Baseline HbA1c Research Articles

Factors contributing to the clinical effectiveness of imeglimin monotherapy in Japanese patients with type 2 diabetes mellitus.

To investigate the effect of patient characteristics on imeglimin effectiveness in Japanese patients with type 2 diabetes mellitus. Data were pooled from two randomized, placebo-controlled, 24-week, double-blind studies of imeglimin monotherapy in Japanese adults with type 2 diabetes mellitus, with the proportion of responders (glycated hemoglobin [HbA1c] < 7.0%) and sustained responders (i.e., achieved and maintained response) in the imeglimin 1,000 mg twice daily group calculated at each visit. Patient factors significantly (P < 0.05) correlated with response were explored through multivariate logistic regression. Subgroup analyses compared the efficacy of imeglimin in patients with a HbA1c improvement less than or equal to -0.3% (early responders) versus greater than -0.3% (early non-responders) at week 4. A total of 38.0% of imeglimin-treated patients and 7.2% of placebo-treated patients were responders (P < 0.001, number needed to treat = 4). The proportion of sustained responders at weeks 4, 8, 12, 16 and 20 was 10.6, 19.0, 24.0, 25.7 and 29.1%, respectively (>70% of responders at each visit). Improvements in HbA1c and fasting glucose were significantly greater in early responders versus early non-responders from week 4; between-group differences remained significant to week 24. Older age (odds ratio 1.09, 95% confidence interval 1.04-1.14; P < 0.001); treatment-naïve status vs previous treatment (odds ratio 3.70, 95% confidence interval 1.55-8.82; P = 0.003), and lower baseline HbA1c (odds ratio 0.06, 95% confidence interval 0.02-0.16; P < 0.001) predicted response. A significantly higher proportion of patients receiving imeglimin 1,000 mg twice daily monotherapy were responders versus placebo. Most (>70%) were sustained responders, suggesting that response is fairly predictable. Older age, treatment-naïve status and early treatment response significantly predicted imeglimin effectiveness.

Oral Semaglutide in Routine Clinical Practice: Characteristics of People with Type 2 Diabetes Started on the Drug and Changes in Their Clinical Parameters after 24 Weeks of Treatment.

Background/Objectives: Semaglutide is the unique once-daily oral glucagon-like receptor agonist presently available. Aims of this study were to describe clinical characteristics of patients with type 2 diabetes (T2D) initiating oral semaglutide, to assess its effects on glycemic control, body weight (BW) and its tolerability in routine clinical practice. Methods: Electronic medical records from two Italian diabetes clinics were evaluated. Mean glycated hemoglobin (HbA1c) and BW were assessed in adults with T2D before and 6 months after oral semaglutide prescription. Treatment discontinuation and safety data were reported. Results: A total of 192 patients initiating oral semaglutide (44% female) presented a mean age of 66 years, a diabetes duration of 10 years, HbA1c of 7.9% and a BW of 82.6 kg. Almost 50% of patients were obese. Mean HbA1c and BW changes from baseline to follow up were -0.7% and -2.6 kg, respectively. Greater HbA1c reduction was observed in patients with baseline HbA1c ≥ 8% and with diabetes duration <5 years. The composite endpoint of HbA1c ≤7% and a weight loss ≥5% was achieved in 22.5% of the participants. A total of 40 patients (20.8%) discontinued treatment: 26 because of gastrointestinal adverse events, and 10 due to limited effectiveness in lowering HbA1c and/or BW. Conclusions: In a real clinical setting, patients initiating oral semaglutide showed suboptimal metabolic control, short diabetes duration and obesity; a significant improvement in HbA1c and BW was achieved mainly in patients with a more recent diabetes diagnosis, supporting the use of oral semaglutide in the early phase of the disease.

#2293 Cardiac autonomic neuropathy: an independent risk factor for renal decline in diabetic kidney disease

