Although the risk of developing diabetic kidney disease is partially determined by your genetic make-up, the onset of the disease can be prevented or at least postponed for a long time by good blood sugar control. This was demonstrated for patients with both Type 1 and Type 2 diabetes by two major trials that were published in the 1990s.

The Diabetes Control and Complications Trial (DCCT) involved about 1400 patients with Type 1 diabetes. They were divided into two treatment groups. One half received ‘intensive’ treatment with intensive education. These patients were injected several times a day with insulin or put on an insulin pump.

They tested their blood sugar levels themselves at least four times a day and adjusted the insulin dose accordingly. They also went to see the doctor every four weeks. The other group were treated ‘conventionally’. They received a single session of dietary advice.

They injected an insulin mixture only once or twice a day, measured their blood sugar levels only occasionally and visited the doctor only once a quarter. As expected, the intensively treated group managed their blood sugar much better. Their HbA1c concentration, which indicates how well the diabetes was controlled in the preceding months, was on average a relatively good 7%.

In the conventionally treated group, on the other hand, the average value was 8.9% – which expert opinion today considers to be far too high. The trials showed that good diabetes management markedly reduced the risk of kidney damage.

The risk of developing microalbuminuria was at least 34% (about one-third) lower in those patients with better metabolic control than in those treated conventionally. What’s more, the beneficial effect of good metabolic control on the risk of nephropathy becomes noticeable only after several years of intensive therapy.

So people have to persevere for some time to see the real advantages. There were some patients in the intensive group in the trial who, despite all efforts, did not achieve good blood sugar control (the HbA1c value of 7% was an average taken over the nine years of observation).

This explains why diabetic kidney disease did develop in this group. A similar study in the United Kingdom showed that what is true for Type 1 diabetes is also true for Type 2. The UK Prospective Diabetes Study (UKPDS) involved nearly 4000 patients with newly-diagnosed Type 2 diabetes, who were allocated to either ‘intensive’ or ‘conventional’ treatment.

For the group on intensive therapy, the goal was a fasting blood sugar level of less than 110 mg/dl. For the conventionally treated group, much higher levels (up to 275 mg/dl) were allowed. Various drugs were used to lower blood sugar concentrations, as well as insulin.

In both treatment groups, the blood sugar control became progressively worse over the years. However, the average HbA1c concentration was always about 1% better in the intensively managed group. The risk of developing diabetic kidney disease was about one-third lower. It made no difference whether the better metabolic control was achieved using drugs or insulin.

Is there a threshold, above which the risk noticeably increases? This question is of great practical interest for patients and doctors. To put it another way, ‘How well must I manage my diabetes for the risk of nephropathy to be minimized? Do I have to reach an HbA1c concentration of 6% or 7% or will 8% be enough?’

The answer is: the lower the HbA1c concentration, the lower the risk of microalbuminuria! Neither the DCCT nor the UKPDS could establish a threshold at which the risk either rose or fell significantly. This relationship was the same for both groups, whether treated intensively or conventionally.

This means that someone who can achieve good blood sugar control by conventional treatment is equally well protected as someone who is treated intensively. Naturally, another question arises: how low should the blood sugar level be? Is a very low concentration actually dangerous?

In the patients treated intensively with insulin, there was a risk of hypoglycaemia (dangerously low blood sugar). In the DCCT, particular attention was paid to the ‘danger’ of intensive therapy. Patients undergoing such therapy did in fact experience hypoglycaemia more frequently than those treated conventionally.

Considering the poor metabolic control observed in the conventionally treated group, this is hardly surprising. In any case, the results of the last few years have shown that good metabolic control can be achieved without greatly increasing the risk of hypoglycaemia (dangerously low blood sugar).

This is particularly true when people with diabetes are well educated about their condition, check their blood sugar regularly and generally participate in the management of their diabetes.

With nephropathy, is there a ‘point of no return’? Another important question is whether there is any benefit of good blood sugar control once the signs of kidney failure, either micro-or even macroalbuminuria, have appeared. This was disputed for a long time.

