Background and Aims

Lipohypertrophy (LH) is a chronic complication of diabetes mellitus that caused by subcutaneous injections of insulin. Nowadays, on the basis of results of ultrasonography of subcutaneous fat prevalence of LH in diabetic patients is still high. The aim has been to develop prevention of insulin induced LH in diabetic patients.

Methods

This study was done on 140 diabetic patients on insulin therapy a mean 8 years. On first stage patients were divided into two groups. First–117 patients with LH, second–23 diabetics without LH. All known LH risk factors were statistically processed using Spearman rank correlation coefficients. Results were statistically significant when p<0,05. On second stage 65 patients from first group were divided into two subgroups. First–50 patients with LH and corrected risk factors, second (control)–15 diabetics with LH and uncorrected risk factors. Ultrasonography were used in assessing new LH in these subgroups after 3 and 6 month.

Results

10 factors were remained after statistic analysis on first stage (p>0,05). Further, in first subgroup only 2 patients (4%) had new LH, while in second–9 diabetics (60%) had new pathologic areas of subcutaneous fat after 3 month. And in first subgroup only 6 patients (12%) had new pathologic areas of subcutaneous fat, while in second–12 diabetics (80%) had new LH after 6 month.

Conclusions

There were stated that only 10 risk factors strongly influence on LH progress. Correction of these risk factors doesn`t lead to development of new subcutaneous fat pathological changes and could be used to prevent LH in diabetic patients in clinical daily practice.

Background and Aims

With the support of the University of Virginia, the ARG controller without pre-meal boluses was successfully tested on the DiAs platform in the first clinical trials in Latin America. To further develop the ARG algorithm, the design of an own platform was carried out in view of future trials.

Methods

The GluControl platform (Figure) is based on the Android APS (AAPS), which is in turn designed from the Open APS. Initially, the connection with the same commercial devices as those used in the clinical trials were considered: Roche Accu-Chek Spirit Combo insulin pump and DexCom G4 Platinum CGM. Thereafter, GluControl was also tested using Freestyle Libre and the MiaoMiao Bluetooth adapter. To run the system, Motorola Moto G5 and One cell-phones were used, in which the ARG controller and a user interface were developed. Multiple-patient remote monitoring and online registry of the main system variables were also implemented.

Results

The base system (GluControl, Dexcom G4 and Roche Spirit Combo) was tested during 240hs, showing adequate CL operation for 93% of total time. Regarding the algorithm, an ARG version with disconnection mitigation techniques was tested using the glucose measurements from the clinical trials. The average relative error in total delivered insulin with respect to Matlab controller implementation was 5,37%, while the difference compared to the clinical trials results with DiAs-based implementation was of 6,94%.

Conclusions

An open-source APS platform including a monitoring system for several patients was introduced. Results are comparable to those obtained by other well-known systems for clinical trials.

Background and Aims

Activation of the hexosamine pathway of glucose metabolism in hyperglycemia leads to the formation of glyoxal, methylglyoxal, and later malonic dialdehyde. These products have a negative effect on the blood vessels wall in patients with type 2 diabetes mellitus (T2DM). The aim of the study was to evaluate the effectiveness of the antioxidant drug N-acetylcysteine in patients with T2DM and lower extremities microangiopathy for correction of glyoxal, metiglyoxal and malonic dialdehyde levels.

Methods

20 men with T2DM and lower extremities microangiopathy with N-acetylcysteine treatment combined with recommended therapy ​​and 30 healthy men (control group) in the study were involved. N-acetylcysteine ​​administered in a daily dose of 600 mg intravenously for 7 days. Methods of high-performance liquid chromatography used.

Results

In patients with T2DM and lower extremities microangiopathy, the glyoxal level increased to the third day (by 56%) and decreased to the control values to the seventh day. The level of methylglyoxal did not change to the third day, but decreased by 5 times to the seventh day. The dynamics of the malonic dialdehyde level decreased on the third (by 15%) and seven (by 47%) days.

Conclusions

The use of N-acetylcysteine allows to decrease the amount of ketoaldehydes in the blood and, thereby, to reduce the manifestation of vascular complications.

