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National Collaborating Centre for Chronic Conditions (UK). Type 2 Diabetes: National Clinical Guideline for Management in Primary and Secondary Care (Update). London: Royal College of Physicians (UK); 2008. (NICE Clinical Guidelines, No. 66.)

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

Cover of Type 2 Diabetes

Type 2 Diabetes: National Clinical Guideline for Management in Primary and Secondary Care (Update).

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7Glucose control levels

7.1. Clinical monitoring of blood glucose control

7.1.1. Clinical introduction

The risk of arterial disease and microvascular complications in people with diabetes are known to be related to the extent of hyperglycaemia with time. While the lifestyle, oral agent, and injectable therapies discussed in this guideline can improve blood glucose control, their efficacy is limited, as the underlying pathogenesis of diabetes worsens with time. As symptoms are not a reliable guide to blood glucose control in people on therapy, it is important to have an accurate means of measuring blood glucose control over time, to enable decision-making.

This section addresses the clinical questions as to the tests of blood glucose control best predictive of future vascular damage from diabetes, the nature of the relationship between test results and such vascular risk, how tests should be deployed in clinical practice, and how they might be interpreted.

7.1.2. Methodological introduction

The UKPDS is a large (N=3,867) landmark study with a 10-year follow-up period. It evaluated whether in people newly diagnosed with Type 2 diabetes more intense therapy to achieve tighter glycaemic control would result in a greater reduction in the incidence of microvascular and macrovascular complications than would conservative therapy. Due to the size and duration of this study, other studies published from 2001 onwards in this area were only considered if they had a sample size of at least N=2,000 people with Type 2 diabetes, or mixed Type 1 and 2 diabetes populations. Studies were not reviewed if they simply found significant associations between HbA1c and diabetes complications without giving further information about that association.

Published results from the UKPDS were included in this review if they specifically reported results on the relationship between HbA1c and microvascular and/or macrovascular complications. One prospective observational study28 was identified which analysed the UKPDS glucose control results in terms of both macrovascular and microvascular complications.

A meta-analysis29 was also identified which assessed the association between glycosylated haemoglobin and cardiovascular (CV) disease in people with diabetes. This included an analysis of 10 studies specifically of people with Type 2 diabetes. As some of the cohorts included in this analysis were participants in the UKPDS study, it is necessary to be alert to double-counting.

Other observational studies identified, which were not published results of the UKPDS study or included in the meta-analysis, considered the relationship between glycaemic control and CV and renal risk,30 and between glycaemic control and heart failure.31

7.1.3. Health economic methodological introduction

One paper was identified which was excluded from further consideration as it was not possible to compare the costs between patients with good or poor control because the well-controlled patients were probably earlier in the course of the disease.32 Two evaluations based on the UKPDS were identified that were considered to be of good quality.33

7.1.4. Evidence statements

7.1.5. Health economic evidence statements

The UKPDS included an analysis of intensive blood glucose control with metformin for overweight patients compared to conventional treatment primarily with diet. The study included 753 overweight (>120% ideal body weight) patients with newly diagnosed Type 2 diabetes from 15 hospital-based clinics in England, Scotland and Northern Ireland. Of these patients 342 were allocated to an intensive blood glucose control policy with metformin and 411 were allocated to conventional treatment, primarily with diet alone. The study was conducted from 1977 to 1991. The median follow-up period was 10.4 years.

In the conventional policy group the glycaemic goal was to obtain the lowest fasting plasma glucose (FPG) attainable with diet alone. In the intensive policy group the aim was a FPG of less than 6.0 mmol/l by increasing the dose of metformin from 500 to 2,550 mg a day as required. Use of metformin for intensive blood glucose control in overweight patients was found to confer a 32% risk reduction for any diabetes related endpoint and a 42% risk reduction for diabetes related deaths compared with a conventional policy.

In the 2001 cost-effectiveness analysis, intensive treatment with metformin cost on average £258 less than conventional treatment, and resulted in a longer life expectancy of 0.4 years.34

In the 2005 cost-utility analysis the discounted cost (6% discount rate) of an intensive blood glucose control policy with insulin or sulphonylureas was on average £884 more per patient and the discounted benefits gained were 0.15 quality of life-adjusted year (QALY), a cost per QALY gained of £6,028.33

The discounted cost of intensive blood glucose control policy with metformin in overweight patients was on average £1,021 less than the conventional policy and had a longer discounted life expectancy of 0.55 QALYs, making this intensive treatment strategy both cost-saving and more effective.34

7.1.6. From evidence to recommendations

There were a number of difficulties agreeing the level at which therapeutic interventions should begin or be enhanced. It was agreed that people with diabetes and the professionals advising them needed a reference level if optimum glucose control is to be obtained. It was noted that treat-to-target studies achieved much better outcomes than studies with less well defined aims.

