Baseline HbA1c Values Research Articles

Association of Clinical Factors with the Development of GDM in the Hoosier Mom’s Cohort

Introduction: Gestational diabetes mellitus (GDM) develops during pregnancy, raising the risk of adverse perinatal outcomes. The objective of this study was to investigate potential therapeutic targets for prepregnancy and early pregnancy interventions to decrease the impact of GDM on health during and after pregnancy. Methods: The Hoosier Mom’s Cohort was a prospective pregnancy cohort designed to assess for predictors of GDM. Inclusion criteria were gestational age <20 weeks, a singleton pregnancy, and being at least 18 years old. Individuals with a pregestational diabetes diagnosis, HbA1c at screening of ≥6.5, or abnormal 3-hour oral glucose tolerance test before 20 weeks of gestation were excluded. Study visits with survey completion and biospecimen collection occurred, one at enrollment, and one in the early third trimester. All participants were given a Garmin activity tracker to collect objective physical activity and sleep data. Sociodemographic, medical, behavioral, and psychosocial characteristics were obtained, and obstetric outcomes were abstracted after delivery by certified chart abstractors. The primary outcome was development of GDM. Associations between categorical variables and GDM were made with Chi-square testing, and those between continuous variables and GDM were done with t-test. Results: Of 411 participants recruited into the Hoosier Moms Cohort, complete data was available for 391 (95.1%). Participants had a mean age of 30 years, a BMI of 28, and 17% were of Hispanic ethnicity. Study participants self-identified mostly as White (71%) or Black (16%). 66% of participants were nulliparous. Additionally, 54% reported a family history of diabetes, with 4% of patients also reporting a prior history of GDM. A total of 39 participants (10.0%) developed GDM. Participants who developed GDM had significantly higher BMI at study entry (31.6 ±8.5 vs 27.2 ±6.5, p=0.003), lower probability of being nulliparous (15.38% vs 33.61%, p=0.02), higher baseline HbA1c values (5.24 ±0.3 vs 5.07 ±0.3, p<0.001), higher triglycerides levels (156.85 ±62 vs 134.16 ±54.5, p=0.022), and higher blood glucose values (85.90 ±14.4 vs 79.96 ±17.7, p=0.025) at first study visit. Additionally, 28% of participants who developed GDM had a prior history of GDM, compared to 2% of participants who did not (p<0.0001). Those who developed GDM had higher rates of chronic hypertension (12.82% vs 1.96%, p=0.0034) and higher insomnia scores (9.62 ±5.1 vs 7.80 ±4.7, p=0.028). Conclusion/ Implications: Multiple clinical factors were found to be statistically associated with the development of GDM. These characteristics will be utilized in a comprehensive predictive model using machine learning methodologies to guide clinical decisions early in pregnancy.

Hypoglycemia in patients with type 2 diabetes mellitus during hospitalization: associated factors and prognostic value

BackgroundThe risk factors for hypoglycemia during hospital admission and its consequences in patients with diabetes are not entirely known. The present study aimed to investigate the risk factors for hypoglycemia, as well as the potential implications of hypoglycemia in patients with type 2 diabetes mellitus admitted to the hospital.MethodsThis retrospective cohort study included 324 patients (214 [66.0%] men; median age 70 years, range 34–95 years) with type 2 diabetes admitted to a university hospital who were consulted the Endocrinology Department for glycemic control during a 12-month period. We investigated the potential role of demographic factors, metabolic factors, therapy, and comorbidities on the development of in-hospital hypoglycemia. We explored the prognostic value of hypoglycemia on mortality (both in-hospital and in the long-term), hospital readmission in the following year, and metabolic control (HbA1c value) after discharge (median follow-up, 886 days; range 19–1255 days).ResultsHypoglycemia occurred in 154 (47.5%) patients during their hospitalization and was associated with advanced age, previous insulin therapy, higher Charlson Comorbidity Index, lower body mass index and lower baseline HbA1c values. Hypoglycemia was associated with greater in-hospital and long-term mortality, longer hospital stays, higher readmission rates, and poorer metabolic control after discharge. These negative consequences of hypoglycemia were more frequent in patients with severe (≤ 55 mg/dL) hypoglycemia and in patients who had hypoglycemia during a greater percentage of hospitalization days.ConclusionsHypoglycemia during hospital admission is a marker of a poor prognosis in patients with type 2 diabetes.

Effectiveness of a Digital Health Application for the Treatment of Diabetes Type II-A Pilot Study.

(1) Background: This study aimed at providing preliminary evidence for mebix, an app-based treatment program for patients with diabetes mellitus type II. The main target was to show a positive healthcare impact as defined by improved blood glucose control, i.e., reduced HbA1c values. (2) Methods: For this, a 3-month, prospective, open-label trial with an intraindividual control group was conducted. Participants received the mebix intervention for 3 months. HbA1c values were observed every 3 months: retrospectively, at baseline, and 3 months after the start of using the app. Additionally, weight and patients' reported outcomes (well-being, diabetes-related distress, and self-management) were assessed. Data generated within the app were summarized and analyzed (steps, physical activity, fulfilled tasks, and food logs). (3) Results: After the usage of mebix for 3 months, participants significantly reduced their HbA1c levels (-1.0 ± 0.8%). Moreover, improvements in weight, well-being, and self-management as well as a reduction in diabetes-related distress were observed. App-generated data mainly supported the other main finding, that higher baseline HbA1c values lead to higher reductions. Overall, the study provided preliminary evidence that mebix can help patients improve metabolic and psychological health outcomes.