Abstract Background and Aims Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) and end stage kidney disease (ESKD) in the UK and worldwide. Due to its unpredictability and incurable nature, novel risk factors associated with incidence and progression of DKD need to be identified. One such factor is cardiac autonomic neuropathy (CAN). Many studies over last 30 years had demonstrated a significant relationship between CAN and incidence and progression of DKD using estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR) as end points. However, no prospective studies have looked into relationship between CAN diagnosed by gold standard cardiac autonomic reflex tests (CARTs) and DKD with different prognostic risks as per KDIGO classification. The aim of the study is to examine this relationship further. Method Data from 91 participants (type 1 and type 2 DM) with eGFR &amp;gt;30 ml/min/1.73 m2 who underwent assessment for CAN using CARTs as per O'Brien's and Ewing's criteria during baseline visits performed between 2007 and 2010 were collected. Additional participants (n = 113) were also recruited in 2021 as part of iBEAt study which is an EU-funded, multi-centre renal imaging study to identify novel biomarkers for DKD. Data analysis for 204 participants in total was performed for this study. CAN was defined as 2 or more abnormal CARTs out of 5 (Table 1). The level of prognostic risk was calculated based on eGFR (G1-G5) and UACR (A1-A3), following KDIGO risk table from 2012 CKD guidelines. eGFR was calculated by chronic kidney disease epidemiology collaboration (CKD-EPI) equation and UACR was assessed by early morning urine sample. Participants were categorised as follow: low risk, moderate risk and high risk. Due to limited numbers of participants with G3 in eGFR, we have combined ‘high risk’ and ‘very high risk’ into one group. CAN was divided into 2 groups—with and without CAN. Differences in proportions were examined using chi-square test. The association between baseline CAN and risk of renal decline was assessed using multinominal logistic regression adjusted for baseline age, HbA1c, ACEi/ARBs use, retinopathy status, total cholesterol and triglyceride. If significant differences were found, individual groups were compared by Bonferroni post hoc test. All analyses were performed in SPSS (version 29.0) and correlations were considered significant if p &amp;lt; 0.05. Results We analysed data of 204 participants (130 T1DM, 74 T2DM), 44.6% (n = 91) of them were women, mean (SD) age at baseline visit was 51 (15.7) years, eGFR 82.6 (13) ml/min/1.73 m2, UACR 5.2 (21.8) mg/mmol, duration of diabetes at baseline 19.7 (12.3) years and 36.8% had hypertension. Baseline eGFR and UACR were available for 198 and 193 participants respectively. Of these, 42.9% (85/198) had G1, 47.5 (94/198) had G2 and 9.6 (19/198) had G3. For UACR, 80.8% (156/193) had A1, 15.5% (30/193) had A2 and 3.6% (7/193) had A3. 53.4% (103/204) of participants had CAN and 46.6% (101/204) had no CAN. A higher proportion of participants was in low prognostic risk category 77.8% (154/198), followed by 13.1% (26/198) with moderate risk and 9.8% (18/198) with high risk for CKD progression. The risk of DKD progression was significantly associated with presence of CAN in multinominal logistic regression analysis (p = 0.020). The presence of CAN was closely related to low risk (95% CI: 1.44 to 22.04, p = 0.013) and moderately increased risk (95% CI: 1.03 to 24.7, p = 0.04). The participants with moderate and high risk had lower eGFR (p &amp;lt; 0.001) and higher UACR with increased risk (p &amp;lt; 0.001) (Table 2). This finding was independent of baseline age, HbA1C, retinopathy, ACEI/ARB use, type of diabetes, cholesterol and triglyceride levels at baseline as measured by logistic regression. Conclusion To our knowledge, this is one of the first studies to examine the relationship between presence of CAN in three stages of prognostic risk in DKD. We demonstrated that presence of CAN was an independent risk factor for decline in renal function in DKD. Further large prospective studies are required to confirm the findings of this study and examine the underlying mechanisms how CAN leads to greater risk of DKD.

Intervention to promote adolescents’ communication and engagement in diabetes clinic encounters: A pilot randomized controlled trial

AimTo conduct a pilot randomized trial of an intervention to improve adolescent question-asking and provider education during paediatric diabetes visits. MethodsAdolescents aged 11 to 17 with type 1 diabetes and their parents were enrolled from two urban tertiary paediatric clinics. Adolescents were randomised to the intervention group or control group. Adolescent consultations were audio-recorded, their HbA1c level was recorded, and they completed surveys after three clinic appointments. The intervention group completed a question prompt list and watched a video on a tablet with their parents before meeting their doctor and completed a short evaluation after each visit. ResultsSix consultant endocrinologists and ninety-nine adolescents and their parents participated. The intervention increased adolescents’ question asking and provider education in diabetes encounters. Total patient question-asking across the 3 consultations and a higher baseline HbA1c at time one was significantly associated with HbA1c at time three. ConclusionsQuestion prompt lists and an educational video are useful tools to increase adolescents’ question-asking and communication between adolescents and their providers. Practice implicationsInterventions that encourage adolescents’ question-asking in healthcare encounters may lead to more meaningful providers-adolescents’ communication and tailored education. Interventions to improve professionals’ listening, communication and educational skills are also required.

Abstract PO4-12-12: An Updated analysis of risk factor identification and Hyperglycemia prevention with alpelisib + fulvestrant in PIKC3A-mutated, hormone-receptor positive, human epidermal growth factor-2 negative advanced breast cancer

