Lower HbA1c Research Articles

Adequate sleep duration accentuates the effect of glucagon-like peptide-1 receptor variant on HbA1c: A gene-environment interaction study

BackgroundBoth glucagon-like peptide-1 receptor (GLP1R) agonists and lifestyle modifications are widely adopted in managing glycemia. However, the joint effects of GLP1R agonists with lifestyle on glycemic traits have not been evaluated. MethodsThis gene-environment study tested the interaction between GLP1R-rs10305492 variant, consistent with the effect of GLP1R agonist therapies, and four lifestyle factors (diet, physical activity, sleep duration, and chronotype) for glucose and glycated hemoglobin (HbA1c) levels among 263,846 UK Biobank participants. Linear regression models were conducted to evaluate the effects of the rs10305492 and lifestyle factors on glucose and HbA1c levels. ResultsGLP1R-rs10305492-AA/AG genotype combined a healthy diet, regular physical activity, adequate sleep duration, or morning chronotype were associated with lower glucose and HbA1c levels (all P for trend < 0.001). A synergistic effect was found between rs10305492 and sleep duration on HbA1c, suggesting a recommended adequate sleep duration (7–8 h/day) may amplify the HbA1c lowering effect of GLP1R agonists. Joint effects of the rs10305492 and adequate sleep were associated with a 26 % reduced risk of hyperglycemia (>7.8 mmol/L) risk and a 22 % lower of high HbA1c (>39 mmol/mol or 5.7 %). ConclusionsCombining GLP1R agonists with adequate sleep may provide additional benefits for glycemic control in clinical practice.

The effect of diabetes education on maternal and neonatal outcomes in pregnant women diagnosed with gestational diabetes.

Education during pregnancy is important for the development of the pregnant woman's ability to adapt to change and for a healthy birth. In this study, we aimed to examine the effects of education through a diabetes education program on maternal and newborn health in women diagnosed with gestational diabetes. In our study, we compared the maternal and neonatal health outcomes of pregnant women who participated in the diabetes education program and were diagnosed with gestational diabetes with the outcomes of pregnant women who did not participate in the diabetes education program and were diagnosed with gestational diabetes. The study included patients who were diagnosed with diabetes between 24and 26 weeks gestation at a tertiary education and research hospital and who underwent a 75-gram OGTT test. Age, BMI, parity, method of delivery, weight gain during pregnancy, newborn birth weight, gestational age and Apgar scores were compared. The study included 119 patients and analyzed maternal-neonatal outcomes. There were no statistically significant differences in age (33 ± 5.7 versus 31 ± 5.2), body mass index (BMI) (32.2 vs. 31.2), gravidity, parity, number of miscarriages, mode of delivery, family history of diabetes, smoking, prenatal corticosteroid use, and gestational age at delivery. The HbA1c value (p: 0.013), the total weight gain during pregnancy (p: 0.015), the need for insulin treatment (p: 0.002), and the birth weight (0.005) were significantly higher in the group without diabetes education. In our study, diabetic school education was associated with lower HbA1c levels, less weight gain and less need for insulin therapy. When the results were categorized by insulin use, it was found that in patients using insulin, those who received diabetic school education had fewer macrosomic fetuses, whereas in patients not using insulin, those who received diabetic school education had lower maternal weight gain during pregnancy.

Abstract 4137914: Eligibility for Semaglutide in US Adults with Diabetes and Potentially Preventable Cardiovascular Events Projected from the SUSTAIN-6 Trial

Background: The Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6) trial showed cardiovascular disease (CVD) benefits of semaglutide therapy in patients with type 2 diabetes mellitus (T2DM). Purpose: To estimate the number of US adults with T2DM that may be eligible for semaglutide based on SUSTAIN-6 eligibility criteria and the number of preventable CVD events from semaglutide treatment based on observed CVD event reductions in SUSTAIN-6. Methods: We included US adults with T2DM from the National Health and Nutrition Examination Survey (NHANES) 2011– 2020 who had eligibility criteria from SUSTAIN-6. This included an HbA1c&gt;7.0%, age &gt; 50 with established CVD, heart failure, or chronic kidney disease or an age &gt; 60 with at least one CVD risk factor. We estimated the number of primary composite and secondary CVD endpoints that would occur based on SUSTAIN-6 treated and placebo published event rates, with the difference indicating the number of preventable events (and annualized based on median 2.1 year follow-up time). Results: Among 5002 (projected to 34.0 million [M]) adults we identified with T2DM, we estimated 1,132 (6.9 million) (20.3%) to fit SUSTAIN-6 eligibility criteria. Compared to SUSTAIN-6 trial participants, our sample was slightly older, had a higher proportion of Black participants, shorter duration of diabetes, lower HbA1c and diastolic blood pressure, but similar body mass index and systolic blood pressure. Prior history of ischemic heart disease, myocardial infarction, and stroke were also less common in our NHANES sample. From SUSTAIN-6 semaglutide and placebo primary composite CVD event rates of 6.6% and 8.9%, respectively, we estimated 456,060 and 614,990 events would occur, respectively, for a total of 159,930 preventable CVD events, or 75,681 on an annualized basis. We similarly estimated annualized preventable events for secondary outcomes as shown in the Figure. Conclusion: Semaglutide may prevent many fatal and non-fatal CVD events if provided to US adults meeting SUSTAIN-6 eligibility criteria. More efforts are needed to educate the healthcare providers on the CVD benefits from newer diabetes therapies, including semaglutide.

