Improved Glucose Control Research Articles

Stay-at-Home Orders During the COVID-19 Pandemic, an Opportunity to Improve Glucose Control Through Behavioral Changes in Type 1 Diabetes.

To investigate the impact of coronavirus disease 2019 lockdown on glycemic control and associated factors in people living with type 1 diabetes. An observational evaluation from a self-reported questionnaire on behavioral changes and glycemic information from flash glucose monitoring (FGM) during the lockdown in 1,378 individuals living with type 1 diabetes who used a French dedicated nationwide web application (CoviDIAB). The main outcome was the change of the mean glucose level 2 months before and 1 month after the lockdown. We found that mean glucose improved from 9.1 ± 1.7 mmol/L to 8.7 ± 1.7 mmol/L (P < 0.001). Factors associated with better glycemic control were a decrease of alcohol consumption (odds ratio [OR] 1.75 [95% CI 1.04-2.94]), an increase in the frequency of FGM scans (OR 1.48 [1.04-2.10]) and in the number of hypoglycemia events (OR 1.67 [1.13-2.46]), and an easier diabetes control perception (OR 1.71 [1.18-2.49]). Our findings suggest that lockdown has a positive impact on glycemic control in people with type 1 diabetes.

Survey about do-it-yourself closed loop systems in the treatment of diabetes in Germany.

Continuous glucose monitoring (CGM) improves treatment with lower blood glucose levels and less patient effort. In combination with continuous insulin application, glycemic control improves and hypoglycemic episodes should decrease. Direct feedback of CGM to continuous subcutaneous insulin application, using an algorithm is called a closed-loop (CL) artificial pancreas system. Commercial devices stop insulin application by predicting hypoglycemic blood glucose levels through direct interaction between the sensor and pump. The prediction is usually made for about 30 minutes and insulin delivery is restarted at the previous level if a rise in blood glucose is predicted within the next 30 minutes (hybrid closed loop system, HCL this is known as a predictive low glucose suspend system (PLGS)). In a fully CL system, sensor and pump communicate permanently with each other. Hybrid closed-loop (HCL) systems, which require the user to estimate the meal size and provide a meal insulin basis, are commercially available in Germany at the moment. These systems result in fewer hyperglycemic and hypoglycemic episodes with improved glucose control. Open source initiatives have provided support by building do-it-yourself CL (DIYCL) devices for automated insulin application since 2014, and are used by a tech-savvy subgroup of patients. The first commercial hybrid CL system has been available in Germany since September 2019. We surveyed 1054 patients to determine which devices are currently used, which features would be in demand by potential users, and the benefits of DIYCL systems. 9.7% of these used a DIYCL system, while 50% would most likely trust these systems but more than 85% of the patients would use a commercial closed loop system, if available. The DIYCL users had a better glucose control regarding their time in range (TIR) and glycated hemoglobin (HbA1c).

Comparison of two carbohydrate intake strategies to improve glucose control during exercise in adolescents and adults with type 1 diabetes

Background and aimsDuring aerobic physical activity (PA), hypoglycemia is common in people with type 1 diabetes (T1D). Few studies have compared the effectiveness of different carbohydrate (CHO) intake strategies to prevent PA-induced hypoglycemia. Our objective was to compare the efficacy of two CHO intake strategies, same total amount but different CHO intake timing, to maintain glucose levels in the target range (4.0–10.0 mmol/L) during PA in people with T1D. Methods and resultsAn open-label, randomized, crossover study in 33 participants (21 adults; 12 adolescents). Participants practiced 60 min PA sessions (ergocyle) at 60% VO2peak 3.5 h after lunch comparing an intake of 0.5 g of CHO per kg of body weight applied in a pre-PA single CHO intake (SCI) or in a distributed CHO intake (DCI) before and during PA. The percentage of time spent in glucose level target range during PA was not different between the two strategies (SCI: 75 ± 35%; DCI: 87 ± 26%; P = 0.12). Hypoglycemia (<4.0 mmol/L) occurred in 4 participants (12%) with SCI compared to 6 participants (18%) with DCI (P = 0.42). The SCI strategy led to a higher increase (P = 0.01) and variability of glucose levels (P = 0.04) compared with DCI. ConclusionsIn people living with T1D, for a 60 min moderate aerobic PA in the post-absorptive condition, a 0.5 g/kg CHO intake helped most participants maintain acceptable glycemic control with both strategies. No clinically significant difference was observed between the SCI and DCI strategies.ClinicalTrials.gov Identifier: NCT03214107 (July 11, 2017).

