Diabetic Subgroups Research Articles

Evaluation and subgroup analysis of the efficacy and safety of intensive rosuvastatin therapy combined with dual antiplatelet therapy in patients with acute ischemic stroke

ObjectivesWe investigated the efficacy of intensive rosuvastatin therapy plus 7-day dual antiplatelet therapy (DAPT) in reducing stroke recurrence for patients with acute ischemic stroke (AIS) and compared subgroups of patients.MethodsWe enrolled patients with AIS whose time of onset to medication was ≤ 72 h, and the baseline scores of NIHSS (bNIHSS) were 0–10. The patients received intensive rosuvastatin therapy plus 7-day DAPT with aspirin and clopidogrel (study group) or rosuvastatin plus single antiplatelet therapy (SAPT, control group). The primary outcomes were recurrence of ischemic stroke, bleeding, statin-induced liver injury, and statin-associated myopathy (SAM) within 90 days. We also performed a subgroup analysis to assess the heterogeneity of the two therapy regimens in reducing recurrent stroke.ResultsRecurrent stroke occurred in 10 patients in the study group and 42 patients in the control group (hazard ratio [HR], 0.373, 95% confidence interval [CI], 0.178–0.780; P = 0.009). Bleeding events occurred in 9 patients in the study group and 14 patients in the control group (HR, 1.019; 95%CI, 0.441–2.353; P = 0.966). Statin-induced liver injury and SAM were not recorded. Intensive rosuvastatin plus 7-day DAPT was generally effective in reducing the risk of recurrent stroke, except in the subgroup with bNIHSS ≤ 2. The therapy was particularly efficient in the elderly, male, high-bNIHSS, and hypertension, diabetes, and hyperlipidemia subgroups, with P < 0.02.ConclusionsWithout increasing bleeding and statin-associated adverse events, intensive rosuvastatin therapy plus 7-day DAPT significantly reduced the risk of recurrent stroke, especially for subgroups with high-risk factors. Clinical trial registration. China Clinical Trial Registration Center (ChiCTR1800017809).

Association between weight-adjusted-waist index and heart failure: Results from National Health and Nutrition Examination Survey 1999-2018.

Weight-adjusted waist circumference index (WWI) is a novel index positively associated with excessive fat accumulation. The current study aims to evaluate the association between WWI and the prevalent heart failure (HF), and to assess the value of WWI to improve the detection of HF in the general population. A total of 25,509 subjects from National Health and Nutrition Examination Survey 1999-2018 were included into our study. WWI was calculated as WC (cm) divided by the square root of weight (kg). HF was identified according to the subjects' reports. The prevalence of reported HF was 2.96%. With adjustment of demographic, anthropometric, laboratory, and medical history data, one SD increment of WWI could cast an additional 19.5% risk for prevalent HF. After separating WWI into quartiles, the fourth quartile had a 1.670 times risk of prevalent HF compared to the first quartile. Furthermore, smooth curve fitting suggested that the association was linear in the entire range of WWI. Moreover, the association was robust to subgroups of age, sex, race, obesity, hypertension, and diabetes. Additionally, ROC analysis revealed a significant improvement for the detection of prevalent HF from WWI (0.890 vs. 0.894, P < 0.001); And continuous net reclassification index (0.225, P < 0.001) and integrated discrimination index (0.004, P < 0.001) also supported the improvement from WWI. Our data demonstrated a significant, linear, and robust association between WWI, a simple surrogate for fat mass accumulation, and the risk for prevalent HF in a representative population. Moreover, our results also suggested the potential value of WWI to refine the detection of prevalent HF in the general population.

Effects of intensive blood pressure lowering in patients with diabetes: A pooled analysis of the STEP and ACCORD-BP randomized trials.

To determine whether intensive systolic blood pressure (SBP) lowering can benefit hypertensive patients with diabetes. We performed a pooled analysis of individual patient data from two randomized trials to compare intensive and standard SBP targets in hypertensive patients with diabetes (STEP diabetes subgroup and ACCORD-BP standard glycaemic group, n=1627 and n=2362, respectively). We defined a modified primary outcome as a composite of stroke, major coronary artery disease (myocardial infarction and unstable angina), heart failure, and cardiovascular death. The secondary outcomes were individual components of the primary outcome and death from any cause. A Cox proportional hazards regression model was used in the main analysis. We conducted one-stage mixed-effect models and two-stage analyses as sensitivity and supplementary analyses to verify the robustness of the findings. A total of 3989 patients were randomized to undergo intensive (n=1984) or standard SBP treatment (n=2005). After a median follow-up of 3.83 years, the primary outcome occurred in 193/1984 patients in the intensive group and in 247/2005 patients in the standard group (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.64-0.93). The incidence rates for secondary outcomes were lower in the intensive group than in the standard group, but were not significantly different, except for stroke (intensive vs. standard: 32/1984 vs. 58/2005; HR 0.56, 95% CI 0.36-0.86). These results remained consistent in the additional sensitivity and supplementary analyses. An intensive SBP-lowering target of 110 to <130 mmHg reduces the cardiovascular outcomes compared with a standard SBP-lowering target of 130 to <150 mmHg. The findings of this study support the favourable effects of intensive SBP lowering in hypertensive patients with diabetes.

