2 Diabetes

1
Type 2 Diabetes
2
What is type 2 diabetes?
3
Definition of diabetes?WHO/International
Diabetes Federation. Definition and diagnosis of
diabetes mellitus and intermediate
hyperglycaemia 2006

• Diabetes
• Fasting plasma glucose 7.0mmol/l (126mg/dl) or
• 2h plasma glucose 11.1mmol/l (200mg/dl)
• Impaired glucose tolerance (IGT)
• Fasting plasma glucose lt 7.0mmol/l (126mg/dl) and
• 2h plasma glucose 7.8 and lt 11.1mmol/l
  (140mg/dl and 200mg/dl)
• Impaired fasting glucose (IFG)
• Fasting plasma glucose 6.1 to 6.9mmol/l (110mg/dl
  to 125mg/dl) and
• 2h plasma glucose lt 7.8mmol/l

4
Change of units for HbA1cDTB 2010 48 23-4,
MeReC Rapid Review No. 356
Conversion chart for HbA1c values Conversion chart for HbA1c values
HbA1c () HbA1c (mmol/mol)
4.0 20
4.5 26
5.0 31
5.5 37
6.0 42
6.5 48
7.0 53
7.5 59
8.0 64
8.5 70
9.0 75
9.5 81
10.0 86
5
Type 1 vs. Type 2 diabetesLambert P, et al.
Medicine 2006 34 47-51Nolan JJ, Medicine 2006
34 52-6

• Features of type 1 diabetes

• Features of type 2 diabetes

• Onset in childhood / adolescence
• Lean body habitus
• Acute onset of osmotic symptoms
• Ketosis-prone
• High levels of islet autoantibodies
• High prevalence of genetic predisposition

• Usually presents in over-30s
• Associated with overweight / obesity
• Onset is gradual and diagnosis often missed (up
  to 50 cases)
• Not associated with ketoacidosis though ketosis
  can occur
• Family history is often positive with almost 100
  concordance in identical twins

6
Burden of type 2 diabetesNICE Clinical Guideline
87, May 2009Royal College of Physicians 2008

• Type 2 diabetes is a cardiovascular disease
  commonly associated with raised BP, disturbance
  of lipid levels and tendency to develop
  thrombosis
• Increased cardiovascular risk (macrovascular
  disease)
• Coronary heart disease (MIs, angina)
• Peripheral artery disease (leg claudication,
  gangrene)
• Carotid artery disease (strokes, dementia)
• Specific microvascular complications
• Eye damage (blindness)
• Kidney damage (sometimes requiring dialysis or
  transplantation)
• Nerve damage (amputation, painful symptoms,
  erectile dysfunction, other problems)

7
Deaths by cause in the general population Men
aged 40-59 years, 1999, UKLaing SP, et al.
Diabetic Medicine 1999 16 466-471Office of
National Statistics 2000General Register Office
2000
CVD 35
Cancer 33
All other causes 15
Accidents and violence 10
Respiratory disease 6
Diabetes 1
Renal disease 0
8
Deaths by cause in people with diabetes Men aged
40-59 years, 1972/99, UK
CVD 63
Renal disease 10
Respiratory disease 6
Accidents and violence 6
Cancer 5
Diabetes 5
All other causes 5
9
What are the management priorities?
10
Management for type 2 diabetes AimsNICE
Clinical Guideline 87 May 2009

• Adopt a healthy lifestyle (stop smoking,
  exercise, weight management etc)
• Manage symptoms associated with having high blood
  glucose levels if patients have them)
• Reduce risk of major life-threatening or
  disabling complications (heart attacks and
  stroke)
• Manage diabetic kidney damage, eye damage and
  nerve damage (foot disease, neuropathic pain,
  erectile dysfunction etc)
• Targets for all the different aspects of this
  condition (BP, lipids, blood glucose etc) can be
  demanding to reach
• Agree the priorities for care and targets for
  each aspect of management on an individualised
  patient basis as aggressive therapy of each
  aspect may not be appropriate for all

11
Type 2 diabetes management is multifactorial

• Education
• Lifestyle
• Dietary advice
• Obesity
• Weight management
• Smoking
• Control BP
• Assessing cardiovascular risk
• Blood lipids
• Aspirin
• Control blood glucose

12
Education
13
Education what does NICE say?NICE Clinical
Guideline 87 May 2009

• Offer structured education to every person /or
  their carer at and around the time of diagnosis,
  with annual reinforcement and review. Inform
  patients and their carers that structured
  education is an integral part of diabetes care
• The necessary lifestyle changes, the complexities
  of management and the side effects of therapy
  make self-monitoring and education for people
  with diabetes central parts of management
• Patient centred care
• People with diabetes should have the opportunity
  to make informed decisions about their care and
  treatment, in partnership with their healthcare
  professionals. Good communication is essential

14
What is the evidence? The DESMOND
programmeDavies MJ, et al. BMJ 2008 336
491-495.Gillett M, et al. BMJ 2010 341 c4093

