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Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a complicated condition genetically, clinically, and treatment wise. Genetically, there are numerus mutations with different effect on enzyme activity that make genetic diagnosis a challenge. Clinically, there are a wide range of presentations from asymptomatic patients to the severe life-threatening classic CAH. Both an asymptomatic heterozygote and a mildly affected non-classical patient can carry a 'severe' mutation and endow it to their offspring. We present a case of non-classic CAH and discuss the problematic relations between biochemical and genetic diagnosis. By integrating the seemingly contradicting literature, we provide a new simple tool to assess the risk of such patients to give birth to a child with classic CAH.

Describes the risk calculation table for congenital adrenal hyperplasia for parents with non classical 21-OH hydroxylase deficiency

Context Congenital adrenal hyperplasia due to 21-hydroxylase deficiency presents with different severities that correlate with the genotype. The salt-losing phenotype requires 2 alleles with “severe” mutations. Case Description We present a case of salt-losing 21-hydroxylase deficiency that was found to be homozygous for 2 “mild” pathogenic variants: V281L and S301Y. Both in silico and heterologous expression functional analysis demonstrated that co-occurrence of these 2 mutations in cis severely impairs the function of the 21-hydroxylase enzyme. Conclusions This case has important implications for genetic counseling. Regarding this combination of 2 “mild” variants as having mild phenotypic effects could lead to inappropriate counseling of heterozygote carriers.

Objective: Current real-time continuous glucose monitoring (CGM) sensors are approved for 7-14 days of wear, whereas insulin infusion sets are indicated for 2-3 days of wear. Development of a closed-loop control system with the same duration of wear for its CGM and insulin infusion consumables necessitates an infusion set with greater longevity. This study assessed the safety and performance of a newly designed Extended Wear Infusion Set (EWIS) for up to 7 days. Method: A single-center feasibility study targeted the recruitment of 26 adult subjects (between 22 and 75 years of age) This was a 1-center, prospective, open label one arm study, with each subject being asked to wear 4 trial devices until the infusion set failed or 7-day use was reached. Result: There were twenty-one participants of whom 20 completed the study, resulting in 82 insertions and 78 wear counts. At 7 days of wear, the overall failure rate for the EWIS was 19.5%, which was comparable to that after 3-day use for a 3-day infusion set (∼23%) (MiniMed™ Quick-set), as previously reported. (Patel et al. Diabetes Technol Ther. 2014; 16:15-19). Over time, EWIS use for 7 days did not significantly increase hyperglycemia (mean SG value Day 3: 150 ± 56 mg/dL; Day 6: 160 ± 50 mg/dL; target < 250 mg/dL) or total daily insulin requirements (TDI at Day 1: 41±17 U/Day; Day 3: 40±17 U/Day; Day 7: 43 ±20 U/Day) There were no events of infusion set blockage or diabetic ketoacidosis during the study. Conclusion: The performance of the EWIS across 7 days of use was equivalent to the performance reported for a 3-day infusion set during 3 days of use. Safety outcomes during EWIS use were acceptable for the intended subcutaneous insulin infusion by an external pump for 7 days. Disclosure J. Ilany: Research Support; Self; Medtronic. O. Cohen: Employee; Self; Medtronic. N. Konvalina: None. G. Zhang: None. S. Chattaraj: Employee; Self; Medtronic. Funding Medtronic

AIMS To evaluate the glycaemic control achieved by prandial once-daily insulin glulisine injection timing adjustment, based on a continuous glucose monitoring sensor, in comparison to once-daily insulin glulisine injection before breakfast in patients with type 2 diabetes who are uncontrolled with once-daily basal insulin glargine. MATERIALS AND METHODS This was a 24-week open-label, randomized, controlled, multicentre trial. At the end of an 8-week period of basal insulin optimization, patients with HbA1c ≥ 7.5% and FPG < 130 mg/dL were randomized (1:1) to either arm A (no sensor) or arm B (sensor) to receive 16-week intensified prandial glulisine treatment. Patients in arm A received pre-breakfast glulisine, and patients in arm B received glulisine before the meal with the highest glucose elevation based on sensor data. The primary outcome was mean HbA1c at week 24 and secondary outcomes included rates of hypoglycaemic events and insulin dosage. RESULTS A total of 121 patients were randomized to arm A (n = 61) or arm B (n = 60). There was no difference in mean HbA1c at week 24 between arms A and B (8.5% ± 1.2% vs 8.4% ± 1.0%; P = .66). The prandial insulin glulisine dosage for arm A and arm B was 9.3 and 10.1 units, respectively (P = .39). The frequency of hypoglycaemic events did not differ between study arms (36.1% vs 51.7%; P = .08). CONCLUSION Using a CGM sensor to identify the meal with the highest glucose excursion and adjusting the timing of prandial insulin treatment did not show any advantage in terms of glycaemic control or safety in our patients.

Background: The safety and effectiveness of the in-home use of a hybrid closed-loop (HCL) system that automatically increases, decreases, and suspends insulin delivery in response to continuous glucose monitoring were investigated. Methods: Adolescents (n = 30, ages 14–21 years) and adults (n = 94, ages 22–75 years) with type 1 diabetes participated in a multicenter (nine sites in the United States, one site in Israel) pivotal trial. The Medtronic MiniMed® 670G system was used during a 2-week run-in phase without HCL control, or Auto Mode, enabled (Manual Mode) and, thereafter, with Auto Mode enabled during a 3-month study phase. A supervised hotel stay (6 days/5 nights) that included a 24-h frequent blood sample testing with a reference measurement (i-STAT) occurred during the study phase. Results: Adolescents (mean ± standard deviation [SD] 16.5 ± 2.29 years of age and 7.7 ± 4.15 years of diabetes) used the system for a median 75.8% (interquartile range [IQR] 68.0%–88.4%) of the time (2977 patient-days). Adults (mean ± SD 44.6 ± 12.79 years of age and 26.4 ± 12.43 years of diabetes) used the system for a median 88.0% (IQR 77.6%–92.7%) of the time (9412 patient-days). From baseline run-in to the end of study phase, adolescent and adult HbA1c levels decreased from 7.7% ± 0.8% to 7.1% ± 0.6% (P