Science demands that questions have answers. These answers are provided by experiment. However, in the absence of any experiment no one knew the answer. Thus the debates.
The experiment was finally started in the 1980s, although the results weren’t known until the 1990s. The experiment was called the Diabetes Control and Complications Trial. A clinical trial is the purest form of science. It declares a hypothesis at the beginning, with specific criteria that will declare success or failure of the hypothesis. It has what’s often called a “control group”, but in this case called a “standard group”. This group of subjects do not receive the care being tested. This standard group should match the experimental group as closely as possible: in age, sex, race and other variables.
The DCCT began in 1983 and followed 1,441 volunteers who had diabetes (type 1 patients only). It compared the effects of tight control of blood glucose levels with the effects of standard control.
The experiment began by splitting the 1,441 volunteers into two groups. Volunteers had no choice, they were assigned at random to either the “tight control” or the “standard” group. The tight control group required that these patients tested their blood glucose levels at least four times per day, injected insulin at least three times per day, adjusted insulin doses based upon daily food intake and exercise, followed a diet and exercise plan, and made monthly visits to a diabetes management team that included a dietitian and a behavioral therapist. The standard group was to maintain the way they had managed their diabetes in the past.
At the beginning of the study, the eyes of each patients were documented with fundus photography. The fundus of the eye is the interior surface of the eye, which includes the retina but not the lens. A fundus camera has special optics to properly illuminate the fundus and a wide field high magnification lens to image the fundus. When the fundus is properly illuminated, tiny blood vessels are visible. In fact, the fundus is the easiest place to visualize the body’s microcirculation, and photographing the fundus was the easiest way to document changes to the body’s microcirculation.
The fundus photographs were studied by trained graders who assessed the degree of retinopathy, damage to the retina’s blood vessels, and assigned a number from 0 to 25 indicating the severity of the retinopathy. The graders did not know whether the subject was part of the standard group or tight control group.
Fundus photography was repeated every six months. A patient was said to have clinically relevant retinopathy when the severity of their retinopathy increased by 3 units over their initial baseline measurement and this increase persisted for at least six months.
The experiment then was straight forward. Every six months all the patients would report for their fundus photography. The photos would be sent to the graders. The graders would assign a degree of severity to each patient. Another team that knew which group each patient was in compiled the results. This team noted the percentage of each group that had developed clinically significant retinopathy.
The results took a long time to draw any conclusions. After one or two years, very few patients had any change in their observed retinopathy scores and no significant difference existed between the two groups. However, after five years, it was clear that the patients in the group with tight control of glucose levels in their blood had significantly less retinopathy than the standard group. The study continued on for nine years. The study also tried to measure differences in nerves (neuropathy), differences in macrovascular disease, and differences in perceived quality of life between the two groups. No difference was noted in the quality of life, which was important because one argument against tight control was that tight control was more trouble for patients and would decrease their quality of life. Nor was any significant difference noted in macrovascular disease, which was not surprising because the patients were younger than when that occurs. A follow on study did see significantly less macrovascular disease in the tight control group compared to the standard.
Almost everything was better, or unchanged, for the tight control group compared to the standard control group. But there were two exceptions: the standard control group had significantly fewer incidents of hypoglycemia and the tight control group gained significantly more weight. The first finding is not surprising, because tight control implies keeping the blood glucose levels closer to the danger zone than standard control.
The second finding was surprising. After five years, the patients in the tight control group gained an average of 10 pounds more than the patients in the other group. Why did these patients gain weight? Experiments don’t answer why questions, they just provide the facts. One possible explanation is that tight control puts your body closer to its natural state, and for the diet and exercise of these patients their natural weight was 10 pounds higher than their starting weight.
The study concluded that tight control over blood glucose levels minimizes long term complications of diabetes. Despite the findings of the DCCT, some doctors still recommended looser control. They conceded that the severity of the complications, particularly vascular disease, was related to the tightness with which blood sucrose was controlled, but argued that tight controlled simply couldn’t be achieved. It was too labor intensive and too costly. In addition, there was always the fear of hypoglycemia (and potential death) to scare patients away from tight control. [Controversies of the Sweet Urine Disease]