• Diabetes Education and Self-Management for
  Ongoing and Newly Diagnosed programme
• Patients taking part were significantly more
  likely to lose a little weight and stop smoking
  than those in the control group
• Primary outcomes of the DESMOND programme trial
  found no statistical differences in HbA1c and no
  benefits for cholesterol levels and BP

15
Lifestyle
16
Dietary adviceNICE Clinical Guideline 87 May
2009

• Provide individualised and ongoing nutritional
  advice from a healthcare professional with
  specific expertise and competencies in nutrition
• Healthy balanced eating applicable to general
  population
• Integrate dietary advice with advice to increase
  physical activity and lose weight
• Target initial weight loss is 5-10 of body
  weight is overweight
• Individualised recommendations for carbohydrate
  and alcohol intake
• Limited substitution for sucrose containing foods
  and other carbohydrates is allowable but take
  care to avoid excess energy intake
• Discourage use of foods specifically marketed for
  people with diabetes

17
Obesity exercise and dietNational Audit Office.
Tackling obesity in England. 15 February
2001Avenell A, et al. Health Technol Assess
2004 8(21) 1-465

• Virtually all obese people develop some
  associated physical symptoms by the age of 40
  years
• The majority require medical intervention for
  diseases that develop as a result of obesity by
  the age of 60 years
• National Audit Office suggests that 47 of type 2
  diabetes can be attributed to obesity
• As obesity rates increase, so will the prevalence
  of type 2 diabetes
• Even modest losses in weight can confer
  significant metabolic and vascular benefits.
  Losing weight is associated with a reduction in
• Mortality (all-cause, cancer, CVD and
  diabetes-related)
• The risk of developing type 2 diabetes
• Hypertension
• Cholesterol

18
Weight managementSIGN 116, Management of
diabetes. March 2010

• Obese adults with type 2 diabetes should be
  offered individualised interventions to encourage
  weight loss (including lifestyle, pharmacological
  or surgical interventions) in order to improve
  metabolic control
• A single approach is not recommended due to an
  absence of head-to-head comparisons
• Consider drug treatment only after dietary,
  exercise and behavioural approaches have been
  started and evaluated
• Consider drug treatment for patients who have not
  reached their target weight loss or have reached
  a plateau on dietary, activity and behavioural
  changes alone

19
Smoking
20
Smoking cessation

• Advising and effectively assisting a person to
  stop smoking is the single most important thing
  that can be done for health
• All healthcare professionals should take the
  opportunity to advise smokers to stop smoking,
  and consider referral to the NHS Stop Smoking
  Service

21
Control BP
22
Blood pressure what does NICE say?NICE
Clinical Guideline 87 May 2009

• Target BP
• lt140/80mmHg
• lt130/80mmHg if kidney, eye or cerebrovascular
  damage
• Drug choices
• ACE inhibitor (first-line)
• Add CCB or diuretic
• Add other drug (CCB or diuretic)
• Add alpha-blocker, beta-blocker or potassium
  sparing diuretic

23
ACE inhibitors first lineNICE Clinical Guideline
87 May 2009NICE Full Diabetes Guideline 66, 2008

• ACE inhibitors have no significant differences in
  CV outcomes compared with other antihypertensives
  but have greater benefits in terms of renal
  outcomes in those with type 2 diabetes
• Exceptions
• Afro-Caribbeans who should receive an ACE
  inhibitor plus either a diuretic or CCB
• Women who may become pregnant should receive a
  CCB
• Those with a continuing intolerance to an ACE
  inhibitor eg cough should substitute an A2RB

24
Blood pressure managementNICE Clinical Guideline
87 May 2009

• Targets
• If kidney, eye or cerebrovascular damage, set a
  target lt130/80mmHg
• Others, set a target , 140/80mmHg
• If on antihypertensive therapy at diagnosis of
  diabetes
• Review BP control and medication use
• Make changes only if BP is poorly controlled or
  current medications are inappropriate because of
  microvascular complications or metabolic problems
• If the persons BP reaches and consistently
  remains at the target
• Monitor every 4-6 months and check for possible
  adverse effects of antihypertensive therapy
  (including those from unnecessarily low BP)
• Measure BP annually if not hypertensive or with
  renal disease
• If BP gt target, repeat measurements within
• 1 month if gt 150/90mmHg
• 2 months if gt 140/80mmHg
• 2 months if gt 130/80mmHg and kidney, eye or
  cerebrovascular damage

25
Summary of BP management

• BP control is very important in patients with
  type 2 diabetes
• Before starting drug therapy
• Use immaculate technique and do at least two
  readings on each of three different occasions
• Drug treatment
• In general ACE inhibitors are 1st line, with CCBs
  or thiazides 2nd line
• Think about switching drug classes if no response
• No robust evidence that A2RB are superior to ACE
  inhibitors
• No evidence to suggest increased effectiveness
  with ACE plus A2RB
• Treat the patient, not the BP
• Compliance is critical a drug not taken will
  not work
• Weigh potential benefits to be gained from
  decreasing BP further against the acceptability
  to the patient of aggressive therapy with
  multiple drugs

