Improved Blood Glucose Control Research Articles

Systemic administration of miR-451 improves autophagy response in an accelerated mouse model of diabetic kidney disease

Diabetic kidney disease (DKD) is a common and severe microvascular complication of both type 1 and type 2 diabetes mellitus. It is the most common cause of end stage renal disease in the United States. Autophagy is a highly conserved pathway that recycles damaged organelles and macromolecules to maintain intracellular homeostasis. There is mounting evidence highlighting the role of autophagy in diabetic kidney disease. MicroRNAs (miRNA) affect the transcription of several genes involved in the development and progression of DKD, regulating key pathways and processes, including fibrotic signaling and autophagy. Thus, the dysregulation of miRs exacerbates kidney injury in the diabetic setting. Previous work from our group suggests that chronic systemic inhibition of miR-451 exacerbates fibrosis in the kidney of an obese insulin resistant mouse model (tallyHo/Jng), indicating a potential renoprotective role for miR-451 in the diabetic kidney. However, few studies have investigated this protective role of miR-451 in the diabetic kidney. This study aimed to understand the renoprotective effects of miR-451 in an accelerated mouse model of DKD. BTBR ob/ob mice rapidly develop morphological renal lesions characteristic of both early and advanced human DKD, with proteinuria typically beginning at 4-weeks of age. 12-week old male black and tan, brachyuric (BTBR) ob/ob mice and BTBR wild-type mice were treated with commercially available miR-451 mimics (2mg/kg/bw; n=3/treatment group; treatment groups: WT, BTBR ob/ob, WT+miR-451, and BTBR ob/ob+miR-451) 1X per week for 3-consective weeks. Spot urine was collected weekly until the end of study. Random blood glucose was measured by tail prick weekly. Mice were humanely euthanized, and kidneys and blood harvested at the end of the treatment period. Western blotting of whole kidney homogenate was performed following a standard protocol. Data was analyzed using students t-test or ANOVA, where appropriate, p<0.05 considered significant. Albumin: creatinine ratio was four times higher (p=0.01) in BTBR ob/ob mice beginning at 5 weeks. Treatment with miR-451 mimics had no significant effect on body weight in either group. Blood glucose was significantly higher in miR-451 treated and untreated BTBR ob/ob mice at 12-weeks (425± 33.1 mg/dL; p=0.04) and 13-weeks (383± 25.3 mg/dL; p=0.007). However, blood glucose decreased significantly from week 13 (554.7± 10.8 mg/dL) to week 14(289± 13.3 mg/dL; p=0.0002) in BTBR ob/ob miR-451 treated mice. Western blot analysis of MiR-451 mimic treated BTBR ob/ob and WT mice whole kidney homogenate revealed a 91% (p=0.02) and 95% (p=0.01) reduction, respectively, in YWHAZ (a predicted miR-451 target). Conversely, western blot analysis of autophagy related proteins revealed a 68% (p=0.01) increase in ATG101 and a 44% increase in Beclin-1 in miR-451 mimic treated BTBR ob/ob mice. Collectively, the findings of this study suggest that miR-451 may offer protection in the diabetic kidney via autophagic signaling and improved blood glucose control. GHUCCTS KL2 Scholar Program (Award Number: KL2TR001432) The Charles and Mary Latham Fund Howard University Department of Medicine Start-Up Funds; Howard University Bridge Fund and Pilot Study Awards. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Delayed prandial insulin boluses are an important determinant of blood glucose control and relate to fear of hypoglycemia in people with type 1 diabetes on advanced technologies

AimsAutomated insulin delivery systems improve blood glucose control in patients with type 1 diabetes (T1D). However, optimizing their performance requires patient's proper compliance to meal insulin bolus administration. We explored real-life prevalence of delayed prandial boluses (DBs) in adults with T1D on advanced technologies, and their association with glycemic control and fear of hypoglycemia (FH). MethodsIn the last two-week web-based reports of 152 adults with T1D on Hybrid Closed Loop Systems (HCLS) or Sensor Augmented Pump (SAP), DBs were identified when a steep increase in blood glucose occurred at CGM before the prandial bolus, and CGM metrics were evaluated. All participants completed an online questionnaire on FH. ResultsMean DBs over two weeks were 10.2 ± 4.7 (M ± SD, range 1–23) and more frequent in women than men (11.0 ± 4.6 vs. 9.4 ± 4.7, p = 0.036). Participants with more DBs (>12) showed significantly lower Time-In-Range (62.4 ± 13.8 vs. 76.6 ± 9.0 %) than those with less DBs (<7.7), along with higher Time-Above-Range, GMI, and Coefficient-of-Variation (ANOVA, p < 0.001 for all). Participants with higher FH score showed more DBs (11.6 ± 5.0) than those in lower tertiles (9.57 ± 4.59 and 9.47 ± 4.45, ANOVA p = 0.045). ConclusionsIn patients on advanced technologies, delayed boluses are extremely common, and associate with significantly worse glycemic control. Utmost attention is needed to bolus timing, mainly tackling fear of hypoglycemia.

