Improvement In Glycemic Control Research Articles

An acute bout of 4 x 4-minute or 10 x 1-minute HIIT improves beta cell glucose sensitivity in post-menopausal females with type 2 diabetes: a secondary analysis.

Aims/hypothesis: Improvements in glycemic control following acute exercise are typically attributed to improved post-exercise insulin sensitivity (IS) with comparatively little known about how acute exercise impacts beta cell function, especially in post-menopausal females. We determined how two high-intensity interval training (HIIT) protocols, matched for total estimated energy expenditure, impact beta cell function in post-menopausal females with type 2 diabetes. Methods: Thirteen post-menopausal females (70 ± 5 years; 12 ± 7 years since diagnosis, 80.9 ± 13.8 kg, 32.4 ± 5.6 kg*m2; HbA1c - 49.8 ± 10.3 mmol/mol [6.7 ± 1.0]) living with type 2 diabetes were included in this semi-randomized crossover trial. The trial involved an initial resting control condition followed by two HIIT conditions [4 X 4-minute HIIT (HIIT4) and 10 X 1-minute HIIT (HIIT10)] completed in a randomized order 2-4 days apart. Beta cell function (glucose sensitivity) and insulin sensitivity were determined from a 2 h mixed-meal tolerance test performed 2 hours after rest or HIIT. Results: Both HIIT4 and HIIT 10 significantly improved beta cell glucose sensitivity compared to control (15 pmol*min-1*m-2[mmol/L]-1, [95% CI 6, 23]; p= 0.002 and 16 pmol*min-1*m-2[mmol/L]-1, [95% CI 7, 25]; p= 0.002, respectively), with no difference between HIIT protocols (1 [-8, 10], P = 0.79). There were no significant differences in IS metrics (Matsuda index, OGIS, Stumvoli, and QUICKI) between the conditions. Conclusions/interpretation: An acute bout of 4 X 4-minute or 10 X 1-minute HIIT improves beta cell glucose sensitivity in post-menopausal females living with type 2 diabetes.

A prospective, multicentre study evaluating safety and efficacy of a fixed dose combination of Remogliflozin etabonate, Vildagliptin, and Metformin in Indian patients with type 2 diabetes mellitus (Triad-RMV)

AimsThe ICMR INDIAB-17 study revealed a diabetes prevalence of 11.4% in India, emphasizing the need for effective treatment for glycemic control. A Phase IV study was conducted to evaluate the safety and efficacy of a Fixed Dose Combination (FDC) of Remogliflozin, Metformin and Vildagliptin (RMV) in Type 2 Diabetes Mellitus (T2DM) patients uncontrolled on Metformin plus SGLT2 inhibitor or Metformin plus DPP4 inhibitor dual therapy.MethodsA total of 215 patients (mean age: 46.4 years; 64% male, 36% female) were enrolled across multiple centers in India. The study population included patients with a baseline HbA1c ≥ 8% at the time of screening. The primary objective was to assess safety based on treatment-emergent adverse events (TEAEs), while the secondary. aim was to evaluate effectiveness in terms of glycemic (HbA1c, fasting plasma glucose, postprandial glucose) and extra-glycemic measures (renal and lipid parameters). Statistical analysis was conducted using paired t-tests and the Wilcoxon signed-rank test for within-group comparisons, and the Bonferroni correction was applied to adjust for multiple comparisons. Effectiveness was evaluated at baseline, week 12, and week 24.ResultsThe study demonstrated statistically significant reductions in mean HbA1c levels from baseline to both week 12 and week 24 (p < 0.00001). At 24, weeks, 45.1% of patients achieved target HbA1c levels of ≤ 7%. Significant reduction was also observed in fasting plasma glucose (FPG) and postprandial glucose (PPG) levels. Renal parameters remained stable or improved, and lipid profile parameters, including LDL-C and triglycerides, showed favorable changes. Adverse events of special interest, including hypoglycemia and urinary tract infections, were reported in 4.7% of patients, with no serious adverse event recorded.ConclusionsThe twice daily triple FDC of RMV was well tolerated, safe and effective in patients with Type 2 Diabetes Mellitus uncontrolled on dual drug therapy of Metformin plus SGLT2i or Metformin plus DPP4i. The treatment led to significant improvements in glycemic control and other metabolic parameters over 24 weeks, without compromising renal function or causing serious adverse events.Trial registrationCTRI, CTRI/2022/05/042581. Registered 17 May 2022, https//ctri.nic.in/Clinicaltrials/rmaindet.php? trialid=68,757&EncHid=36127.16500&modid=1&compid=19.

