HbA1c Outcomes Research Articles

Association of HbA1C with mortality and cardiovascular outcome in patients with type 2 diabetes using drugs with different hypoglycemic risk

Abstract Background Previous clinical trials showed that intensive glucose control did not reduce macrovascular events and mortality. It was speculated that severe hypoglycaemia contributed to these adverse outcomes. More contemporary clinical trials using newer anti-diabetic agents with less hypoglycaemic potential showed a linear relationship between major adverse cardiovascular events (MACE) and HbA1c reduction according to a meta-regression analysis. Purpose The aim of this study was to examine the association between clinical outcomes and HbA1c under different treatment backgrounds in the real-world setting. We hypothesised that when using drugs with minimal hypoglycaemic risk, lower HbA1c would be associated with better outcomes. Methods This was a retrospective population-based cohort study using a multi-centre electronic medical record database. Eligible patients were those diagnosed with type 2 diabetes between 2009 and 2020 who received non-insulin antidiabetic drugs. Patients were stratified into two groups based on the drugs received: drugs with high hypoglycaemic risk (sulphonylurea, meglitinide) and drugs with low hypoglycaemic risk (thiazolidinediones, acarbose, DPP4 inhibitors, GLP1 agonists, SGLT-2 inhibitors). Patients were excluded if they had received these drugs for less than 180 days or had received both high and low hypoglycaemic risk oral drugs simultaneously. HbA1c levels were assessed from the index date to the date of the interested outcome or the end of the study period (31 December 2021), whichever came first. The relationship between HbA1c and clinical outcomes was examined using a Cox proportional hazards model. The outcomes of interest included all-cause mortality and MACE. Results The study population consisted of 6,923 patients, including 3,639 high hypoglycaemic risk drug users and 3,284 low hypoglycaemic risk drug users. Patients with lower HbA1c levels during the follow-up period were older and frailer. After adjusting for baseline covariates, the association between the risk of death and HbA1c presented a U-shaped pattern, and this U-shaped association was similar in the two treatment cohorts (Table 1). On the other hand, the association between the risk of MACE and HbA1c presented a J-shaped pattern. In the high hypoglycaemic risk drug cohort, patients with the highest HbA1c levels (mean HbA1c 9.6%) were associated with a higher risk of MACE compared to the group with a mean HbA1c of 7.2% (hazard ratio [HR] 4.16, 95% confidence interval [CI] 2.07-8.37); lower HbA1c levels were not associated with a lower risk of MACE (Table 2). In contrast, in the low hypoglycaemic risk drug cohort, lower HbA1c levels were associated with a higher risk of MACE (HR 3.82, 95% CI 1.29-11.28). Conclusion Lower HbA1c levels were not associated with a lower risk of all-cause mortality and MACE. Furthermore, this phenomenon was independent of the hypoglycaemic risk of anti-diabetic drugs.

Factors Associated with Achieving HbA1c Targets in Patients with Type 2 Diabetes

Background: Diabetes mellitus is a major global public health concern, particularly due to its complications and associated mortality and morbidity. Ethnic differences in the epidemiology of diabetes necessitate population-specific studies to identify factors influencing glycemic control. Objectives: This study aimed to identify demographic and clinical factors associated with achieving HbA1c targets in patients with type 2 diabetes mellitus (T2DM) at the Yazd Diabetes Center in Iran. Methods: In this retrospective study, data were extracted from the medical records of 3,454 patients with type 2 diabetes at the Yazd Diabetes Research Center (March 2020 - December 2022). Data analysis was performed using chi-squared tests, t-tests, Mann-Whitney U tests, and logistic regression in R version 4.0.2. Results: The cohort, predominantly female (59%) and primarily educated at the elementary level (65%), had an average age of 59.5 years (SD = 10) and a mean diabetes duration of 10.7 years (SD = 7.6). In the multivariable logistic regression model, older age (B = 0.03, OR = 1.03 per year, P < 0.001) and higher education level (secondary school B = 0.664, OR = 1.94, P < 0.001; academic education B = 0.834, OR = 2.30, P < 0.001) remained significant independent predictors of achieving HbA1c < 7%. The interaction term revealed that each additional year of diabetes duration led to a 3% greater reduction in the odds of achieving HbA1c < 7% for females compared to males (B = -0.029, OR = 0.97, P = 0.011), indicating gender-specific impacts of diabetes duration. Conclusions: This study found that demographic factors, including older age and higher education levels, were significantly associated with better glycemic control. The duration of diabetes negatively affected HbA1c outcomes, with a more pronounced impact in females than in males.

