Improved Glucose Control Research Articles

Perioperative Identification and Management of Hyperglycemia in Orthopaedic Surgery.

The consequences of undermanaged perioperative hyperglycemia are notable and can have a serious impact on adverse postoperative outcomes, especially surgical site infections and periprosthetic joint infections (PJIs). Preoperative screening of hemoglobin A1c with a goal threshold of <7.45% is ideal. There are a variety of risk factors that contribute to hyperglycemia that should be considered in the perioperative period, including glucocorticoid use, nutritional factors, patient-specific factors, anesthesia, and surgery. There are expected trends in the rise, peak, and fall of postoperative blood glucose levels, and identifying and treating hyperglycemia as swiftly as possible are the fundamental aims of treatment and improved glucose control. Performing frequent postoperative blood glucose monitoring (in the post-anesthesia care unit, on the day of surgery at 1700 and 2100 hours, and in the morning of postoperative day 1) should be considered to allow for the early detection of alterations in glucose metabolism. In addition, instituting a postoperative dietary restriction of carbohydrates should be considered. The use of insulin as a hypoglycemic agent in orthopaedic patients is relatively safe and is an effective means of controlling fluctuating blood glucose levels. Insulin therapy should be administered to treat hyperglycemia at ≥140 mg/dL when fasting and ≥180 mg/dL postprandially. Insulin therapy should be ceased at blood glucose levels of <110 mg/dL; however, monitoring for glycemic dysregulation should be continued. In all cases of complex diabetes, consultation with diabetes specialty services should be considered. The emerging use of technology, including continuous subcutaneous insulin pump therapy and continuous glucose monitoring, is an exciting area of further research and development as such technology can more immediately detect and correct aberrations in blood glucose levels.

Predictors of HbA1c reduction and hypoglycemia in type 2 diabetes mellitus individuals switching from premixed to basal insulin: an exploratory analysis of optimization study

Objective To identify population with type 2 diabetes mellitus (T2DM) who are more likely to benefit from switching to basal insulin (BI) treatment from premixed insulin. Methods This secondary analysis included data from a previously published study (Optimization: NCT00693771) which was a single-arm, multicenter, 16 weeks, phase IV study. The analysis included participants with T2DM inadequately controlled with premixed insulin plus oral hypoglycemic drugs (OADs) who switched to BI plus OADs. Results Among the 297 participants included for analysis, subjects with fasting C-peptide (FCP)>1.2 nmol/L group showed a trend for greater reduction in HbA1c [Least square mean difference (LSMD), −0.59; 95% confidence interval (CI), −0.98 to −0.21; p = 0.003] and FPG (LSMD, −1.36; 95% CI, −2.20 to −0.53; p = 0.002) than those with FCP ≤ 0.4 nmol/L. The baseline insulin glargine 100 U/mL (Gla-100) dose increased significantly in 0.4 to ≤ 1.2 nmol/L group with LS mean difference (SE) of 0.16 (0.01) U/kg/day (p = 0.008) compared to FCP ≤ 0.4 nmol/L group. When combined with Diabetes Treatment Satisfaction Questionnaire (DTSQ) score, participants with a C-peptide level of 0.4 to ≤1.2 nmol/L (OR, 4.05; 95% CI, 1.08 to 15.22; p = 0.039) had significantly higher odds of achieving HbA1c <7%. The number of participants experiencing documented symptomatic hypoglycaemia (≤3.9 mmol/L) was higher in the FCP ≤0.4 nmol/L group compared to those in 0.4 to ≤1.2 nmol/L FCP group at any time of the day (31.6 vs. 17.1%) and during night (00:00 ∼ 05:59) (17.1 vs. 7.5%). Conclusion The findings from this study proposed that FCP is an important biomarker to identify T2DM participants who experience improved glucose control without compromising on hypoglycemia levels during switch from premixed insulin to BI. Participants especially with FCP levels >1.2 nmol/L may respond better in terms of HbA1c reduction without increased hypoglycemia risk compared to those with lower FCP values.

Avocado Consumption for 12 Weeks and Cardiometabolic Risk Factors: A Randomized Controlled Trial in Adults with Overweight or Obesity and Insulin Resistance