Jamun (Syzygium cumini Linn.) Seed Extract as a Potential Antidiabetic Agent: Effects on Blood Glucose Levels, Haematological Parameters and Biochemical Profiles in Alloxan-Induced Diabetic Albino Rats

Diabetes mellitus is rapidly increasing in India, making it essential to find alternative therapies that minimize side effects and improve patient outcomes. Safer treatment options are needed to manage the growing burden of this chronic condition effectively. This study evaluates the antidiabetic potential of Syzygium cumini seed extract (SCSEt) in alloxan-induced diabetic rats. Diabetes was induced by administering alloxan (120 mg/kg) in albino rats, and diabetes was confirmed with blood glucose levels ≥290 mg/dL. Rats were treated with SCSEt at doses of 2, 4, and 6 g/kg orally, with insulin (1.0 IU/kg/day) serving as a reference treatment. Over four weeks, SCSEt demonstrated a significant reduction in blood glucose levels compared to untreated diabetic controls, though less effective than insulin. Blood glucose levels in SCSEt-treated groups decreased from 286 ± 1.10 mg/dL (low-dose) to 110 ± 3.21 mg/dL (high-dose), compared to insulin-treated rats with levels of 112 ± 1.96 mg/dL. Haematological parameters improved with SCSEt, particularly at higher doses, where packed cell volume (PCV) reached 42.91 ± 0.98% and haemoglobin levels were 17.08 ± 2.06 g/dL. Biochemical analyses revealed reduced serum cholesterol and improved protein levels in high-dose SCSEt rats, with cholesterol dropping to 112 ± 1.92 mg/dL and protein rising to 6.39 ± 0.09 mg/dL. SCSEt also enhanced glucose tolerance, with high-dose SCSEt rats achieving the lowest glucose level of 104 ± 1.62 mg/dL at 100 minutes during the oral glucose tolerance test (OGTT). Although SCSEt was less effective than insulin in glucose management, its potential as a complementary therapy is supported by its significant improvements in glycemic control and lipid profile.

Sleeve Gastrectomy and Its Impact on Insulin Resistance and Metabolic Health: A Cohort Study.

Obesity is a prevalent metabolic disorder that significantly contributes to insulin resistance (IR), type 2 diabetes (T2DM), and metabolic syndrome. Sleeve gastrectomy has emerged as an effective surgical intervention for obesity, with potential benefits on metabolic health. This study investigates the impact of sleeve gastrectomy on serum insulin levels, IR (HOMA-IR), inflammatory markers, C-peptide, kidney function, and various biochemical parameters in diabetic and non-diabetic patients. A prospective cohort study was conducted, involving 199 patients over 18years old who were candidates for sleeve gastrectomy at Luqman Hakim Hospital from 2021 to 2022. Data were collected using standardized questionnaires and anthropometric measurements, and biochemical assessments were performed before surgery and 6months postoperatively. Statistical analyses included descriptive statistics, t-tests, Mann-Whitney tests, and repeated measures analysis of variances (ANOVA). The study included 199 patients (84.4% female) with a mean (± standard deviation (SD)) age of 39.79 ± 11.30years. Significant reductions were observed in weight, BMI, and abdominal circumference across all patient groups. Diabetic patients showed marked improvements in fasting blood sugar, 2-h postprandial blood sugar, and glycosylated hemoglobin levels. Insulin resistance decreased significantly, as did serum insulin and C-peptide levels. Improvements in lipid profiles and inflammatory markers were also noted. Insulin use post-surgery showed a significant inverse relationship with glycemic control improvement. Sleeve gastrectomy is a safe and effective procedure for obese patients, significantly improving insulin resistance and various obesity-associated diseases within 6months post-surgery.

Glycemic Control With Layperson-Delivered Telephone Calls vs Usual Care for Patients With Diabetes: A Randomized Clinical Trial.

