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					2nd Edition August 2000

NOTTINGHAM GUIDELINES ON THE MANAGEMENT OF DIABETES
These guidelines replace the earlier version dated May 1998
OBJECTIVES Of the estimated 13,000 patients with diabetes in Nottingham Health District about 7000 are looked after entirely in Primary Care. These guidelines have been produced by the Nottingham Diabetes Services Liaison Group to help Primary Health Care Teams provide optimal care for their patients with diabetes. They are also intended for the many secondary care clinicians outside the specialism who manage people with diabetes, e.g those dealing with Health Care of the Elderly.  Section 1 - Clinical management guidelines These are a consensus view of Diabetologists at both Trust Hospitals and incorporate, where available, national and international recommendations on standards of care for the management of hyperglycaemia, hypertension and hyperlipidaemia. Section 2 - Resources Information on the resources available locally in primary and secondary care and how they can be accessed.

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DEVELOPMENT  These guidelines update the 1998 version. Contributors include:
Simon Page Pat Clarke Renee Page Bernie Kirk Alan Birchall Lesley Danks Helen Ramwell Jean Pearson Martin Hughes Consultant Physician Diabetes Specialist Nurse Consultant Physician Diabetes Specialist Nurse General Practitioner Specialist Dietician Specialist Dieticians Group Dietetic Service Manager Chiropody Services Manager Nottingham University Hospital Nottingham University Hospital Nottingham City Hospital Nottingham City Hospital Nottingham City Central PCG Nottingham City Hospital Nottingham Community Health Nottingham Community Health Sherwood Health Centre

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The guidelines will be reviewed annually and, in the event of significant changes resulting from new research findings, the guidelines will be updated. It is anticipated that revised guidelines will be produced every two years. Guidelines are meant to guide and inform and should not be rigorously applied in all clinical circumstances. Good clinical practice always involves weighing the advantages and disadvantages of a clinical intervention depending on individual circumstances
Tel: 0115 924 9924 ext 44464 Fax:0115 9701080 E-mail simon.page@qmcuh-tr.trent.nhs.uk

If you have comments on the content of the guidelines, please contact:
Dr Simon Page Department of Diabetes, Endocrinology and Clinical Nutrition, University Hospital Nottingham NG7 2UH

2nd Edition August 2000

Section 1 DIABETES MANAGEMENT GUIDELINES

Contents
Diagnosis of diabetes Gestational Diabetes Does the Patient Need Insulin? Management of Type 2 diabetes    Diet Simple dietary guidelines Patient Education 3 4 5 6 6 7 7 8 9 9 9 9 10 10 10 10 11 12 13 14 15 16 17 17 18 19 20 21 22

Treatment of Hyperglycaemia in Type 2 diabetes Established Oral Hypoglycaemic Drugs

  Sulphonylureas   Biguanides   Alpha-glucosidase inhibitors  Newer oral hypoglycaemic drugs and combination with insulin    Prandial glucose regulators   Thiazolidinediones   Tablets and insulin Monitoring diabetic control  Proteinuria and microalbuminuria Hypertension management in type 1 diabetes Antihypertensive drugs for type 1 diabetes Hypertension management in type 2 diabetes
Antihypertensive drugs for type 2 diabetes Hyperlipidaemia   Secondary prevention Primary prevention

Diabetes and contraception Erectile dysfunction and diabetes The Annual Review Referral Guidelines

2nd Edition August 2000

Diagnosis of Diabetes
A high index of suspicion is needed as up to 50% of cases remain undiagnosed. Symptoms
       Polyuria Polydipsia Weight loss Lassitude Blurred vision Urinary or genital infection Skin infection including pruritis

High Risk Patient Groups
       Age over 40 years Family history of diabetes Obesity especially with central distribution South Asians and Afrocaribbeans History of gestational diabetes Patients with ischaemic heart disease, claudication or hypertension Patients with cataract

Confirmation of the diagnosis requires a LABORATORY plasma glucose. Capillary glucose measurements are not sufficient. The World Health Organisation recommended new diagnostic criteria for diabetes from 1st June 2000 with a lower fasting glucose of 7.0 rather than 7.8 mmol/l. Criteria for diagnosing diabetes mellitus are shown in the box:

Criteria for diagnosing diabetes mellitus
Patient with symptoms of diabetes  Random venous plasma glucose ≥ 11.1 mmol/l OR  Fasting plasma glucose ≥ 7.0 mmol/l OR  2 hour plasma glucose ≥ 11.1 mmol/l after 75g oral glucose (OGTT) Asymptomatic patient Two samples, either random, fasting, or after OGTT are needed to confirm the diagnosis. Samples should be taken on different days Most cases can be confirmed with a random glucose measurement and an OGTT is often not necessary

Other diagnostic categories  Impaired glucose tolerance (IGT) 