Early pregnancy high normal HbA1c: a high risk group?

To determine if high normal early pregnancy HbA1c (35-40mmol/mol), in the absence of diabetes, was associated with increased risk of adverse perinatal outcomes compared to normal HbA1c (<35mmol/mol). A retrospective chart review was carried out on all singleton births in the Wellington region from 1 July 2019 to 31 December 2019. Exclusion criteria were participants domiciled outside the Wellington region, HbA1c ≥50mmol/mol, pre-existing diabetes, gestational diabetes in current pregnancy, no HbA1c performed <20 weeks or the first HbA1c was taken at ≥20 weeks. Baseline characteristics, HbA1c and pregnancy outcomes were obtained. The primary outcome was birth weight and was analysed using multiple linear regression. There were 1,067 participants in the normal HbA1c (nHbA1c) group and 186 in the high normal HbA1c (hnHbA1c) group. There was no difference in birth weight between hnHbA1c and nHbA1c. hnHbA1c had significantly lower odds of post-partum haemorrhage and composite maternal adverse outcomes compared to nHbA1c (OR 0.52, 95% CI 0.35-0.76) and (OR 0.64, 95% CI 0.46-0.89). High normal HbA1c was not associated with increased risk of adverse perinatal outcomes in pregnant people who did not develop gestational diabetes.

The relationship between HbA1c and the activities of daily living in complex chronic patients with and without intracerebral hemorrhage

BackgroundAssociations between HbA1c and adverse outcomes in ischemic and hemorrhagic stroke have been confirmed. It is still unclear whether HbA1c is related to the activities of daily living (ADL) score in complex chronic patients (CCP) with and without intracerebral hemorrhage (ICH).AimThe associations between HbA1c and ADL (Barthel score) in CCP with ICH and without ICH were evaluated, respectively.MethodsWe have analyzed data from a previous cohort study involving in 3594 CCPs without a ICH history at baseline, who were followed up for 5 years to assess ICH episode.ResultsOne hundred sixty-one ICH case were detected in a total of 3594 patients during the period of follow up for 5 years. Our nonlinear analysis suggested positive trends on the association between HBA1c and Barthel score in ICH and non-ICH patients, respectively. The multivariate linear regression analysis showed that elevated HbA1c was positively associated with a higher Barthel score among all study population (β = 1.25, 95% CI: 0.92, 1.59; P < 0.0001) with adjusted age and sex. Among non-ICH patients, increased HbA1c was still positively associated with an increased Barthel score (β = 1.24, 95% CI: 0.90, 1.58; P < 0.001). However, HbA1c appeared to have no any relationship with Barthel score in ICH patients (β = 1.87, 95% CI: -0.07, 3.82; P = 0.0613) after adjustment for age and sex. By additionally using sensitivity analysis, we still observed that the strong relationship was still existed in non-ICH patients (β = 0.90, 95% CI: 0.56, 1.24; P < 0.001) but not in ICH patients (β = 1.88, 95% CI: -0.10, 3.86; P = 0.0649).ConclusionWe observed for the first time that elevated HbA1c is associated with better ADL in CCPs without ICH but not in those with ICH. This interesting discovery contradicts the traditional adverse effects of elevated HbA1c.

Comparative Effects of Diabetes Self-Management Programs on Type 2 Diabetes Clinical Outcomes: A Systematic Review and Network Meta-Analysis.

This systematic review and network meta-analysis compared the effects of various diabetes self-management programs: Diabetes Self-Management Education (DSME), Diabetes Self-Management Support (DSMS), and Diabetes Self-Management Education and Support (DSMES). We searched four electronic databases for eligible articles up to March 1, 2023. Only randomized controlled trials investigating the effects of DSME, DSMS, or DSMES on glycated haemoglobin (HbA1c) level, fasting blood glucose (FBG), total cholesterol (TC), systolic blood pressure (SBP), and diastolic blood pressure (DBP) in adults with type 2 diabetes were included. Cochrane Risk of Bias 2.0 tool was used to assess each study quality, and Confidence in Network Meta-Analysis was applied to evaluate the certainty of the evidence. Data were pooled with a random-effects model under a frequentist framework. A total of 108 studies encompassing 17,735 participants (mean age 57.4years) were analysed. DSMES, compared with usual care, significantly reduced HbA1c level (mean difference=-0.61%, 95% confidence interval [CI]=-0.74 to -0.49; certainty of evidence=moderate), FBG (-23.33mg/dL; -31.33 to -15.34; high), TC (-5.62mg/dL; -8.69 to -2.55; high), SBP (-3.05mmHg; -5.20 to -0.91; high), and DBP (-2.15mmHg; -3.36 to -0.95; high). Compared with DSME, DSMES showed significantly greater improvements in HbA1c levels (-0.23%; -0.40 to -0.07; high) and DBP (-1.82mmHg; -3.47 to -0.17; high). DSMES was ranked as the top treatment for improving diabetes clinical outcomes (0.82-0.97) in people with type 2 diabetes. DSMES, in people with type 2 diabetes, yields the greatest improvement in the key clinical outcomes of HbA1c, fasting blood glucose, and blood pressure levels. Healthcare providers should incorporate the DSMES approach into their daily care routines. Approximately 30% of the studies reviewed raised some concerns about their quality, underscoring the need for high-quality studies in this area.

