Incidence of complications in insulin-dependent diabetes mellitus: A survival analysis. Cathy Lloyd et al. Glossary: Microalbuminuria: The presence of albumin, a protein, in the urine. Proliferative retinopathy: Eye disease associated with diabetes. One of the most frightening aspects of diabetes mellitus is not the disease itself, but the complications it can give rise to. Kidney failure, blindness, nervous disorders, stroke and heart disease are just some of the more obvious problems that can follow from insulin-dependent diabetes. A major aim of modern diabetes treatment is not just to control glucose levels but to do so in a way that minimizes the risk of such serious complications. One study of diabetes patients in Pittsburgh set out to find a link between glycemic control and complications of diabetes in order to determine how best to treat patients over the long term. An encouraging recent discovery is that long-term intensive control of blood glucose levels does have a positive effect on patients' chances of evading the early eye, kidney and nerve complications of diabetes. The downside is weight gain and an increase in hypoglycemic episodes, side-effects which are almost inescapably linked with intensive insulin treatment. One study looked at the effect of glycemic control on later complications of diabetes such as advanced renal disease and heart disease. It focused on insulin-dependent diabetics who had been diagnosed with the illness before reaching 17 years of age. Their average age was 27 at the start of the study. Doctors began by dividing patients into two groups. The first was made up of the one-third of patients who had 11% or more glycosylated hemoglobin (GHb) and were deemed to have "poor" glycemic control. The second group, the two-thirds of patients who had less than 11% GHb, were said to have "fair" control. The two groups were then checked for proliferative retinopathy, microalbuminuria (an indicator of kidney problems), and diminished reflexes and sensory loss (signs of distal symmetrical polyneuropathy -- a dysfunction of the nervous system). Patients were also given electrocardiograms and screened for history of angina or heart attacks, and for symptoms of lower extremity arterial disease (LEAD). All of these tests were repeated at two-year intervals to see how each group fared. Looking first at renal complications, doctors found that "poorly controlled" patients were over three times more likely to have developed microalbuminuria by the end of the study, and almost twice as likely to have progressed to kidney disease or kidney failure. Fourteen percent of all patients developed microalbuminuria while 7% and 5% respectively went on to develop more severe kidney problems. Proliferative retinopathy was the most common of all complications tracked in the study, afflicting 16% of all patients. The incidence of this eye disease was almost four times greater in the "poor controlled" group than among the "fair control" patients. The longer the time since diagnosis with diabetes, the more likely proliferative retinopathy became. Thirteen percent of patients showed signs of distal symmetrical polyneuropathy. The rate was three times higher in the "poor control" group. Macrovascular conditions such as coronary heart disease and LEAD, however, do not appear to be more prevalent among diabetics with particularly poor glycemic control. The incidence of these two diseases -- 5% and 6% respectively -- was about the same in both groups. One interesting conclusion of the study was that neither gender, nor the age at which diabetes is first diagnosed, play a large role in an individual's chances of developing complications of diabetes. Duration, however, does play a role. Generally, the longer a patient has had diabetes, the more likely complications are. In the case of advanced renal disease, for example, duration of diabetes becomes a stronger predictor than glycosylated hemoglobin. In other words, when it comes to avoiding this condition, how long you've had diabetes is more important than how good or bad your glycemic control is. Coronary disease would appear to be the great exception to this rule. Neither duration nor glycemic control have been shown to affect the risk of this disease very much one way or the other. Glycemic control in general is not the major factor in the development of the later complications of diabetes such as macrovascular disease or the later stages of renal disease. No study can cover every variable, and it's clear that other factors come into play which lie outside of the purview of this particular survey. More investigation is needed to determine exactly what risk factors in diabetes predispose people to heart disease and kidney failure, in order to address those factors as early as possible. Questions for Dr. Lloyd: 1. Did the study look at links between diet and behaviour and the incidence of complications? The investigation didn't go into that aspect while I was working on it, though more recently I think they have been exploring that angle. In general, we know that low cholesterol levels and good glycemic control help to avoid complications. Insofar as behaviour affects the development of complications, monitoring your blood sugar levels and taking part in some kind of physical activity - even if it just means walking for 20 minutes every day - are the main things. 2. Did the study show any tendency for certain complications of diabetes to run in families in the way that diabetes itself tends to run in families? The EDC study didn't get into that issue, but there's a separate family study which is now looking specifically at complications. So far, however, that isn't clear at all. 3. Is a person who develops one complication, such as retinopathy, more likely to develop another, such as distal symmetrical polyneuropathy? How are the complications linked to each other? We have found, as have some other studies, that there may well be links between certain kinds of complications. But just because an individual develops one kind of complication does not necessarily mean that he or she will go on to develop either the more severe stages of that complication, or any of the other complications. Some studies have shown that retinopathy and nephropathy -- renal disease -- may be linked; it's what we call concordance between complications. But as I said, that's not always the case. What is more likely is that particular risk factors are being shared by different complications, such as cholesterol levels and glycemic control. 4. So it's not accurate to say that there is always a steady deterioration, beginning with the earlier complications, and then proceeding through to the later complications like end-stage renal disease? No. You can't say that because someone has changes in their eyes, for example, an early sign of background retinopathy, that they're going to go on to develop renal disease. There is a link between them, but it's not followed by every individual. Our study has shown quite strong concordance, but it has also shown some cases of discordance between certain diabetic complications. 5. Your study separated kidney complications into three degrees of severity. Does the first, microalbuminuria, always lead to the last, renal disease? People can survive with microalbuminuria for a very long time. In fact, we recently published a commentary looking at some aspects of this, and another study is coming out this year looking at a small number of patients whose microalbuminuria has actually regressed. That is to say, they've got to a certain level of protein in the urine, and then over the next two years it's actually gotten better. We think that one possible link may be to a change in cholesterol. This has happened in only a small number of patients, but many others go on with microalbuminuria for many, many years and never go to end-stage. Comment: Renal disease, high blood pressure and cholesterol are all quite closely connected. So if you do begin to get some signs of protein in the urine, and you start to exercise more or you lose some weight or reduce your cholesterol levels, that can be a great help. Incidence of complications in insulin-dependent diabetes mellitus: A survival analysis. Lloyd C., Becker D., Ellis D., and Orchard T. The authors used four-year incidence data from the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study to investigate the wider applicability of recent research findings that demonstrate an association between glycemic control and insulin-dependent diabetes mellitus (IDDM) complications. EDC subjects participated in a clinical examination at baseline (1986-1988) and were followed up every 2 years. Results demonstrated that, during the first four years of follow-up, subjects who were in "poor" control (glycosylated hemoglobin [GHb] ³ 11%) at baseline were significantly (p < 0.001) more likely to develop microalbuminuria, proliferative retinopathy, and distal symmetrical polyneuropathy (DSP), compared with subjects who were in "fair" control (GHb < 11%). Subjects who were in poor control were somewhat more likely to develop overt nephropathy (p = 0.08) and renal failure (p = 0.085) during follow-up; however, no associations were observed either with coronary heart disease or lower extremity arterial disease (LEAD). These results confirm the strong association between prior glycemic control and the onset of microalbuminuria, proliferative retinopathy, and DSP observed in the Diabetes Control and Complications Trial study. However, the results of the study suggest weaker associations for the later stages of renal disease, and little relation was seen between glycemic control and LEAD or coronary disease. Other risk factors may be more important for the development of the later complications of IDDM. Further follow-up is necessary in order to rule out type II error. © Mediconsult.com Limited Mediconsult.com is designed for educational purposes only.