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.