The association of haemoglobin A1c variability with adverse outcomes in patients with atrial fibrillation prescribed anticoagulants.

The association of haemoglobin A1c (HbA1c) variability with the risk of adverse outcomes in patients with atrial fibrillation (AF) prescribed anticoagulants remains unclear. This study aimed to evaluate the association of HbA1c variability with the risk of ischaemic stroke (IS)/systemic embolism (SE) and all-cause mortality among patients with non-valvular AF prescribed anticoagulants. Patients newly diagnosed with AF from 2013 to 2018 were included. Variability in HbA1c, indexed by the coefficient of variation (CV), was determined for those with at least three HbA1c measurements available from the time of study enrolment to the end of follow-up. To evaluate whether prevalent diabetes would modify the relationship between HbA1c variability and outcomes, participants were divided into diabetes and non-diabetes groups. The study included 8790 patients (mean age 72.7% and 48.5% female). Over a median follow-up of 5.5 years (interquartile range 5.2, 5.8), the incident rate was 3.74 per 100 person-years for IS/SE and 4.89 for all-cause mortality in the diabetes group. The corresponding incident rates in the non-diabetes group were 2.41 and 2.42 per 100 person-years. In the diabetes group, after adjusting for covariates including mean HbA1c, greater HbA1c variability was significantly associated with increased risk of IS/SE [hazard ratio (HR) = 1.65, 95% confidence interval (CI): 1.27-2.13) and all-cause mortality (HR = 1.24, 95% CI: 1.05-1.47) compared with the lowest CV tertile. A similar pattern was evident in the non-diabetes group (IS/SE: HR = 1.58, 95% CI: 1.23-2.02; all-cause mortality: HR = 1.35, 95% CI: 1.10-1.64). Greater HbA1c variability was independently associated with increased risk of IS/SE and all-cause mortality among patients with AF, regardless of diabetic status.

Correlation Between Hemoglobin A1c (HbA1c) and High-Sensitivity C-Reactive Protein (hs-CRP) in Myocardial Infarction Patients and Their Six-Month Mortality Follow-Up.

Background Acute coronary syndrome (ACS), encompassing unstable angina (UA), non-ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI), poses significant global health challenges because of its associated high mortality and morbidity rates. Vascular inflammation plays a crucial role in the pathogenesis of atherosclerosis, and it is often assessed using biomarkers such as high-sensitivity C-reactive protein (hs-CRP). Hyperglycemia, common in myocardial infarction patients, is linked to increased complications and mortality, with glycosylated hemoglobin A1c (HbA1c) serving as a key indicator of long-term glycemic control. Objective This study investigates the correlation between hs-CRP and HbA1c levels in patients with acute myocardial infarction (AMI) and type 2 diabetes mellitus (T2DM) and evaluates their impact on six-monthmortality outcomes. Methods A prospective observational study was conducted with 80 patients diagnosed with AMI. Data collection included demographic information, medical history, clinical assessments, laboratory investigations (including hs-CRP and HbA1c levels), and imaging studies. Patients received standard treatment and were followed up for six months. Statistical analyses were performed to examine the relationships between hs-CRP, HbA1c, and clinical outcomes. Results Higher HbA1c levels at admission were significantly correlated with elevated hs-CRP levels (p < 0.05). Both biomarkers showed a reduction at six months, correlating with improved glycemic control and reduced inflammation. Each unit increase in HbA1c was associated with a 21% increase in the hazard of mortality, and, similarly, each unit increase in hs-CRP was associated with a 17% increase in the hazard of mortality. The positive correlation between HbA1c and hs-CRP suggests that HbA1c can serve as an independent marker for predictingmortality in this patient population. Conclusion The study demonstrates a significant correlation between hs-CRP and HbA1c levels in patients with AMI and T2DM, with both biomarkers serving as strong predictors of six-monthmortality. HbA1c, because of its positive correlation with hs-CRP, could be used as an independent marker for assessing the risk of adverse outcomes in these patients. These findings highlight the importance of managing both glycemic control and inflammation in diabetic patients with ACSs.