Fasting glucose 2 hour glucose Fasting glucose

< 7 mmol/l ≥ 7.8 but <11.1 mmol/l ≥ 6.1 but < 7.0 mmol/l

Impaired fasting glycaemia (IFG)

IGT and IFG are not clinical entities but should be considered as risk categories for cardiovascular disease and/or future diabetes

Protocol for 75g Oral Glucose Tolerance Test (OGTT) Baseline plasma glucose after a 12 hour fast (water only for comfort). Give 75g oral glucose equivalent to: Lucozade 500ml bottle Lucozade 345, 739, 1L and 1.5L bottles and cans 449 ml 419 ml  Repeat plasma glucose 2 hours later.  Send sample to laboratory (diagnostic criteria shown above).  Patients should refrain from smoking/exercise during the test.
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Gestational Diabetes

2nd Edition August 2000

High Risk
      Prior gestational diabetes th Prior macrosomic baby (97 centile for gestational age approx 4kg at birth) Prior unexplained intrauterine death st Family history (1 degree relative with diabetes) Obesity (BMI >35) Polycystic ovary syndrome 

Emergent Risk 
Large for dates baby th (FAC >97 centile) Polyhydramnios 

Low Risk
Others

Usual antenatal care

Refer to hospital antenatal clinic

Test for glycosuria at each antenatal visit

No Refer for consultant booking

Glycosuria present

Check random glucose and note last time of meal

Glucose > 9mmol/l

Glucose >6mmol/l fasted 7-9 mmol/l within 2 hrs of meal

Glucose < 6 mmol/l fasted <7 mmol/l within 2 hrs of meal

Check urine ketones

Present

Absent

Possible type 1 diabetes Immediate referral diabetes unit

Refer next diabetic antenatal clinic

Refer for OGTT*

Diabetes unlikely

Notes
     The risk of gestational diabetes (GDM) increases with the duration of pregnancy - a normal OGTT in early pregnancy does not exclude the possibility of later GDM. There is no universal agreement about the interpretation of the OGTT in pregnancy. Patients with fasting glucose ≥ 6 or 2 hrs ≥ 9 mmol/l will generally require specialist supervision but this will depend on the individual patient. *Maternal fetal surveillance unit (MAFSU) ext. 45181 at CHN or Pregnancy Assessment Centre (PAC) ext 44873 at UHN 75g OGTT is required at 6-8 weeks and will normally be arranged by the hospital. Women with gestational diabetes have a 50% risk of developing Type 2 diabetes over the following 15 years. The following is recommended: - advice about diet and exercise - annual fasting blood glucose - counselling and assessment prior to future planned pregnancy

Post- Partum

Does the patient need insulin?

2nd Edition August 2000

Algorithm for deciding whether a patient needs immediate insulin treatment
Typical symptoms and a diagnostic blood sugar (Random  11.1 mmol/l)

YES
Is the patient ill (vomiting or semiconscious)?

YES

Admit to hospital

NO
Is there moderate/heavy ketonuria?

YES

Strong indication for insulin

NO
Are one or more of the following present?  Severe symptoms (nocturia x 3-4)  Short history (weeks)  Marked weight loss (irrespective of absolute weight)  A first degree relative with type 1 diabetes  A personal history of autoimmune disease

YES

Two or more are a strong indication for insulin

NO
Is the patient under 30 years of age?

First degree relative on diet or tablets consider Maturity Onset Diabetes of the Young (MODY)

YES
No immediate need for insulin Consider non-urgent referral

NO
No immediate need for insulin. Dietary advice based on healthy eating principles

Contact telephone numbers for advice or referral for insulin therapy
UHN 9249924 Dr SR Page Dr P Mansell Prof SP Allison Diabetes Unit Diabetes Specialist Registrar NCH 9691169 Dr RCL Page Dr NDC Sturrock Dr WJ Jeffcoate Dr F Game Diabetes Centre Diabetes Specialist Registrar Secretary Secretary Secretary Secretary Direct line via switchboard Secretary Secretary Secretary Secretary Manager via switchboard 44464 43834 43862 41215 9709215

46638 46200 46201 34161 46812

2nd Edition August 2000

Management of type 2 diabetes

Diet
The aims of dietary treatment of diabetes are to:  minimise symptoms of hyperglycaemia.  minimise the risk of hypoglycaemia.  minimise the long term macro- and microvascular complication of diabetes. To achieve this dietary advice should aim to:  minimise fluctuations of blood glucose to as near normal as possible.  promote weight loss in people who are overweight.  reduce the risk of coronary artery disease. The recommended diet follows the UK healthy eating guidelines. Advice on diet should be offered following assessment of:  lifestyle.  social circumstances.  current intake.  readiness to make changes to diet and lifestyle. Dietary changes should be negotiated with each patient using the following general principles:  Existing eating habits should be modified rather than an attempt made to totally change the patient's pattern of eating.         Total calorie intake should be restricted to that needed to achieve and then maintain an agreed target weight. At least half of the energy intake should comprise carbohydrate with the majority in the form of complex carbohydrate, with a high fibre content, especially soluble fibre. Fruit and vegetables should be increased to at least 5 portions/day to achieve recommended antioxidant intake. The intake of refined carbohydrate, especially sugary food and drinks should be reduced. Total fat should be reduced and saturated fat replaced with monounsaturated and polyunsaturated fats. Dietary salt should be reduced. Alcohol should be drunk only in moderation. Special diabetic products are high in calories, are likely to cause gastrointestinal upset and are not recommended.

