Benefits of Tight Glycemic Control in Diabetes
A long-term randomized prospective study involving 1441 type patients in 29 medical centers reported in 1993 that “near normal-ization” of blood glucose resulted in a delay in onset and a major slowing of progression of microvascular and neuropathic compli-cations of diabetes during follow-up periods of up to 10 years (Diabetes Control and Complications Trial [DCCT] Research Group, 1993). In the intensively treated group, mean glycated hemoglobin HbA1c of 7.2% (normal < 6%) and mean blood glu-cose of 155 mg/dL were achieved, whereas in the conventionally treated group, HbA1c averaged 8.9% with mean blood glucose of 225 mg/dL. Over the study period, which averaged 7 years, a reduction of approximately 60% in risk of diabetic retinopathy, nephropathy, and neuropathy was noted in the tight control group compared with the standard control group.
The DCCT study, in addition, introduced the concept of glycemic memory, which comprises the long-term benefits of anysignificant period of glycemic control. During a 6-year follow-up period, both the intensively and the conventionally treated groups had similar levels of glycemic control, and both had pro-gression of carotid intimal-medial thickness. However, the inten-sively treated cohort had significantly less progression of intimal thickness.
The United Kingdom Prospective Diabetes Study (UKPDS) was a very large randomized prospective study carried out to study the effects of intensive glycemic control with several types of therapies and the effects of blood pressure control in type 2 diabetic patients. A total of 3867 newly diagnosed type 2 dia-betic patients were studied over 10 years. A significant fraction of these were overweight and hypertensive. Patients were given dietary treatment alone or intensive therapy with insulin, chlor-propamide, glyburide, or glipizide. Metformin was an option for patients with inadequate response to other therapies. Tight control of blood pressure was added as a variable, with an angio-tensin-converting enzyme inhibitor, a β blocker, or in some cases, a calcium channel blocker available for this purpose. Tight control of diabetes, with reduction of HbA1c from 9.1% to 7%, was shown to reduce the risk of microvascular complica-tions overall compared with that achieved with conventional therapy (mostly diet alone, which decreased HbA1c to 7.9%). Cardiovascular complications were not noted for any particular therapy; metformin treatment alone reduced the risk of macro-vascular disease (myocardial infarction, stroke). Epidemiologic analysis of the study suggested that every 1% decrease in the HbA1c achieved an estimated risk reduction of 37% for microvas-cular complications, 21% for any diabetes-related end point and death related to diabetes, and 14% for myocardial infarction.
Tight control of hypertension also had a surprisingly signifi-cant effect on microvascular disease (as well as more conven-tional hypertension-related sequelae) in these diabetic patients. Epidemiologic analysis of the results suggested that every 10 mm Hg decrease in the systolic pressure achieved an esti-mated risk reduction of 13% for diabetic microvascular complica-tions, and 12% for any diabetes-related complication, 15% for death related to diabetes, and 11% for myocardial infarction.
Post-study monitoring showed that 5 years after the closure of the UKPDS, the benefits of intensive management on diabetic end points was maintained and the risk reduction for a myocar-dial infarction became significant. The benefits of metformin therapy were maintained.
These studies show that tight glycemic control benefits both type 1 and type 2 patients.The STOP-NIDDM trial followed 1429 patients with impaired glucose tolerance who were randomized to treatment with acar-bose or placebo over 3 years. This trial demonstrated that normal-ization of glycemic control in subjects with impaired glucose tolerance significantly diminished cardiovascular risk. The acar-bose-treated group had a significant reduction in the develop-ment of major cardiovascular events and hypertension. A prospective placebo-controlled subgroup analysis has shown a marked decrease in the progression of intimal-medial thickness.