GLYCAEMIC CONTROL

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CHAPTER 3 GLYCAEMIC CONTROL

Monitoring 62

Blood glucose-lowering medication 65

Metabolic emergencies 82

OVERVIEW

NSF

QOF

DM5–7

To achieve and maintain the targets (Table 3.1) of optimal glycaemic control can be difficult because of the progressive deterioration of pancreatic insulin secretion. Success is more likely if the patient, in collaboration with the professional and guided by monitoring of glycaemic control, masters the complex task of balancing the three key components of diet, physical activity and blood glucose-lowering medication dosage.

TABLE 3.1 Targets for optimal glycaemic control

Target	Who monitors	Action
Avoiding hypoglycaemia	Patient	Recognises warning signs
		Balances regular meals, correct dose of therapy and physical activity
		Able to correct promptly
	Professional	Assesses needs and educates
Fasting blood glucose of 4 to 7 mmol/l	Patient	Able to do and interpret tests
	Patient	Adjusts therapy accordingly
	Professional	Assesses needs and educates
Glycated haemoglobin of less than 7.0%^*	Patient	Understands significance of test result
	Patient	Adjusts therapy accordingly
	Professional	Repeats regularly
	Professional	Advises on appropriate therapy changes

* Individualised HbA1c targets should be set between 6.5 and 7.5%; the lower value is preferred for patients at significant risk of vascular complications, the higher may be more appropriate for those with limited life expectancy or at risk of iatrogenic hypoglycaemia

This chapter discusses self-monitoring and blood glucose-lowering medication. Diet and physical activity are discussed in Chapter 2.

MONITORING

NSF

Glycaemic control can be assessed in three complementary ways:

1. Glycosylated haemoglobin (or fructosamine)

2. Patient self-monitoring of either blood or urinary glucose

3. Patient symptoms.

GLYCOSYLATED HAEMOGLOBIN (OR FRUCTOSAMINE)

QOF

DMS–7

Glycosylated haemoglobin, or HbA1c, is formed by the non-enzymatic glycation of part of the β-chain of haemoglobin. HbA1c levels correlate to the mean plasma glucose over the preceding 9–10 weeks. The relationship between HbA1c and mean plasma glucose levels is shown in Table 3.2. A recent HbA1c result should normally be available at the full periodic review. HbA1c should be checked more frequently when control is poor or glycaemic management has been altered. The estimation of HbA1c requires expensive equipment and stringent quality control: it is generally not feasible in primary care and is best done by a hospital laboratory.

TABLE 3.2 Correlation between HbA1c level and mean plasma glucose levels (Rohlfing et al 2002)

HbA1c (%)	Mean plasma glucose level (mmol/l)
6	7.5
7	9.5
8	11.5
9	13.5
10	15.5
11	17.5
12	19.5

Serum fructosamine levels, if available, correlate to the mean plasma glucose over the preceding 1–2 weeks and may serve as an alternative if the HbA1c is not “valid”, such as in the presence of anaemia or a haemoglobulinopathy.

PATIENT SELF-MONITORING

Achieving and maintaining good glycaemic control usually requires effective patient self-monitoring and/or monitoring by his carer. Health education is an essential component of self-monitoring. The patient needs to be motivated and able to test accurately, interpret the results correctly and act upon them appropriately: this can only be achieved by regular patient education. Self-monitoring results should be recorded and brought to any diabetes review where glycaemic control is discussed.

Urine testing

Testing urine for the presence of glucose using test strips, such as Diabur-Test 5000, is non-invasive, inexpensive and may be preferred by patients who dislike blood testing, although there is some recent evidence that patients with type 2 diabetes can have negative perceptions about urine testing (Lawton 2004).

However, urine glucose testing has two main drawbacks:

1. The quantity of glucose, if any, in a sample of recently formed urine is more indicative of the mean blood glucose levels over the period of time when the urine was formed than of the blood glucose level at a given moment. Urine levels of glucose do not reflect any sudden fluctuation in blood glucose levels and are, thus, inexact.

2. In some type 2 patients, the renal threshold for glycosuria is abnormally high or low. Thus, it is possible for no glycosuria to be present with a moderately raised blood glucose level, or for glycosuria to be present with a normal blood glucose level.

