VETERANS AFFAIRS COOPERATIVE STUDY ON GLYCEMIC CONTROL AND COMPLICATIONS IN TYPE-II DIABETES (VA CSDM) - RESULTS OF THE FEASIBILITY TRIAL

OBJECTIVE - It is not clear whether intensive pharmacological therapy can be effectively sustained in non-insulin-dependent diabetes mellitu s (NIDDM). The relative risks and benefits of intensive insulin therap y in NIDDM are not well defined. Accordingly, we designed a feasibilit y study that compared standard therapy and intensive therapy in a grou p of NIDDM men who required insulin due to sustained hyperglycemia. RE SEARCH DESIGN AND METHODS - A prospective trial was conducted in five medical centers in 153 men of 60 +/- 6 years of age age who had a know n diagnosis of diabetes for 7.8 +/- 4 years. They were randomly assign ed to a standard insulin treatment group (one morning injection per da y) or to an intensive therapy group designed to attain near-normal gly cemia and a clinically significant separation of glycohemoglobin from the standard arm. A four-step plan was used in the intensive therapy g roup along with daily self-monitoring of glucose: 1) an evening insuli n injection, 2) the same injection adding daytime glipizide, 3) two in jections of insulin alone, and 4) multiple daily injections. Patient a ccrual and adherence, glycohemoglobin (HbA(1c)), side effects, and mea surements of endpoints for a prospective long-term trial were assessed . RESULTS - Accrual goals were met, mean follow-up time was 27 months (range 18-35 months), and patients kept 98.6% of scheduled visits. Aft er 6 months, the mean HbA(1c) in the intensive therapy group was at or below 7.3% and remained 2% lower than the standard group for the dura tion of the trial. Most of the decrease in the mean HbA(1c) in the int ensive group was the obtained by a single injection of evening interme diate insulin, alone or with daytime glipizide. By the end of the tria l, 64% of the patients had advanced to two or more injections of insul in a day, aiming for normal HbAlc. However, only a small additional fa ll in HbA(1c) was attained. Severe hypoglycemia was rare (two events p er 100 patients per year) and not significantly different between the groups, nor were changes in weight, blood pressure, or plasma lipids. There were 61 new cardiovascular events in 40 patients and 10 deaths ( 6 due to cardiovascular causes). CONCLUSIONS - Intense stepped insulin therapy in NIDDM patients who have failed glycemic control on pharmac ological therapy is effective in maintaining near-normal glycemic cont rol for >2 years without excessive severe hypoglycemia, weight gain, h ypertension, or dyslipidemia. Cardiovascular event rates are high at t his stage of NIDDM. A long-term prospective trial is needed to assess the risk-benefit ratio oi intensified treatment of hyperglycemia in NI DDM patients requiring insulin.