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Self-referred subjects (N = 227) thought to be at increased risk of developing diabetes who had fasting plasma glucose (FPG) values in the range of 5.5 to 7.7 mmol.L-1 on two consecutive occasions 2 weeks apart were randomized to sulfonylurea therapy (gliclazide, < or = 160 mg.d-1) or to a control group allocated either to double-blind placebo or to no tablets. Subjects were randomly allocated also to reinforced or basic healthy-living advice in a factorial design. A total of 201 subjects have been evaluated for 1 year in three English and two French hospital outpatient centers. Those allocated to sulfonylurea had a significant (P < .001) reduction in median FPG compared with the control group (6.0 mmol.L-1 to 5.6 mmol.L-1, P < .001, v 6.0 mmol.L-1 to 6.0 mmol.L-1, NS). Median hemoglobin A1c (HbA1c) also improved (P < .0002; 5.8% to 5.6%, P < .001, v 5.7% to 5.6%, NS), as did mean beta-cell function (62% to 70%, P < .01, v 62% to 61%, NS). Mean body weight was unchanged in subjects allocated to sulfonylurea (81.7 kg to 82.4 kg, NS), but decreased in the control group (81.6 kg to 80.4 kg, P < .01). More subjects in the sulfonylurea group versus the control group reported one or more minor symptoms of hypoglycemia over 1 year (50% v 24%, P < .0001). Only two subjects reported major hypoglycemic episodes requiring assistance, both of whom were taking sulfonylurea. Insulin sensitivity did not change between groups. Sulfonylurea therapy with gliclazide improved glycemic control and beta-cell function significantly in subjects with increased but not diabetic FPG levels. The study is being extended to determine whether sulfonylurea therapy prevents progression to non-insulin-dependent diabetes mellitus (NIDDM).

Self-referred subjects (N = 227) thought to be at risk of developing non-insulin-dependent diabetes mellitus (NIDDM) and with fasting plasma glucose (FPG) in the range of 5.5 to 7.7 mmol.L-1 on two consecutive tests 2 weeks apart were randomized to reinforced or basic healthy-living advice. They were simultaneously allocated either to a sulfonylurea group or a control group in a two-by-two factorial design. A total of 201 subjects in three English and two French centers completed 1 year's follow-up study. Reinforced advice recommending dietary modification and increased exercise was given every 3 months, and basic advice was given once at the initial visit. Glycemia was monitored by FPG, dietary compliance by body weight and food diaries, and fitness compliance by bicycle ergometer assessment and exercise diaries. Both reinforced and basic advice groups had a significant mean reduction in body weight (1.5 kg) at 3 months, although the weight subsequently returned to baseline. After 1 year, subjects allocated to reinforced advice versus basic advice (1) reported a lower fat intake (34.1% v 35.8%, P = .04) with no difference in lipid profiles, (2) had improved fitness as shown by increased calculated maximal oxygen uptake ([Vo2max] 2.39 v 2.18 L.min-1, P = .007) with no change in insulin sensitivity, (3) showed no change in FPG, glucose tolerance, or hemoglobin A1c (HbA1c), and (4) showed a greater tendency to withdraw from the study (16% v 7%, P = .03). In conclusion, reinforced healthy-living advice given to self-referred subjects with increased FPG did not encourage sufficiently pronounced life-style changes for significantly greater effects on body weight and glycemia in a 1-year study than basic healthy-living advice.