Background and Aims

Hypoglycaemia remains a prevalent complication with deleterious consequences among individuals with diabetes. We aimed to identify independent predictors of hypoglycaemia and impending hypoglycaemia using real-time continuous glucose monitoring and a physiological data acquisition wristband.

Methods

Six-week longitudinal analysis of 12 adults with type 1 diabetes using real-time continuous glucose monitoring (Dexcom G6) and a clinically validated physiological data acquisition sensor (Empatica E4). A mixed effects logistic regression model was applied to predict hypoglycaemia using measurements recorded during blood glucose levels below 72 mg/dL and 54mg/dL. Measurements within 1-hour before glucose levels fell below 72mg/dL were used to predict impeding hypoglycaemia.

Results

Participants had a median age (IQR) of 40 (30-39) years and were equally stratified by gender and mode of insulin delivery (multiple daily injections and continuous subcutaneous insulin infusion). Hypoglycaemia was negatively predicted by a higher electrodermal activity standard deviation (SD) (p=0.03), higher heart rate (SD) (<0.01), and higher mean skin temperature, (p<0.05). While greater maximum phasic skin conductance responses and mean heart rate increased the odds of hypoglycaemia (p<0.01). Elevation in mean skin temperature and physical activity (SD) were both significant positive predictive factors for impeding hypoglycaemia but not established biochemical hypoglycaemia.

Conclusions

Measurements obtained from wearable physiological wristband data sensors could be integrated alongside CGM data to improve identification and prediction of hypoglycaemia.

Background and Aims

Modern m-health technologies open new perspectives in managing childhood obesity. Within the Greek funded project, named “ENDORSE”, an innovative software ecosystem is developed incorporating Artificial Intelligence and gamification technologies capable of delivering tools and services facilitating self- management of health while engaging the active involvement of formal and informal caregivers.

Methods

ENDORSE applies a parent-child multicomponent intervention including dietary, physical activity, educational and behavioral components. It implements a goal-oriented approach which includes periodic assessment of child’s weight, behavioral lifestyle and needs in order to accordingly adjust goal settings and improve adherence. Obese children are trained and encouraged to adopt healthy diet and physical activity through their interaction with the ENDORSE serious game. Aiming at optimizing the parental role, a mobile application has been developed facilitating daily self-monitoring of goals and communication with healthcare professionals.

Results

The ENDORSE platform has the capability to leverage data from different sources (e.g. activity trackers, mobile apps) in order to create a complete user profile. Personalized, tailored messages and reminders targeting child and parents, along with recommendations for goal settings adjustment and adherence reports, are produced by the ENDORSE recommendation engine with the aim to achieve personalization and adaptation.

Conclusions

The ENDORSE platform implements modern m-health technologies into routine clinical care of obese children. Future work includes the execution of pilot trials to evaluate its effectiveness in terms of improving health outcomes and user’s acceptance. Acknowledgements: Supported within the framework of the ENDORSE project, which is funded by the NSRF (Grant agreement: Τ1ΕΔΚ-03695)

Background and Aims

FFA accumulate not only in adipose tissue during obesity. The high content of FFA contributes to the development of NAFLD. Oxidative stress and mitochondrial dysfunction contribute to the development of T2DM. The adaptive defense mechanism promotes the activation of the antioxidant and cytoprotective response.

The study aimed to identify the role of antioxidant protection associated with liver mitochondrial biogenesis in obese patients.

Methods

Liver biopsies were taken during laparoscopic surgery. The study included 59 obese patients with T2DM (47.6±8.8 years; 47.2±6.1 kg/m²; 23 men and 36 women), 57 obese patients without T2DM (40.7±6.1 years; 41.8±7.1 kg/m²; 26 men and 31 women). The control group consisted of 41 healthy donors. Gene mRNA expression levels were determined by PCR on a CFX96 Touch system (BioRad). MtDNA copies were determined by drop PCR using a QX200 Droplet Digital PCR system (BioRad).

Results

NFE2L2, HSP70 expression decreased in obese patients with T2DM relative to patients without T2DM and healthy donors. In contrast, mtDNA copies and HSF1 expression increased in obese patients with T2DM. SOD1 expression decreased in obese patients with and without T2DM, while MT-ND4 expression increased.

Conclusions

Thus, liver compensatory mechanisms are triggered and reduced the effects of oxidative stress and the development of steatohepatitis in obese patients without T2DM. State assignment in the field of scientific activity [No.FZWN-2020-0010 to Larisa Litvinova]; State of Leading Scientific Schools of the Russian Federation [No.2495.2020.7 to Larisa Litvinova].