BackgroundDiets emphasizing unsaturated fat and high fiber are associated with reducing cardiometabolic risk factors. Avocados are rich in MUFA and PUFA fats and fiber. ObjectivesAssess replacement of carbohydrate energy with avocado energy for 12 wk on glucose homeostasis and cardiometabolic risk factors in self-selecting free-living adults who are overweight or with obesity and have insulin resistance. MethodsIn a single-center, randomized, 2-arm, controlled, 12-wk parallel trial, adults [n = 93; male/female: 39/54; mean ± SD age: 42 ± 12 y; BMI: 32.6 ± 3.9 (in kg/m2); HOMA-IR: 2.7 ± 1.7] were counseled to exchange avocado (AV) or control food (C; low fat, low fiber, energy matched) for carbohydrate food in their usual diet for 12 wk. The primary outcome was the change in Matsuda Insulin Sensitivity Index (MISI) after 12-wk interventions. Secondary outcomes were changes in fasting and post–oral glucose tolerance test glycemic variables, fasting lipids, endothelial activation and inflammation markers. Automated Self-Administered 24-h Dietary Assessment Tool captured weekly dietary intake. Intervention effects were mainly determined by ANCOVA using PC-SAS version 9.4. ResultsDietary total, MUFA, and PUFA fat; fiber; and vegetable intake were higher in the AV group compared with the C group (P < 0.05), and no change in body weight or composition was observed (P > 0.05). Differences between the changes in MISI after AV compared with C were not different (Δ0–12 wk, P = 0.1092). Differences in fasting insulin (Δ0–12 wk, P = 0.0855) and improved glycated hemoglobin (Δ0–12 wk, P = 0.0632) after AV compared with C were suggested. C-reactive protein was significantly lower after AV compared with C at 12 wk (P = 0.0418). Select biomarkers of endothelial activation and lipoproteins by NMR were also influenced by AV compared with C food intake. ConclusionsAvocado intake was associated with a healthier dietary pattern and trends favoring improved glucose control and reduced biomarkers of cardiometabolic risk when replacing avocado energy for carbohydrate energy in free-living adults who are overweight or with obesity and have insulin resistance. This trial was registered at clinicaltrials.gov as NCT 02695433.

GLP-1-mediated delivery of tesaglitazar improves obesity and glucose metabolism in male mice

Dual agonists activating the peroxisome proliferator-activated receptors alpha and gamma (PPARɑ/ɣ) have beneficial effects on glucose and lipid metabolism in patients with type 2 diabetes, but their development was discontinued due to potential adverse effects. Here we report the design and preclinical evaluation of a molecule that covalently links the PPARɑ/ɣ dual-agonist tesaglitazar to a GLP-1 receptor agonist (GLP-1RA) to allow for GLP-1R-dependent cellular delivery of tesaglitazar. GLP-1RA/tesaglitazar does not differ from the pharmacokinetically matched GLP-1RA in GLP-1R signalling, but shows GLP-1R-dependent PPARɣ-retinoic acid receptor heterodimerization and enhanced improvements of body weight, food intake and glucose metabolism relative to the GLP-1RA or tesaglitazar alone in obese male mice. The conjugate fails to affect body weight and glucose metabolism in GLP-1R knockout mice and shows preserved effects in obese mice at subthreshold doses for the GLP-1RA and tesaglitazar. Liquid chromatography–mass spectrometry-based proteomics identified PPAR regulated proteins in the hypothalamus that are acutely upregulated by GLP-1RA/tesaglitazar. Our data show that GLP-1RA/tesaglitazar improves glucose control with superior efficacy to the GLP-1RA or tesaglitazar alone and suggest that this conjugate might hold therapeutic value to acutely treat hyperglycaemia and insulin resistance.

Perioperative Fully Closed-Loop Insulin Delivery in Patients Undergoing Elective Surgery: An Open-Label, Randomized Controlled Trial.

Perioperative management of glucose levels remains challenging. We aimed to assess whether fully closed-loop subcutaneous insulin delivery would improve glycemic control compared with standard insulin therapy in insulin-requiring patients undergoing elective surgery. We performed a single-center, open-label, randomized controlled trial. Patients with diabetes (other than type 1) undergoing elective surgery were recruited from various surgical units and randomly assigned using a minimization schedule (stratified by HbA1c and daily insulin dose) to fully closed-loop insulin delivery with fast-acting insulin aspart (closed-loop group) or standard insulin therapy according to local clinical practice (control group). Study treatment was administered from hospital admission to discharge (for a maximum of 20 days). The primary end point was the proportion of time with sensor glucose in the target range (5.6-10.0 mmol/L). Forty-five patients were enrolled and assigned to the closed-loop (n = 23) or the control (n = 22) group. One patient (closed-loop group) withdrew from the study before surgery and was not analyzed. Participants underwent abdominal (57%), vascular (23%), orthopedic (9%), neuro (9%), or thoracic (2%) surgery. The mean proportion of time that sensor glucose was in the target range was 76.7 ± 10.1% in the closed-loop and 54.7 ± 20.8% in the control group (mean difference 22.0 percentage points [95% CI 11.9; 32.0%]; P < 0.001). No episodes of severe hypoglycemia (<3.0 mmol/L) or hyperglycemia with ketonemia or any study-related adverse events occurred in either group. In the context of mixed elective surgery, the use of fully closed-loop subcutaneous insulin delivery improves glucose control without a higher risk of hypoglycemia.

