Mean Amplitude Of Glycemic Excursions Research Articles

12596 Characterizing Glycemic Variability In Novel Subphenotypes Of Individuals At Elevated Risk For Type 2 Diabetes Using Continuous Glucose Monitoring

Abstract Disclosure: A.J. Kretowski: None. P. Konopka: None. A. Janucik: None. A. Citko: None. A. Paszko: None. M. Klak: None. A. Golonko: None. A. Szklaruk: None. L. Szczerbinski: None. Background: The heterogeneity among individuals at elevated risk for Type 2 Diabetes (T2D) recently has led to the identification of six subphenotypes, each with distinct risks for developing T2D, its complications, and mortality. Our study leveraged Continuous Glucose Monitoring (CGM) to offer a detailed characterization of these subphenotypes, aiming to uncover differences in glycemic variability and control. Methods: CGM data from 616 individuals without diabetes, from the Polish Registry of Diabetes (PolReD) study, classified into six clusters, were analyzed. The PolReD used Freestyle Libre 2 (Abbott) as the CGM device. CGM-derived measures of glucose control and glucose variability were calculated using the iglu R package. We utilized Analysis of Variance (ANOVA) and Analysis of Covariance (ANCOVA), adjusting for age and sex, to identify significant differences in CGM parameters across the clusters. Results: Our analysis identified significant differences in several CGM-derived parameters among the clusters, notably in the Glycemic Risk Assessment Diabetes Equation (GRADE), Standard Deviation of weekly glucose values (SDw), Mean Amplitude of Glycemic Excursions (MAGE), Maximum glucose value, Glucose range, and Mean Absolute Glucose (MAG). Clusters 3 and 5, characterized by beta-cell dysfunction and high insulin resistance respectively, and associated with the highest risk of T2D, exhibited the greatest glucose variability, with elevated risk for glycemic excursions. In contrast, Cluster 4, indicative of a metabolically healthy obesity profile with a low risk of T2D, demonstrated the most stable glycemic control and the lowest variability among the clusters. Conclusions: This study shows that subtypes of patients at elevated risk for T2D exhibit distinct patterns in CGM-derived parameters, indicating variations in glucose control and stability that extend beyond traditional fasting and post-challenge glucose assessments. Notably, we found that subtypes facing the highest T2D risk display increased glycemic variability, despite their differing underlying mechanisms of dysglycemia. These findings highlight the utility of CGM as a tool for identifying individuals at an increased risk of T2D, reducing the need for extensive phenotyping typically required for cluster assignment. Presentation: 6/1/2024

Perioperative Glycemic Variability Influences Infection Rates Differently Following Revision Hip and Knee Arthroplasty

IntroductionRecent investigations have determined that abnormal postoperative glycemia following primary total joint arthroplasty is associated with adverse events. Our study aimed to determine if hyperglycemia and glycemic variability following aseptic revision total joint arthroplasty (rTJA) were associated with periprosthetic joint infection (PJI) within two years postoperatively. MethodsA retrospective review was performed of 2,208 patients within a single institution undergoing aseptic rTJA from 2012 to 2019. Postoperative glucose values were recorded. Glycemic variability was measured via three parameters: coefficient of variation (%CV), mean amplitude of glycemic excursions (MAGE), and J-index. Logistic regression analyses were performed to examine associations with PJI at 90-day, 1-, and 2-year follow-up. ResultsIn revision hips, all glycemic measures were not associated with PJI at any timepoint in logistic regression analyses, except for MAGE, which predicted PJI at one year (P = 0.045); body mass index (BMI) was the only factor associated with PJI at all timepoints in all models. In revision knees, all glycemic measures were not associated with PJI at any timepoint in logistic regression analyses; however, PJI rates differed between diabetics and non-diabetics at all time-points (P < 0.05). ConclusionsOur findings illustrate that decreasing preoperative BMI and postoperative glycemic variability may be critical in reducing PJI rates in revision hips. Furthermore, patients who have diabetes should be counseled that they remain at higher risk of PJI regardless of perioperative glucose control after revision knee surgery.

Efficacy and safety of henagliflozin combined with continuous subcutaneous insulin infusion in the treatment of Chinese inpatients with type 2 diabetes mellitus based on a continuous glucose monitoring system: protocol of a multicentre, open-label, inpatient, randomised, controlled trial

IntroductionThe role of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in diabetes treatment is expanding; however, few studies have investigated the efficacy and safety of combining SGLT2is with insulin pump therapy. Notably,...

Association Between Glycemic Variability and Persistent Acute Kidney Injury After Noncardiac Major Surgery: A Multicenter Retrospective Cohort Study.