Despite these limitations, if adequate glycaemic control (i.e. good HbA1c, infrequent hypoglycaemia) is achieved with urine testing, then blood testing may be unnecessary in type 2 diabetics on diet alone or oral medication. Once diabetic control is stable, the urine should usually be negative for glucose. If it becomes persistently raised (e.g. more than 2% on four consecutive days) or the patient becomes ill, professional advice should be sought.

Blood testing

Blood glucose testing is recommended for diabetics treated with insulin (both types 1 and 2), but may be desirable in patients on diet alone or oral medication, who require accurate blood glucose estimations. Blood glucose testing is more expensive than urine testing, and requires the correct use of a properly calibrated blood glucose meter and appropriate education to develop self-confidence in interpreting and acting upon test results.

Many varieties of finger-pricking lancets, blood glucose machines and test strips or sensors are now available, but only the lancets and strips/sensors can be prescribed on the NHS. Each different make of blood glucose machine has its own unique test strips. The current issue of the Monthly Index of Medical Specialities (MIMS) lists each make of test strip and the machine(s) with which it is compatible. There have been significant technical advances in machines, with sensors allowing the blood drop to be analysed outside the machine. A rigorous evaluation of the different blood glucose meters and lancing devices now available on the UK market was published in 2005 by the Department of Health’s Medicines and Healthcare products Regulatory Agency (details can be downloaded from its website, www.mhra.gov.uk). This useful source should assist in selecting the most suitable machine or device. Recently the MHRA has identified a safety problem with some blood glucose meters, where units of measurement may change and mislead the user.

Although blood glucose machines are not currently available on prescription, many are inexpensive, often costing less than £20 (the manufacturers’ main profit is in the sale of the test strips or sensors). If the GP writes a letter simply confirming the diagnosis of diabetes in a named patient, then that patient is exempt from paying Value Added Tax (VAT) when purchasing his machine, provided that the machine is intended for that patient’s personal use. Lancets need to be disposed of safely; preferably using either a needle clip or a sharps bin (both can be prescribed).

Most official guidance and Diabetes UK advocate regular home blood glucose monitoring, even in type 2 diabetics, but there is not yet a clear consensus on how frequently to test. The latest ADA guidelines recommend 2 to 3 times daily in patients with type 1 diabetes, but possibly more often in patients with type 2 diabetes on insulin (ADA 2007). However, an editorial in the British Medical Journal challenged the conventional advice given about frequency of testing; it suggested that regular monitoring is not always necessary and that properly conducted large-scale studies need to be done to determine whether more frequent testing will improve glycaemic control (Reynolds 2004). It is sensible to test more frequently if control is poor or if the patient is unwell.

Plasma glucose values are 11% higher than whole blood glucose values. Machines will be calibrated to either of these. The blood glucose targets for good control are 4–7 mmol/l pre-meal and < 10 mmol/l post-meal. If glycosuria or raised blood glucose is found, an increased dose of either the oral blood glucose-lowering drug or insulin may be appropriate. Dietary energy intake, if excessive, should be reduced. If the medication is given in divided doses, the dose that covers the tested time of day must be adjusted accordingly. However, if after stabilisation and despite adjustment of treatment, the blood glucose becomes > 20 mmol/l for more than 4 days, or if the patient becomes ill, then he should seek medical help urgently. Persistently abnormal levels should prompt a review of the balance between medication, diet and physical activity.

PATIENT SYMPTOMS

Patient well-being is a much less precise and a potentially misleading method of assessing glycaemic control, particularly as hyperglycaemia is not always symptomatic. However, most professionals and patients recognise that abolition or reduction of diabetic symptoms, such as polydipsia, diuresis, blurred vision and fatigue is both necessary and desirable.

Recurrent hypoglycaemia indicates poor glycaemic control; these episodes may occur when there has been an error in dosage of blood glucose-lowering medication (usually insulin), a small or missed meal or unplanned exercise (when medication dosage has not been correctly reduced). Sometimes, there is no apparent cause for hypoglycaemia.