Improving Health and Reducing Chronic Disease Disparities with Latinx Communities: Evaluating the Role of Documented Community-Based Intervention Participation.

Limited evidence exists on the impact of participation in community-based chronic disease self-management and prevention programs on health disparities. The purpose of this research was to determine the effects of participation in the Healthy Here Wellness Referral System on existing disparities in glycated hemoglobin (HbA1c), systolic blood pressure (BP), and diastolic BP among Hispanic/Latinx adults compared with non-Hispanic White adults. We merged administrative clinical and referral data from 2018 through 2022 for adult patients in six focus ZIP codes in New Mexico resulting in a sample of 1331 patients and used regression models to examine predictors of intervention participation as well as propensity-adjusted impacts of participation on HbA1c and BP outcomes. Non-Hispanic White patients who were referred to community-based programming but did not participate saw statistically significant increases in HbA1c. Hispanic/Latinx patients saw statistically significant decreases in HbA1c with referral alone, with no added benefit from program participation. The impact of participation differed statistically significantly (t(683) = 3.55, p < .001) between these two groups for HbA1c levels, as well as for systolic (t(958) = 2.11, p = .04) and diastolic BP outcomes (t(958) = 2.96, p = .003). Results of this study support the promise of using centralized referral systems to co-produce health improvement in community settings. Mixed findings highlight the need for further uptake of theory-informed measurement in evaluations seeking to understand heterogeneous program impacts by race and ethnicity.

The quality of care in type 1 and type 2 diabetes – A 2023 update of the AMD Annals initiative

AimsAn initiative of continuous monitoring of the quality of diabetes care, promoted by the Association of Medical Diabetologists, is in place in Italy since 2006 (AMD Annals). The initiative was effective in improving quality of care indicators, assessed periodically through standardized measures. Here, we show the 2023 AMD Annals data on type 2 (T2D) and type 1 (T1D) diabetes. MethodsA network of over 1/3 of diabetes centers in Italy periodically extracts anonymous data from electronic medical records, using a standardized software. Process, treatment and outcome indicators, and a validated score of overall care, the Q-score, were evaluated. Results296 centers provided data on 573,164 T2D (mean age 69.7 ± 11.2 years) and 42,611 T1D subjects (mean age 48.6 ± 16.9 years). A HbA1c value ≤ 7.0 % was documented in 56.3 % of patients with T2D and 35.9 % of those with T1D. Only 6.6 % of T2D patients and 3.5 % of those with T1D reached the composite outcome of HbA1c ≤ 7.0 % + LDL-C < 70 mg/dl + BP < 130/80 mmHg. Notably, only 2.8 % and 3.2 % of T2D and T1D patients, respectively, showed a Q score < 15, which correlates with an 80 % higher risk of incident CVD events compared to scores > 25. ConclusionsWe documented an overall good quality of care in both T1D and T2D subjects. However, the failure to achieve the targets of the main risk factors, especially if combined, in a still too large proportion of patients testify the difficulty to apply the more and more stringent indications recommended by guidelines in the everyday clinical practice.

EMBARK: A Randomized, Controlled Trial Comparing Three Approaches to Reducing Diabetes Distress and Improving HbA1c in Adults With Type 1 Diabetes.

To compare the effectiveness of three interventions to reduce diabetes distress (DD) and improve HbA1c among adults with type 1 diabetes (T1D). Individuals with T1D (n = 276) with elevated DD (a score >2 on the total Type 1 Diabetes Distress Scale) and HbA1c (>7.5%) were recruited from multiple settings and randomly assigned to one of three virtual group-based programs: 1) Streamline, an educator-led education and diabetes self-management program; 2) TunedIn, a psychologist-led program focused exclusively on emotional-focused DD reduction; or 3) FixIt, an integration of Streamline and TunedIn. Assessments of the primary outcomes of DD and HbA1c occurred at baseline and at 3, 6, and 12 months. All three programs demonstrated substantive and sustained reductions in DD (Cohen's d = 0.58-1.14) and HbA1c (range, -0.4 to -0.72) at 12-month follow-up. TunedIn and FixIt participants reported significantly greater DD reductions compared with Streamline participants (P = 0.007). Streamline and TunedIn participants achieved significantly greater HbA1c reductions than did FixIt participants (P = 0.006). DD can be successfully reduced among individuals with T1D with elevated HbA1c using both the educational/behavioral and emotion-focused approaches included in the study. Although both approaches are associated with significant and clinically meaningful reductions in DD and HbA1c, TunedIn, the emotion-focused program, had the most consistent benefits across both DD and HbA1c. The study findings suggest the overall value of group-based, fully virtual, and time-limited emotion-focused strategies, like those used in TunedIn, for adults with T1D.

