Title: GP VTS Programme Diabetes: Hot topics and case histories
1GP VTS ProgrammeDiabetes Hot topics and case
histories
- Dr Masud Haq
- Consultant in Diabetes Endocrinology
- Maidstone Tunbridge Wells NHS Trust
11th Feb 2009
2Diabetes - WHO 2002 criteria
- Symptoms of diabetes plus
- - FPG 7.0 mmol/l
- (fasting for at least 8hrs) OR
- - Random PG 11.1 mmol/l
- In the absence of symptoms
- 2 FPG 7.0 mmol/l OR
- 2 random PG 11.1 mmol/l OR
- 11.1 mmol/l 2hrs post OGTT
3Classification of diabetes
- Type 1 (previously IDDM)
- ?-cell destruction
- Autoimmune or idiopathic
- Type 2 (previously NIDDM)
- Insulin resistance
- Progressive ?-cell failure
Other types Maturity onset diabetes of the young
(MODY) Genetic defects of ?-cell function or
insulin action Disorders of exocrine
pancreas Endocrinopathies Drug induced
(steroids) Gestational diabetes
World Health Organization. Definition, diagnosis
and classification of Diabetes Mellitus and its
complications. Geneva WHO, 1999.
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5WHO 2002
6How common is Diabetes in West Kent Primary Care
Trust ?
674,000 residents 23,082 people with diabetes
26,771 by 2010 29,195 if obesity continues to
rise
Acute NHS Trusts
Quality and Outcomes Framework Data (Dept of
Health) 2007 PBS Diabetes Population
Prevalence Model Phase 2 (YHPHO)
7Why is the local population at risk?
- Prevalence of obesity trebled since 1980
- Growth in over 65yrs population by 54 in next
25yrs
Annual Public Health Report (West Kent PCT)
2007
Cost to NHS considerable
- 10 of all hospital expenditure
- highest single prescribing budget cost (500
million per yr)
Prescribing for Diabetes in England (NHS
Information Centre) 2007
8Magnitude of Diabetes
- Approx. 2 million people in UK
- Approx. 85 - 90 due to T2DM
- Prevalence of T2DM 6 of all adults
- 5 fold increase in last 40 yrs
- earlier age of onset
Diabetes UK 2007
9Case histories
10Case 1
- 35yr woman
- Type 2 diabetes Rx rosiglitazone and metformin
(recent HbA1c 10) - Other Rx - statin
- Background retinopathy and microalbuminuria
- Overweight
-
- Wants to fall pregnant
-
11What issues do you need to discuss?
- Glycaemic Control
- Renal function
- Last retinal screen
- Complications
- Drugs
- Weight
- Folate
- Need for contraception
12Confidential enquiry in maternal and childrens
health (CEMACH 2002)
- Women with diabetes have high risk pregnancies,
their babies - x5 stillborn
- x3 die in first month
- x2 congenital malformation
- x2 macrosomia
- x5 preterm
13Risks of diabetes in pregnancy
- Congenital malformation
- Miscarriage
- Fetal macrosomia
- Birth trauma
- Stillbirth / neonatal death
- Need for induction / caesarian section
14Pre-conception care
- Benefits of pre-conception glycaemic control
- Avoid unplanned pregnancy
- Use contraception
- Review drugs stop statins, ACE inhibitors,
ARBs, glitazones, weight loss drugs - Metformin and insulin are both safe
- Start folate 5mg od until 12 weeks gestation
- Stop smoking
- Please refer to pre-conception diabetes clinic
for advice
15Case 2
- 45 year old male
- 2 yr history of urinary frequency and 6kg weight
loss - 12 months of lethargy
- FH Mother coeliacs disease
- O/E BMI 22
- No ketones
16Case 2 (Continued)
- Commenced on gliclazide
- But converted to insulin therapy within a month.
17Case 2 Question
- What type of diabetes has this patient got ?
