DIABETES - INSULIN INITIATION - BACKGROUND INFORMATION (1)

DIABETES - INSULIN INITIATION - BACKGROUND INFORMATION (1) KEY PRINCIPLES Many patients with Type 2 diabetes will require insulin therapy. In the UKPDS over 50% of patients by 6 years required additional insulin therapy. Initiation of insulin therapy in Type 2 diabetes still remains more of an art than a science at the present time, and this area creates much confusion. It is impossible to produce simple guidelines applicable for every patient with Type 2 diabetes for insulin initiation. There is no clear evidence to suggest that any particular approach has significant advantages over and above an alternative approach. In normal and overweight patients with Type 2 diabetes, Metformin therapy should be continued at the maximum tolerated dose, as long as there is no contra-indication, e.g. creatinine >130, unstable heart failure. (It is important to check that the person has no symptoms of intolerance of Metformin therapy.) INDICATIONS FOR INSULIN: Newly Diagnosed Type 1 Diabetes All previous attempts to achieve desired target have failed i.e. lifestyle measures, maximum oral therapy Persistent failure to achieve desired HbA1c Patient symptomatic, i.e. weight loss, lethargy Type 2 Diabetes where early insulin is indicated (see Glycaemic Management Guidelines) Steroid induced Diabetes Gestational Diabetes Post acute myocardial infarction Intolerance to oral agents More suitable to patients lifestyle Acute neuropathies such as proximal amytrophy PRINCIPLES OF GOOD PRACTICE: In Type 2 Diabetes the issue of insulin should be discussed early on in the diagnosis. In Type 2 Diabetes think about insulin early, i.e. when HbA1c is progressively rising and is consistently above >7.4% and maximum tolerated oral therapy and lifestyle changes are in place. In Type 1 Diabetes start insulin within 24 hours. The way in which the subject is approached should be sensitive to the persons needs. The decision to start insulin should be done in agreement and partnership and the choice of regime tailored to the individual s needs. Insulin initiation should be part of a structured care plan and educational programme. The person should agree to and understand the benefits of insulin; in addition they should also understand the implication of insulin (see Supporting Information (1) and (2)). The person initiating insulin should be trained and competent. In Gestational Diabetes insulin should be managed by the secondary care team. (See Referral Criteria to Specialist Services.) Tel: LRI - 0116 258 6403: LGH - 0116 258 4855. There should be provision for adequate structured follow up. Access to appropriate dietary advice is essential. Animal insulins are not recommended for new insulin starts. POTENTIAL BARRIERS TO STARTING INSULIN: Occupational issues (See Insulin Initiation - Supporting Information 1). Fear of injections Fear of hypoglycaemia Fear of weight gain LOGISTICS FOR INSULIN INITIATION: Identify dedicated time by competent health care professional for initiation and follow up. One to one consultations or Group sessions. Identify and agree the most appropriate insulin regimes (see Insulin Inititiation - Indications for Insulin and Potential Regimens). Make sure appropriate equipment and educational material is available. Identify appropriate environment. Provide ongoing support and contact details.

DIABETES - INSULIN INITIATION - BACKGROUND INFORMATION (2) OVERVIEW OF INSULIN AND ACTIONS Soluble Human Insulin: Actrapid, Humulin S Onset: 30 mins Peak: 2-4 hours Duration: 6-8 hours Insulin activity Insulin activity 0 2 4 6 8 10 12 14 16 18 20 22 24 Rapid Acting Insulin Analogue: Novorapid Aspart, Humalog Lispro. Onset: 0-15 mins Peak: 1-2 hours Duration: 3-5 hours Insulin activity 0 2 4 6 8 10 12 14 16 18 20 22 24 Intermediate Human Isophane Insulin s: Insulatard, Humulin I Onset: - Peak: 4-8 hours Duration: 14-16 hours 0 2 4 6 8 10 12 14 16 18 20 22 24 Long Acting Basal Analogues: Glargine (Lantus), Detemir (Levemir) Onset: Peak: Duration: ~ 2 hours None 18-24 hours Insulin activity Insulin activity 0 2 4 6 8 10 12 14 16 18 20 22 24 Pre-mixed Human Soluble/Isophane: Mixtard 30, Humulin M3 etc Onset: See above Peak: See above Duration: See above Mixtard 30, M3 refers to % of soluble insulin ie. 30% Soluble 70% Isophane Insulin activity 0 2 4 6 8 10 12 14 16 18 20 22 24 Pre-mixed Analogues/Isophane: Novo Mix 30, Humalog Mix50, Mix25 Onset: See above Peak: See above Duration: See above Novo Mix 30, Humalog Mix50/Mix25 refers to % of rapid acting analogue insulin 0 2 4 6 8 10 12 14 16 18 20 22 24 ANIMAL INSULINS Some patients on animal insulins are adequately controlled and do not require a change in insulin regimen. Indications for changing to Human or Analogue Insulin regime: Poor or erratic control Problems with hypoglycaemia Patient choice Failure to reach glucose targets Use of devices Problems at injection sites When changing from animal to an alternative insulin a 20% reduction in dose is recommended, initially they will require weekly review of monitoring. May wish to seek specialist advice. NB: Rarely, some patients who previously changed from animal to human insulin may experience difficulties with hypoglycaemia and prefer to revert back to animal insulin. This should be discussed with the Specialist Team on an individual basis. OVERVIEW OF THE USE OF ORAL HYPOGLYCAEMIC AGENTS IN COMBINATION WITH INSULIN:(for detailed description see Diabetes Management - Oral Agents). In relation to combination with insulin in Type 2 Diabetes only: Biguanides: Metformin. Evidence support combination with insulin due to benefits in weight management, glycaemic control and CHD risk. Sulphonylureas, Insulin Secretagogues, Prandial Glucose Regulators (Nateglinide, Repaglinide) Generally are discontinued when commencing insulin. Evidence supports some combinations (See Insulin Initiation - Detailed Guide). Glitazones: Pioglitazone, Rosiglitazone. Discontinue when insulin commenced. Presently not licensed with insulin. Acarbose: In our practice we do not use in combination with insulin although there is some evidence to support this.