Safety and Efficacy of GLP-1 Receptor Agonists in Type 2 Diabetes Mellitus with Advanced and End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

Background and Objectives: Limited evidence exists regarding the safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) patients with advanced chronic kidney disease (CKD) or end-stage kidney disease (ESKD). Thus, we conducted a systematic review and meta-analysis to assess the safety and efficacy of GLP-1RAs in T2DM patients with advanced CKD and ESKD. Materials and Methods: We performed a systematic literature search in MEDLINE, EMBASE, and Cochrane database until 25 October 2023. Included were clinical trials and cohort studies reporting outcomes of GLP-1RAs in adult patients with T2DM and advanced CKD. Outcome measures encompassed mortality, cardiovascular parameters, blood glucose, and weight. Safety was assessed for adverse events. The differences in effects were expressed as odds ratios with 95% confidence intervals (CIs) for dichotomous outcomes and the weighted mean difference or standardized mean difference (SMD) with 95% confidence intervals for continuous outcomes. The Risk of Bias In Non-randomized Studies-of Interventions (ROBIN-I) tool was used in cohort and non-randomized controlled studies, and the Cochrane Risk of Bias (RoB 2) tool was used in randomized controlled trials (RCTs). The review protocol was registered in the International Prospective Register of Systematic Reviews (CRD 42023398452) and received no external funding. Results: Eight studies (five trials and three cohort studies) consisting of 27,639 patients were included in this meta-analysis. No difference was observed in one-year mortality. However, GLP-1RAs significantly reduced cardiothoracic ratio (SMD of -1.2%; 95% CI -2.0, -0.4) and pro-BNP (SMD -335.9 pmol/L; 95% CI -438.9, -232.8). There was no significant decrease in systolic blood pressure. Moreover, GLP-1RAs significantly reduced mean blood glucose (SMD -1.1 mg/dL; 95% CI -1.8, -0.3) and increased weight loss (SMD -2.2 kg; 95% CI -2.9, -1.5). In terms of safety, GLP-1RAs were associated with a 3.8- and 35.7-time higher risk of nausea and vomiting, respectively, but were not significantly associated with a higher risk of hypoglycemia. Conclusions: Despite the limited number of studies in each analysis, our study provides evidence supporting the safety and efficacy of GLP-1RAs among T2DM patients with advanced CKD and ESKD. While gastrointestinal side effects may occur, GLP-1RAs demonstrate significant improvements in blood glucose control, weight reduction, and potential benefit in cardiovascular outcomes.

Factors associated with Adherence to Insulin Self-Administration among Children and Adolescents with Type 1 DM in Iraq

Abstract Adolescents and children with type 1 diabetes have been reported to have challenges regarding adherence to treatment regimens compared with other age groups with diabetes. The study aimed to determine the level of commitment and investigate the effects of different factors on insulin adherence in type 1 diabetes patients in Iraq. This cross-sectional study included face-to-face interview questionnaires with caregivers of children and adolescents. Interviews were conducted in the Specialized Center of Endocrinology and Diabetes in Nasiriyah City, Iraq, from October 4, 2022, to March 30, 2023. The adherence questionnaire consisted of two sections; each consisted of five questions, including insulin and blood glucose recommendations. Blood samples were obtained from the patient to determine fasting blood glucose (FBG) and glycated hemoglobin (HBA1c)—results: 180 patients (86 males and 94 females) with type 1 DM. The mean age, weight, and disease duration were 10.75 (4.36) years, 36.30 (16.41) kg, and 6.24 (3.70) years, respectively. They had uncontrolled blood glucose (208.42 95.0 mg/dl) and HBA1c (9.90 2.85%). The patients (52.2%) were girls with primary school qualifications (43.3%). Most of the caregivers (parents and guardians) were either illiterate (30.6%) or had completed primary school (33.9%). In addition, the patient's families (43.9%) had low income (0.5 million ID cards). Therefore, most patients (60%) did not visit a doctor regularly or check their blood glucose. Adherence in the studied population could be higher. Focusing on raising their patients' awareness is pivotal to enhancing their medication adherence to reduce their short- and long-term diabetic complications, improve blood glucose control, and improve clinical outcomes. Keywords: Diabetes, Adherence, Insulin self-medication, Iraqi patients.