Glycated Hemoglobin Variability Is Associated With Adverse Outcomes in Patients With Heart Failure Irrespective of Diabetic Status.

The effect of glycated hemoglobin (HbA1c) variability on adverse outcomes in patients with heart failure (HF) is unclear. We aim to investigate the predictive value of HbA1c variability on the risks of all-cause death and HF rehospitalization in patients with HF irrespective of their diabetic status. Using a previously validated territory-wide clinical data registry, HbA1c variability was assessed by average successive variability (ASV) or SD of all HbA1c measurements after HF diagnosis. Multivariable Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) and its corresponding 95% CI. A total of 65 950 patients with HF were included in the study. Over a median follow-up of 6.7 (interquartile range, 4.0-10.6) years, 34 508 patients died and 52 446 required HF rehospitalization. Every unit increment of variability in HbA1c was significantly associated with higher HF rehospitalization (HR ASV, 1.20 [95% CI, 1.18-1.23]) and all-cause death (HR ASV, 1.50 [95% CI, 1.47-1.53]). Diabetes significantly modified the association between HbA1c variability and outcomes (Pinteraction<0.001). HbA1c variability in patients with HF without diabetes conferred a higher risk of rehospitalization (HR ASV, 1.92 [95% CI, 1.70-2.17] versus HR ASV, 1.19 [95% CI, 1.17-1.21]), and all-cause death (HR ASV, 3.90 [95% CI, 3.31-4.61] versus HR ASV, 1.47 [95% CI, 1.43-1.50] compared with patients with diabetes). HbA1c variability is significantly associated with greater risk of rehospitalization and all-cause death in patients with HF, irrespective of their diabetic status. These observations were more pronounced in patients with HF without diabetes.

Evaluation of effects from hemoglobin variants on HbA1c measurements by different methods.

The impact of seven hemoglobin variants (Hb Q-Thailand, Hb G-Honolulu, Hb Ube-2, Hb New York, Hb J-Bangkok, Hb G-Coushatta, and Hb E) on the outcome of HbA1c was investigated for six methods by comparing withliquid chromatography-tandem mass spectrometry (LC/MS/MS) reference method. Twenty-nine normal and 112 variant samples were measured by LC/MS/MS, Sebia Capillarys 3 TERA, Intelligene Biosystems QuanTOF, Premier Hb9210, Arkray HA-8190V, Bio-Rad D-100, and Tosoh G11, then evaluated for correlation, consistency, and mean relative bias among six methods. The lowest biological variation bias of ±2.8 % was an acceptable standard. All methods showed poor correlation and consistency with LC/MS/MS for Hb E. The unacceptable biases were observed for Capillarys 3 TERA (-14.4 to-3.7 % for Hb Q-Thailand, Hb Ube-2, Hb New York, Hb J-Bangkok and Hb E), QuanTOF (-8.3 to-2.9 % for Hb Ube-2, Hb New York and Hb G-Coushatta), Premier Hb9210 (-18.3 to-3.6 % for Hb Q-Thailand, Hb Ube-2, Hb New York, Hb J-Bangkok and Hb E), HA-8190V variant mode (-17.3 to 6.6 % for Hb G-Honolulu, Hb Ube-2, Hb New York, Hb G-Coushatta and Hb E). All variant samples showed larger biases than ±2.8 % comparing HA-8190V fast mode, D-100, and G11 with LC/MS/MS. The accuracy of different HbA1c methods was influenced by some Hb variants, especially Hb Ube-2 and Hb New York. Thus, laboratories need to choose appropriate methods to measure HbA1c with different Hb variants.

Correlation between centre size, metabolic variation and mean HbA1c in major paediatric diabetes centres.