DIABETES - INSULIN INITIATION - SUPPORTING INFORMATION (1) HYPOGLYCAEMIA Key points to consider: People worry about it. Need to identify symptoms, potential causes and treatment. Prevention. When to seek help. MONITORING Self blood glucose monitoring (SBGM) usually recommended. Those unable to SBGM may find urine testing helpful and may require more frequent HbAIC measurement. See monitoring glycaemic control guidelines. WEIGHT MANAGEMENT Generally people gain weight on insulin treatment mainly due to improved glycaemic control. Consider: Early discussion of appropriate weight for individual. Discussion of weight management strategies. Unexplained weight loss or gain, consider referral for specialist advice. HYPOGLYCAEMIA DRIVING MONITORING EMPLOYMENT WEIGHT MANAGEMENT HEALTHY EATING COPING WITH ILLNESS COPING WITH ILLNESS Insulin doses may need adjusting during illness. Patients may require additional support. More frequent monitoring may be required. Generally insulin should never be stopped in Type 2 Diabetes. TYPE 1 DIABETES Insulin should never be stopped as there is a risk of ketoacidosis. Patients should test urine or blood for ketones to identify risk of ketoacidosis. They may require specialist advice. DRIVING Key points to consider: Risk of hypoglycaemia. Loss of livelihood. Implications for insurance and DVLA. Ensure individual understands their responsibilities in terms of safety. See Diabetes UK information. EMPLOYMENT Diabetes is covered by the Disability Discrimination Act 1995. Certain occupations are limited for those on insulin, e.g. Emergency Services, Forces. Contact Diabetes UK Careline for more details. Shift patterns and activity levels will need to be considered. Further information is available from Diabetes UK Careline: 0207 4241000. HEALTHY EATING The need for a healthy diet is not affected by insulin initiation. Additional snacks are not automatically required and should be tailored to the individuals needs. Care must be taken to ensure that advice given about changing eating habits is not detrimental to the individual s weight management goals.

DIABETES - INSULIN INITIATION - SUPPORTING INFORMATION (2) EXERCISE Most people would benefit from increasing physical activity levels. Care must be taken to avoid hypoglycaemia. Some insulin regimes may be more suitable for people with active or varied lifestyles. Most sports are possible for people on insulin, however there are a few exceptions eg. deep sea diving, free-fall parachuting. All types of activity have an effect on glycaemic control. TRAVEL Insulin does not restrict travel opportunities, but planning is required. Consider destination, climate, illness, change in activity, mode of travel, availability and storage of supplies. Carry adequate identification. A supporting letter from a healthcare professional on headed paper may be necessary. ONGOING CARE Regular follow up is required tailored and agreed with the individual. Requirements may change over time. Care should be patient centred. Education should support self management skills. EXERCISE ALCOHOL TRAVEL SPECIAL OCCASIONS AND CULTURAL ISSUES ON GOING CARE HELP AND SUPPORT HELP AND SUPPORT Supporting literature available from: Leicestershire Diabetes Website - for healthcare professionals and people with diabetes. www.leicestershirediabetes.org.uk Diabetes UK Tel: 0207 424 1000 Website www.diabetes.org.uk NovoCare Customer Care Centre Tel: 0845 600 5055 Website: www.novonordisk.co.uk Lilly Diabetes Care UK Tel: 01256315000 Website: www.lilly.co.uk Aventis Customer Services Tel: 01732 258 4000 ALCOHOL Government guidelines on alcohol intake are the same for people on insulin. Alcohol beverages have different effects on blood glucose levels. The risk of delayed hypoglycaemia needs to be discussed. Where alcoholic intake exceeds recommended levels, people need appropriate advice to minimise risks. SPECIAL OCCASIONS AND CULTURAL ISSUES Patients may need additional advice to manage these situations, especially around feasting and fasting Cultural awareness and sensitivity are essential. Participation in events does not have to be restricted. Further information is available from: www.leicestershirediabetes.org.uk Diabetes UK Website - www.diabetes.org.uk Servier - 01753 662744. Some health care professionals find it useful to compile a checklist to document advice given when initiating and managing insulin. An example of one can be found on the Leicestershire Diabetes website - www.leicestershirediabetes.org.uk