Impact of glycated hemoglobin on 2-year clinical outcomes in elderly patients with atrial fibrillation: sub-analysis of ANAFIE Registry, a large observational study

BackgroundThis ANAFIE Registry sub-analysis investigated 2-year outcomes and oral anticoagulant (OAC) use stratified by glycated hemoglobin (HbA1c) levels among Japanese patients aged ≥ 75 years with non-valvular atrial fibrillation (NVAF) with and without clinical diagnosis of diabetes mellitus (DM).MethodsThe ANAFIE Registry was a large-scale multicenter, observational study conducted in Japan; this sub-analysis included patients with baseline HbA1c data at baseline. The main endpoints evaluated (stroke/systemic embolic events [SEE], major bleeding, intracranial hemorrhage, cardiovascular death, all-cause death, and net clinical outcome [a composite of stroke/SEE, major bleeding, and all-cause death]) were stratified by HbA1c levels (< 6.0%; 6.0% to < 7.0%; 7.0% to < 8.0%; and ≥ 8.0%).ResultsOf 17,526 patients with baseline HbA1c values, 8725 (49.8%) patients had HbA1c < 6.0%, 6700 (38.2%) had 6.0% to < 7.0%, 1548 (8.8%) had 7.0% to < 8.0%, and 553 (3.2%) had ≥ 8.0%. Compared with other subgroups, patients with HbA1c ≥ 8.0% were more likely to have lower renal function, higher CHA2DS2-VASc and HAS-BLED scores, higher prevalence of non-paroxysmal AF, and lower direct OAC (DOAC) administration, but higher warfarin administration. The HbA1c ≥ 8.0% subgroup had higher event rates for all-cause death (log-rank P = 0.003) and net clinical outcome (log-rank P = 0.007). Similar trends were observed for stroke/SEE. In multivariate analysis, risk of all-cause death (adjusted hazard ratio [aHR]: 1.46 [95% confidence interval 1.11–1.93]) and net clinical outcome (aHR 1.33 [1.05–1.68]) were significantly higher in the HbA1c ≥ 8.0% subgroup. No significant differences were observed in risks of major bleeding or other outcomes in this and other subgroups. No interaction was observed between HbA1c and OACs. Use/non-use of antidiabetic drugs was not associated with risk reduction; event risks did not differ with/without injectable antidiabetic drugs.ConclusionsAmong elderly Japanese patients with NVAF, only HbA1c ≥ 8.0% was associated with increased all-cause death and net clinical outcome risks; risks of the events did not increase in other HbA1c subgroups. Relative event risks between patients treated with DOACs and warfarin were not modified by HbA1c level.Trial registrationUMIN000024006; date of registration: September 12, 2016.

117-LB: Impact of Bigfoot Unity Integrated CGM on HbA1c

Introduction: Continuous glucose monitoring (CGM) is a preferred method of glucose monitoring. Bigfoot Unity Diabetes Management is an integrated CGM (iCGM) system that incorporates remote patient monitoring with a mobile app, smart pen caps, and CGM via Libre Freestyle 2 sensors. Smart pen caps attach to rapid-acting and long-acting insulin pens and sync with patients’ CGM sensors to provide insulin dose recommendations based on the health care provider's (HCP) instructions. The smart pen caps also allow patients to view their last insulin dose and receive alerts for possible missed doses. The mobile app allows patients to review their HCP's instructions and receive critical alerts. Likewise, HCP can more closely track data to guide clinical assessments and plans. Objectives: Examine the efficacy of the Bigfoot Unity system in improving glycemic control. Methods: Baseline HbA1c values were obtained from 91 patients enrolled in the iCGM system and compared with Glucose Management Indicators (GMI), or estimated future HbA1c, after at least 30 days of iCGM use. Results: Patients were in the target blood glucose range 59.9% of the time with low incidences (0.01%) of very low blood glucose. Patients’ mean baseline HbA1c was 8.87% (SD 1.91). After at least 30 days of iCGM, patients’ mean GMI was 7.55%, (SD 1.02) indicating a statistically significant mean difference of 1.32%, (95% CI 0.86 to 1.79%, p &amp;lt;0. 0001). Conclusions: Use of Bigfoot Unity improves HbA1c. Disclosure P. Haque: None. S. Hall: None. P. Walker: None. K. Latif: None.

