Higher Baseline HbA1c Levels Research Articles

The Supporting Emerging Adults With Diabetes (SEAD) Program: An Adult-Based Real-World Clinical Model That Improves Hospitalizations, Diabetes Technology Uptake, and Glycemic Outcomes in Underserved Young Adults With Type 1 Diabetes.

Underserved young adults (YA) with type 1 diabetes (T1D) experience the worst outcomes across the life span. We developed and integrated the Supporting Emerging Adults with Diabetes (SEAD) program into routine endocrinology care to address unmet social and medical challenges. This study was designed as a longitudinal cohort study, with prospective data collection over 4 years on YA in SEAD compared with usual endocrine care. We used propensity-weighted analysis to account for differences in baseline characteristics, and multivariate regression and Cox proportional hazard models to evaluate change in outcomes over time. Primary outcomes included incidence of hospitalizations, diabetes technology uptake, and annual change in HbA1c levels. We included 497 YA with T1D in SEAD (n = 332) and usual endocrine care (n = 165); mean age 25 years, 27% non-Hispanic Black, 46% Hispanic, 49% public insurance, mean HbA1c 9.2%. Comparing YA in SEAD versus usual care, 1) incidence of hospitalizations was reduced by 64% for baseline HbA1c >9% (HR 0.36 [0.13, 0.98]) and 74% for publicly insured (HR 0.26 [0.07, 0.90]); 2) automated insulin delivery uptake was 1.5-times higher (HR 1.51 [0.83, 2.77]); and 3) HbA1c improvement was greater (SEAD, -0.37% per year [-0.59, -0.15]; usual care, -0.26% per year [-0.58, 0.05]). SEAD meaningfully improves clinical outcomes in underserved YA with T1D, especially for publicly insured and high baseline HbA1c levels. Early intervention for at-risk YA with T1D as they enter adult care could reduce inequity in short and long-term outcomes.

Impact of HCV eradication by directly acting antivirals on glycemic indices in chronic hepatitis C patients -a nationwide Taiwan HCV registry

Background/AimsHepatitis C virus (HCV) eradication using antiviral agents augments the metabolic profile. Changes in glycated hemoglobin (HbA1c) levels in chronic hepatitis C patients who receive glecaprevir/pibrentasvir (GLE/PIB) remain elusive. MethodsData from 2417 patients treated with GLE/PIB from the Taiwan HCV Registry were analyzed, and pretreatment HbA1c levels were compared with 3-months after the-end-of treatment levels. A sustained virological response (SVR) was defined as undetectable HCV RNA at 12 weeks after the end of treatment. A significant change in HbA1c level was defined as the 75th percentile of the change in the HbA1c level before and after treatment (decrement >0.2%). ResultsSerum HbA1c levels decreased significantly (6.0 vs 5.9%, P < 0.001). Post-treatment HbA1c levels decreased in all subgroups, except in non-SVR patients (5.7 vs 5.7%, P = 0.79). Compared to patients without significant HbA1c improvement (decrement >0.2%), those with HbA1c improvement were older (60.2 vs 58.6 years, P < 0.001), had higher serum creatinine levels (1.9 vs 1.6 mg/dL, P < 0.001), triglycerides (129.8 vs 106.2 mg/dL, P < 0.001), fasting glucose (135.8 vs 104.0 mg/dL, P < 0.001), and pretreatment HbA1c (7.1 vs 5.7%, P < 0.001) and had a higher proportion of male sex (57.9% vs 50.9%, P = 0.003), diabetes (84.3 vs 16.8%, P < 0.001), more advanced stages of chronic kidney disease (CKD) (15.7 vs 11.1 %, P < 0.001), anti-diabetic medication use (47.3 vs 16.4%, P < 0.001) and fatty liver (49.6 vs 38.3 %, P < 0.001). Multivariate analysis revealed that the factors associated with significant HbA1c improvement were age (odds ratio [OR]/95% confidence intervals [CI]: 1.01/1.00–1.02, P = 0.01), HbA1c level (OR/CI: 2.83/2.48–3.24, P < 0.001) and advanced CKD stages (OR/CI: 1.16/1.05–1.28, P = 0.004). If the HbA1c variable was not considered, the factors associated with significant HbA1c improvement included alanine aminotransferase level (OR/CI, 1.002/1.000–1.004, P = 0.01), fasting glucose level (OR/CI: 1.010/1.006–1.013, P < 0.001), and diabetes (OR/CI: 3.35/2.52–4.45, P < 0.001). ConclusionsThe HbA1c levels improved shortly after HCV eradication using GLE/PIB. The improvement in glycemic control can be generalized to all subpopulations, particularly in patients with a higher baseline HbA1c level or diabetes.

