Mean Amplitude Of Glycemic Excursions Research Articles

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 < 3.9 or ≥ 3.9 mmol/L, while HbA1c levels were classified as < 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 (< 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 (< 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 < 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.

Influence of blood glucose fluctuations on chemotherapy efficacy and safety in type 2 diabetes mellitus patients complicated with lung carcinoma.

Patients with type 2 diabetes mellitus (T2DM) have large fluctuations in blood glucose (BG), abnormal metabolic function and low immunity to varying degrees, which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy. Controlling hyperglycemia may have important therapeutic implications for cancer patients. To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma (LC). The clinical data of 60 T2DM + LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed. All patients underwent chemotherapy and were grouped as a control group (CG; normal BG fluctuation with a mean fluctuation < 3.9 mmol/L) and an observation group (OG; high BG fluctuation with a mean fluctuation ≥ 3.9 mmol/L) based on their BG fluctuations, with 30 cases each. BG-related indices, tumor markers, serum inflammatory cytokines and adverse reactions were comparatively analyzed. Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers. The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG, together with markedly higher mean amplitude of glycemic excursions (MAGE), mean of daily differences, largest amplitude of glycemic excursions and standard deviation of blood glucose (P < 0.05). In addition, the OG exhibited evidently higher levels of carbohydrate antigen 19-9, carbohydrate antigen 125, carcinoembryonic antigen, neuron-specific enolase, cytokeratin 19, tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein than the CG (P < 0.05). Pearson analysis revealed a positive association of MAGE with serum tumor markers. The incidence of adverse reactions was significantly higher in the OG than in the CG (P < 0.05). The greater the BG fluctuation in LC patients after chemotherapy, the more unfavorable the therapeutic effect of chemotherapy; the higher the level of tumor markers and inflammatory cytokines, the more adverse reactions the patient experiences.

Effect of glycemic variability on infectious outcomes in critically Ill burn patients

After acute burn injury, patients experience a hypermetabolic state often complicated by a stress-induced hyperglycemia. Recent research points towards glycemic variability as a contributing factor in adverse outcomes in critically ill patients. In burn patients, greater glycemic variability has been associated with increased rates of mortality and sepsis. However, no studies to date have examined the impact of glycemic variability on rates of infection in this population or determined which measure may be most useful. Infection, and subsequent sepsis, remains the leading contributor to morbidity and mortality after burn injury. The primary objective of this study is to evaluate the relationship between different measures of glycemic variability and infectious complications in burn patients. This retrospective study included patients admitted to a single American Burn Association-verified burn center between January 1, 2020 and December 31, 2020 with burn or inhalation injury. The primary outcome was a composite of autograft loss, mortality, and proven infection. Secondary outcomes included hospital length of stay and a further analysis of the proven infection component of the composite primary outcome. In addition to mean glucose, several different measures of glycemic variability were used for comparison, including standard deviation, coefficient of variation, mean amplitude of glycemic excursions, and J-index. Outcomes were analyzed using multiple logistic regression analysis while controlling for revised Baux score. A quantile analysis was performed to do determine the optimal mean threshold. Three hundred and ninety-two patients were admitted and screened for inclusion during the study period. Most patients were excluded due to a LOS less than 72 h. 112 patients were included in the study. Of the 112 patients, 22.3% experienced an infectious complication (25 patients with 28 complications). Mean glucose (OR 1.024; 95% CI 1.004–1.045) and J-index (OR 1.044; 95% CI 1.003–1.087) were associated with occurrence of infectious complications. Regarding target mean glucose threshold, a daily mean glucose above 150 mg/dL showed the strongest association with infectious complications (OR 3.634; 95% CI 1.008–13.101). Mean glucose, standard of deviation, and J-index were all independently associated with proven infection.