Effectiveness of management protocol for insulin balls in diabetics: a scoping review.

In order to achieve good glycemic control, the prevention and management of insulin balls is important for diabetic patients during insulin therapy. However, insulin balls still occur within the clinical setting. This review evaluated the effectiveness of programs designed to manage insulin balls. A scoping review was conducted based on the Japanese and English literature available from a systematic literature search conducted from January 1964 to March 2022. Three databases were searched: PubMed, CINAHL, and Ichushi-Web. A total of 33 articles met the inclusion criteria, which consisted of 3 for prevention management of insulin balls and 30 for management after the occurrence of insulin balls. Findings for prevention management suggested that the insulin injection technique education (avoidance of repeated injections to the same site) and providing knowledge (about insulin balls) prevented the appearance of insulin balls. As for post-occurrence management, insulin injection technique education (avoidance of injections to the insulin ball, avoidance of repeated injections to the same site, and switching the injection site) improved blood glucose control. Hypoglycemia was observed in all studies that included an assessment of hypoglycemia. None of the studies evaluated long-term effects of either preventive or post-occurrence management. Providing insulin injection technique education is an effective management protocol for insulin balls. Moreover, education about hypoglycemia is important for patients with insulin balls. Further studies to investigate the long-term effects in the management of insulin balls are needed.

Effectiveness of a Digital Health Application for the Treatment of Diabetes Type II-A Pilot Study.

(1) Background: This study aimed at providing preliminary evidence for mebix, an app-based treatment program for patients with diabetes mellitus type II. The main target was to show a positive healthcare impact as defined by improved blood glucose control, i.e., reduced HbA1c values. (2) Methods: For this, a 3-month, prospective, open-label trial with an intraindividual control group was conducted. Participants received the mebix intervention for 3 months. HbA1c values were observed every 3 months: retrospectively, at baseline, and 3 months after the start of using the app. Additionally, weight and patients' reported outcomes (well-being, diabetes-related distress, and self-management) were assessed. Data generated within the app were summarized and analyzed (steps, physical activity, fulfilled tasks, and food logs). (3) Results: After the usage of mebix for 3 months, participants significantly reduced their HbA1c levels (-1.0 ± 0.8%). Moreover, improvements in weight, well-being, and self-management as well as a reduction in diabetes-related distress were observed. App-generated data mainly supported the other main finding, that higher baseline HbA1c values lead to higher reductions. Overall, the study provided preliminary evidence that mebix can help patients improve metabolic and psychological health outcomes.

Novel α-Glucosidase Inhibitory Peptides Identified In Silico from Dry-Cured Pork Loins with Probiotics through Peptidomic and Molecular Docking Analysis.

Diabetes mellitus is a serious metabolic disorder characterized by abnormal blood glucose levels in the body. The development of therapeutic strategies for restoring and maintaining blood glucose homeostasis is still in progress. Synthetic alpha-amylase and alpha-glucosidase inhibitors can improve blood glucose control in diabetic patients by effectively reducing the risk of postprandial hyperglycemia. Peptides of natural origin are promising compounds that can serve as alpha-glucosidase inhibitors in the treatment of type 2 diabetes. Potential alpha-glucosidase-inhibiting peptides obtained from aqueous and saline extracts from dry-cured pork loins inoculated with probiotic LAB were evaluated using in vitro and in silico methods. To identify the peptide sequences, liquid chromatography-mass spectrometry was used. For this purpose, in silico calculation methods were used, and the occurrence of bioactive fragments in the protein followed the ADMET approach. The most promising sequences were molecularly docked to test their interaction with the human alpha-glycosidase molecule (PDB ID: 5NN8). The docking studies proved that oligopeptides VATPPPPPPPK, DIPPPPM, TPPPPPPG, and TPPPPPPPK obtained by hydrolysis of proteins from ripening dry-cured pork loins showed the potential to bind to the human alpha-glucosidase molecule and may act effectively as a potential antidiabetic agent.

Use of a Smartphone-Based Medication Adherence Platform to Improve Outcomes in Uncontrolled Type 2 Diabetes Among Veterans: Prospective Case-Crossover Study.