2nd Edition August 2000

Dietary Guidelines
The following information should be given to all patients with diabetes:   Eating, Drinking and Diabetes – a Guide for You. This is a booklet giving comprehensive dietary advice on the dietary management of diabetes. AND/OR Healthy Eating for Diabetes – Advice for Lowering Blood Sugar Levels This is an A4 sheet giving basic guidance on dietary management of diabetes.

These are both available from Nutrition and Dietetic Services, Nottingham Community Health, Linden House, 261 Beechdale Road, Aspley Nottingham NG8 3EY. Telephone 0115 9428744.

Patient Education
People learn partly by what they are told or read, but mainly from their own experiences of living with the condition. For example, hypoglycaemia can be explained but is often meaningless until the individual has experienced the symptoms. The education of diabetes needs to be specific to individual needs. This is best achieved by one to one conversation with the doctor, nurse, dietitian or chiropodist or by group teaching sessions. It is important that the information given is accurate, clear, concise and not conflicting or ambiguous. The following are a few points to consider when providing education to the patient with diabetes:  Allow sufficient time.        Avoid information overload - it is important to proceed at an appropriate pace for each patient. Be aware of the patient's saturation point. Ensure that everyone is saying the same things. Use information booklets but be aware of the contents. Written material should enhance teaching, not replace it. Messages often need to be re-iterated several times. Much of what is said is forgotten, not heard or not understood. Include a relative or friend where appropriate. Be aware of language and cultural implications. Education needs to be recorded as having been done. Education may have legal implications e.g. driving and hypoglycaemia, DVLA and insurance and employment.

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To facilitate the education process it is useful to use a checklist. An example of a checklist is included and can be copied for use in the practice.

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Treatment of hyperglycaemia in type 2 diabetes
BMI = weight/height2 (kg/m2)

Diet for 6 weeks - 3 months Glycaemic target achieved?

NO
Normal weight (BMI 20- 25) Gliclazide 40-80mg od Overweight (BMI 25-30 ) or Obese (BMI > 30) Metformin 500mg bd

YES

Review every 3-6 months

Dose adjustment every 1-3 months to optimise glycaemic control or maximum tolerated dose reached Glycaemic target achieved?

NO
Add metformin 500 mg bd Consider glitazone Add gliclazide 40-80mg od Consider glitazone

YES

Review every 3-6 months

Dose adjustment every 1-3 months to optimise glycaemic control or maximum tolerated dose reached Glycaemic target achieved?

NO
Trial of insulin

YES

Review every 3-6 months

A glycaemic target should be set for each patient.
  Tight control (HBA1c<7.0%) is an appropriate aim for most patients under 70 providing they are not having frequent hypoglyaemia. In the very elderly, symptom control is the priority.

Approximate comparisons between fasting glucose and DCCT-corrected HBA1c are shown below. These only apply in type 2 diabetes. Fasting glucose (mmol/l) HBA1c Control <7.0 < 6.7% Excellent <8.0 < 8.0% Acceptable <9.0 <9.5% Poor >9 >9.5% Very poor

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Established oral hypoglycaemic drugs

Sulphonylureas
      We recommend Gliclazide, initially 40-80 mg od, with titration every 4-6 weeks to achieve glycaemic target or until maximum dose of 160mg bd is reached. Tablets should be taken before meals. Adding a second sulphonylurea in a patient already taking maximum doses of one will NOT improve glycaemic control but may increase the risk of side effects. Weight gain averaging 2-4 kg is a recognised consequence of sulphonylurea therapy; in some patients it may exceed 10kg. Always re-assess the patient and emphasise dietary compliance before prescribing. ALL patients should be told about recognition and management of hypoglycaemia when prescribed a sulphonylurea. AVOID long acting sulphonylureas, (Glibenclamide and Chlorpropamide) in patients over 70 yr and in those with poor renal function. We do not recommend changing established patients to shorter acting agents unless there is a clinical indication. The newer long-acting sulphonylurea (Glimepiride) may offer advantages of a lower risk of hypoglycaemia and less weight gain compared with glibenclamide.

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Metformin
       Start with 500mg daily for 1-2 weeks. Titrate every 2-4 weeks to achieve glycaemic target or until the maximum dose of 1 gram tds is reached. Tablets should be taken with or immediately after a meal. Not associated with weight gain - hence first line therapy in overweight patients. Diarrhoea occurs in up to 20% and may limit its use. Diarrhoea is dose dependent and may resolve with dose reduction. AVOID in patients with creatinine >150 µmol/l, severe heart failure or severe liver disease because of the increased risk of lactic acidosis. Metformin should be stopped 48 hours before any radiological procedure needing intravenous contrast.