Abstract 4137917: Eligibility and Preventable CVD Events in US Adults with Cardiovascular Disease and Overweight or Obesity: Projections from the SELECT Trial

Background: The Trial to Evaluate Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT) showed cardiovascular disease (CVD) benefits of semaglutide therapy in patients with preexisting CVD and overweight or obesity. Purpose: To estimate the number of US adults with CVD and overweight or obesity that may be eligible for semaglutide based on SELECT eligibility criteria and the number of preventable CVD events from semaglutide treatment based on observed CVD event reductions in SELECT. Methods: We included US adults from the National Health and Nutrition Examination Survey (NHANES) 2011-2020 who had eligibility criteria from SELECT. This included patients aged &gt; 45 years who had preexisting CVD and a BMI of &gt; 27kg/m 2 but no history of diabetes. Using NHANES sample weighting, we estimated the number of SELECT-eligible US adults and primary composite and secondary CVD endpoints that would occur based on SELECT treated and placebo published event rates, with the difference indicating the number of preventable events (and annualized based on mean 3.3-year follow-up). Results: Among 8783 (projected to 77.9 million [M]) adults with overweight or obesity, we estimated 493 (4.1 million) (5.61%) to fit SELECT eligibility criteria. Compared to SELECT trial participants, our sample had a higher proportion of Black participants and was older with higher levels of diastolic blood pressure, total, LDL and HDL-cholesterol, and lower BMI, HbA1c, eGFR and triglycerides. Prior myocardial infarction was less common, but stroke was more common in our sample. From SELECT semaglutide and placebo primary composite CVD event rates of 6.5% and 8.0%, respectively, we estimated 79949 and 98399 CVD events would occur annually, the difference being 18450 potentially preventable CVD events. Moreover, we similarly estimated 104,549 and 357,928 annual preventable cases of diabetes and pre-diabetes, respectively. The Figure shows the estimated number of primary and secondary CVD outcomes that could be prevented annually. Conclusion: Semaglutide may prevent many fatal and non-fatal CVD events, as well as incident cases of diabetes and pre-diabetes if provided to US adults meeting SELECT eligibility criteria. More efforts are needed to educate clinicians and patients on the benefits of semaglutide 2.4mg in those with preexisting CVD and overweight or obesity.

Postnatal levels of glycated albumin and glycated hemoglobin A1c in mothers of large-for-gestational-age newborns

BackgroundGestational diabetes mellitus (GDM) is an important cause of macrosomia. The value of glycated albumin (GlyA) has been demonstrated to be a useful marker of glycemic control in pregnancy and a predictor of adverse perinatal outcomes. The aim of this study was to investigate the relationship between the postnatal levels of GlyA and glycated hemoglobin A1c (HbA1c) regarding the prenatal diagnosis of GDM in mothers of large-for-gestational-age (LGA) newborns.MethodsThe study included mothers and their LGA newborns born between July 2017 and September 2019. The mothers were grouped according to the prenatal diagnosis of GDM, and measurements of GlyA and HbA1c levels in their serum were performed on the first day after delivery of a LGA newborn.ResultsA total of 61 LGA newborns and their mothers were enrolled in the study. The median GlyA level was higher, at 16.4% (81.0 µmol/L), whereas the HbA1c level was lower in the group without a prenatal diagnosis of GDM; the differences between groups regarding the GlyA and HbA1c levels were not significant (p &amp;gt; 0.05). The postnatal level of maternal GlyA was positively correlated with birth weight (β = 0.022, p = 0.007), but no correlation with the presence of other adverse perinatal outcomes was found.ConclusionMothers of LGA newborns who were not diagnosed with GDM during pregnancy had higher median levels of GlyA and lower HbA1c levels than mothers with prenatal diagnosis of GDM. Values of GlyA in mothers were positively correlated with the birth weight of their newborns but no correlation with other adverse perinatal outcomes was found. Our results indicate the potential value of GlyA for screening of GDM in the last trimester of pregnancy.