26
Assessing cardiovascular risk
27
What about assessing CV risk?NICE Clinical
Guideline 87 May 2009

• NICE recommends annual review of CV risk
• Assess risk factors
• Note changes in personal or family history
• Perform a full lipid profile
• Consider to be at high CV risk unless all of the
  following apply
• Not overweight
• Normotensive
• No microalbuminuria
• Non-smoker
• No high-risk lipid profile
• No history of CV disease
• No family history of CV disease

28
Blood lipids
29
Management of blood lipids (1)NICE Clinical
Guideline 87 May 2009

• Offer simvastatin 40mg or a statin of similar
  efficacy or cost
• Give to those
• Aged 40 and normal to high CV risk with type 2
  diabetes
• Aged 40 and low CV risk with type 2 diabetes but
  CV risk gt20 risk when assessed using UKPDS risk
  engine
• Aged lt40 and poor CV risk factor profile
• Assess lipid profile and modifiable risk factors
  1-3 months after starting therapy. Continue to
  monitor annually
• Do not use in women who may become pregnant
  unless issues discussed and agreement reached

30
Management of blood lipids (2)NICE Clinical
Guideline 87 May 2009

• Increase to simvastatin 80mg unless TC lt4.0mmol/l
  or LDL lt2.0mmol/l
• If there is existing or newly diagnosed CV
  disease or increased albumin excretion rate
  consider intensifying therapy with or more
  effective statin or ezetimibe to achieve a TC
  lt4.0mmol/l or LDL lt2.0mmol/l

31
NICE guidance comparedNICE Diabetes CG 87, May
2009NICE Lipids CG 67, May 2008
Type 2 diabetes (CG 87 formerly 66) CV risk assessment and lipids (CG 67)
People without established CVD but gt20 10y CVD risk Simvastatin 40mg, Increase to 80mg if TC gt4mmol/l and also LDL gt2mmol/l Simvastatin 40mg No lipid target
People with established CVD (no ACS) or increased albumin excretion rate (type 2 diabetes) Simvastatin 40mg Consider intensifying with a more effective statin or ezetimibe (if primary hypercholesterolaemia) to achieve TC lt4mmol/l or LDL lt2mmol/l Simvastatin 40mg Consider increasing to 80mg if TC gt4mmol/l and also LDL gt2mmol/l
32
Lipid modification in T2DMSummary

• Lipid modification is very important
• Baseline risk is the key to the size of absolute
  benefits
• Most patients should be on a statin
• Simvastatin 40mg is first line
• Increase to 80mg if TC gt4mmol/l and also LDL
  gt2mmol/l
• If existing or newly diagnosed CV disease or
  increased albumin excretion rate consider
  intensifying therapy (with more effective statin
  or ezetimibe (if primary hypercholesterolaemia)
  to achieve TC lt4mmol/l or LDL lt2mmol/l
• NICE recommends fibrates only in particular
  circumstances

33
Aspirin
34
Anti-thrombotic therapyNICE Clinical Guideline
87 May 2009

• NICE says offer aspirin 75mg daily
• To a person who is 50 years if BP is
  lt145/90mmHg
• To a person lt50 years and has significant other
  risk factors (features of metabolic syndrome,
  strong early FH of CV disease, smoking,
  hypertension, microalbuminuria)
• MRHA advice
• Aspirin is not licensed for the primary
  prevention of vascular events. If used the
  balance of benefits and risks should be
  considered for each individual, particularly the
  presence of risk factors for vascular disease
  (including conditions such as diabetes) and the
  risk of GI bleeding

35
AspirinSummary

• Aspirin should still be offered to patients with
  diabetes and evidence of CV disease ie for
  secondary prevention of CV events
• In primary prevention a more individualised
  approach should be adopted as the presence of
  personal risk factors may change the risk
  benefit profile
• Aspirin is not licensed for primary prevention

36
Control blood glucose
37
What does NICE say?NICE Clinical Guideline 87
May 2009

• Setting a target HbA1c
• Involve the patient in decision making
• Encourage the patient to maintain their
  individual target unless the resulting side
  effects or efforts to achieve this impair their
  quality of life
• Offer therapy (lifestyle and medication) to help
  achieve and maintain the target level
• Inform the patient with a higher HbA1c that any
  reduction is advantageous to future health
• Avoid pursuing highly intensive management plans
  to level of lt 6.5

38
What does NICE say?NICE Clinical Guideline 87
May 2009

• Levels of HbA1c for addition of extra glucose
  lowering drugs
• 6.5 (or other higher level) for people on one
  oral glucose lowering drug
• 7.5 (or other higher level) for people on two or
  more oral glucose lowering drugs or insulin

