Carnitine concentrations were measured in the milk of sheep, cows, goats, and horses, in human milk of term and preterm infants and in European infant formulas. There were significant species’ differences in carnitine milk content. Acylcarnitme concentrations ranged from 13 to 47% of total carnitine. This may be related to differences in maternal and/or mammary gland metabolism. The concentration of long-chain acylcarnitine in milk was under 1 % in all investigated species. In cow’s milk, there was a decrease in acylcarnitine concentration during the first 2 months of lactation. In human milk, carnitine concentrations did not change during the 1 st month postpartum, but maternal plasma carnitine concentrations increased and plasma concentrations of acylcarnitine were always lower than those in simultaneously sampled milk. Milk carnitine concentrations in mothers of premature infants were not different from those in mothers of term infants. European formulas based on cow’s milk contained somewhat more carnitine than human milk. However, very low carnitine concentrations were found in soy-based or protein hydrolysate formulas. This may lead to nutritional carnitine deficiency in infants receiving these formulas without carnitine supplementation.

The rapidly absorbed analog of human insulin, insulin lispro (LP), is characterized by a faster onset of action, a higher peak insulin level, and a shorter duration of action compared with regular insulin (RI). The aim of this study was to investigate whether intensified treatment with either LP or RI influences insulin receptor status. Twelve patients with insulin-dependent diabetes mellitus (IDDM) participating in a multicenter randomized cross-over trial were allocated to this study. Four patients began with LP, whereas eight patients started with RI. Each patient was switched to the other insulin after a 3-month treatment period. Competitive [125I]A-14-insulin binding studies were performed with isolated monocytes. Treatment with insulin lispro increased the total number of insulin binding sites from 9,400 +/- 2,200 (RI) to 20,300 +/- 3,000 (LP)/monocyte (P < 0.001). The insulin concentration required for a 50% competition of [125I]insulin binding (IC50) decreased from 0.6 +/- 0.2 (RI) to 0.1 +/- 0.03 (LP) nmol/L, indicating significantly higher affinity of insulin binding sites during LP treatment (P < 0.001). In additional experiments, the time course of insulin binding was determined after an oral meal. In LP-treated IDDM patients, the affinity and capacity of insulin binding showed a nadir 1 h after insulin injection and a regained binding affinity and capacity 5 h later. These changes observed after LP treatment were comparable to the effect of endogenous insulin secretion in healthy control subjects. In contrast, the IDDM patients who injected RI showed a decreasing insulin binding affinity and capacity, most markedly expressed after 5 h. The corresponding serum levels of insulin were inversely correlated with the affinity and capacity of insulin-binding sites. Pretreatment of cultured human IM-9 lymphoblasts with LP or RI yielded no difference in the down-regulation of insulin binding. In summary, intensified conventional insulin therapy with LP increased the number and affinity of insulin receptors on circulating monocytes to a level similar to that observed in healthy subjects. We conclude that the improved insulin receptor status observed during LP treatment is caused by its more physiological pharmacokinetic profile.

The effects of dexfenfluramine on 24-hour profiles of ACTH, GH, norepinephrine, insulin and FFA were studied in a group of obese male patients. A controlled comparison trial under metabolic ward conditions was conducted. Dexfenfluramine (15 mg twice daily) was given for 8 days, while patients adhered to a weight maintaining diet. 9 obese patients were treated with dexfenfluramine. 9 obese patients who were randomized on the basis one after another served as a control group. After a 3 day run-in period at 8 am, 10 am, and 4 pm, 8 pm and 12 pm, and 8 am of the following day ACTH, GH, norepinephrine, insulin and FFA were measured before and during the 8th day of dexfenfluramine treatment. During the study body weight slightly decreased in both groups. In the DF group systolic and diastolic blood pressure declined during treatment. The norepinephrine levels were depressed during DF treatment over the entire day. The 24-hour profile of ACTH levels changed in the treatment group to a more distinct circadian rhythm with slightly higher levels in the morning and lower levels at night. The 24-hour profile of GH changed in the drug treated group with a diminished peak of GH secretion at night. Serum concentrations of insulin and FFA were decreased during DF treatment. The hormonal changes during dexfenfluramine treatment suggest that the drug affects endocrine mechanisms that may be involved in regulation of energy balance. Treatment with dexfenfluramine results in decrease of FFA. The mechanisms by which dexfenfluramine operates and displays its various effects on hormones and lipolysis have not been studied.

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