Abstract Background: SOLAR-1 investigated use of alpelisib (ALP) + fulvestrant (FLV) in patients (pts) with hormone-receptor positive (HR+)/human epidermal growth factor-2 negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC) after progression on endocrine-based therapy and demonstrated a clinically significant increase in all-grade (G) and G3-4 hyperglycemia (HG) compared to placebo + FLV. Current guidance recommends an insulin sensitizer (metformin, thiazolidinedione, SGLT2i) at HG onset. Given high rates of HG, a preventative protocol and identification (ID) of associated risk factors (RFs) was implemented to minimize HG, dose reductions and discontinuation. Although METALLICA investigated the implementation of metformin for hyperglycemia prophylaxis, there is limited data for alpelisib use and hyperglycemia prevention in high risk or controlled type 2 diabetic patients. Duke Breast Oncology Clinic (DBOC) implemented a preventive strategy to minimize HG and treatment disruptions in patients receiving alpelisib, including pre-diabetic and controlled-diabetic patients. Methods: This single-center, retrospective study included pts receiving at least one 28-day cycle of ALP+FLV between June 2019 and April 2023. One week prior to ALP initiation, pts initiated an insulin-sensitizer. Pts had fasting plasma glucose (FPG) levels drawn on day 8, 15, 28, and monthly while on ALP. The primary outcome was incidence of G2-4 HG. Descriptive statistics were used to summarize results. Number of RFs for HG (age ≥ 65 years, BMI ≥ 25 kg/m2, baseline FPG ≥ 100 mg/dL, and A1c ≥ 5.7%) were compared between pts with and without HG using Wilcoxon rank-sum test. Results A total of 30 pts (29 females; 1 male) were included with a median age of 60 years. The cohort was 70% White, 23% Black, while 67% were overweight/obese, and 50% had a history of type 2 diabetes mellitus (T2DM), gestational diabetes, or pre-diabetes. 29 pts received a CDK4/6 inhibitor prior to starting ALP. By day 28, 13 pts (43%) had G2-4 HG, with only 4 (13%) having G3 HG and zero having grade 4. Pts with G2-4 HG had a median of 2 RFs compared to only 1 RF if no HG. 8 pts (27%) required a temporary hold of ALP and 5 pts (17%) required a dose reduction in ALP due to HG. 25 pts permanently discontinued ALP; 14 due to disease progression and 8 due to an adverse event with only 3 due to HG. Median duration of ALP was 86 days (range 24-442), with 5 pts continuing to receive ALP at time of analysis. Patients with grade 2-4 HG by day 28 after ALP initiation had an older median age (66 years), higher BMI (median 28.1 kg/m2), higher baseline FPG (median 100 mg/dL), and higher baseline HbA1c (median 5.6%) compared to those without grade 2-4 HG (Table). Conclusions: Implementation of a HG prevention protocol with ALP in the real-world setting demonstrated fewer G3-4 HG events compared to that seen in SOLAR-1 (13% vs 36.6%) but slightly higher than METALLICA (6%) although we included a higher risk patient population. An increase in HG-associated RFs correlated with a higher incidence of G2-4 HG. Early risk identification and optimization of prophylactic antihyperglycemics can reduce ALP dose reductions and discontinuations secondary to HG. ALP use in higher-risk patients can be considered with a HG prevention protocol. Table 1. Hyperglycemia outcomes Citation Format: Heather Moore, Sarah Burnette, Emily Poehlein, Hui-Jie Lee, Kelly Westbrook, Thomas Bagwell, Kervin Novido, Susan Dent. An Updated analysis of risk factor identification and Hyperglycemia prevention with alpelisib + fulvestrant in PIKC3A-mutated, hormone-receptor positive, human epidermal growth factor-2 negative advanced breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-12.

A randomized controlled trial of an app-based intervention on physical activity and glycemic control in people with type 2 diabetes.

We investigated the effects of a physical activity encouragement intervention based on a smartphone personal health record (PHR) application (app) on step count increases, glycemic control, and body weight in patients with type 2 diabetes (T2D). In this 12-week,single-center, randomized controlled, 12-week extension study, patients with T2D who were overweight or obese were randomized using ratio 1:2 to a group using a smartphone PHR app (control group) or group using the app and received individualized motivational text messages (intervention group) for 12weeks. During the extension period, the sending of the encouraging text messages to the intervention group was discontinued. The primary outcome was a change in daily step count after 12weeks and analyzed by independent t-test. The secondary outcomes included HbA1c, fasting glucose, and body weight analyzed by paired or independent t-test. Of 200 participants, 62 (93.9%) and 118 (88.1%) in the control and intervention group, respectively, completed the 12-week main study. The change in daily step count from baseline to week 12 was not significantly different between the two groups (P = 0.365). Among participants with baseline step counts < 7,500 steps per day, the change in the mean daily step count at week 12 in the intervention group (1,319 ± 3,020) was significantly larger than that in control group (-139 ± 2,309) (P = 0.009). At week 12, HbA1c in the intervention group (6.7 ± 0.5%) was significantly lower than that in control group (6.9 ± 0.6%, P = 0.041) and at week 24, changes in HbA1c from baseline were significant in both groups but, comparable between groups. Decrease in HbA1c from baseline to week 12 of intervention group was greater in participants with baseline HbA1c ≥ 7.5% (-0.81 ± 0.84%) compared with those with baseline HbA1c < 7.5% (-0.22 ± 0.39%) (P for interaction = 0.014). A significant reduction in body weight from baseline to week 24 was observed in both groups without significant between-group differences (P = 0.370). App-based individualized motivational intervention for physical activity did not increase daily step count from baseline to week 12, and the changes in HbA1c levels from baseline to week 12 were comparable. ClinicalTrials.gov (NCT03407222).

Switching to Tirzepatide 5 mg From Glucagon-Like Peptide-1 Receptor Agonists: Clinical Expectations in the First 12 Weeks of Treatment