Increased glycemic variability results in abnormal differentiation of T cell subpopulation in type 2 diabetes patients

AimsWe aimed to investigate the association between glycemic variability (GV) and the abnormal differentiation of T-cell subpopulations in patients with type 2 diabetes mellitus (T2DM). MethodsIn total, 108 hospitalized patients with T2DM were enrolled and divided into two subgroups (normal glycemic excursion (NGE) and high glycemic excursion (HGE)) according to their mean amplitude of glycemic excursion (MAGE) level. The MAGE was evaluated via continuous glucose monitoring for 72 h consecutively. Flow cytometry was used to determine the proportions of T cell subpopulations. ResultsThe T helper (Th) 1 cell/Th2 cell ratio was significantly higher, and the proportion of regulatory T cells (Tregs) was significantly lower in the NGE group than in the HGE group (all P < 0.05). After fully adjusting for confounders, the MAGE was positively associated with the Th1 cell/Th2 cell ratio (β = 0.370; P = 0.009) and negatively associated with the proportion of Tregs (β = −0.554; P = 0.001). ConclusionThe MAGE was an independent risk factor for abnormally high Th1 cell/Th2 cell ratio and proportion of Tregs. Abnormal differentiation of T cell subpopulations induced by GV may impair β-cell function, aggravate insulin resistance, and contribute to the development of diabetic complications.

Continuous Glucose Monitoring Profiles and Health Outcomes after Dapagliflozin Plus Saxagliptin vs Insulin Glargine.

Glycemic variability and hypoglycemia during diabetes treatment may impact therapeutic effectiveness and safety, even when glycated hemoglobin (HbA1c) reduction is comparable between therapies. We employed masked continuous glucose monitoring (CGM) during a randomized trial of dapagliflozin plus saxagliptin (DAPA+SAXA) vs insulin glargine (INS) to compare glucose variability and patient-reported outcomes (PROs). 24-week sub-study of a randomized, open-label, two-arm, parallel-group, phase 3b study. Multicenter study (112 centers in 11 countries). 283 adults with type 2 diabetes (T2D) inadequately controlled with metformin ± sulfonylurea. DAPA+SAXA vs INS. Changes in CGM profiles, HbA1c, and PROs. Changes from baseline in HbA1c with DAPA+SAXA were similar to those observed with INS, with mean difference [95% CI] between decreases of -0.12% [-0.37 to 0.12%], P = .33. CGM analytics were more favorable for DAPA+SAXA, including greater percent time in range (> 3.9 and ≤ 10 mmol/L; 34.3 ± 1.9 vs 28.5 ± 1.9%, P = .033), lower percent time with nocturnal hypoglycemia (area under the curve ≤ 3.9 mmol/L; 0.6 ± 0.5 vs 2.7 ± 0.5%, P = .007), and smaller mean amplitude of glycemic excursions (-0.7 ± 0.1 vs -0.3 ± 0.1 mmol/L, P = .017). Improvements in CGM were associated with greater satisfaction, better body weight image, less weight interference, and improved mental and emotional well-being. DAPA+SAXA and INS were equally effective in reducing HbA1c at 24 weeks, but people with T2D treated with DAPA+SAXA achieved greater time in range, greater reductions in glycemic excursions and variability, less time with hypoglycemia, and improved patient-reported health outcomes.

Comparative Effectiveness of Oral Hypoglycemic Agents for Glycemic Control and Glycemic Variability in Patients with Type 2 Diabetes Mellitus: Using Flash Glucose Monitoring.

The study aimed to compare the effectiveness of oral hypoglycemic agents (OHAs) as monotherapy, dual and quadruple therapy for glycemic control (GC) and glycemic variability (GV) in patients with type-2 diabetes (T2DM) using flash glucose monitoring system (FGM). Diabetes management largely relies on HbA1c monitoring. Glycemic variability (GV) has been an evolving glycemic target for preventing complications related to type 2 diabetes mellitus (T2DM). The purpose of the study was to compare glycemic control (GC) measures and glycemic variability (GV) measures among study groups and to study the relationships between GC and GV indices. Retrospectively, FGM data were collected from 50 T2DM patients. The patients were classified based on prescribed number of OHAs as monotherapy [group 1: dipeptidyl peptidase- 4 (DPP-4) inhibitors (n=10), group 2: sodium-glucose co-transporter-2 (SGLT2) inhibitors (n=10), group 3: sulphonylureas (n=10), group 4: dual therapy (n=10), and group 5: quadruple therapy (n=10)]. Measures of GC and GV were evaluated. Significant differences between study groups were observed in GC and GV measurements. The SGLT2 inhibitors monotherapy group demonstrated optimal GC [eA1c (%): 6.5 ± 2.2; MBG: 140.80 ± 63.94; TIR: 60.60 ± 19.96] and GV (SD: 42.38 ± 34.57; CV: 27.85 ± 6.68; MAGE: 96.76 ± 52.47; MODD: 33.96 ± 22.91) in comparison to other study groups. On using Pearson correlation analysis, mean blood glucose (MBG) and mean amplitude of glycemic excursion (MAGE) showed moderate correlation (r = 0.742)(r2 = 0.551), depicting distinct glucose variabilities at the same mean blood glucose levels. The monotherapy group of SGLT2 inhibitors demonstrated glucose-lowering effects with reduced glycemic variability. Hence, optimum glycemic control is associated with decreased glycemic variability.