Elevated Remnant Cholesterol is Associated with Adverse Cardiovascular Outcomes in Patients with Acute Coronary Syndrome.

This study aimed to investigate the association of elevated RC levels with adverse cardiovascular outcomes in acute coronary syndrome (ACS) patients with and without diabetes. We analyzed data from 1716 patients with ACS undergoing percutaneous coronary intervention. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol. RC ＞75th percentile of the cohort (＞0.79 mmol/L) was defined as abnormally elevated RC. Cox-regression models and Kaplan-Meier analyses were used to assess the relationship between RC ＞0.79 mmol/L and major adverse cardiovascular events (MACE). During a median follow-up of 927 days, a total of 354 patients had at least one event. In the overall population, compared with those with RC ≤ 0.79 mmol/L, patients with RC ＞0.79 mmol/L had a significantly higher risk of MACE after adjustment for potential confounders (hazard ratio: 1.572, 95% confidence interval: 1.251-1.975, P＜0.001). In addition, RC ＞0.79 mmol/L was associated with an increased risk of MACE of 66.7% (P=0.001) and 50.1% (P=0.022) in the diabetic and non-diabetic subgroups (P for interaction=0.073), respectively. The addition of RC significantly improved the predictive ability of baseline models for MACE in diabetic patients (all P＜0.05), but not in non-diabetic patients (all P＞0.05). Abnormally elevated RC was significantly associated with worse prognosis in both diabetic and non-diabetic patients with ACS; however, the prognostic value of RC might be superior among diabetic patients.

Findings for iGlarLixi versus BIAsp 30 confirmed in groups of people with type 2 diabetes with different biomedical characteristics.

To report prespecified and post hoc analyses of the SoliMix dataset exploring the impact of baseline participant characteristics on the original SoliMix study outcomes, to enable informed treatment choices for people with different biomedical characteristics. SoliMix (EudraCT 2017-003370-13) compared once-daily iGlarLixi (a fixed-ratio combination of insulin glargine 100 U/mL and the glucagon-like peptide-1 receptor agonist lixisenatide) with twice-daily BIAsp 30 (30% insulin aspart and 70% insulin aspart protamine). In this analysis, the original primary outcomes of noninferiority of iGlarLixi versus BIAsp 30 in terms of glycated haemoglobin (HbA1c) change and superiority in terms of body weight change, together with change in basal insulin dose and hypoglycaemia outcomes, were investigated by baseline age, duration of diabetes, insulin dose, HbA1c level, body mass index (BMI), and renal function. No evidence of difference in comparative treatment effect was detected across baseline age, duration of diabetes, insulin dose, HbA1c level, BMI and renal function subgroups for any endpoint (all heterogeneity P> 0.05), except American Diabetes Association Level 2 hypoglycaemia event rate when stratified by insulin dose (P= 0.011), which may be a chance difference given multiple testing and the small numbers of Level 2 events. Treatment effects of iGlarLixi were consistent irrespective of baseline HbA1c, insulin dose, BMI, age, duration of diabetes and renal function, supporting the use of iGlarLixi as an efficacious and well-tolerated treatment option in people with type 2 diabetes with a wide range of biomedical characteristics.

Causal Associations Between Age at Diagnosis of Diabetes and Cardiovascular Outcomes: A Mendelian Randomization Study.

