Dr. S.M.Sadikot.
Hon. Endocrinologist,
Jaslok Hospital and Research Centre,
Mumbai 400026

Today, we are in a position where we can manage most of the acute complications associated with diabetes quite adequately. Unfortunately, the same cannot be said about the long term complications. The commonest cause of death in a person with diabetes over the age of thirty is still from cardiovascular disease especially coronary artery disease. Peripheral vascular disease in association with diabetic neuropathy is a major cause of foot problems in India. In fact, lower limb amputations due to diabetes associated complications ranks only second to accidents. 5% of all diabetics may go on to become legally blind and after cataracts, diabetes eye disease is the leading cause for this blindness. The kidneys may be commonly involved in diabetes and some studies have shown that one out of every three to four patients undergoing dialysis or a renal transplant has diabetes.

Whilst it is true that with the help of modern day medical facilities, one can treat many of these complications, this is not without a tremendous socio-economic consequence and even then one cannot be sure of success. Personally, I feel that trying extremely hard to manage the severe long term problems is a little like trying to buy the best possible lock for the house after everything there has been stolen. I feel that the best management for these long term complications would be to try and prevent them in the first place or at least try and diagnose the presence of these complications in the early stages.

This brings us to very important questions. Firstly, can the long term problems associated with diabetes be prevented? Secondly, how are these complications to be diagnosed at an early stage? The latter question brings up another question. Even if we do diagnose the complications at an early stage, is there anything we can do to either reverse these complications or at least retard the development of these complications so that they do not reach a severe stage and remain at a level at which they do still allow a patient to live a basically "normal" life?

There are a few authorities who feel that there is nothing that one can do to avoid the long term complications. They feel that these complications are a "part and parcel" of the diabetes syndrome and that the very genes that predispose one to diabetes also makes one prone to the complications. In other words, there is nothing that the patient or his doctor can do to avoid the complications and that this is basically in the "stars" of the patient, The genes of the patient not only predispose the patient to the complications but also determine the severity of these complications.

This is not a view that is universally shared. Most authorities feel that it is in our "hands" to do something about these complications. It is widely accepted that the presence and the severity of the complications is determined by the degree of control of the blood glucose levels. The higher the levels of the blood glucose, the greater are the chances of the diabetic getting the complications. The severity of the hyperglycemia and the duration to which the body is exposed to high blood glucose levels will also determine the extent of these complications. In other words it is in our "hands" to prevent the complications or at least retard their progression so that they tend to remain at a mild level. In view of these directly opposite views, what is the real situation?

Without going into any more controversial aspects, I feel that there is enough evidence before us to feel that the chronic complications have both, a genetic as well as an environmental component. Whilst genes may predispose a diabetic to these complications, there must be the presence of additional "environmental" factors which together determine the onset, progression and severity of the long term complications. In the rare person, the genetic propensity to get these complications to a severe degree is so strong that even the slight presence of environmental factors may cause the patient to get these severe complications. Conversely, there are those rare patients who have such a mild genetic trend to get these problems, that even a large amount or the environmental factors may allow them to escape from these complications. People at these two extremes are a miniscule portion of the diabetic populations and as far as the vast majority of the patients are concerned, their genes confer on them a certain amount of susceptibility but they require the presence of environmental factors to get the complications especially to any significant extent.

Since, we are not in a position to alter the genetic background of the patient, it becomes essential that we understand these environmental factors so that controlling them can help in preventing or alleviating the long term complications. Thus, one can say that the answer lies both in our "stars" and in our "hands"!

Incidently, I am often asked whether that miniscule portion of diabetics who seem to be immune to the chronic complications can be delineated. The reason being that such patients can be left quite well alone without insisting on an optimal control. Unfortunately, at the present times we do not have in our means the capacity to pick out these patients. In any case, the number of such patients is so small that one would come across a very few of these patients even in a fully diabetes practice. We should be more concerned with the vast majority of patients in whom the management and optimal control of the environmental factors is of utmost importance.

Before we consider these environmental factors, let us see whether it is possible to reverse the complications once they have set in. Here again there seems to be some sort of a controversy but the general consensus is that it may be possible to revert the complications if they are diagnosed at the early stages and corrective measures taken. In later stages, once the long term complications have set in to a severe extent, it may not be plausible to completely revert the complications. I am not convinced that that this is true for all the complications. I have seen a number of patients who come with "burning" feet and who get a significant relief with adequate nutrition and optimal control. Even if all the other complications may not revert back completely to normal, it is true that we can definitely arrest the progression or at least slow down the rate of progression of the complications and thereby better the quality of life of the patient as well as prolong the life.

I have always referred to the non-genetic factors as "environmental". This is with a definite purpose in mind. We are often under the mistaken notion that diabetes control is the same as control of the blood glucose levels. This is a fallacy. Although blood glucose control is one of the most important aspects of diabetic control, there are other significant risk factors to which a person with diabetes is prone and which definitely contribute to the long term complications. Thus, excellent diabetes management not only means that the blood glucose levels would be optimally controlled, but also other risk factors will have to be adequately and optimally managed.

What are these "environmental" risk factors?

First, let us consider the management of the blood glucose levels. These should be "optimal", but what level constitutes an optimal control? Ideally, the blood glucose levels should approximate normal throughout the 24 hours. Such a tight control may not be feasible with the currently available means in our hands without exposing the patient to some risk. Therefore, one has to opt for optimal control. Although the values that constiute optimal control would vary according to the individual and the circumstances, one can generalise and say that the fasting blood glucose levels should be below 120gm%, the 2 hour postmeal level should be below 160mg%, with the blood glucose levels remaining below this value throughout the 24 hours. The glycosylated hemoglobin level should be within the acceptable range. I would like to make it clear that these values are just generalisations that may not hold good for every individual patient. As an example, I would feel that these values would be too high for a pregnant diabetic or those who may be on the verge of losing their eyesight due to macular edema. Conversely, in a 80 year old man without any other major problem, these values may be thought of as being a little too rigorous. Thus, whilst these values would need to be adjusted for every patient, they would still hold good for the vast majority.

