Major advances in recent years have resulted in an actualdecrease of some complications, notably nephropathy.
Primary prevention of diabetic complications, together with retardation
of their progression, is now possible, chiefly by tight control of
the diabetes and of hypertension, together with reduction of
other “risk factors”
Even when the complications are established, their progression leading to
serious damage can be delayed.
Although many attempts have been made to develop
specific pharmacological agents to alter the course of diabetic
complications, and although many trials are in progress at the
present time, none have proved unequivocally successful and
none are licensed.
There is at present intense interest in and
optimism for the use of protein kinase-C inhibitors.
Two major studies
DCCT:
a multicentre study of 1441 Type 1 diabetic patients in
the United States examining the effects of tight control on the
development of microvascular complications, terminated after
nine years because of highly significant benefits reported in
1993. The benefits on the microvascular complications were
considerable.
UKPDS:
a multicentre study of 5102 Type 2
diabetic patients co-ordinated from Oxford, assessed both
the harmful effects of persistent hyperglycaemia and
hypertension on the development of microvascular and
macrovascular complications, and also demonstrated the
benefits of 10 years of better, compared with less satisfactory,
control of both glycaemia and blood pressure reported in 1998.
Benefits were achieved regardless of the drugs used to reach
the required standards of either blood glucose or blood
pressure control.
The long-term effects of treatment in the two studies are
shown in the two figures demonstrating the stable control in
Type 1 diabetes (DCCT) compared with the deteriorating
control in Type 2 diabetes as the disease progresses (UKPDS).
Persistent hyperglycaemia
Over many years this is the principal underlying cause of the
microvascular complications of diabetes.
It is also anindependent risk factor for the development of macrovascular
coronary artery disease and cataract formation. The UKPDS
showed precisely the increasing hazard in relation to
continuously rising HbA1c levels, without any specific threshold
point, and then demonstrated the benefits of tight control.
Once complications are established additional factors, notably
hypertension, may accelerate their progression (for further
details see chapters on specific complications).
For every 1% increase in HbA1c:
• microvascular complications increased by 37%
•
any end point (micro and macrovascular) related to diabetes
increased by 21%
• deaths related to diabetes increased by 21%.
(Microvascular complications are here defined as
retinopathy requiring photocoagulation, vitreous haemorrhage,
and fatal or non-fatal renal failure.)
The progression of neuropathy assessed in a group of
Type 1 diabetic patients in a prospective 14-year study
conducted in Dusseldorf has also shown clearly that the decline
of numerous measurements of nerve function occurs almost
exclusively in those with poor glycaemic control.
The effect of better blood glucose control on the
microvascular complications was as follows:
• reduction of microvascular complications (chiefly the need
for photocoagulation) by 25%
• reduction of any diabetes end point by 12%
• reduction of any diabetes related death by 10%.
Glycaemic control was also shown to reduce the evolution
of microalbuminuria after nine years, and the loss of vibration
perception after 15 years of the study. Tight blood glucose
control had a non-significant effect on reduction of myocardial
infarction, and none on diabetes related mortality.
The DCCT (Type 1 diabetes) demonstrated that primary
prevention and retardation of progression of diabetic
complications can be achieved over a decade if tight diabetic
control is achieved. Retinopathy, nephropathy, and neuropathy
were reduced by 35-70% if HbA1c was maintained around 7%.
Maintaining tight control requires optimisation of insulin
regimen and diet (see chapters 5 and 6), careful blood glucose
monitoring, and substantial professional support.
Five years after termination of the DCCT, the EPIC study
showed that, despite lapse of the earlier tight blood glucose
control, the benefits with regard to amelioration of
complications persisted.
Hypertension
This is the principal underlying risk factor for the development
of coronary artery disease leading to myocardial infarction,
and increases the risk of strokes and heart failure as well
It also exacerbates the progression of retinopathy, the
evolution of proteinuria, and probably the deterioration of
nerve function as well.
The UKPDS (Type 2 diabetes) has shown that for every
10mm Hg increase in systolic blood pressure:
• any complication related to diabetes is increased by 12%
• deaths related to diabetes are increased by 15%
• myocardial infarction is increased by 11%
• microvascular complications are increased by 13%.
By achieving a mean blood pressure of 144/82,
representing a reduction of systolic blood pressure of
10mm Hg compared with the less intensively treated group,
microvascular end points (chiefly the need for
photocoagulation) were reduced by 37%, and risk of
vision declining by three lines on the Snellen chart was
reduced by 47%, chiefly by protection from the development
of macular disease.
Better control of blood pressure also resulted in a 32%
reduction in deaths related to diabetes, and a 44% reduction in
strokes; there was a non-significant reduction in myocardial
infarction.
Further details on the benefits of good blood pressure
control in general and on established nephropathy in
particular are described in chapters 16 and 17.
Smoking
This exacerbates all the complications of diabetes, both
microvascular and macrovascular.
Dyslipidaemias
These increase the propensity to macrovascular disease: targets
for control are described in chapter 17.
The presence of the above factors in combination additively
increases the risks of developing complications.
Targets for control and reduction of risk factors
Blood glucose
The facility for patients to measure their own blood glucose
empowers them to achieve optimal control by their own
interventions. The aims are as follows:
• Type 1 diabetes: achieve preprandial blood glucose readings
mainly in the range 4·5-7·7 mmol/l, postprandial readings in
the range 6·0-9·0 mmol/1, and 7·0-9·0 mmol/1 at bedtime,
and preferably never below 4·0 mmol/l to avoid blunting of
hypoglycaemic awareness.
• Type 2 diabetes: fasting 5·5 mmol/l;
postprandial 9·0 mmol/l.
Glycated haemoglobin
Aim for an HbA1c6·5% (normal value 4·0-6·0%) as an ideal,
since values 7% are increasingly associated with development
of all microvascular and macrovascular complications, and
reduction of HbA1c has been shown to diminish microvascular
complications substantially
Values up to 8% areacceptable in those who cannot readily achieve the ideal (and
there are many). When HbA1c values exceed 9%, additional
education and counselling should be attempted although
even then patients may not succeed, and some show no
inclination to do so
Blood pressure
Targets for control are
Weight
Body mass index 25 is ideal; 27 acceptable;
greater than 30 represents obesity.
Lipids
Targets for control are to be decreased
Smoking
Aim: to stop smoking
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