Whether diabetes diagnosed at different age groups is causally associated with cardiovascular diseases (CVDs) is unknown. We conducted 2-sample Mendelian randomization analyses to investigate the causal associations of diabetes by age at diagnosis with 5 type-specific CVDs and 11 cardiometabolic traits. We selected 208 single nucleotide polymorphisms (SNPs) for diabetes and 3, 21, 57, and 14 SNPs for diabetes diagnosed at <50, 50-60, 60-70, and >70 years, respectively, based on the genome-wide association study (GWASs) (24 986 cases/187 130 controls) in the UK Biobank, and extracted genetic associations with stroke, myocardial infarction, heart failure, atrial fibrillation, and CVD mortality, as well as blood pressures, adiposity measurements, and lipids and apolipoproteins from corresponding European-descent GWASs. The inverse variance-weighted method was used as the main analysis with several sensitivity analyses. Diabetes diagnosed at all 4 age groups was causally associated with increased risks of stroke (5-8%) and myocardial infarction (8-10%), higher systolic blood pressure (0.56-0.94 mmHg) and waist to hip ratio (0.003-0.004), and lower body mass index (0.31-0.42 kg/m2), waist circumference (0.68-0.99 cm), and hip circumference (0.57-0.80 cm). Diabetes diagnosed at specific age groups was causally associated with increased risks of heart failure (4%) and CVD mortality (8%), higher diastolic blood pressure (0.20 mmHg) and triglycerides (0.06 SD), and lower high-density lipoprotein cholesterol (0.02 mmol/L). The effect sizes of genetically determined diabetes on CVD subtypes and cardiometabolic traits were comparable and the corresponding 95% confidence intervals largely overlapped across the 4 age groups. Our findings provide novel evidence that genetically determined diabetes subgroups by age at diagnosis have similar causal effects on CVD and cardiometabolic risks.

Efficacy and safety of dapagliflozin in patients with heart failure with mildly reduced or preserved ejection fraction by baseline glycaemic status (DELIVER): a subgroup analysis from an international, multicentre, double-blind, randomised, placebo-controlled trial

Type 2 diabetes and prediabetes are risk factors for heart failure and adverse heart failure outcomes. The Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure (DELIVER) trial showed that dapagliflozin was associated with a reduction in the primary outcome of worsening heart failure or cardiovascular mortality in patients with heart failure with mildly reduced or preserved ejection fraction. We aimed to assess the efficacy and safety of oral dapagliflozin in these patients by their baseline glycaemia categories. DELIVER was an international, multicentre, double-blind, randomised, placebo-controlled trial done in 350 health-care centres and hospitals across 20 countries. Patients aged 40 years or older with New York Heart Association class II-IV, left ventricular ejection fraction of more than 40%, elevated natriuretic peptides (N-terminal pro B-type natriuretic peptide ≥300 pg/mL or ≥600 pg/mL for patients in atrial fibrillation or flutter), and evidence of structural heart disease were randomly assigned (1:1) to 10 mg dapagliflozin or placebo, administered orally, and followed up for a median of 2·3 years (IQR 1·7-2·8). The primary outcome, a composite of time from randomisation to first worsening heart failure events (defined as an unplanned hospitalisation or urgent heart failure visit requiring intravenous therapy) or cardiovascular death, in participants with type 2 diabetes (history of or identified by HbA1c ≥6·5% [48 mmol/mol] at baseline) or prediabetes (HbA1c 5·7 to <6·5% [39 mmol/mol to <48 mmol/mol] at baseline) was compared with those with normoglycaemia (HbA1c <5·7% [39 mmol/mol]). Efficacy of dapagliflozin versus placebo was assessed according to glycaemic status and based on HbA1c as a continuous measure. The full-analysis set comprised all patients who were randomly assigned to study treatment, with patients analysed according to their randomised treatment assignment, irrespective of the treatment received (ie, intention to treat). The safety analysis set comprised patients who were randomly assigned to study treatment and who took at least one dose of investigational product, with patients analysed according to the treatment actually received. This trial is registered with ClinicalTrials.gov, NCT03619213. Between Sept 1, 2018, and Jan 18, 2021, 6263 patients were randomly assigned to oral dapagliflozin (n=3131) or placebo (n=3132). Of these patients, 1175 had normoglycaemia, 1934 had prediabetes, and 3150 had type 2 diabetes and were included in the glycaemia subgroup analysis (3515 [56·2%] of 6263 patients were men and 4435 [70·9%] were White). The incidence rate of the primary outcome was 6·9 per 100 patient-years in the normoglycaemia subgroup (reference), increasing to 7·6 per 100 patient-years in the prediabetes subgroup (hazard ratio 1·09 [95% CI 0·90-1·31]) and 10·1 per 100 patient-years in the type 2 diabetes subgroup (1·46 [1·24-1·73]; p<0·0001 for trend). Dapagliflozin reduced the risk of the primary outcome versus placebo in each subgroup (hazard ratio 0·77 [95% CI 0·57-1·04], log-rank p=0·088, for patients with normoglycaemia, 0·87 [0·69-1·08], log-rank p=0·21, for patients with prediabetes, and 0·81 [0·69-0·95], log-rank p=0·0077, for patients with type 2 diabetes; pinteraction=0·82) and across the continuous HbA1c range (pinteraction=0·85). Volume-related or renal serious adverse events or adverse events leading to discontinuation of the study drug, hypoglycaemia, and amputations were not differentially affected by treatment in any of the glycaemia categories. In patients with heart failure with mildly reduced or preserved ejection fraction, oral dapagliflozin improved heart failure outcomes to a similar extent in three glycaemia subgroups: normoglycaemia, prediabetes, and type 2 diabetes. Moreover, the heart failure benefits of dapagliflozin seem to be consistent across a continuous glycaemic range. AstraZeneca.