Association between high levels of physical activity and improved glucose control on active days in youth with type 1 diabetes.

Sixty minutes per day of at least moderate to vigorous physical activity (MVPA) is recommended for children for a variety of physical and psychological reasons. Adherence to these guidelines is confounded by challenges with glucose control during exercise in type 1 diabetes (T1D). This study examined the potential association between physical activity level on active days and glucose control in youth with T1D. Blinded continuous glucose monitors (CGM: Abbott Libre Pro) and physical activity data as measured from a body monitor patch (Metria IH1) were collected for up to 3 weeks in youth aged 9-17 years with T1D. The association between physical activity levels, expressed as mean active metabolic equivalent minutes (MET-minutes) per day, with CGM-based mean glucose, percent time in range (TIR: 70-180 mg/dl), % time above range (TAR) and % time below range (TBR) were assessed using a linear regression model adjusted for age, gender, and baseline HbA1c. Study participants were deemed physically active, as defined by at least 10 min of continuous moderate-to-vigorous activity, on 5.2 ± 1.9 days per week, with a median accumulated physical activity time of 61 [IQR: 37-145] minutes per day. Higher physical activity levels were associated with lower mean glucose levels (r=-0.36; p=0.02) and lower TAR (r=-0.45; p=0.002) on active days. Higher activity levels were also associated with greater TIR (r=0.54; p < 0.001) without being associated with more, or less, TBR. Higher amounts of physical activity are associated with improvements in TIR without significantly increasing TBR. These data suggest that youth ages 9-17 years with T1D can benefit from a high level of physical activity without undue fear of hypoglycemia.

Type 1 Diabetes Hypoglycemia Prediction Algorithms: Systematic Review.

BackgroundDiabetes is a chronic condition that necessitates regular monitoring and self-management of the patient’s blood glucose levels. People with type 1 diabetes (T1D) can live a productive life if they receive proper diabetes care. Nonetheless, a loose glycemic control might increase the risk of developing hypoglycemia. This incident can occur because of a variety of causes, such as taking additional doses of insulin, skipping meals, or overexercising. Mainly, the symptoms of hypoglycemia range from mild dysphoria to more severe conditions, if not detected in a timely manner.ObjectiveIn this review, we aimed to report on innovative detection techniques and tactics for identifying and preventing hypoglycemic episodes, focusing on T1D.MethodsA systematic literature search following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was performed focusing on the PubMed, Google Scholar, IEEE Xplore, and ACM Digital Library to find articles on technologies related to hypoglycemia detection in patients with T1D.ResultsThe presented approaches have been used or devised to enhance blood glucose monitoring and boost its efficacy in forecasting future glucose levels, which could aid the prediction of future episodes of hypoglycemia. We detected 19 predictive models for hypoglycemia, specifically on T1D, using a wide range of algorithmic methodologies, spanning from statistics (1.9/19, 10%) to machine learning (9.88/19, 52%) and deep learning (7.22/19, 38%). The algorithms used most were the Kalman filtering and classification models (support vector machine, k-nearest neighbors, and random forests). The performance of the predictive models was found to be satisfactory overall, reaching accuracies between 70% and 99%, which proves that such technologies are capable of facilitating the prediction of T1D hypoglycemia.ConclusionsIt is evident that continuous glucose monitoring can improve glucose control in diabetes; however, predictive models for hypo- and hyperglycemia using only mainstream noninvasive sensors such as wristbands and smartwatches are foreseen to be the next step for mobile health in T1D. Prospective studies are required to demonstrate the value of such models in real-life mobile health interventions.

A multi-centered trial investigating gestational treatment with ursodeoxycholic acid compared to metformin to reduce effects of diabetes mellitus (GUARD): a randomized controlled trial protocol