39

• Intensive blood glucose control has benefits but
  also harms
• Reduction in CHD and CVD risk, but no reduction
  in mortality
• Recent studies show mixed results on
  microvascular endpoints
• Increased risk of severe hypoglycaemia
• ACCORD intensive therapy associated with
  increased risk of death
• Other interventions to reduce CV risk (smoking
  cessation, exercise, losing weight, controlling
  BP, lowering cholesterol, taking metformin) may
  have more benefit overall
• The Goldilocks effect
• Observational study identified that HbA1c of
  about 7.5 is associated with lowest risk of
  all-cause mortality (increase above or decrease
  below) is associated with greater risk

40
Drug treatment for blood glucose control
41
Hypoglycaemic drugs used in type 2 diabetesBNF
60, September 2010
Class Drug NICE guidance
Biguanidines Metformin CG87
Sulphonylureas Glibenclamide, gliclazide CG87
Rapid acting insulin secretagogues Nateglinide, repaglinide CG87
Glitazones Pioglitazone CG87
Glitazones Rosiglitazone CG87
Gliptins (DPP-4 inhibitors) Sitagliptin CG87
Gliptins (DPP-4 inhibitors) Vildagliptin CG87
Gliptins (DPP-4 inhibitors) Saxagliptin None
GLP-1 mimetics Exenatide CG87
GLP-1 mimetics Liraglutide TA203
Insulins Human NPH insulin etc CG87
Long acting insulin analogues Insulin detemir CG87
Long acting insulin analogues Insulin glargine CG87
42
Drug treatment for blood glucose controlBased on
NICE Clinical Guideline 87 May 2009
43
What does the NICE guideline say (1)NICE
Clinical Guideline 87 May 2009MeReC Rapid
review No. 355

• Same levels of HbA1c for addition of extra
  glucose lowering drugs
• 6.5 (or other higher level) for people on one
  oral glucose lowering drug
• 7.5 (or other higher level) for people on two or
  more oral glucose lowering drugs or insulin
• Metformin still first line hypoglycaemic drug
• Sulphonylurea is an option if
• Patient is not overweight
• A rapid therapeutic response is required
• Metformin is contraindicated / not tolerated
• If blood glucose control is inadequate on
  monotherapy dual therapy with metformin and a
  sulphonylurea remains the usual second line
  therapy
• Rapid acting insulin secretagogues (rapaglinide
  and nateglinide) still only recommended as a
  consideration for people with erratic lifestyles
• Other alternatives may be considered in
  particular patient circumstances

44
What does the NICE guideline say (2)NICE
Clinical Guideline 87 May 2009MeReC Rapid
review No. 355

• Glitazones (and gliptins) can be considered for
  dual therapy with either metformin or
  sulphonylurea
• Pioglitazone, sitagliptin or vildagliptin should
  be continued only if the person has a beneficial
  metabolic response (reduction of at least 0.5 in
  HbA1c in 6 months)
• Which to choose?
• Gliptin may be preferred if further weight gain
  would be a significant problem
• Glitazone may be preferred if a person has marked
  insulin insensitivity

45
What does the NICE guideline say (3)NICE
Clinical Guideline 87 May 2009MeReC Rapid
review No. 355

• Normal third line option is insulin in addition
  to metformin and a sulphonylurea
• Intermediate acting human isophane insulin (human
  NPH insulin) remains preferred basal insulin
  taken at bedtime or twice daily according to need
• Combining pioglitazone with insulin can be
  considered in a person with previous marked
  glucose lowering response to glitazone, or person
  on high-dose insulin whose blood glucose is
  inadequately controlled

46
What does the NICE guideline say (4)NICE
Clinical Guideline 87 May 2009MeReC Rapid
review No. 355

• What are the alternatives to insulin?
• Sitagliptin or glitazones can be considered for
  triple therapy with metformin and SU instead of
  insulin if insulin is unacceptable /
  inappropriate because of
• Employment
• Social issues related to hypoglycaemia
• Injection anxieties
• Other personal issues
• obesity
• Exenatide can be used for triple therapy in
  addition to metformin and SU if
• BMI 35kg/m² in people of European descent and
  specific psychological / medical problems
  associated with high body weight
• BMI lt 35kg/m² and insulin would have significant
  occupational implications or weight loss would
  benefit other significant obesity related
  comorbidities
• Exenatide should be continued only if the person
  has a beneficial metabolic response (reduction of
  at least 1 in HbA1c and a body weight loss of at
  least 3 of initial body weight at 6 months)

47
Established oral hypoglycaemics

• Metformin
• Sulphonylureas

48

• Step up dose of metformin to minimise GI side
  effects consider trial of MR metformin if
  tolerability prevents continuation
• Review metformin if serum creatinine gt 130 or
  eGFR lt45
• Stop metformin if serum creatinine gt150 or eGFR
  lt30