Background and Aims

Chronic kidney disease (CKD) is considered as an important factor in the disruption of the synthesis and regulation of 25(OH) vitamin D. Also, in patients with CKD terminal stage the thyroid function decrease is considered as one of the risk factors of adverse outcomes. Comparative analysis of the vitamin 25(OH)D and thyroid hormones levels in patients with diabetes mellitus and CKD was this research aim

Methods

Patients with type 1 and type 2 diabetes mellitus (DM) (n = 14, average age 54.5 years) and comparison group without carbohydrate metabolism disorders (n = 17, average age 52 of the year) were examined. In both groups, patients had a terminal stage of CKD and received renal replacement (лучше substitution therapy) therapy. The thyroid-stimulating hormone, thyroxine levels and vitamin 25(OH)D in the blood were determined

Results

The incidence of severe deficiency of vitamin 25(OH)D in the group of patients with DM was higher (81.8%) compared with the group of patients without DM (45.5%) (p<0.05). Correlation analysis revealed the presence of a feedback relations between the content of vitamin 25(OH)D in the blood and the daily average glycaemia in patients with DM (r=-0.66, p<0.05). An analysis of the thyroid hormones profile revealed thyroid hypofunction - subclinical hypothyroidism in 28.5% of all examined patients. A comparative analysis of this parameters not detected statistically significant differences (p>0.05) between two groups.

Conclusions

High prevalence of vitamin 25(OH)D deficiency in patients with end-stage renal failure and DM were found. More than a quarter of patients receiving renal substitution therapy had subclinical hypothyroidism.

Background and Aims

Endogenous hyperinsulinism caused by an insulinoma is a rare condition, potentially causing severe hypoglycaemia. The definite therapy for insulinoma is a pancreas-sparing surgery. That is why accurate preoperative localization of the tumour is important. However, most insulinomas are solitary, benign and rather small in size, which often makes their localization difficult. In about 10% of insulinomas, conventional imaging (CT, EUS, MRI, somatostatin receptor scintigraphy) is negative. Glucagon-like peptide-1 receptors (GLP-1R) are expressed in high percentage and density in virtually all insulinomas. The aim of this study was to evaluate GLP-1R imaging with the use of [Lys⁴⁰(Ahx-HYNIC-^99mTc/EDDA)NH₂]-exendin-4 in localization of insulinoma, when conventional imaging was negative or inconclusive.

Methods

Whole-body GLP-1R SPECT/CT was performed four hours after administration of [Lys⁴⁰(Ahx-HYNIC-^99mTc/EDDA)NH₂]-exendin-4 in patients with suspected insulinoma and negative or inconclusive conventional imaging (CT/EUS/MRI/SRS). The results of the GLP-1R scintigraphy were evaluated by an experienced nuclear medicine physician. Following surgical excision of the lesion, the diagnostic performance of the GLP-1R scintigraphy was analysed using histopathological evaluation and patient’s symptoms resolution as the gold standard.

Results

Seven female patients with biochemically confirmed endogenous hyperinsulinism during fasting test were enrolled in our study. In all patients, focal uptake of the radiopharmaceutical in the pancreas was found and surgery was performed. No metastases were found. In all cases, insulin-producing neuroendocrine tumors were confirmed by histopathological analysis and patient’s symptoms resolved after surgery. The sensitivity and specificity of GLP-1R scintigraphy were 100%.

Conclusions

GLP-1R imaging with the use of [Lys⁴⁰(Ahx-HYNIC-^99mTc/EDDA)NH₂]-exendin-4 is a highly efficient diagnostic modality for localization of insulinoma.

Background and Aims

For an artificial pancreas (AP) to effectively limit postprandial glucose excursions, it is necessary that the insulin’s glucose lowering effect starts early in relation to meal onset. Automated and reliable early meal onset detection could therefore enhance the control outcome of APs.

A typical AP depends on continuous glucose monitoring (CGM) for insulin dosing. Because of the slow dynamics of the glucose sensing, current CGM based meal detection approaches typically exhibit a delay of 10 minutes between actual meal onset and reliable detection. In contrast, the processes of ingestion and digestion produce sounds even before meal glucose enters the blood.

Therefore, the focus of the present work is towards the early meal onset detection based on abdominal sounds (AS).

Methods

In this work we employ AS recorded in two healthy volunteers with a condenser microphone, and present an automated approach. We use the Mel-frequency cepstral coefficients and wavelet entropy as features. These features are fed to a feed forward neural network for discriminating the “meal” and “no-meal” classes

Results

This approach detects meal onset with an average delay of 4.3 minutes in our limited number of subjects. Importantly, it provides lesser delay than the state-of-the-art CGM based approach .

Conclusions

Preliminary results indicate that the AS-based approach [1] may provide early meal onset information. This can be exploited in an AP through allowable earlier meal insulin boluses, resulting in improved glycemic control.