BackgroundEach year in the UK, approximately 35,000 women develop gestational diabetes mellitus (GDM). The condition increases the risk of obstetric and neonatal complications for mother and child, including preeclampsia, preterm birth, and large for gestational age babies. Biochemical consequences include maternal hyperglycemia, neonatal hypoglycemia, and dyslipidemia. Metformin is the most commonly used firstline pharmacological treatment. However, there are concerns about its widespread use during pregnancy, due to its limited efficacy and potential safety concerns. Therefore, there is a need for additional therapies that improve both maternal–fetal glucose and lipid metabolism.Ursodeoxycholic acid (UDCA) is not currently used for treatment for GDM. However, it can improve glucose control in type 2 diabetes, and it improves fetal lipid profiles in gestational cholestasis. Consequentially, it is hypothesized that treatment with UDCA for women with GDM may improve both maternal metabolism and neonatal outcomes. The primary outcome of this trial is to assess the efficacy of UDCA compared with metformin to improve glucose levels in women with GDM.MethodsThe trial is a two-armed, open-label, multi-center, randomized controlled trial. Women are eligible if they have been diagnosed with GDM by an oral glucose tolerance test between 24 + 0 and 30 + 6 weeks’ gestation, and if they require pharmacological intervention. In total, 158 pregnant women will be recruited across seven NHS Trusts in England and Wales. Women who consent will be recruited and randomized to either metformin or UDCA, which will be taken daily until the birth of their baby. Maternal and neonatal blood samples will be taken to evaluate the impact of the treatments on maternal glucose control, and maternal and neonatal lipid metabolism. Maternal and fetal outcomes will be evaluated, and acceptability of UDCA compared with metformin will be assessed.DiscussionThis trial has the potential to identify a potential new treatment for women with GDM. If successful, a future large multi-center trial will be designed to investigate where decisions can be personalized to identify which women will respond more effectively to UDCA than alternatives to improve maternal and baby outcomes.Trial registrationClinicalTrials.gov NCT04407650.

Telehealth for the Management of Diabetes in Pregnancy.

Purpose of ReviewTelehealth initiatives are becoming ubiquitous in clinical practice and can be a useful tool in the management of diabetes in pregnancy. The purpose of this review is to summarize new techniques in telemedicine delivery and offer details on how to leverage telehealth in delivering care to pregnant women with diabetes.Recent FindingsUsing mobile phone technology to collect glucose values in women with gestational diabetes has been found to be beneficial by increasing the amount of glucose data available for interpretation. Remote patient monitoring in non-pregnant people with type 2 diabetes has shown a modest improvement in glucose control. In pregnant women with diabetes, the use of remote patient monitoring does not appear to improve outcomes but can decrease in-office visits and lower healthcare costs. However, telehealth may not be the only solution to helping patients with diabetes in pregnancy who have difficulty engaging in their care.SummaryTelehealth affords improvements in convenience, efficiency, and frequency of communication with healthcare professionals, and the amount of data available to patients and providers alike, yielding the potential for better outcomes when telehealth modalities are adopted.

Improved Aerobic Capacity and Adipokine Profile Together with Weight Loss Improve Glycemic Control without Changes in Skeletal Muscle GLUT-4 Gene Expression in Middle-Aged Subjects with Impaired Glucose Tolerance.

(1) Objective: The aim of this study was to clarify the role of adipokines in the regulation of glucose metabolism in middle-aged obese subjects with impaired glucose tolerance in response to a long-term exercise and dietary intervention. (2) Methods: Skeletal muscle, plasma and serum samples were examined in 22 subjects from an exercise–diet intervention study aiming to prevent type 2 diabetes. The subjects were further divided into two subgroups (non-responders n = 9 and responders n = 13) based on their achievement in losing at least 3 kg. (3) Results: The two-year exercise–diet intervention reduced leptin levels and increased adiponectin levels in responders; the changes in leptin levels were significantly associated with changes in their weights (r = 0.662, p < 0.01). In responders, insulin sensitivity (Bennett and McAuley index) increased and was associated with changes in maximal oxygen uptake (VO2peak) (r = 0.831, p < 0.010 and r = 0.890, p < 0.01). In addition, the VO2peak and oxidative capacity of skeletal muscle improved in responders, but not in non-responders. However, there were no changes between the two groups in expressions of the glucose transporter protein-4 (GLUT-4) gene or of AMP-activated protein kinase (AMPK)-α1 or AMPK-α2 proteins. (4) Conclusions: The exercise–diet intervention decreased serum leptin and increased serum adiponectin concentrations, improved glucose control without affecting GLUT-4 gene expression in the skeletal muscle in responders.

Addressing healthcare disparities and managed care considerations with continuous glucose monitoring.

About 37 million people in the United States have diabetes. Diabetes-related complications are costly and associated with substantial morbidity. By improving glucose control, continuous glucose monitoring (CGM) can reduce costs due to diabetes-related hospitalizations, hypoglycemia, and diabetic ketoacidosis. However, people of color and low socioeconomic status, populations with disproportionately high prevalence of diabetes, face significant inequity in accessing CGM technology. Potential reasons for CGM inequity include implicit bias and differences in coverage between commercial and government insurance. Recent changes to Medicare CGM eligibility criteria have eliminated blood glucose monitoring requirements. However, cost and CGM coverage requirements remain as barriers to the recommended use of this technology as defined in current clinical practice guidelines. Coverage expansion from durable medical equipment to the pharmacy benefit may improve access. Other strategies to optimize CGM utility overall include integrating CGM data directly into electronic health records for population health management and diabetes control performance measures based on CGM data in value-based contracts (VBCs). VBCs may encourage real-world data generation which in turn may bolster stakeholder support for the equitable use and coverage of CGM in diabetes management.