49
Newer agents

• Glitazones
• Gliptins
• GLP-1 mimetics

50
How do the newer drugs compare?NICE Clinical
Guideline 66 May 2008NICE Clinical Guideline
87 May 2009
Positives Negatives
Glitazones Pioglitazone Oral Similar HbA1c reductions to metformin or SU Safety concerns (HF, fractures) Weight gain Cost
Gliptins Sitagliptin Vildagliptin Saxagliptin Oral Similar HbA1c reductions to glitazones No weight gain No long term safety data Cost
GLP-1 mimetics Exenatide Liraglutide Similar HbA1c reduction to insulin Weight loss Parenteral No long term safety data Cost
51
Glitazones

• Pioglitazone

52

• Can be used 2nd line as dual therapy with
  metformin or SU if either is CI / not tolerated,
  or if significant risk of hypoglycaemia with SU
• Can be used 3rd line as triple therapy with
  metformin or SU BUT insulin preferred
• Only use glitazones if beneficial metabolic
  response
• Pioglitazone
• CI in heart failure
• Monitor for signs / symptoms of fluid retention,
  weight gain or oedema
• Stop treatment if any deterioration in cardiac
  status occurs
• Do not commence / continue in people with higher
  risk of fracture

53
Gliptins

• Oral DPP-4 inhibitors
• Sitagliptin and Vildagliptin

54

• Sitagliptin and vildagliptin can be 2nd line
  agents (at HbA1c 6.5), as dual therapy with
  metformin or SU if either of these is CI or not
  tolerated, or hypoglycaemia on SU a particular
  issue
• Sitalgliptin can be a 3rd line agent, as triple
  therapy with metformin and SU if glycaemic
  control is insufficient (HbA1c 7.5) BUT
  insulin is preferred
• Only continue gliptins if beneficial metabolic
  response
• Reduction of at least 0.5 in HbA1c in 6 months
• Only sitagliptin is licensed for use with
  metformin and a SU

55
GLP-1 mimetics

• Parenteral exenatide or liraglutide

56

• Exenatide can be a 3rd line agent as triple
  therapy with metformin and SU is glycaemic
  control is insufficient (HbA1c 7.5) and
• BMI 35kg/m² in people of European descent and
  specific psychological / medical problems
  associated with high body weight, or
• BMI lt 35kg/m² and insulin would have significant
  occupational implications or weight loss would
  benefit other significant obesity related
  comorbidities
• NPH insulin is preferred
• Can be used instead of insulin or if insulin
  unacceptable or inappropriate
• Only continue exenatide if beneficial metabolic
  response
• Reduction of at least 1 in HbA1c and weight loss
  of at least 3 of initial body weight at 6 months

57
Insulin

• Human NPH insulin
• Long-acting insulin analogues
• (insulin determir, insulin glargine)

58
What is the guidance from NICE?NICE Clinical
Guideline 87 May 2009

• Usual 3rd line option is to initiate insulin
  therapy in addition to metformin and SU
• Intermediate acting human isophane insulin (human
  NPH insulin) remains preferred basal insulin,
  taken at bedtime or twice daily according to need

59
Summary

• Increasing number of people with diabetes being
  identified and recorded
• Costs of dispensing for diabetes increasing
  markedly
• Managing type 2 diabetes is multifactorial and
  requires individualised evidence based care of
  several risk factors
• Keep it simple and safe
• Blood glucose control is important. Helping
  patients stop smoking, implement lifestyle
  changes (diet and exercise), control their BP,
  and encouraging them to take a statin and
  metformin may be more effective at preventing
  adverse cardiovascular outcomes and death than
  intensive control of blood glucose alone

60
Case studies
61

• Case 1 - Initial management of type 2 diabetes
• Case 2 - Ongoing management of type 2 diabetes
• Case 3 - Prevention of type 2 diabetes

62
Case study 1

• Ted is a 56y old salesman. He is married to
  Carol. He smokes 20 cigarettes per day and drinks
  2-3 units of alcohol per day. He spends a lot of
  time driving. Recently he has needed to pass
  urine more frequently. His older brother recently
  had a MI. Urine dipstick shows marked glycosuria
  suggesting type 2 diabetes. He does not have
  proteinuria or microalbuminuria

63
What further investigation(s) would you do (if
any) to confirm a diagnosis of diabetes to WHO
standards?
64

• WHO guidelines on definition and diagnosis says
  appropriate diagnostic tests are either
• Oral glucose tolerance test (gold standard test)
• Identifies those with impaired glucose tolerance
• Fasting plasma glucose test or
• This test alone fails to diagnose approximately
  30 of cases of previously undiagnosed diabetes
• May be a more acceptable test to have
• Dipstick has low sensitivity (missed nearly
  4/5ths of those who really have diabetes
• Random plasma glucose has poor sensitivity and
  specificity compared with the OGTT and FPG test

65

• Ted decides to have the FPG test which comes back
  at 12mmol/l
• As he has symptoms suggestive of diabetes you
  diagnose that he has type 2 diabetes on the basis
  of this single abnormal result
• If he was asymptomatic at lest one other
  additional abnormal glucose level is essential