BLOOD GLUCOSE-LOWERING MEDICATION

In patients with type 2 diabetes, there is likely to be a progressive deterioration over time of pancreatic β-cell function, resulting in most patients eventually requiring insulin to achieve acceptable glycaemic control. The main classes of oral blood glucose-lowering medication act by improving either insulin secretion (insulin secretagogues) or insulin action. For a drug to stimulate insulin secretion, it is necessary for the pancreatic β-cells to still be functioning. Further details about the drug classes discussed below can be found in the British National Formulary (BNF, section 6.1.2).

A stepped approach to achieving and maintaining metabolic control is sensible. Starting with lifestyle changes and the early introduction of monotherapy, it moves progressively onto logical and effective combinations of different agents if the HbA1c remains greater than 7.0%. This is summarised in Table 3.3, with more than one option at some numbered steps, choice depending upon the clinical circumstances and patient preference (ADA 2007). It is the authors’ personal view that, in primary care, basal insulin is best introduced only when maximal oral therapy (including triple therapy, if feasible) cannot achieve good metabolic control.

TABLE 3.3 Summary of the stepped treatment of raised blood glucose in type 2 diabetes

At each numbered step, letter “a” is first choice option, subject to drug contraindications, clinical circumstances and patient preference.
Step	Evaluation	Intervention
1	HbA1c <7.0%	Lifestyle advice (diet and physical activity)
2a	a. HbA1c ≥7.0% b. Absence of significant renal (eGFR <45 ml/min), hepatic or cardiac impairment or risk of sudden deterioration

Metformin 2b

a. HbA1c ≥7.0%

b. Metformin not tolerated orcontraindicated

Insulin secretagogue (usually sulphonylurea) or glitazone (alternative in renal impairment) 3a HbA1c ≥7.0% on first-line drug (maximum tolerated dose) Combination of: metformin and insulin secretagogue (usually sulphonylurea) 3b

a. HbA1c ≥7.0% on first-line drug (maximum tolerated dose)

b. Insulin secretagogue not tolerated or likely high level of insulin resistance

Combination of: metformin and glitazone 4a

a. HbA1c ≥7.0% (but less than 8.0%) on two oral drugs (maximum tolerated doses)

b. Very obese or unwilling to consider insulin therapy

c. Absence of contraindications

Combination of metformin and sulphonylurea and rosiglitazone 4b

a. HbA1c ≥7.0% on two oral drugs (maximum tolerated doses)

b. Triple therapy not tolerated/contraindicated or unlikely to work (very raised HbA1c)

Add basal insulin^* 5 HbA1c ≥7.0% on combination of basal insulin and oral agent(s) Intensify insulin regimen (consider adding rapid-or short-acting)

* Of the two glitazones, only pioglitazone currently has a licence to be prescribed in combination with insulin.

Changes to treatment should be guided not only by a recent HbA1c, but also self-monitoring results, opportunities to optimise lifestyle and the patient’s well-being and concordance. The interval between any dose changes must allow sufficient time for their effect to be seen, but prompt action is indicated in the event of repeated hypoglycaemia or significant hyperglycaemia. Ideally, additional medication should be introduced only after the maximum recommended dose of current medication has failed to achieve reasonable glycaemic control or is not tolerated.

Other medical problems must be managed appropriately. If uncertain about any aspect of management, it is sensible to seek specialist help.

INSULIN SECRETAGOGUES (DRUGS THAT IMPROVE INSULIN SECRETION)

Currently, there are two main groups of drugs that increase insulin secretion:

1. Sulphonylureas, some of which have been available for many years

and

2. Post-prandial regulators of glucose (PPRGs), also known as meglitinide analogues. These have been introduced more recently and have a rapid onset and short duration of action.

NICE’s Clinical Guidelines in 2002 recommended that “a generic sulphonylurea should normally be the insulin secretagogue of choice” (NICE 2002).

Sulphonylureas

This class of drugs acts by stimulating insulin secretion from pancreatic β-cells (although there is less stimulation of first-phase secretion than by the PPRGs), but do not affect insulin resistance. In the absence of ketonuria, sulphonylureas are indicated in nonobese patients whose blood glucose is not controlled by diet. Sulphonylureas can be combined with either metformin, a glitazone, basal insulin or acarbose. The following agents are available: tolbutamide, glibenclamide (glyburide), gliclazide (also available in a modified-release formulation), glimepiride, gliquidone, glipizide and chlorpropamide. Sulphonylureas should be introduced slowly with the dose titrated according to self-monitoring and HbA1c results.