Medication nonadherence is a problem that impacts both the patient and the health system. The objective of this study was to evaluate the impact of a novel smartphone app with patient-response-directed clinical intervention on medication adherence and blood glucose control in noninsulin-dependent patients with type 2 diabetes mellitus (T2DM). We enrolled 50 participants with T2DM not on insulin with smartphones from a rural health care center in Northern Nevada for participation in this case-crossover study. Participants underwent a standard of care arm and an intervention arm. Each study arm was 3 months long, for a total of 6 months of follow-up. Participants had a hemoglobin A1c (HbA1c) lab draw at enrollment, 3 months, and 6 months. Participants had monthly "medication adherence scores" (MAS) and "Self-Efficacy for Appropriate Medication Use Scale" (SEAMS) questionnaires completed at baseline and monthly for the duration of the study. Our primary outcomes of interest were the changes in HbA1c between study arms. Secondary outcomes included the evaluation of the difference in the proportion of participants achieving a clinically meaningful reduction in HbA1c and the difference in the number of participants requiring diabetes therapy escalation between study arms. Exploratory outcomes included the analysis of the variation in medication possession ratio (MPR), MAS, and SEAMS during each study arm. A total of 30 participants completed both study arms and were included in the analysis. Dropouts were higher in participants enrolled in the standard of care arm first (9/25, 36% vs 4/25, 16%). Participants had a median HbA1c of 9.1%, had been living with T2DM for 6 years, had a median age of 66 years, and had a median of 8.5 medications. HbA1c reduction was 0.69% in the intervention arm versus 0.35% in the standard of care arm (P=.30). A total of 70% (21/30) of participants achieved a clinically meaningful reduction in HbA1c of 0.5% in the app intervention arm versus 40% (12/30) in the standard of care arm (odds ratio 2.29, 95% CI 0.94-5.6; P=.09). Participants had higher odds of a therapy escalation while in the standard of care arm (18/30, 60% vs 5/30, 16.7%, odds ratio 4.3, 95% CI 1.2-15.2; P=.02). The median MPR prior to enrollment was 109%, 112% during the study's intervention arm, and 102% during the standard of care arm. The median real-time MAS was 93.2%. The change in MAS (1 vs -0.1; P=.02) and SEAMS (1.9 vs -0.2; P<.001) from baseline to month 3 was higher in the intervention arm compared to standard of care. A novel smartphone app with patient-response-directed provider intervention holds promise in the ability to improve blood glucose control in complex non-insulin-dependent T2DM and is worthy of additional study.

Exercise therapy for diabetes mellitus

Background: Exercise lowers blood glucose levels, improves insulin sensitivity, and helps prevent complications; therefore, it is highly effective for prevention and treatment of diabetes mellitus. However, many patients with diabetes do not meet the recommendations for the amount of exercise. In this study, we focus on the latest recommendations and discuss exercise therapies that are helpful for patients with diabetes.Current Concepts: Many studies have shown that exercise helps to improve blood glucose control, physical strength, and cardiorespiratory capacity in patients with type 1 or 2 diabetes. Patients with diabetes are advised to perform both aerobic and resistance exercises. Aerobic exercise is suitable for most patients and can rapidly lower blood glucose levels. Resistance exercise improves muscle strength and endurance and is useful for long-term stabilization of blood glucose levels. Combined aerobic and resistance exercise improves insulin resistance and additionally controls blood glucose levels. Patients with diabetes are recommended moderate intensity exercise for at least 150 min/week, at least thrice a week, without interruption in exercise for &gt;2 consecutive days.Discussion and Conclusion: Exercise is an essential recommended lifestyle intervention for patients with diabetes, and regular exercise is important. Furthermore, patients with diabetes should avoid low-energy activities and minimize sitting time.

Soluble Dietary Fibers as Antihyperlipidemic Agents: A Comprehensive Review to Maximize Their Health Benefits.

The number of hypercholesterolemic people is increasing rapidly worldwide, with elevated lipid profiles representing a major risk factor of coronary heart diseases. Dietary intervention was shown to improve the lipid profile, thus enhancing the quality of life. Dietary fiber is a nondigestible form of carbohydrates, due to the lack of the digestive enzyme in humans required to digest fiber, and is classified according to its water solubility properties as either soluble (SDF) or insoluble dietary fiber (IDF). Consumption of SDF is associated with several health benefits such as reduced lipid levels, lower blood pressure, improved blood glucose control, improved immune function, and reduced inflammation. SDF has been shown to lower blood cholesterol by several action mechanisms including directly due to the gelling, mucilaginous, and viscous fiber nature, and indirectly due to its fermented products and modulation of the gut microbiome. This review aims to provide a holistic overview on how SDF impacts the lipid profile. We start by providing an overview of the chemical structure of the major SDFs including mucilage, gums (gum arabic and guar gum), pectin, and inulin.