While the relationship between glycemic variability (GV) and acute kidney injury (AKI) has been a subject of interest, the specific association of GV with persistent AKI beyond 48 hours postoperative after noncardiac surgery is not well-established. This retrospective cohort study aimed to describe the patterns of different GV metrics in the immediate 48 hours after noncardiac surgery, evaluate the association between GV indices and persistent AKI within the 7-day postoperative window, and compare the risk identification capabilities of various GV for persistent AKI. A total of 10,937 patients who underwent major noncardiac surgery across 3 medical centers in eastern China between January 2015 and September 2023 were enrolled. GV was characterized using the coefficient of variations (CV), mean amplitude of glycemic excursions (MAGE), and the blood glucose risk index (BGRI). Multivariable logistic regression was used to examine the relationship between GV and AKI. Optimal cutoff values for GV metrics were calculated through the risk identification models, and an independent cohort from the INformative Surgical Patient dataset for Innovative Research Environment (INSPIRE) database with 7714 eligible cases served to externally validate the risk identification capability. Overall, 274 (2.5%) of the 10,937 patients undergoing major noncardiac surgery met the criteria of persistent AKI. Higher GV was associated with an increased risk of persistent AKI (CV: odds ratio [OR] = 1.26, 95% confidence interval [CI], 1.08-1.46; MAGE: OR = 1.31, 95% CI, 1.15-1.49; BGRI: OR = 1.18, 95% CI, 1.08-1.29). Compared to models that did not consider glycemic factors, MAGE and BGRI independently contributed to predicting persistent AKI (MAGE: areas under the curve [AUC] = 0.768, P = .011; BGRI: AUC = 0.764, P = .014), with cutoff points of 3.78 for MAGE, and 3.02 for BGRI. The classification of both the internal and external validation cohorts using cutoffs demonstrated good performance, achieving the best AUC values of 0.768 for MAGE in the internal cohort and 0.777 for MAGE in the external cohort. GV measured within 48 hours postoperative period is an independent risk factor for persistent AKI in patients undergoing noncardiac surgery. Specific cutoff points can be used to stratify at-risk patients. These findings indicate that stabilizing GV may potentially mitigate adverse kidney outcomes after noncardiac surgery, highlighting the importance of glycemic control in the perioperative period.

Investigation of Glucose Metabolism by Continuous Glucose Monitoring and Validation of Dipeptidyl Peptidase 4 Inhibitor Use in Patients with Myotonic Dystrophy Type 1.

Objectives: We characterized blood glucose fluctuations in patients with myotonic dystrophy type 1 (DM1). After confirming the incretin secretion capacity of patients with DM1, we intended to clarify whether dipeptidyl peptidase 4 (DPP-4) inhibitor administration was appropriate in cases of DM1 with diabetes mellitus. Methods: A 48 h continuous glucose monitoring (CGM) was performed in 29 Japanese patients with DM1. An oral glucose tolerance test (OGTT) was performed in patients with DM1 and five disease controls, and levels of blood glucose, insulin, and incretin (glucagon-like peptide-1 and gastric inhibitory polypeptide) were measured. DPP-4 inhibitors were administered to patients with diabetes mellitus complicated by DM1, and the CGM results were compared. Results: The CGM showed distinct patterns of blood glucose variability among patients classified by an OGTT pattern with significant differences in glucose parameters such as time above 140 mg/dL and mean amplitude of glycemic excursions between the groups. High sensor glucose values were observed in a certain number of patients who were classified as having normal or impaired glucose tolerance by the OGTT. The CGM confirmed the presence of low glucose levels in several patients. Incretin secretion, the target of DPP-4 inhibitors, was preserved in patients with DM1. DPP-4 inhibitor treatment resulted in lower glucose levels and improved insulin secretion in some patients. Conclusions: This is the first CGM study for DM1 patients. The CGM identified potential early abnormalities in glucose metabolism in DM1. In the future, it will be crucial to explore effective methods for harnessing CGM and assessing it quantitatively in DM1.

Therapeutic effects of high monounsaturated fatty acid and low carbohydrate formula on blood glucose levels and diarrhea in critically ill neurological patients

