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Impaired fasting glycaemia

Progression to diabetes
Results
Risk factors
Results
Lifestyle intervention
Results
Comment

In recent years the diagnostic cut-off value for fasting glucose has been reduced from 7.8 mmol/L to 7.1 mmol/L. A new category of intermediate impairment of glucose metabolism has been introduced, that of impaired fasting glycaemia, with a fasting glucose of 6.1 to 6.9 mmol/L, to define a state intermediate between diabetes and normal glucose metabolism. This poses some questions, about the risk of progressing to diabetes with impaired fasting glycaemia, and about the risk factors, and how to deal with the condition.

Progression to diabetes

A study from Helsinki provides an answer about the risk of progressing to diabetes with impaired fasting glycaemia [1]. In 1987 it recruited several thousand adults aged 45-64 years and measured fasting glucose, and glucose two hours after a 75 gram oral load. Impaired fasting plasma glucose was defined as 6.1 to 6.9 mmol/L, and impaired glucose tolerance was defined as a two-hour plasma glucose between 7.8 and 11 mmol/L.

Those free of diabetes at baseline (fasting plasma glucose below 7 mmol/L and/or two-hour glucose below 11 mmol/L) were followed for 10 years, and details of incident diabetes obtained from a computerised record linkage system.

Results

There were 2,593 participants free of diabetes at baseline who provided 26,700 years of follow up. Impaired glucose tolerance was more common than impaired fasting glucose, and only 1.5% of participants had both impaired fasting glucose and impaired glucose tolerance (Table 1).

The risk of progression to diabetes over 10 years was significantly higher with impaired fasting glucose (Figure 1) and with impaired glucose tolerance (Figure 2). The risk of developing diabetes over 10 years was 1 in 50 for an adult aged 45-64 years with normal fasting glucose and glucose tolerance, and rose to 1 in 2 for an adult with both tests impaired. For impaired fasting glucose the risk was 1 in 22 (Table 1). Men and women had the same level of risk.



Figure 1: Initial fasting plasma glucose and risk of diabetes over 10 years







Figure 2: Plasma glucose 2 hours after 75 g load and risk of diabetes over 10 years







Table 1: Risk of developing diabetes over 10 years at different levels of normal or impaired glucose metabolism in a Finnish population



Fasting plasma glucose
Oral glucose load
Percent of total
Normal
Normal
82.1
Impaired
Normal
4.0
Normal
Impaired
12.4
Impaired
Impaired
1.5


Risk factors

A Danish study [2] looked at risk factors in persons with impaired fasting glycaemia and those with impaired glucose tolerance. It surveyed 1,374 adults aged 20-69 from a single practice (66% of eligible patients), and under standardised conditions measured both fasting blood glucose and performed a glucose tolerance test with a 75 gram oral load. Physical examination and patient questionnaire gathered information on risk factors.

Results

Of the 1,374 patients, 50 had diabetes according to the WHO (1999) criteria. Nineteen had been previously diagnosed, but 31 (2.3%) were previously not known to have diabetes. In all of them the diagnosis was confirmed on re-examination.

Fifty-one adults (3.7%) had impaired fasting glycaemia (defined here as fasting blood, as opposed to plasma, glucose of 5.6 to 6.0 mmol/L), and 90 (6.6%) had impaired glucose tolerance (two hour blood glucose of 6.7 to 9.9 mmol/L). There were no differences between these two groups for any of a whole range of risk factors for vascular disease. The mean age was about 50 years, about half were women, the average BMI was 28, and the average cholesterol 5.6 mmol/L.