Safety and efficacy of once-weekly basal insulin Fc in people with type 2 diabetes previously treated with basal insulin: a multicentre, open-label, randomised, phase 2 study

The burden of daily basal insulins often causes hesitancy and delays in the initiation of insulin therapy. Basal insulin Fc (BIF, insulin efsitora alfa), designed for once-weekly administration, is a fusion protein combining a novel single-chain insulin variant with a human immunoglobulin G (IgG) Fc domain. In this study, we explored the safety and efficacy of BIF in people with type 2 diabetes who had been previously treated with basal insulin. For this phase 2, 44-site (clinical research centres and hospitals), randomised, open-label, comparator-controlled, 32-week study in the USA, Puerto Rico, and Mexico, we enrolled participants with type 2 diabetes. Eligible participants had to be adults (aged ≥18 years) and to have been treated with basal insulin and up to three oral antidiabetic medicines. Participants were randomly assigned (1:1:1) to subcutaneous administration of BIF (BIF treatment group 1 [BIF-A1] or 2 [BIF-A2]) or insulin degludec. Randomisation was stratified by country, baseline HbA1c values (<8·5% or ≥8·5%; <69·4 or ≥69·4 mmol/mol), use of sulfonylureas (yes or no), and baseline BMI (<30 or ≥30 kg/m2). The randomisation scheme was performed using an interactive web-response system, which ensured balance between treatment groups. Different fasting glucose targets for the BIF-A1 (≤7·8 mmol/L or ≤140 mg/dL; titrated every 2 weeks), BIF-A2 (≤6·7 mmol/L or ≤120 mg/dL; titrated every 4 weeks), and degludec (≤5·6 mmol/L or ≤100 mg/dL) groups were selected. Patients randomly assigned to BIF received a one-time loading dose ranging from 1·5-3 times their calculated weekly dose. The first weekly dose was administered 1 week after the loading dose. We used interstitial fasting glucose measurements from the Dexcom G6 continuous glucose monitoring system to titrate the basal insulin. The primary measure of glycaemic control was change in HbA1c from baseline to week 32 for BIF. BIF was also compared with degludec (with a non-inferiority margin of 0·40%). The efficacy analysis set consisted of data from all randomised study participants who received at least one dose of the study medication and participants were analysed according to the treatment they were assigned. The safety population was the same as the efficacy analysis set. The completed trial is registered at ClinicalTrials.gov (NCT03736785). Between Nov 15, 2018 and Feb 18, 2020, 399 participants were enrolled and randomised to BIF-A1 (n=135), BIF-A2 (n=132), or degludec (n=132); 202 (51%) were female and 197 (49%) were male. 379 were analysed for the primary outcome (BIF-A1: n=130; BIF-A2: n=125; degludec: n=124). Mean HbA1c change from baseline to week 32, the primary outcome, was -0·6% (SE 0·1%) for BIF-A1 and BIF-A2. Degludec achieved a change from baseline of -0·7% (0·1%). The pooled BIF analysis achieved non-inferiority versus degludec for the treatment difference in HbA1c (0·1% [90% CI -0·1 to 0·3]). The hypoglycaemia (≤3·9 mmol/L or ≤70 mg/dL) event rates (hypoglycaemia events per patient per year) in the BIF groups were 25% lower than those in the degludec group (treatment ratio BIF-A1 vs degludec was 0·75 [0·61-0·93]; and BIF-A2 vs degludec was 0·74 [0·58-0·94]). BIF was well tolerated; treatment-emergent adverse events were similar across groups. Weekly BIF achieved a similar efficacy compared with degludec despite higher fasting glucose targets in the BIF groups. Higher fasting glucose targets and lower glucose variability might have contributed to lower hypoglycaemia rates for BIF compared with degludec. These findings support continued development of BIF as a once-weekly insulin treatment for people with diabetes. Eli Lilly and Company.

Risk factors associated with glycated hemoglobin A1c trajectories progressing to type 2 diabetes

Background and objective The notion of prediabetes, defined by the ADA as glycated hemoglobin A1c (HbA1c) of 5.7–6.4%, implies increased vascular inflammatory and immunologic processes and higher risk for developing diabetes mellitus and major cardiovascular events. We aimed to determine the risk factors associated with rapid progression of normal and prediabetes patients to type 2 diabetes mellitus (T2DM). Methods Retrospective cohort study in a single 8-hospital health system in southeast Michigan, between 2006 and 2020. All patients with HbA1c <6.5% at baseline and at least 2 other HbA1c measurements were clustered in five trajectories encompassing more than 95% of the study population. Multivariate linear regression analysis was performed to examine the association of demographic and comorbidities with HbA1c trajectories progressing to diabetes. Results A total of 5,347 prediabetic patients were clustered based on their HbA1c progression (C1: 4,853, C2: 253, C66: 102, C12: 85, C68: 54). The largest cluster (C1) had a baseline median HbA1c value of 6.0% and exhibited stable HbA1c levels in prediabetic range across all subsequent years. The smallest cluster (C68) had the lowest median baseline HbA1c value and also remained stable across subsequent years. The proportion of normal HbA1c in each of the pre-diabetic trajectories ranged from 0 to 12.7%, whereas 81.5% of the reference cluster (C68) were normal HbA1c at baseline. The C2 (steady rising) trajectory was significantly associated with BMI (adj OR 1.10, 95%CI 1.03–1.17), and family history of DM (adj OR 2.75, 95%CI 1.32–5.74). With respect to the late rising trajectories, baseline BMI was significantly associated with both C66 and C12 trajectory (adj OR 1.10, 95%CI 1.03–1.18) and (adj OR 1.13, 95%CI 1.05–1.23) respectively, whereas, the C12 trajectory was also significantly associated with age (adj OR 1.62, 95%CI 1.04–2.53) and history of MACE (adj OR 3.20, 95%CI 1.14–8.93). Conclusions We suggest that perhaps a more aggressive preventative approach should be considered in patients with a family history of T2DM who have high BMI and year-to-year increase in HbA1c, whether they have normal hemoglobin A1c or they have prediabetes. KEY MESSAGES Progression to diabetes from normal or prediabetic hemoglobin A1c within four years is associated with baseline BMI. A steady rise in HbA1c during a four-year period is associated with age and family history of T2DM, whereas age and personal history of MACE are associated with a rapid rise in HbA1c. A more aggressive preventative approach should be considered in patients with a family history of T2DM who have high BMI and year-to-year increase in HbA1c.