To investigate the effects of using a high monounsaturated fatty acid (MUFA) and low carbohydrate formula on blood glucose levels and diarrhea treatment effects in critically ill neurological patients. A self-controlled before-and-after study design was employed, with 13 patients admitted to the neurology intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from November to December 2023, who were treated with a high MUFA and low carbohydrate formula [Glucerna enteral nutrition (EN) preparation]. Changes in blood glucose parameters within 7 days before and after the use of Glucerna EN preparation were analyzed, including standard deviation (SD) of blood glucose, mean blood glucose (MG), median blood glucose, mean amplitude of glycemic excursions (MAGE), largest amplitude of glycemic excursions (LAGE), coefficient of variation (CV) of blood glucose, the incidence of hyperglycemia (> 7.8 mmol/L) and severe hyperglycemia (> 13.9 mmol/L), and daily insulin dose. Changes in total protein (TP), albumin (ALB), hemoglobin (Hb), C-reactive protein (CRP), and white blood cell count (WBC) were observed before and after intervention. Improvement in diarrhea symptoms, Hart diarrhea score, Bristol Stool classification score, and incontinence dermatitis classification were also analyzed before and after the use of Glucerna EN preparation. A total of 13 critically ill neurological patients were enrolled, among whom 9 patients had a history of hyperglycemia and 8 patients had diarrhea symptoms. After intervention with Glucerna, the patients' SD of blood glucose, MG, median blood glucose, MAGE, LAGE, CV of blood glucose, incidence of hyperglycemia, incidence of severe hyperglycemia, and daily insulin dose were all lower than those before the intervention [SD of blood glucose (mmol/L): 1.83±1.11 vs. 2.10±1.13, MG (mmol/L): 8.87±2.03 vs. 9.75±1.37, median blood glucose (mmol/L): 9.12±1.67 vs. 10.17±0.48, MAGE (mmol/L): 0.66±0.31 vs. 0.78±0.32, LAGE (mmol/L): 4.95±3.64 vs. 5.58±3.10, CV of blood glucose: 16.00% (11.00%, 28.50%) vs. 18.00% (12.50%, 27.50%), hyperglycemia incidence: 47.31% vs. 74.66%, severe hyperglycemia incidence: 6.08% vs. 6.71%, daily insulin dose (U): 5.25 (0.00, 32.59) vs. 20.76 (0.00, 66.88)], with a significant decrease in daily insulin dose after the intervention (P < 0.05); TP, ALB, Hb, CRP and WBC showed no significant changes before and after the intervention with Glucerna EN preparation. The improvement time of diarrhea symptoms after intervention was (3.50±1.41) days, and the Hart diarrhea score on the seventh day after intervention (4.88±3.48 vs. 10.00±3.38) and the Bristol Stool classification score on the third and seventh days after intervention (5.87±0.35, 5.50±0.53 vs. 6.50±0.53) were significantly lower than before the intervention (all P < 0.05). Before the intervention with Glucerna EN preparation, the classification of incontinence dermatitis was mainly classified as Grade 2 severity (71.43%); after the intervention, it significantly improved by the seventh day, with Grade 1 being the main classification (57.14%). The high MUFA and low carbohydrate formula has a positive effect on blood glucose control and diarrhea treatment in critically ill neurological patients.

Initiation of Insulin Degludec in Chinese Hospitalized Patients with Type 2 Diabetes - A Single Center's Experience.

The long-acting insulin analogue insulin degludec (IDeg) is increasingly recommended for type two diabetes (T2DM), yet clinical experience in China remains limited. This retrospective study aimed to delineate the initiation strategy for IDeg in Chinese hospitalized patients with T2DM. We retrospectively analyzed 217 Chinese hospitalized patients with T2DM who initiated IDeg from December 2018 to June 2020, calculating the initial dose and examining correlations between clinical characteristics and glucose profiles. The initial IDeg doses ranged from 0.15 to 0.18 IU/kg·d, showing no association with clinical characteristics. During titration, mean blood glucose levels (MEAN) correlated positively with diabetes duration, age, and Glycosylated Hemoglobin (HbA1c), and negatively with body mass index (BMI), triglycerides (TG), and low-density lipoprotein (LDL). The coefficient of variation (CV) in glucose levels correlated positively with HbA1c and negatively with BMI and TG. The mean amplitude of glycemic excursions (MAGE) mirrored these trends, with additional negative correlations to estimated glomerular filtration rate (eGFR) and serum albumin (ALB). Notably, glycemic variability parameters did not correlate with the presence of diabetic ketoacidosis (DKA) at admission. Hypoglycemia was observed in 21 patients, with differences in MEAN and CV during titration being the only significant findings. The initial IDeg dosing was inadequate and not tailored to clinical features, and there were weak correlations between diabetes duration, age, BMI, eGFR, LDL, and ALB levels and glucose profile post-initiation.

Effects of postprandial exercise timing on blood glucose and fluctuations in patients with type 2 diabetes mellitus.

The aim of this study was to assess how moderate-intensity aerobic exercise performed 45 minutes and 90 minutes after a meal affects blood glucose levels and fluctuations in individuals diagnosed with type 2 diabetes mellitus (T2DM). Twenty-two patients with T2DM, who were solely receiving oral hypoglycemic medication, were enrolled and divided randomly into two categories: those exercising 45 minutes after a meal (45-minute postprandial exercise group) and those exercising 90 minutes post-meal (90-minute postprandial exercise group). Both groups engaged in a 30-minute session of moderate-intensity aerobic stationary bike exercise following breakfast. This aerobic exercise regimen consisted of two stages, with the groups switching exercise timings after the initial phase. Continuous glucose monitoring (CGM) was utilized to evaluate the blood glucose levels and fluctuations in the participants. After breakfast, both overall daily blood glucose levels and the area under the curve for blood glucose following breakfast were reduced in the 45-minute postprandial exercise group compared to the 90-minute postprandial exercise group. The 45-minute postprandial exercise group demonstrated greater time spent within the target glucose range and less time above the target range than the 90-minute postprandial exercise group. Additionally, measures such as standard deviation, mean amplitude of glycemic excursions, largest amplitude of glycemic excursions, and postprandial glucose excursion for breakfast, peak postprandial glucose levels, and duration of elevated glucose levels were all lower in the 45-minute postprandial exercise group compared to the 90-minute postprandial exercise group. Moderate-intensity aerobic exercise lasting 45 minutes after meals was found to be more efficient in decreasing blood glucose levels and minimizing fluctuations compared to exercising 90 minutes after meals in patients with T2DM. Additionally, it notably reduced the peak in blood glucose levels after meals.