Diabetes is associated with emotional distress and poor mental health, especially for individuals with low income, hindering patients' ability to manage their condition. The health care system's workforce constraints limit its capacity to holistically support patients. To assess the effectiveness of layperson-delivered empathetic engagement over the telephone in helping improve glycemic management for patients with diabetes. This parallel-arm randomized clinical trial with blinded outcome assessment was conducted from February 12, 2022, to April 15, 2023, with final measurements on November 18, 2023, among 260 patients with uncontrolled diabetes from a federally qualified health center in Austin, Texas, engaging telephonically from home. Patients assigned to the intervention group received empathy-oriented telephone calls by community-hired laypeople for 6 months, while those assigned to the control group received usual care. Patients were stratified by baseline score (≥5 vs <5) on the depressive symptom scale of the 9-item Patient Health Questionnaire (PHQ-9). The primary outcome was hemoglobin A1c level at baseline, 3 months, and 6 months, assessed for interaction between time and trial arm. Secondary outcomes were self-perceptions of managing diabetes, diabetes-related behaviors and distress, and mental health symptoms (measured via surveys). Analysis was performed on an intention-to-treat basis. Of 260 participants (mean [SD] age, 49.5 [10.1] years; 163 of 259 women [62.9%]; 176 of 203 [86.7%] with annual income <$40 000) enrolled, 6 withdrew. At 6 months, 204 of 254 (80.3%; intervention, 109 of 127 [85.8%] and control, 95 of 127 [74.8%]) returned for measurements. Participants in the intervention group had statistically significant mean (SD) decreases in hemoglobin A1c level at 6 months (from 10.0% [1.9%] to 9.3% [2.0%]) compared with those in the control group (from 9.8% [1.6%] to 9.7% [2.3%]) (P = .004). The within-person change in hemoglobin A1c level was -0.7% (95% CI, -1.0% to -0.4%) for the intervention group and 0.02% (95% CI, -0.4% to 0.4%) for the control group. For the subgroup with a PHQ-9 score of 5 or more at baseline (38.1% [99 of 260]), the within-person change in hemoglobin A1c was -1.1% (95% CI, -1.8% to -0.5%) for the intervention group and 0.1% (95% CI, -0.7% to 0.8%; P = .004) for the control group. For the subgroup with a PHQ-9 score less than 5, the within-person change in hemoglobin A1c was -0.4% (95% CI, -0.8% to -0.1%) for the intervention group and -0.02% (95% CI, -0.5% to 0.5%; P = .21) for the control group. At 6 months, 91.7% of the participants (99 of 108) responded that the program was very or extremely beneficial. In this randomized clinical trial of telephone-based layperson-delivered empathetic engagement, patients with diabetes and low income achieved clinically meaningful improvements in glycemic control. With workforce constraints, layperson-delivered programs for diabetes show promise. ClinicalTrials.gov Identifier: NCT05173675.

Cardiologists vs Endocrinologists in Glycemic Control for Coronary Artery Disease Patients with Type 2 Diabetes: A Cross-Sectional Study.

The comorbidity of coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) presents significant challenges in clinical management, particularly regarding glycemic control. The clinical management of CAD complicated by T2DM requires coordinated glycemic control, as poor management can exacerbate cardiovascular risks and increase morbidity and mortality. While endocrinologists traditionally manage diabetes, cardiologists are increasingly involved due to the cardiovascular risks associated with poor glycemic control. This study explores the current practices of glycemic management by cardiologists and endocrinologists in patients with CAD and T2DM, focusing on treatment intensification in a Chinese hospital setting. This cross-sectional study included 1,074hospitalized patients with both CAD and T2DM, admitted to the Cardiology Department of Ruijin Hospital between January 2021 and December 2023. Data were retrospectively collected from electronic medical records, including demographic information, clinical characteristics, and treatment interventions. Patients were stratified by year, and differences in treatment strategies between cardiologists and endocrinologists were analyzed. Glycemic control was assessed using HbA1c levels, with treatment intensification defined by any adjustment in antidiabetic therapy and consideration for comprehensive cardiovascular risk factors. Endocrinologists were significantly more likely to initiate treatment intensification, especially in cases of severe hyperglycemia (HbA1c ≥9.0%), while cardiologists' role in glycemic management was limited, with a preference for outpatient endocrinology referrals over in-hospital adjustments. Despite improvements in glycemic control, the percentage of patients achieving comprehensive cardiovascular risk management targets remained low. This study underscored the distinct yet complementary roles of cardiologists and endocrinologists in managing glycemic control among patients with CAD and T2DM, noting endocrinologists' more active involvement in treatment intensification. Future integrated care models should harness the unique expertise of both specialties to optimize patient outcomes, better address glycemic control needs, and enhance overall cardiovascular risk management in this high-risk patient population.