Benchmarking the medication efficiency and technological progress of diabetes drugs

BackgroundDiabetes poses a serious global challenge, given its increasing prevalence, detrimental effects on public health, and substantial economic burden. Since 1950s, tens of drugs have been approved by the United States (US) Food and Drug Administration (FDA). In the past decade, the medical community and regulatory agencies have moved away from the glucose-centric paradigm and increasingly call for a holistic approach to assess different treatments’ benefits and harms.ObjectiveThis study aimed to assess the medication efficiency and technological progress of Type 2 Diabetes (T2D) drugs, by considering their physiological outcomes, including both benefits (i.e., glucose lowering and weight loss) and adverse effects (mortality), relative to dosing frequency.MethodsTo derive medication efficiency, this study utilized data from the US FDA and prominent meta-analyses. Given that both the benefits and adverse effects of medications are multidimensional, this study employed a nonparametric frontier method, the data envelopment analysis (DEA) model, to integrate these factors into a measure of medication efficiency. Physiological outcomes could assume both positive and negative values. Adverse effects were regarded undesirable outputs. The DEA model was built under the framework of directional distance function and was able to handle negative and undesirable values which naturally arose in the case of T2D medications.ResultsThe paper presented a ranking of 20 T2D drugs in terms of medication efficiency. Three of them were able to attain the highest medication efficiency, all of which were in the GLP-1 class, including oral Semaglutide, subcutaneous Semaglutide and Dulaglutide. However, the other two GLP-1 drugs, Lixisenatide and Liraglutide, were less efficient. The average medication efficiency of drugs approved post-2010 was significantly higher than pre-2010 drugs. High dose frequency, low HbA1c reduction and insignificant weight loss were the main driving factors behind inefficiencies. Overall, medication efficiency provided an alternative perspective on treatment effectiveness other than conventional measures such as cost-effectiveness.

Do hybrid closed loop insulin pump systems improve glycemic control and reduce hospitalizations in poorly controlled type 1 diabetes?

Hybrid closed-loop (HCL) systems improve glycemic control in type 1 diabetes mellitus (T1D), but their effectiveness in young, poorly controlled populations is notestablished and requires study. A pre-post study was performed using electronic health records of patients 3-24 years with baseline HbA1c≥9 % prescribed HCL within the New York City Health+Hospitals System assessing HbA1c levels and hospitalizations before and after HCL initiation and factors associated with achieving HbA1c<9 % after HCLinitiation. Of 47 children and adolescents who met inclusion criteria, 4.68 % female, 95.72 % non-White, and 82.22 % covered by public insurance, with a baseline average HbA1c10.6 % (2.28 IQR). The most prevalent pump type wasOmnipod 5 (70.21 %). The HbA1c was significantly lowerinthe postperiod than baseline (HbA1c before=median 10.6 (IQR2.28), HbA1c after=median 9.33 (IQR 2.97), difference 1.00 (IQR 1.64), p<0.05) with a decrease in median diabetes-related hospitalizations (preperiod 1.00 (IQR 1.00), postperiod 0.00 (IQR 1.00), difference-1.00, IQR 2, p<0.05). Lower baseline HbA1c levels made reaching HbA1c<9 % more likely. Multivariable analysis showed thatthe odds of having HbA1c of <9 % was 2.1 times less likely for every one point increase in baseline HbA1c and 12.5 times less likely for those with a pump at (p<0.05). HCL therapy improved glycemic control and decreased diabetes-related hospitalizations in youth with poorly controlled T1DM. Higher baseline HbA1c levels predicted less success with HCL therapy so those who standto benefit most benefit least.