Ramadan fasting in people with type 1 diabetes during COVID-19 pandemic: The DaR Global survey

ObjectivesThe DaR Global survey was conducted to determine the impact of the COVID-19 pandemic on the intentions to fast and the outcomes of fasting in <18 years versus ≥18 years age groups with type 1 diabetes mellitus (T1DM). MethodsMuslim people with T1DM were surveyed in 13 countries between June and August 2020, shortly after the end of Ramadan (23rd April–23rd May 2020) using a simple questionnaire. Results71.1% of muslims with T1DM fasted during Ramadan. Concerns about COVID-19 were higher in individuals ≥18 years (p = 0.002). The number of participants who decided not to fast plus those who received Ramadan-focused education were significantly higher in the ≥18-year group (p < 0.05). Hypoglycemia (60.7%) as well as hyperglycemia (44.8%) was major complications of fasting during Ramadan in both groups irrespective of age. ConclusionCOVID-19 pandemic had minor impact on the decision to fast Ramadan in T1DM cohort. This was higher in the age group of ≥18 years compared to those <18 years group. Only regional differences were noted for fasting attitude and behavior among T1DM groups. This survey highlights the need for Ramadan focused diabetes education to improve glucose control and prevent complications during fasting.

A Meal Detection Algorithm for the Artificial Pancreas: A Randomized Controlled Clinical Trial in Adolescents With Type 1 Diabetes.

We developed a meal detection algorithm for the artificial pancreas (AP+MDA) that detects unannounced meals and delivers automatic insulin boluses. We conducted a randomized crossover trial in 11 adolescents aged 12-18 years with HbA1c ≥7.5% who missed one or more boluses in the past 6 months. We compared 1) continuous subcutaneous insulin infusion (CSII), 2) artificial pancreas (AP), and 3) AP+MDA. Participants underwent three 9-h interventions involving breakfast with a bolus and lunch without a bolus. In AP+MDA, the meal detection time was 40.0 (interquartile range 40.0-57.5) min. Compared with CSII, AP+MDA decreased the 4-h postlunch incremental area under the curve (iAUC) from 24.1 ± 9.5 to 15.4 ± 8.0 h ⋅ mmol/L (P = 0.03). iAUC did not differ between AP+MDA and AP (19.6 ± 10.4 h ⋅ mmol/L, P = 0.21) or between AP and CSII (P = 0.33). The AP+MDA reduced time >10 mmol/L (58.0 ± 26.6%) compared with CSII (79.6 ± 27.5%, P = 0.02) and AP (74.2 ± 20.6%, P = 0.047). The AP+MDA improved glucose control after an unannounced meal.

Continuous Glucose Monitoring for Underserved and Minority Patients with Type 2 Diabetes in an Interprofessional Internal Medicine Clinic.

Evaluate the impact of interprofessional continuous glucose monitoring (CGM) on glycemic control in underserved and minority patients with type 2 diabetes mellitus (T2DM). The IRB-approved, retrospective quasi-experimental study was conducted between August 2018 and August 2019 at an internal medicine residency clinic. Adult patients with diagnosed T2DM, an indication for CGM (hyperglycemia, hypoglycemia, and/or glycemic variability), and at least 10 consecutive days of CGM data were included. Patients who were pregnant and/or missed one or more clinic appointments were excluded. Patients were followed weekly over a 14-day period during which data from the CGM sensor were downloaded and interpreted by the interprofessional team. Interventions with shared decision-making were made at each visit. Fifty-five patients were included, with a mean age of 61+11.2 years, 86% were of non-white race, and 56% were female. Average blood glucose levels decreased from 208.39 mg/dL at week 1 to 190.74 mg/dL at week 2, a 17.65 mg/dLreduction (p = 0.0281). Time within target range (70-180 mg/dL) increased by 6.16% (p = 0.0038), while time above range (>180 mg/dL) decreased by 5.5% (p = 0.0168). Average number of hypoglycemic events (readings <70 mg/dL) did not change significantly from week 1 to week 2 (2.94 vs. 3.64, p > 0.05). Of the 66 interventions made after week 1, 33% were made by the pharmacy team, 56% were made by the attending or resident physicians, and 11% were made by the dietician. Of 59 interventions made after week 2, 32% were made by the pharmacy team, 49% were made by the attending or resident physicians, and 19% were made by the dietician. The interprofessional collaborative CGM service was associated with improvements in glucose control based on increased time within target range and reduced hyperglycemia, without increasing the risk of hypoglycemia or medication burden.