Predictors and Effects of Participation in Peer Support: A Prospective Structural Equation Modeling Analysis.

Peer support provides varied health benefits, but how it achieves these benefits is not well understood. Examine a) predictors of participation in peer support interventions for diabetes management, and b) relationship between participation and glycemic control. Seven peer support interventions funded through Peers for Progress provided pre/post data on 1,746 participants' glycemic control (hemoglobin A1c), contacts with peer supporters as an indicator of participation, health literacy, availability/satisfaction with support for diabetes management from family and clinical team, quality of life (EQ-Index), diabetes distress, depression (PHQ-8), BMI, gender, age, education, and years with diabetes. Structural equation modeling indicated a) lower levels of available support for diabetes management, higher depression scores, and older age predicted more contacts with peer supporters, and b) more contacts predicted lower levels of final HbA1c as did lower baseline levels of BMI and diabetes distress and fewer years living with diabetes. Parallel effects of contacts on HbA1c, although not statistically significant, were observed among those with baseline HbA1c values > 7.5% or > 9%. Additionally, no, low, moderate, and high contacts showed a significant linear, dose-response relationship with final HbA1c. Baseline and covariate-adjusted, final HbA1c was 8.18% versus 7.86% for those with no versus high contacts. Peer support reached/benefitted those at greater disadvantage. Less social support for dealing with diabetes and higher PHQ-8 scores predicted greater participation in peer support. Participation in turn predicted lower HbA1c across levels of baseline HbA1c, and in a dose-response relationship across levels of participation.

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.

The influence of SLC22A3 rs543159 and rs1317652 genetic variants on metformin therapeutic efficacy in newly diagnosed patients with type 2 diabetes mellitus: 25 weeks follow-up study

Background and aimsAmong anti-diabetic medications, metformin has been proven to be the preferred initial pharmacologic agent for type 2 diabetes mellitus (T2DM) treatment. Despite its safety and efficacy, the response to metformin varies between individuals. Genetic variations, especially within genes involved in pharmacokinetics and pharmacodynamics of metformin (e.g SLC22A3), have been suggested to be responsible for the observed inter-individual differences. By considering the undeniable role of organic cation transporter 3 in hepatic uptake of metformin, this study was aimed to investigate the association of rs543159 and rs1317652 variants in SLC22A3 gene with response to metformin monotherapy in newly diagnosed patients with T2DM. MethodsThe study included 200 T2DM patients who received metformin monotherapy for 25 weeks. The patients were classified into 2 groups according to their HbA1c values: the responders (reduction in HbA1c levels by at least 1% after 25 weeks treatment with metformin) and non-responders (less than 1% reduction in HbA1c levels after 25 weeks treatment with metformin). We used tetra ARMS-PCR method to determine genotypes of the target variants. ResultsFor the rs543159, CA and AA genotypes were more frequent in responders as compared to non-responders (OR = 2.48; 95% CI = 1.28–4.78, P-value = 0.0057) under the dominant model. In case of rs1317652 CC and CT genotypes were more frequent in metformin responders as compared to non-responder group (OR = 2.49; 95% CI = 1.32–4.70, P-value = 0.0043) under the dominant model. Parameters such as fasting blood sugar (FBS), HbA1c, and total cholesterol (TC) levels were significantly lower in the responder group after 25 weeks of metformin monotherapy. Moreover, according to the result of multiple linear regression rs543159 and base line HbA1c values are significantly associated with response to metformin monotherapy. ConclusionOur results suggested that rs543159 and rs1317652 in SLC22A3 gene might be associated with variability in response to metformin therapy in T2DM patients.