Improvement of Glycogenic Hepatopathy with Minimal Corresponding Improvement of Glycemic Control in a Person with Type 1 Diabetes: Case Report and Literature Review

Improvement of Glycogenic Hepatopathy with Minimal Corresponding Improvement of Glycemic Control in a Person with Type 1 Diabetes: Case Report and Literature Review

The status of blood glucose monitoring and its influencing factors in Chinese patients with type 2 diabetes initiating premixed insulin: A prospective real-world study

ObjectiveThis study aimed to assess the current state of self-monitoring of blood glucose (SMBG) in Chinese patients initiating premixed insulin and its influential factors. Research Design and MethodsThis is a single-arm, multi-center, prospective real-world study enrolling a total of 8214 adult patients with type 2 diabetes mellitus (T2DM) newly initiated premixed insulin analogues. Each patient was followed up for 12 weeks, and the data related to SMBG was collected at week 1, week 4, week 8 and week 12, while data related to glycated hemoglobin were collected at week 1 and week 12. The primary outcome was the frequency of SMBG over 12 weeks. ResultsAt week 12, 83.3 % monitored blood glucose at least once, while 20.3 % of participants continued SMBG every week. The average monitoring frequency was 4.78 times/week over the first 4 weeks and 3.33 times/week over 12 weeks. The patients with a higher frequency of SMBG had better control of blood glucose. ConclusionsThis study found that most T2DM patients would take SMBG but the adherence decreased over time. The adherence to SMBG in Chinese T2DM patients was influenced by age, insulin dosage, education level, and diabetes duration. SMBG benefited the improvement of glycemic control.

GLP-1 and GIP agonism has no direct actions in human hepatocytes or hepatic stellate cells

The use of incretin agonists for managing metabolic dysfunction-associated steatohepatitis (MASH) is currently experiencing considerable interest. However, whether these compounds have a direct action on MASH is still under debate. This study aims to investigate whether GLP-1R/GIPR agonists act directly in hepatocytes and hepatic stellate cells (HSCs). For this, human hepatocyte and HSCs lines, as well as primary human hepatocytes and HSCs treated with Liraglutide, Acyl-GIP or the GLP-1/GIP dual agonist (MAR709) were used. We show that the concentrations of each compound, which were effective in insulin release, did not induce discernible alterations in either hepatocytes or HSCs. In hepatocytes displaying elevated fatty acid content after the treatment with oleic acid and palmitic acid, none of the three compounds reduced lipid concentration. Similarly, in HSCs activated with transforming growth factor-β (TGFb), Liraglutide, Acyl-GIP and MAR709 failed to ameliorate the elevated expression of fibrotic markers. The three compounds were also ineffective in phosphorylating CREB, which mediates insulinotropic actions, in both hepatocytes and HSCs. These findings indicate that incretin agonists have no direct actions in human hepatocytes or hepatic stellate cells, suggesting that their beneficial effects in patients with MASH are likely mediated indirectly, potentially through improvements in body weight, insulin resistance and glycemic control.

Prevent hypoglycaemia when using automated insulin delivery systems in type 1 diabetes requires near normal glycaemic variability

AimAlthough newer technologies of insulin delivery in type 1 diabetes have facilitated an improvement in glycaemic control the risk of hypoglycaemia remains a threat. Therefore, it is important to define the thresholds of glycaemic variability below which the risk of hypoglycaemia can be eliminated or at least minimized. MethodsRandomized controlled trials conducted from 2017 to 2023 comparing Sensor-Augmented-Pumps and Augmented Insulin Delivery Systems (n = 16 and 22 studies, respectively) were selected. A weighted linear model of regression was used to compute the relationship between glycaemic variability and times spent below glucose range. The intercepts of regression lines with the abscissa axis (time below range = 0 %) defined the glycaemic variability thresholds. ResultsPositive relationships were observed between the 2 metrics. The scatter plots indicated that the times spent below range never reached the value of 0 % and that the glycaemic variability never fell below 28 %. By extrapolating the regression lines, the glycaemic variability at intercepts with time below range < 70 mg/dL of 0 % was 30.1 % with sensor augmented pumps and 18.9 % with automated insulin delivery. For a time below range < 54 mg/dL of 0 % the respective glycaemic variability values were 32.7 % and 19.9 % (with sensor augmented pumps and automated insulin delivery, respectively). ConclusionsImportantly, glycaemic variability targets and ambient hyperglycaemia are interdependent. Users of automated insulin delivery need to reach a glycaemic variability of 18 % to 20 % to minimize or eradicate the risk of hypoglycaemia. Such values are those observed in healthy non-diabetic people.

Is Automated Insulin Delivery System Therapy Safe and Effectıve in Children Under 7 Years Old?

