EVALUATIONS OF RETINOPATHY IN THE VA COOPERATIVE STUDY ON GLYCEMIC CONTROL AND COMPLICATIONS IN TYPE-II DIABETES (VA CSDM)

OBJECTIVE - The main goal of the study of 153 male veterans was to det ermine whether a statistically and clinically significant difference i n HbA(1c) could be achieved between a standard therapy and an intensiv ely treated group of patients with type II diabetes. A second major go al was to assess the feasibility of collecting reliable high-quality e ndpoint data, including microvascular and macrovascular events. Retino pathy was defined as a key microvascular endpoint. RESEARCH DESIGN AND METHODS - This was a randomized prospective trial of 153 men between the ages of 40 and 69 years,with type II diabetes for 15 years or less . Of the patients, 78 were assigned to the standard therapy arm and 75 to the intensive therapy arm. The goal of standard therapy was good g eneral medical care and well-being and avoiding excessive hyperglycemi a, glycosuria, ketonuria, or hypoglycemia. This was generally accompli shed with one shot of insulin per day. The goal of intensive therapy w as to obtain an HbA(1c) within two standard deviations of the mean of nondiabetic subjects (4.0-6.1%). This was obtained by a four-step mana gement technique, with patients moving to the next step only if operat ional goals were not met. The steps were as follows: step 1: evening i ntermediate or long-acting insulin only; step 2: evening insulin with daytime glipizide; step 3: insulin, twice a day no glipizide; and step 4: more than two injections of insulin, no glipizide. Retinopathy was assessed at baseline, 12, and 24 months by seven-field stereo fundus photography done at each of the five participating VA medical centers and read at the Central Reading Center at the Department of Ophthalmol ogy, University of Wisconsin Medical School, Madison Visual acuity was determined by ophthalmologists at each of the participating hospitals . RESULTS - After the 6th month of the 24-month study an average HbA(1 c) of similar to 7.1% in the intensively treated group was sustained f or the full study and was significantly lower than that seen in the st andard group (9.2%, P < 0.001). Compliance in obtaining fundus photogr aphs was excellent. Near normalization of glycemia did not cause trans ient worsening of retinal morphology nor did it prevent the onset or d elay the progression of retinopathy. There was no effect on visual acu ity. CONCLUSIONS - 1) A glycemic control intervention study in people with type II diabetes is feasible and safe; 2) intensive control did n ot cause transient deterioration of retinopathy; and 3) although no im provement was seen in retinopathy, the follow-up was 24 months, an int erval shorter than the 3 years or more of intensive therapy before imp rovement is seen in type I diabetic studies. This does not rule out th e possibility that longer periods of intensive therapy would have impr oved retinopathy. A full-scale intervention trial in type II diabetes is needed to resolve this issue.