Everyone likes to be normal. Quite aside from this natural human impulse, there were good reasons for scientists to assume that lowering blood sugar levels to nearly normal would reduce the risk of complications and extend the lives of patients with diabetes.
Several observations lent weight to this strategy of so-called tight blood sugar control, or intensive therapy. First, scientists believe that high blood sugar levels actually damage blood vessels over time, both directly and indirectly. When levels are high, glucose will stick to proteins, cell structures, blood fats, and platelets. Like the hemoglobin in red blood cells, the target molecules become glycosylated, which impairs their function. Proteins stick together and the membranes around small arteries thicken, so less oxygen reaches the tissues and waste products build up. The result is organ damage, which progresses slowly and steadily if blood sugar levels stay high.
Second, studies from the 1970s onward suggest that even within the “normal” range, higher blood sugar and HbA1C levels predict a higher risk of cardiovascular disease. Third, a study of 4,662 men found that blood sugar levels were directly linked to the death rate, both in men with and without diabetes; in all, a 1% percent rise in HbA1C was linked to a worrisome 28% rise in the death rate.
Biologic theory and observational studies gave rise to the very reasonable assumption that lower blood sugar levels would translate to better health for diabetics. The next step was to test that belief with clinical trials, which are much more definitive than observational studies. Indeed, two important trials from the 1990s provided additional support for the strategy of tight blood sugar control:
The Diabetes Control and Complications Trial studied 1,441 patients with type 1 diabetes. As compared with standard blood sugar control, tight control helped slow the progression of microvascular complications involving kidney, eye, and nerve damage. And a subsequent report covering 17 years of follow-up also linked tight control with a substantial reduction in macrovascular complications, including heart attack, stroke, and death from cardiovascular disease.
The United Kingdom Prospective Diabetes Study compared intensive blood sugar control with standard control in 3,867 patients with type 2 diabetes. Intensive treatment significantly decreased the risk of microvascular complications, adding weight to the argument that lower blood sugar levels are better. At the same time, though, intensive control failed to provide significant protection against macrovascular complications, the leading cause of death in diabetics.
Based on all these considerations, the strategy of tight blood sugar control was widely recommended for both type 1 and type 2 diabetes. But that was not the end of the story; instead, scientists launched additional studies.