A comprehensive review of immune checkpoint inhibitor-related diabetes mellitus: incidence, clinical features, management, and prognosis

Immune checkpoint inhibitor-related diabetes mellitus (ICI-DM) is a rare complication that medical oncologists seldom encounter in routine practice. The sporadic nature and intrinsic complexity of ICI-DM make it challenging to analyze comprehensively in experimental settings. In this review, we examine phase 3 clinical trials on ICIs and published case reports of ICI-DM, aiming to summarize its incidence, clinical features, management, and prognosis. Phase 3 clinical trials reveal that the incidence of ICI-DM is higher with combination therapies, such as anti-PD-1 and anti-CTLA-4 or anti-PD-L1, compared to anti-PD-1 monotherapy. ICI-DM typically presents as severe hyperglycemia with a fulminant onset and is often associated with diabetic ketoacidosis, accompanied by unexpectedly low HbA1c and C-peptide levels. ICI-DM shares similarities with classic type 1 diabetes, particularly in terms of autoimmunity and genetic predisposition. This includes a high prevalence of islet autoantibodies and susceptibility to certain HLA haplotypes, often with concurrent endocrine gland dysfunction. This suggests that genetic susceptibility and exposure to ICIs may both be necessary for triggering islet autoimmunity and inducing ICI-DM. Notably, patients with positive islet autoantibodies, such as glutamic acid decarboxylase antibody and islet-associated antigen 2 antibody, tend to experience rapid onset of ICI-DM after ICI exposure. Although patients with ICI-DM generally show a high objective response rate to immunotherapy, a significant proportion also face the need to permanently discontinued treatment. Further research is urgently needed to determine whether permanent discontinuation of immunotherapy is necessary and whether this discontinuation negatively impacts overall survival.

Impact of Opuntia ficus-indica Juice and Empagliflozin on Glycemic Control in Rats

Diabetes mellitus (DM) is a major global health concern characterized by high blood glucose levels. This study investigates the effects of Opuntia ficus-indica (cactus) juice and empagliflozin, both alone and in combination, on glycated hemoglobin (HbA1c) levels in healthy and streptozotocin-induced diabetic rats. Eighty Wistar albino male rats were divided into eight groups, with four groups being diabetic. Treatment options included cactus juice, empagliflozin, or both. HbA1c levels were measured at baseline and 100 days later using ELISA. In diabetic and non-diabetic rats treated with cactus juice or empagliflozin, HbA1c levels were significantly reduced, but diabetic rats had significantly lower HbA1c values than non-diabetic rats. The combined treatment provided no additional benefits over individual therapies. These findings indicate that cactus juice and empagliflozin effectively lower HbA1c levels, making their use a promising complementary approach to diabetes management. However, the combined treatment of Opuntia ficus-indica juice and empagliflozin did not yield additional reductions in HbA1c levels compared to individual treatments, with no significant synergistic effects observed throughout the study period. More research is needed to better understand the clinical applications and mechanisms in humans.

Severe Hypertriglyceridemia in Patients with Type 2 Diabetes Mellitus Participating in the AMD Annals Initiative.

Background: Familial chylomicronemia syndrome (FCS) is a rare inherited condition due to lipoprotein lipase deficiency, characterized by hyperchylomicronemia and severe hypertriglyceridemia. Diagnosis is often delayed, thus increasing the risk of acute pancreatitis and hospitalization. Hypertriglyceridemia is a common finding in patients with type 2 diabetes (T2D), who may harbor FCS among the most severe forms. Aim of the Study: We investigated the prevalence and clinical characteristics associated with severe hypertriglyceridemia in a range indicative of FCS, in a large population of subjects with T2D. Methods: Within the large population of the AMD Annals Initiative, patients with T2D with a lipid profile suggestive of FCS [triglycerides >880 mg/dL and/or high-density lipoprotein (HDL)-cholesterol <22 mg/dL or non-HDL-cholesterol ≤70 mg/dL] and their clinical features have been identified. Results: Overall, 8592 patients had triglyceride values >880 mg/dL in a single examination, 613 in two examinations, and 34 in three or more measurements. Patients with high triglyceride levels were mostly male (80%), with a relatively young age (54 years), short duration of diabetes (6.3 years), and elevated hemoglobin A1c (HbA1c) levels (9.4%). By stratifying this group of patients according to the severity of hypertriglyceridemia, more severe hypertriglyceridemia (triglyceride levels ≥2000 mg/dL) was associated with an even younger age (52 vs. 54 years), even higher mean HbA1c values (10.0% vs. 9.4%), and significantly higher HDL-cholesterol levels (37.9 vs. 32.4 mg/dL; P < 0.0001). Patients with persistently elevated triglyceride levels (n = 34), on three measurements, had a younger age; lower body mass index, HbA1c, and HDL-cholesterol levels; more frequent use of fibrates and insulin; and a higher prevalence of major cardiovascular events. Conclusions: Severe hypertriglyceridemia is a frequent condition in outpatients with T2D participating in the AMD Annals Initiative, and it is associated with male sex, young age, short disease duration, and a worse glycemic profile. Among patients with persistent severe hypertriglyceridemia, hidden FCS may be present.