To exploit a relatively homogeneous national health care context and a national diabetes database to address the questions: Is there an optimal clinic/centre size in determining outcomes?; and Can improvement in median centre outcomes be driven by reducing variability in outcome? Using the Australasian Diabetes Database Network, data from seven tertiary hospital paediatric diabetes clinics for patients with type one diabetes from Australia were recorded from 6-month uploads: September 2017, March 2018, September 2018 and March 2019. Data from 25 244 patient visits included demographic variables, HbA1C, number of patient visits and insulin regimens. There was no association between centre size and median HbA1C. On the other hand, there was a significant association between or median absolute deviation of HbA1C outcomes and the median HbA1C result between centres. On average every two thirds of a median absolute deviation increase in clinic HbA1C was associated with a 1.0% (10.9 mmol/mol) increase in median clinic HbA1C. Our data have shown that it is likely difficult for centres to have a low median HbA1C if there is high variance of HbA1C's within centres or within centre treatment groups. This appears to be true regardless of centre size. These findings need to be carefully considered by teams who wish to lower their clinic median HbA1C.

Relationship between glycated hemoglobin levels and three-month outcomes in acute ischemic stroke patients with or without diabetes: a prospective Korean cohort study

ObjectiveIn patients experiencing acute ischemic stroke, there is ongoing debate surrounding the connection between chronic hyperglycemic status and their initial clinical outcomes. Our objective was to examine the connection between glycated hemoglobin (HbA1c) levels and adverse clinical outcomes at both 3-months adverse clinical outcomes in individuals with acute ischemic stroke (AIS) with and without diabetes.MethodsThe present prospective cohort study involved 896 AIS patients without diabetes and 628 with diabetes treated at a South Korean hospital from January 2010 to December 2016. The target independent variable is HbA1c. The outcome variable is a modified Rankin scale score ≥ 3. A binary logistic regression model was applied to assess the connection between HbA1c levels and 3-month poor clinical outcomes in AIS patients with and without diabetes. Additionally, a generalized additive model and smoothed curve fitting were utilized to explore potential nonlinear associations between HbA1c levels and 3-month adverse clinical outcomes in AIS patients with and without diabetes.ResultsThe binary logistic regression model could not identify any statistically significant connection between HbA1c and 3-month adverse clinical outcomes in AIS patients, both those with and without diabetes, after correcting for various factors. However, a nonlinear relationship emerged between HbA1c and 3-month adverse clinical outcomes in AIS patients with diabetes. The inflection point for HbA1c was determined to be 6.1%. For HbA1c values ≤ 6.1%, an inverse association was observed between HbA1c and 3-month adverse clinical outcomes in diabetic AIS patients, and each 1% increase in HbA1c in AIS patients with DM was associated with an 87% reduction in 3-month adverse clinical outcomes (OR = 0.13, 95% CI: 0.02–0.81). Conversely, when HbA1c exceeded 6.1%, a positive association between HbA1c and 3-month adverse clinical outcomes became apparent in diabetic AIS patients, and each 1% increase in HbA1c in AIS patients with DM was associated with a 23% increase in 3-month adverse clinical outcomes (OR = 1.23, 95%CI: 1.03–1.47). However, it’s important to note that no significant linear or nonlinear relationships were observed between HbA1c levels and 3-month adverse clinical outcomes in AIS patients without diabetes.ConclusionOur findings suggest a nonlinear connection and threshold effect between HbA1c and 3-month adverse clinical outcomes in AIS patients with diabetes. AIS patients with diabetes had a lower risk of 3-month adverse clinical outcomes when their HbA1c control was close to 6.1%. Our findings may aid treatment decision-making and potentially guide interventions to optimize glycemic control in AIS patients.

Treatment Patterns, Effectiveness, and Safety of Originator Insulin Glargine versus Insulin Glargine-yfgn within the Veterans Health Administration

We described insulin glargine (originator) and insulin glargine-yfgn (biosimilar) treatment patterns, assessed effectiveness and safety outcomes, and identified reasons for switching back to the originator product from the biosimilar. This retrospective study included 328,463 Veterans 18 years of age and older who received one or more outpatient prescriptions for insulin glargine and/or insulin glargine-yfgn between 1 June 2021 and 31 December 2022. Patients were assigned to subgroups based on the initial prescription during the study period, prevalent versus incident use for originator insulin glargine, and prior versus no prior use of the originator before the biosimilar (i.e., prevalent originator non-switcher (n = 189,734), originator switch to biosimilar (n = 81,010), incident originator non-switcher (n = 49,401), and incident biosimilar (n = 8318)). There were no differences in the outcome of mean HbA1c (7.9% for all subgroups). There were also no differences in the unadjusted rates of hospitalization and/or emergency room visits for hyper- and hypoglycemia between the prevalent originator non-switcher and originator switched to biosimilar subgroups (p = 0.09 and 0.38, respectively) or the incident originator non-switcher and incident biosimilar subgroups (p = 0.054 and 0.61, respectively). Finally, none of the HbA1c or hyperglycemia outcomes adjusted for baseline characteristics were statistically different. Adjusted analyses for rates of hospitalization and/or emergency room visits for hypoglycemia could not be performed due to the low number of events. Overall, patients who received insulin glargine-yfgn had similar effectiveness and safety outcomes as patients who received the originator.

