Intensive Replacement of Basal Insulin in Patients With Type 1 Diabetes Given Rapid-Acting Insulin Analog at Mealtime

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Abstract
OBJECTIVE—To establish differences in blood glucose between different regimens of optimized basal insulin substitution in type 1 diabetic patients given lispro insulin at meals, i.e., NPH injected four times a day versus glargine insulin once daily at dinner or at bedtime. RESEARCH DESIGN AND METHODS—A total of 51 patients with type 1 diabetes on intensive therapy (NPH four times/day and lispro insulin at each meal) were randomized to three different regimens of basal insulin substitution while continuing lispro insulin at meals: continuation of NPH four times/day (n = 17), once daily glargine at dinnertime (n = 17), and once daily glargine at bedtime (n = 17) for 3 months. Blood glucose targets were fasting, preprandial, and bedtime concentrations at 6.4–7.2 mmol/l and 2 h after meals at 8.0–9.2 mmol/l. The primary end point was HbA1c. RESULTS—Mean daily blood glucose was lower with dinnertime glargine (7.5 ± 0.2 mmol/l) or bedtime glargine (7.4 ± 0.2 mmol/l) versus NPH (8.3 ± 0.2 mmol/l) (P < 0.05). A greater percentage of blood glucose values were at the target value with glargine at dinner and bedtime versus those with NPH (P < 0.05). HbA1c at 3 months did not change with NPH but decreased with glargine at dinnertime (from 6.8 ± 0.2 to 6.4 ± 0.1%) and glargine at bedtime (from 7.0 ± 0.2 to 6.6 ± 0.1%) (P < 0.04 vs. NPH). Total daily insulin doses were similar with the three treatments, but with glargine there was an increase in basal and a decrease in mealtime insulin requirements (P < 0.05). Frequency of mild hypoglycemia (self-assisted episodes, blood glucose ≤4.0 mmol/l) was lower with glargine (dinnertime 8.1 ± 0.8 mmol/l, bedtime 7.7 ± 0.9 mmol/l) than with NPH (12.2 ± 1.3 mmol/l) (episodes/patient-month, P < 0.04). In-hospital profiles confirmed outpatient blood glucose data and indicated more steady plasma insulin concentrations at night and before meals with glargine versus NPH (P < 0.05). There were no differences between glargine given at dinnertime and at bedtime. CONCLUSIONS—Regimens of basal insulin with either NPH four times/day or glargine once/day in type 1 diabetic patients both result in good glycemic control. However, the simpler glargine regimen decreases the HbA1c level and frequency of hypoglycemia versus NPH. In contrast to NPH, which should be given at bedtime, insulin glargine can be administered at dinnertime without deteriorating blood glucose control.