Pharmacokinetic and pharmacodynamic interaction of DWP16001, a sodium-glucose cotransporter-2 inhibitor, with phentermine in healthy subjects

ABSTRACT Background DWP16001, a sodium-glucose cotransporter-2 inhibitor, has shown promise for improving blood glucose control and facilitating weight loss. Co-administration with phentermine could enhance these effects. So, we aimed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) interactions of DWP16001 and phentermine. Methods We conducted a randomized, open-label, 3-treatment, 6-sequence, 3-period crossover study involving 24 healthy adults. Participants received either DWP16001 (2 mg), phentermine (37.5 mg), or a combination of both once daily for 7 days. Blood samples, urine samples, and body weights were collected to evaluate the PK and PD. Results The PK of the combination was found to be similar to that of the monotherapy. The geometric mean ratio (GMR) of Cmax,ss, and AUCtau,ss were 0.98 and 1.00, respectively, for DWP16001, and 1.01 and 0.94, respectively, for phentermine. Co-administration did not significantly affect the 24-hour urinary glucose excretion compared to DWP16001 monotherapy, and the GMR was 0.90. Participants tended to experience greater weight loss in the combination therapy group, and all demonstrated good tolerance. Conclusions Our findings indicate that there were no significant interactions during co-administration. These results suggest that the combination of DWP16001 and phentermine may be safe and effective for the treatment of obesity and diabetes. Clinical trial registration NCT05321732

1826-PUB: Efficacy of Digital Diabetes Care Program in India—Retrospective Analysis

Background: Lack of knowledge in self-management and limited access to specialized healthcare services leads to uncontrolled diabetes. Continuous digital care delivered through a mobile healthcare app aid in metabolic control. Aims: To analyze the efficacy of BeatO’s digital diabetes care management program among people with diabetes Methods: A retrospective analysis of 721 participants enrolled in BeatO’s mobile app-based diabetes care program for 3 months, the period of enrollment was between 28th February to 31st August 2022. Participants received remote access to health professionals for diabetes education, nutritional guidance and doctor consultation through the BeatO app. Throughout the care program, they were connected with a dedicated health coach. The medication prescribed by the doctor was delivered to the participant’s home. Regular blood glucose monitoring was done using BeatO’s smartphone-connected glucometer that works in accordance with the BeatO app. The parameters like FBG, PPBG, HbA1c, lipid profile and weight was recorded at baseline and after 3 months. Results: Of the 721 participants, 96.5 % had Type 2 diabetes. The mean age of the participants was 47.5 years, and the majority (80.8%) were males. T2DM was present in 696, T1DM (11), LADA (9), Prediabetes (3) and GDM (2). Out of these, 704 participants completed the program. A significant improvement in blood glucose control was observed, as reflected by a mean decrease in FBG by 38 mg/dL (p &amp;lt;0.0001), PPBG by 37 mg/dL (p &amp;lt;0.0001) and HbA1c reduced by 2.16% (p &amp;lt; 0.0001) at the end of 3 months. There was a significant weight loss of about 1.8 kg (p = 0.01) and a reduction in total cholesterol by 15 mg/dl through this remote personalized care. Conclusions: BeatO's digital diabetes care management program among people with diabetes showed good efficacy in terms of glycemic control and weight loss. Hence, the implementation of digital technology in diabetes care can help in increasing access and awareness of diabetes care and achieving glycemic targets. Disclosure N.Agrawal: Advisory Panel; Biocon, Eris Lifesciences Ltd., Lupin Pharmaceuticals, Inc., Sanofi, USV Private Limited, Other Relationship; BeatO, Health Arx Technologies Pvt LTD. A.Panjabi: Advisory Panel; Torrent Pharmaceuticals Ltd, USV Private Limited, Consultant; BeatO, Health Arx Technologies. P.K.Dixit: Advisory Panel; USV Private Limited, Intas Pharmaceuticals Ltd., Consultant; Beato, Health Arx Technologies. B.D: Consultant; BEAT-O, HEALTH ARX TECHNOLOGIES.