Short-term glycemic variability in non-diabetic, non-obese dogs assessed by common glycemic variability indices

Glycemic variability (GV) refers to swings in blood glucose levels and is an emerging measure of glycemic control in clinical practice. It is associated with micro- and macrovascular complications and poor clinical outcomes in diabetic humans. Although an integral part of patient assessment in human patients, it is to a large extent neglected in insulin-treated diabetic dogs.This prospective pilot study was performed to describe canine within-day GV in non-diabetic dogs with the aim to provide a basis for the interpretation of daily glucose profiles, and to promote GV as an accessible tool for future studies in veterinary medicine.Interstitial glucose concentrations of ten non-diabetic, non-obese beagles were continuously measured over a 48-h period using a flash glucose monitoring system. GV was assessed using the common indices MAGE (mean amplitude of glycemic excursion), GVP (Glycemic variability percentage) and CV (coefficient of variation).A total of 2260 sensor measurements were obtained, ranging from 3.7 mmol/L (67 mg/dL) to 8.5 mmol/L (153 mg/dL). Glucose profiles suggested a meal-dependent circadian rhythmicity with small but significant surges during the feeding periods. No differences in GV indices were observed between day and night periods (p > 0.05). The MAGE (mmol/L), GVP (%) and CV (%) were 0.86 (± 0.19), 7.37 (± 1.65), 6.72 (± 0.89) on day one, and 0.83 (± 0.18), 6.95 (± 1.52), 6.72 (± 1.53) on day two, respectively.The results of this study suggest that GV is low in non-diabetic dogs and that glucose concentrations are kept within narrow ranges.

Glycemic Variability As a Prognostic Factor for Mortality in Patients With Critical Illness: A Systematic Review and Meta-Analysis.

To perform a systematic review and meta-analysis to evaluate the association of various measures of glycemic variability, including time-domain and complexity-domain, with short-term mortality in patients with critical illness. We searched Embase Classic +, MEDLINE, and the Cochrane Database of Systematic Reviews from inception to November 3, 2023. We included English language studies that assessed metrics of glycemic variation or complexity and short-term mortality in patients admitted to the ICU. Two authors performed independent data abstraction and risk-of-bias assessments. We used a random-effects model to pool binary and continuous data and summarized estimates of effect using odds ratios and mean difference. We used the Quality in Prognosis Studies tool to assess risk of bias and the Grading of Recommendations, Assessment, Development and Evaluations to assess certainty of pooled estimates. We included 41 studies (n = 162,259). We demonstrate that increased sd, coefficient of variance, glycemic lability index, and decreased time in range are probably associated with increased mortality in critically ill patients (moderate certainty) and that increased mean absolute glucose, mean amplitude of glycemic excursion, and detrended fluctuation analysis may be associated with increased mortality (low certainty). We found a consistent association between increased measures of glycemic variability and higher short-term mortality in patient with critical illness. Further research should focus on standardized measurements of glycemic variation and complexity, along with their utility as therapeutic targets and prognostic markers.

Continuous glucose monitoring captures glycemic variability in obesity after sleeve gastrectomy: A prospective cohort study.

HbA1c is an insensitive marker for assessing real-time dysglycemia in obesity. This study investigated whether 1-h plasma glucose level (1-h PG) ≥155mg/dL (8.6mmol/L) during an oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM) measurement of glucose variability (GV) better reflected dysglycemia than HbA1c after weight loss from metabolic and bariatric surgery. This was a prospective cohort study of 10 participants with type 2 diabetes compared with 11 participants with non-diabetes undergoing sleeve gastrectomy (SG). At each research visit; before SG, and 6weeks and 6months post-SG, body weight, fasting lipid levels, and PG and insulin concentrations during an OGTT were analyzed. Mean amplitude of glycemic excursions (MAGE), a CGM-derived GV index, was analyzed. The 1-h PG correlated with insulin resistance markers, triglyceride/HDL ratio and triglyceride glucose index in both groups before surgery. At 6months, SG caused 22% weight loss in both groups. Despite a reduction in HbA1c by 3.0±1.3% in the diabetes group (p<0.01), 1-h PG, and MAGE remained elevated, and the oral disposition index, which represents pancreatic β-cell function, remained reduced in the diabetes group when compared to the non-diabetes group. Elevation of GV markers and reduced disposition index following SG-induced weight loss in the diabetes group underscores persistent β-cell dysfunction and the potential residual risk of diabetes complications.