Accessibility and Openness to Diabetes Management Support With Mobile Phones: Survey Study of People With Type 1 Diabetes Using Advanced Diabetes Technologies.

BackgroundLittle is known about the feasibility of mobile health (mHealth) support among people with type 1 diabetes (T1D) using advanced diabetes technologies including continuous glucose monitoring (CGM) systems and hybrid closed-loop insulin pumps (HCLs).ObjectiveThis study aims to evaluate patient access and openness to receiving mHealth diabetes support in people with T1D using CGM systems or HCLs.MethodsWe conducted a cross-sectional survey among patients with T1D using CGM systems or HCLs managed in an academic medical center. Participants reported information regarding their mobile device use; cellular call, SMS text message, or internet connectivity; and openness to various channels of mHealth communication (smartphone apps, SMS text messages, and interactive voice response [IVR] calls). Participants’ demographic characteristics and CGM data were collected from medical records. The analyses focused on differences in openness to mHealth and mHealth communication channels across groups defined by demographic variables and measures of glycemic control.ResultsAmong all participants (N=310; female: n=198, 63.9%; mean age 45, SD 16 years), 98.1% (n=304) reported active cellphone use and 80% (n=248) were receptive to receiving mHealth support to improve glucose control. Among participants receptive to mHealth support, 98% (243/248) were willing to share CGM glucose data for mHealth diabetes self-care assistance. Most (176/248, 71%) were open to receiving messages via apps, 56% (139/248) were open to SMS text messages, and 12.1% (30/248) were open to IVR calls. Older participants were more likely to prefer SMS text messages (P=.009) and IVR calls (P=.03) than younger participants.ConclusionsMost people with T1D who use advanced diabetes technologies have access to cell phones and are receptive to receiving mHealth support to improve diabetes control.

FGF21 contributes to metabolic improvements elicited by combination therapy with exenatide and pioglitazone in patients with type 2 diabetes.

Fibroblast growth factor 21 (FGF21) is increased acutely by carbohydrate ingestion and is elevated in patients with type 2 diabetes (T2D). However, the physiological significance of increased FGF21 in humans remains largely unknown. We examined whether FGF21 contributed to the metabolic improvements observed following treatment of patients with T2D with either triple (metformin/pioglitazone/exenatide) or conventional (metformin/insulin/glipizide) therapy for 3 yr. Forty-six patients with T2D were randomized to receive either triple or conventional therapy to maintain HbA1c < 6.5%. A 2-h 75-g oral glucose tolerance test (OGTT) was performed at baseline and following 3 years of treatment to assess glucose tolerance, insulin sensitivity, and β-cell function. Plasma total and bioactive FGF21 levels were quantitated before and during the OGTT at both visits. Patients in both treatment arms experienced significant improvements in glucose control, but insulin sensitivity and β-cell function were markedly increased after triple therapy. At baseline, FGF21 levels were regulated acutely during the OGTT in both groups. After treatment, fasting total and bioactive FGF21 levels were significantly reduced in patients receiving triple therapy, but there was a relative increase in the proportion of bioactive FGF21 compared with that observed in conventionally treated subjects. Relative to baseline studies, triple therapy treatment also significantly modified FGF21 levels in response to a glucose load. These changes in circulating FGF21 were correlated with markers of improved glucose control and insulin sensitivity. Alterations in the plasma FGF21 profile may contribute to the beneficial metabolic effects of pioglitazone and exenatide in human patients with T2D.NEW & NOTEWORTHY In patients with T2D treated with a combination of metformin/pioglitazone/exenatide (triple therapy), we observed reduced total and bioactive plasma FGF21 levels and a relative increase in the proportion of circulating bioactive FGF21 compared with that in patients treated with metformin and sequential addition of glipizide and basal insulin glargine (conventional therapy). These data suggest that FGF21 may contribute, at least in part, to the glycemic benefits observed following combination therapy in patients with T2D.

Glycaemic Control Achieves Sustained Increases of Circulating Endothelial Progenitor Cells in Patients Hospitalized for Decompensated Diabetes: An Observational Study.