DIABETES - INSULIN ADMINISTRATION AND DEVICES (1) POINTS FOR CONSIDERATION Having made the decision to commence Insulin (See Insulin Initiation - Background Information sheet) the following points may influence choice of regime and devices: Dexterity Vision Eating patterns Lifestyle Occupation Agreed frequency of injections Ability to grasp techniques NB: Choice may be influenced by available format of insulin, eg. 10ml vials for use with syringes, 3ml cartridges for use with pens or preloaded disposable pens etc. LIST OF LEAFLETS AVAILABLE Leicestershire Diabetes Website www.leicestershirediabetes.org.uk Diabetes and Insulin Novo Nordisk - 0845 600 5055 Diabetes - The Way to Good Nutrition Leicestershire Nutrition & Dietetic Service UHL Diabetes Department - leaflets LRI - 0116 2585545 LGH - 0116 2584369 Lilly - leaflets on all aspects of Diabetes and Insulin 0125 6315 999 (Customer Care Line) PEN DEVICES Spare Insulin cartridges/pre-filled pen - keep in fridge. Pen currently being used can be kept at room temperature for up to 1 month. SYRINGES Spare Insulin vials should be kept in the fridge. The Insulin vial that is in current use may be kept at room temperature for up to 1 month, Insulin remaining in vial after this length of time should be disposed of. Injection sites should be checked regularly. Lipohypertrophy can effect the absorption of Insulin - if a patient stops using a "lumpy" injection site blood glucose levels should be monitored closely as a reduction in Insulin may be required to avoid hypoglycaemia. Buttocks can also be used. Arms should be used with caution due to rapid onset of action. HOW TO INJECT Dial or draw up correct dose of Insulin as per chosen device. Remember to agitate Insulin if required. Choose injection site (see picture). Pinch up subcutaneous fat for 8mm and above needles (no pinch up required for 5 mm x 6 mm needles). Insert needle directly into raised area. Depress plunger or button to deliver Insulin as per manufacturers instructions. Hold needle in place for 10 seconds then remove needle from area. STORAGE OF INSULIN INJECTION SITES POINTS TO REMEMBER Insulin is affected by extremes of temperature i.e. very hot or freezing. Avoid keeping in contact with direct heat or sunlight or risk of freezing e.g. in the hold of an aircraft. REMEMBER that between injections some Insulin particles separate and to ensure correct concentration/consistency these Insulins need to be mixed by inverting 20 times prior to injecting them. Encourage the practice of rotating place if injecting within a chosen site. Rotating injection sites may result in differing rates of absorption between sites and needs to be taken into consideration, eg. insulin is absorbed more quickly from the abdomen than the thighs. SHARP DISPOSAL There is national guidance for disposal of sharps. See www.leicestershirediabetes.org.uk. Guidance should include advice around: Use of safe clip device as a needle clipper. Issue and disposal of sharps boxes or alternative containers to meet individuals needs. Avoidance of disposal of sharps in general refuse to prevent needle stick injuries etc. Your PCT will have local guidelines on sharp disposal.

DIABETES - INSULIN ADMINISTRATION AND DEVICES (2) PEN NEEDLES The following table highlights pen needles currently available in the UK. There are five different needle lengths available - 5mm, 6mm, 8mm, 12mm, and 12.7mm - and four different alternative gauges or widths - 28G, 29G, 30G, and 31G. All needles should fit all Insulin pens (except the OptiPen Pro insulin pen from Aventis, which can only use the Penfine needle from Disetronic). Product Name Manufacturer Length Width BD Microfine + Becton Dickinson 12.7 mm 29 G 8 mm 31 G 5 mm 31 G Novofine Novo Nordisk 12 mm 28 G 8 mm 30 G 6 mm 31 G Unifine Pentips Owen Mumford 6 mm 30 G 8 mm 30 G 12 mm 29 G Penfine Disetronic 6 mm 31 G 8 mm 31 G 12 mm 29 G The recommendation is that a new needle is used for each injection. SYRINGES Name Manufacturer Syringe Needle Length Capacity Available BD Microfine + Becton Dickinson 0.3 ml 8 mm 0.5 ml 8 mm/12.7mm 1.0 ml 8mm/12.7mm Use a fresh syringe for each injection. GUIDE TO INSULIN PENS Company & Pen Name Insulin Used Min-Max Cartridge Reusable or On Dose Size Pre-filled Prescription NOVO NORDISK Novopen 3 Classic Novo Nordisk 1-70 units 300 units (3ml) Reusable Yes Penfill 3ml cartridge Novopen Junior Novo Nordisk 0.5-35 units 300 units (3ml) Reusable Yes Penfill 3ml cartridge Novopen 3 Fun Novo Nordisk 1-70 units 300 units (3ml) Reusable Yes Penfill 3ml cartridge Flexpens Novo Nordisk 2-70 units 300 units (3ml) Prefilled Yes 3ml prefilled insulin Innovo Novo Nordisk 1-70 units 300 units (3ml) Reusable Yes Innolet Only Insulatard, Mixtard 30 1-50 units 300 units (3ml) Prefilled Yes LILLY Humapen Luxura Lilly 3ml cartridges 1-60 units 300 units (3ml) Reusable Yes Humapen Ergo Lilly 3ml cartridges 1-60 units 300 units (3ml) Reusable Yes Lilly prefilled pen Lilly Prefilled Range 1-60 units 300 units (3ml) Prefilled Yes Humaject prefilled pen Lilly Humaject Range 2-96 units 300 units (3ml) Prefilled Yes AVENTIS PHARMA OptiPen Pro 1 Insuman Range & Lantus 1-60 units 300 units (3ml) Reusable No (only available from the diabetes specialist nurse) Aventis Optiset Insuman Range & Lantus 2-40 units 300 units (3ml) Prefilled Yes Autopen 24 Lantus 2-40 units 300 units (3ml) Reusable Yes OWEN MUMFORD Autopen 1.5 ml All types of 1.5 ml cartridges 1-16 units 150 units (1.5 ml) Reusable Yes Autopen 1.5 ml All types of 1.5 ml cartridges 2-32 