1346-P: Investigation of Changes in Urinary Titin N-terminal Fragment during Hospitalization for Glycemic Control

Background: Urinary titin N-terminal fragment concentration (urinary titin) has been reported to be negatively correlated with muscle mass, grip strength, and knee joint extension strength, and is considered a biomarker that reflects sarcopenia, muscle damage, and the catabolic state of muscle. Sarcopenia and skeletal muscle dysfunction occur in the person with diabetes, but it is unclear how urinary titin changes with improved blood glucose control. Methods: One hundred and five Japanese patients with diabetes (85 type 2 and 20 type 1) who were hospitalized for glycemic control for approximately 2 weeks were included. Patients who were hospitalized with acute complications of diabetes or who had infections were excluded. Urinary titin was measured in all patients at admission and discharge, and skeletal muscle mass index (SMI) was measured in 49 patients. Results: Patients were 55 males and 50 females. Median age was 62.0 years, BMI was 25.5, and HbA1c was 9.2%. There was no correlation between urinary titin at admission and age, BMI, SMI, and HbA1c, but it tended to be higher in men (p=0.08). Urinary titin was 2.31±5.40 nmol/gCr at admission and 1.30±1.48 nmol/gCr at discharge, showing a significant decrease (p=0.049). Body weight loss of -1.8% was observed during hospitalization, and SMI decreased by -1.4% from admission. There was no correlation between changes in urinary titin during hospitalization and age, BMI, HbA1c, and changes in body weight and SMI during hospitalization. Conclusion: Urinary titin significantly decreased in patients with diabetes who were hospitalized for glycemic control for approximately 2 weeks, and no correlation was observed with changes in SMI. The short-term changes in urinary titin suggested that skeletal muscle dysfunction was improved by improvement of blood glucose control. However, in this study, the quality of skeletal muscle such as muscle strength could not be evaluated, and additional examination is necessary. Disclosure S.Yoshida: None.

Trends &amp; Technology

Trends & Technology| June 2023 Trends & Technology ASA Monitor June 2023, Vol. 87, 16–17. https://doi.org/10.1097/01.ASM.0000938808.42211.e6 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Search Site Citation Trends & Technology. ASA Monitor 2023; 87:16–17 doi: https://doi.org/10.1097/01.ASM.0000938808.42211.e6 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll PublicationsASA Monitor Search Advanced Search Topics: trend In the NIH-funded Pediatric Artificial Pancreas (PEDAP) Trial, artificial pancreas technology improved blood glucose control in young children between ages 2 and 5 with type 1 diabetes. The study was a 13-week randomized, controlled trial that enrolled 102 participants between ages 2 and 5 at three pediatric diabetes centers across the U.S. The participants were randomly assigned to either the artificial pancreas group or the standard care comparison group. The artificial pancreas, also known as closed-loop control, is a diabetes management system that tracks blood glucose levels using a continuous glucose monitor (CGM) and automatically delivers the insulin when needed using an insulin pump. The system replaces reliance on testing by fingerstick or CGM with delivery of insulin by multiple daily injections or a pump controlled by the patient or caregiver. Participants in the artificial pancreas group spent 12% more time within their target blood glucose range compared to the... You do not currently have access to this content.

Abstract #1406118: Improving Inpatient Diabetes Management in a Community Hospital: A Resident-Run Quality Improvement Initiative

Diabetes mellitus is one of the most encountered co-morbidities in outpatient and inpatient settings. Treatment varies from oral hypoglycemic agents (OHAs) to injectable agents to insulin based on average glucose levels. Guidelines recommend discontinuation of OHAs during inpatient hospitalization and using long and short-acting insulin as treatment, to avoid unpredictable glucose levels. In our community hospital, it was noted that if home OHAs are discontinued on admission, physicians tend to use only the insulin sliding scale (ISS) or short-acting pre-prandial and bedtime insulin as treatment. Recent studies have shown that stand-alone ISS is inferior to a basal/bolus insulin regimen in achieving adequate blood glucose control in hospitalized patients. Our aim is to improve blood glucose control in our community hospital by implementing an insulin policy as a standard treatment for diabetes management. We used the Institute Healthcare Improvement (IHI) model to guide our quality improvement (QI) project. Root cause analysis through a fishbone revealed contributing factors. A multidisciplinary team, which included IT, pharmacy, and resident physicians, was created to implement the proposed solutions. Several PDSA cycles were used to test changes. Despite guidelines to assist in the management of inpatient diabetes, our hospital lacked a standard approach. PDSA 1 involved education about guidelines, discontinuation of OHAs, and utilizing insulin for management. Post-implementation, >50% of physicians still ordered OHAs. PDSA 2 cycle, a pharmacy checkpoint was placed to discontinue OHAs, and physicians were prompted to use insulin. This led to the elimination of OHAs and the initiation of insulin. However, stand-alone ISS was being used, causing hyperglycemia. PDSA 3 re-education was provided. Policy changes were implemented to incorporate a basal insulin regimen along with ISS for inpatient management. We proposed 10 units of long-acting insulin plus ISS. The new policy was implemented with the aid of the pharmacy. A review of post-intervention data from 250 patients through a 6-month period showed that OHAs were continued in only 1.2% of the patients. Stand-alone ISS therapy was started in 24% of the patients, whereas 62% of patients received a combination of basal insulin along ISS. We noted hypoglycemic events (glucose <60 mg/dl) in 7.6% of the patients, and hyperglycemia (glucose >160 mg/dl) in 60% of the patients. Limiting the use of OHAs in the hospital resulted in fewer hypoglycemic episodes. Prior to our QI, we noted an inconsistent approach to diabetes management leading to hypo and severe hyperglycemic events. As a part of this QI initiative, a new hospital-wide policy, which included basal and short-acting insulin, was incorporated with the help of a multidisciplinary team. We noticed that incorporating a standardized approach led to an improved trend in glucose control and fewer complications secondary to severe hyperglycemia or hypoglycemia.