The opinion was that there was a point of no return, after which there could be no reversing the course of the disease – it would progress inexorably until dialysis was necessary, regardless of how well controlled the blood sugar level was. But the studies of recent years have shown clearly that good blood sugar control brings benefits, even at this stage.

The progression of the nephropathy can be prevented, or at least delayed, by good management. This is true for both Type 1 and Type 2 diabetes. We should add, however, that the beneficial effect of good metabolic control on the course of nephropathy is greater, the lower the pre-existing damage.

This was proved to be equally true for Type 1 diabetes as for Type 2 diabetes by two studies. People with Type 1 diabetes who had already developed microalbuminuria and who were treated intensively, as in the DCCT, showed a significant delay in the progress to macroalbuminuria.

Kidney function deteriorated in only 8% of these, whereas it worsened in 31% of the conventionally treated group. The same result was obtained in the Kumamoto Trial, which enrolled people with Type 2 diabetes and microalbuminuria. Good blood sugar control reduced the risk of kidney damage progressing from 32% to 12%.

The more advanced the kidney damage is, the smaller the effect that blood sugar control can exert on its progression. However, the impact of another factor that can be influenced grows – blood pressure. Once macroalbuminuria or even renal insufficiency has developed, high blood pressure plays a deciding role in the progression of the disease. For the patient and doctor, this means:

How failing kidney function affects diabetes management. To achieve good blood sugar control in the presence of failing kidney function is a difficult task for patient and doctor. There are various reasons for this. In some people with diabetes the insulin sensitivity changes, for reasons that are often unclear: the tissues no longer respond as well to insulin.

This can lead to a worsening of the diabetes. Insulin – whether made by the body or injected as a drug – is partly broken down in the kidneys. When the kidneys are not functioning properly, less insulin is metabolized, so that the effect of the insulin is prolonged.

This partially compensates for the reduced insulin sensitivity mentioned above, but can also result in hypoglycaemia – dangerously low blood sugar. Someone who has advanced nephropathy often also suffers from other complications of diabetes. These may include damage to the nerves that regulate the gastrointestinal tract.

Then food is no longer digested and absorbed properly. Typical signs are bloating, feeling full, irregular bowel movements, diarrhea, nausea and vomiting. The irregular absorption of food can cause the blood sugar levels to swing violently.

Additionally, remember that many drugs, including those that reduce blood pressure, are excreted via the kidneys. If kidney function deteriorates and excretion does not occur properly, these drugs may persist in the circulation. This means that their effects are heightened and prolonged, which can lead to hypoglycaemia or other complications.

Therefore, not all drugs are suitable for the treatment of people with impaired kidney function. The drugs that should not be given include the biguanides, the most common of which is metformin. It is excreted exclusively via the kidneys and accumulates even in cases of mild kidney impairment.

If the dose is too high, it can lead to life-threatening acidosis. Many of the heavily prescribed sulphonylurea drugs are excreted via the kidneys, although in very different amounts. For nearly all preparations, the dose should be reduced (in consultation with a doctor) to avoid hypoglycaemia.

An exception is gliquidone (Glurenorm1), of which only a small fraction is excreted by the kidneys. There is a new generation of blood-lowering substances that includes repaglinide (NovoNor1) and nateglinide (Starlix1). These drugs are taken only at mealtimes and cause a short burst of insulin secretion that prevents a rise in blood sugar levels after eating.

The drugs persist for only a short time in the blood. Repaglinide is broken down and excreted mainly (up to 92%) by the liver. Thus, it may be given to patients with impaired kidney function, as demonstrated in a recent study. Even in the presence of advanced kidney damage, blood sugar can be well controlled without an increased risk of hypoglycaemia.

Nateglinide is also metabolized mainly in the liver and may therefore be given to patients with kidney failure. However, there are no large studies and no great experience with this drug as yet. The newly introduced insulin-sensitizers, rosiglitazone (Avandia1) and pioglitazone (Actos1) improve diabetes control by making the tissues more responsive to insulin, so that the hormone works better.