units 150 units (1.5 ml) Reusable Yes Autopen 3 ml All types of 3ml cartridges 1-21 units 300 units (3ml) Reusable Yes except Novo Nordisk 3ml Autopen 3 ml All types of 3ml cartridges 2-42 units 300 units (3ml) Reusable Yes except Novo Nordisk 3ml Choice of needle manufacturer will depend primarily on patient choice. Choice of needle length will be determined by both patient choice and BMI, but most patients will only require 5mm - 8mm needles. Although there is no evidence of needle length relating to pain, there is psychological benefit to the shorter needles. There is a risk that 12mm - 12.7mm needles may result in insulin being injected intramuscularly, especially if the patient is thin and does not pinch up subcutaneous tissue before injecting.

DIABETES - POTENTIAL REGIMENS (TYPE 2 DIABETES) FACTORS INFLUENCING CHOICE OF REGIMEN Is the patient s lifestyle variable? (e.g. do they work shifts, do any sport or activity, have a job which requires lots of travelling and irregular eating patterns?) Has the person got special needs or need assistance with administration of insulin? (e.g. problems with dexterity, problems with eyesight, cognitive dysfunction?) Is weight an issue? Is the number of injections per day an issue? Is this person at particular risk of hypoglycaemia, or could hypoglycaemia cause particular problems (e.g. an elderly person living alone or cultural reasons such as fasting?) Would a move to insulin therapy particularly affect the person s quality of life or occupational choices (e.g. are they a taxi driver, or hold a HGV licence?) Are there any specific cultural needs or cultural reasons which would affect their perceptions of insulin therapy? BACKGROUND INFORMATION An appropriate insulin regime is usually required to address both basal, i.e fasting and pre-prandial glucose levels and post-prandial (post-meal) excursions. A traditional isophane (medium acting) insulin given twice daily such as Humulin I and Human Insulatard addresses basal hyperglycaemia. However, the long-acting insulin analogues such as insulin glargine and insulin detemir which are becoming more popular. They have the advantage of greater predictability, potentially less weight gain, and lower risk of hypoglycaemia, particularly at night. Address post-meal glucose excursions with the use of the shortacting insulins, either used alone or in combination as a mixed insulin. The disadvantages are that they have to be injected 20/30 minutes before a meal. Patients need to snack between meals and there is a risk of hypoglycaemia. Short-acting insulin analogues such as insulin aspart and insulin lispro have advantages in terms of convenience, can be injected with, or indeed, after meals, are better at controlling post-prandial glucose, and have a lower risk of hypoglycaemia. TITRATING DOSES - KEY PRINCIPLES Blood glucose targets should be agreed between the HCP and the patient. Do not adjust the dose in response to individual blood glucose readings. Try to look for patterns and establish the overall picture. Use the monitoring diary to establish if patterns exist at different times of the day. Take into account any comments discussed or recorded in the monitoring diary. Are they related to the blood glucose readings, eg. eating patterns, changes in activity. View the blood glucose results in relation to the type of insulin and timing of injections. Where possible, decision re: titrating the doses should be made by the patient or in partnership with the HCP. Is the problem dose related or does it indicate that the regimen is not meeting that person s needs? Generally, increases are made in 10% increments Prevention of hypoglycaemia takes precedence and generally where no other cause can be found a 20% reduction in insulin dose is required. Most commonly used Insulin Regimens Metformin can be continued in combination with all insulin regimes, as outlined here, in patients with Type 2 Diabetes: 1. Twice daily pre-mixed insulin which includes conventional mixtures of short-acting and isophane insulin, e.g. Human Mixtard. The most commonly used ratio is 30/70. Insulins are available with a percentage of short-acting insulin from 10%, in 10% increments, up to 50%. More recently, short-acting insulin analogue mixtures such as Novomix 30 and Humalog Mix 25 and Mix 50, are now available and may have particular advantages in terms of patient convenience (no need to wait before eating) and control of post-meal glucose. 2. Once-daily basal insulin in combination with oral hypoglycaemic agent, to include either a sulphonylurea or a prandial glucose regulator with Metformin if tolerated. Evidence suggests that conventional isophane insulin when used in this regime is best administered either in the evening or before bed. Basal insulin analogues including insulin glargine and detemir have been suggested for use once a day in combination with oral agents as they have particular advantages in terms of nocturnal hypoglycaemia. 