References:

Background and Aims

The founder of Inreda Diabetic, manufacturer of a fully-automated bihormonal artificial pancreas system (AP) suffers from type 1 diabetes himself. After further improvements of the AP tested before in ten patients at home, he started AP therapy in November 2018 and has been using it ever since. To our knowledge a bihormonal AP has not yet been used for such a long period.

Methods

This case report describes self-experimentation during daily life. Patient’s treatment before using the AP consisted of multiple daily insulin injections and SMBG. The AP, which uses two sensors that continuously monitor the glucose level and administers insulin or glucagon accordingly, stores the glucose values and sends this to a secured server. HbA1c values were measured during regular hospital visits.

Results

Presented values are median [IQR] values over the period from November 18, 2018 until September 30, 2019. The daily time in range (3.9-10 mmol/l) was 92.6 [88.1 – 96.7]% , the median glucose was 7.1 [6.7 – 7.5] mmol/l. The daily time in hypoglycemia was 0.0 [0.0 – 1.0]%. Last measured HbA1c before AP therapy was 66 mmol/mol. Six weeks after the start of AP therapy the HbA1c was 54 mmol/mol and then remained stable.

Conclusions

The bihormonal AP provides good long-term glucose control in this patient. The improved HbA1c values indicate clear health benefits for this patient. Although long-term data is only available for one patient, we expect that the AP will provide good long-term glucose control in other patients with type 1 diabetes as well.

Background and Aims

Artificial pancreas is considered as the state-of-the-art treatment for type-I diabetes while islets transplantation (IT) is the only curative method. IT is associated with significant drawbacks, primarily tissue availability and mandatory use of immunosuppressive drug therapy. The first could be met by employing stem-cell-derived products or porcine islets, the second – by separating the graft from the host immune system. Using parting approach renders the graft avascular so nutrients and waste products are transferred across the membrane by diffusion only. Exercising minimally invasive surgery, encapsulated islets are implanted into an oxygen-poor subcutaneous site. Islets cells, however, are metabolically active and their functionality is oxygen-dependent.

Methods

To meet regulatory, medical and functional requests, we developed a retrievable BAP macro-device - the βAir. It includes three modules: islets, air chamber, and membrane. Gaseous oxygen is supplied to the islets from the air chamber.

Results

We evaluated the potency of the βAir BAP to cure experimental diabetes in allogeneic small animal models for a period of six months. Xenogeneic islets were implanted into mini-swine and monkeys with remarkable results. Two clinical trials, using minimal islets dose demonstrated clear clinical advantage.

Conclusions

Altogether, the capacity of the technology to achieve close to normal control over blood glucose in diabetic models was demonstrated. The direction towards a commercial BAP is understood. We now present Gen2 BAP in which building materials were optimized; the one-piece device was separated into its components – the islets module and the air chamber. Clinical trials using this device will commence in two years.

Background and Aims

Exercise remains challenging to current generation closed-loop (CL) systems relying on glucose as the sole measured input determining insulin delivery. Interstitial lactate may be an additional signal modulating insulin delivery with exercise. We aimed to explore the feasibility of continuous interstitial lactate measurements and their relationship to venous lactate in individuals with T1D during exercise.

Methods

Six adults with T1D (mean ± SD; age: 40.0 ± 9.5y; HbA_1c: 7.6 ± 1.3%) had a prototype optochemical continuous lactate monitor (CLM) inserted subcutaneously in their flank. All participants undertook 40min high intensity exercise. Forearm venous samples for lactate measurement by YSI analyser were collected at 20min intervals from exercise commencement until 240min post-exercise. Exploratory comparisons between CLM and venous lactate profiles included comparisons of time-to-peak and lag-time.

Results

Preliminary data was analysed from six participants. Unacceptable signal loss occurred in two participants post-exercise, with data only included for time-to-peak analysis. There was high variability in lag-time of CLM versus venous lactate, with a difference in time-to-peak ranging from -11 (faster in CLM) to +47 min (n=6) and lactate clearance ranging from -40 (faster in CLM) to +114min (n=4).

Conclusions

This early data suggests that interstitial lactate as measured by a prototype CLM in T1D participants undertaking high intensity exercise mirrored the rise and fall in venous lactate with variable lag. This lag appeared greater when lactate levels were falling post-exercise. These differences between interstitial and venous lactate may have implications for interstitial lactate as a CL additional signal candidate.