Expert eValuation of Efficacy and Rationality of Vildagliptin "EVER-Vilda": An Indian Perspective.

Vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor is effective in reducing HbA1c levels in patients with type 2 diabetes (T2DM) when administered as monotherapy, dual or triple combination therapy. In India, Vildagliptin is commonly prescribed in T2DM patients because it reduces mean amplitude of glycemic excursion (MAGE), has lower risk of hypoglycemia and is weight neutral. Early combination therapy with vildagliptin and metformin is effective and well-tolerated in patients with T2DM, regardless of age or ethnicity. In view of already existing data on vildagliptin and the latest emerging clinical evidence, a group of endocrinologists, diabetologists and cardiologists convened for an expert group meeting to discuss the role and various combinations of vildagliptin in T2DM management. This practical document aims to guide Physicians and Specialists regarding the different available strengths and formulations of vildagliptin for the initiation and intensification of T2DM therapy.

Improved pregnancy outcome in gestational diabetes mellitus patients treated with insulin aspart and metformin: a comparative study.

To investigate the impact of combining metformin with insulin aspart on blood glucose control, renal injury, and pregnancy outcome in gestational diabetes mellitus (GDM) patients. In this retrospective analysis, the clinical data of 140 GDM patients treated at Baoji Maternal and Child Health Hospital between March 2020 and March 2022 were studied. The patients were divided into a control group (insulin aspart alone, n=64) and an observation group (combination of insulin aspart and metformin, n=76) according to their treatment regimen. The blood glucose metabolism, renal injury markers, and pregnancy outcomes between the two groups were assessed and compared. The observation group demonstrated significantly lower levels of blood glucose metabolism markers (fasting plasma glucose [FPG], fasting insulin [FINS], mean amplitude of glycemic excursions [MAGE], and mean of daily differences [MODD]), renal injury indicators (microalbuminuria [mAlb], serum cystatin C [CysC], free fatty acids [FFA], and neutrophil gelatinase-associated lipocalin [NGAL]), and inflammatory markers (interleukin-6 [IL-6], transforming growth factor-β1 [TGF-β1], and lipoprotein-associated phospholipase A2 [Lp-PLA2]) compared to the control group (all P<0.05). Additionally, the incidence of adverse pregnancy outcomes in both newborns and mothers was lower in the observation group (P<0.05). Logistic regression analysis identified the treatment regimen, patient age, and pre-pregnancy BMI as independent risk factors for adverse pregnancy outcome. The combination of metformin and insulin aspart in treating GDM can effectively reduce blood glucose levels, mitigate renal injury, and improve pregnancy outcome. This treatment approach presents a viable option for optimizing maternal and fetal health in GDM cases.

Early time-restricted eating improves markers of cardiometabolic health but has no impact on intestinal nutrient absorption in healthy adults

Early time-restricted eating (eTRE) improves aspects of cardiometabolic health. Although the circadian system appears to regulate nutrient absorption, little is known about the effects of eTRE on intestinal absorption. In this randomized crossover trial, 16 healthy adults follow a controlled, weight maintenance diet for 9days, consuming all calories between 0800 and 1400 (eTRE schedule) or 0800 and 2000 (control schedule). We measure the energy content of the diet, stool, and urine with bomb calorimetry and calculate intestinal energy absorption. The eTRE schedule is more effective than the control eating schedule for improving markers of cardiometabolic health, including 24-h mean glucose concentrations and glycemic variability, assessed as the mean amplitude of glycemic excursions. However, eTRE has no effect on intestinal energy and macronutrient absorption, gastrointestinal transit time, colonic hydrogen gas production, or stool microbial composition, suggesting eTRE does not impact gastrointestinal function. This trial is registered (ClinicalTrials.gov: NCT04877262).

Effects of a Novel Glucokinase Activator, Dorzagliatin, on Glycemic Control and Glucose Fluctuation in Drug-Naïve Patients with Type 2 Diabetes Mellitus.