Background and AimDiabetes reduces the levels of circulating endothelial progenitor cells (EPCs), which contribute to vascular homeostasis. In turn, low EPCs levels predict progression of chronic complications. Several studies have shown that hyperglycaemia exerts detrimental effects on EPCs. Improvement in glucose control with glucose-lowering medications is associated with an increase of EPCs, but only after a long time of good glycaemic control. In the present study, we examined the effect of a rapid glycaemic amelioration on EPC levels in subjects hospitalized for decompensated diabetes.MethodsWe used flow cytometry to quantify EPCs (CD34+/CD133+KDR+) in patients hospitalized for/with decompensated diabetes at admission, at discharge, and 2 months after the discharge. During hospitalization, all patients received intensive insulin therapy.ResultsThirty-nine patients with type 1 or type 2 diabetes were enrolled. Average (± SEM) fasting glucose decreased from 409.2 ± 25.9 mg/dl at admission to 190.4 ± 12.0 mg/dl at discharge and to 169.0 ± 10.3 at 2 months (both p < 0.001). EPCs (per million blood cells) significantly increased from hospital admission (13.1 ± 1.4) to discharge (16.4 ± 1.1; p = 0.022) and remained stable after 2 months (15.5 ± 1.7; p = 0.023 versus baseline). EPCs increased significantly more in participants with newly-diagnosed diabetes than in those with pre-existing diabetes. The increase in EPCs was significant in type 1 but not in type 2 diabetes and in those without chronic complications.ConclusionIn individuals hospitalized for decompensated diabetes, insulin therapy rapidly increases EPC levels for up to 2 months. EPC defect, reflecting impaired vascular repair capacity, may be reversible in the early diabetes stages.

140-LB: Management of Inpatient Hyperglycemia Guided by Continuous Glucose Monitoring (CGM) in Insulin-Treated Patients with Diabetes—A Randomized Clinical Trial

Inpatient use of CGM results in higher detection of hypoglycemic and hyperglycemic events compared to point of care testing (POC) but its efficacy and safety in adjusting insulin therapy has not been evaluated. This randomized controlled trial included 181 general medicine and surgery patients with type 1 (n= 18) and type 2 (n= 155) diabetes treated with a basal bolus insulin regimen. All patients underwent POC testing AC &amp; HS. Patients in the POC group wore a blinded Dexcom G6 CGM with insulin dose adjusted based on POC results; while in the CGM group, insulin adjustment was based on daily Dexcom G6 CGM profile review. Hypoglycemia alarms were set at 80 mg/dl in the CGM group. Primary endpoints were differences in time in range (70-180 mg/dl) and hypoglycemia (&amp;lt;70 mg/dl and &amp;lt;54 mg/dl) . Results: There were no differences on admission clinical characteristics, HbA1c or diabetes type between POC and CGM groups. There were no differences in mean daily glucose (186.8±39 mg/dl vs. 183.2±40 mg/dl, p=0.36) , total daily insulin dose (36.1±28 U/day vs. 40.7±29 U/day, p=0.33) , % patients with CGM values &amp;lt;70 mg/dl (39% vs. 36%, p=0.68) or &amp;lt;54mg/dl (24% vs. 14%, p=0.12) between the two groups. Among patients with ≥ 1 hypoglycemic event, compared to POC, CGM use resulted in significant reduction in hypoglycemia recurrence with an incidence-ratio for glucose &amp;lt;70mg/dl (0.53, 95% CI:0.31-0.92) and incidence-ratio for glucose &amp;lt;54mg/dl (0.37 (95% CI:0.17-0.83) . The percent time &amp;lt;70 mg/dl among those with hypoglycemia was smaller in the CGM (1.9±3.3% vs. 5.5±8.5, p=0.024) compared to the POC group, with group difference in hypoglycemia confirmed by zero-inflated Beta Regression analysis (p&amp;lt;0.001) . Conclusion: Our results indicates that the inpatient use of Dexcom G6 CGM is safe and effective in guiding insulin adjustment resulting in similar improvement in glucose control and in significant reduction of recurrent hypoglycemic events compared to POC testing. Disclosure I. Spanakis: Other Relationship; Dexcom, Inc. L. G. Singh: None. C. Gothong: None. I. Marcano: None. S. Lizama: None. K. M. Munir: None. C. Chesney: None. R. D. Maguire: None. W. H. Scott: None. L. Peng: None. G. E. Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk. M. A. Urrutia: None. M. F. Scioscia: None. R. J. Galindo: Advisory Panel; Sanofi, WW International, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk. P. Vellanki: n/a. A. L. Migdal: None. G. Davis: Consultant; Medscape, Research Support; Insulet Corporation. T. Idrees: None. F. J. Pasquel: Consultant; AI Health LLC, Boehringer Ingelheim International GmbH, Dexcom, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Merck &amp; Co., Inc.