Trends in the process and outcome indicators of type 2 diabetes care: a cohort study from Eastern Finland, 2012\u20132017

BackgroundEvidence-based guidelines include concrete treatment targets that can be used as process and outcome indicators in the evaluation of the quality of healthcare services and diabetes care. Quality improvement can be evaluated by monitoring longitudinal trends in the care indicators on the system level. The aim of this study is to describe trends in the processes and outcomes of care among people with type 2 diabetes in North Karelia, Finland.MethodsThe data consist of all adults with type 2 diabetes (identified from the EHRs using ICD-10 codes) who used primary or specialized care services in North Karelia during 2012–2017. The diabetes care was evaluated using the measurement activity, treatment levels, and the achievement of the treatment targets for HbA1c and LDL as care indicators. Logistic and linear models with generalized estimating equations were used to assess the differences between years, sexes, and age groups.ResultsThe proportion of patients with annual measurement varied between 75.8 and 78.1% for HbA1c and between 67.4 and 69.1% for LDL during a five-year follow-up. The changes in average levels were moderate: a 0.2% (2 mmol/mol) increase for HbA1c and a 0.1 mmol/l decrease for LDL. Anyway, the proportion of patients meeting the treatment target for HbA1c decreased from 72.7 to 67.3% (age-adjusted decrease: 5.7%p, 95% CI: 4.5–6.9) and for LDL it increased from 53.4 to 59.5% (age-adjusted increase: 5.6%p, 95% CI: 4.2–7.0). Women were measured and met the HbA1c target level more often compared with men. Conversely, men met the LDL target level more often than women, and the age-adjusted difference between sexes increased smoothly from 7.9%p to 11.7%p.ConclusionsThe achievements in relation to type 2 diabetes care in North Karelia are very good, but no major improvement was observed during follow-up. HbA1c levels had a rising tendency and LDL levels declining tendency indicating quality improvement in LDL management, but challenges in further improvement in glucose control.

A Meta-Analysis of the Impact of Resveratrol Supplementation on Markers of Renal Function and Blood Pressure in Type 2 Diabetic Patients on Hypoglycemic Therapy.

Evidence on the beneficial effects of resveratrol supplementation on cardiovascular disease-related profiles in patients with type 2 diabetes (T2D) is conflicting, while its impact on renal function and blood pressure measurements remains to be established in these patients. The current meta-analysis included randomized controlled trials (RCTs) reporting on the impact of resveratrol supplementation on markers of renal function and blood pressure in patients with T2D on hypoglycemic medication. Electronic databases such as MEDLINE, Cochrane Library, Scopus, and EMBASE were searched for eligible studies from inception up to June 2020. The random and fixed effects model was used in the meta-analysis. A total of five RCTs met the inclusion criteria and involved 388 participants with T2D. Notably, most of the participants were on metformin therapy, or metformin in combination with other hypoglycemic drugs such as insulin and glibenclamide. Pooled estimates showed that resveratrol supplementation in patients with T2D lowered the levels of fasting glucose (SMD: −0.06 [95% CI: −0.24, 0.12]; I2 = 4%, p = 0.39) and insulin (SMD: −0.08 [95% CI: −0.50, 0.34], I2 = 73%, p = 0.002) when compared to those on placebo. In addition, supplementation significantly lowered systolic blood pressure (SMD: −5.77 [95% CI: −8.61, −2.93], I2 = 66%, p = 0.02) in these patients. Although resveratrol supplementation did not affect creatinine or urea levels, it reduced the total protein content (SMD: −0.19 [95% CI: −0.36, −0.02]; I2 = 91%, p = 0.001). In all, resveratrol supplementation in hypoglycemic therapy improves glucose control and lowers blood pressure; however, additional evidence is necessary to confirm its effect on renal function in patients with T2D.