Acute Effect of Imeglimin Add-on Therapy on 24-h Glucose Profile and Glycemic Variability in Patients with Type 2 Diabetes Receiving Metformin.

Imeglimin is a novel antidiabetic drug with insulinotropic and insulin-sensitizing effects that targets mitochondrial bioenergetics. We investigated acute effects of add-on therapy with imeglimin to preceding metformin on the 24-h glucose profile and glycemic variability assessed by continuous glucose monitoring (CGM) in patients with type 2 diabetes. We studied 30 outpatients with type 2 diabetes inadequately controlled with metformin. CGM was used for 14 days straight during the research period. Imeglimin 2,000 mg/day was started on day 7 after initiating CGM. Several CGM parameters were compared between days 4-6 (prior to imeglimin treatment) and 11-13 (following the initiation of imeglimin treatment). After treatment with imeglimin, 24-h mean glucose was acutely decreased from 161.6 ± 48.0 mg/dL to 138.9 ± 32.2 mg/dL (p &lt; 0.0001), while time in range (i.e., at a glucose level of 70-180 mg/dL) was significantly increased from 69.9 ± 23.9% to 80.6 ± 21.0% (p &lt; 0.0001). Addition of imeglimin to metformin significantly decreased the standard deviation (SD) of 24-h glucose and mean amplitude of glycemic excursions, 2 indexes of glycemic variability. Baseline serum high-density lipoprotein (HDL) cholesterol was negatively correlated with changes in mean 24-h glucose (r = -0.3859, p = 0.0352) and those in SD (r = -0.4015, p = 0.0309). Imeglimin add-on therapy to metformin acutely lowered 24-h glucose levels and improved glycemic variability in patients with type 2 diabetes on metformin. A higher serum HDL cholesterol at baseline was associated with a better response to acute effects of imeglimin on 24-h glucose levels and glycemic variability.

Potential Benefits of Continuous Glucose Monitoring for Predicting Vascular Outcomes in Type 2 Diabetes: A Rapid Review of Primary Research.

(1) Background: Chronic hyperglycaemia is a cause of vascular damage and other adverse clinical outcomes in type 2 diabetes mellitus (T2DM). Emerging evidence suggests a significant and independent role for glycaemic variability (GV) in contributing to those outcomes. Continuous glucose monitoring (CGM) provides valuable insights into GV. Unlike in type 1 diabetes mellitus, the use of CGM-derived GV indices has not been widely adopted in the management of T2DM due to the limited evidence of their effectiveness in predicting clinical outcomes. This study aimed to explore the associations between GV metrics and short- or long-term vascular and clinical complications in T2DM. (2) Methods: A rapid literature review was conducted using the Cochrane Library, MEDLINE, and Scopus databases to seek high-level evidence. Lower-quality studies such as cross-sectional studies were excluded, but their content was reviewed. (3) Results: Six studies (five prospective cohort studies and one clinical trial) reported associations between GV indices (coefficient of variation (CV), standard deviation (SD), Mean Amplitude of Glycaemic Excursions (MAGE), Time in Range (TIR), Time Above Range (TAR), and Time Below Range (TBR)), and clinical complications. However, since most evidence came from moderate to low-quality studies, the results should be interpreted with caution. (4) Conclusions: Limited but significant evidence suggests that GV indices may predict clinical compilations in T2DM both in the short term and long term. There is a need for longitudinal studies in larger and more diverse populations, longer follow-ups, and the use of numerous CGM-derived GV indices while collecting information about all microvascular and macrovascular complications.

Diabetes Telemedicine Mediterranean Diet (DiaTeleMed) Study: study protocol for a fully remote randomized clinical trial evaluating personalized dietary management in individuals with type 2 diabetes