66
When explaining the diagnosis of type 2 diabetes
to Ted what other information should be given?
67

• Education is a central part of management
• Structured education should be offered to all at
  the time of diagnosis with annual reinforcement
  and review
• The preferred format in NICE guidance are group
  educational programmes
• Suitable topics to cover include
• Nature of diabetes
• Day to day management of diabetes
• Specific issues
• Living with diabetes
• Sick day rules

68
Have structured education programmes been shown
to be effective in improving management and
reducing complications of type 2 diabetes?
69

• Teds smoking history, age, sex, family history
  and now type 2 diabetes suggest that he is at
  high risk of macrovascular (CVD eg MI and stroke)
  and microvascular disease (retinopathy, renal
  disease and peripheral neuropathy)
• Further clinical examination and blood test
  results for him are as follows
• BP 152/94mmHg
• BMI 31kg/m²
• HDL cholesterol 0.9mmol/l
• LDL cholesterol 2.2mmol/l
• Total cholesterol 5.5mmol/l
• HbA1c 7.5

70
Should you do a formal assessment to determine
Teds risk of CVD?
71

• No
• Nearly all people with type 2 diabetes are at
  high CVD risk
• People with type 2 diabetes are considered at
  high risk unless they have all of the following
• Not overweight
• Normotensive
• No microalbuminuria
• Non-smoker
• No high-risk lipid profile
• No history of CVD
• No FH of CVD
• He has type 2 diabetes, is overweight, may be
  hypertensive, is a smoker and has a FH of CVD

72
How should high risk of CVD be explained to him?
73

• He should be given information about his absolute
  risk of CVD and the benefits and harms of an
  intervention over a 10 year period using
  appropriate diagrams and text
• Use everyday jargon free language
• He should be involved in developing a shared
  management plan that will include lifestyle
  changes acceptable to him

74
What lifestyle advice should be given to him to
reduce his CV risk?
75

• Stop smoking
• Adopt a cardioprotective diet
• Take regular exercise
• Manage his weight
• Keep alcohol intake below recommended levels

76
Should Ted start taking an antihypertensive
medication on the basis of these results?
77

• No
• Offer lifestyle advice (diet and exercise) on how
  to help reduce BP
• Further measurements are required to confirm
  hypertension

78
Should Ted start taking a lipid lowering
medication on the basis of these results?
79

• Yes
• Irrespective of initial levels, people with type
  2 diabetes aged 40 years and over should be
  considered for treatment with simvastation 40mg
  daily unless they are at low CV risk
• He should start on 40mg daily and the profile
  assessed 1-3 months later. The dose should be
  increased to 80mg unless his TC is lt4mmol/l or
  his LDL is lt2mmol/l. If either figure is below
  that level increasing the dose is not recommended

80
Should Ted start blood glucose lowering therapy
immediately, and if so what is the most
appropriate 1st line treatment for him?
81

• Metformin start at low dose and step up
  gradually over weeks to minimise the risk of GI
  side effects
• Use a sulphonylurea if
• Not overweight
• Metformin contraindicated
• Rapid response required due to hyperglycaemic
  symptoms

82
What parameter should be measured to determine
blood glucose control and how should this be
monitored?
83

• HbA1c
• Measure at 2-6 monthly intervals (tailored to
  individual need) until blood glucose is stable on
  unchanging therapy
• Once blood glucose level and blood glucose
  lowering therapy are stable measure HbA1c every 6
  months

84
Should Ted monitor his blood glucose?
85

• Advantages
• Enables him to see the effects of lifestyle
  interventions on his blood glucose levels
• Disadvantages
• Time consuming
• Painful
• Potentially raises anxiety
• Unnecessary expense

86
Should Ted take an antiplatelet drug?
87

• Aspirin is effective for secondary prevention of
  CV events
• NICE recommends 75mg aspirin in those who are
• 50 years old
• If BP is lt 145/90mmHg
• New data suggests that aspirin is ineffective for
  the primary prevention of CV events in patients
  with type 1 or type 2 diabetes and asymptomatic
  peripheral arterial disease (a risk factor for
  CVD)
• Weight up pros and cons

88
Case study 2

• Two months later he has stopped smoking with the
  help of a smoking cessation service. He continues
  to drink 2-3 units per day. He has lost some
  weight and is doing more exercise but he has now
  been diagnosed with hypertension. You decide to
  offer him drug treatment for his hypertension

89
What is the first choice antihypertensive for him?
90

• Angiotensin-converting enzyme inhibitor (ACE-1)
• Exceptions
• African-Caribbean descent
• women for whom there is a possibility of becoming
  pregnant
• NICE found no significant differences in terms of
  cardiovascular (CV) outcomes when treatment with
  ACEIs was compared with other antihypertensive
  therapies
• ACEIs also failed to demonstrate superiority over
  other agents on the basis of BP-lowering power
• However, the evidence suggested that treatment
  with an ACEI is related to greater benefits in
  terms of renal outcomes in patients with type 2
  diabetes compared with other BP-lowering agents