The different sulphonylureas appear to have a comparable effect upon blood glucose-lowering, but with different durations of action. Although both once-daily and twice-daily dosing are associated with better concordance, once-daily preparations have the advantages of reducing the total number of tablets that a patient needs to take and of potentially simplifying the drug regimen.

Sulphonylureas are contraindicated in severe hepatic and renal impairment, porphyria, during breast feeding and pregnancy, or when ketoacidosis is present. The short-acting tolbutamide can be used in renal impairment, as can gliclazide and gliquidone, which are metabolised mainly in the liver.

The two main drawbacks associated with sulphonylureas are that they can induce hypoglycaemia and can encourage weight gain. Glibenclamide is associated with the rare but potentially fatal occurrence of nocturnal hypoglycaemia in the elderly. Weight gain was recorded with both chlorpropamide and glibenclamide (but less than with insulin) in the intensively treated group of patients in the UKPDS (UKPDS 1998). However, hypoglycaemia and weight gain are not inevitable with sulphonylureas, and the risks of either occurring may be minimised by:

• Avoiding the long-acting agents, chlorpropamide (no longer recommended) and glibenclamide.

• Avoiding use in patients with mild to moderate hepatic and renal impairment, and being careful about use in the elderly (shorter-acting agents are safer and to be preferred).

• Careful introduction and dose titration of the drug (according to the results of self-monitoring and HbA1c).

• Using the lowest dose that achieves and maintains normoglycaemia.

The side-effects of sulphonylureas are mild and infrequent, and include gastrointestinal disturbances and hypersensitivity reactions (a skin rash that usually appears within 6–8 weeks of initiation).

Post-prandial regulators of glucose (PPRGs)

These drugs are also known as meglitinide analogues or rapid-acting insulin secretagogues. The two available drugs in this group are repaglinide and nateglinide. Both can be used in combination with metformin, but nateglinide is not currently licensed for monotherapy.

The main action of PPRGs is to increase (more than sulphonylureas) the first-phase insulin secretion in response to rising plasma glucose levels by pancreatic β-cells, with the effect of reducing the mealtime “glucose spike”. PPRGs are best initiated at an earlier stage in the disease process, when pancreatic β-cells have more capacity to secrete insulin. PPRGs have a quicker onset (usually within 15 minutes) and shorter duration of action (up to 3 hours) than sulphonylureas. Nateglinide appears to have a slighter quicker onset and shorter duration of action than repaglinide. PPRGs may be preferable to sulphonylureas in a patient who either wishes or needs to fast (e.g. during Ramadan), or whose meal times are unpredictable and/or irregular.

PPRGs should be avoided in patients with severe liver disease or on dialysis, and in pregnancy, breast feeding and ketoacidosis. Their side-effects include hypoglycaemia, particularly in elderly patients and in those with adrenal or pituitary insufficiency (probably less risk than with sulphonylureas) and hypersensitivity reactions. Weight gain is also possible, although less so than with sulphonylureas. Other side-effects reported with repaglinide include gastrointestinal disturbances, rash and visual disturbances. Nateglinide interacts with ACE inhibitors, diuretics and corticosteroids.

DRUGS THAT IMPROVE INSULIN ACTION

Biguanides

Metformin is the only available drug in this class. It remains the first-choice drug in obese type 2 diabetics and a first-line option in the nonobese. Metformin acts by decreasing gluconeogenesis in the liver and by increasing glucose uptake in peripheral tissues. Its excretion is entirely renal and it has a short half life. Metformin is not associated with either weight gain or serious hypoglycaemia. Metformin can be combined with all secretagogues, both glitazones and the different insulins.

In addition to its efficacy in helping to achieve and maintain glycaemic control, metformin has been shown to increase survival, particularly in the obese. In the UKPDS study, treatment with metformin was shown to reduce all-cause mortality by 36%, compared to treatment with either insulin or a sulphonylurea (UKPDS1998). This is why metformin remains the first-line oral hypoglycaemic agent.