3. Twice-daily Isophane insulin used as basal insulin therapy. This approach is likely to be superseded by the use of oncedaily basal insulin analogues as data suggests they are as effective in terms of A1c lowering and have a reduced risk of hypoglycaemia. Other factors such as costs and choice of insulin device may mean the continued use of twice-daily isophane insulin (i.e. Human Insulatard or Humulin I) in some patients. 4. Formal basal bolus regime (i.e. four injections of insulin per day). Short-acting insulin or short-acting analogues before each of the main meals and basal insulin (either once or twice daily isophane insulin or once daily long-acting insulin analogue, i.e. insulin glargine or detemir). Often used in patients with Type 1 diabetes. Rarely the first choice in patients with Type 2 diabetes. TARGETS OF THERAPY Patients need to have targets individualised. Optimum HbA1c target should be in line with NICE and evidence base. Patients with Type 2 diabetes should be <7% (6.5% in those at particular risk of cardiovascular disease). Aim for a pre-breakfast or fasting glucose level of <5.5mmol/l. Pre-prandial levels at other times of the day at <6mmol/l. Post-prandial (i.e. 2 hours after a main meal) <8mmol/l. Post-prandial glucose monitoring may not be appropriate for all patients.

DIABETES - POTENTIAL REGIMENS (TYPE 2 DIABETES) TWICE DAILY PREMIXED INSULIN TWICE DAILY PRE-MIXED INSULIN Either conventional short-acting and isophane insulin, e.g. Mixtard 30/70, Humulin M3 or analogue mixed insulin, e.g. Novomix 30 or Humalog Mix25. The advent of short-acting insulin analogue mixtures means that this regime is now available with a short acting insulin analogue, either as Novomix 30 with 30% short-acting insulin analogue or Humalog Mix 25 (25% short acting insulin analogue). The particular choice of which pre-mixed insulin is used may be influenced by: choice of insulin injection device perceived convenience for patients potential for weight gain and risk of hypoglycaemia. ADVANTAGES This regime is relatively easy to teach and simple for the patient to understand. It has potential for better post-prandial glucose control. DISADVANTAGES SIMPLE APPROACH TO INITIATION OF INSULIN THERAPY Before breakfast and before evening meal: Use 10 units b.d. Consider a lower starting dose in some circumstances, eg. frail, elderly or slim patients. Remember they will need regular review for titration of doses. TITRATION OF DOSES See Key Principles from Potential Regimens sheet. Morning dose of insulin titrated against pre-lunch and preevening meal blood glucose tests: suggest 2 unit increments increase with a target glucose of <6 before lunch and before evening meal. Evening dose titrated against pre-bed and pre-breakfast test. Titrate to try to achieve a before breakfast blood glucose of 5.5-6. Beware of before bed tests of <6: aim for a before bed test between 6 and 8. Watch carefully for the risk of nocturnal hypoglycaemia. In patients with Type 2 Diabetes and BMI >19, Metformin therapy should be continued at the maximum tolerated dose, as long as there is no contra-indication, e.g. creatinine >130, unstable heart failure. (It is important to check that the person has no symptoms of intolerance of Metformin therapy.) INDICATION FOR CHANGE OF REGIMEN If glycaemic targets are not reached after titration, change may be required. For example:- If control remains suboptimal. Hypoglycaemia (particularly in the night). Excessive weight gain despite continued Metformin. Patient s preference or lack of flexibility with the regime for patients to undertake lifestyle (e.g. erratic job or exercise). If before the evening meal dose blood glucose remains high but further titration causes mid-morning hypoglycaemia. There are several options: continue premixed insulin and add in short acting insulin at lunchtime if high blood glucose before evening meal. stick to pre-mix twice a day but change the proportion of insulin (i.e. move to a 10/90 mixture). move to a basal bolus regime (see appropriate sheet). offer the patient free mixing of insulin. However, the disadvantage of this is that it is complicated to explain and teach to patients, accuracy is an issue, and the patients would need to move away from a pen device back to a needle and syringe. Potentially higher risk of hypoglycaemia (particularly midmorning and at night). Potential for more weight gain (this may be reduced by the analogue mixtures). There is less flexibility (i.e. unable to adjust the short or basal component of insulin independently). Patients may not achieve optimal glycaemic control. Time delay of injection with conventional mixture (need to inject 20-30 minutes before a meal). The need for snacks between meals (with the new analogue mixture the delay in injection time is not required and the need for snacks may be reduced). Titration may get complicated and difficult to teach. ADVANCED APPROACH TO INSULIN INITIATION The approach to insulin therapy is continuously changing. Recent evidence suggesting a more proactive and calculated dose and titration may be more appropriate for those experienced in insulin management. To adopt this approach see the Leicestershire Diabetes website: www.leicestershirediabetes.org.uk