The efficacy of combining adjuvants with non-surgical periodontal therapy in individuals with type 2 diabetes: A Bayesian network meta-analysis.

This Bayesian network meta-analysis of randomized controlled trials assessed the effect of adjuvant periodontal treatment in both periodontal and HbA1c outcomes in adult individuals with type 2 diabetes (T2DM). A systematic search was done up to February 2023 comparing sub-gingival debridement (SD) in combination with local or systemic adjuvant treatment with SD alone for individuals with T2DM. The primary outcomes were changes in absolute HbA1c levels and full-mouth probing depth reported at 3- to 6-month post-treatment. Seventy-two eligible publications evaluating 27 adjuvant treatments were retrieved. The combination of SD and systemic antibiotic metronidazole or SD and antioxidant alpha lipoic acid provided, respectively, 1.4% (95% credible interval [CrI] 0.48; 2.20) and 2.4% (95% CrI 1.50; 3.30) more significant improvement on HbA1c levels, and 0.89 mm (95% CrI 0.23; 1.50) and 0.92 mm (95% CrI 0.02; 0.92) greater periodontal probing depth reductions. Other adjuvant treatments provided added benefit to the periodontal outcomes without discernible effects on HbA1c. Adjuvant use of metronidazole or alpha lipoic acid was the best adjunct option to provide clinically meaningful HbA1c levels and probing depth reductions. However, no strong recommendation can be drawn due to the scarcity of studies for each adjuvant treatment and the low certainty of the resultant evidence.

Clinical attachment loss is cross-sectionally associated with elevated glucose among adults without diabetes.

We investigated whether periodontal measures are cross-sectionally associated with prediabetes and cardiometabolic biomarkers among non-diabetic younger adults. One thousand seventy-one participants (mean age = 32.2 years [SE = 0.3]; 73% female) from the Oral Infections, Glucose Intolerance and Insulin Resistance Study were enrolled. Full-mouth clinical attachment loss (fm-CAL), probing depth (fm-PD) and bleeding on probing were ascertained. Interproximal CAL (i-CAL) and probing depths (i-PD) served as our primary exposures. Glucose, HbA1c, insulin and insulin resistance (HOMA-IR) outcomes were assessed from fasting blood. Prediabetes was defined per American Diabetes Association guidelines. Prediabetes prevalence ratios (PR [95% CI]) and mean [SE] cardiometabolic biomarkers were regressed on periodontal variables via multivariable robust variance Poisson regression or multivariable linear regression. Prevalence of prediabetes was 12.5%. Fully adjusted prediabetes PR in Tertiles 3 versus 1 of mean i-CAL was 2.42 (1.77, 3.08). Fully adjusted fasting glucose estimates across i-CAL tertiles were 83.29 [0.43], 84.31 [0.37], 86.48 [0.46]; p for trend <.01. Greater percent of sites with i-PD ≥3 mm showed elevated natural-log-HOMA-IR after adjustment (0%-12% of sites = 0.33 [0.03], 13%-26% of sites = 0.39 [0.03], ≥27% of sites = 0.42 [0.03]; p for trend = .04). i-CAL (vs. fm-CAL) was associated with elevated fasting glucose and prediabetes, whereas i-PD (vs. fm-PD) was associated with insulin resistance. Future studies are needed to examine periodontal disease and incident prediabetes.