410-P: Preoperative Diabetes Optimization and Clinical Outcomes

A diabetes optimization pathway for elective surgical patients with uncontrolled diabetes (A1c&amp;gt; 8%) has been in place at our institution for the last 5 years. Although we reported on improvement in glucose control before surgery in patients undergoing the intervention, impact on longer-term clinical outcomes was not known. We extracted EPIC medical record data for adult surgical patients in the diabetes optimization program between January 2016 and October 2021 (n=85) . The control group had uncontrolled diabetes and underwent surgery but had no intervention (n=1,111) . Logistic regression, GLM and Cox proportional hazard models were used to investigate relationship with 30 day complications, glucose at surgery, and overall mortality. Table 1 shows bivariate comparisons for the study cohort. The rates of perioperative complications were numerically lower in the intervention group, however, were not statistically significant. Unadjusted regression analyses found significantly lower glucose at surgery (β =-14.19, 95% CI=-27.94,-0.43) , and significantly lower hazard ratio for overall mortality (HR=0.34, 95% CI=0.13,0.93) for the intervention. After adjusting for demographics, clinical risk, and comorbidities, only glucose at surgery maintained significance (β =-16.89, 95% CI=-30.83,-2.95) . Prospective studies or a larger sample may be needed to confirm findings. Disclosure C.E.Mendez: Advisory Panel; Monarch Medical Technologies . R.J.Walker: None. E.Garacci: None. K.Pfeifer: None.

722-P: Tirzepatide Improves Multiple Aspects of Beta-Cell Function

We investigated the effect of tirzepatide (TZP) 15 mg (novel GIP-GLP-1 dual receptor agonist) , placebo and semaglutide 1 mg (SEMA) on beta-cell function using euglycaemic and hyperglycemic glucose clamps (EGC, HGC) and Mixed Meal Tolerance Tests (MMTT) in a 28-week double-blind randomized controlled trial of people with type 2 diabetes. During EGC and HGC, TZP improved insulin sensitivity (M-value) , first and second phase insulin secretion (ISR) and beta-cell glucose sensitivity (ratio of ISR and glucose increments) more than SEMA and placebo (Table; EASD symposium 2021) . During MMTT, both fasting and AUC glucose were reduced more with TZP than with SEMA or placebo, while incremental glucose AUC was reduced with TZP and SEMA vs. placebo similarly. Despite similarly reduced incremental glucose AUC, insulin AUC and incremental insulin AUC were reduced by TZP but not by SEMA. Model-derived beta-cell glucose sensitivity was increased with TZP and SEMA from baseline similarly. In contrast, ISR at 7.2 mmol/L glucose increased more with TZP than with placebo and SEMA (Table) . The glucose-lowering effect of TZP is mediated through improvements in multiple aspects of beta-cell function, including beta-cell glucose sensitivity and ISR, and in insulin sensitivity, resulting in pronounced lowering of fasting and postprandial glucose. These effects help explain the superior improvement in glucose control seen with TZP vs. comparators in clinical trials. Disclosure A. Mari: Consultant; Lilly. Research Support; Lilly. J. Li: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. S. Urva: Employee; Eli Lilly and Company. T. Heise: Advisory Panel; Novo Nordisk A/S. Research Support; ADOCIA, AstraZeneca, Biocon, Boehringer Ingelheim International GmbH, Crinetics Pharmaceuticals, Inc., Eli Lilly and Company, Gan &amp; Lee Pharmaceuticals, Genova, Nestlé, Neuraly Inc., Novo Nordisk A/S, Sanofi, Zealand Pharma A/S. Speaker's Bureau; Eli Lilly and Company, Gan &amp; Lee Pharmaceuticals, Novo Nordisk A/S. J. De Vries: Advisory Panel; ADOCIA, Novo Nordisk A/S, Zealand Pharma A/S. Speaker's Bureau; Novo Nordisk A/S. E.J. Pratt: Employee; Eli Lilly and Company. R.J. Heine: Employee; Eli Lilly and Company. M.K. Thomas: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. Z. Milicevic: Employee; Eli Lilly and Company. K.J. Mather: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company

668-P: Increased Step Count but No Improvements in Glucose Control: Using CGM as Visualization Tool in Adults with T2D

Background: Physical inactivity is common in people with T2D and behavior modification can be difficult due to lack of timely and knowledgeable feedback. Real-time CGM (rtCGM) visualization of impact of efforts on glucose can highlight opportunities for medication and behavior modification to clinicians and individuals. Methods: Glucose and step data in an observational study were collected with Dexcom G6 rtCGMs and activity trackers for 12 weeks in US adults with T2D. Participants did not receive education beyond standard of care. Paired T-tests were used to evaluate changes in step count, % time in range, peak glucose, and hyper- and hypoglycemic events between first and last weeks. Results are presented for the full T2D population (n=183) and a subgroup who increased average daily step count by ≥ 1000 steps (n=63) . Results: Morning steps significantly increased across all participants and steps in all meal-related time periods significantly increased for subgroup (Table 1) . There was not a sustained, significant glucose impact. Conclusion: Adding steps alone, supported by rtCGM, did not result in improvements in glucose. Such visualization provides information for individuals and clinicians to understand opportunities for therapy optimization, including activity and medication regimen. This is promising preliminary data and further research with prescribed intervention is required. Disclosure M.A.Crawford: Employee; Dexcom, Inc. D.R.Cherñavvsky: Employee; Dexcom, Inc. K.Barnard: Advisory Panel; Roche Diabetes Care, Sanofi, Research Support; Dexcom, Inc., Novo Nordisk. X.Wang: None. P.Genge: Employee; Dexcom, Inc. K.Greenawald: None. M.Tressler: Employee; Dexcom, Inc.