- Type 1 diabetes
- Type 2 diabetes
- Something else
18Latent Autoimmune Diabetes of Adulthood (LADA)
- Known as slow-onset type 1
- Slowly progressive form of autoimmune diabetes
- Features of both type 1 and type 2 diabetes
- May account for up 10 of all diabetes patients
19Features of LADA
- Age at diagnosis (gt30 yrs)
- Presentation as for type 2 (non-ketotic) but
often normal / low body weight - May be other autoimmune diseases (or family
history) - Usually no family history of type 2 diabetes
- Positive pancreatic autoantibodies
- Low C-peptide levels
20MODY
- Rare hereditary form diabetes mellitus (autosomal
dominant) - Onset of diabetes before 25 years of age
- Non-ketotic non-insulin dependent at
presentation - Negative pancreatic autoantibodies
- Diagnosis-
- Mild hyperglycaemia is often detected at routine
screening - Fasting glucose is elevated
- Oral glucose tolerance test is less elevated than
expected
21Genetics of MODY
MODY 2 Glucokinase (14)
MODY X (11)
Transcription factors (75)
MODY 1 HNF4? (3)
MODY 3 HNF1? (69)
MODY 4 IPF-1 (lt1)
MODY 5 HNF1 ? (3)
MODY 6 NeuroD1 (lt1)
22Not all diabetes is type 1 or type 2
- MODY patients have strong family history
- MODY 2 needs no treatment has no long-term
complications - MODY 3 is v. sensitive to sulphonylureas can ?
diabetic complications
- LADA patients may have other autoimmune diseases
- Pancreatic autoantibody positive
- Likely to need insulin
- Risk of diabetic complications
23Case 3
- 50 year old female
- Type 2 diabetes (diagnosed age 35)
- Osteoarthritis, hyperlipidaemia, obstructive
sleep apnoea - DH Gliclazide 160 mg bd
- Metformin 1 g tds
- Atorvastatin 40 mg od
- Ramipril 10mg od
24Case 3 (Continued)
- BMI 45
- BP 160/80
- No complications
- HbA1c 13.1
- eGFR normal
25Case 3 Questions
- 1. What key issues need to be addressed ?
- 2. What is the next move to help
- a) diabetes ?
- 3. Any other therapeutic strategies ?
26Case 3 Key Issues
- Lifestyle diet, weight, exercise
- Drug compliance
- BP
- Hyperlipidaemia
27Case 3 options
- Low dose aspirin
- anti-obesity agents ?
- Exenatide ?
- Insulin ?
- Obesity surgery ?
28- What are Incretin Hormones?
29The Incretin Effect is Reduced in Subjects with
Type 2 Diabetes
The Incretin Effect accounts for 60 of total
Insulin release following a meal
Time (min)
Nauck MA, et al. Diabetologia
1986294652. P .05
compared with respective value after oral load.
30GLP-1 effects in humansUnderstanding the
natural role of incretins
GLP-1 secreted upon the ingestion of food
5.Brain promotes satiety and reduces appetite4,5
2.a-cell suppresses postprandialglucagon
secretion1
3.Liver reduces hepatic glucose output2
1.?-cellenhances glucose-dependent insulin
secretion in the pancreas1
4.Stomach slows the rate of gastric emptying3
Adapted from 1Nauck MA, et al. Diabetologia
199336741744 2Larsson H, et al. Acta Physiol
Scand 1997160413422 3Nauck MA, et al.
Diabetologia 19963915461553 4Flint A, et al.
J Clin Invest 1998101515520 5Zander et al.
Lancet 2002359824830.
31Exenatide (byetta)
- 1st GLP 1 analogue
- Twice daily sc injection
- Initial 5mcgs bd then 10 mcgs bd maintenance dose
- European licence late 2006
- Long acting once weekly preparation in pipeline
32Benefits
- Sustained weight loss (can be substantial)
- HbA1c reduction (1-2 or more)
- Beneficial effect on lipids and BP
- Possible benefit on LV function ??
33Side effects
- GI
- - nausea vomiting most freq problems
- - also diarrhoea, very rarely pancreatitis
- Hypoglycaemia
- - rare and only if concurrent sulphonylureas
- Antibodies
- - but not assoc. with any effect on outcome or
adverse events -
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35Oral incretin mimetics - gliptins
36Sitagliptin (Januvia) use in T2DM
- License combination therapy with
- either metformin or sulphonylurea or glitazone
- add on to metformin plus sulphonylurea
- - Tablet form
- - Weight neutral
- - Modest reductions in HbA1C
- - Expensive
- Pembury Diab Centre-
- limited use to pts with previous hypoglycaemia
and/or allergic reaction to sulphonylureas
37Gliptins
- Side-effects-
- GI effects nausea, vomiting
- Nasopharyngitis, skin rash
- Safety-
- Animal studies using non-selective DPP-IV
inhibitors skin and neurological toxicity - Selective DPP-IV inhibitors (eg., sitagliptin)
long-term effects ?? unknown
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40Case 4
- 75 year old female
- Type 2 diabetes
- Hypertension hyperlipidaemia
- DH Gliclazide 80 mg bd
- Metformin 1 g bd
- Perindopril 4 mg od
- Amlodipine 5 mg od
- Simvastatin 40 mg od
- Aspirin 75 mg od
41Case 4
- BMI 34
- BP 154/84
- Retinopathy (previous laser therapy)
- Mild peripheral neuropathy
42Case 4 (Results)
43Case 4 Questions
- What would you do with metformin?