The Effect of Exercise on Quality of Life in Type 2 Diabetes: A Systematic Review and Meta-analysis.

Exercise is a proven therapy for managing cardiometabolic risk factors in type 2 diabetes (T2D). However, its effects on patient-reported outcome measures such as quality of life (QoL) in people with T2D remain unclear. Consequently, the primary aim of this study was to determine the effect of regular exercise on QoL in adults with T2D. A secondary aim was to determine the effect of different exercise modalities on QoL. The third aim was to determine whether improvements in QoL were associated with improvements in gly'cated hemoglobin (A1C). Relevant databases were searched to May 2022. Eligible studies included randomized trials involving ≥2 wk of aerobic and/or resistance exercise and assessed QoL using a purpose-specific tool. Mean differences and 95% confidence intervals (CI) were calculated as standardized mean difference (SMD) or weighted mean difference. A regression analysis was undertaken to examine the interaction between change in QoL with change in A1C. Of the 12,642 studies retrieved, 29 were included involving 2354 participants. Exercise improved QoL when compared with control (SMD, 0.384; 95% CI, 0.257 to 0.512; P < 0.001). Aerobic exercise, alone (SMD, 0.475; 95% CI, 0.295 to 0.655; P < 0.001) or in combination with resistance training (SMD, 0.363; 95% CI, 0.179 to 0.548; P < 0.001) improved QoL, whereas resistance training alone did not. Physical components of health-related QoL (HRQoL) improved with all exercise modalities, but mental components of HRQoL remained unchanged. Exercise improved A1C (mean difference, -0.509%; 95% CI, -0.806% to -0.212%; P = 0.001), and this change was associated with improvements in HRQoL ( β = -0.305, SE = 0.140, Z = -2.18, P = 0.030). These results provide robust evidence that regular aerobic exercise alone or in combination with resistance training is effective for improving QoL in adults with T2D. Such improvements seem to be mediated by improvements in physical components of HRQoL and are associated with improved blood glucose control. Further studies should be undertaken to determine the relative importance of exercise duration, intensity, and frequency on patient-reported outcomes such as QoL.

IoMT-Enabled Real-Time Blood Glucose Prediction With Deep Learning and Edge Computing

Blood glucose (BG) prediction is essential to the success of glycemic control in type 1 diabetes (T1D) management. Empowered by the recent development of the Internet of Medical Things (IoMT), continuous glucose monitoring (CGM) and deep learning technologies have been demonstrated to achieve the state of the art in BG prediction. However, it is challenging to implement such algorithms in actual clinical settings to provide persistent decision support due to the high demand for computational resources, while smartphone-based implementations are limited by short battery life and require users to carry the device. In this work, we propose a new deep learning model using an attention-based evidential recurrent neural network and design an IoMT-enabled wearable device to implement the embedded model, which comprises a low-cost and low-power system on a chip to perform Bluetooth connectivity and edge computing for real-time BG prediction and predictive hypoglycemia detection. In addition, we developed a smartphone app to visualize BG trajectories and predictions, and desktop and cloud platforms to backup data and fine-tune models. The embedded model was evaluated on three clinical data sets including 47 T1D subjects. The proposed model achieved superior performance of root mean square error (RMSE), mean absolute error, and glucose-specific RMSE, and obtained the best accuracy for hypoglycemia detection when compared with a group of machine learning baseline methods. Moreover, we performed hardware-in-the-loop in silico trials with ten virtual T1D adults to test the whole IoMT system with predictive low-glucose management, which significantly reduced hypoglycemia and improved BG control.

