The association between anti-insulin aspart antibodies and the pharmacokinetic and pharmacodynamic characteristics of fast-acting insulin aspart in children and adolescents with type 1 diabetes.

BACKGROUND: Fast-acting insulin aspart (faster aspart) is a novel formulation of insulin aspart (IAsp) ensuring ultrafast absorption and effect. AIM: To compare the pharmacokinetics between faster aspart and IAsp, based on free or total IAsp measurement, and investigate the association between anti-IAsp antibodies and faster aspart and IAsp pharmacological properties in children and adolescents with type 1 diabetes (T1D). METHODS: In a randomized, two-period crossover trial, 12 children, 16 adolescents, and 15 adults (6-11, 12-17, and 18-64 years) received 0.2 U/kg double-blindsingle-dose subcutaneous faster aspart or IAsp followed by a standardized liquid meal test. RESULTS: Across age groups, the pharmacokinetic profile was left-shifted including greater early exposure for faster aspart vs IAsp irrespective of free or total IAsp assay. Onset of appearance occurred 2.4 to 5.0 minutes (free) or 1.8 to 3.0 minutes (total) earlier for faster aspart vs IAsp (P < .05). Treatment ratios (faster aspart/IAsp) for 0 to 30 minutes IAsp exposure were 1.60 to 2.11 and 1.62 to 1.96, respectively (children, free: P = .062; otherwise P < .05). The ratio of free/total IAsp for overall exposure (AUCIAsp,0-t ) was negatively associated with anti-IAsp antibody level across age. Pooling with a previous similar trial showed no clear association between anti-IAsp antibodies and meal test 1- or 2-hour postprandial glucose increment independent of age and insulin treatment (R2 ≤ .070; P ≥ .17). CONCLUSIONS: In children and adolescents with T1D, faster aspart provides ultrafast pharmacokinetics irrespective of free or total IAsp assay. Elevated anti-IAsp antibodies are associated with higher total IAsp concentration, but do not impact faster aspart and IAsp glucose-lowering effect.

High intake of dairy during energy restriction does not affect energy balance or the intestinal microflora compared with low dairy intake in overweight individuals in a randomized controlled trial.

During weight loss, dairy calcium is proposed to accelerate weight and fat-mass loss through increased fecal fat excretion. The primary objective was to investigate if a high-dairy energy-restricted diet is superior to low dairy in terms of changes in body weight, body composition, and fecal fat excretion over 24 weeks. Secondary objectives included fecal energy and calcium excretion, resting energy expenditure, blood pressure, lipid metabolism, and gut microbiota. In a randomized, parallel-arm intervention study, 11 men and 69 women (body mass index, 30.6 ± 0.3 kg/m2; age, 44 ± 1 years) were allocated to a 500-kcal (2100 kJ) -deficit diet that was either high (HD: 1500 mg calcium/day) or low (LD: 600 mg calcium/day) in dairy products for 24 weeks. Habitual calcium intake was ∼1000 mg/day. Body weight loss (HD: -6.6 ± 1.3 kg, LD: -7.9 ± 1.5 kg, P = 0.73), fat-mass loss (HD: -7.8% ± 1.3%, LD: -8.5% ± 1.1%, P = 0.76), changes in fecal fat excretion (HD: -0.57 ± 0.76 g, LD: 0.46 ± 0.70 g, P = 0.12), and microbiota composition were similar for the groups over 24 weeks. However, total fat-mass loss was positively associated with relative abundance of Papillibacter (P = 0.017) independent of diet group. Consumption of a high-dairy diet did not increase fecal fat or accelerate weight and fat-mass loss beyond energy restriction over 24 weeks in overweight and obese adults with a habitual calcium intake of ∼1000 mg/day. However, this study indicates that Papillibacter is involved in body compositional changes.