This study aims to evaluate the off-label use of the MiniMed™ 780G system in children under seven years old, as clinical outcomes in this age group are less established despite the improvements in glycemic control seen with MiniMed™ 780G therapy. Children under seven years old with type 1 diabetes (T1D) using MiniMed™ 780G pump therapy were retrospectively compared with children of similar age and gender using MiniMed™ 640G insulin pump therapy and multiple-dose insulin (MDI) therapy with continuous glucose monitoring systems (CGMs). CGM metrics, total daily insulin dose (TDI), and HbA1c levels were evaluated retrospectively at baseline and at the 3rd, 6th, and 12th months. At the initiation of MiniMed™ 780G therapy, the mean age was 5,25±1,22 years (range: 2,8-6,8 years), and the mean TDI was 10,12±4,34 U/day (range: 4,5-17 U/day). The glucose management indicator (GMI) and HbA1c remained lower in the MiniMed™ 780G group at the 3rd, 6th, and 12th months compared to baseline (p=0,009 and p<0,001, respectively). In the MiniMed™ 780G group, Time Above Range (TAR) was significantly lower at the 3rd, 6th, and 12th months (p=0,018, 0,017, and 0,04, respectively), and Time in Range (TIR) was higher at the 3rd and 12th months (p=0,026 and 0,019, respectively). The coefficient of variation (CV) and HbA1c were lower at the 12th month (p=0,008 and 0,015, respectively) compared to the other groups. No instances of ketoacidosis or severe hypoglycemic events were observed in any of the children during the follow-up period. The absence of significantly higher levels of hypoglycemia compared to other groups at any time point, along with a significant decrease in TAR across all time points, a significant increase in TIR at the 3rd and 12th months, and a significant decrease in HbA1c and CV, indicates that the MiniMed™ 780G system is both safe and effective for children under seven years old.

Overcoming therapeutic inertia in newly diagnosed type 2 diabetes: Protocol of a randomized, quality improvement trial

Therapeutic inertia, the delay in the appropriate initiation and intensification of recommended therapies, is a major contributor to the lack of improvement in type 2 diabetes outcomes over the past decade. Therapeutic inertia during the period following diagnosis, when improvements in glycemic control can have lasting benefits, is often overlooked. Technology and team-based care approaches can effectively address therapeutic inertia. Here, we describe the protocol for a randomized, quality improvement trial targeting metformin-related therapeutic inertia among adults with recently diagnosed type 2 diabetes and a hemoglobin A1c <8 %. Service areas within an integrated healthcare delivery system were randomized to 1) usual care, 2) physician education on therapeutic inertia, and 3) physician education on therapeutic inertia paired with proactive outreach by a clinical pharmacist. The physician education sessions were offered to primary care providers working in the service areas randomized to Arm 2 and Arm 3, and proactive outreach by a clinical pharmacist was performed for patients of the providers in service areas randomized to Arm 3. Outcomes will be abstracted from the EHR at 6, 12, and 18 months following the physician education sessions. The primary outcome will be the proportion of patients with an HbA1c <7 % at each of the follow-up time points. Outcome abstraction and analyses will occur in late 2024. This trial seeks to rigorously evaluate care strategies that can shift stagnant type 2 diabetes outcomes. Our protocol, along with the pending results, may offer examples to other healthcare systems working to improve type 2 diabetes care.

Initiating continuous glucose monitoring is associated with improvements in glycemic control and reduced health care resource utilization for people with diabetes in a large US-insured population: A real-world evidence study.

To examine the real-world impact of continuous glucose monitoring (CGM) use on glycemic management and health care resource utilization (HCRU) in people with diabetes in a large US-insured population. This retrospective observational study used Aetna administrative claims data from a cohort of fully insured commercial and Medicare Advantage beneficiaries with diabetes and with coverage for medical and pharmacy benefits. The index date was the first CGM pharmacy or medical claim observed between January 1, 2019, and December 31, 2021. Change in hemoglobin A1c was calculated using values from 3 months before and the latest values 10-12 months after the index date. HCRU was measured 12 months before and after the index date. Data were analyzed by the following patient groups: type 1 diabetes, type 2 diabetes (T2D) on intensive insulin therapy, T2D on basal-only insulin therapy, and T2D not on insulin therapy. Data from 7,336 patients (74% T2D, mean age 57 years, 42% Medicare-insured, 54% male, 56% White) were analyzed. Beneficiaries with available A1c data (n = 1,063) showed a significant improvement in A1c after CGM initiation (-0.7%, P < 0.0001), including -0.9% change in the T2D not on insulin group (n = 264). For the overall cohort, the number of patients with diabetes-related hospitalizations and emergency department visits decreased significantly by 67% and 40%, respectively (P < 0.0001 for both). This study showed that CGM use was associated with clinically meaningful improvements in A1c and reduced HCRU, suggesting potential for population-level clinical benefits, especially for patients not using insulin.