Acarbose
     Useful in occasional overweight patients in whom metformin is contraindicated. Start with 25-50 mg daily and titrate to 50mg - 100mg tds over several weeks. Tablets should be taken with the first mouthful of a meal. Up to 50% of patients unable to tolerate Acarbose because of gastrointestinal side effects. Dose reduction in renal or hepatic disease not necessary.

All patients who remain symptomatic or who do not achieve their glycaemic targets despite two oral hypoglycaemic drugs should be considered for a trial of insulin

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Newer oral hypoglycaemics and combinations with insulin

Prandial glucose regulators (Repaglinide)
     Repaglinide stimulates insulin release from the pancreas. It is rapidly absorbed and has a short half-life (~1hr). Take immediately before meals to provide improved glucose control in the post-prandial state. Repaglinide is as effective as other sulphonylureas (anticipated HBA1c fall of 1-1.5%) and may offer advantages to patients who want flexibility with mealtimes. Expensive relative to established sulphonylureas.

Thiazolidinediones (Glitazones)
   New class of oral hypoglycaemic agent. Reduces insulin resistance and increases glucose uptake into peripheral tissues. As a result of the effect on insulin resistance, plasma insulin levels are reduced. Two agents– rosiglitazone (Avandia – Smithkline Beecham) and pioglitazone (Actos – Takeda) will receive approval this year. Oral medication – both Avandia and Actos taken once daily. Licensed for ‘add on’ therapy in patients already taking an established oral hypoglycaemic drug when intolerant of established oral hypoglycaemic agent Anticipated falls in HBA1c of approximately 1%. No additional risk of hypoglycaemia when combined with sulphonylurea. Side effect profile includes fluid retention (mild ankle oedema) and a small fall in haemoglobin concentration. Avoid in patients with class I-IV NYHA heart failure. No current indication of liver toxicity with either drug (compared with troglitazone). With rosiglitazone, monitoring of liver function tests recommended at baseline and every 2 months for the first year and periodically thereafter. Discontinue glitazone therapy if the ALT increases above 3 times the upper limit of normal. The National Institute for Clinical Excellence (NICE) endorsed the use of Rosiglitazone in August 2000.

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Combination therapy: Tablets and insulin
    Combination of metformin and insulin is becoming increasingly popular because shortterm studies have show advantage in limiting weight gain compared with insulin alone. Common regimens – 30/70 mixed insulin and metformin both twice daily Twice daily metformin and bedtime NPH insulin Metformin/insulin combination indicated particularly in overweight patients transferred to insulin and in those who gain excessive amounts of weight on insulin. Combination of insulin with a glitazone is logical and does provide an ‘insulin sparing’ effect with improved control. NOT CURRENTLY LICENCED . Combination of sulphonylurea with insulin can be useful especially when transferring to insulin.

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Monitoring diabetic control

Type 1 diabetes
    Most patients should be taught self-blood glucose monitoring. A wide choice of meters is available. Patients can view a selection at the diabetes unit at UHN or Edward's Lane Diabetes Centre. Patients vary in how often they test. An 'ideal' would be a four-point profile twice weekly but relatively few keep this up long-term. Many use testing occasionally when they feel unwell or ‘want to know’. A few do no tests at all. Testing is only part of the process of improving glucose control. Unless results are interpreted and diet or insulin adjusted glycaemic control will not improve.

50% of self-monitored glucose measurements are inaccurate, usually due to operator error. Patients, doctors and nurses using blood glucose monitoring with or without a meter MUST RECEIVE APPROPRIATE EDUCATION

Type 2 diabetes
 Most should do urinalysis. Advantages and disadvantages of each of the available test strips are shown below. Time (s) 30-60 Comment Accurate and sensitive. Also allows testing for protein, ketones and leucocytes Not quantitative, useful only as a screening test Accurate and sensitive. Scale rather elaborate. Can be read after 120 sec with no loss of accuracy Difficult to distinguish between 0.5, 1 and 2% in poor light. Must be read at 30 seconds for accurate result. Colour change inhibited by heavy ketonuria
Relative cost

Test strip Range Up to 55.5 BHR Medi-test mmol/l Clinistix Diabur Test 5000 Diastix Low/medium /high Up to 5%

Cheapest Most expensive Mid-range

10 120

Up to 2%

30

Mid -range

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Testing should be done twice weekly - before breakfast - 2 hours after the largest meal Some patients should be taught self blood glucose monitoring - where there is a low renal threshold - to assess control to decide if transfer to insulin is needed - personal preference

HBA1c
 Both hospitals now provide a DCCT-standardised HBA1c assay.