The putative binding site and SAR rationalization of small molecules against glucagon-like peptide-1 receptor using homology model and crystal structures: a comparative study

Glucagon-like peptide-1 (GLP-1) is involved in glucose-stimulated insulin secretion and weight regulating actions through the activation of the GLP-1 receptor (GLP-1R). Clinical effectiveness of GLP-1 mimetics is effective in improving glucose control in patients. Thus, identifying and developing orally active small-molecule agonists are highly desirable. This study summarizes the structure-function relationship of hGLP-1R through computational approaches and search of small molecule GLP-1R agonists. We carried out mutation guided data-driven study, for developing the GLP-1R model to explore and validate the putative site for quinoxaline analogues. The developed GLP-1R homology model was subjected to 500 ns MD simulation for validation. Various snapshots were considered to identify the best structure of GLP-1R based on correlation between experimental pEC50 and various theoretical parameters (docking score, MM-GBSA ΔG bind, WM/MM ΔG bind). The putative binding site (Sitemap and WaterMap has been predicted and it matched well with the available data. Excellent correlation (R2 =0.94), between pEC50 and WM/MM ΔG bind for the snapshot at 350 ns was observed after including induced-fit docking results of the most potent molecule. Enrichment calculation indicates better AUC (=0.75) for predicted complex structure. A comparison of the developed GLP-1R model with the available crystal structure shows excellent similarities and it was used for virtual screening to find small molecule agonists. The good correlation of our model with crystal structures of GLP-1R may help to understand the structure-function relationship of other secretin families.

Recent Updates on Free Fatty Acid Receptor 1 (GPR-40) Agonists for the Treatment of Type 2 Diabetes Mellitus.

The global incidence of type 2 diabetes mellitus (T2DM) has enthused the development of new antidiabetic targets with low toxicity and long-term stability. In this respect, free fatty acid receptor 1 (FFAR1), which is also recognized as a G protein-coupled receptor 40 (GPR40), is a novel target for the treatment of T2DM. FFAR1/GPR40 has a high level of expression in β-cells of the pancreas, and the requirement of glucose for stimulating insulin release results in immense stimulation to utilise this target in the medication of T2DM. The data used for this review is based on the search of several scienctific databases as well as various patent databases. The main search terms used were free fatty acid receptor 1, FFAR1, FFAR1 agonists, diabetes mellitus, G protein-coupled receptor 40 (GPR40), GPR40 agonists, GPR40 ligands, type 2 diabetes mellitus and T2DM. The present review article gives a brief overview of FFAR1, its role in T2DM, recent developments in small molecule FFAR1 (GPR40) agonists reported till now, compounds of natural/plant origin, recent patents published in the last few years, mechanism of FFAR1 activation by the agonists, and clinical status of the FFAR1/GPR40 agonists. The agonists of FFAR1/GRP40 showed considerable potential for the therapeutic control of T2DM. Most of the small molecule FFAR1/GPR40 agonists developed were aryl alkanoic acid derivatives (such as phenylpropionic acids, phenylacetic acids, phenoxyacetic acids, and benzofuran acetic acid derivatives) and thiazolidinediones. Some natural/plant-derived compounds, including fatty acids, sesquiterpenes, phenolic compounds, anthocyanins, isoquinoline, and indole alkaloids, were also reported as potent FFAR1 agonists. The clinical investigations of the FFAR1 agonists demonstrated their probable role in the improvement of glucose control. Though, there are some problems still to be resolved in this field as some FFAR1 agonists terminated in the late phase of clinical studies due to "hepatotoxicity." Currently, PBI-4050 is under clinical investigation by Prometic. Further investigation of pharmacophore scaffolds for FFAR1 full agonists as well as multitargeted modulators and corresponding clinical investigations will be anticipated, which can open up new directions in this area.

