Machine Learning-Based Time in Patterns for Blood Glucose Fluctuation Pattern Recognition in Type 1 Diabetes Management: Development and Validation Study.

BACKGROUND: Continuous glucose monitoring (CGM) for diabetes combines noninvasive glucose biosensors, continuous monitoring, cloud computing, and analytics to connect and simulate a hospital setting in a person's home. CGM systems inspired analytics methods to measure glycemic variability (GV), but existing GV analytics methods disregard glucose trends and patterns; hence, they fail to capture entire temporal patterns and do not provide granular insights about glucose fluctuations. OBJECTIVE: This study aimed to propose a machine learning-based framework for blood glucose fluctuation pattern recognition, which enables a more comprehensive representation of GV profiles that could present detailed fluctuation information, be easily understood by clinicians, and provide insights about patient groups based on time in blood fluctuation patterns. METHODS: Overall, 1.5 million measurements from 126 patients in the United Kingdom with type 1 diabetes mellitus (T1DM) were collected, and prevalent blood fluctuation patterns were extracted using dynamic time warping. The patterns were further validated in 225 patients in the United States with T1DM. Hierarchical clustering was then applied on time in patterns to form 4 clusters of patients. Patient groups were compared using statistical analysis. RESULTS: In total, 6 patterns depicting distinctive glucose levels and trends were identified and validated, based on which 4 GV profiles of patients with T1DM were found. They were significantly different in terms of glycemic statuses such as diabetes duration (P=.04), glycated hemoglobin level (P<.001), and time in range (P<.001) and thus had different management needs. CONCLUSIONS: The proposed method can analytically extract existing blood fluctuation patterns from CGM data. Thus, time in patterns can capture a rich view of patients' GV profile. Its conceptual resemblance with time in range, along with rich blood fluctuation details, makes it more scalable, accessible, and informative to clinicians.

Clinical practice guidelines for management of hyperglycaemia in adults with diabetic kidney disease.

A significant percentage of people with diabetes develop chronic kidney disease and diabetes is also a leading cause of end-stage kidney disease (ESKD). The term diabetic kidney disease (DKD) includes both diabetic nephropathy (DN) and diabetes mellitus and chronic kidney disease (DM CKD). DKD is associated with high morbidity and mortality, which are predominantly related to cardiovascular disease. Hyperglycaemia is a modifiable risk factor for cardiovascular complications and progression of DKD. Recent clinical trials of people with DKD have demonstrated improvement in clinical outcomes with sodium glucose co-transporter-2 (SGLT-2) inhibitors. SGLT-2 inhibitors have significantly reduced progression of DKD and onset of ESKD and these reno-protective effects are independent of glucose lowering. At the time of this update Canagliflozin and Dapagliflozin have been approved for delaying the progression of DKD. The Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) Diabetic Kidney Disease Clinical Speciality Group have undertaken a literature review and critical appraisal of the available evidence to inform clinical practice guidelines for management of hyperglycaemia in adults with DKD. This 2021 guidance is for the variety of clinicians who treat people with DKD, including GPs and specialists in diabetes, cardiology and nephrology.

Association of British Clinical Diabetologists and Renal Association guidelines on the detection and management of diabetes post solid organ transplantation.

Post-transplant diabetes mellitus (PTDM) is common after solid organ transplantation (SOT) and associated with increased morbidity and mortality for allograft recipients. Despite the significant burden of disease, there is a paucity of literature with regards to detection, prevention and management. Evidence from the general population with diabetes may not be translatable to the unique context of SOT. In light of emerging clinical evidence and novel anti-diabetic agents, there is an urgent need for updated guidance and recommendations in this high-risk cohort. The Association of British Clinical Diabetologists (ABCD) and Renal Association (RA) Diabetic Kidney Disease Clinical Speciality Group has undertaken a systematic review and critical appraisal of the available evidence. Areas of focus are; (1) epidemiology, (2) pathogenesis, (3) detection, (4) management, (5) modification of immunosuppression, (6) prevention, and (7) PTDM in the non-renal setting. Evidence-graded recommendations are provided for the detection, management and prevention of PTDM, with suggested areas for future research and potential audit standards. The guidelines are endorsed by Diabetes UK, the British Transplantation Society and the Royal College of Physicians of London. The full guidelines are available freely online for the diabetes, renal and transplantation community using the link below. The aim of this review article is to introduce an abridged version of this new clinical guideline ( https://abcd.care/sites/abcd.care/files/site_uploads/Resources/Position-Papers/ABCD-RA%20PTDM%20v14.pdf).

Defining Phenotypes in Diabetic Nephropathy: a novel approach using a cross-sectional analysis of a single centre cohort.