Metformin’s main side-effects are on the gastrointestinal tract; these can be minimised by a stepped approach to increasing the dose and by the medication being taken with or after food. Strict adherence to all the published contraindications, related to a perceived increased risk of precipitating lactic acidosis is not supported by systemic reviews (Salpeter et al 2002), and would result in metformin being prescribed only rarely, despite its undoubted value to many patients.

There is a slight risk of precipitating lactic acidosis with metformin in vulnerable individuals. Specific contraindications and guidelines for withdrawing metformin now include (Jones et al 2003, modified by authors):

• If impaired renal function develops: reduce dose (maximum 500 mg twice daily) if serum creatinine is > 130 μmol/l; stop if serum creatinine is > 200 μmol/l.

• Avoid if hepatic (such as those with alcohol dependence) or cardiac (if there is concurrent treatment with a β-blocker) “impairment” are present.

• Withdraw during periods of suspected tissue hypoxia (e.g. through myocardial infarction, sepsis or respiratory failure).

• Withdraw for 3 days after contrast medium that contains iodine has been given and reinstate when renal function is normal and stable.

• Withdraw 2 days before general anaesthesia and reinstate when renal function is normal and stable.

As this guidance was published before the Renal NSF, clinicians may need to revisit the definition given above for renal impairment. It is reasonable to reduce metformin dose if the eGFR is < 60 ml/min and to stop metformin if the eGFR is < 45 ml/min, but any decision must balance the benefits against the risks. Metformin is contraindicated in people with heart failure; however, it has been suggested recently that metformin may not only be safe, but may potentially improve clinical outcomes (Eurich et al 2005). Further studies are required to clarify this issue.

As a precaution, some experts recommend regular renal monitoring (serum creatinine or eGFR) and serum B12 estimations in patients on long-term metformin.

Glitazones or thiazolidinediones (TZDs)

These are also known as peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists (Krentz et al 2000). They act by promoting glucose utilisation peripherally, which enhances insulin action, but does not affect insulin secretion. Glitazones are thought to activate nuclear receptors, located mainly in adipose tissue, that affect glucose and lipid metabolism, and to maintain insulin secretion by pancreatic β-cells (Day 1999) by reducing the effect of glucose “toxicity”. Once initiated, it may take 6–10 weeks for glitazones to work fully.

The two currently available glitazones, rosiglitazone and pioglitazone, were launched in the UK in 2000. Troglitazone was launched in the UK in October 1997 and voluntarily withdrawn by its manufacturers weeks later, following reports of serious hepatic reactions worldwide. Current evidence suggests that neither rosiglitazone nor pioglitazone are hepatotoxic, but liver function should be monitored. These drugs are licensed as monotherapy, in combination with either metformin OR a sulphonylurea, or in triple therapy with metformin AND a sulphonylurea (only rosiglitazone is licensed for triple therapy). Their current UK licence does not include prescribing in combination with meglitinide analogues, but pioglitazone can now be prescribed in combination insulin. When compared with placebo, both glitazones significantly reduced HbA1c levels, either as monotherapy or in combination with other anti-diabetic agents (Chiquette et al 2004). Glitazones can cause weight gain, in part through fluid retention, which may precipitate heart failure, particularly if a glitazone is combined with insulin. Recently there have been reports of a rare association between glitazones and the development of macular oedema.

The use of these agents has been the subject of debate and evolving guidance, possibly in part because both glitazones are very expensive when compared to metformin or to most sulphonylureas and because of ongoing uncertainty about their effect on outcomes. The NICE Appraisal Committee issued guidance first in 2000/1, then updated in August 2003 on the use of both rosiglitazone and pioglitazone within their current UK licences. NICE recommends their use mainly in those unable to take metformin and a sulphonylurea in combination because of lack of tolerance or a contraindication to one of these drugs (NICE Appraisal Committee 2003). However, in September 2003 the European Agency for the Evaluation of Medicinal products (EMEA) extended the licence of glitazones as preferred second-line drugs in addition to metformin in obese patients (Bailey et al 2003).