91
What target BP is appropriate for him and how
often should his BP be monitored?
92

• Below 140/80 mmHg as there is no evidence of
  kidney, eye or cerebrovascular damage
• If Ted had any signs of kidney, eye or
  cerebrovascular damage the target would be lower,
  less than 130/80 mmHg
• Monitor BP every 1-2 months and intensify therapy
  accordingly
• If Ted's BP is not reduced to lt140/80mmHg or an
  individually agreed target with an ACEI add a
  thiazide diuretic or calcium-channel blocker
• If the target is not reached on dual therapy add
  the other drug
• If Ted's BP is still not reduced to the agreed
  target on triple therapy, an alpha blocker, a
  beta blocker or a potassium sparing diuretic (the
  last with caution if taking an ACEI or
  angiotension-2 receptor antagonist) can be added
• However, the potential benefits to be gained from
  decreasing BP ever further must be weighed
  against the acceptability to the patient of
  aggressive therapy with multiple drugs
• When Ted has attained and is consistently at his
  BP target, monitoring of BP should be every 4-6
  months.

93

• Ted attends for a further diabetes check up 8
  months after diagnosis. He has lost a bit more
  weight, is exercising and adjusted his diet. His
  initial diabetes symptoms have improved. His has
  continued to stop smoking. His BP 8 weeks ago was
  stable. He started metformin 2 months after
  diagnosis as his HbA1c had increased to 7.8. He
  is now taking 1g daily
• His current medication is
• Ramipril 5mg daily
• Bendroflumethazide 2.5mg OD
• Sinvastatin 40mg OD
• Metformin 500mg BD

94

• He injured his knee and was prescribed diclofenac
  75mg BD which he has taken regularly for 2 months
• Latest results show
• BP 138/80mmHg
• BMI 27kg/m²
• HDL 1.1mmol/l
• LDL 2.2mmol/l
• TC 3.6mmol/l
• HbA1c 8.1
• Negative for microalbuminuria / proteinuria
• He previously tried to increase his dose of
  metformin but this gave him diarrhoea

95
How concerned are you that his HbA1c is 8.1. How
would you suggest managing this?
96

• The evidence that tight control of blood glucose
  prevents complications of diabetes is
  controversial
• The UKPDS study showed that while taking
  metformin and controlling blood pressure reduces
  the risk of diabetic complications (including
  cardiovascular events and death from diabetic
  complications), controlling blood glucose using a
  sulfonylurea or insulin-based regimen had no
  statistically significant beneficial effect on
  all-cause mortality, macrovascular events or most
  microvascular events. Tight control of blood
  glucose to achieve an HbA1c of less than 6 may
  even be associated with harm
• NICE advises agreeing individual targets for
  HbA1c which may be above the aspiration of less
  than 6.5. For most people, keeping blood glucose
  levels below about 10mmol/L will prevent symptoms
  associated with hyperglycaemia and Ted should be
  encouraged to try and achieve this

97

• Also in keeping with NICE guidance, an HbA1c
  target of 7 to 7.5 is a reasonable aspiration
  for Ted given that he has expressed that he hates
  taking tablets and is not prepared to put up with
  diarrhoea again, or feeling unwell, especially as
  he is training for the walk. This may be feasible
  to attain without increasing the risk of harm,
  from possible hypoglycaemic episodes and the need
  for multiple hypoglycaemic agents
• As Ted is already taking a statin, has good
  control of his blood pressure, is leading a
  healthier lifestyle and, most important of all,
  has stopped smoking, he will have significantly
  reduced his risk of having a cardiovascular event
• Maximising the metformin regimen may be worth
  attempting. The usual maximum dose for metformin
  is 2 g/day in divided doses, so Ted is currently
  only taking one-half of the maximum licensed
  dose. The side effect of diarrhoea is usually
  transient, so Ted should be encouraged to
  persevere for an adequate trial period. Other
  gastrointestinal (GI) side effects such as
  anorexia, nausea and vomiting are more common at
  higher doses of metformin, but again may be
  transient. Taking an extra metformin 500 mg
  tablet at lunchtime rather than two tablets at
  night may reduce the GI side effects Ted
  previously experienced

98

• NICE recommend that metformin therapy should be
  stepped up gradually over weeks to minimise the
  risk of GI side effects
• NICE found that there was no evidence that the
  use of extended-release metformin preparations
  reduced GI side effects, so recommends that these
  products should only be considered for a trial
  where GI tolerability prevents continuation of
  metformin therapy
• Caution is needed when prescribing metformin, or
  increasing the dose, in people with renal
  impairment, so before increasing the dose of
  metformin Ted's renal function should be checked.
  This is particularly important as he has recently
  been prescribed and is taking diclofenac, a NSAID