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.

Effectiveness and safety of glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes: evidence from a retrospective real-world study.

Global phase III clinical trials have shown superior hypoglycemic efficacy to insulin and other oral hypoglycemic agents. However, there is a scarcity of real-world data comparing different glucagon-like peptide 1 receptor agonist (GLP-1RA) directly. This study aimed to assess the safety and effectiveness of various GLP-1RA in treating type 2 diabetes mellitus (T2DM) in a real-world clinical setting and identify predictive factors for favorable treatment outcomes. This was a retrospective, single-center, real-world study. The changes in HbA1c, fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), and the percentage of participants who achieved HbA1c of <7%, 7%-8%, and ≥ 8% after GLP-1RA treatment was analyzed. The clinical factors that affect the effectiveness of GLP-1RA were analyzed. At baseline, the 249 participants had a mean baseline HbA1c of 8.7 ± 1.1%. After at least three months of follow-up, the change in HbA1c was -0.89 ± 1.3% from baseline. Dulaglutide exerted a more significant hypoglycemic effect than immediate-release exenatide. The percentage of participants who achieved HbA1c<7% was substantial, from 6.0% at baseline to 28.9%. Average body weight decreased by 2.02 ± 3.8 kg compared to baseline. After GLP-1RA treatment, the reduction in SBP was 2.4 ± 7.1 mmHg from baseline. A shorter duration of diabetes and a higher baseline HbA1c level were more likely to achieve a good response in blood glucose reduction. This study provided real-world evidence showing that GLP-1RA significantly improved HbA1c, body weight, and SBP. The results can inform the decision-making about GLP-1RA treatment in daily clinical practice.

A randomized, double-blind, placebo controlled, phase 3 trial to evaluate the efficacy and safety of cetagliptin added to ongoing metformin therapy in patients with uncontrolled type 2 diabetes with metformin monotherapy.

This trial was designed to assess the efficacy and safety of cetagliptin added to metformin in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy. In total, 446 patients with type 2 diabetes on metformin monotherapy were randomized to receive the addition of once-daily cetagliptin 100 mg, cetagliptin 50 mg and placebo in a 2:2:1 ratio for 24-week double-blind treatment. At week 24, patients initially randomized to cetagliptin 50 mg and placebo were switched to cetagliptin 100 mg for 28 weeks open-label treatment. The primary endpoint was the change in haemoglobin A1c (HbA1c) from baseline, and the efficacy analyses were based on an all-patients-treated population using an analysis of co-variance. After 24 weeks, both add-on therapies led to greater glycaemic control. Reductions in HbA1c from baseline were -1.17 ± 0.794%, -1.23 ± 0.896% in cetagliptin 100 mg and 50 mg plus metformin group, respectively. No difference was observed between the cetagliptin 100 mg and 50 mg plus metformin group. Patients with higher baseline HbA1c levels (≥8.5%) experienced greater reductions in HbA1c. A significantly greater proportion of patients achieved an HbA1c <7.0% with cetagliptin 100 mg (49.4%) and cetagliptin 50 mg (51.1%) plus metformin than metformin monotherapy (14.4%). Both combination therapies also improved the homeostasis model assessment β-function index and decreased systolic blood pressure. There was no increased risk of adverse effects with combination therapy, and both combination therapies were generally well tolerated. The addition of cetagliptin once daily to metformin was more efficacious and well tolerated than metformin monotherapy in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy.

Real-World Effectiveness and Safety of Hydrogen Inhalation in Chinese Patients with Type 2 Diabetes: A Single-Arm, Retrospective Study.