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

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

Efficacy and Safety of Sotagliflozin in Patients with Type 1 Diabetes and CKD.

This analysis evaluated the efficacy and safety of sotagliflozin, a dual SGLT1&2 inhibitor, added to insulin in patients with type 1 diabetes and chronic kidney disease (CKD). We used data from the 52-week pooled inTandem1&2 trials and the 24-week inTandem3 trial to assess the effects of sotagliflozin (200mg [inTandem 1&2 only] or 400mg daily) versus placebo on glycated hemoglobin (HbA1c; primary endpoint), body weight, systolic blood pressure (BP), insulin dose, and safety endpoints including adjudicated severe hypoglycemia and diabetic ketoacidosis (DKA), stratified by CKD. CKD was identified in 237/1575 of inTandem1&2 participants and 228/1402 of inTandem3 participants. At week-24, significant, placebo-adjusted reductions in HbA1c were observed - inTandem1&2: Non-CKD subgroup (sotagliflozin 200mg: -0.4%, 95% CI -0.4 to -0.3; 400mg: -0.4%, 95% CI -0.5 to -0.3) and CKD subgroup (sotagliflozin 200mg: -0.4%, 95% CI -0.6 to -0.1; 400mg: -0.3%, 95% CI -0.5 to -0.1). For systolic BP, there was a significant reduction at week-24 with sotagliflozin in the non-CKD subgroup but no effect in the CKD subgroup in inTandem1&2. At week-52, the incidence of severe hypoglycemia was lower with sotagliflozin (7% on 200 mg and 4% on 400 mg) compared to placebo (17%) in the CKD subgroup of inTandem1&2, whereas the incidence of severe hypoglycemia was 5-6% across non-CKD subgroups. The incidence of adjudicated DKA at week-52 was 1%, 5%, and 3% for placebo, 200 mg, and 400 mg in the CKD subgroup compared to 0%, 3%, and 4% in the non-CKD subgroup. Results were generally similar in inTandem3 except systolic BP was significantly reduced with sotagliflozin versus placebo in CKD and non-CKD subgroups. In participants with type 1 diabetes and CKD, sotagliflozin treatment had similar HbA1c, body weight, and systolic BP lowering effects as in participants with type 1 diabetes without CKD. Additionaly, sotagliflozin was associated with a lower to neutral risk of severe hypoglycemia and did not significantly increase the risk of DKA among a small number of DKA events.

Correlations between the long noncoding RNA MEG3 and clinical characteristics for diabetic kidney disease in type 2 diabetes mellitus

Background and aimsDiabetic kidney disease (DKD) is a common complication of type 2 diabetes mellitus (T2DM) that leads to systemic inflammation. Maternally expressed gene 3 (MEG3) is a tumor suppressor that is involved in inflammation regulation. The current study investigated the association between DKD and the prevalence of the single-nucleotide polymorphisms (SNPs) of MEG3.MethodsA total of 706 and 735 patients were included in the DKD and non-DKD groups, respectively. The five SNPs of MEG3, namely rs4081134 (G/A), rs10144253 (T/C), rs7158663 (G/A), rs3087918 (T/G), and rs11160608 (A/C), were genotyped using TaqMan allelic discrimination.ResultsOur results revealed that, in the DKD group, the distribution of the GG genotype of the MEG3 SNP rs3087918 was significantly lower than that of the wild-type genotype (AOR: 0.703, 95% CI: 0.506–0.975, P = 0.035). In addition, in the pre-ESRD DKD subgroup, the distribution of the TG + GG genotype of the MEG3 SNP rs3087918 was significantly lower than that of the wild-type genotype (AOR: 0.637, 95% CI: 0.421–0.962, P = 0.032). In addition, among men in the DKD subgroup, the distribution of the GG genotype of the MEG3 SNP rs3087918 was significantly lower than that of the wild-type genotype (AOR: 0.630, 95% CI: 0.401–0.990, P = 0.045). Glycated hemoglobin (HbA1c) level was significantly higher in all T2DM patients with the wild-type genotype of the MEG3 SNP rs3087918 (P = 0.020). In addition, HbA1c levels were significantly higher in male patients and male DKD patients with the wild-type genotype of the MEG3 SNP rs3087918 (P = 0.032 and 0.031, respectively).ConclusionMEG3 SNP rs3087918 is significantly less prevalent in patients with DKD, and the SNP rs3087918 of MEG3 is associated with lower HbA1c levels.

