Effects of dapagliflozin on insulin-requirement, glucose excretion and ß-hydroxybutyrate levels are not related to baseline HbA1c in youth with type 1 diabetes.

Youth with type 1 diabetes (T1D) infrequently achieve HbA1c targets. Therefore, this placebo-controlled, randomized, crossover study was set up to assess the safety, effect and pharmacokinetics of a single dose of 10 mg dapagliflozin (DAPA) as add-on to insulin in relationship to HbA1c in youth. A total of 33 youths (14 males, median age 16 years, diabetes duration 8 years) were included and stratified into 3 baseline HbA1c categories (<7.5%, 7.5%-9.0% or >9.0; n = 11 each). During the study period of 24 hours, intravenous insulin administration and glucose-infusion kept blood glucose levels at 160 to 220 mg/dL. DAPA reduced mean insulin dose by 13.6% ( P < .0001 by ANOVA) and increased urinary glucose excretion by 610% (143.4 vs 22.4 g/24 h; P < .0001), both irrespective of baseline HbA1c. Six independent episodes in 6 patients with plasma ß-hydroxybutyrate levels between ≥0.6 and <1.0 mmol/L were observed after liquid meal challenges, 5 episodes in the DAPA group and 1 in the placebo group. This study provides a proof-of-concept, irrespective of preexisting HbA1c levels, for adjunct SGLT2-inhibitor therapy in the paediatric age group by lowering insulin dose and increasing glucose excretion.

Faster-acting insulin aspart provides faster onset and greater early exposure vs insulin aspart in children and adolescents with type 1 diabetes mellitus.

BACKGROUND: Faster-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation with additional excipients (L-arginine and niacinamide). In adults, faster aspart provides faster onset and greater early exposure and action vs IAsp. AIM: This randomized, double-blind, 2-period crossover trial investigated the pharmacological properties of faster aspart vs IAsp in 12 children (6-11 years), 13 adolescents (12-17 years), and 15 adults (18-64 years) with type 1 diabetes mellitus. METHODS: Subjects received 0.2 U/kg subcutaneous dosing (mean of 8.3, 12.8, and 15.6 U, respectively) immediately prior to a standardized meal (17.3 g carbohydrate/100 mL; amount adjusted by body weight). RESULTS: Consistently across age groups, onset of appearance occurred approximately twice-as-fast (5-7 minutes earlier) and early exposure (AUCIAsp,0-30min ; area under the IAsp curve from 0 to 30 minutes) was greater (by 78%-147%) for faster aspart vs IAsp, with no treatment differences in total exposure (AUCIAsp,0-t ) or maximum concentration (C max ). Two-hour postmeal plasma glucose excursion was reduced for faster aspart vs IAsp (although only reaching statistical significance in children). In accordance with the absolute dose administered for each age group, AUCIAsp,0-t for faster aspart was lower in children (estimated ratio children/adults [95% confidence interval]: 0.59 [0.50;0.69], P < .001) and adolescents (0.78 [0.67;0.90], P = .002) vs adults. No age group differences were seen in C max (0.91 [0.70;1.17], P = .445, and 0.99 [0.77;1.26], P = .903). The age effect on AUCIAsp,0-t and C max did not differ statistically significantly between treatments. Faster aspart and IAsp were well-tolerated. CONCLUSION: The current findings in children and adolescents suggest a potential for faster aspart to improve postprandial glycemia over current rapid-acting insulins also in younger age groups. http://ClinicalTrials.gov identifier: NCT02035371.

MD-Logic overnight type 1 diabetes control in home settings: A multicentre, multinational, single blind randomized trial.

AIMS: To evaluate the safety, efficacy and need for remote monitoring of the MD-Logic closed-loop system during short-term overnight use at home. METHODS: Seventy-five patients (38 male; aged 10-54 years; average A1c, 7.8% ± 0.7%, 61.8 ± 7.2 mmol/mol) were enrolled from 3 clinical sites. Patients were randomly assigned to participate in 2 overnight crossover periods, each including 4 consecutive nights, 1 under closed-loop control and 1 under sensor-augmented pump (SAP) therapy in the patient's home. Both study arms were supervised using a remote-monitoring system in a blinded manner. Primary endpoints were time spent with glucose levels below 70 mg/dL and percentage of nights in which mean overnight glucose levels were within 90 to 140 mg/dL. RESULTS: The median [interquartile range] percentage of time spent in hypoglycaemia was significantly lower on nights when MD-Logic was used, compared to SAP therapy (2.07 [0, 4.78] and 2.6 [0, 10.34], respectively; P = .004) and the percentage of individual nights with a mean overnight glucose level in target was significantly greater (75 [42, 75] and 50 [25,75], respectively; P = .008). The time spent in target range was increased by a median of 28% (P = .001), with the same amount of insulin (10.69 [7.28, 13.94] and 10.41[6.9, 14.07], respectively; P = .087). The remote monitoring triggered calls for hypoglycaemia at twice the rate during SAP therapy compared to closed-loop control (62 and 29, respectively; P = .002). CONCLUSIONS: The MD-Logic system demonstrated a safe and efficient profile during overnight use by children, adolescents and adults with type 1 diabetes and, therefore, provides an effective means of mitigating the risk of nocturnal hypoglycaemia.

Lipoatrophy in children with type 1 diabetes: an increasing incidence?

The objectives were to evaluate the current prevalence of lipoatrophy at insulin injection sites in young patients with type 1 diabetes. Standardized examination of insulin injection sites in all 678 patients with type 1 diabetes treated in 2013 in our outpatient clinic were conducted. In case of lipoatrophy photo documentation and standardized interview with parents and patients were performed. We identified a total of 16 patients (43.8% male) with lipoatrophy (overall prevalence 2.4%). The current mean age (±SD) of the affected patients was 14.4 ± 3.9 years, age and diabetes duration at onset of lipoatrophy were 11.5 ± 3.8 years and 5.4 ± 3.6 years, respectively. All patients were using analogs at the onset of lipoatrophy. In all, 14 of 16 patients (87.5%) were on insulin pump compared with 52% without lipoatrophy (P = .0018). The use of steel needle and Teflon catheter was equal between the pump patients. Concomitant autoimmune diseases were present in 37.5% of the patients (thyroiditis: n = 3, thyroiditis and celiac disease: n = 2, celiac disease: n = 1) compared with 15.0% in those without lipoatrophy (P = .0128). Lipoatrophy was present in young patients treated with modern insulins and pumps; however, the prevalence was relatively low as expected with the use of modern insulins. Our data may support the hypothesis that a constant mechanical element such as a subcutaneous catheter may trigger the development of lipoatrophy, particularly in those patients with more than 1 autoimmune disease.