In 2004, the Association of British Clinical Diabetologists (ABCD) produced a position statement that included the following recommendations for patients with type 2 diabetes (Higgs et al 2004):

• A glitazone is the preferred second-line oral agent in addition to metformin in the obese.

• A glitazone can replace metformin in renal impairment.

• A glitazone is not a substitute for insulin if poor control on maximal tolerated metformin and sulphonylurea combination.

• Triple therapy, with rosiglitazone, metformin and a sulphonylurea, may be considered in the very obese or in patients unwilling to go onto insulin.

• Glitazones should not be used in combination with insulin, in heart failure, or in patients with pre-treatment serum transaminase levels more than 2.5 times the upper limit of normal.

In obese type 2 patients (particularly from some ethnic groups), insulin resistance is likely to be significant. This needs to be tackled by a combination of nonpharmacological (improving diet and levels of physical activity) and pharmacological interventions. If monotherapy with metformin fails to achieve adequate glycaemic control, then, as the next step, a metformin–glitazone combination may be preferred to a metformin–sulphonylurea combination, since sulphonylureas do not reduce insulin resistance.

Possibly the greatest benefit comes from using glitazones earlier in the natural history of type 2 diabetes when there is more pancreatic β-cell activity. The NICE guidelines warn that the substitution of a glitazone for a first-line drug, after failure of the metformin–sulphonylurea combination, does risk an initial worsening of glycaemic control, which may not be recoverable. Introducing insulin at this stage may be preferable to the substitution with a glitazone.

Although metformin, sulphonylureas and glitazones all reduce HbA1c, the big question is whether glitazones also have disease-modifying effects, particularly on cardiovascular outcomes.

In assessing the effect of glitazones on cardiovascular risk factors, a meta-analysis found that pioglitazone had a better effect than rosiglitazone on lipids (rosiglitazone increased LDL-C and total cholesterol and had no effect on TG levels; pioglitazone had no effect on LDL-C or total cholesterol and lowered TG levels), although both significantly increased HDL-C. No significant differences were shown between rosiglitazone and placebo in changes to systolic or diastolic blood pressure. Both glitazones are associated with weight gain (Chiquette et al 2004).

Looking at “hard” cardiovascular outcomes:

• The PROactive Study recruited 5238 type 2 diabetics with existing CVD (excluding heart failure), comparing treatment with 45 mg pioglitazone against placebo (plus existing glucose-lowering and other medications in both groups). It reported that over 3 years in the treatment group there was a statistically significant absolute risk reduction of 2.1% (NNT = 48) for a pre-specified secondary composite event rate consisting of all-cause mortality, nonfatal myocardial infarction (excluding silent myocardial infection), and stroke. However, there was no statistically significant difference between the two groups in the primary (mixed medical and surgical) endpoint for which the study was powered (Dormandy et al 2005). The interpretation of the clinical outcomes’ data is still under debate (Freemantle 2005).

There are two studies involving rosiglitazone:

• The ADOPT study recruited 4360 drug-naïve subjects, comparing treatment with rosiglitazone or metformin or glibenclamide on disease progression, β-cell function, risk markers for macrovascular complications over 4 years. The primary outcome was time to monotherapy failure (defined as a confirmed fasting plasma glucose >10 mmol/l. The cumulative monotherapy failure was 15% for rosiglitazone, 21% for metformin and 34% for glibenclamide. Rosiglitazone was associated with more weight gain and oedema than either metformin or glibenclamide, but with fewer gastrointestinal side effects than metformin and less hyperglycaemia than glibenclamide (Kahn 2006).

• The RECORD study, due to report in 2009, recruited 3966 subjects, inadequately controlled on either metformin or sulphonylurea, comparing treatment with rosiglitazone plus metformin or sulphonylurea against metformin plus sulphonylurea on cardiovascular outcomes.

Are clinicians too preoccupied with achieving and maintaining tight glycaemic control? Should the reduction of cardiovascular risk be the priority over optimising glycaemic control? It is worth noting the advice of the National Prescribing Centre in January 2006: “… before pioglitazone is even considered, it would seem sensible to ensure that the use of hypertensives, statins, aspirin and metformin is optimised according to current guidelines.” (MeReC 2006).