The evidence base has not significantly moved on since the earlier guideline, except to support the conclusions of the UKPDS epidemiological analysis (that CV risk fell linearly well into the normal range of HbA1c). A single target figure is unhelpful as this may vary in individuals depending on the:

  • quality of life that might have to be sacrificed in reaching the target
  • extent of side effects
  • resources available for management.

An individual requiring insulin for adequate control, who is at risk and prone to hypoglycaemia would have a higher personal target of glucose control than someone newly diagnosed who had adopted significant lifestyle changes.

Microvascular risk data suggests higher glucose control targets. This led to a stronger recommendation in the NICE/RCP Type 1 diabetes guideline for those at no added macrovascular disease risk. Most of those with Type 2 diabetes can be regarded as at high macrovascular risk, by reason of phenotype or age.

Cardiovascular risk can be reduced by 10–15% per 1.0 % reduction of HbA1c, the treatment effect and epidemiological analysis of UKPDS giving the same conclusions. Mean levels of close to 6.5 % were achieved in the first 5 years of the UKPDS in both the main glucose study and the obese (‘metformin’) study in the active treatment arms. The epidemiological analysis supports a linear fall in macrovascular risk down to 6.0 % or below, and this will largely reflect data from the more actively managed group.

However, expensive therapies or very intensive interventions are required to achieve glucose control in the normal range in most people with diabetes. Consequently a population target should not be any tighter than the HbA1c of 6.5 % previously chosen for those at macrovascular risk. Nearly all people with Type 2 diabetes are of high CV risk, usually in association with insulin insensitivity, but if not with age. Additionally there has been very recent concern (no evidence yet to review) about pursuing very intensive glucose control (target <6.0 %) in people with higher CV risk and longer duration of diabetes, mostly on multiple insulin injection therapy.35

The GDG were made aware of the issue of postprandial plasma glucose control, and that it could be specifically targeted in some circumstances and with some interventions. A review of the literature in this regard had not been performed for the present guideline. However, the GDG were informed that an evidence-based guideline had been published by the IDF since completion of the current guideline draft, and that no RCTs addressing the question with true health outcomes as an endpoint had been identified. Accordingly a view to treat this aspect specifically relied on weaker evidence. Accordingly the GDG were content only to make recommendations on the identification of pre-meal and postprandial hyperglycaemia, and levels for intervention.

The GDG expressed concern that intervention levels for enhancement of therapy should not be confused with audit or reimbursement standards. These types of standards are set with much greater attention being paid to attainability.



When setting a target glycated haemoglobin HbA1c:

  • involve the person in decisions about their individual HbA1c target level, which may be above that of 6.5 % set for people with Type 2 diabetes in general
  • encourage the person to maintain their individual target unless the resulting side effects (including hypoglycaemia) or their efforts to achieve this impair their quality of life
  • offer therapy (lifestyle and medication) to help achieve and maintain the HbA1c target level
  • inform a person with a higher HbA1c that any reduction in HbA1c towards the agreed target is advantageous to future health
  • avoid pursuing highly intensive management to levels of less than 6.5 %.

Measure the individual’s HbA1c levels at:

  • 2–6-monthly intervals (tailored to individual needs), until the blood glucose level is stable on unchanging therapy; use a measurement made at an interval of less than 3 months as an indicator of direction of change, rather than as a new steady state
  • 6-monthly intervals once the blood glucose level and blood glucose lowering therapy are stable.

If HbA1c levels remain above target levels, but pre-meal self-monitoring levels remain well controlled (<7.0 mmol/l), consider self-monitoring to detect postprandial hyperglycaemia (>8.5 mmol/l), and manage to below this level if detected (see chapters 911).


Measure HbA1c using high-precision methods and report results in units aligned with those used in DCCT Trial (or as recommended by national agreement after publication of this guideline).218


When HbA1c monitoring is invalid (because of disturbed erythrocyte turnover or abnormal haemoglobin type), estimate trends in blood glucose control using one of the following:

  • fructosamine estimation
  • quality-controlled plasma glucose profiles
  • total glycated haemoglobin estimation (if abnormal haemoglobins).

Investigate unexplained discrepancies between HbA1c and other glucose measurements. Seek advice from a team with specialist expertise in diabetes or clinical biochemistry.

Copyright © 2008, Royal College of Physicians of London.

All rights reserved. No part of this publication may be reproduced in any form (including photocopying or storing it in any medium by electronic means and whether or not transiently or incidentally to some other use of this publication) without the written permission of the copyright owner. Applications for the copyright owner’s written permission to reproduce any part of this publication should be addressed to the publisher.

Bookshelf ID: NBK53890


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