Background and Aims

Obesity is a worldwide epidemic with a clear-cut tendency for progression, now recognized as a disease. Nevertheless, a non-operative approach for its treatment remains a challenge.

This study evaluated the efficacy of our new obesity-treatment algorithm.

Methods

Twenty-seven patients files with uncomplicated obesity were analyzed. GLP1 analogue Liraglutide (Saxenda) treatment was implemented for all. In 17 patients (63%), Metformin therapy was additionally implemented due to Impaired Fasting Glucose (IFG). Routine professional CGM (Medtronic iPRO2) was performed in most of participants in order to exclude hypoglycemia, mainly at nights. Our specific therapeutic (Gravicentric) algorithm was used, based on several specific food behavior recommendations, combining this therapy with metformin and physical activity guidance.

Results

The mean age was 58.5 years, therapy duration - 10.5 months, body weight before therapy was 97.3 kg, BMI was 32.7 kg/m².

By using our treatment algorithm, we achieved significant reduction in body weight by 6.8 kg and BMI by 2.4 kg/m² on average. No patients received Saxenda doses higher than 1.8 mg/day, while 70% were managed on 1.2 mg per day or less.

Conclusions

Our real-life weight and BMI resembles to the Liraglutide large RCT results (average reduction of weight by 6.5 kg and BMI by 2.4 kg/m²) while using mild–to-moderate Saxenda dose regimens, without clinically significant side effects. No hypoglycemia time-below-range elevation was noticed at CGM investigations. This therapeutic scheme provides us the unique opportunity to achieve maximal effect at minimal dose. It additionally reduces the probability of side effects (including hypoglycemia and ketosis), and cut treatment costs.

Background and Aims

Insulin, the main hormone for modulating blood glucose levels, is used for diabetes treatment mainly through subcutaneous injections. This can lead to poor patient compliance and side-effects. To face this problem, Medicsen is developing a Smartpatch with a wide range of tested technologies, focused on the non-invasive, controlled and painless insulin transdermal delivery through sonophoresis.

Methods

In vitro and in vivo tests, such as the permeability phenomenon using Franz diffusion Cell and swine model, or biochemical, chromatography or circular dichroism tests, among others, have been performed to prove the efficacy and safety of the technology.

Results

Lack of damage was observed on insulin molecule, which maintain its biological function and stability, as seen in vivo, in HPLC studies and in the circular dichroism spectra of the samples (Fig. 1), which shows no variability, reaching the characteristic minimum at 219nm (sd+/-8.31) in all groups tested. TEM images of skin, ELISA of skin damage markers TNF a and IL-2 (Fig. 2), and other biochemical tests, show no significant changes in the tissue or in the expression and concentration of relevant compounds. Lastly, the technology proved to be effective in the non-invasive insulin delivery through the skin, as observed in our system and in the in vivo model of blood glucose reduction.

Conclusions

All evidence collected during in vitro and in vivo studies show promising results, indicating that the technology developed by Medicsen is safe and effective. Thus, human trials will be performed in order to demonstrate its potential on diabetes treatment.

Background and Aims

Background: Intraperitoneal insulin delivery provides more rapid onset of action and shorter duration compared with subcutaneous insulin. These attributes are critical for improving management of diabetes with sensor-augmented pump therapy or automated insulin dosing. We present data on the stability of insulin delivered through a novel system for continuous intraperitoneal insulin infusion (CIPII) using an Insulin Delivery Conduit (IDC) made up of a subcutaneous port and tunneled catheter that is accessed by a customized traditional external pump infusion set in an ex-vivo environment that mimics the intraperitoneal space.

Aim: This study aims to examine three system configurations to evaluate compatibility with insulin over 6 weeks.

Methods

Methods: Each system was maintained at 37°C. Regular insulin was pumped through the IDC using a Medtronic insulin pump at a basal rate of 0.6U/hr and three manual daily 5-unit boluses. Infusion sets and pump cartridges (with fresh insulin) were replaced every 7 days. Samples for all test replicates were collected on Day 1, 7, 14, 21, 28, 35 and 42 just prior to weekly infusion set/pump cartridge replacement, and tested for physical and chemical degradation, using Thioflavin T (ThT) fluorescence and HPLC, respectively.

Results

Results: All insulin samples were negative for ThT response indicating absence of insulin aggregates, and had purity levels greater than 97.3%, which meets specification of less than 6% loss in target purity. Therefore, target acceptance criteria for insulin stability were met.

Conclusions

Conclusion: This novel IDC approach for CIPII is a promising method to effectively deliver insulin without insulin degradation.