Targeting glucose control in preterm infants: Pilot studies of continuous glucose monitoring

Objective Hyperglycaemia is common in very preterm infants and is associated with adverse outcomes. Preventing hyperglycaemia without increasing the risk of hypoglycaemia is difficult. Real time tracking with continuous glucose monitors (CGM) may improve glucose control. We assessed the feasibility and safety of CGM to target glucose control in preterm infants, to inform a randomised controlled trial (RCT). Design We performed a single centre study in very preterm infants during the first week of life. Accuracy was assessed by comparison of CGM with blood glucose levels (n=20 infants). In a separate pilot study of efficacy (n=20), real-time CGM combined with a paper guideline to target glucose control (2.6–10 mmol/L) was compared with standard neonatal care (masked CGM). Questionnaires were used to assess staff acceptability. Results No concerns were raised about infection or skin integrity at sensor site. The sensor performed well compared with point-of-care blood glucose measurements, mean bias of −0.27 (95% CI −0.35 to −0.19). Per cent time in target range (sensor glucose 2.6–10 mmol/L) was greater with CGM than POC (77% vs 59%, respectively) and per cent time sensor glucose >10 mmol/L was less with CGM than POC (24% vs 40%, respectively). The CGM also detected clinically unsuspected episodes of hypoglycaemia. Staff reported that the use of the CGM positively improved clinical care. Conclusions This study suggests that CGM has sufficient accuracy and utility in preterm infants to warrant formal testing in a RCT.

Walking for subjects with type 2 diabetes: a systematic review and joint AMD/SID/SISMES evidence-based practical guideline

AimsRegular exercise is considered a cornerstone in the management of type 2 diabetes mellitus (T2DM). It improves glucose control and cardiovascular risk factors, contributes to weight loss, and also improves general well-being, likely playing a role in the prevention of chronic complications of diabetes. However, compliance to exercise recommendations is generally inadequate in subjects with T2DM. Walking is the most ancestral form of physical activity in humans, easily applicable in daily life. It may represent, in many patients, a first simple step towards lifestyle changes. Nevertheless, while most diabetic patients do not engage in any weekly walking, exercise guidelines do not generally detail how to improve its use. The aims of this document are to conduct a systematic review of available literature on walking as a therapeutic tool for people with T2DM, and to provide practical, evidence-based clinical recommendations regarding its utilization in these subjects.Data synthesisAnalysis of available RCTs proved that regular walking training, especially when supervised, improves glucose control in subjects with T2DM, with favorable effects also on cardiorespiratory fitness, body weight, and blood pressure. Moreover, some recent studies have shown that even short bouts of walking, used for breaking prolonged sitting, can ameliorate glucose profiles in diabetic patients with sedentary behavior.ConclusionsThere is sufficient evidence to recognize that walking is a useful therapeutic tool for people with T2DM. This document discusses theoretical and practical issues for improving its use.

Effect of zinc supplement on glycemic control and lipid abnormalities in Type 2 diabetic patients.

To evaluate the effects of zinc on glycemic control and lipid profile in type 2 diabetic patients. Objectives: The zinc deficiency is reported in with diabetes, which increases oxidative stresses leading to complications of diabetes. Previous studies demonstrated that zinc supplementation improved glucose control in patients with diabetes, but limited data is available and single blind trials. Study Design: Randomized Controlled study. Setting: Combined Military Hospital (CMH) Malir Cantt, Karachi. Period: 1st December 2018 to 30th June, 2019. Material &amp; Methods: Patients (n=350) were randomly divided into two groups. The first group (n=175) was supplemented with oral zinc sulfate 30 mg/day and second group (n=175) received placebo for a period of 3 months. Blood samples were taken at baseline and after 3 months to assess fasting blood glucose (FBS), glycosylated hemoglobin (HbA1C %) and serum lipid levels and BMI which were compared by t test for paired samples. Results: The mean age of all subjects was 51.80+10.281 years and male to female ratio was 1.08:1. The mean BMI was 31.74+5.806. There was no statistical difference in age and gender between two groups but more obese patient received placebo. The zinc supplemented group had a significant reduction in FBS (p= 0.032) compared to placebo (p= 0.158). The HbA1C% level reduced significantly in zinc supplemented group (p&lt;0.001).compared to the placebo group (p=0.273). Serum lipid levels reduced significantly in the zinc supplemented group (p&lt;0.001) but no significant changes observed in the placebo group (p=0.395). Conclusions: Zinc supplementation improved glycemic control and decreased levels of serum cholesterol, LDL and triglyceride.

Faith Community Nursing: Using Spiritual Interventions in Diabetes Prevention.