Lifestyle intervention

A large US randomised trial [3] shows that lifestyle modification is an effective intervention for preventing or delaying progression from impaired fasting glycaemia to diabetes. The study recruited adults of 25 years or older with a BMI of 24 or higher and a fasting plasma glucose of 5.3 to 6.9 mmol/L or plasma glucose two hours after a 75 gram oral load of 7.8 to 11 mmol/L. They were randomised to placebo plus standard lifestyle recommendations in the form of written information and an annual session encouraging healthy lifestyle, or intensive lifestyle interventions aimed at weight reduction, exercise, and low-calorie, low-fat diet taught on a personal basis in 16 sessions over the initial 24 weeks. The outcome was progression to diabetes. There was also a metformin-treated group, but that is not reported here.

Results

In the three groups there were 3,234 participants, with 2,161 in placebo and intensive lifestyle groups. They were followed for an average of 2.8 years. Half the participants in the intensive lifestyle group had lost 7% or more of their body weight at 24 weeks, and 38% maintained their weight loss to the end of the study. The majority (60%) had maintained a weekly goal of 150 minutes of physical exercise a week by the end of the study. After one year, the average daily calorie reduction was 250 kcal in the placebo group and 450 kcal in the intensive lifestyle group.

Diabetes incidence was 58% lower in the intensive lifestyle group than the placebo group (Table 2), with a crude number needed to treat to prevent one case of diabetes over 2.8 years of 16. Metformin treatment without the intensive lifestyle intervention achieved a 31% reduction in incidence of diabetes.



Table 2: Development of diabetes over 2.8 years with placebo and lifestyle modification



Percent with diabetes
Placebo
Lifestyle
Crude NNTp
Overall
11
4.8
16.1
Fasting plasma glucose (mmol/L)
5.3-6.1
6.4
2.9
28.6
6.1-6.9
22.3
8.8
7.4
Two hours after 75 gram oral glucose load (mmol/L)
7.8-8.5
7.1
1.8
18.9
8.5-9.6
10.3
4.4
16.9
9.6-11
16.1
8.5
13.2


The largest impact of intensive lifestyle intervention was in participants (about one third of the total) who had impaired fasting glycaemia with fasting plasma glucose of 6.1 to 6.9 mmol/L (Table 2).

Comment

Impaired fasting glycaemia is not uncommon. It affected about 4% of adults aged 20-64 in the two Scandinavian studies (Table 3). But of equal interest was that as many as 15% (1 in 8) adults had some form of impairment of glucose metabolism. Cardiovascular risk factors were about the same with whichever form of impaired glucose metabolism.



Table 3: Percentage of adults in Scandinavia with different levels of glycaemic control



Fasting plasma glucose status Glucose load status
Percent
Normal Normal
84.6
Impaired Normal
4.0
Normal Impaired
10.2
Impaired Impaired
1.3


The bad news is that type 2 diabetes is much more likely to develop in people with impaired glucose metabolism, especially those with both impaired fasting glycaemia and impaired glucose tolerance, where the risk was 1 in 2 over 10 years. In the randomised trial [3] progression to diabetes in people with impaired fasting glycaemia was 22% over less than three years, while the Scandinavian study had only 5% over 10 years. The cause of this large discrepancy is not obvious. There was not such a big difference in participant characteristics, so perhaps it represents something of a cultural divide between the USA and Finland.

The good news is that people with impaired fasting glycaemia can change their lifestyle to stave off, or delay, the onset of diabetes. It's the same old story: lose weight, exercise, and eat a healthy diet. But the sting in the tail is that if progression to diabetes is lower in Europe than the USA, the effects of better lifestyle, while good for their own sake, may be less evident. Getting to the root of the large differences in progression to diabetes would be illuminating.

References:

  1. Q Qiao et al. Progression to clinically diagnosed and treated diabetes from impaired glucose tolerance and impaired fasting glycaemia. Diabetes Medicine 2003 20: 1027-1033.
  2. PE Heldgaard et al. Impaired fasting glycaemia resembles impaired glucose tolerance with regard to cardiovascular risk factors: population-based, cross-sectional study of risk factors for cardiovascular disease. Diabetes Medicine 2004 21: 363-370.
  3. Diabetes Prevention Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. New England Journal of Medicine 2002 346: 393-403.

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