ObjectiveThis prospective study aimed to describe the clinical course in terms of glycemic outcomes, body weight, and adverse events during the first 12 weeks following a switch from glucagon-like peptide-1 receptor agonists (GLP-1 RAs) directly to tirzepatide 5 mg. MethodsParticipants were ≥18 years with type 2 diabetes (T2D), glycated hemoglobin (HbA1c) ≥6.5% to ≤9.0%, body mass index ≥25 kg/m2 and were on a stable treatment dose of GLP-1 RAs (liraglutide every day [1.2, 1.8 mg], semaglutide once-weekly [0.5, 1.0, 2.0 mg], or dulaglutide once-weekly [0.75, 1.5, 3.0, and 4.5 mg]) for ≥3 months at baseline. The primary end point was HbA1c change from baseline at week 12. Secondary end points included change from baseline in fasting serum glucose, body weight, and glucose assessed by continuous glucose monitoring. Safety was also assessed. ResultsParticipants were 58.3 years on average, with baseline HbA1c 7.39%, body mass index 35.18 kg/m2, T2D duration around 12.4 years, and included 55% females. Semaglutide (55%) and dulaglutide (42%) were the most commonly used GLP-1 RAs at baseline with semaglutide 1.0 mg and dulaglutide 1.5 mg being the most common treatment doses. At week 12, mean HbA1c changed from baseline by −0.43%, fasting serum glucose by −7.83 mg/dL, and body weight by −2.15 kg (all P < .01). Glycemic outcomes and body weight improved in participants in all baseline GLP-1 RA subgroups. Twenty participants (13.2%) developed gastrointestinal events. Three (2%) participants discontinued tirzepatide due to adverse events. There were no severe hypoglycemic events or deaths. ConclusionIn this prospective study, when people with T2D on stable GLP-1 RA treatment were switched directly to tirzepatide 5 mg, they experienced improved glycemic outcomes and additional weight reduction with an acceptable risk of adverse gastrointestinal events over 12 weeks.

Comparing advanced hybrid closed loop therapy and standard insulin therapy in pregnant women with type 1 diabetes (CRISTAL): a parallel-group, open-label, randomised controlled trial

Advanced hybrid closed loop (AHCL) therapy can improve glycaemic control in pregnant women with type 1 diabetes. However, data are needed on the efficacy and safety of AHCL systems as these systems, such as the MiniMed 780G, are not currently approved for use in pregnant women. We aimed to investigate whether the MiniMed 780G can improve glycaemic control with less hypoglycaemia in pregnant women with type 1 diabetes. CRISTAL was a double-arm, parallel-group, open-label, randomised controlled trial conducted in secondary and tertiary care specialist endocrinology centres at 12 hospitals (11 in Belgium and one in the Netherlands). Pregnant women aged 18-45 years with type 1 diabetes were randomly assigned (1:1) to AHCL therapy (MiniMed 780G) or standard insulin therapy (standard of care) at a median of 10·1 (IQR 8·6-11·6) weeks of gestation. Randomisation was done centrally with minimisation dependent on baseline HbA1c, insulin administration method, and centre. Participants and study teams were not masked to group allocation. The primary outcome was proportion of time spent in the pregnancy-specific target glucose range (3·5-7·8 mmol/L), measured by continuous glucose monitoring (CGM) at 14-17 weeks, 20-23 weeks, 26-29 weeks, and 33-36 weeks. Key secondary outcomes were overnight time in target range, and time below glucose range (<3·5 mmol/L) overall and overnight. Analyses were conducted on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov (NCT04520971). Between Jan 15, 2021 and Sept 30, 2022, 101 participants were screened, and 95 were randomly assigned to AHCL therapy (n=46) or standard insulin therapy (n=49). 43 patients assigned to AHCL therapy and 46 assigned to standard insulin therapy completed the study. At baseline, 91 (95·8%) participants used insulin pumps, and the mean HbA1c was 6·5% (SD 0·6). The mean proportion of time spent in the target range (averaged over four time periods) was 66·5% (SD 10·0) in the AHCL therapy group compared with 63·2% (12·4) in the standard insulin therapy group (adjusted mean difference 1·88 percentage points [95% CI -0·82 to 4·58], p=0·17). Overnight time in the target range was higher (adjusted mean difference 6·58 percentage points [95% CI 2·31 to 10·85], p=0·0026), and time below range overall (adjusted mean difference -1·34 percentage points [95% CI, -2·19 to -0·49], p=0·0020) and overnight (adjusted mean difference -1·86 percentage points [95% CI -2·90 to -0·81], p=0·0005) were lower with AHCL therapy than with standard insulin therapy. Participants assigned to AHCL therapy reported higher treatment satisfaction. No unanticipated safety events occurred with AHCL therapy. In pregnant women starting with tighter glycaemic control, AHCL therapy did not improve overall time in target range but improved overnight time in target range, reduced time below range, and improved treatment satisfaction. These data suggest that the MiniMed 780G can be safely used in pregnancy and provides some additional benefits compared with standard insulin therapy; however, it will be important to refine the algorithm to better align with pregnancy requirements. Diabetes Liga Research Fund and Medtronic.

Effect of hemoglobin A1c change on 24-month clinical outcomes in patients with diabetes after acute myocardial infarction.

The average glycated hemoglobin (HbA1c) may not accurately reflect glycemic control status during the mid-term after acute myocardial infarction (AMI). We aimed to evaluate changes in HbA1c and their effect on mid-term clinical outcomes in patients with diabetes and AMI. We enrolled patients with diabetes ( n = 967) who underwent HbA1c measurement in the Korean nationwide registry. These patients were categorized into three groups based on changes in HbA1c from index admission to the 1-year follow-up visit: a decrease in HbA1c > 1%, changes in HbA1c within 1%, and an increase in HbA1c > 1%. Clinical outcomes at 24 months were examined. The baseline HbA1c levels were 8.55 ± 0.85, 7.00 ± 0.98 and 7.07 ± 1.05 ( P = 0.001) and HbA1c levels after 1 year were 6.62 ± 0.73, 7.05 ± 0.98 and 9.26 ± 1.59 ( P = 0.001) for patients with 3 groups, respectively. Patients with a 1% decrease in HbA1c had significantly lower incidence of major adverse cardiovascular events (MACE), cardiac death, and rehospitalization after 24 months than those with a 1% increase in HbA1c. However, in the Cox regression analysis, a >1% decrease in HbA1c change was not an independent factor for MACE, cardiac death, and rehospitalization. Our analysis indicates that an HbA1c decrease of >1% within the first 12 months was not an independent prognostic factor until the 24-month mark. Therefore, standard diabetic control is recommended for patients with diabetes and AMI for up to 2 years.