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Diabetes and sick day rules
Key points  Intercurrent illness may cause a deterioration of glucose control and an increased risk of diabetic   
ketoacidosis. All insulin-treated patients should be familiar with the SICK DAY RULES (see below) and be provided with a supply of soluble insulin (e.g. disposable pen). Patients with type-1 diabetes should have foil wrapped ketostix (Ames) available. Checking BOTH the blood glucose AND urine for ketones is an ESSENTIAL part of the assessment of ANY patient with diabetes who is unwell irrespective of whether they have type 1 or type 2 diabetes.

REPLACE SECTION WITH CONTENTS OF SICKDAY RULES 2

Sick Day Rules for People with Insulin-Treated Diabetes
Any illness such as ‘flu’ or a chest infection may cause the blood sugar to rise because during illness other hormones prevent insulin from working normally.
      NEVER STOP INSULIN INJECTIONS Measure blood sugars at least four times each day (before breakfast, lunch tea and bedtime. In the blood sugar is below 11 mmol/l continue the usual insulin doses. If the blood sugar is between 11 and 17 mmol/l, give 4 units extra of clear insulin before each meal and at bedtime. If the blood sugar is more than 17 mmol/l give 6 units extra of clear insulin before each meal and at bedtime. If appetite is poor replace normal meals with fluids such as milk, Lucozade® or fruit juice. Drink plenty of sugar free liquids (suggest 5 pints each day). Seek medical advice if the blood sugars are continuously over 17 mmol/l, if vomiting develops, or if you do not know what to do.

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END

Ketones and type-1 diabetes Ketones – advise for people with diabetes
What are ketones?
  Ketones are acids produced from the breakdown of body fat. Insulin controls the production of ketones. Ketones can be detected in the urine using test strips (Ketostix). Moderate or large amounts of ketones in the urine usually means more insulin is needed.

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When to check for ketones?
 The urine should be checked for ketones if any of the following develop: A temperature, Excessive thirst Abdominal pain Frequency passing urine Vomiting A higher blood sugar than normal

What to do if ketones are present

2nd Edition August 2000

Proteinuria and Microalbuminuria

Proteinuria is an important finding in patients with type 1 and type 2 diabetes . Type 1 - Increased risk of progressive renal impairment due to diabetic nephropathy Increased risk of macrovascular disease . Type 2 4-fold excess risk of macrovascular disease . ALL patients with diabetes should have an annual urine test for protein (Boerhinger 5L or Albustix test strips). Persistent proteinuria needs careful assessment of cardiovascular risk factors, glycaemic control and renal function. Referral is recommended.

Microalbuminuria and Type 1 diabetes
      Defined as urine albumin excretion (UAE) of 30-300mg/24 hours. Persistent microalbuminuria predicts diabetic nephropathy. Optimal glycaemic control and treatment with ACE-inhibitor slows progression to overt proteinuria. Screen annually from 5 years after diagnosis until 65 years of age. Urinary protein excretion rates show high test-to-test variability. Confirm abnormal result with 2-3 further tests over three months before suspecting microalbuminuria. Persistent raised albumin creatine ratio (ACR) requires confirmation with a 24-hour urine collection for UAE.

Microalbuminuria and Type 2 diabetes
 Type 2 diabetes carries a 2-3-fold excess risk of vascular disease. Microalbuminuria is associated with an additional 2-4-fold risk, independent of other factors. It also predicts nephropathy but most patients die from vascular disease before developing renal failure. There is NO consensus on screening for microalbuminuria in type 2 diabetes because evidence is not available from intervention trials. Two approaches can be adopted: highlights patients at particularly high cardiovascular risk who MAY benefit from more aggressive risk reduction strategies (eg, treat cholesterol according to secondary rather than primary prevention guidelines). Low dose aspirin may be indicated in the absence of clinically evident vascular disease. This approach does NOT mean that vascular risk should be ignored in screen-negative patients. ALL patients should be screened for modifiable vascular risk factor (hypertension, hyperlipidaemia, smoking and obesity) and treated accordingly, irrespective of their microalbuminuria status

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Screening

Not screening

Laboratory screening 10 ml early morning 'first pass' urine sample in a 'Universal' specimen container. Clinical chemistry form for albumin/creatinine ratio ('ACR' in mg/mmol).

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Interpretation

Action
Repeat in 1 year Repeat in 6 months Confirm with 2-3 further ACR

<2.5 <3.5 Normal 2.5-7.5 3.5-10 Possible microalbuminuria >7.5 >10 Probable microalbuminuria measurements

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Hypertension management in type 1 diabetes
Assessment
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Blood pressure measurement on at least three occasions Urine for stick-positive proteinuria or microalbuminuria on three occasions (exclude UTI). Urea, electrolytes and creatinine. Treat > 140/90 Target < 140/80 - without microvascular complications Target < 130/80 - with microvascular complications

Algorithm

Type 1 diabetes BP > 140/90

NO 6/12 Review

YES YES
Microalbuminuria or proteinuria?

