Bedtime insulin for suppression of overnight free-fatty acid, blood glucose, and glucose production in NIDDM

Abstract

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 (greater than 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 less than .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 less than .001), 674 +/- 61 vs. 491 +/- 57 vs. 484 +/- 36 microM (P less than 0.01) and 12.7 +/- 1.6 vs. 18.1 +/- 2.2 vs. 20.7 +/- 2.4 microU/L (P less than .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 less than .001). The nocturnal profile of plasma lactate was similar before and during bedtime insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)