Adults living with type 2 diabetes experiences of a randomised adapted diabetes nutrition education programme: a qualitative process evaluation

Aim: The purpose of this study was to investigate how a randomised controlled trial (RCT) of an adapted diabetes nutrition education programme (NEP) was received by adults with sub-optimally controlled (HbA1c of ≥ 8%) type 2 diabetes in a tertiary setting. This could aid in understanding the small effect of NEP on HbA1c and other outcomes and the high attrition rate. Methods: This qualitative study was done alongside the year-long RCT. In the RCT, intervention participants received four NEP components, and both intervention and control group participants received education materials (fridge/wall poster). Five focus-group discussions were held with the intervention group participants at two time periods: after they completed the NEP curriculum (7th month) (n = 26; 67% of randomised participants [RP]( and at the end of the study (12 months) [n = 24; 61.5% RP). Nineteen (50% RP) control group participants were individually interviewed at the end of the study. Data were analysed using a thematic framework. Results: All participants (control and intervention) reported high satisfaction with the NEP. Participants emphasised the value of the fridge/wall poster for themselves and their families. Participants (control and intervention) reported various benefits of the NEP: improved diabetes knowledge, skills in dietary self-care, family support for self-care, better health and motivation for appropriate self-care. Some participants also reported positive changes to their diet and physical activity behaviours. The perceived benefits were the main reason for completing the study. Conclusions: Irrespective of the arm of participation, the NEP was well received, and perceived benefits inspired participation. The limited NEP impact and the sub-optimal programme participation do not appear to be related to participants’ perceptions of the adapted NEP.

Factors predicting glucose and weight response to injectable semaglutide (Ozempic): real-world data from the Association of British Clinical Diabetologists’ audit programme

Background: Previous randomised controlled trials have observed individual differences in response to Glucagon-Like Peptide-1 Receptor Agonists (GLP1RA) according to baseline characteristics such as glycated haemoglobin (HbA1c) and weight. The Association of British Clinical Diabetologists (ABCD) launched a nationwide UK audit in January 2019 to assess the clinical utility, efficacy and safety of injectable semaglutide in routine practice. The aim of this analysis was to investigate associations between baseline characteristics and HbA1c and weight reductions with semaglutide in real-world use. Methods: Data were extracted from the secure online tool and individuals who had baseline and follow-up data available within a defined 6 (3-9) month window were included. Variables were assessed as both continuous variables and categorical variables in a multivariate regression model. Missing data were multiply imputed. Results: In total, 620 individuals were included. Baseline characteristics: (mean±SD) age was 58.7±10.7 years, HbA1c 81.6±18.5 mmol/mol (9.5±1.7%), weight 108.2±24.2 kg and body mass index (BMI) 37.6±7.6 kg/m2. Median diabetes duration was 11.2 years (IQR 6.6-16) and 50.5% (313/620) of subjects were male. The median follow-up time was 0.5 years. HbA1c reduced by 14.9 mmol/mol (95% CI 13.5, 16.1) [-1.4% (95% CI - 1.2, -1.5)]; p&lt;0.001; and weight reduced by 4.2kg (95% CI 3.6, 4.8; p&lt;0.001). Higher HbA1c, younger age and GLP1RA naïvety were associated with larger HbA1c reduction. Higher baseline weight/BMI and GP1RA naïvety were associated with larger weight reduction. Conclusion: In this real-world study, baseline HbA1c and weightwere important predictors of HbA1c and weight reduction outcomes following initiation of semaglutide in routine clinical practice. Our data mirror existing randomised controlled trial data, but further evidence is being collected over a longer follow-up period.

Evidence that highly canalized fetal traits are sensitive to intergenerational effects of maternal developmental nutrition.

Maternal experiences before pregnancy predict birth outcomes, a key indicator of health trajectories, but the timing and pathways for these effects are poorly understood. Here we test the hypothesis that maternal pre-adult growth patterns predict pregnancy glucose and offspring fetal growth in Cebu, Philippines. Using multiple regression and path analysis, gestational age-adjusted birthweight and variables reflecting infancy, childhood, and post-childhood/adolescent weight gain (conditional weights) were used to predict pregnancy HbA1c and offspring birth outcomes among participants in the Cebu Longitudinal Health and Nutrition Survey. Maternal early/mid-childhood weight gain predicted birth weight, length, and head circumference in female offspring. Late-childhood/adolescent weight gain predicted birth length, birth weight, skinfold thickness, and head circumference in female offspring, and head circumference in male offspring. Pregnancy HbA1c did not mediate relationships between maternal growth and birth size parameters. In Cebu, maternal growth patterns throughout infancy, childhood, and adolescence predict fetal growth via a pathway independent of circulating glucose, with stronger impacts on female than male offspring, consistent with a role of developmental nutrition on offspring fetal growth. Notably, the strength of relationships followed a pattern opposite to what occurs in response to acute pregnancy stress, with strongest effects on head circumference and birth length and weakest on skinfolds. We speculate that developmental sensitivities are reversed for stable, long-term nutritional cues that reflect average local environments. These findings are relevant to public health and life-history theory as further evidence of developmental influences on health and resource allocation across the life course.