Truncated Albumins as Novel Surrogate Biomarkers in Diabetes Therapy: Epiphenomena and Potential Clinical Applications.

Aims/Hypothesis: Among various albumin posttranslational modifications (PTMs), N- and C-terminal truncations (HSA-DA and HSA-L) have also shown biomarker potential in disease states. We examined albumin truncation longitudinal trends and correlations during diabetes therapy toward possible future clinical applications. Methods: In a preliminary longitudinal therapy investigation, mass spectrometry was employed to track PTMs of human serum albumin (HSA), including glycation (GA), cysteinylation (CA or HNA1; reversible), di/trioxidation (OA or HNA2; irreversible), and truncation (TA). These modifications were correlated with ongoing therapy in four distinct subject groups: type 1 diabetes (T1DM), type 2 diabetes (T2DM), prediabetes-obesity (PDOB), and healthy controls (NORM), observed over a follow-up period extending up to 280 days. Results: Diabetes was associated with significant reduction ("deficiency") of measured albumin truncations (For HSA-DA: T2DM = 0.32 ± 0.3%, p = 2E-08; T1DM = 1.02 ± 0.4%, p = 3E-05; PDOB = 1.61 ± 0.2%, p = 0.004; compared to NORM = 2.08 ± 0.2%). Albumin truncation reduction was more striking in T2DM (HSA-DA: T2DM vs. T1DM: p = 0.004). Improvements in glycemic control and decrease of albumin glycation during diabetes therapy were associated with concomitant increase of albumin truncations toward the "healthy" normal ranges, and vice versa ("mirror image" trends). Accordingly, albumin truncation correlated inversely with albumin glycation (HSA-DA vs. GA: R = -0.53, p = 1E-09). Conclusions: The "epiphenomenon" of albumin truncation (reflecting the severity of mean hyperglycemia and also insulin resistance) can possibly provide novel, sensitive, and complementary biomarkers (e.g., via simpler HSA-DA peptide fragment immunoassays) to monitor efficacy of diabetes therapy and also progression from "healthy" to prediabetes and type 2 diabetes, highlighting potential diagnostic and prognostic utility in clinical diabetes care.

Genetic Evidence for GLP-1 and GIP Receptors as Targets for Treatment and Prevention of MASLD/MASH.

Glucagon-like peptide-1 receptor (GLP1R) agonists and glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists may help treat metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). However, their definitive effects are still unclear. Our study aims to clarify this uncertainty. We utilised conventional Mendelian randomisation (MR) analysis to explore potential causal links between plasma GLP-1/GIP concentrations and MASLD and its related traits. Next, we conducted drug-target MR analysis using highly expressed tissue data to assess the effects of corresponding drug perturbation on these traits. Finally, mediation analysis was performed to ascertain whether the potential causal effect is direct or mediated by other MASLD-related traits. Circulating 2-h GLP-1 and GIP concentrations measured during an oral glucose tolerance test showed hepatoprotective effects on MASLD risk (ORGLP-1 = 0.168 [95% CI 0.033-0.839], p = 0.030; ORGIP = 0.331 [95% CI 0.222-0.494], p = 6.31 × 10-8). GLP1R expression in the blood had a minimal causal effect on MASLD risk, whereas GIPR expression significantly affected MASLD risk (OR = 0.671 [95% CI 0.531-0.849], p = 9.07 × 10-4). Expression levels of GLP1R or GIPR in the blood significantly influenced MASLD-related clinical traits. Mediation analysis revealed that GIPR expression protected against MASLD, even after adjusting for type 2 diabetes or body mass index. GLP-1/GIP receptor agonists offer promise in lowering MASLD/MASH risk. GIP receptor agonists can exert direct and indirect effects on MASLD mediated by weight reduction or glycemic control improvement.

Real-Life Achievements of MiniMed 780G Advanced Closed-Loop System in Youth with Type 1 Diabetes: AWeSoMe Study Group Multicenter Prospective Trial.