BackgroundThe Diabetes Telemedicine Mediterranean Diet (DiaTeleMed) Study is a fully remote randomized clinical trial evaluating personalized dietary management in individuals with type 2 diabetes (T2D). The study aims to test the efficacy of a personalized behavioral approach for dietary management of moderately controlled T2D, versus a standardized behavioral intervention that uses one-size-fits-all dietary recommendations, versus a usual care control (UCC). The primary outcome will compare the impact of each intervention on the mean amplitude of glycemic excursions (MAGE).MethodsEligible participants are between 21 and 80 years of age diagnosed with moderately controlled T2D (HbA1c: 6.0 to 8.0%) and managed on lifestyle alone or lifestyle plus metformin. Participants must be willing and able to attend virtual counseling sessions and log meals into a dietary tracking smartphone application (DayTwo), and wear a continuous glucose monitor (CGM) for up to 12 days. Participants are randomized with equal allocation (n = 255, n = 85 per arm) to one of three arms: (1) Personalized, (2) Standardized, or (3) UCC. Measurements occur at 0 (baseline), 3, and 6 months. All participants receive isocaloric energy and macronutrient targets to meet Mediterranean diet guidelines, in addition to 14 intervention contacts over 6 months (4 weekly then 10 biweekly) to cover diabetes self-management education. The first 4 UCC intervention contacts are delivered via synchronous videoconferences followed by educational video links. Participants in Standardized receive the same educational content as those in the UCC arm, following the same schedule. However, all intervention contacts are conducted via synchronous videoconferences, paired with Social Cognitive Theory (SCT)-based behavioral counseling, plus dietary self-monitoring of planned meals using a mobile app that provides real-time feedback on calories and macronutrients. Participants in the Personalized arm receive all elements of the Standardized intervention, in addition to real-time feedback on predicted post-prandial glycemic response (PPGR) to meals and snacks logged into the mobile app.DiscussionThe DiaTeleMed Study aims to address an important gap in the current landscape of precision nutrition by determining the contributions of behavioral counseling and personalized nutrition recommendations on glycemic control in individuals with T2D. The fully remote methodology of the study allows for scalability and innovative delivery of personalized dietary recommendations at a population level.Trial registrationClinicalTrials.gov NCT05046886. Registered on September 16, 2021.

An Update on the iglu Software Package for Interpreting Continuous Glucose Monitoring Data.

Background: Continuous glucose monitors (CGMs) are increasingly used to provide detailed quantification of glycemic control and glucose variability. An open-source R package iglu has been developed to assist with automatic CGM metrics computation and data visualization, providing a comprehensive list of implemented CGM metrics. Motivated by the recent international consensus statement on CGM metrics and recommendations from recent reviews of available CGM software, we present an updated version of iglu with improved accessibility and expanded functionality. Methods: The functionality was expanded to include automated computation of hypo- and hyperglycemia episodes with corresponding visualizations, composite metrics of glycemic control (glycemia risk index and personal glycemic state), and glycemic metrics associated with postprandial excursions. The algorithm for mean amplitude of glycemic excursions has been updated for improved accuracy, and the corresponding visualization has been added. Automated hierarchical clustering capabilities have been added to facilitate statistical analysis. Accessibility was improved by providing support for the automatic processing of common data formats, expanding the graphical user interface, and providing mirrored functionality in Python. Results: The updated version of iglu has been released to the Comprehensive R Archive Network (CRAN) as version 4. The corresponding Python wrapper has been released to the Python Package Index (PyPI) as version 1. The new functionality has been demonstrated using CGM data from 19 subjects with prediabetes and type 2 diabetes. Conclusions: An updated version of iglu provides comprehensive and accessible software for analyses of CGM data that meets the needs of researchers with varying levels of programming experience. It is freely available on CRAN and on GitHub at https://github.com/irinagain/iglu.

Effects of basic carbohydrate counting versus standard dietary care for glycaemic control in type 2 diabetes (The BCC Study): a randomised, controlled trial

BackgroundClinical guidelines recommend basic carbohydrate counting (BCC), or similar methods to improve carbohydrate estimation skills and to strive for higher consistency in carbohydrate intake potentially improving glycaemic control. However, evidence for this approach in type 2 diabetes (T2D) is limited.ObjectiveTo examine the efficacy of a structured education program in BCC as add-on to standard dietary care on glycaemic control in individuals with T2D.MethodsThe BCC Study was a randomized, controlled, open-label, parallel-group trial. Individuals with T2D aged 18-75 years with glycated haemoglobin A1c (HbA1c) 53–97 mmol/mol (7.0–11.0%) were randomly assigned (1:1) to BCC or standard dietary care. The primary outcomes were differences in changes in HbA1c or glycaemic variability (calculated as mean amplitude of glycaemic excursions [MAGE]) between groups after six months of intervention.ResultsBetween September 2018 and July 2021, 48 participants were randomly assigned, 23 to BCC and 25 to standard dietary care. Seven participants did not receive the allocated intervention. From a baseline-adjusted mean of 65 mmol/mol (95% CI 62-68 [8.1%, 7.8-8.4]), HbA1c changed by −5 mmol/mol (−8 to −1 [−0.5%, −0.7 to −0.1]) in BCC and -3 mmol/mol (−7 to 1 [−0.3%, −0.6 to 0.1]) in standard care with an estimated treatment effect of −2 mmol/mol (−7 to 4 [−0.2%, −0.6 to 0.4]); p = 0.554. From a baseline-adjusted mean of 4.2 mmol/l (3.7 to 4.8), MAGE changed by −16% (−33 to 5) in BCC and by −3% (−21 to 20) in standard care with an estimated treatment effect of −14% (−36 to 16); p = 0.319. Only median carbohydrate estimation error in favour of BCC (estimated treatment difference −55% (−70 to −32); p < 0.001) remained significant after multiple testing adjustment.ConclusionsNo glycaemic effects were found but incorporating BCC as a supplementary component to standard dietary care led to improved skills in estimating carbohydrate intake among individuals with T2D.