NO

ACE inhibitor:  Titrate to maximal tolerated dose

Treat with antihypertensive agent to suit patient profile

YES

Blood pressure target achieved?

NO

Arrange:  3/12thly review  Monitor ACR or urine protein  Check serum creatinine every 3-6
months

Consider 2nd line agent  Diuretic  Calcium antagonist  Cardioselective betablocker  Alpha blocker

YES

Blood pressure target achieved?

NO
Consider referral

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Antihypertensive drugs for type 1 diabetes
ACE inhibitors
     Drug of first choice in type 1 diabetes with microalbuminuria or proteinuria. Adequate contraception advised if used in women of child bearing age. ACE inhibitors must be stopped in the event of pregnancy. Combination with diuretic (frusemide 20-40mg or bendrofluazide 2.5mg) can be useful. U&E and creatinine should be checked before and 7-10 days after starting an ACE inhibitor and after every dose adjustment. Consider angiotensin II blocker in patients intolerant of ACE inhibitor due to cough.

Diuretic
     Bendrofluazide 2.5 mg od Cheap & effective

Ca Antagonists
Long acting non-dihydropyridine agents recommended. Suggest diltiazem XL 90-360mg od Metabolically neutral

Beta-blockers
     Use cardioselctive agents (eg atenolol or metoprolol). Greater cardiovascular protective effects in diabetic patients with IHD than in nondiabetics. Useful in patients with angina/post myocardial infarction. Cheap/effective: Equal efficacy with Captopril in UKPDS trial. Avoid in heart failure/severe peripheral vascular disease/asthma. May cause impotence.

Alpha blocker
  Suggest doxazosin 1-16mg daily. Better tolerated than prazosin Check lying and standing blood pressure to detect significant postural hypotension

2nd Edition August 2000

Hypertension management in type 2 diabetes
 The United Kingdom Prospective Diabetes Study has shown clear benefit of lowering blood pressure in middle-aged patients with type 2 diabetes and hypertension to 140/80 mmHg. Approximately one third of patients needed one antihypertensive agent, one third needed two and one third needed three or more agents. The following recommendations are 'ideal' and may be difficult, impossible or unnecessary to achieve in certain patients (ie. the elderly). Individual targets should be established for each patient. Systolic hypertension is common in diabetes and the recommended targets may be difficult to attain. Aim to lower the systolic pressure by 20 mmHg in the first instance and then review. It is important to minimise ALL vascular risk factors, especially in patients with established end-organ damage (see box). End-organ damage  Retinopathy  Proteinuria  Left ventricular hypertrophy  Ischaemic heart disease  Cerebrovascular disease   Treatment initiation threshold > 140/90 Target blood pressure < 140/80 (see bullet point 2)

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Algorithm
BP > 140/90 mmHg (sustained over three at least three readings)

YES
Lifestyle advice  Smoking  Alcohol  Weight reduction  Exercise  No added salt diet  Lipids

NO

Repeat blood pressure measurement annually

BP remains > 140/90 mmHg

YES
TREAT to target for individual patient

NO

Repeat blood pressure measurement 6-12/12

2nd Edition August 2000

Antihypertensive drugs in type 2 diabetes
General points
    At least three BP readings should be taken before starting drug treatment. Therapy must be tailored to individual patients’ clinical state. There is no clear 'first choice' agent in type 2 diabetes. All have advantages and disadvantages that must be weighed up before prescribing. ACE inhibitors and beta-blockers are less effective in Afro-Caribbean patients. Calcium antagonists and diuretics should be first line agents in these patients. Thiazide diuretics  Use low doses (e.g bendrofluazide 2.5 mg od) to minimise metabolic side effects.  Cheap and effective agents.  May cause impotence. Beta-blockers  Use cardioselctive agents (eg atenolol or metoprolol).  Greater cardiovascular protective effects in diabetic patients with IHD than in nondiabetics. Useful in patients with angina/post myocardial infarction.  Cheap/effective: Equal efficacy with Captopril in UKPDS trial.  Avoid in heart failure/severe peripheral vascular disease/asthma.  May cause impotence. ACE inhibitors  Likely renoprotective effect in patients with proteinuria.  Should be used in hypertensive patients with heart failure unless contraindicated.  Metabolically neutral.  Caution in those on loop diuretics due to first dose hypotension.  Avoid in patients with extensive clinical evidence of macrovascular disease because of risk of associated renal artery stenosis.  Check U+E and creatinine 7-10 days after starting treatment. Calcium antagonists  Useful in patients with co-existent angina.  Metabolically neutral.  Use non-dihydropyridine class if possible (eg diltiazem).  Peripheral oedema can be a problem. Alpha-blockers  Doxazosin better tolerated than prazosin.  May improve lipid profile. Angiotensin II blockers  New agents.  Few data in type 2 diabetes.  Well tolerated.  May offer benefits of ACE inhibitors without the cough.