De-Intensification from Basal-Bolus Insulin Therapy to Liraglutide in Type 2 Diabetes: Predictive Value of Mean Glycaemia during Fasting Test.

Successful conversion from insulin therapy to glucagon-like peptide 1 receptor agonist (GLP-1RA) with basal insulin in well-controlled patients has already been demonstrated. However, the data concerning individuals with poor glycaemic control are scarce. The aim of this work was to assess the success rate of insulin therapy to liraglutide transition in poorly controlled diabetes in a real-world clinical setting and to define predictors of success. We are the first to present the method of a fasting test as a way to identify the patients at higher risk of failure after treatment de-intensification. The retrospective observational study analyzed data of 62 poorly controlled obese diabetic patients on high-dose insulin therapy, who were subjected to a 72 h fasting test during hospitalization and subsequently switched to liraglutide ± basal insulin therapy. During the fasting, all antidiabetic treatment was discontinued. Patients were classified as responders if they remained on GLP-1RA treatment after 12 months. Non-responders restarted the basal-bolus insulin (BBI) regimen. Development of glycated hemoglobin (HbA1c) and body weight in both groups, alongside with parameters associated with the higher risk of return to the BBI regimen, were analyzed. A total of 71% of patients were switched successfully (=responders). Responders had more significant improvement in HbA1c (-6.4 ± 19.7 vs. -3.4 ± 22.9 mmol/mol) and weight loss (-4.6 ± 7.1 vs. -2.5 ± 4.0). Statistically significant difference between groups was found in initial HbA1c (75.6 ± 17.9 vs. 90.5 ± 23.6; p = 0.04), total daily dose of insulin (67.6 ± 36.4 vs. 90.8 ± 32.4; p = 0.02), and mean glycaemia during the fasting test (6.9 ± 1.7 vs. 8.6 ± 2.2 mmol/L; p < 0.01). This study confirms that therapy de-intensification in poorly controlled patients with a BBI regimen is possible. Higher baseline HbA1c, total daily insulin dose, and mean glucose during fasting test are negative predictive factors of successful therapy de-escalation.

The psychosocial outcomes of advanced hybrid closed-loop system in children and adolescents with type 1 diabetes

The study was carried out to determine the psychosocial outcomes of advanced hybrid closed-loop (AHCL) systems in children and adolescents with type 1 diabetes (T1D). Single-center and cohort study with a duration 6 months consisted of 60 children and adolescents with T1D. Standard clinical procedures, including both glycemic indicators, e.g., sensor-measured time within the 70–180 mg/dL range and glycated hemoglobin (HbA1c) levels, and psychosocial metrics were used for data collection. The psychosocial metrics included the Pediatric Quality of Life Inventory (PedsQL) 3.0 Diabetes Module for both children (8–12 years) and parents; the Quality of Life for Youth scale for adolescents (13–18 years); the Strengths and Difficulties Questionnaire (SDQ); the Hypoglycemia Fear Survey for Children (HFS-C); the Revised Child Anxiety and Depression Scale (R-CADS); and AHCLS-specific DTSEQ satisfaction and expectation survey. These metrics were evaluated at the baseline and after 6 months of AHCL use. Of the 60 children and adolescents with T1D for whom the AHCL system was utilized, 41 of them, 23 female and 18 male, completed the surveys. The mean age of the 41 children and adolescents was 12.5 ± 3.2 (min. 6.7, max. 18) years. The time spent within the target glycemic range, i.e., time-in-range (TIR), improved from 76.9 ± 9% at the baseline to 80.4 ± 5% after 6 months of AHCL system use (p = 0.03). Additionally, HbA1c levels reduced from 7.1% ± 0.7% at the baseline to 6.8% ± 0.8% after 6 months of AHCL system use (p = 0.03). The most notable decline in HbA1c was observed in participants with higher baseline HbA1c levels. All patients’ HFS-C and AHCL system-specific DTSEQ satisfaction and expectation survey scores were within the normal range at the baseline and remained unchanged during the follow-up period. No significant difference was found in the R-CADS scores of children and adolescents between baseline and after 6 months of AHCL system use. However, there was a significant decrease in the R-CADS scores of the parents. Patients’ PedsQL scores were high both at the baseline and after 6 months. The SDQ scores were high at baseline, and there was no significant improvement at the end of 6 months. Conclusion: This is the first study to investigate in detail the psychosocial outcomes of AHCL system use in T1D patients and their parents. Although state-of-the-art technologies such as AHCL provide patients with more flexibility in their daily lives and information about glucose fluctuations, the AHCL resulted in a TIR above the recommended target range without a change in QOL, HFS-C, SDQ, and R-CADS scores. The scores obtained from the R-CADS conducted by the parents of the children indicated that the use of pumps caused a psychological improvement in the long term, with a significant decrease in the R-CADS scores of the children and adolescents with T1D.What is Known:• Previous studies focused on clinical outcomes of AHCL systems in pediatric T1D patients, showing glycemic control improvements.• Limited attention given to psychosocial outcomes of AHCL systems in children and adolescents with T1D.• Crucial psychosocial factors like quality of life, emotional well-being, and fear of hypoglycemia underexplored in AHCL system context.What is New:• First study to comprehensively examine psychosocial outcomes of AHCL systems in pediatric T1D patients.• Study's robust methodology sets new standard for diabetes technology research and its impact on qualiy of life.