Video Telehealth Access and Changes in HbA1c Among People With Diabetes

Video telehealth can offer people convenient, real-time access to clinicians without arranging transportation or time off work. Among people with diabetes, this study examines the association between video telehealth access and changes in HbA1c. This longitudinal cohort study (2016-2019) used linear regression with person-level fixed effects, stratified by baseline HbA1c (last value in 2015), to examine the association between video visit access and changes in HbA1c. HbA1c values were categorized into 3 periods of video visit exposure: (1) before any video visit, (2) during video visit transition year (calendar year of the first video visit), and (3) after video visits. The model compared changes in HbA1c values collected before the patient had any video visits with those collected after the transition year. Analyses were conducted in September 2020. Among 204,301 people with diabetes, video visit access was associated with a statistically significant reduction of 0.15 (95% CI= -0.19, -0.11) percentage points in HbA1c, with greater reductions among patients with an elevated baseline HbA1c value (-0.22 percentage points, 95% CI= -0.32, -0.11) and with no baseline HbA1c measurement (-0.39 percentage points, 95% CI= -0.71, -0.07). Gaining access to video telehealth was associated with reductions in HbA1c among people with diabetes. Video telehealth offers people with chronic conditions a new, convenient way to access health care, is not associated with worsening HbA1c, and may support better disease management, particularly among patients with higher baseline HbA1c.

Analysis of an Indian diabetes prevention programme on association of adipokines and a hepatokine with incident diabetes

To study the association and possible predictive role of visfatin, resistin, fetuin-A and chemerin with incident type 2 diabetes (T2DM) among Asian Indians with prediabetes. Their association with insulin resistance, β-cell function, glycaemia and anthropometry were also studied. This is a nested case–control study of a large 2-year prospective prevention trial in persons at high risk of developing T2DM. Baseline HbA1c values between 6.0% (42 mmol/mol) and 6.2% (44 mmol/mol) were chosen for this analysis (n = 144). At follow-up, persons with incident T2DM (HbA1c ≥ 6.5%, 48 mmol/mol) were grouped as cases (n = 72) and those reverted to normoglycaemia, (HbA1c < 5.7% (39 mmol/mol) as controls (n = 72). Insulin resistance showed the strongest association with incident T2DM ((Odds Ratio (OR): 23.22 [95%CI 6.36–84.77]; p < 0.0001). Baseline visfatin (OR: 6.56 [95%CI 2.21–19.5]; p < 0.001) and fetuin-A (OR: 1.01 [95%CI (1.01–1.04)]; p < 0.0001) independently contributed to the conversion of prediabetes to T2DM. The contribution was significantly higher when their elevated levels coexisted (OR: 12.63 [95%CI 3.57–44.63]; p < 0.0001). The area under the curve was 0.77 ± SE 0.4 (95%CI 0.69–0.85) and 0.80 ± SE 0.04 (95%CI 0.73–0.88) for visfatin (median 17.7 ng/ml, sensitivity and specificity: 75%, p < 0.0001) and fetuin-A (mean 236.2 µg/ml, sensitivity: 71%, specificity: 75%, p < 0.0001) respectively. Higher baseline visfatin and fetuin-A concentrations are strongly associated with incident T2DM and are predictive of future diabetes.

The bidirectional longitudinal association between depressive symptoms and HbA1c : A systematic review and meta-analysis.

AimTo investigate whether there is a bidirectional longitudinal association of depression with HbA1c.MethodsWe conducted a systematic literature search in PubMed, PsycINFO, CINAHL and EMBASE for observational, longitudinal studies published from January 2000 to September 2020, assessing the association between depression and HbA1c in adults. We assessed study quality with the Newcastle‐Ottawa‐Scale. Pooled effect estimates were reported as partial correlation coefficients (rp) or odds ratios (OR).ResultsWe retrieved 1642 studies; 26 studies were included in the systematic review and eleven in the meta‐analysis. Most studies (16/26) focused on type 2 diabetes. Study quality was rated as good (n = 19), fair (n = 2) and poor (n = 5). Of the meta‐analysed studies, six investigated the longitudinal association between self‐reported depressive symptoms and HbA1c and five the reverse longitudinal association, with a combined sample size of n = 48,793 and a mean follow‐up of 2 years. Higher levels of baseline depressive symptoms were associated with subsequent higher levels of HbA1c (partial r = 0.07; [95% CI 0.03, 0.12]; I238%). Higher baseline HbA1c values were also associated with 18% increased risk of (probable) depression (OR = 1.18; [95% CI 1.12,1.25]; I20.0%).ConclusionsOur findings support a bidirectional longitudinal association between depressive symptoms and HbA1c. However, the observed effect sizes were small and future research in large‐scale longitudinal studies is needed to confirm this association. Future studies should investigate the role of type of diabetes and depression, diabetes distress and diabetes self‐management behaviours. Our results may have clinical implications, as depressive symptoms and HbA1c levels could be targeted concurrently in the prevention and treatment of diabetes and depression.RegistrationPROSPERO ID CRD42019147551.