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.

What characterizes normotensive individuals with obesity and normal systolic heart function? A descriptive study from the SCAPIS cohort

Abstract Background Heart failure and cardiovascular disease are strongly related to obesity, and the incidence of these conditions shows a linear relationship with increasing body mass index (BMI). Despite these known facts, some individuals with obesity show no clinical signs of heart disease or arterial hypertension (AH). Purpose We aimed to investigate the characteristics of individuals with obesity without impaired left ventricular function and left ventricular hypertrophy (termed systolic heart function, SHF) and AH, compared to individuals with obesity with signs of impaired SHF or AH, and individuals without obesity with and without signs of impaired SHF or AH. Method A cross-sectional analysis was performed of the 4,692 individuals who had undergone a transthoracic echocardiography within the Swedish CArdioPulmonary bioImage Study (SCAPIS). Participants were divided into four groups: 1) individuals with obesity (BMI³30 kg/m2) without impaired SHF (normal left ventricular systolic function and left ventricular mass) and no AH (based upon the absence of antihypertensive treatment) (ObSHF/AH-, n=623; 13%), 2) individuals with obesity with impaired SHF or AH (ObSHF/AH+, n=252; 5%), 3) individuals without obesity and without impaired SHF and no AH (NObSHF/AH-, n=3179; 68%) and 4) individuals without obesity with impaired left ventricular systolic function, left ventricular hypertrophy or AH (NObSHF/AH+, n=638; 14%). Individuals in group 1 (ObSHF/AH-;) were compared to those in groups 2-4 through descriptive analyses. Results Compared to ObSHF/AH+ individuals, ObSHF/AH- subjects showed significantly lower HbA1c (p&amp;lt;0.001), fasting plasma glucose (p&amp;lt;0.001), triglyceride (p&amp;lt;0.001), NT-proBNP (p=0.035) and troponin I (p&amp;lt;0.001) levels. Furthermore, no significant differences between the two obese groups could be seen regarding BMI (p=0.074), whereas waist-to-hip ratio was lower in ObSHF/AH- subjects (p&amp;lt;0.001). ObSHF/AH- individuals had higher glucose and lipid levels as well as higher blood pressure than individuals without obesity. Interestingly, no differences were seen between ObSHF/AH- and NObSHF/AF- subjects regarding NT-proBNP (p=0.864) and troponin I levels (p=0.110). Furthermore, left ventricular mass index (LVMI) was significantly higher in ObSHF/AH- subjects compared to NObSHF/AH- individuals (73.8 vs. 72.1 g/m2, p=0.015) and the ejection fraction was significantly lower (57.4 vs. 59.6 %, p&amp;lt;0.001). Conclusion When ObSHF/AH- and NObSHF/AH- subjects were compared, markers of cardiac damage/remodeling did not differ significantly, indicating that heart function might be preserved despite a worsened metabolic profile and an obese phenotype, through putative protective mechanisms yet to be explored. However, parameters of SHF were unfavorable for ObSHF/AH- when compared to NObSHF/AH-, further implicating preclinical cardiac impairment in individuals with obesity.

The Impact of Health Literacy on Diabetes Control

Abstract Introdution People with diabetes have a significant impact on treatment outcomes through their daily decisions. Therefore, health literacy (HL) is crucial for effectively managing the disease and maintaining overall health. This study aimed to explore the relationships between different dimensions of health literacy, self-care behaviors, and Diabetes Control (HbA1c). Methods HLwas assessed using the Health Literacy Questionnaire. 706 individuals with diabetes participated in the study, the majority of whom were male (60.2%), had more than 9 years of schooling (84.7%), and over half were employed (52.4%). To examine the relationship between dimensions of HLand HbA1c, multiple linear regression analysis was conducted. Results The study revealed a significant association between higher levels of HLand lower HbA1c levels. There is a statistically significant positive linear correlation between adherence to general nutrition and HLdimensions. In terms of physical activity, a positive correlation was also found with HLdimensions, and blood glucose monitoring showed a positive correlation with health literacy. Greater adherence to nutrition was linked to a decrease in HbA1c levels, while higher adherence to self-monitoring and medication was associated with an increase in HbA1c levels Conclusions This study emphasizes the importance of HLin managing diabetes. It underscores the impact of HLin diabetes compensation. The results reveal that higher levels of feeling understood and supported by healthcare professionals, having sufficient information to manage health, actively managing health, and appraising health information among people with diabetes lead to better adherence to blood glucose self-monitoring. Based on these findings, a crucial aspect of effectively managing diabetes will involve empowering individuals with the necessary skills for self-management of their condition, overall health, and treatment regimen. Key messages • The present research reinforces the importance of health literacy for diabetes compensation and self care activies. • One critical success factor in dealing with diabetes will be investing of health literacy of people with diabetes and health care providers responsiveness.