DIABETES - POTENTIAL REGIMENS (TYPE 2 DIABETES) BASAL INSULIN WITH ORAL HYPOGLYCAEMIC AGENTS ONCE DAILY BASAL INSULIN Either isophane insulin (Humulin I, Insulatard) or a long-acting insulin analogue (Glargine (Lantus), Detemir (Levemir)) with continued oral hypoglycaemic agents. Once a day insulin analogues (Glargine (Lantus), Detemir (Levemir)) are designed to work throughout a 24 hour period with a peakless action. Pre-breakfast (fasting) blood sugars are a good indicator of their effectiveness, but remember that it in some individuals they do not last for 24 hours and may be required twice daily. (BD dosing more likely with Detemir) The peakless insulins are not effective in lowering mealtime (prandial) rises in blood sugar. If this cannot be adequately controlled with long-acting insulin and oral hypoglycaemic agents, short acting insulin will need to be added. Basal insulin analogues should not be mixed in syringes with other insulins. Should be injected at approximately the same time every day (2 hour window). ADVANTAGES It is simple and easy for early facilitation to insulin. Potentially less weight gain. Potential for less risk of hypoglycaemia. Relatively easy regime for healthcare professionals to support. Useful for symptom relief if tight control is not a major issue. SIMPLE APPROACH TO INITIATION OF INSULIN THERAPY Use 10 units once daily usually given at bedtime (9-10pm) or with evening meal for Isophane. Long-acting analogues may be given morning or evening at a time suitable for the patient, but it must be consistent from day to day. TITRATION OF DOSES See Key Principles from Potential Regimens sheet. Regime for basal insulin analogue is : Fasting plasma glucose level 5.5mmol/l - 6.0mmol/l, increase insulin glargine or detemir dose 2 units every 3 days until prebreakfast blood glucose 5.5mmol/l and there is no nocturnal hypoglycaemia. CHOICE OF ORAL HYPOGLYCAEMIC AGENT Your choice of oral hypoglycaemic agent, particularly the insulin secretagogue, may be important if choosing this regime. Always continue Metformin in the normal and overweight patients at the current dose unless contra-indicated or not tolerated. Always check for symptoms of Metformin intolerance in patients. Continue previous sulphonylurea at unchanged dose. For ease of therapy one may wish to consider a change to once-daily Glimepiride titrated up to a dose of 4-6 mg or Gliclazide MR. This is a good choice if ease of administration is an issue. Remember: Use three consecutive self-monitored fasting glucose level (before breakfast) to adjust doses. Wait 3-4 days between adjustments. Reduce the dose if fasting glucose falls below 4 or an unexplained hypoglycaemic episode was experienced. The amount of decrease needs to be at least 2-4 units or 10%, whichever is greater. INDICATION FOR CHANGE OF REGIMEN Fasting glucose levels are at target but pre- or post-prandial control unacceptable despite maximum tolerated oral hypoglycaemic agent. Control remains suboptimal. Recurrent unexplained hypoglycaemia. Patient s preference or need for greater flexibility with regard to lifestyle (eg. exercise, employment). Consider twice daily pre-mixed insulin or formal basal bolus regimen. If post-prandial glucose levels are high, weight or risk of hypoglycaemia is an issue and flexibility is important, then the use of Repaglinide titrated up to 4mg t.d.s is a good choice. During the active titration phase of Repaglinide, use post-meal glucose levels 2 hours after meals to achieve this. If post-prandial glucose levels remain high despite maximum tolerated oral agents, it may be appropriate to stop these and change to a formal basal bolus regimen. See relevant guidance. DISADVANTAGES Patients may not achieve optimal control. The regime may not offer optimum control of post-meal (postprandial) hyperglycaemia. ADVANCED APPROACH TO INSULIN INITIATION The approach to insulin therapy is continuously changing. Recent evidence suggesting a more proactive and calculated dose and titration may be more appropriate for those experienced in insulin management. To adopt this approach see the Leicestershire Diabetes website: www.leicestershirediabetes.org.uk