869-P: Patient-Provider Video Visit Use and HbA1c Control among Patients with Diabetes

Video telemedicine can offer patients direct real-time convenient access to clinicians without arranging transportation or work time-off, improving access to diabetes care and self-management support. We examined the association between video visit use and hemoglobin A1c (HbA1c) among patients with diabetes. In a longitudinal study, within a large integrated delivery system where patients were first able to self-schedule real-time physician video visits in 2016, we used the clinical registry to identify patients with diabetes (2015), and followed their video visit use and subsequent HbA1c values over time (2016-2019). Using linear regression with patient-level fixed effects (within-patient changes), adjusting for calendar year and month and time-changing patient mobile portal access, we measured the association between use of video visits as a time-changing variable and the patient’s yearly HbA1c values (in subsequent calendar years after video visit use). We then stratified analyses by baseline HbA1c value: &amp;lt;8%, ≥8%, no value (defined as lower patient engagement). Among 204,301 patients with diabetes, 50% were 65 years or older, 48% were women, and 45% were of white race/ethnicity. Overall, 95% of patients had a baseline HbA1c value, 24% had HbA1c values ≥8%. Patient use of video visits was associated with an overall statistically significant reduction in HbA1c value by 0.15% (95% CI: 0.11%-0.19%). Among those with baseline HbA1c values ≥8%, using video visits was associated with a HbA1c value reduction of 0.22% (95% CI: 0.12%-0.32%), and among patients with lower baseline engagement (i.e., no baseline HbA1c measurement), using video visits was associated with a HbA1c reduction of 0.39% (95% CI: 0.07%-0.71%). Use of video visit was associated with improved glycemic control among patients with diabetes, with greater improvements found among patients with worse baseline control and lower engagement. Video visits may offer convenient health care access to improve diabetes management. Disclosure M. Reed: None. A. Gopalan: None. I. Graetz: None. L. Hsueh: None. J. Huang: None. E. Muelly: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK085070)

Predictors of Normalization of Fasting Glucose in Patients With Prediabetes Using Remote Continuous Care Emphasizing Low Carbohydrate Intake

Background: Prediabetes phenotypes differ based on whether an individual exhibits impaired glucose tolerance (IGT), impaired fasting glucose (IFG), or both. The traditional diabetes prevention approach focused on weight loss via fat/caloric restriction and exercise appears less effective in those with IFG. Given that even transient regression to normal glucose regulation is associated with reduced risk of progression to type 2 diabetes, interventions that elicit normal fasting glucose (NFG) may be beneficial. Here, we explored predictors of normalization of fasting glucose (FG) over one-year treatment with carbohydrate restricted nutrition therapy (Carb-R) delivered via a continuous remote care model. Methods: Data were obtained from medical records of adults with prediabetes who were treated at least one year at time of analysis. Of 738 patients with an antecedent prediabetes diagnosis, 460 had IFG (100mg/dL to 125mg/dL) at enrollment in the clinic and were included in this analysis. Patients were counseled on Carb-R targeting nutritional ketosis (NK) and reported fasting blood glucose, blood beta-hydroxybutyrate (BHB), and weight via an app facilitating remote monitoring and medical/coaching support. BHB ≥0.5 mM indicated NK. Cox proportional hazard regression was used to model time of first incidence of NFG at 3, 6, 9, and 12 months and to assess if normalization of fasting glucose was associated with baseline factors, weight change, metformin use, and degree or frequency of NK achieved, analyzed separately. Mean±SE is reported. Results: Patients with IFG were 53.9±0.4 years of age, 64.0% female, HbA1c 5.92±0.02%, and fasting glucose 114.5±0.8 mg/dL at enrollment. During treatment, 199 (43.3%) patients normalized FG at ≥1 time point with mean weight loss of 10.0±0.4 kg (-8.9%) at time of normalization, 192 (41.7%) did not, and 69 (15.0%) were missing glucose data. In an adjusted multivariate model, lower baseline HbA1c (HR 0.60, p=0.03), female sex (HR 1.39, p=0.04), and greater mean BHB value (HR 1.83, p<0.001) or higher proportion of days on which NK was reported (HR 3.23, p<0.001) were associated with reversion to NFG. Age, metformin use, weight change, and baseline fasting glucose, weight, triglycerides, HDL-C, and LDL-C were not associated with reversion to NFG (p>0.05). Conclusions: Greater adherence to Carb-R indicated by greater BHB values and a greater proportion of days in NK were strongly associated with normalization of FG in prediabetes patients with IFG. Weight loss, a common goal for diabetes prevention, was not associated with reversion to NFG. Future studies should assess the effects of Carb-R including NK in other prediabetes phenotypes and on progression to type 2 diabetes.

Long-Term Effectiveness and Safety of Once Weekly Dulaglutide as Add-on to Metformin or Metformin Plus Insulin Secretagogues in Obesity and Type 2 Diabetes