Intermittently scanned continuous glucosemonitoring compared with blood glucose monitoring is associated with lower HbA1c and a reduced risk of hospitalisation for diabetes-related complications in adults with type 2 diabetes on insulin therapies.

We assessed the impact of initiating intermittently scanned continuous glucose monitoring (isCGM) compared with capillary blood glucose monitoring (BGM) on HbA1c levels and hospitalisations for diabetes-related complications in adults with insulin-treated type 2 diabetes in Sweden. This retrospective comparative cohort study included adults with type 2 diabetes who had a National Diabetes Register initiation date for isCGM after 1 June 2017. Prescribed Drug Register records identified subgroups treated with multiple daily insulin injections (T2D-MDI) or basal insulin (T2D-B), with or without other glucose-lowering drugs. The National Patient Register provided data on hospitalisation rates. We identified 2876 adults in the T2D-MDI group and 2292 in the T2D-B group with an isCGM index date after 1 June 2017, matched with 33,584 and 43,424 BGM control participants, respectively. The baseline-adjusted difference in the change in mean HbA1c for isCGM users vs BGM control participants in the T2D-MDI cohort was -3.7 mmol/mol (-0.34%) at 6 months, and this was maintained at 24 months. The baseline-adjusted difference in the change in HbA1c for isCGM users vs BGM control participants in the T2D-B cohort was -3.5 mmol/mol (-0.32%) at 6 months, and this was also maintained at 24 months. Compared with BGM control participants, isCGM users in the T2D-MDI cohort had a significantly lower RR of admission for severe hypoglycaemia (0.51; 95% CI 0.27, 0.95), stroke (0.54; 95% CI 0.39, 0.73), acute non-fatal myocardial infarction (0.75; 95% CI 0.57, 0.99) or hospitalisation for any reason (0.84; 95% CI 0.77, 0.90). isCGM users in the T2D-B cohort had a lower RR of admission for heart failure (0.63; 95% CI 0.46, 0.87) or hospitalisation for any reason (0.76; 95% CI 0.69, 0.84). This study shows that Swedish adults with type 2 diabetes on insulin who are using isCGM have a significantly reduced HbA1c and fewer hospital admissions for diabetes-related complications compared with BGM control participants.

HbA1c and leukocyte mtDNA levels as major factors associated with post-COVID-19 syndrome in type 2 diabetes patients

Post-COVID-19 syndrome (PCS) is an emerging health problem in people recovering from COVID-19 infection within the past 3–6 months. The current study aimed to define the predictive factors of PCS development by assessing the mitochondrial DNA (mtDNA) levels in blood leukocytes, inflammatory markers and HbA1c in type 2 diabetes patients (T2D) with regard to clinical phenotype, gender, and biological age. In this case-control study, 65 T2D patients were selected. Patients were divided into 2 groups depending on PCS presence: the PCS group (n = 44) and patients who did not develop PCS (n = 21) for up to 6 months after COVID-19 infection. HbA1c and mtDNA levels were the primary factors linked to PCS in different models. We observed significantly lower mtDNA content in T2D patients with PCS compared to those without PCS (1.26 ± 0.25 vs. 1.44 ± 0.24; p = 0.011). In gender-specific and age-related analyses, the mt-DNA amount did not differ significantly between the subgroups. According to the stepwise multivariate logistic regression analysis, low mtDNA content and HbA1c were independent variables associated with PCS development, regardless of oxygen, glucocorticoid therapy and COVID-19 severity. The top-performing model for PCS prediction was the gradient boosting machine (GBM). HbA1c and mtDNA had a notably greater influence than the other variables, indicating their potential as prognostic biomarkers.