Effects of a diverse prebiotic fibre supplement on HbA1c, insulin sensitivity and inflammatory biomarkers in pre-diabetes: a pilot placebo-controlled randomised clinical trial.

Prebiotic fibre represents a promising and efficacious treatment to manage pre-diabetes, acting via complementary pathways involving the gut microbiome and viscosity-related properties. In this study, we evaluated the effect of using a diverse prebiotic fibre supplement on glycaemic, lipid and inflammatory biomarkers in patients with pre-diabetes. Sixty-six patients diagnosed with pre-diabetes (yet not receiving glucose-lowering medications) were randomised into treatment (thirty-three) and placebo (thirty-three) interventions. Participants in the treatment arm consumed 20 g/d of a diverse prebiotic fibre supplement, and participants in the placebo arm consumed 2 g/d of cellulose for 24 weeks. A total of fifty-one and forty-eight participants completed the week 16 and week 24 visits, respectively. The intervention was well tolerated, with a high average adherence rate across groups. Our results extend upon previous work, showing a significant change in glycated haemoglobin (HbA1c) in the treatment group but only in participants with lower baseline HbA1c levels (< 6 % HbA1c) (P = 0·05; treatment -0·17 ± 0·27 v. placebo 0·07 ± 0·29, mean ± sd). Within the whole cohort, we showed significant improvements in insulin sensitivity (P = 0·03; treatment 1·62 ± 5·79 v. placebo -0·77 ± 2·11) and C-reactive protein (P FWE = 0·03; treatment -2·02 ± 6·42 v. placebo 0·94 ± 2·28) in the treatment group compared with the placebo. Together, our results support the use of a diverse prebiotic fibre supplement for physiologically relevant biomarkers in pre-diabetes.

Real-World Effectiveness of the Gla-300 + Cap + App Program in Adult Users Living with Type2 Diabetes in Taiwan.

Health2Sync (H2S) is a digital health technology platform that provides coaching and titration support to patients with diabetes. The Mallya cap converts a conventional insulin pen into a smart connected device that can automatically synchronize dose values and associated timestamps (upon injection) to the H2S platform. This single-arm real-world study evaluated the effectiveness of insulin glargine 300U/mL (Gla-300) combined with H2S and Mallya cap (Gla-300 + Cap + App program) on clinical outcomes among users with type 2 diabetes (T2D) in Taiwan. Adults (aged ≥ 20years) with T2D who were registered H2S users and initiated Mallya cap for a new/existing Gla-300 regimen (identification period May1, 2021-May31, 2022) were included in this retrospective cohort study. Follow-up data from H2S were collected for 90days. Glycated hemoglobin (HbA1c) change (baseline to follow-up) and HbA1c goal attainment were primary outcomes. Hypoglycemia incidence and usage metrics of Mallya cap were secondary outcomes. Of 83 participants, 38.6% were new Gla-300 users. HbA1c was reduced in both new (- 2.4 [2.7] %, - 26.2 [29.5] mmol/mol) and previous Gla-300 users (- 0.5 [1.6] %, - 5.5 [17.5] mmol/mol). Reduction in HbA1c was significant (p < 0.05) in both groups. At follow-up, 43.4% of users had a reduction of > 0.5%. Mean HbA1c reductions increased numerically with higher baseline HbA1c and with longer duration of Mallya cap usage. Use of digital technology within a connected ecosystem such as Gla-300 + Cap + App program could help people with type2 diabetes to improve their glycemic condition.

Continuous glucose monitoring with structured education in adults with type 2 diabetes managed by multiple daily insulin injections: a multicentre randomised controlled trial.

The aim of this study was to compare the effectiveness of stand-alone intermittently scanned continuous glucose monitoring (isCGM) with or without a structured education programme and blood glucose monitoring (BGM) in adults with type 2 diabetes on multiple daily insulin injections (MDI). In this 24 week randomised open-label multicentre trial, adults with type 2 diabetes on intensive insulin therapy with HbA1c levels of 58-108 mmol/mol (7.5-12.0%) were randomly assigned in a 1:1:1 ratio to isCGM with a structured education programme on adjusting insulin dose and timing according to graphical patterns in CGM (intervention group), isCGM with conventional education (control group 1) or BGM with conventional education (control group 2). Block randomisation was conducted by an independent statistician. Due to the nature of the intervention, blinding of participants and investigators was not possible. The primary outcome was change in HbA1c from baseline at 24 weeks, assessed using ANCOVA with the baseline value as a covariate. A total of 159 individuals were randomised (n=53 for each group); 148 were included in the full analysis set, with 52 in the intervention group, 49 in control group 1 and 47 in control group 2. The mean (± SD) HbA1c level at baseline was 68.19±10.94 mmol/mol (8.39±1.00%). The least squares mean change (± SEM) from baseline HbA1c at 24 weeks was -10.96±1.35 mmol/mol (-1.00±0.12%) in the intervention group, -6.87±1.39 mmol/mol (-0.63±0.13%) in control group 1 (p=0.0367 vs intervention group) and -6.32±1.42 mmol/mol (-0.58±0.13%) in control group 2 (p=0.0193 vs intervention group). Adverse events occurred in 28.85% (15/52) of individuals in the intervention group, 26.42% (14/53) in control group 1 and 48.08% (25/52) in control group 2. Stand-alone isCGM offers a greater reduction in HbA1c in adults with type 2 diabetes on MDI when education on the interpretation of graphical patterns in CGM is provided. ClinicalTrials.gov NCT04926623. This study was supported by Daewoong Pharmaceutical Co., Ltd.