Aim of this monocentric retrospective observational study was to evaluate the 18-month effectiveness and safety of once weekly 1.5 mg GLP-1 receptor agonist (GLP-1 RA) dulaglutide (DU) as add-on to metformin (MET) or MET plus conventional insulin secretagogues (SFU/glinide) in a study cohort with excess body weight (BW) and type 2 diabetes (T2D). Comparative efficacy versus once daily 1.2/1.8 mg liraglutide (LIRA) in a study sample naïve to GLP-1 RAs, matching for age, gender, BMI, T2D duration, cardiovascular comorbidities and medications, was addressed as a secondary aim. Clinical and biochemical data for efficacy outcomes and information on drug discontinuation due to adverse events (AEs) were collected from digital records. Initial analysis included 126 overweight and obese T2D patients (48.4% females). Out of these, 13 discontinued DU due to moderate-severe gastrointestinal AEs after a median follow-up of 6 (3 to 8) months, while 65 completed 18 months of continuous therapy. At 6 months, there was a significant median HbA1c reduction of -0.9 (-1.50 to -0.20) % with respect to baseline values (p<0.001), which remained stable during 18 months of follow-up. These results were accompanied by a moderate BW loss sustained over time, with a median reduction of -1.16 (-4,29 to 0.45) % at 6 months and -1.47 (-4.2 to 0.72) % at 18 months (p=0.048). At univariate Spearman analysis, a negative correlation between baseline BMI and risk of drug discontinuation due to gastrointestinal AEs was observed. The protective effect of obesity (BMI ≥ 30kg/m2) against drug discontinuation was confirmed by an exploratory logistic regression analysis, while adjusting for confounders [OR 0.211 (95%CI 0.058–0.771), p=0.019]. Neither gender, nor age, nor T2D duration, nor concomitant SUF/glinide use, nor shifting to DU from other GLP-1 RAs influenced its long-term effectiveness. However, higher baseline HbA1c values emerged as predictors of clinically relevant efficacy outcomes, either in form of HbA1c reduction ≥ 0.5% [OR 2.961 (95%CI 1.394–6.290), p=0.005] or BW loss ≥ 5% [OR 2.571 (95%CI 1.171–5.644), p=0.019]. The efficacy outcomes were corroborated by head-to-head comparison with LIRA, a GLP-1 RA with durable beneficial effects on glycemic control and BW in real word scenarios (1). With the advantage of once weekly administration, at 18-month follow-up, a significant larger fraction of patients on DU therapy reached glycemic targets (HbA1c ≤ 7.0%) when compared to those on LIRA: from 14.8% at baseline (both groups) to 64.8% with DU and 42.6% with LIRA (p=0.033). Although limited by a retrospective design and lack of constant up-titration for LIRA to the highest dose, these findings indicate that the beneficial glycometabolic responses to DU on a background of MET or MET plus SFU/glinide are durable, especially in presence of obesity and greater HbA1c impairment.(1) Ref: Mirabelli et al. IJERPH. 2019;17(1):207.

Clinical Effectiveness and Safety of Once-Weekly GLP-1 Receptor Agonist Dulaglutide as Add-On to Metformin or Metformin Plus Insulin Secretagogues in Obesity and Type 2 Diabetes.

Aims and methods: The aim of this monocentric retrospective observational study was to evaluate the 18-month safety and effectiveness of GLP-1 receptor agonist (GLP-1 RA) dulaglutide (DU) 1.5 mg/once weekly as an add-on to metformin (MET) or MET plus conventional insulin secretagogues in a study cohort with excess body weight and type 2 diabetes (T2D). Comparative efficacy versus liraglutide (LIRA) 1.2–1.8 mg/once daily in a study sample naïve to GLP-1 RAs, frequency matching for age, gender, T2D duration, degree of glycemic impairment, cardiovascular comorbidities, and medications, was addressed as a secondary aim. Clinical and biochemical data for efficacy outcomes and information on drug discontinuation due to adverse events (AEs) were collected from digital records. Results: Initial analysis included 126 overweight and obese T2D patients (48.4% females). Out of these, 13 discontinued DU due to moderate–severe gastrointestinal AEs after a mean follow-up of 6 (4 standard deviations (SD)) months, while 65 completed 18 months of continuous therapy. At 6 months, there was a significant mean HbA1c reduction of −0.85% (1.17 SD) with respect to baseline values (p < 0.001), which remained stable during 18 months follow-up. These results were accompanied by a moderate weight loss sustained over time, with a mean reduction of −2.0% (4.3 SD) at 6 months and −1.3% (4.8 SD) at 18 months (p = 0.091). At univariate analysis, a negative correlation between baseline body mass index (BMI) and risk of drug discontinuation due to gastrointestinal AEs was observed. The protective effect of obesity against drug discontinuation was confirmed by logistic regression analysis. Neither gender, nor age, nor T2D duration, nor concomitant conventional insulin secretagogue use, nor switching to DU from other GLP-1 RAs influenced its long-term effectiveness. However, higher baseline HbA1c values emerged as predictors of clinically relevant efficacy outcomes, either in terms of HbA1c reduction ≥ 0.5% or body weight loss ≥ 5%. The efficacy outcomes were corroborated by head-to-head comparison with LIRA, a GLP-1 RA with durable beneficial effects on glycemic control and body weight in real-world experiences. With the advantage of once-weekly administration, at 18-month follow-up, a significantly larger fraction of patients on DU therapy reached glycemic targets (HbA1c ≤ 7.0%) when compared to those on LIRA: from 14.8% at baseline (both groups) to 64.8% with DU and 42.6% with LIRA (p = 0.033). Conclusions: Although limited by a retrospective design and lack of constant up-titration for LIRA to the highest dose, these findings indicate that the beneficial responses to DU on a background of MET or MET plus insulin secretagogues are durable, especially in the presence of obesity and greater HbA1c impairment.

