Bedtime Insulin for Suppression of Overnight Free–Fatty Acid, Blood Glucose, and Glucose Production in NIDDM

We studied the clinical effectiveness and mechanism underlying the glucose-lowering effect of evening insulin therapy. Nocturnal profiles of blood glucose, plasma free fatty acid (FFA), glycerol, and lactate and overnight glucose kinetics ([3-³H] glucose infusion) were measured in 15 non-insulin-dependent diabetic (NIDDM) patients with a relative body weight of 128 ± 4% who were poorly controlled with oral therapy alone. The patients were studied before and 2 wk and 3 mo after bedtime insulin (23 ± 3 IU) was given in addition to oral therapy. An early-morning rise in blood glucose (>31 mg/dl = 1.5 mM) was present in two-thirds of the patients and was associated with an overnight rise in plasma FFA and an increase in glucose production (Ra) during the early-morning hours (change 0.42 ± 0.10 mg · kg⁻¹ · min⁻¹ P < .05, between 0300 and 0800). The overnight mean levels of blood glucose, plasma FFA, and serum insulin averaged 212 ± 9 vs. 137 ± 11 vs. 133 ± 11 mg/dl (P < .001), 674 ± 61 vs. 491 ± 57 vs. 484 ± 36 μM (P < 0.01) and 12.7 ± 1.6 vs. 18.1 ± 2.2 vs. 20.7 ± 2.4 μU/ (P < .01) before and 2 wk and 3 mo after the combination therapy. The decrements in overnight glucose and FFA levels after 2 wk of bedtime insulin therapy were closely correlated (r = .86, P < .001). The nocturnal profile of plasma lactate was similar before and during bedtime insulin therapy. The overnight mean glucose R_a fell significantly after insulin administration (2.31 ± 0.13 vs. 1.83 ± 0.09 vs. 1.83 ± 0.10 mg · kg⁻¹ min⁻¹ P < .01, respectively). There was a positive correlation between the overnight mean values of R_a and the plasma FFA concentration (r = .58, P < .001). These data raise the possibility the improvement in overall glycemic control by the administration of evening insulin is related to the suppression of overnight plasma FFA concentrations and to a consequent reduction in overnight glucose production.