Diabetes Telemedicine Mediterranean Diet (DiaTeleMed) Study: study protocol for a fully remote randomized clinical trial evaluating personalized dietary management in individuals with type 2 diabetes.

The Diabetes Telemedicine Mediterranean Diet (DiaTeleMed) Study is a fully remote randomized clinical trial evaluating personalized dietary management in individuals with type 2 diabetes (T2D). The study aims to test the efficacy of a personalized behavioral approach for dietary management of moderately-controlled T2D, versus a standardized behavioral intervention that uses one-size-fits-all dietary recommendations, versus a usual care control (UCC). The primary outcome will compare the impact of each intervention on the mean amplitude of glycemic excursions (MAGE). Eligible participants are between 21 to 80 years of age diagnosed with moderately-controlled T2D (HbA1c: 6.0-8.0%), and managed on lifestyle alone or lifestyle plus metformin. Participants must be willing and able to attend virtual counseling sessions and log meals into a dietary tracking smartphone application (DayTwo), and wear a continuous glucose monitor (CGM) for up to 12 days. Participants are randomized with equal allocation (n = 255, n = 85 per arm) to one of three arms: 1) Personalized, 2) Standardized, or 3) UCC. Measurements occur at 0 (baseline), 3, and 6 months. All participants receive isocaloric energy and macronutrients targets to meet Mediterranean diet guidelines plus 14 intervention contacts over 6 months (4 weekly then 10 biweekly) to cover diabetes self-management education. The first 4 UCC intervention contacts are delivered via synchronous videoconferences followed by educational video links. Participants in Standardized receive the same education content as UCC on the same schedule. However, all intervention contacts are conducted via synchronous videoconferences, paired with Social Cognitive Theory (SCT)-based behavioral counseling, plus dietary self-monitoring of planned meals using a mobile app that provides real-time feedback on calories and macronutrients. Participants in the Personalized arm receive all elements of the Standardized intervention, plus real-time feedback on predicted post-prandial glycemic response (PPGR) to meals and snacks logged into the mobile app. The DiaTeleMed study will address an important gap in the current landscape of precision nutrition by determining the contributions of behavioral counseling and personalized nutrition recommendations on glycemic control in individuals with T2D. The fully remote methodology of the study allows for scalability and innovative delivery of personalized dietary recommendations at a population level. The DiaTeleMed Study is registered with ClinicalTrials.gov (Identifier: NCT05046886).

Markers of chronic low-grade inflammation and serum cytokine levels in patients with type 1 diabetes: associations with time in ranges and glucose variability

BACKGROUND: Increased glucose variability is recognized as a risk factor for vascular diabetic complications. It is assumed that deteriorating effect of GV on blood vessels can be realized through the activation of inflammatory signaling pathways.AIM: to determine associations of low-grade inflammation markers and serum cytokines with time in ranges and GV parameters derived from continuous glucose monitoring (CGM) in patients with type 1 diabetes (T1D).MATERIALS AND METHODS: In 470 adult patients with T1D, high-sensitivity C-reactive protein (hsCRP) and fibrinogen was measured, neutrophil-lymphocyte ratio (NLR) and the Systemic Immune-inflammation Index (SII) were calculated. In a sample of 130 patients and 20 healthy individuals (control), serum concentrations of interleukins (IL-1β, IL-4, IL-6, sIL-6Rα, IL-19, IL-20, IL-22, IL-26, IL-27, IL-28A, IL-29, IL-32, IL-34, IL-35) were assessed by multiplex analysis. Time in the ranges and GV parameters: Coefficient of Variability (CV), Mean Amplitude of Glycemic Excursions (MAGE), and Mean Absolute Glucose rate of changes (MAG) were derived from CGM data.RESULTS: Patients with Time In Range (TIR) &lt;70% had higher concentrations of hs-CRP and fibrinogen, higher SII values, and demonstrated a trend toward higher TIR compared with those with TIR ≥70% (p=0.018, p=0.026, p=0.037, p=0.101, respectively). Patients with T1D, when compared to control, demonstrated increased concentrations of IL-1β (p&lt;0.0001), IL-6 (p&lt;0.0001), decreased levels of IL-4 (p=0.002), and a tendency to decrease IL-22 and IL-29 (p=0.1). Patients with TIR&gt;70% had higher levels of IL-4 (p=0.02) as well as lower concentrations of IL-1β (p=0.0003) and IL-6 (p=0.007) than patients with TIR≤70%. In a multivariate stepwise regression analysis including clinical data and CGM parameters as independent variables, body mass index was positive predictor of hsCRP and fibrinogen levels, TIR was negatively associated with IL-20 and IL-34, time above range was associated positively with IL-1β, MAGE showed positive association with SII, IL-26 and IL28A, while MAG was positively associated with IL-29.CONCLUSION: T1D patients with non-target TIR (&lt;70%) have higher levels of low-intensity inflammatory markers and serum pro-inflammatory cytokines than patients with TIR&gt;70%. Both hyperglycemia and increased GV are associated with intensity of low-grade inflammation in T1D.

Time With Rapid Change of Glucose.

