Newly presenting maturity-onset diabetic subjects were put on diet and if, after 3–4 mo, their fasting plasma glucose continued >6 mmol/L, they were randomized to three therapies: (1) continuing diet alone, (2) with additional sulfonylurea, or (3) with additional basal insulin supplement provided by ultralente insulin. Obese patients were also randomized to metformin therapy. The aim was to lower the fasting plasma glucose to <6 mmol/L and the degree to which this reduced the hemoglobin A1c (HbA1c) concentration was studied in 195 patients over 1 yr. Sulfonylurea and insulin similarly reduced (P < 0.001) the fasting plasma glucose from 8.3 ± 1.9 to 6.7 ±1.3 mmol/L (mean ± 1 SD) and 8.6 ± 2.2 to 6.8 ±1.4 mmol/L, respectively. This was accompanied by a significant reduction (P < 0.001) of the HbA1c to the high normal range, from 9.1 ± 2.1% to 7.8 ± 1.2%, and from 9.1 ± 1.9% to 8.1 ± 1.3%, respectively, both values at 1 yr being significantly (P < 0.05) lower than in patients randomized to diet alone. Patients randomized to diet alone had little change in fasting plasma glucose (8.6 ± 1.8 to 9.3 ± 2.3 mmol/L) or HbA1c (8.8 ± 1.7% to 9.1 ± 1.6%, respectively). Thus, the simple therapeutic aim of trying to reduce the fasting plasma glucose to <6 mmol/L is an effective means of reducing the HbA1c to a high-normal level. The HbA1c and fasting plasma glucose concentrations were similarly related for all three therapies (HbA1c [%] = 0.47 × fasting plasma glucose [mmol/L] + 4.7). If the fasting plasma glucose concentration after dieting was >10 mmol/L, maximal-dose sulfonylurea therapy rarely reduced the fasting plasma glucose to 6 mmol/L and such patients could be started on maximum sulfonylurea therapy. Similar patients randomized to a basal insulin supplement alone required high insulin doses (mean 25 U/day), and also had mean fasting plasma glucose and HbA1c levels above the normal range.

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