A Pair of Siblings With Wolfram Syndrome: A Review of the Literature and Treatment Options.

Wolfram syndrome (WS) is a rare genetic disorder typically characterized by juvenile onset diabetes mellitus, optic atrophy, hearing loss, diabetes insipidus, and neurodegeneration. There would be a high index of clinical suspicion for WS when clinical manifestations of type 1 diabetes and optic atrophy present together. Genetic analysis is often required to confirm the diagnosis. We describe a pair of Chinese siblings diagnosed with WS at ages 20 and 24 years, respectively. DNA sequencing of the WFS1 gene which encodes for Wolframin ER Transmembrane Glycoprotein identified a heterozygous nonsense variant NM_006005.3: c.1999C>T p.(Gln667*) and a heterozygous missense variant c.2170C>T p.(Pro724Ser) in exon 8 of the gene for both siblings. There is no curative treatment for WS and management of this debilitating disease is aimed at treating individual clinical manifestations, slowing disease progression, and improving quality of life. Treatment with liraglutide, a glucagon-like-peptide-1 receptor agonist, and tauroursodeoxycholic acid was started for the younger sibling, the proband. There was reduction in insulin requirements and improvement in glycemic control. The other sibling was not offered liraglutide due to her complex treatment regimen for end-organ failure. Genetic testing is a valuable tool to detect WS early to allow precise and prompt diagnosis, thereby facilitating the coordinated care from a multidisciplinary team of clinicians.

A head-to-head comparison between Guardian Connect and FreeStyle Libre systems and an evaluation of user acceptability of sensors in patients with type 1 diabetes.

AIMS: A user-calibrated real-time continuous glucose monitoring (rt-CGM) system is compared to a factory-calibrated flash glucose monitoring (FGM) system and assessed in terms of accuracy and acceptability in patients with type 1 diabetes (T1D). METHODS: Ten participants with T1D were enroled from a specialist diabetes centre in Singapore and provided with the Guardian Connect with Enlite Sensor (Medtronic, Northridge, CA, USA) and first-generation Freestyle Libre System (Abbott Diabetes Care, Witney, UK), worn simultaneously. Participants had to check capillary blood glucose four times per day. At the end of week 1 and week 2, participants returned for data download and were given a user evaluation survey. RESULTS: Accuracy evaluation between Guardian Connect and Freestyle Libre includes the overall mean absolute relative difference value (9.7 ± 11.0% vs. 17.5 ± 10.9%), Clarke Error Grid zones A + B (98.6% vs. 98.1%), sensitivity (78.9% vs. 63.4%), and specificity (93.4% vs. 81.0%). Notably, time below range (<3.9 mmol/L) was 10.5% for FGM versus 2% for rt-CGM. From the evaluation survey, 90% of participants perceived rt-CGM to be accurate versus 40% for FGM, although the majority found both devices to be easy to use, educational, and useful in improving glycaemic control. However, due to the cost of sensors, only 30% were keen to use either device for continuous monitoring. CONCLUSIONS: Although rt-CGM was superior to FGM in terms of accuracy, the value of glucose trends in both devices is still useful in diabetes self-management. Patients and clinicians may consider either technology depending on their requirements.

Glucose Awareness to Motivate and Enable Solutions (GAMES) in diabetes mellitus using flash glucose monitoring: A clinical programme.

AIMS: This real-world observational clinical programme evaluated short and medium-term effects of intermittent flash glucose monitoring on HbA1c, glycaemic variability and lifestyle behavioural changes. METHODS: Two first-generation Libre flash glucose monitoring sensors were provided 3-4 months apart with a food, activity diary, user evaluation survey and treatment modification after each sensor wear. T-tests were used to compare glucose variables within each sensor (week 1 vs. week 2) and between sensors (1st sensor vs. 2nd sensor). EasyGV software was used to calculate glycaemic variability. RESULTS: From 42 type 1 diabetes and 120 type 2 diabetes participants, there was no statistically significant change in mean HbA1c for participants with type 1 diabetes at 3-4 months after the 1st sensor but there was a statistically significant HbA1c reduction for participants with type 2 diabetes [-4 mmol/mol (-0.4%), p = 0.008], despite no statistically significant differences in carbohydrate intake, exercise frequency and duration. Greater reduction was seen in those with baseline HbA1c> 86 mmol/mol (10%) in both type 1 [-12 mmol/mol (-1.1%), p = 0.009] and type 2 diabetes [-11 mmol/mol (-1.0%), p = 0.001). Both type 1 and type 2 diabetes showed improvements in Glucose Management Indicator and percentage time-above-range when comparing week 1 versus week 2 of the same sensor. Higher scan frequency resulted in improved glycaemic parameters and certain measures of glycaemic variability. The majority of participants (85%) agreed that flash glucose monitoring is a useful device but only 60% were keen to use it for daily monitoring. CONCLUSION: Constant feedback from flash glucose monitoring improves glycaemic parameters within the first week of wear. Intermittent use 3-4 months apart resulted in greater improvements for those with higher baseline HbA1c.