To evaluate the real-life effectiveness and safety of Chinese patients with type 2 diabetes mellitus (T2DM) receiving hydrogen inhalation (HI) treatment as a supplementary treatment. This retrospective, multicenter, observational 6-months clinical study included T2DM patients maintaining HI, visited at 4 time points. The primary outcome is the mean change in glycated hemoglobin (HbA1c) at the end of the study compared to baseline. The secondary outcome is analyzing the mean change of fasting plasma glucose (FPG), weight, lipid profile, insulin dose and homeostasis model assessment. Linear regression and logistics regression are applied to evaluate the effect of HI after the treatment. Of the 431 patients comprised, it is observed a significant decrease in HbA1c level (9.04±0.82% at baseline to 8.30±0.99% and 8.00±0.80% at the end, p<0.001), FPG (165.6±40.2 mg/dL at baseline to 157.1±36.3mg/dL and 143.6±32.3mg/dL at the end, p<0.001), weight (74.7±7.1kg at baseline to 74.8±10.0kg and 73.6±8.1kg at the end, p<0.001), insulin dose (49.3±10.8U/d at baseline to 46.7±8.0U/d and 45.2±8.7U/d, p<0.001). The individuals in subgroup with higher baseline HbA1c and longer daily HI time duration gain greater HbA1c decrease after 6 months. Linear regression shows that higher baseline HbA1c level and shorter diabetes duration are significantly in relation to greater HbA1c reduction. Logistics regression reveals that lower weight is associated with a higher possibility of reaching HbA1c<7%. The most common adverse event is hypoglycemia. HI therapy significantly improves glycemic control, weight, insulin dose, lipid metabolism, β-cell function and insulin resistance of patients with type 2 diabetes after 6 months. Higher baseline HbA1c level and shorter diabetes duration is related to greater clinical response to HI.

Effectiveness and Tolerability of the Intensification of Canagliflozin Dose from 100 mg to 300 mg Daily in Patients with Type 2 Diabetes in Real Life: The INTENSIFY Study

Aim: This study aimed to evaluate the effectiveness and tolerability of intensifying the dose of canagliflozin from 100 mg/day (CANA100) to 300 mg/day (CANA300) in patients with type 2 diabetes (T2DM) and suboptimal metabolic control in a real-world setting. Methods: A multicenter observational study was conducted on adult patients with T2DM who initiated treatment with CANA100 and subsequently required intensification to CANA300. The primary outcome measures were changes in HbA1c and weight at 6 months after the switch and at the end of the follow-up period. Results: A total of 317 patients met the inclusion criteria (59.6% male, mean age 62.2 years, baseline HbA1c 7.55%, weight 88.6 kg, median duration of treatment with CANA100 9.9 months). Switching to CANA300 resulted in a significant reduction in HbA1c (6 months: −0.33%; last visit: −0.47%, both p &lt; 0.0001) and weight (6 months: −1.8 kg; last visit: −2.9 kg, both p &lt; 0.0001) over a median follow-up period of 20.8 months. The proportion of patients that achieved HbA1c &lt; 7% increased from 26.7% with CANA100 to 51.6% with CANA300 (p &lt; 0.0001). Among individuals with poor baseline glycemic control (HbA1c &gt; 8%, mean 9.0%), HbA1c was significantly reduced by −1.24% (p &lt; 0.0001). Furthermore, significant improvements were observed in fasting plasma glucose (FPG), blood pressure (BP), liver enzymes, and albuminuria. No unexpected adverse events were reported. Conclusions: Intensifying the treatment to CANA300 in a real-world setting resulted in further significant and clinically relevant reductions in FPG, HbA1c, weight, and BP in patients with T2DM. The switch was particularly effective in patients with higher baseline HbA1c levels.

Positive Impact of the Bionic Pancreas on Diabetes Control in Youth 6-17 Years Old with Type 1 Diabetes: A Multicenter Randomized Trial.

Objective: To evaluate the insulin-only configuration of the iLet® bionic pancreas (BP) in youth 6-17 years old with type 1 diabetes (T1D). Research Design and Methods: In this multicenter, randomized, controlled trial, 165 youth with T1D (6-17 years old; baseline HbA1c 5.8%-12.2%; 35% using multiple daily injections, 36% using an insulin pump without automation, 4% using an insulin pump with low glucose suspend, and 25% using a hybrid closed-loop system before the study) were randomly assigned 2:1 to use BP (n = 112) with insulin aspart or insulin lispro (BP group) or to a control group (n = 53) using their personal standard care insulin delivery (SC group) plus real-time continuous glucose monitoring (CGM). The primary outcome was HbA1c at 13 weeks. Results: Mean HbA1c decreased from 8.1% ± 1.2% at baseline to 7.5% ± 0.7% at 13 weeks with BP versus 7.8% ± 1.1% at both baseline and 13 weeks with SC (adjusted difference = -0.5%, 95% CI -0.7% to -0.2%, P < 0.001). Participants with baseline HbA1c ≥9.0% (n = 34) decreased mean HbA1c from 9.7% ± 0.8% to 7.9% ± 0.6% after 13 weeks with BP compared with 9.7% ± 0.5% to 9.8% ± 0.8% with SC. Over 13 weeks, mean time in range (TIR) 70-180 mg/dL increased by 10% (2.4 h per day) and mean CGM glucose was reduced by 15 mg/dL with BP compared with SC (P < 0.001). Analyses of time >180 mg/dL, time >250 mg/dL, and standard deviation of CGM glucose favored BP (P < 0.001). Time <54 mg/dL was low at baseline (median 0.2%) and not significantly different between groups over 13 weeks (P = 0.24). A severe hypoglycemia event occurred in 3 (2.7%) participants in the BP group and in 1 (1.9%) in the SC group. Conclusions: In youth 6-17 years old with T1D, use of insulin-only configuration of BP improved HbA1c, TIR, and hyperglycemic metrics without increasing CGM-measured hypoglycemia compared with standard of care. Improvement in glycemic metrics was most pronounced in participants with high baseline HbA1c levels. Clinical Trial Registry: clinicaltrials.gov; NCT04200313.

