Burden of chronic kidney disease and rapid decline in renal function among adults attending a hospital-based diabetes center in Northern Europe.

INTRODUCTION: This study aimed to determine the prevalence of diabetic kidney disease (DKD) and rapid renal function decline and to identify indices associated with this decline among adults attending a diabetes center in Northern Europe. RESEARCH DESIGN AND METHODS: This is a retrospective cohort study of 4606 patients who attended a diabetes center in Ireland between June 2012 and December 2016. Definition/staging of chronic kidney disease used the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 classification based on data from the most recently attended appointment. Relevant longitudinal trends and variabilities were derived from serial records prior to index visit. Rapid renal function decline was defined based on per cent and absolute rates of estimated glomerular filtration rate (eGFR) change. Multiple linear regression was used to explore the relationships between explanatory variables and per cent eGFR change. RESULTS: 42.0% (total), 23.4% (type 1 diabetes), 47.9% (type 2 diabetes) and 32.6% (other diabetes) had DKD. Rapid decline based on per cent change was more frequent in type 2 than in type 1 diabetes (32.8% vs 14.0%, p<0.001). Indices independently associated with rapid eGFR decline included older age, greater number of antihypertensives, higher log-normalized urine albumin to creatinine ratio (LNuACR), serum alkaline phosphatase, thyroid stimulating hormone, variability in systolic blood pressure and variability in LNuACR, lower glycated hemoglobin, high-density lipoprotein cholesterol and diastolic blood pressure, and lack of ACE inhibitor/angiotensin receptor blocker prescription. CONCLUSIONS: DKD (using the KDIGO 2012 classification) and rapid eGFR decline were highly prevalent among adults attending a hospital-based diabetes clinic in a predominantly Caucasian Northern European country. The burden was greater for adults with type 2 diabetes. Expected as well as potentially novel clinical predictors were identified.

Use of continuous glucose monitoring for sport in type 1 diabetes.

BACKGROUND: The benefits of exercise for patients with type 1 diabetes (T1D) are difficult to balance with associated glycaemic excursions. The aim of this cohort study was to show that continuous glucose monitoring (CGM) could reduce glycaemic excursions in patients with T1D already using insulin pumps, exercising at moderate to high intensity. METHODS: Questionnaires were used to identify patients with T1D using insulin pumps and naive to CGM use, who reported regular exercise. Six were enrolled and trained on Enlite sensor use with Medtronic Minimed Paradigm Veo system and given activity trackers and written advice on adjustment of insulin or carbohydrate intake for exercise. Resting heart rate (HR) and age were used to determine HR surrogates of moderate and high-intensity exercise. They were to exercise as usual for 3 weeks (run-in week, week 1 and week 2) using the activity trackers and heart rate monitors. Problem areas in Diabetes, Hypoglycaemia fear survey II, Diabetes Technology Questionnaire and Gold scores were completed prior to run-in and at the end. The downloaded sensor glucose data were used to compare the change in time in range (glucose 3.9-10.0 mmol/L) from week 1 to week 2. RESULTS: For the duration of exercise, this time in glucose range increased from 72±20 to 88%±16 %, p=0.05. The time in hypoglycaemia range (glucose < 3.9 mmol/L) went from 3.9±7.9 to 2.4%±4.8 %, p=0.39. The time in hyperglycaemia range (> 10 mmol/L) reduced from 24±19 to 10%±17%, p=0.04. CONCLUSION: These results demonstrate the benefit of CGM use for patients with T1DM doing moderate-intensity to high-intensity exercise.

Role of continuous glucose monitoring in the management of diabetic pregnancy.

Self-monitoring of blood glucose (SMBG) with intermittent capillary glucose fingerstick tests is currently the universally accepted method of glucose monitoring in pregnancy. During pregnancy SMBG tests are recommended before and after meals and before bed (typically 7 values/d). Continuous glucose monitoring systems consist of a disposable subcutaneous glucose-sensing device, electrochemically measuring glucose levels in subcutaneous tissues every 10 seconds, providing an average interstitial glucose value every 5 minutes (typically 288 values/d). From a research perspective this provides unprecedented insights into the pathophysiology of glucose metabolism, while from a clinical perspective it can facilitate enhanced patient-professional decision making, patient motivation, and improved glycaemic control. CGM has thus been described as a "roadmap for effective self-management" and as a "stepping stone in the journey towards a cure." This review will consider the lessons learned and evidence supporting current and potential future use of CGM in the management of diabetes in pregnancy.