A variety of metrics are used to describe glycemic variation, some of which may be difficult to comprehend or require complex strategies for smoothing of the glucose curve. We aimed to describe a new metric named time with rapid change of glucose (TRC), which is presented as percentage of time, similar to time above range (TAR), time in range (TIR), and time below range (TBR). We downloaded glucose data for 90 days from 159 persons with type 1 diabetes using the Abbott Freestyle Libre version 1. We defined TRC as the proportion of time (%) with an absolute rate of change of glucose > 1.5 mmol/L/15 minutes (1.8mg/dL/min) corresponding to a minimum rate of change for glucose in the 3.9-10.0 mmol/L (70-180 mg/dL) range within 1 hour. TRC is related to the other glucose variability metrics: CV within day (CVw) and mean amplitude of glycemic excursion (MAGE). The more than 1.27 million glucose rates were t-location scale distributed with SD 0.91 mmol/L/15 min (1.1 mg/dL/15 min). The median TRC was 6.9% (IQR 4.5%-9.5%). The proportion of TRC with positive slope was 3.9% (2.6%-5.3%) and significantly higher than the proportion with negative slope 2.8% (1.5%-4.4%) P < .001. TRC correlated with CVw and MAGE (Spearman's correlation coefficient .56 and .65, respectively, P < .001). TRC is proposed as an easily perceived metric to compare the performance of hybrid or fully automated closed-loop insulin delivery systems to obtain glucose homeostasis.

Efficacy and safety of avatrombopag in aplastic anemia patients with liver disease.

Abstract Background and Objectives Hyperglycemia is associated with adverse outcomes in patients with acute myocardial infarction (AMI) as well as in patients with heart failure. However, the significance of admission glycemic variability (GV) in predicting outcomes among diabetes patients with heart failure (HF) following acute ST-segment elevation myocardial infarction (ASTEMI) remains unclear. This study aims to explore the prognostic value of admission GV and admission glycosylated hemoglobin (HbA1c) levels in individuals diagnosed with type 2 diabetes and HF following ASTEMI. Methods We measured GV and HbA1c upon admission in 484 consecutive patients diagnosed with type 2 diabetes and HF following ASTEMI. GV, indicated as the mean amplitude of glycemic excursions (MAGE), was assessed utilizing a continuous glucose monitoring system (CGMS). admission MAGE values were categorized as &lt; 3.9 or ≥ 3.9 mmol/L, while HbA1c levels were classified as &lt; 6.5 or ≥ 6.5%. Participants were followed up prospectively for 12 months. The relationship of admission MAGE and HbA1c to the major adverse cardiac event (MACE) of patients with type 2 diabetes and HF following ASTEMI was analyzed. Results Among the 484 enrolled patients, the occurrence of MACE differed significantly based on MAGE categories (&lt; 3.9 vs. ≥ 3.9 mmol/L), with rates of 13.6% and 25.3%, respectively (P = 0.001). While MACE rates varied by HbA1c categories (&lt; 6.5 vs. ≥ 6.5%) at 15.7% and 21.8%, respectively (P = 0.086). Patients with higher MAGE levels exhibited a notably elevated risk of cardiac mortality and an increased incidence of HF rehospitalization. The Kaplan-Meier curves analysis demonstrated a significantly lower event-free survival rate in the high MAGE level group compared to the low MAGE level group (log-rank test, P &lt; 0.001), while HbA1c did not exhibit a similar distinction. In multivariate analysis, high MAGE level was significantly associated with incidence of MACE (hazard ratio 3.645, 95% CI 1.287–10.325, P = 0.015), whereas HbA1c did not demonstrate a comparable association (hazard ratio 1.075, 95% CI 0.907-1.274, P = 0.403). Conclusions Elevated admission GV emerges as a more significant predictor of 1-year MACE in patients with type 2 diabetes and HF following ASTEMI, surpassing the predictive value of HbA1c.

Day-to-Day Glycemic Variability Using Continuous Glucose Monitors in Endurance Athletes.

The application of continuous glucose monitors (CGMs) to measure interstitial glucose in athletic populations is limited by the lack of accepted athlete-specific reference values. The aim of this study was to develop athlete-specific reference ranges for glycemic variability under standardized diet and exercise conditions. A total of 12 elite racewalkers (n = 7 men, 22.4 ± 3.5 years, VO2max 61.6 ± 7.3 mL kg-1 min-1) completed two 4-d trials separated by 4-d. Athletes were provided a high-energy, high-carbohydrate diet (225 ± 1.6 kJ kg-1 day-1, 8.4 ± 0.3 g kg-1 day-1 carbohydrate) and completed standardized daily exercise. The timing of food consumed and exercise undertaken were matched each day across the 4-d trials. Interstitial glucose data were collected via Freestyle Libre 2 CGMs. Glycemic variability was calculated as the mean amplitude of glycemic excursions (MAGEs), mean of daily differences (MODD), and standard deviation (SD). Twenty-four hour MODD, MAGE, and SD for interstitial glucose were 12.6 ± 1.8 mg/dL (0.7 ± 0.1 mmol/L), 36.0 ± 5.4 mg/dL (2.0 ± 0.3 mmol/L), and 16.2 ± 1.8 mg/dL (0.9 ± 0.1 mmol/L), respectively. Twenty-four hour mean glucose (MG; 102.6 ± 5.4 mg/dL [5.7 ± 0.3 mmol/L]) was higher than overnight (91.8 ± 5.4 mg/dL [5.1 ± 0.3 mmol/L]; P < .0001) and was lower in women than men (99.0 ± 3.6 mg/dL [5.5 ± 0.2 mmol/L] vs 104.4 ± 3.6 mg/dL [5.8 ± 0.2 mmol/L]; P = .059, d = 1.4). This study provides reference indices under standardized diet and exercise conditions for glycemic variability derived from CGMs in endurance athletes which are similar than previously reported for healthy individuals, despite strenuous daily training and a high daily energy and carbohydrate diet.