Association of baseline hemoglobin A1c levels with bleeding in patients with non-ST-segment elevation acute coronary syndrome underwent percutaneous coronary intervention: insights of a multicenter cohort study from China.

OBJECTIVETo investigate the association between baseline hemoglobin A1c (HbA1c) levels and bleeding in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) who underwent percutaneous coronary intervention (PCI).METHODSThis observational cohort study enrolled 6283 consecutive NSTE-ACS patients undergoing PCI from January 1, 2010 to December 31, 2014. Based on baseline HbA1c levels, the patients were divided into the group with HbA1c < 7% ( n = 4740) and the group with HbA1c ≥ 7% (n = 1543). The primary outcomes are major bleeding (BARC grades 3-5) and all-cause death during follow-up. RESULTSOf patients enrolled, 4705 (74.9%) were male, and 2143 (34.1%) had a history of diabetes mellitus, with a mean (SD) age of 64.13 (10.32) years. The median follow-up duration was 3.21 years. Compared with the patients with HbA1c < 7%, the risk of major bleeding events during follow-up was higher in patients with HbA1c ≥ 7% (adjusted hazard ratio [HR] = 1.57; 95% confidence interval [CI]: 1.01-2.44; P = 0.044), while the risk of all-cause death during follow-up was not associated with the higher HbA1c levels (adjusted HR = 0.88; 95% CI: 0.66-1.18; P = 0.398). CONCLUSIONSCompared with the lower baseline HbA1c levels, the higher baseline HbA1c levels were associated with an increase in long-term bleeding risk in NSTE-ACS patients undergoing PCI, though higher baseline HbA1c levels were not associated with the higher risk in all-cause death.

Safety and Effectiveness of Empagliflozin in Korean Patients with Type 2 Diabetes Mellitus: Results from a Nationwide Post-Marketing Surveillance.

To evaluate the safety and effectiveness of empagliflozin in routine clinical settings, we collected and assessed the clinical profiles of Korean patients with type 2 diabetes mellitus. This was a post-marketing surveillance study of empagliflozin 10 and 25 mg. Information on adverse events and adverse drug reactions (ADRs) was collected as safety data sets. Available effectiveness outcomes, including glycosylated hemoglobin (HbA1c) level, fasting plasma glucose, body weight, and blood pressure, were assessed. The incidence rate of ADRs was 5.14% in the safety dataset (n=3,231). Pollakiuria, pruritis genital, and weight loss were the most common ADRs. ADRs of special interest accounted for only 1.18%, and there were no serious events that led to mortality or hospitalization. In the effectiveness data set (n=2,567), empagliflozin significantly reduced the mean HbA1c level and body weight during the study period by -0.68%±1.39% and -1.91±3.37 kg (both P<0.0001), respectively. In addition, shorter disease duration, absence of dyslipidemia, and higher baseline HbA1c levels were identified as the clinical features characteristic of a "responder" to empagliflozin therapy. Empagliflozin is a safe and potent glucose-lowering drug in routine use among Korean patients with type 2 diabetes mellitus. It is expected to have better glycemic efficacy in Korean patients with poorly controlled type 2 diabetes mellitus.

Efficacy and safety outcomes of dulaglutide by baseline HbA1c: A post hoc analysis of the REWIND trial.