- Stop it?
- Continue on same dose? yes
- Increase dose?
- Decrease dose?
- Something else?
44Case 4 Questions
- What would you do with perindopril?
- Stop it?
- Continue on same dose?
- Increase dose? yes
- Decrease dose?
- Something else?
45Case 4 Questions
- What would be a reasonable BP target ?
- lt 140/80?
- lt 135/80?
- lt 130/80? desirable
- lt 120/70? ideal
46Chronic kidney disease
47Metformin and CKD
- Clinical scenario 1
- Rapidly declining eGFR falling to below 50
ml/min - Action
- Stop metformin.
- Investigate cause for marked decline in renal
function.
48Metformin and CKD
- Clinical scenario 2
- eGFR between 40-50 ml/min over long period of
time with no change - Action
- Continue metformin.
- Advise to stop metformin temporarily during
acute illness, especially assoc. with dehydration.
49Metformin and CKD
- Clinical scenario 3
- Two consecutive eGFR measurements below 40
ml/min - Action
- Stop metformin.
- Consider other OHA if necessary (gliclazide is
safest) or insulin.
50Glitazones concerns raised
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52Does NOT appear to be a class effect
53West Kent guidance on the use of glitazones
- For new pts, pioglitazone (PG) is the glitazone
of choice when indicated - Rosiglitazone (RG) not recommended for pts with
IHD or PVD - Consider stopping treatment if HbA1C has not
fallen by at least 1 from start despite maximal
doses - Avoid glitazone use in pts with heart failure
- Action plan for GPs-
- Option 1 - switch all pts from RG to equivalent
dose PG - Option 2 - pts with any history of IHD or PVD
switch to PG - Option 3 - pts with active or significant IHD or
PVD switch to PG
54Lipid management in Diabetes
- 1 prevention
- Statins if 10yr risk gt20
- All type II diabetics with total cholesterol gt
3.5 - All type I gt 40yrs treated with a statin
- Some higher risk type I and II diabetics aged 18
- 40
55Decision to treat
Simvastatin 40 mg
Total cholesterol lt4
Total cholesterol gt4
Simvastatin 80 mg Alternative statin /- Ezetimibe
Monitor
Specialist review
56Hypertension
- Hypertension doubles CV risk in diabetics
57Who to treat
lt130 80
gt130 80
Confirm over 4 8 weeks
130 - 139 80 - 89
gt140 90
Consider lifestyle changes Reassess at 3
months Commence drug treatment if fails to
achieve target
Commence drug therapy
Reassess yearly
58Decision made to treat
ACE i or AIIRB
NB Microlbuminuria or albuminuria
Calcium Channel blocker Thiazide
diuretic ß-blocker
BP difficult to control / renal
insufficiency Consider Renal artery stenosis
59ACEi for all diabetics?
- Micro - HOPE
- Diabetic established CHD or 1 risk factor
- Placebo vs Ramipril
- Significant reduction in
- CV death, stroke, MI
- Development of diabetic nephropathy
- Need for revascularisation
60Aspirin for all diabetics?
- US Physicians health study
- 5 years follow up
- MI reduced from 10 to 4
- HOT trial
- Aspirin reduced MI risk by 36
- Aspirin 75mg od for diabetics gt 40 or younger
with additional risk factors
61 NICE 2008
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63Lowering HbA1C reduces the risk of diabetic
complications
- In intensively-treated patients, HbA1c was 7.0
compared with 7.9 in conventionally-treated
patients - This decreased HbA1C (equivalent to an 11
reduction over 10 years) is associated with a
reduction in risk for diabetic complications
-12
Any diabetes-related endpoint
Significant
-16
Myocardial infarction (MI)
Borderline significance
Retinopathy
-21
Significant
-22
Cataract extraction
Borderline significance
-25
Microvascular endpoint
Significant
Albuminuria at 12 years
-33
Significant
0
-10
-20
-30
-40
-50
Reduction in risk ()
UK Prospective Diabetes Study (UKPDS) Group (33).
Lancet 1998 352 837853
64Thankyou