OTHER ORAL DRUG THERAPY

Alpha-glucosidase inhibitors

The only drug in this class currently available in the UK is acarbose (Glucobay). It inhibits intestinal alpha-glucosidase, delaying the digestion of starch and sucrose which increase blood glucose levels after carbohydrate ingestion. The result is a fall in post-prandial glucose and insulin levels. Acarbose can be prescribed either as monotherapy or in combination with other oral agents. It does not cause weight gain and is unlikely to cause hypoglycaemia as monotherapy. Its widespread use is limited by gastrointestinal side-effects, which occur in up to 60% of patients. These are dose dependent, and include flatulence, bloating and diarrhoea. As these occur most frequently at the initiation of treatment, careful titration may reduce their incidence. Acarbose is best taken with meals rich in starch. It should be considered as an alternative in patients unable to use the other oral drugs. Acarbose is expensive.

INSULIN

Insulin preparations

A wide variety of insulin preparations is currently available. Insulins can be classified according to their onset and duration of action, summarised in Table 3.4. They also vary according to their origin and method of manufacture (animal-derived, semisynthetic or synthetic), modifications that alter the duration of action, and their mode of delivery (e.g. syringe, pen, infusion device).

TABLE 3.4 Overview of insulin preparations (revised from Krentz 2001)

If the primary care team takes charge, an agreed and effective protocol should be followed. Success is possible: in one of the authors’ practice, the average HbA1c of the first 15 patients transferred onto insulin dropped from 9.7 to 6.9% (Curley, personal communication). Some innovatory teams have looked at a group approach, in which six to 10 patients can attend together, with the benefits of increased cost-effectiveness and of greater mutual support between often-anxious individuals in a similar situation.

In assessing the person who requires insulin, the following issues should be considered:

• Implications to lifestyle. Patients who switch to insulin are no longer eligible for a group 2 driving licence and for certain jobs.

• Level of support at home. This is particularly important if dexterity and/or vision are impaired and the patient may not be able to administer his or her own insulin.

• Cultural and religious beliefs. For example, animal-derived insulins are unacceptable to Muslims, Jews and strict vegans. The insulin regimen used must avoid hypoglycaemia when the patient is required to fast.

• Psychological and physical health issues. In very obese insulin-resistant patients, insulin may cause further weight gain. Many type 2 diabetics who switch to insulin may be frightened of needles and may regard the switch as a “failure”. A clear explanation of the likely benefits that arise from good diabetic control with a demonstration using a syringe or pen may go some way to alleviating these fears.

Key educational points for insulin conversion

Clear and correct advice on the following aspects of self-administering insulin should be given to patients, and suitable written literature should be made available for reference (Avery & Moore 1999).

Equipment: choosing a suitable injection device

The choice is between a disposable U100 insulin syringe with an attached needle and one of the wide range of pen-injector devices. Both have their respective advantages and disadvantages. Staying in touch with a friendly diabetes specialist nurse should enable the primary care team to keep up-to-date with developments. MIMS is a useful source of information about the syringes, pen needles and most pens that are available free on FP10 prescription. Syringes are smaller and lighter than pens, but pens are more portable, may be more suitable for those with visual problems and the patient does not need to carry a vial of insulin to be drawn up for each injection. Both syringes and pens require some degree of manual dexterity to use.

Mixing insulins

If free-mixing insulins, the short-acting preparation must be drawn into the syringe before the intermediate-acting preparation to avoid contamination of the short-acting vial with protamine or zinc.

Injection technique

The injection technique is as important as the type of insulin injected or the device used. The three key factors that influence insulin absorption are depth, site and technique (see Table 3.5):

TABLE 3.5 Guidance for choosing appropriate needle size and injection technique (Wilbourne 2002)

Patient	Injection technique	Needle size (mm)
Overweight adult	Pinch-up, 90°	12.7
	No pinch-up, 45°	12.7
	No pinch-up	8
Normal-weight adult	Pinch-up, 90°	8
Thin adult	No pinch-up, 90°	5 or 6
Children, adolescents	No pinch-up, 90°	5 or 6