Background: We assessed real-life glycemic outcomes and predictors of composite measures of optimal glycemic control in children and adolescents with type 1 diabetes (T1D) during their initial 12 months of the MiniMed™ 780G use. Methods: This prospective observational multicenter study collected demographic, clinical, and 2-week 780G system data at five time points. Optimal glycemic control was defined as a composite glycemic control (CGC) score requiring the attainment of four recommended continuous glucose monitoring (CGM) targets, as well as the glycemia risk index (GRI) of hypoglycemia and hyperglycemia and composite CGM index (COGI). Outcome measures included longitudinal changes in multiple glycemic parameters and CGC, GRI, and COGI scores, as well as predictors of these optimal measures. Results: The cohort included 93 children, 43% girls, with a median age of 15.1 years (interquartile range [IQR] 12.9,17.0). A longitudinal analysis adjusted for age and socioeconomic index yielded a significant improvement in glycemic control for the entire cohort (ptime < 0.001) after the transition to 780G. The mean hemoglobin A1c (HbA1c) (SE) was 8.65% (0.12) at baseline and dropped by >1% after 1 year to 7.54% (0.14) (ptime < 0.001). Optimal glycemic control measures improved at 12 months post 780G; CGC improved by 5.6-fold (P < 0.001) and was attained by 24% of the participants, the GRI score improved by 10-fold (P = 0.009) and was achieved by 10% of them, and the COGI improved by 7.6-fold (P < 0.001) and was attained by 20% of them. Lower baseline HbA1c levels and increased adherence to Advanced Hybrid Closed-Loop (AHCL) usage were predictors of achieving optimal glycemic control. Conclusions: The AHCL 780G system enhances glycemic control in children and adolescents with T1D, demonstrating improvements in HbA1c and CGM metrics, albeit most participants did not achieve optimal glycemic control. This highlights yet ongoing challenges in diabetes management, emphasizing the need for continued proactive efforts on the part of health care professionals, youth, and caregivers.

Use of Technology in the Management and Treatment of Prediabetes, A New Era: A Case Report Series

Introduction: The escalating prevalence of prediabetes has positioned it as a silent precursor to a looming public health crisis, particularly as it paves the way for type 2 diabetes mellitus (T2DM). This case series report explores the transformative role of technology, specifically the Sugar Fit’s Diabetes Reversal and Management Program (SDRMP), in the treatment and management of prediabetic patients. Methods: The case series follows the progress of two patients aged 31-44 with prediabetes utilizing the SDRMP to prevent the progression to diabetes. The interventions for both patients involved continuous glucose monitoring, personalized nutrition plans, fitness strategies, and behavioral modifications. The patients also engaged in regular communication with their life coaches through the Sugar Fit application, ensuring ongoing support and adherence to the program. Results: The results revealed significant improvements in glycemic control, lipid profiles, and overall well-being. The first patient, a 44-year-old male, demonstrated a successful return to normal glycemic control in 177 days through a comprehensive approach involving dietary changes, exercise, and lifestyle modifications. The second patient, a 31-year-old male, achieved normal glycemic control in a comparable timeframe, showcasing the effectiveness of the SDRMP. Discussion and Conclusion: These cases demonstrate that patients were able to adhere to the goals of care, preventing the progression of prediabetes to diabetes and improving insulin resistance. The study also underscores the potential impact of technology on public health outcomes, bridging the gap between traditional interventions and the evolving needs of a tech-savvy population. The synergy between healthcare expertise and technological innovation not only arrests the progression of prediabetes but also contributes to a broader societal shift towards metabolic well-being, paving the way for a healthier future. Future monitoring is essential to ensure the maintenance of lifestyle modifications and continued success in preventing diabetes.

Effectiveness and Safety of GLP-1 Receptor Agonists in Patients with Type 1 Diabetes.