AimTo assess cardiovascular, glycaemic, weight and safety outcomes of long‐term treatment with dulaglutide 1.5 mg compared with placebo in patients with a baseline HbA1c of less than 7% versus 7% or higher.Materials and MethodsIntention‐to‐treat analyses were performed on REWIND participants with a baseline HbA1c measurement, using Cox proportional hazards regression and mixed model for repeated measures. Subgroup analyses with factors for baseline HbA1c categories and their interaction with treatment group, as well as analyses within the HbA1c subgroups, were conducted. Additionally, sensitivity analyses were performed for baseline HbA1c subgroups of 6.5% or less and more than 6.5%.ResultsOf the 9876 eligible participants, 3921 and 5955 had a baseline HbA1c of less than 7% and 7% or higher, respectively. Mean baseline HbA1c was 6.3% and 8.0% and the mean duration of diabetes was 9.0 and 11.6 years in the respective subgroups. The less than 7% subgroup was slightly older and less frequently insulin‐treated. There was no evidence of a differential dulaglutide treatment effect on body mass index (BMI) reduction, cardiovascular or safety outcomes of interest between the baseline HbA1c subgroups. Treatment‐by‐baseline HbA1c group interaction was significant for HbA1c change from baseline (P < .001), with a greater reduction in the subgroup with higher baseline HbA1c values. Sensitivity analyses by baseline HbA1c subgroups of 6.5% or less and more than 6.5% showed similar results.ConclusionsThe reduced incidence of cardiovascular events, and the reduction in BMI in participants treated with once‐weekly dulaglutide, were independent of the baseline HbA1c level. Conversely, participants with a higher baseline HbA1c level had greater reductions in HbA1c. Dulaglutide has a positive benefit–risk profile and can be considered in patients with comparatively well‐controlled HbA1c levels seeking optimal metabolic control and cardiovascular benefits.

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme.

AimsTo evaluate the efficacy and safety of oral semaglutide versus comparators by patient characteristic subgroups in patients with type 2 diabetes.Materials and MethodsChange from baseline in glycated haemoglobin (HbA1c) and body weight, and achievement of HbA1c <7.0% with oral semaglutide 7 mg, oral semaglutide 14 mg, flexibly dosed oral semaglutide (flex) and comparators were assessed across baseline subgroups (age, race, ethnicity, diabetes duration, body mass index and HbA1c) from the PIONEER programme. Treatment differences were analysed using a mixed model for repeated measurements for continuous variables and a logistic regression model for the binary endpoint. Pooled safety data were analysed descriptively.ResultsChanges from baseline in HbA1c and body weight, and the odds of achieving HbA1c <7.0%, were greater with oral semaglutide 14 mg/flex (n = 1934) and higher or similar with oral semaglutide 7 mg (n = 823) versus comparators (n = 2077) across most subgroups. Changes in HbA1c with oral semaglutide 14 mg/flex were greater for patients with higher baseline HbA1c (HbA1c >9.0%: –1.7% to –2.6%; HbA1c <8.0%: –0.7% to –1.2%). In some trials, Asian patients experienced greater HbA1c reductions with oral semaglutide 14 mg/flex (–1.5% to –1.8%) than other racial groups (–0.6% to –1.6%). The overall incidence of adverse events (AEs) with oral semaglutide was similar to that with comparators and was consistent across subgroups. More gastrointestinal AEs were observed with oral semaglutide, versus comparators, across subgroups.ConclusionsOral semaglutide demonstrated consistently greater HbA1c and body weight reductions across a range of patient characteristics, with greater HbA1c reductions seen at higher baseline HbA1c levels.

Real-world evaluation of weekly subcutaneous treatment with semaglutide in a cohort of Italian diabetic patients

PurposeRegistered trials and real-world evidence (RWE) studies provided evidence on the efficacy of once-weekly (OW) semaglutide on hyperglycaemia and cardiovascular risk factors as add-on or de-novo treatment in type 2 diabetes (T2D).MethodsIn a retrospective analysis of electronic data files from 258 T2D patients, this RWE study aimed to explore the impact of OW semaglutide on biochemical and anthropometric outcomes after 6 and 12 months in patients receiving at least one prescription of OW semaglutide between September 2019 and May 2021.ResultsDuring the study period, 154 and 56 consecutive patients completed the 6 and 12 months of OW semaglutide treatment. HbA1c levels decreased by -1.02±0.1% after 6 months and -1.1±0.1% after 12 months of OW semaglutide (p<0.0001 for both). At these time-points, HbA1c values were <7% in 61% and 57% of cases. HbA1c reduction was greater in patients with higher baseline HbA1c levels and it occurred irrespective of gender, age, insulin therapy and complications. The residual number of cases with HbA1c ≥9% by the study end was low (5.3% vs 18.9% at baseline). Weight loss occurred in 73.5% and 78.1% of cases and, compared to baseline, it was ≥5% in 21.2- 25.4% and ≥10% in 6.8-18.2% after 6 and 12 months, respectively. Significant predictors of HbA1c reduction after 6 months of OW semaglutide treatment were baseline HbA1c (p<0.0001), bodyweight reduction (p<0.0001) and disease duration (p<0.001), while baseline HbA1c was the only predictor of HbA1c response after 12 months (p<0.0001). Reported adverse events were consistent with the known safety profile of semaglutide.ConclusionsReal-world evaluation of weekly subcutaneous treatment with semaglutide in a cohort of Italian diabetic patients.