DIABETES - POTENTIAL REGIMENS (TYPE 2 DIABETES) TWICE DAILY ISOPHANE TWICE-DAILY ISOPHANE INSULIN In people with Type 2 Diabetes and BMI 19 Metformin therapy should be continued at the maximum tolerable dose as long as there is no contra-indication, eg. creatinine >130, unstable heart failure. It is important to check that the person has no symptoms of intolerance of metformin therapy. ADVANTAGES Relatively easy. Less risk of hypoglycaemia. Particularly suitable when somebody has a problem with high pre-prandial glucose levels. DISADVANTAGES Difficult to obtain optimal control. Difficult to manage post-prandial hyperglycaemia. Does not particularly allow flexibility. New long acting insulin analogues have added benefits. The evidence base is changing for other insulin regimens. SIMPLE APPROACH TO INITIATION OF INSULIN THERAPY To start 10 units b.d of isophane insulin, i.e. human Insulatard or Humulin I. Choice of device may influence the patient s choice. TITRATION OF DOSES See Key Principles from Potential Regimens sheet. To titrate up 2 units per day until the patient is on 20 units per day when the 10% rule is applied. Adjust the insulin up every 3-4 days in relation to home monitoring results, e.g. Pre-evening meal results relate to morning insulin, pre-breakfast results relate to evening insulin. Key point: With the advent of the basal insulin analogues and the advantages in terms of weight gain, predictability and reduced nocturnal hypoglycaemia. It is not likely that this regime will remain a popular choice. See Potential Regimens - Basal Insulin with Oral Hypoglycaemic Agents. INDICATION FOR CHANGE OF REGIMEN Hypoglycaemia. Suboptimal control. Fluctuations in blood glucose levels in relation to insulin action. ADVANCED APPROACH TO INSULIN INITIATION The approach to insulin therapy is continuously changing. Recent evidence suggesting a more proactive and calculated dose and titration may be more appropriate for those experienced in insulin management. To adopt this approach see the Leicestershire Diabetes website: www.leicestershirediabetes.org.uk

DIABETES - POTENTIAL REGIMENS (TYPE 2 DIABETES) FORMAL BASAL BOLUS REGIME BASAL BOLUS REGIME At least four injections of insulin per day. Short acting or short acting insulin analogues before each of the main meals, and basal insulin (either once or twice daily isophane or long acting insulin analogues, eg. glargine or detemir). Often used in people with Type 1 Diabetes. Rarely a first choice in patients with Type 2 Diabetes. Useful for patients who require flexibility on a daily basis, with irregular lifestyles, varied mealtimes or irregular eating patterns, shift work etc. An example of someone in whom this may be useful is an active, motivated person with an erratic lifestyle who wants to improve glycaemic control. ADVANTAGES Offers optimum flexibility in terms of diet and activity. Potential for the low risk of hypoglycaemia. Potential for better metabolic control if used optimally. Closely mimics normal insulin physiology. Potential for the best control of basal and post-prandial hyperglycaemia. Potential for better weight management and lifestyle choice. DISADVANTAGES Requires multiple insulin injections. More complicated to support and teach. Requires more regular glucose testing. Generally more complicated. SIMPLE APPROACH TO TRANSFER TO BASAL BOLUS INSULIN THERAPY If already taking once or twice daily basal insulin - continue this and simply add quick acting insulin or quick acting analogue before each main meal. If taking premixed unsulin, calculate how the present dose of pre-mixed insulin is divided into short and long acting, and use this to influence decision. OR change to: Basal bolus regimen with basal analogue (Glargine, Detemir) Add total daily dose of premixed insulin. Usually take off 20%. In some circumstances it may not be appropriate to take off 20%, e.g. very poor glycaemic control or symptomatic of high blood sugars. Give 50% as basal insulin. Divide remainder to cover meals with quick acting insulin dependant on their eating habits. Eg. Mixtard 30: 50 units am, 50 units pm. Total daily dose = 100 units - 20% = 80 units. Give 40 units as basal insulin remainder given as 12-14 units of quick acting insulin with each meal dependant on eating habits. TITRATION OF DOSES See Key Principles from Potential Regimens sheet. Adjust the basal insulin (long acting) to achieve satisfatory prebreakfast blood glucose levels, waiting 3-4 days between adjustments. Reduce the dose if blood sugar is too low during the night or prebreakfast result is 5mmol/l on more than one occasion or <4.5mmol/l on one occasion. Adjust the short acting insulin to achieve satisfactory blood glucose levels 2 hours after the meal or before the next meal. ADVANCED APPROACH TO INSULIN INITIATION Basal bolus regimen with twice daily intermediate insulin (Humulin I, Insulatard) Add total daily dose of premixed insulin. Usually take off 20%. In some circumstances it may not be appropriate to take off 20%, e.g. very poor glycaemic control or symptomatic of high blood sugars. Give 50% as basal insulin divided into two equal doses. Divide remainder to cover meals with quick acting insulin dependant on their eating habits. Eg. Mixtard 30: 50 units am, 50 units pm. Total daily dose = 100 units - 20% = 80 units. 50% of dose divided into two injections of intermediate insulin. 20 units am and 20 units pm. Remainder given as quick acting insulin with 12-14 units each meal dependant on eating habits. INDICATION FOR CHANGE OF REGIMEN Difficulty in giving multiple injections. Change to a more regimented lifestyle, where patient does not require the flexibility. The approach to insulin therapy is continuously changing. Recent evidence suggesting a more proactive and calculated dose and titration may be more appropriate for those experienced in insulin management. To adopt this approach see the Leicestershire Diabetes website: www.leicestershirediabetes.org.uk Date of preparation: March 2005. For review: March 2007