The prevalence rate of type 2 diabetes mellitus (T2DM) has been increasing and a large proportion of patients still do not achieve adequate or sustainable glycemic control on the basis of previous hypoglycemic treatment. In this present study, we explored whether dorzagliatin, a novel glucokinase activator (GKA), could improve glycemic control and lessen glucose fluctuation in drug-naïve patients with T2DM. A self-comparative observational study of 25 drug-naïve patients with T2DM (aged 18-75 years and HbA1c of 7.5%-11.0%) treated with dorzagliatin 75 mg twice daily for 52 weeks. Before and after dorzagliatin intervention, the serum levels of hemoglobin A1c (HbA1c), insulin, and C-peptide were measured repeatedly during fasting and after a mixed meal. The continuous glucose monitoring (CGM) device was also used to obtain 24-hour glucose profiles and assess the changes in glycemic variability parameters. After 52 weeks of treatment with dorzagliatin, a numerally greater reduction in HbA1c of 1.03% from the baseline was observed in patients with T2DM, accompanied by significant improvement in insulin resistance and insulin secretion. Moreover, the standard deviation of blood glucose (SDBG) and the mean amplitude of glycemic excursion (MAGE) derived from CGM data were significantly decreased after dorzagliatin therapy. The 24-h glucose variation profile showed that study patients had obviously lower mean glucose levels during the postprandial period from the baseline to week 52, an effect also demonstrated by the significant decrease in the incremental area under glucose concentration versus time curve for 2 h (iAUC0-2 h) after meals. This study suggests that dorzagliatin therapy could effectively improve glycemic control and glucose fluctuation in drug-naïve patients with T2DM.

Glycemic Variability and Its Correlation with Large for Gestation-age Babies in Gestational Diabetic Pregnancies.

Although glycemic variability (GV) has been shown to be associated with endothelial dysfunction in diabetes mellitus (DM), there is a dearth of literature on its correlation in gestational diabetic pregnancies. To compare GV and 24-hour ambulatory glucose profile (AGP) in gestational diabetic pregnancies with and without large for gestation-age (LGA) babies. It was a cross-sectional observational study. A total of 40 pregnant females between 19 and 35 years with gestational DM (GDM) controlled on pharmacotherapy fulfilling inclusion criteria were recruited. A flash glucose monitor (FGM) was used to record AGP between 32 and 36 weeks of gestation in these women. A total of 400 patient days with 38,400 glucose values in the study group were analyzed. Various glucose measures were compared between the GDM pregnancies with or without LGA babies. The incidence of LGA was 15% in these pregnant women who were on pharmacotherapy and apparently controlled as evidenced by self-monitoring of blood sugar values. All the parameters of 24-hour AGP except dinner values were significantly high in the LGA group when compared with the non-LGA group [mean amplitude of glycemic excursion (MAGE) LGA vs non-LGA 74.58 ± 16.83 vs 49.86 ± 12.83 mg/dL, p = 0.002; standard deviation (SD) LGA vs non-LGA 30.19 ± 9.69 vs 20.10 ± 5.97 mg/dL, p = 0.001]. Variables of GV: MAGE and SD were significantly high in the LGA group (p < 0.001). Time below range (TBR) and time above range (TAR) were also significantly altered in the LGA group (p < 0.001). High GV and time in the range are the important parameters that can be well correlated with LGA babies in gestational diabetic pregnancies on pharmacotherapy. An FGM is a good monitoring device to measure this parameter and can be used as an adjunct to modify measures to control the glucose values within range in these pregnancies.

Effects of mulberry twig alkaloids(Sangzhi alkaloids) and metformin on blood glucose fluctuations in combination with premixed insulin-treated patients with type 2 diabetes.