I do not intend to discuss in detail in this section how these optimal values are to be achieved. But I will only touch upon those aspects of the management which may have a direct bearing on the long term complications. In trying to achieve optimal control, it is very important that the patient is not exposed to repeated and/or severe episodes of hypoglycemia. It is now well established that such episodes of hypoglycemia may bring about a start of, or a rapid progression of, the very long term complications that we are trying to avoid.

Another aspect about the management of the blood glucose levels is that one should avoid bringing down the levels of the blood glucose too rapidly unless there is a definite reason for this. Often, efforts are made to bring the blood glucose down very rapidly by using heavy doses of medications and putting the patient on severely restricted diets. This can precipitate problems. It is known that such therapeutic manoevres can lead to problems like burning neuropathies!

In order to achieve "tight" control, a few doctors are offerring what I would term as a completely indiscriminate use of the so-called insulin "pumps". 1 have extensively used these insulin pumps as a research method and agree with the general consensus that in their present forms they are associated with too many complications including death, for them to be allowed to be used routinely on our patients. In so far as the long term complications only are concerned, they are associated with an unacceptable level of hypoglycemic reactions and interestingly, in a initial study carried out abroad, the prevalence of retinopathy increased when patients are put on the pump inspite of what was felt to be a better control!

One of the other major risk factor that we see often in a diabetic is the increase in the levels of the triglycerides and the LDL-cholesterol associated with a decrease in the HDL-cholesterol levels. The latest recommendations state that in adults with diabetes, the optimal LDL-C level is less than 100 mg/dL and the optimal HDL-C level is more than 45 mg/dL; triglyceride levels of less than 200 mg/dL are desirable. You will realize that these recommendations are much more stringent than those evolved in the past. A few years back, levels of LDL-C greater than 160mg% were considered as being in the "high risk" category. Levels between 130 and 159mg% were in the "borderline risk" category whilst levels of LDL-C below the 139mg% value are felt to be safe. Levels of HDL-C below 35mg% were are considered to be in the "high risk" category for the development of atherosclerosis. It has been shown that even changes of as small a magnitude as 5-10mg% in the HDL-C levels will bring about significant change in the relative risk involved.

It was also felt in the past that fasting triglyceride levels below 250mg% were safe and should not merit active therapy unless the associated levels of LDL-C were more than 160mg% Levels, between 250mg% and 500mg% were considered "borderline" high whilst those above 500% are considered as being in the "high risk" category. I do not accept these values and feel that the serum triglycerides should be kept below the 200mg% mark at the very least. In fact, for a diabetic patient, active efforts must be made to lower the TG values as much as is possible and I feel that the aim of treatment should be to lower the TG levels to around 150mg%, especially in view of the recent evidence that TG itself is an independent risk factor for macrovascular disease.

Hypertension is much more common in a person with diabetes, often being a part of the so-called "metabolic syndrome". It is an extremely important risk factor in the pathogenesis the long term complication especially, nephropathy, retinopathy and cardiovascular disease. All patients who have high blood pressure should have this normalised. At one time it was felt that maintaining the blood pressure at 140/90 would be adequate, but now we know that in a person with diabetes, one should aim for a blood pressure reading of 120/80. This is very crucial as we tend to get so involved at looking at the blood glucose levels that we often ignore what we feel is just a slightly raised blood pressure levels.

I usually ask patients who have hypertension to keep a meter at home so that they can closely monitor the blood pressure levels themselves.

The role of controlling the hypertension should never be minimised. Even those doctors who feel that long term diabetic complications can reach a level of "no return", in the sense that the complication will relentlessly progress irrespective of the blood glucose control, believe that controlling the blood pressure will still be of immense help in retarding the progression. Diabetic nephropathy is a case in point. It is essential that the blood pressure be controlled irrespective of the stage of the renal involvement. This can help in retarding the progression of the nephropathy.

Even if the patient does not have high blood pressure at the initial examination, this should be evaluated at every opportunity. Often, the slight rise in the blood pressure may be the first indication of involvement of the kidneys. More commonly, a sudden appearance of high blood pressure in a patient who is usually normotensive may be a clue to the presence of subclinical hypoglycemia and allow us to take adequate preventive measures to avoid precipitating a complete and severe attack of hypoglycemia. I feel that the blood pressure should be recorded in the lying down, sitting and the standing positions. The presence of postural hypotension may be the first clue to the involvement of the autonomic nerves in diabetes.

At the same time, it should be clear that the management of hypertension in a diabetic is not very simple. Without going into details about the drugs that should be used to manage the hypertension, I will only say that the drugs have to be chosen very carefully as many of the drugs have side effects which affect blood glucose control or even the long term complications themselves! It may not be easy to control the hypertension in a diabetic, but it is definitely possible and the benefits that the patient gets from this control far outweigh the trouble that doctors have to take to control the raised blood pressure.

The management of hypertension is a patient with diabetes is discussed in a separate chapter.

The weight of the diabetic should be optimal. I have discussed this aspect in detail in the section dealing with diet therapy and will only mention here that the best parameter to judge the optimal body weight is to use the Body Mass Index, and the Waist-Hip ratio.

The sex, age, and the duration of diabetes are other risk factors over which we do not have much control. The environmental factors that I have discussed till now are those what I would term as "general" factors having an impact on many of the long term complications. There are risk factors which are relatively specific for some of the chronic complications and I will discuss these in the next section where I will also describe how the long term complications are diagnosed at an early stage.