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Diabet. Med. 27, 480–484 (2010) Aims We assessed an extended interruption of subcutaneous insulin delivery during overnight closed-loop glucose control in children and adolescents with Type 1 diabetes (T1D). Methods In seven young subjects with T1D [age 14.2 ± 2.1 years, diabetes duration 6.9 ± 4.0 years, glycated haemoglobin (HbA1c) 8.0 ± 1.5%, body mass index (BMI) 21.4 ± 4.0 kg/m2, total daily insulin dose 0.9 ± 0.2 units/kg/day; mean ± sd) participating in overnight closed-loop glucose control studies, insulin delivery was interrupted for at least 90 min on the basis of predicted hypoglycaemia, low prevailing glucose levels or a too-steep decline in glucose levels. Results Insulin delivery was interrupted for 165 (105, 210) min [median, interquartile range (IQR)]. Plasma glucose was 6.2 ± 3.2 mmol/l at the time of interruption and 5.5 ± 2.0 mmol/l 105 min later ( P = 0.15, paired t-test). Plasma glucose declined during the first hour of the interruption at a rate of 0.02 ± 0.03 mmol/l per min and reached a nadir of 5.2 ± 2.7 mmol/l; 105 min after the interruption, plasma glucose was increasing at a rate of 0.01 ± 0.03 mmol/l per min. When insulin delivery restarted, plasma glucose was 6.4 ± 2.2 mmol/l and peaked at 7.9 ± 2.1 mmol/l in 60 min ( P = 0.01). Physiological levels of plasma insulin were measured throughout with a nadir of 119 ± 78 pmol/l. Conclusions A prolonged interruption of insulin delivery during overnight closed-loop glucose control to prevent hypoglycaemia was not associated with an increased risk of hyperglycaemia in young people with T1D. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. We measured insulin clearance rates in children and young adults with Type I (insulin-dependent) diabetes mellitus to establish their relation with insulin sensitivity and with factors such as growth hormone secretion and body mass index.¶Methods. We studied 46 subjects [mean (range) age 14.4 (9.8–24.6) years), body mass index 21.1 (15.8–29.6)Kgm2] using an overnight (1800–0800 hours) variable rate insulin infusion euglycaemic clamp protocol (5 mmol/l). Plasma free insulin concentrations during steady-state euglycaemia were used as an index of insulin sensitivity and insulin clearance determined as a ratio of insulin infusion rate to plasma free insulin.¶Results. During steady-state euglycaemia (0500–0730 hours), insulin sensitivity [mean (SEM) plasma insulin 0.020 (0.002) mU/l] and insulin clearance rates [19.1 (1.8) ml · kg–1· min] varied with age non-linearly and in a reciprocal fashion to each other (cubic regression F = 4.09, p = 0.01; F = 3.55, p = 0.02, respectively). Insulin sensitivity was negatively related to BMI (r = –0.37, p = 0.011) and mean overnight growth hormone concentrations (r = –0.40, p = 0.007). Insulin clearance was only related to growth hormone concentrations (r = –0.37, p = 0.014). These relations were still evident after stepwise multiple regression analysis (potential determinants: C peptide, sex, age, puberty stage, HbA1 c, duration of diabetes): insulin sensitivity r = 0.55, p < 0.001; insulin clearance r = 0.37, p < 0.02.¶Conclusions/interpretation. Insulin clearance rates vary with age in young subjects with Type I diabetes and are highest during mid-adolescence when insulin sensitivity is at its lowest. Both insulin sensitivity and insulin clearance are related to circulating growth hormone concentrations. [Diabetologia (2000) 43: 61–68] [ABSTRACT FROM AUTHOR]