We aimed to evaluated the effect of premixed insulin (Ins), premixed insulin combined with metformin (Ins+Met) or mulberry twig alkaloids(Ins+SZ-A) on blood glucose fluctuations in patients with type 2 diabetes (T2DM) using continuous glucose monitors (CGM). Thirty patients with T2DM and poor blood glucose control using drugs were evaluated for eligibility during the screening period. Subsequently, their original hypoglycemic drugs were discontinued during the lead-in period, and after receiving Ins intensive treatment for 2 weeks, they were randomly assigned to receive either Ins, Ins+Met, or Ins+SZ-A treatment for the following 12 weeks. The main efficacy endpoint comprised changes in their CGM indicators changes (mean blood glucose level [MBG], standard deviation of blood glucose [SDBG], mean amplitude of glycemic excursions [MAGE], postprandial glucose excursions [PPGE], the largest amplitude of glycemic excursions [LAGE], mean of daily difference [MODD], time in range between 3.9-10.0 mmol/L [TIR] and area under the curve for each meal [AUCpp]) during the screening, lead-in, and after 12-week treatment period. Changes in glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), 1-h postprandial blood glucose (1h-PBG), 2-h postprandial blood glucose (2h-PBG), fasting blood lipids and postprandial blood lipids were also measured at baseline and after 12 weeks of treatment. The CGM indicators of the three groups during the lead-in period all showed significant improvements compared to the screening period (P<0.05). Compared with those in the lead-in period, all of the CGM indicators improved in the the Ins+Met and Ins+SZ-A groups after 12 weeks of treatment (P<0.05), except for MODD. After 12-week treatment, compared with the Ins group, Ins+Met and Ins+SZ-A groups showed improved MBG, SDBG, TIR, breakfast AUCpp,lunch AUCpp, HbA1c, FBG, 1h-PBG, fasting blood lipid and postprandial blood lipid indicators (P<0.05). Further, the LAGE, PPGE, MAGE, dinner AUCpp and 2h-PBG levels of the Ins+SZ-A group were significantly lower than those of the Ins+Met and Ins groups (P<0.05). Our findings highlight the efficacy of combination therapy (Ins+SZ-A or Ins+Met) in improving blood glucose fluctuations, as well as blood glucose and lipid levels. Ins+SZ-A reduces postprandial blood glucose fluctuations more than Ins+Met and Ins groups. ISRCTN20835488.

Serum 25-hydroxyvitamin D level is associated with short-term glycemic variability metrics derived from continuous glucose monitoring in T2DM

This study aims to investigate the association between 25-hydroxyvitamin D (25OHD) and continuous glucose monitoring-assessed short-term glycemic variability (GV) and HbA1c among patients with type 2 diabetes mellitus (T2DM). We conducted a cross-sectional study recruiting 325 patients. The association between 25OHD and GV metrics (mean amplitude of glycemic excursions [MAGE], coefficient of variation [CV], standard deviation of sensor glucose [SD], and TIR) and HbA1c were analyzed using multivariable linear and logistic regression analyses. The 25OHD level and GV metrics showed significant differences among HbA1c groups (P < 0.01). CV, MAGE, SD and HbA1c decreased, and TIR increased with ascending 25OHD tertiles (P < 0.05). Serum 25OHD was inversely associated with CV (β = − 0.211 [− 0.350 to − 0.071], P < 0.01) and HbA1c (β = − 0.061 [− 0.114 to − 0.031], P < 0.01), and further multivariable analyses confirmed these results (P < 0.05). However, no association of HbA1c and 25OHD was found with the highest tertile of CV. These findings revealed that increased GV and HbA1c were both associated with lower 25OHD, and the relationship between HbA1c and 25OHD was attenuated with higher glucose CV in T2DM. Taken together, the analyses suggest that increasing vitamin D status has effects on improvements in long-term glycemic control and low glycemic variability.

Two novel GCK mutations in Chinese patients with maturity-onset diabetes of the young.

Heterozygous inactivating mutations in the glucokinase (GCK) gene result in the asymptomatic fasting hyperglycemia named as GCK-MODY or MODY2. The genetic testing can effectively avoid the misdiagnosis and inappropriate treatment for GCK-MODY. A total of 25 unrelated families with MODY were screened for mutations in coding region of GCK by using direct sequencing. Three different bioinformatics tools such as PolyPhen2, Mutation Taster and PROVEAN were performed to predict the function of mutant proteins. The glucose profile was recorded by continuous glucose monitoring system (CGMS) to evaluate the glycemic variability for the GCK-MODY patient. Our study identified five GCK mutations in 24% of the families (6/25): two novel mutations (I126fs and G385A) and three already described mutations (G44S, H50fs and S383L). In silico analyses predicted that these mutations altered structural conformational changes. The values of mean amplitude of glycemic excursions (MAGE), an important index of blood glucose fluctuation in CGMS system, were 0.81 in the first 24 h and 1.61 in the second 24 h record in the patient with GCK-MODY (F3), suggesting little glucose fluctuation. The genetic testing is suggested to be important to differentiate GCK-MODY from other types of diabetes. CGMS might be used to screen GCK-MODY cases prior to genetic testing.