Incorporating Sparse and Quantized Carbohydrates Suggestions in Model Predictive Control for Artificial Pancreas in Type 1 Diabetes

People with type 1 diabetes (T1D) face the challenge of administering exogenous insulin to maintain blood glucose (BG) levels in a safe physiological range, so as to avoid (possibly severe) complications. By automatizing insulin infusion, the artificial pancreas (AP) assists patients in this challenge. While insulin can decrease BG, having another input inducing glucose increase could further improve BG control. Here, we develop a model predictive control (MPC) algorithm that, in addition to insulin infusion, also provides suggestions of carbohydrates (CHOs) as a second, glucose-increasing, control input. Since CHO consumption has to be manually actuated, great care is paid in limiting the extra burden that may be caused to patients. By resorting to a mixed logical-dynamical MPC formulation, CHO intake is designed to be sparse in time and quantized. The algorithm is validated on the UVa/Padua T1D simulator, a well-established large-scale model of T1D metabolism, accepted by Food and Drug Administration (FDA). Compared with an insulin-only MPC, the new algorithm ensures increased time spent in the safe physiological range in 75% of patients. The improvement is limited for those already well controlled by the state-of-art strategy but relevant for the others: the 25th percentile of this metric is increased from 74.75% to 79.06% in the population. This is achieved while simultaneously decreasing time spent in hypoglycemia (from 0.5% to 0.12% in median) and with limited manual interventions (2.86 per day in median).

Early Experience With an Endocrinology Preoperative Fast-Track Program for Optimizing Spine Surgery Candidates With Poorly Controlled Diabetes Mellitus.

Previous studies demonstrated an increase in adverse outcomes for patients undergoing elective surgeries with poorly controlled diabetes mellitus. At a large, tertiary-care spine center with a notable population of patients with poorly controlled diabetes, an Endocrinology Fast-Track (EFT) program was developed to improve patient optimization before elective spine surgery. The purpose of this study was to report our early experience. Seventy-five patients who were scheduled for elective spine surgery were noted to have Hgb A1c > 7 on preoperative evaluation. Thirty-two patients accepted referral to the EFT program and 43 declined (non-EFT). Mean preoperative Hgb A1c was similar between groups (EFT: 8.79 versus non-EFT: 9.26, P = 0.221). The Fast-Track program included counseling, education, and medical management. Patients in the two groups were similar in number of females (EFT: 17 versus non-EFT: 17, P = 0.348), age (EFT: 57.7 versus non-EFT: 60.6, P = 0.280), and body mass index (EFT: 34.6 versus non-EFT: 33.0, P = 0.341). A smaller number of smokers were there in the EFT group (1) compared with the non-EFT group (15, P = 0.003). The proportion of patients on insulin (EFT: 19 versus non-EFT: 23, P = 0.814) and oral hypoglycemics (EFT: 29 versus non-EFT: 39, P = 0.983) was similar between the two groups. Surgical clearance for patients with a documented preoperative Hgb A1c of < 7 or equivalent fructosamine level was significantly better in the Fast-Track group compared with the non-Fast-Track group (91% versus 42%, P = 0.000). Although most patients who declined the Fast-Track program did not obtain clearance for surgery, mean Hgb A1c was improved at the latest follow-up in both groups for those who obtained surgical clearance (7.10 versus 6.78, P = 0.470). A novel EFT program was successful in obtaining acceptable blood glucose control in patients recommended for spine surgery who had poorly controlled diabetes mellitus on preoperative evaluation. The improved blood glucose control was maintained at the latest follow-up.

Liver-Secreted Hexosaminidase A Regulates Insulin-Like Growth Factor Signaling and Glucose Transport in Skeletal Muscle.

Nonalcoholic fatty liver disease (NAFLD) and impaired glycemic control are closely linked; however, the pathophysiological mechanisms underpinning this bidirectional relationship remain unresolved. The high secretory capacity of the liver and impairments in protein secretion in NAFLD suggest that endocrine changes in the liver are likely to contribute to glycemic defects. We identify hexosaminidase A (HEXA) as an NAFLD-induced hepatokine in both mice and humans. HEXA regulates sphingolipid metabolism, converting GM2 to GM3 gangliosides-sphingolipids that are primarily localized to cell-surface lipid rafts. Using recombinant murine HEXA protein, an enzymatically inactive HEXA(R178H) mutant, or adeno-associated virus vectors to induce hepatocyte-specific overexpression of HEXA, we show that HEXA improves blood glucose control by increasing skeletal muscle glucose uptake in mouse models of insulin resistance and type 2 diabetes, with these effects being dependent on HEXA's enzymatic action. Mechanistically, HEXA remodels muscle lipid raft ganglioside composition, thereby increasing IGF-1 signaling and GLUT4 localization to the cell surface. Disrupting lipid rafts reverses these HEXA-mediated effects. In this study, we identify a pathway for intertissue communication between liver and skeletal muscle in the regulation of systemic glycemic control.