Real-world effectiveness and safety of insulin glargine 100 U/mL plus lixisenatide in adults with type 2 diabetes: An international, multicentre, 12-month, prospective observational study.

To assess the impact of insulin glargine (100 U/mL) and lixisenatide (iGlarLixi) fixed-ratio combination therapy on the overall management of glycaemia in patients with type 2 diabetes (T2D), previously inadequately controlled with oral antidiabetic drugs ± basal insulin or glucagon-like peptide-1 receptor agonists (GLP-1 RAs). This 12-month, international, multicentre, prospective, observational study included patients (age ≥ 18 years) with T2D who had initiated iGlarLixi within 1 month prior to study inclusion. Data were collected at study inclusion, month 3, month 6 and month 12 from patient diaries, self-measured plasma glucose, and questionnaires. The primary endpoint was change in HbA1c from baseline to month 6. Of the 737 eligible participants (mean age: 57.8 [standard deviation: 11.2] years; male: 49%), 685 had baseline and post-baseline HbA1c data available. The least squares mean change in HbA1c from baseline to month 6 was -1.4% (standard error [95% confidence interval (CI)]: 0.05 [-1.5, -1.3]). The absolute change from baseline at month 12 was -1.7% ± 1.9% (95% CI: -1.9, -1.5). There were 72 hypoglycaemia events reported during the study period, with a very low incidence of severe hypoglycaemia (two participants [rate: 0.003 events per patient-year]). This real-world observational study shows that initiation of iGlarLixi in people with T2D inadequately controlled on oral antidiabetic drugs ± basal insulin or GLP-1 RAs improves glycaemic control with a low incidence of hypoglycaemia.

Baseline glycated albumin level and risk of type 2 diabetes mellitus in Healthy individuals: a retrospective longitudinal observation in Korea

Glycated albumin (GA) reflects glycemic status for the past three weeks. GA level demonstrates a strong correlation with HbA1c level and is used as an adjunctive biomarker for diagnosis and monitoring of type 2 diabetes mellitus (T2DM). In this study, we validated the predictive performance of baseline GA for development of T2DM in healthy individuals in Korea. From August 2013 to September 2014, the medical records of 3,771 healthy Koreans were retrospectively reviewed. Each participant was categorized into tertiles based on initial GA level. During the follow-up period through May 2020, study participants were evaluated for T2DM using HbA1c, fasting glucose level, and a self-reported diagnosis history. Baseline GA level by tertile (T1 to T3) was 10.4 ± 0.8% (mean ± SD), 12.1 ± 0.3%, and 13.7 ± 0.9%, respectively. The median follow-up was 5.97 years, during which 4.9% (186 of 3,771) of the participants developed T2DM. After adjusting for confounding factors, the hazard ratio for the development of T2DM in the highest GA level group (T3) compared to the reference group (T1) was 2.46 (95% CI, 1.7 to 3.58, p < 0.001 for trend) with a Harrell’s C index of 0.80 (95% CI, 0.76 to 0.83). Also, within highest group of baseline HbA1c and FG levels, higher GA levels were associated with an increased HRs for T2DM. In conclusion, Our study confirms that the risk of T2DM increases with baseline GA level. Additional follow-up of the cohort is warranted to investigate the correlations between GA and other clinical indicators including diabetic complications.

Metabolic control in type 2 diabetic patients treated with empagliflozin: A case series.

Type 2 diabetes mellitus is a highly prevalent disease and is associated with increased morbidity and mortality. Due to the low percentage of adequate glycemic control, new strategies for the treatment of type 2 diabetes mellitus have been sought, including sodium-glucose cotransporter type 2 inhibitorss. To describe the evolution of patients with type 2 diabetes mellitus with insulin requirements treated with empagliflozin at the Peñaflor Hospital. The primary objective was to evaluate the efficacy of the medication regarding glycosylated hemoglobin A1c (HbA1c). The secondary objectives were: 1) achievement of HbA1c equal to or less than 7.5% according to survival analysis. 2) Change in glomerular filtration rate and urinary albumin excretion post treatment. Review of clinical records of all patients treated with empagliflozin from November 2019 to June 2023. Average follow-up of 19 (16.3 to 40) months. To compare HbA1c values according to follow-up ranges, the paired T test or Wilcoxon test was used. We included 58 patients, 15 men and 43 women (74.1%), with an average age of 58.5 ± 9.2 years, ranging from 35 to 75 years. Baseline HbA1c of 10.3 ± 1.6% and 8.98% ± 2.2 in a follow-up of 18 to 24 months post-treatment, resulted in a decrease of 1.27% (p = 0.002; confidence interval 95%: 0.5 to 2.03). The most common adverse effect was urinary tract infection. Patients with type 2 diabetes mellitus with insulin requirements treated with empagliflozin at the Peñaflor Hospital achieved better glycemic control with few adverse effects.