Background and Aims

INTRODUCTION: Diabetes technology improves glycaemic control. However, hypoglycaemia remains the main challenge for optimizing it. Integrated systems such as Do It Yourself (DIY) Artificial Pancreas (AP), known worldwide although not FDA approved, can be a major breakthrough in overcoming this barrier.

Methods

METHODS: We present data from a patient using DIY AP (hybrid closed-loop system) consisting of a Roche Combo pump with faster insulin aspart (Fiasp), linked to Dexcom G6 CGM and an open source app that acts as an AP system (Android APS). Real time access to CGM data is provided via Nightscout Open Source (CGM in the cloud). We compare glycaemic data before and after AP system.

Results

RESULTS: 42-year-old male with type 1 DM. Diabetes duration of 28 years, basal-bolus insulin therapy Degludec/Lispro, with good metabolic control but high frequency of hypoglycaemias. Last 3 months FreeStyle Libre Flash CGM readings showed: Mean of 15 scans/day. Estimated Hba1c 5.5%.228 low glucose events. 104 min of time spent in hypoglycaemia. Time in range (TIR) 77% (70-180 mg/dl), 16% below and 7% above target. Hypoglycaemic events were systematically more than 3/day, several of them <54 mg/dl, various were severe. With AP system, Nightscout 3 months reporting showed a significant improve in TIR (77% to 93.2%), and in low values (16% to 4.0%), these averaged 61.1 +/- 6.9 mg/dl. Estimated Hba1c 5.4%.0 severe hypoglycaemias.

Conclusions

CONCLUSION: Elimination of hypoglycaemia is a major challenge in type 1 DM. AP system shows promising results demonstrating a reduction in hypoglycaemia, improving glycaemic control and quality of life.

Background and Aims

Light-emitting diode (LED) phototherapy regenerates pancreatic islets and alters carbohydrate metabolism Phototherapy has shown good results for cell proliferation and regeneration.We investigated the effects of LED (LED) irradiation in the pancreas injured to induction of experimental diabetes and we evaluated the morphological changes in pancreatic β cells.

Methods

For the experiment, we used twenty randomly selected Wistar rats in three groups: non-diabetic diabetic and diabetic control treated with LED Diabetes was induced by injection of streptozotocin. The irradiated group was treated with LED (λ = 805 nm; 40 mW, 22 s; 0.88 J), applied to the anatomical area of the pancreas for 5 consecutive days and evaluated after 30 days.

Results

Islet and duct regeneration in the pancreas was observed after 30 days in the diabetic group treated with LED, and this regeneration was statistically significant when compared to the control group (p = 0.01). In the diabetic control group, hepatic glycogen content was lower when compared to diabetics with LED (p = 0.03). When performing the intraperitoneal insulin tolerance test, we observed differences between diabetic control and diabetic treatment groups (p = 0.03).

Conclusions

This study demonstrated that LED phototherapy allowed regeneration of pancreatic tissue, especially pancreatic islets and altered carbohydrate metabolism in an experimental model.

Background and Aims

We evaluated the function of the insulin-only iLet bionic pancreas delivering Fiasp vs. iLet delivering insulin lispro or aspart vs. usual care in a home-use study in adults on pump and MDI therapy with type 1 diabetes.

Methods

We performed a 3-way, random-order cross-over, home use study comparing the iLet delivering Fiasp (iLet-F) vs. the iLet delivering insulin lispro or aspart according to the usual-care insulin (iLet-LA) vs. usual care (UC) for 7 days each. Bionic pancreas sessions were initiated by entering only the body weight; the iLet autonomously and continuously adapts to individual insulin needs. The PK setting in the iLet algorithm was not adjusted for Fiasp.

Results

The mean CGMG in the iLet-F arm (155±11, p=0.042), but not in the iLet-LA (155±13, p=0.097), was significantly lower than in the UC arm (162±26). There was no difference in mean CGMG between the iLet-F and iLet-LA arms (p=0.64). There were no differences in median % time <54 mg/dl between the arms (0.49 [0.0,1.0] vs. 0.53 [0.2,1.0] vs. 0.35 [0.1,1.2], p>0.64). The % time in range was greater in the iLet-F (70.6±8.1%, p=0.001) and iLet-LA (70.1±9.2%, p=0.006) arms vs. the UC arm (61.5%). There was no difference between the iLet-F and iLet-LA arms (p=0.54). There were no differences in mean insulin TDD between arms (p>0.45).

Conclusions

The iLet can provide effective glucose control when delivering Fiasp, insulin aspart, or insulin lispro. Adjustment to the PK settings of the iLet may be necessary to further improve glycemic outcomes with Fiasp.