Association between Lung Function and New-Onset Diabetes Mellitus in Healthy Individuals after a 6-Year Follow-up.

BackgroundWe analyzed hemoglobin A1c (HbA1c) levels and various lung function test results in healthy individuals after a 6-year follow-up period to explore the influence of lung function changes on glycemic control.MethodsSubjects whose HbA1c levels did not qualify as diabetes mellitus (DM) and who had at least two consecutive lung function tests were selected among the people who visited a health promotion center. Lung function parameters, including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV/FVC ratio, and forced expiratory flow 25% to 75% (FEF25%−75%), were divided into four groups based on their baseline quantiles. To evaluate future DM onset risk in relation to lung function changes, the correlation between baseline HbA1c levels and changes in lung function parameters after a 6-year follow-up period was analyzed.ResultsOverall, 17,568 individuals were included; 0.9% of the subjects were diagnosed with DM. The individuals included in the quartile with FEV1/FVC ratio values of 78% to 82% had lower risk of DM than those in the quartile with FEV1/FVC ratio values of ≥86% after adjusting for age, sex, and body mass index (P=0.04). Baseline percent predicted FEV1, FVC, FEV1/FVC ratio, and FEF25%−75%, and differences in the FEV1/FVC ratio or FEF25%−75%, showed negative linear correlations with baseline HbA1c levels.ConclusionHealthy subjects with FEV1/FVC ratio values between 78% and 82% had 40% lower risk for future DM. Smaller differences and lower baseline FEV1/FVC ratio or FEF25%−75% values were associated with higher baseline HbA1c levels. These findings suggest that airflow limitation affects systemic glucose control and that the FEV1/FVC ratio could be one of the factors predicting future DM risk in healthy individuals.

Association between weight change and remission of type 2 diabetes: a retrospective cohort study in primary care

AbstractThe purpose of this study was to quantify the association between weight change and the likelihood of remission of type 2 diabetes in a population‐based cohort without intensive interventions.We undertook a retrospective analysis of adults with type 2 diabetes registered across 150 primary care practices in Southern England, United Kingdom, within the electronic Care and Health Information Analytics (CHIA) database between 2013 and 2020. Stepwise mixed logistic models were constructed to examine the association between percentage weight change over five‐years, and the likelihood of remission in the subsequent two years using four categories: weight gain ≥2.5%; weight loss ≤2.5–5% or ≥5–10% or ≥10%.The study cohort included 56,120 people with type 2 diabetes with a mean (SD) disease duration of 8.0 (6.7) years. In total, 17,035 (30.4%) had microvascular complications and 10,661 (19.0%) had macrovascular complications. A total of 19.4% (10,896) lost ≥10% of their baseline weight with 1646 (15.1%) of these achieving remission. Overall, those who lost ≥10% in weight had a significantly higher likelihood of remission in both unadjusted and adjusted models; RR 1.53 (95% CI 1.40–1.68); and RR 1.51 (95% CI 1.37–1.66), respectively. Remission was still achievable but less likely among younger men with a longer diabetes duration (≥5 years), higher baseline HbA1c level, or pre‐existing microvascular or macrovascular complications.It was concluded weight loss of &gt;10% is associated with remission of type 2 diabetes even among those with advanced disease and established microvascular or macrovascular complications. Our findings could motivate people with diabetes to lose weight in order to increase likelihood of remission. Copyright © 2021 John Wiley &amp; Sons.