HOW TO ADJUST INSULIN USING BLOOD GLUCOSE RESULTS FOR A TWICE DAILY PREMIXED INSULIN PREMIXED INSULIN REGIMEN IS NB. YOU MAY NEED A BEDTIME SNACK ON THIS REGIME! TARGET BLOOD TESTS BEFORE MEALS Target 5-6 Target >4-6 Target >4-6 Target >6-8 In the absence of nocturnal hypoglycaemia INSULIN INSULIN BREAKFAST LUNCH EVENING MEAL BEDTIME High = increase previous evenings insulin by 2 units or 10%, whichever is greater High = increase breakfast insulin by 2 units or 10%, whichever is greater High = increase breakfast insulin by 2 units or 10%, whichever is greater High = increase evening meal insulin but not if blood tests at breakfast are 4-5 POINTS TO REMEMBER Low = decrease previous evenings insulin by 2 units or 10%, whichever is greater Low = decrease breakfast insulin by 2 units or 10%, whichever is greater Note: Exclude other causes of high or low blood glucose, such as timings of injections, injection sites, lifestyle changes etc. prior to adjusting insulin dose. Look for trends over 3-4 days. Adjust insulin every 3-4 days until targets are reached or hypoglycaemia becomes a problem. Low = decrease breakfast insulin by 2 units or 10%, whichever is greater Low = decrease evening meal insulin by 2 units or 10%, whichever is greater Consider 2am blood glucose reading if blood sugar is in target at bedtime but low, high or variable before breakfast. Alter insulin dose by 10% or by 2-4 units. Speak with your diabetes specialist if unsure. Date of preparation: March 2005. For review: March 2007

HOW TO ADJUST INSULIN USING BLOOD GLUCOSE RESULTS FOR A BASAL INSULIN REGIME WITH ORAL HYPOGLYCAEMIC AGENTS (eg. GLARGINE OR DETEMIR) ORAL HYPOGLYCAEMIC AGENTS ARE LONG ACTING INSULIN IS TARGET BLOOD TESTS Target >4-6 In the absence of nocturnal hypoglycaemia Long acting (24hr) insulin is usually given at bedtime (9-10pm) or with evening meal, although long acting analogues (Glargine and Detemir) can be given am or pm but must be consistent from day to day INSULIN BREAKFAST LUNCH EVENING MEAL BEDTIME High = increase basal insulin by 2 units or 10%, whichever is greater Low = decrease basal insulin by 2 units or 10%, whichever is greater High = review oral medication Low = review oral medication High = review oral medication Low = review oral medication High = review oral medication Low = review oral medication WHEN USING LONG ACTING ANALOGUES: IF MOST BLOOD TESTS ARE HIGH OVER 24 HOURS INCREASE THE DOSE BY 2 UNITS OR 10%, WHICHEVER IS GREATER IF MOST BLOOD TESTS ARE LOW OVER 24 HOURS DECREASE THE DOSE BY 2 UNITS OR 10%, WHICHEVER IS GREATER POINTS TO REMEMBER Note: Exclude other causes of high or low blood glucose, such as timings of injections, injection sites, lifestyle changes etc. prior to adjusting insulin dose. Look for trends over 3-4 days. Adjust insulin every 3-4 days until targets are reached or hypoglycaemia becomes a problem Consider 2am blood glucose reading if blood sugar is in target at bedtime but low, high or variable before breakfast. Alter insulin dose by 10% or by 2-4 units. eg. 30 units would require an adjustment of 3 units. Speak with your diabetes specialist if unsure. Date of preparation: March 2005. For review: March 2007

HOW TO ADJUST INSULIN USING BLOOD GLUCOSE RESULTS FOR A BASAL BOLUS REGIME MEAL RELATED INSULIN IS BACKGROUND INSULIN IS TARGET BLOOD TESTS BEFORE MEALS Target >4-6 Target 4-6 Target 4-6 Target >6-8 In the absence of nocturnal hypoglycaemia MEAL RELATED INSULIN (quick or short acting) BACKGROUND INSULIN (SEE NOTE BELOW) BREAKFAST LUNCH EVENING MEAL BEDTIME High = increase bedtime background insulin (unless hypo overnight) Low = decrease bedtime background insulin High = increase breakfast related insulin Low = decrease breakfast realted insulin High = increase lunch related insulin Low = decrease lunch related insulin High = increase evening meal related insulin Low = decrease evening meal related insulin NB: In certain circumstances POINTS TO REMEMBER Note: Exclude other causes of high or low blood glucose, such as timings of injections, injection sites, lifestyle changes etc. prior to adjusting insulin dose. Look for trends over 3-4 days. Adjust insulin dose the next day to improve blood glucose control. Change one type of insulin at a time. Consider 2am blood glucose reading if blood sugar is in target at bedtime but low, high or variable before breakfast Alter insulin dose by 10% or by 2-4 units. eg. 30 units would require an adjustment of 3 units. Speak with your health care professional if unsure. background insulin may be given at other times of day or twice daily dependent on individual needs, such as BGM, hypoglycaemia or lifestyle issues, but must be consistent from day to day.