Association between HbA1C (Glycated Hemoglobin) and Clinical Outcomes in Patients with Subarachnoid Hemorrhage After Neuro-intervention

Our study investigated the association between the level of HbA1c (glycated hemoglobin) at admission and the prognosis of aneurysmal subarachnoid hemorrhage (SAH). A total of 510 patients treated with neuro-intervention for aneurysmal SAH and with data for admission HbA1c (glycated hemoglobin) were included. Favorable clinical outcome was defined as modified Rankin Scale (mRS) score of 0-2 at 3 months. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff value of HbA1C for unfavorable clinical outcomes. Logistic regression was used to evaluate the association between HbA1C level and outcomes. The optimal cutoff value of HbA1C was identified as 6.0% (P < 0.001), and patients with a high HbA1C (≥ 6.0%) had a lower prevalence of favorable clinical outcomes than patients with low HbA1C (< 6.0%) (P < 0.001). High HbA1C (≥ 6.0%) was independently associated with unfavorable clinical outcome (OR 2.84; 95% CI: 1.52-5.44; P = 0.004). The risk of unfavorable clinical outcome was significantly increased in patients with HbA1C (≥ 7.0%, < 8%) and HbA1C (≥ 8.0%) compared with lower baseline HbA1C (≥ 6.0%, < 7%) values (OR 2.17; 95% CI: 1.87-5.13; P = 0.011 and OR 4.25; 95% CI: 3.17-8.41; P = 0.005). Our study showed that HbA1C could be an independent predictor of worse outcomes following neuro-intervention for aneurysmal SAH. High HbA1C (≥ 6.0%) was associated with unfavorable clinical outcomes, and gradual elevation of HbA1C contributed to an increase in the risk of worse clinical outcomes after SAH.

A Japanese Study Assessing Glycemic Control with Use of IDegAsp Co-formulation in Patients with Type2 Diabetes in Clinical Practice: The JAGUAR Study.

IntroductionThe aim of this study was to evaluate the glycemic control and safety of insulin degludec/insulin aspart (IDegAsp) co-formulation in Japanese patients with type 2 diabetes (T2D) in a real-world clinical setting, including elderly patients (aged > 75 years).MethodsPatients (≥ 18 years) diagnosed with T2D, previously treated with insulin were included from the Japanese Medical Data Vision database. Baseline data were taken at the index date, defined as the first IDegAsp prescription claim. Change in glycated hemoglobin (HbA1c) at 12 months was estimated using a mixed model repeated measures analysis. The proportion of patients achieving target HbA1c < 8.0% without experiencing hypoglycemia (identified by International Classification of Disease codes) was calculated at 12 months (365 ± 90 days) after baseline.ResultsOverall, 10,798 patients were included, 3940 were aged > 75 years, and 913 had baseline HbA1c values available. Switching to IDegAsp was associated with significantly improved HbA1c values at 12 months (− 1.23% [− 1.43, − 1.02]95%CI, p < 0.001) versus baseline. Moreover, relative to baseline, a significantly greater proportion of patients achieved HbA1c < 8.0% without hypoglycemia at 12 months, relative rate (RR) 1.30 [1.15, 1.45]95%CI, p < 0.001. Results were similar for patients aged ≤ 75 years and aged > 75 years; 66% and 64% of patients, respectively, achieved HbA1c < 8.0% without hypoglycemia at 12 months.ConclusionSwitching from insulin to IDegAsp co-formulation was associated with significantly improved glycemic control and a reduction in hypoglycemia rate during 12 months of follow-up in Japanese patients with T2D, including those aged > 75 years.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01623-y.

Remote patient monitoring sustains reductions of hemoglobin A1c in underserved patients to 12 months

AimsWe sought to determine whether underserved patients enrolled in a statewide remote patient monitoring (RPM) program for diabetes achieve sustained improvements in hemoglobin A1c at 6 and 12 months and whether those improvements are affected by demographic and clinical variables. MethodsDemographic and clinical variables were obtained at baseline, 6 months and 12 months. Baseline HbA1c values were compared with those obtained at 6 and 12 months via paired t-tests. A multivariable regression model was developed to identify patient-level variables associated with HbA1c change at 12 months. ResultsHbA1c values were obtained for 302 participants at 6 months and 125 participants at 12 months. Compared to baseline, HbA1c values were 1.8% (19 mmol/mol) lower at 6 months (p < 0.01) and 1.3% (14 mmol/mol) lower at 12 months (p < 0.01). Reductions at 12 months were consistent across clinical settings. A regression model for change in HbA1c showed no statistically significant difference for patient age, sex, race, household income, insurance, or clinic type. ConclusionsPatients enrolled in RPM had improved diabetes control at 6 and 12 months. Neither clinic type nor sociodemographic variables significantly altered the likelihood that patients would benefit from this type of technology. These results suggest the promise of RPM for delivering care to underserved populations.