The global increase in Diabetes Mellitus (DM) has led to an increase in DM-Chronic Kidney Disease (DM-CKD). In this cross-sectional observational study we aimed to define phenotypes for patients with DM-CKD that in future may be used to individualise treatment We report 4 DM-CKD phenotypes in 220 patients recruited from Imperial College NHS Trust clinics from 2004-2012. A robust principal component analysis (PCA) was used to statistically determine clusters with phenotypically different patients. 163 patients with complete data sets were analysed: 77 with CKD and 86 with DM-CKD. Four different clusters were identified. Phenotypes 1 and 2 are entirely composed of patients with DM-CKD and phenotypes 3 and 4 are predominantly CKD (non-DM-CKD). Phenotype 1 depicts a cardiovascular phenotype; phenotype 2: microvascular complications with advanced DM-CKD; phenotype 3: advanced CKD with less anaemia, lower weight and HbA1c; phenotype 4: hypercholesteraemic, younger, less severe CKD. We are the first group to describe different phenotypes in DM-CKD using a PCA approach. Identification of phenotypic groups illustrates the differences and similarities that occur under the umbrella term of DM-CKD providing an opportunity to study phenotypes within these groups thereby facilitating development of precision/personalised targeted medicine.

CCL18 synergises with high concentrations of glucose in stimulating fibronectin production in human renal tubuloepithelial cells.

BACKGROUND: Diabetic nephropathy is the leading cause of end stage kidney disease worldwide. The pathogenesis of this disease remains elusive and multiple factors have been implicated. These include the effects of hyperglycaemia, haemodynamic and metabolic factors, and an inflammatory process that stimulates cellular signalling pathways leading to disease progression and severe fibrosis. Fibronectin (Fn) is an important protein of the extracellular matrix that is essential in fibrosis and its presence in increased amounts has been identified in the kidney in diabetic nephropathy. METHODS: Proximal tubuloepithelial (HK-2) cells were stimulated with high glucose (30 mM D-glucose) or glycated albumin (500 µg/mmol) + 4 mM D-glucose or their controls, Mannitol (26 mM + 4 mM D-glucose) and 4 mM D-glucose, respectively. Following 48 h of stimulation the supernatant was collected and MTT [3-(4,5-dimethylthiazole-2,5-diphenyltetrazolium bromide] assay performed to assess cell viability. HK-2 cells were also stimulated in the above environments with recombinant CCL18 (rCCL18) or MCP-1 (rMCP-1) for 48 h with quantification of Fn levels using ELISA. RESULTS: Co-stimulation of HK-2 cells with high concentrations of glucose and rCCL18 significantly increased Fn (p < 0.001), in comparison to high concentrations of glucose alone. HK-2 cells stimulated with glycated albumin consistently produced Fn and this did not alter following co-stimulation with rCCL18 or rMCP-1. CONCLUSION: This study demonstrates how stimulation with a specific chemokine CCL18 in high glucose upregulates the production of Fn from proximal tubuloepithelial cells. This may be relevant to the development of renal fibrosis in diabetic nephropathy.

Staged Hand-Assisted Bilateral Native Nephrectomy for Management of Posttransplant Polyuria in an Adult with Dent's Disease.

Polyuria after kidney transplantation causes graft dysfunction and increased thrombotic risk. We present a case of a polyuric adult with Dent's disease who underwent staged bilateral native nephrectomies, the first operation before transplant and the second four months after transplant. This led to improved allograft function maintained during four years of follow-up. The retroperitoneal laparoscopic approach was well tolerated and allowed continuation of peritoneal dialysis before transplantation. A staged approach helps regulate fluid balance perioperatively and may be tailored to individual need according to posttransplant urine output. This novel approach should be considered for polyuric patients with tubular dysfunction including Dent's disease.

Amyloid-beta peptide is toxic to neurons in vivo via indirect mechanisms.

We have studied the neurotoxicity of amyloid-beta (Abeta) after a single unilateral intravitreal injection. Within the retina apoptotic cells were seen throughout the photoreceptor layer and the inner nuclear layer but not in the ganglion cell layer at 48 h after injection of Abeta(1-42) compared to vehicle control and control peptide. At 5 months, there was a significant reduction in total cell numbers in the ganglion cell layer in Nissl stained retinas. There was glial cell dysfunction with upregulation of glial fibrillary acidic protein and a reduction in the expression of Müller cell associated proteins in the injected retinas. These results suggest an indirect cytotoxic effect of Abeta on retinal neurons and an important role for dysfunction of Müller glia in mediating Abeta neurotoxicity.