HbA1c Evidence for a Prediabetes Diagnosis Delays Onset of Type 2 Diabetes

Objective: This study examined the influential role of making a prediabetes diagnosis resulting in the subsequent delay in onset of type 2 diabetes. Research Design and Methods: Using electronic medical records, a multivariable logistic regression model examined demographic and clinical risk factors associated with a prediabetes diagnosis among patients with HbA1c evidence of prediabetes. A multivariable non-proportional Cox regression examined development to type 2 diabetes (maximum 7 year follow-up). Results: Analysis includes 40,970 patients with incident prediabetes (76.8% undiagnosed). Logistic regression showed higher baseline HbA1c levels significantly influenced assigning a prediabetes diagnosis: compared to patients with HbA1c level 5.7-5.9% (low), OR 1.66 (99% CI 1.54-1.78) for HbA1c level 6.0-6.2% (medium) and OR 1.62 (CI 1.43-1.83) for HbA1c level 6.3-6.4% (high). Cox model results, which included an interaction between HbA1c and prediabetes diagnosis, found HbA1c the most significant predictor. Patients with diagnosed prediabetes progressed to type 2 diabetes slower than those undiagnosed. Comparing diagnosed patients to undiagnosed within the same HbA1c level, HRs ranged from 0.47 (CI 0.37-0.61) in the high HbA1c level to 0.83 (CI 0.67-1.02) in the low HbA1c level. Conclusions: From the LEADR cohort (1) HbA1c levels were the principle factor associated with risk for prediabetes diagnosis. Modeling development to diabetes, baseline HbA1c was the significant predictor of risk. Findings suggest assignment of a prediabetes diagnosis is associated with slower development of diabetes and this protective benefit of being diagnosed increases with a higher baseline HbA1c. Prediabetes diagnosis is useful for delaying onset of type 2 diabetes.

Effect of flash glucose monitoring in adults with type 1 diabetes: a nationwide, longitudinal observational study of 14,372 flash users compared with 7691 glucose sensor naive controls

Aims/hypothesisThe aim of this work was to evaluate changes in glycaemic control (HbA1c) and rates of severe hypoglycaemia over a 2 year period after initiation of flash glucose monitoring (FM) in type 1 diabetes.MethodsUsing data from the Swedish National Diabetes Registry, 14,372 adults with type 1 diabetes with a new registration of FM during 2016–2017 and with continued FM for two consecutive years thereafter, and 7691 control individuals using conventional self-monitoring of blood glucose (SMBG) during the same observation period, were included in a cohort study. Propensity sores and inverse probability of treatment weighting (IPTW) were used to balance FM users with SMBG users. Changes in HbA1c and events of severe hypoglycaemia were compared.ResultsAfter the start of FM, the difference in IPTW change in HbA1c was slightly greater in FM users compared with the control group during the follow-up period, with an estimated mean absolute difference of −1.2 mmol/mol (−0.11%) (95% CI −1.64 [−0.15], −0.75 [−0.07]; p < 0.0001) after 15–24 months. The change in HbA1c was greatest in those with baseline HbA1c ≥70 mmol/mol (8.5%), with the estimated mean absolute difference being −2.5 mmol/mol (−0.23%) (95% CI −3.84 [−0.35], −1.18 [−0.11]; p = 0.0002) 15–24 months post index. The change was also significant in the subgroups with initial HbA1c ≤52 mmol/mol (6.9%) and 53–69 mmol/mol (7.0–8.5%). Risk of severe hypoglycaemic episodes was reduced by 21% for FM users compared with control individuals using SMBG (OR 0.79 [95% CI 0.69, 0.91]; p = 0.0014)].Conclusions/interpretationIn this large cohort, the use of FM was associated with a small and sustained improvement in HbA1c, most evident in those with higher baseline HbA1c levels. In addition, FM users experienced lower rates of severe hypoglycaemic events compared with control individuals using SMBG for self-management of glucose control.Graphical abstract

Baseline HbA1c Level Influences the Effect of Periodontal Therapy on Glycemic Control in People with Type 2 Diabetes and Periodontitis: A Systematic Review on Randomized Controlled Trails

IntroductionThe question of whether periodontal therapy is an effective strategy for achieving glycemic control in people with type 2 diabetes mellitus (T2DM) and periodontitis continues to be open to debate. To clarify this issue, we conducted a systematic review and meta-analysis.MethodsA systematic literature search of randomized controlled trials (RCTs) was carried out by searching four electronic databases and four journals up to April 2020. RCTs that evaluated the effect of periodontal therapy on glycemic control in people with T2DM were included.ResultsA total of 23 RCTs were included in this systematic review and meta-analysis. We found that after 3 and 6 months, periodontal therapy could significantly reduce glycosylated hemoglobin (HbA1c) level (3-month: weighted mean difference [WMD] − 0.514, 95% confidence interval [CI] − 0.730, − 0.298, p = 0.000; 6-month: WMD − 0.548, 95% CI − 0.859, − 0.238, p = 0.000). However, huge heterogeneity existed. Further analyses on 11 potential sources of heterogeneity found that baseline HbA1c of the included studies was the most significant factor causing heterogeneity. The benefit of periodontal therapy on glycemic control was much more obvious in studies with a higher baseline HbA1c level than in those with a lower baseline HbA1c level.ConclusionsPeriodontal therapy significantly contributed to glycemic control in T2DM patients, especially in patients with higher baseline HbA1c level.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01000-6.