As the incidence of diabetes rises in the United States, education on diabetes prevention and management is paramount. Diabetes programs offered in churches or community settings have reported positive outcomes such as weight loss and improved glucose control. Delphi Survey technique was used to identify spiritual interventions used by faith-based and community-based coaches in leading Diabetes Prevention Program (DPP) courses. Results showed that faith-based coaches reported using prayer, active listening, and emotional support in their DPP course; giving hope, incorporating humor, and using spiritual/sacramental activities were rated as important or very important by most coaches and can be used by faith community nurses in their practice.

The antidiabetic effect and potential mechanisms of natural polysaccharides based on the regulation of gut microbiota

• Polysaccharides reverse gut microbiota dysbiosis and improve SCFAs in diabetes. • Polysaccharides decrease gut permeability and reduce inflammation in diabetes. • Polysaccharides enhance colonic Tregs and prevent autoimmune diabetes. • Polysaccharides improve glucose control via affecting GLP-1 and BAs production. Polysaccharides have been widely shown to suppress hyperglycemia, reverse insulin resistance and prevent diabetes complications. Therefore, polysaccharides intervention is considered as a promising option for management of diabetes. However, the underlying mechanisms responsible for antidiabetic activity of polysaccharides remain unclear. Currently, it has been reported that gut microbiota dysbiosis may impair systemic glucose metabolism and facilitate the appearance of diabetes. Polysaccharides intervention appears to modulate the composition of gut microbiota, which in turn enhances intestinal barrier integrity, maintains gut immune homeostasis, promotes the production of gut hormone and changes bile acids profiles, resulting in the improvement of diabetes. Thus, this review provides an overview of polysaccharides against diabetes based on gut microbiota alteration and wishes to stimulate further works on the relationships among polysaccharides, gut microbiota and diabetes.

Adoption of Hypocaloric High Protein Nutrition Formula Improves Glucose Control in the Surgical ICU

Journal of the American College of Surgeons 231(4):p S304, October 2020. | DOI: 10.1016/j.jamcollsurg.2020.07.625

Effect of nutrition on postprandial glucose control in hospitalized patients with type 2 diabetes receiving fully automated closed-loop insulin therapy.

Fully automated closed-loop insulin delivery may offer a novel way to manage diabetes in hospital. However, postprandial glycaemic control remains challenging. We aimed to assess the effect of nutritional intake on postprandial glucose control in hospitalized patients with type 2 diabetes receiving fully closed-loop insulin therapy. The effects of different meal types and macronutrient composition on sensor glucose time-in-target (TIT, 3.9-10.0 mmol/L) and mean sensor glucose were assessed with hierarchical linear models using a Bayesian estimation approach. TIT was lower and the mean sensor glucose slightly higher, after breakfast compared with lunch and dinner, whereas the insulin dose was higher. Across meals, when carbohydrates were replaced by fat, or to a lesser extent by protein, postprandial glucose control improved. For breakfast, a 3.9% improvement in TIT was observed when 10% of the energy from carbohydrates was replaced by fat. Improvements were slightly lower during lunch and dinner (3.2% and 3.4%) or when carbohydrates were replaced by protein (2.2 and 2.7%, respectively). We suggest that reducing carbohydrate at the expense of fat or protein, could further improve glucose control during fully closed-loop insulin therapy in hospital.

The Diabits App for Smartphone-Assisted Predictive Monitoring of Glycemia in Patients With Diabetes: Retrospective Observational Study.