Sustained Effectiveness of an Advanced Hybrid Closed-Loop System in a Cohort of Children and Adolescents With Type 1 Diabetes: A 1-Year Real-World Study.

To investigate glucose metrics and identify potential predictors of the achievement of glycemic outcomes in children and adolescents during their first 12 months of MiniMed 780G use. This multicenter, longitudinal, real-world study recruited 368 children and adolescents with type 1 diabetes (T1D) starting SmartGuard technology between June 2020 and June 2022. Ambulatory glucose profile data were collected during a 15-day run-in period (baseline), 2 weeks after automatic mode activation, and every 3 months. The influence of covariates on glycemic outcomes after 1 year of MiniMed 780G use was assessed. After 15 days of automatic mode use, all glucose metrics improved compared with baseline (P < 0.001), except for time below range (P = 0.113) and coefficient of variation (P = 0.330). After 1 year, time in range (TIR) remained significantly higher than at baseline (75.3% vs. 62.8%, P < 0.001). The mean glycated hemoglobin (HbA1c) over the study duration was lower than the previous year (6.9 ± 0.6% vs. 7.4 ± 0.9%, P < 0.001). Time spent in tight range (70-140 mg/dL) was 51.1%, and the glycemia risk index was 27.6. Higher TIR levels were associated with a reduced number of automatic correction boluses (P < 0.001), fewer SmartGuard exits (P = 0.021), and longer time in automatic mode (P = 0.030). Individuals with baseline HbA1c >8% showed more relevant improvement in TIR levels (from 54.3% to 72.3%). Our study highlights the sustained effectiveness of MiniMed 780G among youth with T1D. Findings suggest that even children and adolescents with low therapeutic engagement may benefit from SmartGuard technology.

Comparison of incident hypertension between SGLT2 inhibitors vs. DPP4 inhibitors

Although several randomized clinical trials have reported the potential benefit of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in reducing blood pressure (BP), whether SGLT2i can reduce incident hypertension is unknown. We analyzed individuals with diabetes who were newly prescribed SGLT2i or dipeptidyl peptidase 4 inhibitors (DPP4i) in a large-scale epidemiological database. The primary outcome was the incidence of hypertension. A propensity score matching algorithm was employed to compare the subsequent development of hypertension between the SGLT2i and DPP4i groups. After propensity score matching, 5708 well-balanced pairs of SGLT2i and DPP4i users were identified. SGLT2i administration was associated with a reduced risk of hypertension (HR 0.91, 95% CI: 0.84–0.97). The advantage of SGLT2i use over DPP4i use for incident hypertension was generally consistent in several sensitivity analyses, and subgroup analyses showed that SGLT2i use was significantly associated with a lower risk of hypertension in men, patients with baseline HbA1c of <7.5%, and baseline systolic blood pressure ≥127 mmHg. Our investigation using nationwide real-world data demonstrated the potential advantage of SGLT2i over DPP4i in reducing the development of hypertension in individuals with diabetes.

An Obesity-Centric Approach with and Without Anti-Obesity Medications Compared to the Usual-Care Approach to Management of Patients with Obesity and Type2 Diabetes in an Employer Setting: A Pragmatic Randomized Controlled Trial (EMPOWER-T2D).

This study aimed to compare weight loss and glycated hemoglobin (HbA1c)-reduction effects of two obesity-centric, weight-loss management approaches (with or without anti-obesity medication) versus usual glucose-centric care in patients with obesity and type2 diabetes. Single-center, randomized, open-label, 3-armed, parallel-group, pragmatic, noninferiority trial, July 2020 to August 2022. Adults enrolled in the Cleveland Clinic Employee Health Plan (body mass index [BMI] ≥ 30kg/m2, type2 diabetes diagnosis, HbA1c > 7.5%) were randomized to usual glucose-centric management ("Usual-Care" group) or one of two obesity-centric management strategies: participation in a weight management program plus anti-obesity medication ("WMP + AOM" group), or WMP participation without anti-obesity medication ("WMP-Only" group). Primary endpoints were changes in weight and HbA1c, baseline to month12. Due to enrollment and retention challenges, largely related to COVID-19, only 74/300 planned participants were randomized and the study was terminated early. Participants were predominantly female (59%), median (interquartile range [IQR]) age 53.5 (47, 60) years, 68% white, with baseline median (IQR) BMI and HbA1c of 37.4 (34.2, 42.7) kg/m2 and 8.8% (7.9%, 10.4%), respectively. At month12, mean (90% confidence interval [CI]) percentage weight change in the Usual-Care, WMP-Only, and WMP + AOM groups was - 4.5% (- 6.5%, - 2.5%), - 6.7% (- 8.7%, - 4.7%), and - 8.7% (- 10.7%, - 6.8%), respectively; mean (90%CI) HbA1c change was - 1.7% (- 2.1%, - 1.2%), - 2.2% (- 2.7%, - 1.8%), and - 2.2% (- 2.6%, - 1.7%), respectively. WMP + AOM was superior to Usual-Care for weight change (P = 0.02); both WMP + AOM and WMP-Only were noninferior (P ≤ 0.01) to Usual-Care for change in HbA1c. Including anti-obesity medication was associated with superior weight loss with noninferior HbA1c reductions, warranting further evaluation in larger study populations of obesity-focused approaches to type2 diabetes management. Graphical abstract available for this article. ClinicalTrials.gov NCT03799198.