Whole Body Production of Butyrate, but Not of Acetate or Propionate, Is Reduced in Adults With Prediabetes

ObjectivesAccording to the CDC, 38% of the adult US population have prediabetes. Previous studies reported a reduced abundance of butyrate producing bacteria in the colon of participants with prediabetes, potentially contributing to the progression to Type 2 Diabetes. We now studied whether the whole body production of short-chain fatty acids (SCFA: acetate, propionate, butyrate) are altered in middle aged/older adults with prediabetes. MethodsWe measured SCFA kinetics in 12 prediabetic (fasting glucose: 5.7–6.5 mM) and 25 healthy (fasting glucose < 5.7 mM) subjects, 40 years or older. In the fasted state, a pulse containing acetate[13C2], propionate[1-13C] and butyrate[1-13C] was administered intravenously while blood was sampled 4 times over a 30 min period. We measured tracer enrichments in plasma by GC-MS, whole body SCFA production from the area under the curve (AUC) and statistics by ANCOVA corrected for age, sex, and lean body mass as covariates with significance set at P< 0.05 and results expressed as means [95% CI]. ResultsThe prediabetic subjects had a lower butyrate WBP (362 [270, 454] vs. 534 [403, 665] μmol/h, P = 0.021) while acetate WBP (18996 [15270, 23631] vs. 17431 [13478, 22544] μmol/h, P = 0.6049) and propionate WBP (1250 [1041, 1459] vs. 1322 [1053, 1590] μmol/h, P = 0.6624) were comparable. Plasma SCFA concentrations did not differ between the groups (all P >0.05). ConclusionsThe reduced whole body production of butyrate observed in the prediabetic middle aged/older adults is probably related to the altered colonic bacterial composition. More research is required whether specific nutritional modulation of the colonic bacterial composition (e.g. fiber supplementation) is able to restore the butyrate WBP and can improve glucose control in adults with prediabetes. Funding SourcesNone

1005-P: A Multimodel Model Predictive Controller Can Improve Glucose Control in Children with Type 1 Diabetes (T1D)

Background: Many youth with type 1 diabetes do not achieve glycemic targets motivating the development of new therapeutic options for this population. We tested an automated insulin delivery system (AID) that uses a multi-model model predictive controller in children with T1D. Methods: We conducted a 40-hour free-living clinical trial to assess our automated insulin delivery algorithm in children aged 7-13 years old with T1D (mean age 10.5±2.0 years, HbA1c 7.9±0.7%, duration of T1D 5.2±2.8 years) . Participants underwent a 7-day run-in period on sensor-augmented pump therapy followed by two 40-hour intervention periods composed of four hours of open-loop and 36 hours of AID use. Controller settings were identical in both intervention periods. Mean time-in-ranges were compared by paired T-test. Results: Time in target (3.9-10mmol/L) and time in hyperglycemia (&amp;gt;10mmol/L) improved during intervention periods vs. run-in (52.2% vs. 65.6%; p&amp;lt;0.and 45.1% vs. 30.8%; p=0.respectively) while time in hypoglycemia (&amp;lt;3.9mmol/L) during intervention periods was unchanged from the run-in (1.8 vs. 2.0%, p=0.96) . Conclusion: Early results suggest our advanced model predictive controller improves glucose control in a 7-13-year-old population with T1D. Larger and longer trials are warranted. Disclosure E.Palisaitis: Other Relationship; Eli Lilly and Company. R.Jones: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. M.Katz: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. H.Wolpert: Employee; Lilly Diabetes. A.El fathi: Other Relationship; Eli Lilly and Company. A.Haidar: Consultant; Eli Lilly and Company, Research Support; ADOCIA, Dexcom, Inc., Eli Lilly and Company, Tandem Diabetes Care, Inc. J.E.Von oettingen: None. L.Legault: Advisory Panel; Abbott Diabetes, Insulet Corporation, Novo Nordisk A/S, Other Relationship; Eli Lilly and Company, Research Support; AstraZeneca, Merck &amp; Co., Inc. Funding Eli Lilly