BackgroundDiabetes mellitus, which causes dysregulation of blood glucose in humans, is a major public health challenge. Patients with diabetes must monitor their glycemic levels to keep them in a healthy range. This task is made easier by using continuous glucose monitoring (CGM) devices and relaying their output to smartphone apps, thus providing users with real-time information on their glycemic fluctuations and possibly predicting future trends.ObjectiveThis study aims to discuss various challenges of predictive monitoring of glycemia and examines the accuracy and blood glucose control effects of Diabits, a smartphone app that helps patients with diabetes monitor and manage their blood glucose levels in real time.MethodsUsing data from CGM devices and user input, Diabits applies machine learning techniques to create personalized patient models and predict blood glucose fluctuations up to 60 min in advance. These predictions give patients an opportunity to take pre-emptive action to maintain their blood glucose values within the reference range. In this retrospective observational cohort study, the predictive accuracy of Diabits and the correlation between daily use of the app and blood glucose control metrics were examined based on real app users’ data. Moreover, the accuracy of predictions on the 2018 Ohio T1DM (type 1 diabetes mellitus) data set was calculated and compared against other published results.ResultsOn the basis of more than 6.8 million data points, 30-min Diabits predictions evaluated using Parkes Error Grid were found to be 86.89% (5,963,930/6,864,130) clinically accurate (zone A) and 99.56% (6,833,625/6,864,130) clinically acceptable (zones A and B), whereas 60-min predictions were 70.56% (4,843,605/6,864,130) clinically accurate and 97.49% (6,692,165/6,864,130) clinically acceptable. By analyzing daily use statistics and CGM data for the 280 most long-standing users of Diabits, it was established that under free-living conditions, many common blood glucose control metrics improved with increased frequency of app use. For instance, the average blood glucose for the days these users did not interact with the app was 154.0 (SD 47.2) mg/dL, with 67.52% of the time spent in the healthy 70 to 180 mg/dL range. For days with 10 or more Diabits sessions, the average blood glucose decreased to 141.6 (SD 42.0) mg/dL (P<.001), whereas the time in euglycemic range increased to 74.28% (P<.001). On the Ohio T1DM data set of 6 patients with type 1 diabetes, 30-min predictions of the base Diabits model had an average root mean square error of 18.68 (SD 2.19) mg/dL, which is an improvement over the published state-of-the-art results for this data set.ConclusionsDiabits accurately predicts future glycemic fluctuations, potentially making it easier for patients with diabetes to maintain their blood glucose in the reference range. Furthermore, an improvement in glucose control was observed on days with more frequent Diabits use.

Hypoxia-inducible factors and diabetes

Hypoxia can be defined as a relative deficiency in the amount of oxygen reaching the tissues. Hypoxia-inducible factors (HIFs) are critical regulators of the mammalian response to hypoxia. In normal circumstances, HIF-1α protein turnover is rapid, and hyperglycemia further destabilizes the protein. In addition to their role in diabetes pathogenesis, HIFs are implicated in development of the microvascular and macrovascular complications of diabetes. Improving glucose control in people with diabetes increases HIF-1α protein and has wide-ranging benefits, some of which are at least partially mediated by HIF-1α. Nevertheless, most strategies to improve diabetes or its complications via regulation of HIF-1α have not currently proven to be clinically useful. The intersection of HIF biology with diabetes is a complex area in which many further questions remain, especially regarding the well-conducted studies clearly describing discrepant effects of different methods of increasing HIF-1α, even within the same tissues. This Review presents a brief overview of HIFs; discusses the range of evidence implicating HIFs in β cell dysfunction, diabetes pathogenesis, and diabetes complications; and examines the differing outcomes of HIF-targeting approaches in these conditions.

TRAIL treatment prevents renal morphological changes and TGF-β-induced mesenchymal transition associated with diabetic nephropathy.

TNF-related apoptosis-inducing ligand (TRAIL) has attracted attention not only as an anti-cancer agent, but also as a potential treatment for diabetes. Animal studies have shown that TRAIL delivery ameliorated glucose control in type 1 and type 2 diabetes. It is currently unknown whether TRAIL positive effects are maintained in more severe forms of type 2 diabetes, and whether they include renoprotection. Our study aimed at evaluating TRAIL effects in a severe form of type 2 diabetes with nephropathy. A total of 20 db/db mice were treated with saline or TRAIL twice per week for 12 weeks. In parallel, renal tubular epithelial cells were cultured with TGF-β1 in the presence and absence of TRAIL, with and without silencing TRAIL-specific receptor (DR5) and leptin receptor. TRAIL did not improve glucose control, but it significantly reduced circulating interleukin (IL)-6 and resistin. In the kidney, TRAIL treatment significantly ameliorated glomerular and tubular morphology with an improvement in kidney function, but no effect on proteinuria. Our in vitro studies on TGF-β1-treated cells, showed that by binding to DR5, TRAIL rescued normal tubular cell morphology, increasing E-cadherin and reducing α-smooth muscle actin (SMA) expression, with no effects on cell viability. Interestingly, both in vivo and in vitro, TRAIL reduced the accumulation of the autophagy substrate p62. Our data confirm TRAIL protective effects against organ damage and shed light on to promising anti-fibrotic actions, which are independent of glucose control. TRAIL anti-fibrotic actions might be due to the rescue of autophagy in diabetes.