Evaluations of retinopathy in the VA Cooperative Study on Glycemic Control and Complications in Type II Diabetes (VA CSDM). A feasibility study.

OBJECTIVE: The main goal of the study of 153 male veterans was to determine whether a statistically and clinically significant difference in HbA1c could be achieved between a standard therapy and an intensively treated group of patients with type II diabetes. A second major goal was to assess the feasibility of collecting reliable high-quality endpoint data, including microvascular and macrovascular events. Retinopathy 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 general medical care and well-being and avoiding excessive hyperglycemia, glycosuria, ketonuria, or hypoglycemia. This was generally accomplished with one shot of insulin per day. The goal of intensive therapy was to obtain an HbA1c within two standard deviations of the mean of nondiabetic subjects (4.0-6.1%). This was obtained by a four-step management technique, with patients moving to the next step only if operational goals were not met. The steps were as follows: step 1: evening intermediate 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 Ophthalmology, 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 HbA1c of approximately 7.1% in the intensively treated group was sustained for the full study and was significantly lower than that seen in the standard group (9.2%, P < 0.001). Compliance in obtaining fundus photographs was excellent. Near normalization of glycemia did not cause transient worsening of retinal morphology nor did it prevent the onset or delay the progression of retinopathy. There was no effect on visual acuity. CONCLUSIONS: 1) A glycemic control intervention study in people with type II diabetes is feasible and safe; 2) intensive control did not cause transient deterioration of retinopathy; and 3) although no improvement was seen in retinopathy, the follow-up was 24 months, an interval shorter than the 3 years or more of intensive therapy before improvement is seen in type 1 diabetic studies. This does not rule out the possibility that longer periods of intensive therapy would have improved retinopathy. A full-scale intervention trial in type II diabetes is needed to resolve this issue.

The ABCD (Appropriate Blood Pressure Control in Diabetes) trial. Rationale and design of a trial of hypertension control (moderate or intensive) in type II diabetes.

OBJECTIVE: The primary objective of the ABCD (Appropriate Blood Pressure Control in Diabetes) Trial is to determine the efficacy of intensive versus moderate antihypertensive control on the outcome of type II diabetic end-organ complications in normotensive and hypertensive populations. The secondary objective is to determine whether any differential effect on end-organ complications exists between an angiotensin converting enzyme inhibitor (enalapril) and a calcium channel blocker (nisoldipine). DESIGN: The ABCD Trial is a prospective, controlled, randomized, double-blind trial, with a planned follow-up of 5 years. SETTING: All patients are seen at the Colorado Prevention Center, site of the ABCD Trial, for follow-up visits. PATIENTS: Patients are type II diabetic males and females between the ages of 40 and 74 years with entry diastolic blood pressures > or = 80 mmHg. Patients were recruited from University of Colorado-affiliated hospitals, several health maintenance organizations, and mailing lists from the Colorado affiliate of the American Diabetes Association. INTERVENTIONS: Patients were randomized to intensive antihypertensive drug therapy or moderate antihypertensive drug therapy. Patients were also randomized to nisoldipine or enalapril, with open-label medications added if further blood pressure control was necessary. MAIN OUTCOME MEASURES: The primary outcome measure is glomerular filtration rate as assessed by 24-hour creatinine clearance. Secondary outcome measures are microalbumin urinary excretion, left ventricular hypertrophy, retinopathy, and neuropathy. Cardiovascular morbidity and mortality will also be evaluated. CONCLUSION: Given the data showing the impact of hypertension on diabetic complications, the ABCD Trial was designed to determine if intensive antihypertensive therapy will be more efficacious than moderate antihypertensive therapy on the outcome of these complications. Results from the ABCD Trial are expected to lend interpretable and clinically relevant findings with regards to the treatment of hypertension in type II diabetes.