The relationship between resting heart rate and new-onset microalbuminuria in people with type 2 diabetes: An 8-year follow-up study.

AimsMicroalbuminuria is an indicator of adverse cardiovascular events and chronic kidney disease. Studies have described an elevated resting heart rate as a risk factor for microalbuminuria in people with cardiovascular disease, but none have clarified its role in microalbuminuria development in people with type 2 diabetes. Therefore, this study investigated the relationship between resting heart rate and new‐onset microalbuminuria in type 2 diabetes.MethodsA total of 788 people from a glycaemic control trial in Taiwan were enrolled. Microalbuminuria was defined as a fasting urine albumin‐to‐creatinine ratio ≥30 mg/g in two consecutive urine tests. Resting heart rate and other covariates were measured at baseline. The quartile of resting heart rates, categorized as <70, 70–74, 75–80 and >80 beats/min, was used for analysis. Cox proportional hazard models were used to evaluate the association between resting heart rate and risk of microalbuminuria.ResultsDuring the follow‐up period, 244 people (31%) developed microalbuminuria. Those who developed microalbuminuria had a longer diabetes duration (median = 3.0 vs. 2.0 years, p < 0.001), higher rate of hypertension (77% vs. 66%, p = 0.003), higher rate of angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker treatment (50% vs. 38%, p = 0.001) and higher baseline HbA1c level (70 vs. 64 mmol/mol, 8.6 vs. 8.0%, p < 0.001). After adjusting for demographics, metabolic profiles and inflammatory markers, developing microalbuminuria was significantly associated with baseline resting heart rate of 70–74, 75–80 and >80 beats/min (with hazard ratios [95% CI] of 2.05 [1.32, 3.18], 2.10 [1.32, 3.32] and 1.62 [1.01, 2.59], respectively) compared to resting heart rates <70 beats/min. An average increased risk of microalbuminuria for increment of 10 beats/min was about 24% among those with hypertension (with hazard ratios of 1.24 [1.05, 1.47] in the multivariable Cox model).ConclusionsThis prospective cohort study showed that resting heart rate may be an associative risk factor for developing microalbuminuria in type 2 diabetes.

Clinical Efficacy of Quadruple Oral Therapy for Type2 Diabetes in Real-World Practice: A Retrospective Observational Study.

IntroductionWe aimed to evaluate the effectiveness of quadruple oral therapy in patients with inadequately controlled type 2 diabetes (T2D) with the use of three types of oral hypoglycemic agents.MethodsMedical records of 318 patients with T2D who were prescribed quadruple therapy in the Asan Medical Center were reviewed. Changes in glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels from baseline were assessed. The regimens of quadruple oral therapy included the following: (1) thiazolidinedione (TZD) add-on to metformin (MET) + sulfonylurea (SU) + dipeptidyl peptidase 4 inhibitor (DPP4i), (2) sodium-glucose cotransporter 2 inhibitor (SGLT2i) add-on to MET + SU + DPP4i, and (3) DPP4i add-on to MET + SU + TZD.ResultsThe TZD add-on significantly reduced HbA1c levels by 1.1% (from 9.0 ± 1.1 to 7.9 ± 1.1%, P < 0.001) and FPG levels by 41.4 mg/dL (from 188.9 ± 45.9 to 147.4 ± 51.3 mg/dL, P < 0.001). The SGLT2i add-on changed the mean HbA1c level from 8.9 ± 1.0 to 7.8 ± 1.0%, a reduction of 1.1% (P < 0.001) and changed the mean FPG level from 193.4 ± 46.2 to 152.6 ± 37.0 mg/dL, a reduction of 40.8 mg/dL (P < 0.001). Finally, the DPP4i add-on reduced HbA1c levels by 1.3% (from 9.1 ± 1.3 to 7.8 ± 1.4%, P < 0.001) and FPG levels by 39.3 mg/dL (from 190.7 ± 45.3 to 151.4 ± 41.6 mg/dL, P < 0.001). Patients with higher baseline HbA1c levels (≥ 9.0%) showed a better response to quadruple therapy than those with baseline HbA1c levels lower than 9.0% for all three regimens.ConclusionQuadruple oral hypoglycemic therapy can be a feasible option in patients with T2D.Electronic supplementary materialThe online version of this article (10.1007/s13300-020-00881-3) contains supplementary material, which is available to authorized users.