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Hyperlipidaemia in diabetes – secondary prevention
Patients with:  Myocardial Infarction      CABG or angioplasty Heart transplant for coronary artery disease Angina Peripheral vascular disease Atherosclerotic cerebrovascular disease Advice  Smoking  Diet  Exercise Aspirin 75 mg daily (Unless contraindicated) Blood tests  Fasting lipid profile  Check LFT's, thyroid function and assess alcohol intake  Review diabetic control (HBA1c)

Statin – initiate treatment at time of diagnosis

OPTIMAL TARGET    Total cholesterol LDL cholesterol Triglyceride < 5.0 mmol/l < 3.0 mmol/l < 2.2 mmol/l

Points
 Very few patients with diabetes in the secondary prevention category will have an initial cholesterol below 5 mmol/l. Initiation of treatment should occur at the time of diagnosis and should not await the return of the cholesterol result. A lipid profile should be performed after three months of statin therapy with dose adjustment to achieve target. Consider starting a fibrate if fasting triglycerides > 5.0 mmol/l (statins are less effective than fibrates in the treatment of combined hyperlipidaemia) Combination statin and fibrate therapy should be considered if targets are not reached. Consider referral if Cholesterol > 6.5 Fasting Triglycerides > 5 mmol/l despite maximum dose despite maximum dose

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2nd Edition August 2000

Hyperlipidaemia in diabetes – primary prevention
 Measure total cholesterol in patients at diagnosis and if normal (< 5.0 mmol/l) monitor every 5 years.  Diabetes is associated with an increased risk of vascular disease related, in part, to an atherogenic lipid profile:  Modest increases in total cholesterol Atherogenic lipid profile in  Raised (harmful) LDL cholesterol type 2 diabetes  Low (protective) HDL cholesterol  Raised triglycerides

To date, there are no primary intervention trials in patients with type 2 diabetes to suggest when treatment is appropriate. Until such evidence is available we recommend the following approach:

Patients with clinical evidence of vascular disease but no MI
Treat using the secondary prevention guidelines..
(routine use of aspirin, 75mg od)

     

Angina Absent foot pulse (s) Femoral or carotid bruits Previous stroke Microalbuminuria/proteinuria ECG with signs of previous ischaemic heart disease

Patients with no clinical evidence of vascular disease
Assess total vascular risk (see figure) and offer healthy lifestyle advice.     Age and sex Smoking history Hypertension Family history of cardiovascular disease ECG showing left ventricular hypertrophy



We suggest using a risk factor stratification chart or computer programme to aid decisionmaking. We enclose diabetic risk factor charts recommended by the British Cardiac Society that have been endorsed by Diabetes UK. An estimated 10-year coronary risk of 30% using primary prevention tables or a computer programme identifies those at highest risk in whom treatment is most cost effective.

Aspirin (75 mg od)
 Any patient over 50 years of age with diabetes and one other cardiovascular risk factor can be considered to have a 15% 10-year risk coronary risk and should be advised to take aspirin. Patients with no other risk factors but an estimated 10-year coronary risk of 15%, using primary prevention tables or a computer programme should take aspirin.

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2nd Edition August 2000

Diabetes and contraception
As with all patients seeking contraception, discussion should be in the context of what attributes will best suit the need of the patient and condom use is encouraged to help prevent STIs.

Combined oral contraceptives
    Combined oral contraceptives are safe for use in patients with type 1 diabetes unless there are other contra-indications such as vascular disease. Low dose combined pills with gestodene or desogestrel (3 rd generation) have a minimal effect on carbohydrate and lipid metabolism but a higher thromboembolic risk. Low dose combined pills containing levonorgestrel (2 nd generation) have a greater effect on carbohydrate and lipid metabolism but a lower thromboembolic risk. Low dose combined pills are especially suited to the young patient.

Progestogen only pill
   Metabolically neutral but less reliable than low dose combined contraceptive pill. Safe in patients with diabetes.

Depo Provera
Injectables may alter the dosage requirements for diabetic control, but these are suitable for use in patients with diabetes.

Implanon
 Suitable for patients with diabetes

IUCD/US
  As safe in patients with diabetes as non-diabetic women. Avoid in women with multiple sexual partners

Barrier methods



Safe but less reliable than hormonal contraceptives - but encourage use in all patients in addition to main method for safer sex.
Under 35 years choose from  Combined oral contraceptives  IUCD/IUS POP  Depo Provera Implanon  Barrier Consider switch from combined pill to progestogen only pill if other cardiovascular risk factors present Over 35 years consider  switch from combined pill to progestogen only pill if other cardiovascular risk factors present.  IUCD/IUS or sterilisation if family complete

Hormone Replacement Therapy
   Very little trial evidence with HRT and patients with diabetes. Recommendation to use HRT in patients with diabetes based on extrapolation of benefits from non-diabetic population. Preparations using non-androgenic progestogens (Premique and Tridestra) have better cardiovascular risk profile than those containing norethisterone (Climagest and Estrapak) or levonorgestrel (Prempak-C) Patient tolerability is likely to play a major part in selection of suitable HRT.

