Impact of Body Composition and Anemia on Accuracy of a Real-Time Continuous Glucose Monitor in Diabetes Patients on Continuous Ambulatory Peritoneal Dialysis.

Continuous glucose monitoring (CGM) is proposed as an alternative for glycemic assessment in peritoneal dialysis, but volume overload and anemia may affect sensor accuracy. This is an exploratory analysis of a study of Guardian Connect™ with Guardian Sensor™ 3 in 30 participants with diabetes on continuous ambulatory peritoneal dialysis (CAPD) (age [mean ± standard deviation] 64.7 ± 5.6 years, 23 men, body mass index [BMI] 25.4 ± 3.9 kg/m2, blood hemoglobin [Hb] 10.7 ± 1.3 g/dL). The mean absolute relative difference (MARD) was calculated between paired sensor and YSI 2300 STAT venous glucose readings (n = 941) during an 8-h in-clinic session with glucose challenge. Body composition was evaluated using bioimpedance. The overall MARD was 10.4% (95% confidence interval 9.6-11.7). There were no correlations between BMI, extracellular water, relative hydration index, and lean or fat mass with MARD. No correlations were observed between MARD and Hb (r = 0.016, P > 0.05). In summary, this real-time CGM demonstrated good accuracy in CAPD with minimal influence from body composition and anemia.

ROOTS - Circular policies for changing the biowaste system.

The circular economy has a huge potential to make our societies more sustainable and decarbonised, with a reduced impact on the planet's resources. The deployment of innovative solutions in the field of urban biowaste valorisation and reuse is still hindered by numerous bottlenecks, such as technological readiness, funding and financing tools availability, quality and quantity of biowaste and regulatory barriers. The European Green Deal and associated legislative initiatives provide the opportunity to overcome the last ones. To promote innovative solutions for the European circular bioeconomy and help to overcome the barriers for the deployment of a circular bioeconomy, five Horizon 2020 projects working on biowaste valorisation have teamed up. This joint initiative is named ROOTS - circulaR pOlicies for changing the biOwasTe System. The projects HOOP, VALUEWASTE, SCALIBUR, WaysTUP! and CITYLOOPS are piloting new solutions to transform urban biowaste (food waste and green waste) and wastewater into valuable products like feed, fertilisers, bioplastics, biopesticides, proteins and bioethanol. They use different processes and technologies, but they all rely on high levels of recycling/upcycling and propose valorisation solutions relevant to the uptake of a truly circular bioeconomy. As a result of the work performed and experience acquired, a number of bottlenecks have been identified, on the following topics: biowaste prevention, recycling targets and treatment plants, waste and by-products, biopesticides, insects for animal feed, single cell protein, citizen behaviour, investment needs. For each identified bottleneck, this open letter proposes specifically 1) policy recommendations for each level of governance, and 2) information about solutions, good practices and concrete experiences from the participating projects.

Higher dietary magnesium and potassium intake are associated with lower body fat in people with impaired glucose tolerance.

Introduction: Obesity and diabetes are public health concerns worldwide, but few studies have examined the habitual intake of minerals on body composition in people with prediabetes. Methods: In this prospective cross-sectional study, 155 Chinese subjects with IGT [median age: 59 (53-62) years, 58% female] had an assessment of body composition including body fat percentage, oral glucose tolerance tests (OGTT), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and 3-day food records from nutritional programme analysis. Results: Dietary intake of minerals was negatively correlated with body fat. People with obesity had the lowest daily consumption of iron median (IQR) 10.3 (6.9-13.3) mg, magnesium 224 (181-282) mg, and potassium 1973 (1563-2,357) mg when compared to overweight [10.5 (8.0-14.5) mg, 273 (221-335) mg, and 2,204 (1720-2,650) mg] and normal weight individuals [13.2 (10.0-18.6) mg, 313 (243-368) mg, and 2,295 (1833-3,037) mg] (p = 0.008, <0.0001, and 0.013 respectively). Amongst targeted minerals, higher dietary magnesium and potassium intake remained significantly associated with lower body fat after the adjustment of age, gender, macronutrients, fibre, and physical activity. Conclusion: Dietary magnesium and potassium intake may be associated with lower body fat in people with impaired glucose tolerance. Inadequate dietary mineral intake may play contribute to obesity and metabolic disorders independent of macronutrients and fibre consumption.

Evaluation of a Fourth-Generation Subcutaneous Real-Time Continuous Glucose Monitor (CGM) in Individuals With Diabetes on Peritoneal Dialysis.