Islets transplanted in immunoisolation devices: a review of the progress and the challenges that remain.

The concept of using an immunoisolation device to facilitate the transplantation of islets without the need for immunosuppression has been around for more than 50 yr. Significant progress has been made in developing suitable materials that satisfy the need for biocompatibility, durability, and permselectivity. However, the search is ongoing for a device that allows sufficient oxygen transfer while maintaining a barrier to immune cells and preventing rejection of the transplanted tissue. Separating the islets from the rich blood supply in the native pancreas takes its toll. The immunoisolated islets commonly suffer from hypoxia and necrosis, which in turn triggers a host immune response. Efforts have been made to improve the supply of nutrients by using proangiogenic factors to augment the development of a vascular supply in the transplant site, by using small islet cell aggregates to reduce the barrier to diffusion of oxygen, or by creating scaffolds that are in close proximity to a vascular network such as the omental blood supply. Even if these efforts are successful, the shortage of donor islet tissue available for transplantation remains a major problem. To this end, a search for a renewable source of insulin-producing cells is ongoing; whether these will come from adult or embryonic stem cells or xenogeneic sources remains to be seen. Herein we will review the above issues and chart the progress made with various immunoisolation devices in small and large animal models and the small number of clinical trials carried out to date.

Quantitative assessment of islets of Langerhans encapsulated in alginate.

Improved methods have recently been developed for assessing islet viability and quantity in human islet preparations for transplantation, and these measurements have proven useful for predicting transplantation outcome. The objectives of this study were to adapt these methods for use with microencapsulated islets, to verify that they provide meaningful quantitative measurements, and to test them with two model systems: (1) barium alginate and (2) barium alginate containing a 70% (w/v) perfluorocarbon (PFC) emulsion, which presents challenges to use of these assays and is of interest in its own right as a means for reducing oxygen supply limitations to encapsulated tissue. Mitochondrial function was assessed by oxygen consumption rate measurements, and the analysis of data was modified to account for the increased solubility of oxygen in the PFC-alginate capsules. Capsules were dissolved and tissue recovered for nuclei counting to measure the number of cells. Capsule volume was determined from alginate or PFC content and used to normalize measurements. After low oxygen culture for 2 days, islets in normal alginate lost substantial viable tissue and displayed necrotic cores, whereas most of the original oxygen consumption rate was recovered with PFC alginate, and little necrosis was observed. All nuclei were recovered with normal alginate, but some nuclei from nonrespiring cells were lost with PFC alginate. Biocompatibility tests revealed toxicity at the islet periphery associated with the lipid emulsion used to provide surfactants during the emulsification process. We conclude that these new assay methods can be applied to islets encapsulated in materials as complex as PFC-alginate. Measurements made with these materials revealed that enhancement of oxygen permeability of the encapsulating material with a concentrated PFC emulsion improves survival of encapsulated islets under hypoxic conditions, but reformulation of the PFC emulsion is needed to reduce toxicity.

Microfabrication of homogenous, asymmetric cell-laden hydrogel capsules.

Cell encapsulation has been broadly investigated as a technology to provide immunoprotection for transplanted endocrine cells. Here we develop a new fabrication method that allows for rapid, homogenous microencapsulation of insulin-secreting cells with varying microscale geometries and asymmetrically modified surfaces. Micromolding systems were developed using polypropylene mesh, and the material/surface properties associated with efficient encapsulation were identified. Cells encapsulated using these methods maintain desirable viability and preserve their ability to proliferate and secrete insulin in a glucose-responsive manner. This new cell encapsulation approach enables a practical route to an inexpensive and convenient process for the generation of cell-laden microcapsules without requiring any specialized equipment or microfabrication process.