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2nd Edition August 2000

Erectile dysfunction in diabetes
Erectile dysfunction? – inability to obtain and sustain and erection suitable for intercourse Are there clues to psychogenic or organic origin?

Suggests psychogenic
      Sudden onset Early collapse of erection Good quality spontaneous/self stimulation/waking erections Premature ejaculation or inability to ejaculate Relationship problems Major life events Psychological problems



Suggests organic  Gradual onset  Lack of tumescence  Normal ejaculation  Normal libido  Risk factors  Operations/radiotherapy or trauma to pelvis/scrotum  Current medication  Smoking  Alcohol Recommended investigations  Glucose/HBA1c  Creatinine  LH/FSH and testosterone  Prolactin

Consider psychosexual therapy

Referral for endocrine opinion if testosterone or prolactin abnormal

Is physical treatment appropriate/desired?

Poor response/not tolerated – try alternative choice

Discuss treatment options Arrange a trial of  Sildenafil *  Vacuum device  Urethral alprostadil  Intracavernosal alprostadil In surgery or after referral to diabetes erectile dysfunction clinics
* HSC 99/115 and 99/148 include men with diabetes in list of patients to whom GPs may prescribe

Details of UHN and NCH erectile dysfunction clinics are available in the Resource section (2) of these guidelines

2nd Edition August 2000

Annual Review
This is an essential part of the planned management of people with diabetes. The following should be covered during the annual review process :

Clinical
        Weight/BMI Patient’s monitoring records Symptoms of hyperglycaemia Episodes of hypoglycaemia Problems with medication Injection sites for lipohypertrophy Problems with eyesight, parasthesia, erectile dysfunction Macrovascular disease – angina, TIA, claudication

Biochemical
     Fasting glucose or HBA1c Creatinine Lipids (see guidelines) Urine albumin for proteinuria Albumin/creatinine ratio (if no proteinuria and under 65 yrs)

Screening Retinopathy
Optometrist screening programme  See section 2 Hospital screening  Check result is available GP screening to include  Visual acuity (Snellen chart)  Pupil dilatation  Direct fundoscopy

Foot care
      Deformity/callus Check dorsalis pedis and posterior tibial foot pulses Pinprick sensation Light touch 10g Seimes-Weinstein monofilament (if available) Active foot ulcers

Renal
   Blood pressure Urine for proteinuria and/or microalbuminuria Creatinine

Vascular
  Advise to stop smoking Diet review Advise on exercise

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Establish management plans and treatment targets for
     Hyperglycaemia Hypertension Hyperlipidaemia Cardiovascular protection with aspirin Hormone replacement therapy (if appropriate)

2nd Edition August 2000

Referral criteria
Urgent (same day)
   Diabetes in childhood - if newly diagnosed to paediatric on call team. Newly diagnosed type 1 diabetes to diabetes SpReg at UHN or NCH. Protracted vomiting or ketonuria in a patient with type 1 diabetes - emergency referral to on call team. The 'hot foot' ie cellulitis/deep infection in the context of a new or chronic foot ulcer to diabetes SpReg at UHN or NCH. Sudden visual loss, most commonly due to a vitreous haemorrhage to eye casualty, UHN.

 

Elective
 Pregnancy *as soon as diagnosed referral to joint obstetric/diabetes clinic - Dr Margaret Ramsey University Hospital - Mr Toby Fay Nottingham City Hospital - Prof Phil Baker Nottingham City Hospital * to diabetes team/diabetes nurse specialist if pregnancy planned to intensify control.  Management problems with difficulty achieving: - glycaemic targets - blood pressure targets - lipid targets. Frequent hypoglycaemic episodes. Long-term complications - Sight threatening retinopathy (to eye clinic if other aspects of management ok) - Microalbuminuria - Proteinuria - Elevated serum creatinine - Painful neuropathy, mononeuropathy and amyotrophy - 'Chronic' foot ulcers - Foot deformity/problems with persistent callus - Impotence - Angina, claudication, cerebrovascular disease

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Version 2. May 2000

References used in compiling these guidelines

BHS Guidelines: Guidelines for the management of hypertension: report of the third working party of the British Hypertension Society. Journal of Human Hypertension 1999, 15, 569-592. European Diabetes Policy Group 1998. A desktop guide to type 1 (insulin-dependent) diabetes mellitus. Diabetic Medicine 1999, 16, 253-266. European Diabetes Policy Group 1999. A desktop guide to type 2 diabetes mellitus. Diabetic Medicine 1999, 16,716-730. Nottingham Health Authority Draft Guidelines on Vascular Risk (2000) ACKNOWLEDGEMENTS Novo Nordisk Pharmaceuticals Ltd have kindly provided sponsorship for the printing of these guidelines. They have had no influence over their content.


				
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