OBJECTIVE: To evaluate the performance of a real-time continuous glucose monitor (CGM) in individuals with diabetes on peritoneal dialysis (PD). RESEARCH DESIGN AND METHODS: Thirty participants with type 2 diabetes on continuous ambulatory PD wore a Guardian Sensor 3 on the upper arm paired with Guardian Connect for 14 days. We compared CGM readings against Yellow Springs Instrument (YSI) venous glucose during an 8-h in-clinic session with glucose challenge. RESULTS: The mean absolute relative difference (MARD) was 10.4% (95% CI 9.6, 11.7) from 941 CGM-YSI matched pairs; 81.3% of readings were within %15/15 of YSI values in the full glycemic range. Consensus error grid analysis showed 99.9% of sensor values in zones A and B. There were no correlations between pH, uremia, hydration status, and MARD. CONCLUSIONS: We showed satisfactory performance of a real-time CGM sensor in PD patients with diabetes, supporting future use to facilitate treatment decisions.

The potential role of lactulose pharmacotherapy in the treatment and prevention of diabetes.

The non-absorbable disaccharide lactulose is mostly used in the treatment of various gastrointestinal disorders such as chronic constipation and hepatic encephalopathy. The mechanism of action of lactulose remains unclear, but it elicits more than osmotic laxative effects. As a prebiotic, lactulose may act as a bifidogenic factor with positive effects in preventing and controlling diabetes. In this review, we summarized the current evidence for the effect of lactulose on gut metabolism and type 2 diabetes (T2D) prevention. Similar to acarbose, lactulose can also increase the abundance of the short-chain fatty acid (SCFA)-producing bacteria Lactobacillus and Bifidobacterium as well as suppress the potentially pathogenic bacteria Escherichia coli. These bacterial activities have anti-inflammatory effects, nourishing the gut epithelial cells and providing a protective barrier from microorganism infection. Activation of peptide tyrosine tyrosine (PYY) and glucagon-like peptide 1 (GLP1) can influence secondary bile acids and reduce lipopolysaccharide (LPS) endotoxins. A low dose of lactulose with food delayed gastric emptying and increased the whole gut transit times, attenuating the hyperglycemic response without adverse gastrointestinal events. These findings suggest that lactulose may have a role as a pharmacotherapeutic agent in the management and prevention of type 2 diabetes via actions on the gut microbiota.

Continuous Glucose Monitoring Metrics in the Assessment of Glycemia in Moderate-to-Advanced CKD in Diabetes.

Introduction: Glycated hemoglobin A1c (HbA1c) has reduced reliability in advanced chronic kidney disease (CKD) owing to factors influencing red cell turnover. Recent guidelines support the use of continuous glucose monitoring (CGM) in glycemic assessment in these patients. We evaluated relationships between HbA1c and CGM metrics of average glycemia and glucose variability (GV) in moderate-to-advanced CKD. Methods: There were a total of 90 patients with diabetes in CKD stages G3b (n = 33), G4 (n = 43), and G5 (nondialysis) (n = 14) (age [mean ± SD] 65.4 ± 9.0 years, estimated glomerular filtration rate [eGFR] 26.1 ± 9.6 ml/min per 1.73 m2, and HbA1c 7.4 ± 0.8%). CGM metrics were estimated from blinded CGM (Medtronic Ipro2 with Enlite sensor) and compared with HbA1c in the same week. Results: Correlations between glucose management indicator (GMI) and HbA1c attenuated with advancing CKD (G3b [r = 0.68, P < 0.0001], G4 [r = 0.52, P < 0.001], G5 [r = 0.22, P = 0.44], P = 0.01 for CKD stage). In G3b and G4, HbA1c correlated significantly with time-in-range (TIR) (3.9-10.0 mmol/l) (r = -0.55 and r = -0.54, respectively) and % time > 13.9 mmol/l (r = 0.53 and r = 0.44, respectively), but not in G5. HbA1c showed no correlation with % time <3.0 mmol/l (r = -0.045, P = 0.67) or % coefficient of variation (CV) (r = -0.05, P = 0.64) in any CKD stage. Only eGFR was a significant determinant of bias for the difference between GMI and HbA1c (difference -0.28%, 95% CI [-0.52 to -0.03] per 15 ml/min per 1.73 m2 decrement, P = 0.03). Conclusion: CGM-derived indices might serve as an adjunct to HbA1c monitoring to guide glycemic management, especially in those with eGFR <30 ml/min per 1.73 m2. Time in hypoglycemia and glycemic variability are relevant glycemic targets for optimization not reflected by HbA1c.

Use of Continuous Glucose Monitoring in the Assessment and Management of Patients With Diabetes and Chronic Kidney Disease.

