To test whether a suppertime injection of human ultralente insulin in patients with type I diabetes would result in a larger inhibition of basal hepatic glucose production (HGP) and improvement in fasting and mean daily plasma glucose levels.
We studied 16 type I diabetic patients (41 ± 4 years of age; body mass index [BMI] = 23.3 ± 0.3 kg/m2; diabetes duration >3 years) with a crossover protocol of therapy with an intermediate and ultralente insulin. All patients were already treated with three injections per day of regular insulin in addition to intermediate-acting (NPH) insulin at suppertime. After a 14-day run-in period, patients were randomly assigned to treatment with equivalent doses (10.8 ± 0.8 U, at 1900) of intermediate (Humulin 1) or ultralente (Humulin U) insulin. After 1 month of treatment, patients were crossed over. No change of the insulin dosage was performed during the study period. Basal HGP was measured by β-glucose infusion. Plasma glucose concentration was measured in the fasting state and monitored during the day.
Before starting the study period, fasting plasma glucose was 13.4 ±1.1 mM and plasma free-insulin was 48.0 ± 4.8 pM. Daily plasma glucose concentration averaged 10.3 ± 0.3 mM and the area under the curve (AUC) was 1.41 ± 0.05 mol/14 h. NPH insulin, given at suppertime for a month, did not induce significant changes in fasting plasma insulin (40.2 ± 4.8 pM), glucose concentration (14.0 ± 0.9 mM) or HGP (20.2 ± 2.2 jamol · kg–1 · min–1). Accordingly, no change occurred in the average daily plasma glucose (10.3 ± 0.3 mM) or AUC (1.41 ± 0.9 mol/14 h). Glycated hemoglobin also was not affected (8.2 ± 0.4 vs. 8.2 ± 0.3%). On the contrary, a 4-week treatment with ultralente insulin, also given at suppertime, was associated with a decline in the basal HGP (16.0 ±1.3 /Ltmol · kg–1 · min–1), fasting (11.3 ± 0.9 mM) and average daily (9.4 ± 0.3 mM) plasma glucose concentrations, and AUC (1.29 ± 0.07 mol/14 h) of plasma glucose level (all P < 0.05). Glycated hemoglobin was reduced (7.9 ± 0.4%). In each condition, fasting plasma glucose concentration was correlated with the average daily plasma glucose level (basal = 0.78; intermediate = 0.89; ultralente = 0.62; all P < 0.05), which suggests that ultralente insulin likely induces the improvements of metabolic control through reducing fasting plasma glucose.
Our results suggest that treating type I diabetic patients with ultralente insulin at suppertime provides a better modulation of basal HGP so that lower fasting plasma glucose levels are ensured. The reduction of fasting hyperglycemia is likely to affect positively aily plasma glucose control.
