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Objective: To review the results from the Veterans Affairs Cooperative Study on Glycemic Control and Complications in NIDDM (VACSDM) and to discuss the implications of the results from this feasibility trial., Design: A randomized clinical trial comprising 153 men with non-insulin-dependent diabetes mellitus (NIDDM) who remained hyperglycemic on usual pharmacologic therapy. Patients were randomized into two groups receiving either standard or intensive insulin therapy and were followed for 27 months., Setting: Five Veterans Affairs medical centers., Patients: 153 men with NIDDM, aged 40 to 69 years, who had hemoglobin A1c (HbA1c) levels of greater than 6.55% while receiving sulfonylurea or insulin therapy., Intervention: Standard insulin therapy was one or two insulin injections daily. Intensive insulin therapy was done using a stepwise approach: 1) evening intermediate or long-acting insulin; 2) addition of daytime glipizide; 3) insulin twice daily, with no glipizide; and 4) insulin three to four times daily, with no glipizide., Measurements: Fasting blood glucose and HbA1c levels, retinopathy, lipid and urinary albumin levels, cardiovascular events, hypoglycemia, and body mass index., Results: In the intensive group, the HbA1c level fell 2.07 percentage points; the mean HbA1c level was 7.3% from 6 months onward. The standard group experienced little change. These changes occurred without significant weight gain and with a very low rate of severe hypoglycemia. Sixteen patients (20.5%) in the standard group and 24 patients (32%) in the intensive group had cardiovascular events (P = 0.1)., Conclusions: It is feasible to achieve excellent glycemic control in men with NIDDM in whom standard pharmacologic therapy has failed. The benefit/risk ratio of intensive insulin management in this patient group is not established and has been made the subject of a long-term prospective clinical trial.

The participants of Forum Two addressed the unanswered research questions about metabolic control and non-insulin-dependent diabetes mellitus (NIDDM). The most compelling issue was the effect of metabolic control on both the development and progression of macrovascular disease in patients with NIDDM. Associated questions that could be answered by a well-controlled clinical trial related to the goal of blood glucose control in NIDDM in the elderly and in persons with clinical vascular disease. The specific suggestion was a trial similar to the Veterans Affairs Cooperative Study on Glycemic Control and Complications in NIDDM. Another important research issue that was discussed was the benefit of treating other risk factors such as hypertension and hyperlipidemia in diabetic patients. Yet another area discussed was the study of health services delivery to examine the best care-delivery methods for diabetes and other chronic diseases. Other areas of discussion centered on basic research, that is, the fundamental cause of insulin resistance and the genetics of NIDDM and the loss of protection against atherosclerosis in postmenopausal women with diabetes.

In view of the tendency toward vascular disease in diabetes mellitus, we studied platelet aggregation in 15 normal, 7 prediabetic, 12 latent, and 20 frankly diabetic subjects. Platelets from latent and frank diabetics showed increased platelet aggregation 4 minutes after adding adenosine 5'-diphosphate (60% verus 29% at 1.0 mu-M), epinephrine (46% versus 14% at 0.25 mu-M), and collagen (72% versus 17% at 0.25 mu-g/ml). Three prediabetics had increased platelet aggregation. Platelet sensitivity to aggregating agents was most marked in frank diabetics, intermediate in latent diabetics, and least in prediabetics. Second-phase platelet aggregation was reversed with acetylsalicylic acid, intravenous tolbutamide, and oral glucose administration. We conclude that platelet aggregation may be increased early in diabetes mellitus and may be involved in the genesis of diabetic microangiopathy. Prospective studies on the effect of therapeutic agents such as acetylsalicylic acid on the natural course of diabetic vascular disease are indicated.