In developed countries, diabetes is the leading cause of chronic kidney disease (CKD) and accounts for 50% of incidence of end stage kidney disease. Despite declining prevalence of micro- and macrovascular complications, there are rising trends in renal replacement therapy in diabetes. Optimal glycemic control may reduce risk of progression of CKD and related death. However, assessing glycemic control in patients with advanced CKD and on dialysis (G4-5) can be challenging. Laboratory biomarkers, such as glycated haemoglobin (HbA1c), may be biased by abnormalities in blood haemoglobin, use of iron therapy and erythropoiesis-stimulating agents and chronic inflammation due to uraemia. Similarly, glycated albumin and fructosamine may be biased by abnormal protein turnover. Patients with advanced CKD exhibited heterogeneity in glycemic control ranging from severe insulin resistance to 'burnt-out' beta-cell function. They also had high risk of hypoglycaemia due to reduced renal gluconeogenesis, frequent use of insulin and dysregulation of counterregulatory hormones. Continuous glucose monitoring (CGM) systems measure glucose in interstitial fluid every few minutes and provide an alternative and more reliable method of glycemic assessment, including asymptomatic hypoglycaemia and hyperglycaemic excursions. Recent international guidelines recommended use of CGM-derived Glucose Management Index (GMI) in patients with advanced CKD although data are scarce in this population. Using CGM, patients with CKD were found to experience marked glycemic fluctuations with hypoglycemia due to loss of glucose and insulin during haemodialysis (HD) followed by hyperglycemia in the post-HD period. On the other hand, during peritoneal dialysis, patients may experience glycemic excursions with influx of glucose from dialysate solutions. These undesirable glucose exposure and variability may accelerate decline of residual renal function. Although CGM may improve the quality of glycemic monitoring and control in populations with CKD, further studies are needed to confirm the accuracy, optimal mode and frequency of CGM as well as their cost-effectiveness and user-acceptability in patients with advanced CKD and dialysis.

Glycemic Variability and Time in Range During Self-titration of Once Daily Insulin Glargine 300 U/ml Versus Neutral Protamine Hagedorn Insulin in Insulin-naïve Chinese Type 2 Diabetes Patients.

INTRODUCTION: To compare glycemic variability (GV) and time in range (TIR) in Chinese patients with type 2 diabetes (T2D) initiated on once-daily bedtime insulin glargine 300U/ml (Gla-300) versus neutral protamine Hagedorn (NPH) insulin using continuous glucose monitoring (CGM). METHODS: This was a 24-week, open-label exploratory study with 1:1 randomization comparing patient-adjusted titration of Gla-300 (n = 23) versus NPH (n = 23) at bedtime in insulin-naïve T2D patients on maximum oral glucose-lowering drugs. The starting dose was 0.2 U/kg/day and with self-titration of one unit per week to achieve a target fasting glucose of 4.4-6 mmol/l, without hypoglycemia. Participants had masked CGM at baseline, weeks 11 and 24. The primary outcome was between-treatment differences in CGM glucose standard deviation (SD) at week 24. RESULTS: HbA1c at week 24 were similar, with 21% of Gla-300 versus 4% of NPH-treated patients achieving HbA1c < 7% without confirmed hypoglycemia. There were no differences in anytime glucose SD at week 24 (LS mean difference - 0.08 mmol/l, 95% CI [- 0.42-0.26], p = 0.63). Anytime %TIRs (3.9-10.0 mmol/l) at week 24 were similar (p = 0.91). Nocturnal % time below range < 3.9 mmol/l was significantly lower in the Gla-300 group (least squares (LS) mean difference - 5.03% [- 9.92 to - 0.14], p = 0.04) with lower % coefficient of variation (LS mean difference - 4.5% [- 8.1 to - 0.8], p = 0.018). Diurnal TIR was higher in Gla-300 patients at week 11 but there were no differences at week 24. CONCLUSIONS: Once-daily bedtime Gla-300 was associated with lower nocturnal GV, time below range and self-reported hypoglycemia in insulin-naïve Chinese T2D patients over a 24-week study period, as compared with NPH insulin. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03389490.

Impacts and outcomes of diabetes care in a high risk remote Indigenous community over time: implications for practice.

The aim of this study was to determine diabetes care processes and intermediate clinical outcomes in a remote primary care service in 2009 compared with 2004. A retrospective review of diabetes care from January 2009 to January 2010 was conducted using a chronic disease register (Project Ferret). Completeness of ascertainment was verified by a manual audit of charts. The results from this audit were compared with a similar study conducted in this community in 2004. The main outcome measure was diabetic management: in terms of (a) regular monitoring of diabetic care processes, and (b) compliance with national optimal management guidelines and comparison with diabetic outcomes data from a 2004 audit and the National data from 2009. People with diabetes on the register increased from 60 in 2004 to 77 in 2009. They were younger and heavier with a shorter duration of diagnosed diabetes. Recording of diabetic care processes in 2009 decreased between 5 and 32% compared with 2004 data. Intermediate clinical measures (e.g. glycosylated haemoglobin, blood pressure, triglycerides, albumin creatinine ratio) indicate stable or poorer diabetic control across all measures except total cholesterol. When compared with non-Indigenous diabetics, diabetes is diagnosed earlier and rates of smoking, hypertension, dyslipidaemia and diabetic nephropathy are higher in this population. Insulin use appears to be lower in the study population than reported in the national sample. Improved diabetic care processes and outcomes reported from 1999 to 2003 have not been sustained, and intermediate clinical measures have become more adverse over a 5 year period in this high risk remote community. Chronic care systems, including quality improvement, require renewed investment.