Effect of needle-free injection on psychological insulin resistance and insulin dosage in patients with type 2 diabetes.

Psychological insulin resistance (PIR), which refers to the reluctance of diabetic patients to use insulin, is a frequently encountered clinical issue. Needle-free injection (NFI) offers advantages in terms of expediting insulin absorption and mitigating adverse reactions related to injection. To evaluate the effects of subcutaneous injection of insulin aspart 30 with NFI on PIR and insulin dosage in patients with type 2 diabetes mellitus (T2DM). Sixty-four patients with T2DM participated in this randomized, prospective, open, crossover study. Insulin aspart 30 was administered subcutaneously to each subject via QS-P NFI and Novo Pen 5 (NP) successively. The effects of NFI on PIR were analyzed. Differences in insulin dosage, glycemic variability, and injection safety were compared at similar levels of glycemic control. After the administration of NFI, the insulin treatment attitude scale score decreased (53.7 ± 7.3 vs. 58.9 ± 10.7, p<0.001), the insulin treatment adherence questionnaire score increased (46.3 ± 4.9 vs. 43.8 ± 7.1, p<0.001), and the insulin treatment satisfaction questionnaire score increased (66.6 ± 10.5 vs. 62.4 ± 16.5, p<0.001). At the same blood glucose level, NFI required a smaller dosage of insulin aspart 30 compared with that of NP (30.42 ± 8.70 vs. 33.66 ± 9.13 U/d, p<0.001). There were no differences in glycemic variability indices (standard deviation, mean amplitude of glycemic excursion or coefficient of variation) between the two injection methods. Compared with NP, NFI did not increase the incidence of hypoglycemia (17.2% vs. 14.1%, p=0.774), and it decreased the incidence of induration (4.7% vs. 23.4%, p=0.002) and leakage (6.3% vs. 20.3%, p=0.022) while decreasing the pain visual analog scale score (2.30 ± 1.58 vs. 3.11 ± 1.40, p<0.001). NFI can improve PIR in patients with T2DM and be used with a smaller dose of insulin aspart 30 while maintaining the same hypoglycemic effect. https://www.chictr.org.cn/, identifier ChiCTR2400083658.

Correlation Between Blood Urea Nitrogen and Short- and Long-Term Glycemic Variability in Elderly Patients with Type 2 Diabetes Mellitus Who Were hospitalized:A Retrospective Study.

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and progressively impaired insulin secretion resulting in dynamic fluctuations in glucose levels.High blood urea nitrogen (BUN) levels have been linked to decreased insulin sensitivity, suppressed insulin synthesis and increased risk of incident diabetes mellitus in humans as well as insulin use in patients with T2DM.This study characterize the association between BUN levels and short-term and long-term glycemic variability(GV) in the elderly patients with T2DM who were hospitalized. A total of 927 elderly patients with T2DM were included in the study. The short-term GV was quantified using parameters such as standard deviation (SD), coefficient of variation (CV), time in range (TIR), and mean amplitude of glycemic excursions (MAGE), based on multi-point fingertip blood glucose monitoring. The long-term GV was quantified using parameters such as SD, CV, variation independent of the mean (VIM), and average successive variability (ARV), based on fasting blood glucose(FPG). The relationship between BUN levels and short-term and long-term GV in elderly T2DM who were hospitalized was explored using methods such as Spearman correlation coefficient, linear regression analysis, logistic regression analysis, and interaction tests. In elderly patients with T2DM were hospitalized, there is a significant correlation between BUN levels and both short-term and long-term GV. BUN is negatively correlated with the GV parameter TIR (r=-0.12, P=0.000), and positively correlated with SD (r=0.12, P=0.000), CV (r=0.07, P=0.026), MAGE (r=0.11, P=0.001), FPG-SD (r=0.08, P=0.013), and FPG-CV (r=0.08, P=0.014).Furthermore, the association remains consistent across different age, gender, BMI, and haemoglobin A1c (HbA1c) subgroups (P interaction > 0.05). In elderly patients with T2DM were hospitalized, BUN levels were positively associated with GV.Therefore, monitoring BUN levels were beneficial in assessing the degree of GV.