Cellular Characteristics and Protein Signatures of Human Adipose Tissues from Donors With or Without Advanced Coronary Artery Disease

Background/Objectives: Perivascular adipose tissue (PVAT) exerts a paracrine effect on blood vessels and our objective was to understand PVAT molecular signatures related to cardiovascular disease. Methods: We studied two groups: those undergoing mitral valve repair/replacement (VR, n = 16) and coronary artery bypass graft (CABG, n = 38). VR donors did not have coronary artery disease, whereas CABG donors had advanced coronary artery disease. Clinical and tissue pathologies and proteomics from adipose tissue were assessed. Results: Donors undergoing VR had a lower body mass index (p = 0.01), HbA1C (p = 0.0023), and incidence of diabetes (p = 0.022) compared to CABG. VR donors were overall healthier, with higher cardiac function compared to CABG donors, based on ejection fraction. Although adipose histopathology between groups was not markedly different, PVAT had smaller and more adipocytes compared to subcutaneous adipose tissues. These differences were validated by whole specimen automated morphological analysis, and anisotropy analysis showed small (2.8–7.5 μm) and large (22.8–64.4 μm) scale differences between perivascular and subcutaneous adipose tissue from CABG donors, and small scale changes (2.8–7.5 μm) between perivascular and subcutaneous adipose tissue from VR donors. Distinct protein signatures in PVAT and subcutaneous adipose tissue include those involved in secretion, exosomes and vesicles, insulin resistance, and adipocyte identity. Comparing PVAT and subcutaneous adipose tissue from CABG donors, there were 82 significantly different proteins identified with log fold change ≥ 0.3 or ≤−0.3 (p &lt; 0.05). Using this threshold, there were 36 differences when comparing PVAT and subcutaneous adipose tissue from VR donors, 58 differences when comparing PVAT from CABG or VR donors, and 55 when comparing subcutaneous adipose tissue from CABG vs. VR donors. Conclusions: Routine histopathology cannot differentiate between PVAT from donors with or without coronary artery disease, but multiscale anisotropy analysis discriminated between these populations. Our mass spectrometry analysis identified a cohort of proteins that distinguish between adipose depots, and are also associated with the presence or absence of coronary artery disease.

49 Effects of numeracy and literacy on glycemic control and self-perceived efficacy in youth with type 1 diabetes in Haiti

Abstract Background The management of type 1 diabetes (T1D) in low-resource settings remains a challenge in the context of unfavourable social determinants of health. The effects of literacy and numeracy on glycemic control and self-perceived efficacy in youth living with T1D in low-resource settings have been insufficiently investigated. Objectives We described literacy and numeracy in Haitian youth with T1D and their caregivers and we evaluated their association with hemoglobin A1c (HbA1c) and perceived diabetes management self-efficacy. Design/Methods We conducted a cross-sectional cohort study of youth with T1D treated at the Montrouis clinic in Haiti, between June to December 2017. Inclusion criteria were a diagnosis of T1D at age 0-25 years and at least one parent of Haitian ancestry. One principal caregiver of each youth was also included. Exclusion criteria were inability of informed consent and declined home visit. The study was approved by our Institution Research Ethics Board. Data collection included demographics, clinical data, numeracy questionnaire adapted to the population and the standardized self-efficacy 8-item Perceived Diabetes Self-Management Scale (PDSMS). We used univariate and multivariate linear regression models to evaluate predictors of HbA1c and PDSMS scores. Results We included 85 patients (60% female) and 73 caregivers. Median age at diagnosis and diabetes duration were 14.3 and 3.1 years, respectively. Over 90% of patients had suboptimal (HbA1c &amp;gt;7.0%), poor (HbA1c &amp;gt;9%) or very poor (HbA1c &amp;gt;12%) glycemic control. 76 patients (90.5%) self-reported being able to read, 78 (91.8%) to write and 84 (98.8%) to count. Mothers’ and fathers’ median education years were 7.0 and 11, respectively. 54 parents (74.0%) self-reported being able to read and write. Normalized to 100%, median patient numeracy score was 75.0% and the mean PDSMS score was 65.9%. In univariate models, lower HbA1c was predicted by younger age (p=0.013), but not by gender, diabetes duration, numeracy score, mother’s education or PDSMS score. Higher PDSMS score was predicted by higher numeracy scores (p=0.003), marginally by sex (p=0.057), but not by age, diabetes duration, or mother’s education; in a multivariate model adjusted for age, sex and diabetes duration, higher numeracy remained significant (p=0.006). Conclusion In youth with T1D in Haiti who have ubiquitously poor glycemic control and suboptimal family literacy and numeracy, numeracy is a predictor of self-perceived efficacy of T1D. Further public health interventions addressing numeracy in youth living with T1D in low-resource settings are advised.