99

• NICE recommends that the metformin dose should be
  reviewed if serum creatinine exceeds
  130micromol/litre or the estimated glomerular
  filtration rate is below 45mL/min/1.73 m2.
  Metformin should be stopped if serum creatinine
  exceeds 150micromol/litre or the estimated
  glomerular filtration rate is below 30mL/min/1.73
  m2. Metformin should be prescribed with caution
  in people at risk of a sudden deterioration in
  kidney function and those at risk of estimated
  glomerular filtration rate falling below
  45mL/min/1.73 m2. However, the benefits of
  metformin therapy should be discussed with a
  person with mild to moderate liver dysfunction or
  cardiac impairment so that due consideration can
  be given to the cardiovascular-protective effects
  of this drug
• Metformin is the only oral hypoglycaemic drug
  that has been shown to reduce macrovascular
  complications in high-quality randomised
  controlled trials, and it remains the drug of
  choice for first-line use in the majority of
  patients with type 2 diabetes

100
If Ted did still have symptoms and his blood
glucose remained extremely high which second
glucose lowering treatment would be the most
appropriate choice?
101

• If increasing the dose of metformin is not
  possible, and blood glucose control remains or
  becomes inadequate with metformin alone, then a
  sulphonylurea drug should be added. NICE
  recommend a sulphonylurea with a low acquisition
  cost (but not glibenclamide)
• A recent systematic review found that newer, more
  expensive oral hypoglycaemic agents offer no
  advantages over metformin and sulphonylureas. In
  addition, the evidence of benefit for newer
  agents on patient orientated, clinical outcome
  data, such as effects on CV endpoints, is very
  limited
• Thiazolidinedione (glitazone) treatment is also
  an option in people with HbA1c levels of at least
  6.5 either in addition to a sulphonylurea if
  metformin is not tolerated or contraindicated, or
  in addition to metformin if a sulphonylurea is
  not appropriate eg if hypoglycaemia is a
  particular issue. However, there is less
  experience with these drugs and there are on
  going safety concerns

102
If Ted wished to use insulin to control his blood
glucose what would be the preferred regimen?
103

• NICE recommend intermediate acting human isophane
  insulin (or human NPH insulin as it is also
  called) as the preferred basal insulin, taken at
  bed-time or twice-daily according to need
• For Ted they would recommend continuing metformin
  and sulphonylurea treatment when insulin is
  initiated, reviewing the use of the sulphonylurea
  if hypoglycaemia occurs
• If using insulin is likely to be unacceptable to
  Ted or ineffective, NICE suggest that glitazones
  can be added to metformin and a sulphonylurea

104
If considering glitazone treatment what issues
should be discussed with Ted?
105

• Lack of evidence of long-term benefit from taking
  a glitazone
• There is no convincing evidence that
  patient-orientated outcomes, such as mortality,
  morbidity, adverse effects, costs or quality of
  life, are positively influenced by either
  pioglitazone or rosiglitazone
• There is consistent evidence that both
  rosiglitazone and pioglitazone can cause weight
  gain, fluid retention, and lead to new or
  worsening heart failure. This is not a rare
  occurrence, and can be serious and sometimes
  fatal
• Glitazones increase the risk of fractures. This
  has been seen in women, not men

106
Should Ted continue to monitor his blood glucose?
107

• As Ted has established diabetes relatively
  well-controlled with oral drugs and monitors his
  blood glucose infrequently, little is to be
  gained in promoting self-monitoring blood glucose
  (SMBG), even with an education programme
• SMBG should be reserved for patients with type 2
  diabetes treated with insulin and conceivably, in
  some very specific circumstances, such as
  patients who are at risk of hypoglycaemia during
  intercurrent illness or fasting
• Attention and resources could then be directed to
  interventions likely to make a difference to
  patients' symptoms and CV risk, these include
  support and advice around nutrition, exercise,
  smoking cessation, and foot care, etc

108
What concerns would you have regarding Ted taking
a NSAID?
109

• NSAIDs can cause GI, CV and renal side effects,
  all of which are relevant to Ted
• As Ted is at high risk of a CV event due to his
  type 2 diabetes, smoking history, history of
  hypertension and his family history, and has had
  GI side effects with metformin already, it is
  appropriate to review the need for an NSAID, and
  consider conventional analgesia and/or
  non-pharmacological management of his knee
  problem
• If treatment with an NSAID is essential the
  choice of drug should be reviewed

110

• Diclofenac 150 mg/day appears to be associated
  with an excess risk equivalent to about 3 extra
  CV events per 1000 users treated for 1 year.
  Low-dose ibuprofen (less than or equal to 1200
  mg/day) and naproxen (1000 mg/day) appear to be
  associated with a lower risk, so may be a more
  appropriate anti-inflammatory drug choice for
  Ted, as he is already at high risk of a CV event
• Of the traditional NSAIDS, low-dose ibuprofen is
  associated with a lower GI risk than diclofenac
  and naproxen. Clinicians should consider
  prescribing a proton pump inhibitor (PPI) with
  any NSAID to reduce the risk of adverse GI
  effects, particularly in those who are at high GI
  risk (includes anybody aged 65 years or older)
  and long-term NSAID users
• NSAIDs can provoke renal failure, especially in
  patients with renal impairment, and this can
  limit the utility of many drugs but for Ted it
  can cause problems with metformin in particular