Background: GLP-1 receptor agonists (GLP-1RA) are used in the management of type II diabetes mellitus or obesity, although its role in patients with type I diabetes mellitus (T1DM) has been debated. This study aimed to investigate the efficacy and safety of GLP-1RA in patients with T1DM using real-world data. Methods: This multicenter, retrospective study was conducted at three tertiary medical centers in Riyadh, Saudi Arabia. The study followed up patients (>16 years old) with T1DM treated with insulin followed by GLP-1RA add-on therapy. The efficacy outcomes included changes in HbA1c, body weight, and insulin requirements from baseline to each follow-up visit. The main safety outcomes assessed included hypoglycemic events and gastrointestinal (GI) adverse events. Results: The study included 144 patients with a mean age of 33.0 ± 10.1 years. Semaglutide was the most used GLP-1RA (63.9%) followed by liraglutide (34.0%). From baseline to 3-month follow-up, HbA1c (mean difference (MD) = -0.8%; p = 0.0053), weight (MD = -2.4 kg; p = 0.0253), and daily basal insulin dose (MD = -2.1 units; p = 0.0349) were significantly reduced. Likewise, HbA1c (MD = -0.5%; p = 0.0004), weight (MD = -3.6 kg; p < 0.0001), and daily basal insulin (MD = -2.4 units; p = 0.0282) were significantly reduced at the 4-6-month follow-up. The significant reductions in HbA1c, weight, and daily basal insulin levels were consistent for up to 18-month follow-up. Only one patient had a major hypoglycemic event, whereas 8.3% of the patients had GI adverse events. Conclusions: Overall, significant improvements in glycemic control, weight loss, and insulin requirements were observed with the use of GLP-1RA in patients with T1DM, with a limited number of GI adverse events.

Twelve-Month Real-World Use of an Advanced Hybrid Closed-Loop System Versus Previous Therapy in a Dutch Center For Specialized Type 1 Diabetes Care.

Complexity of glucose regulation in persons with type 1 diabetes (PWDs) necessitates increased automation of insulin delivery (AID). This study aimed to analyze real-world data over 12 months from PWDs who started using the MiniMed 780G (MM780G) advanced hybrid closed-loop (aHCL) AID system at the Diabeter clinic, focusing on glucometrics and clinical outcomes. Persons with type 1 diabetes switching to the MM780G system were included. Clinical data (e.g. HbA1c, previous modality) was collected from Diabeter's electronic health records and glucometrics (time in range [TIR], time in tight range [TITR], time above range [TAR], time below range [TBR], glucose management indicator [GMI]) from CareLink Personal for a 12-month post-initiation period of the MM780G system. Outcomes were age-stratified, and the MM780G system was compared with previous use of older systems (MM640G and MM670G). Longitudinal changes in glucometrics were also evaluated. A total of 481 PWDs were included, with 219 having prior pump/sensor system data and 334 having monthly longitudinal data. After MM780G initiation, HbA1c decreased from 7.6 to 7.1% (P < .0001) and the percentage of PWDs with HbA1c <7% increased from 30% to 50%. Glucose management indicator and TIR remained stable with mean GMI of 6.9% and TIR >70% over 12 months. Age-stratified analysis showed consistent improvements of glycemic control across all age groups, with older participants achieving better outcomes. Participants using recommended system settings achieved better glycemic outcomes, reaching TIR up to 77% and TTIR up to 55%. Use of MM780G system results in significant and sustained glycemic improvements, consistent across age groups and irrespective of previous treatment modalities.

Exploring the Cardiorenal Benefits of SGLT2i: A Comprehensive Review

The history of sodium-glucose cotransporter 2 inhibitors (SGLT2i) is so long and started in 1835 when Petersen extracted a compound called phlorizin from apple tree bark. About fifty years later, von Mering discovered its glucosuric properties. In the 1980s, it was discovered that the glucosuria resulted from inhibition by phlorizin of glucose reabsorption by the renal tubules, which lowered blood glucose levels in diabetic rats. Nowadays, beyond their glucose-lowering effects, growing evidence suggests significant cardiorenal benefits associated with SGLT2i therapy. Indeed, several clinical trials, including landmark studies such as EMPA-REG OUTCOME, CANVAS Program, and DECLARE-TIMI 58, have demonstrated robust reductions in cardiovascular events, particularly heart failure hospitalizations and cardiovascular mortality, among patients treated with SGLT2i. However, subsequent trials showed that SGLT2i benefits extend beyond the diabetic population, encompassing individuals with and without diabetes. Additionally, SGLT2i exhibit nephroprotective effects, manifesting as a slowing of the progression of chronic kidney disease and a reduction in the risk of end-stage kidney disease. The mechanisms underlying the cardiorenal benefits of SGLT2i are multifactorial and include improvements in glycemic control, reduction in arterial stiffness, modulation of inflammation and oxidative stress, reduction of intraglomerular pression and promotion of natriuresis and diuresis through inhibition of SGLT2 in the luminal brush border of the first segments of the proximal kidney tubule. This narrative review aims to explore the cardiorenal outcomes of SGLT2i, encompassing their mechanisms of action, clinical evidence, safety profile, and implications for clinical practice.