LBODP042 Lean Type Two Diabetes: Risk Factors And Outcomes Compared To Typical Presenting Type Two Diabetes

Abstract Background Lean type 2 diabetes (LT2D) is a prevalent manifestation of type 2 diabetes (T2D). However, it has been an understudied subgroup of T2D. Aim To compare characteristics and outcomes of patients with LT2D with that of typical presenting T2D. Methods A retrospective review of electronic health records was performed between 2013 and 2020. The study included 254 patients with LT2D and 429 patients with typical T2D located in the South Bay of Southern California. LT2D and typical T2D were defined as having a body mass index (BMI) of 18.5 to 24.9 kg/m2 and 25 to 29.9 kg/m2, respectively. Patient-level variables included age, sex, race, ethnicity, educational level, area of deprivation index (ADI), microvascular and macrovascular comorbidities, alcohol use, tobacco use, and diabetes family history. Labs and vital signs obtained included hemoglobin A1c (HbA1c), glomerular filtration rate (GFR), creatinine, albumin, and blood pressure. Student's t-test and Chi-square tests/Fisher's exact tests were performed with SAS version 9.4 to compare differences between the LT2D and typical T2D groups. Results Between the diabetes subgroups, there were several statistically significant differences identified. The LT2D population was older, with a mean age of 78.2 years compared with 74.6 years in the typical T2D (p &amp;lt; 0. 001). The LT2D group had a higher percentage of Asians at 40.6% and fewer Caucasians at 35. 0%, while the typical T2D consisted of 22.4% Asians and 46.4% Caucasians (p=0. 0007). Diastolic blood pressure was lower in the LT2D group at 71.6 compared to 73.9 in the typical T2D group (p=0. 0053). There were no differences in sex, HbA1c, systolic blood pressure, hypertension, dyslipidemia, chronic kidney disease, cardiovascular events, peripheral vascular disease, combined microvascular complications, combined macrovascular complications, substance use, education level, ADI, GFR, creatinine, albumin, or number of relatives with diabetes. Conclusion We identified several key differences between the LT2D and typical T2D cohort, including age, race, and diastolic blood pressure. Further investigation and large studies are warranted to explore the risk factors and long term outcomes of patients presenting with LT2D. Knowing what the key differences are may help identify appropriate diabetes medical treatments and lifestyle interventions for this particular target population rather than using T2D treatments that are used for a more general population of patients. Presentation: No date and time listed

PSUN201 Efficacy and Safety of Lemborexant in Diabetic Patients With Insomnia Disorder

Abstract Background Patients with diabetes report sleep problems more often than healthy individuals. Notably, ∼50% of the patients with Type 2 diabetes have reported insomnia. However, literature on the efficacy and safety of commonly prescribed sleep promoting drugs in this patient group is limited. Lemborexant (LEM) is a dual orexin receptor antagonist approved in multiple countries for the treatment of adults with insomnia. In Study 303 (NCT02952820), LEM provided significant benefit on subject-reported sleep measures versus placebo (PBO). This analysis evaluated sleep diary-based efficacy and safety of LEM over 12mo in the subgroup of participants with diabetes. Methods Study 303 was a 12mo randomized, double-blind, PBO-controlled (first 6mo [Period 1]), phase 3 study in participants ≥18y with insomnia disorder and baseline Insomnia Severity Index total score ≥15. Patients with diabetes Type 1 or Type 2, identified by concomitant medications, were allowed to participate as long as their condition was considered stable and likely to be so during the year of treatment. During Period 1, participants received LEM 5mg (LEM5), LEM 10mg (LEM10), or PBO. During Period 2 (second 6mo), LEM participants continued their assigned dose and PBO participants were rerandomized to LEM5 or LEM10. Outcome measures included patient-reported (subjective [s]) sleep onset latency (sSOL), wake after sleep onset (sWASO), sleep efficiency (sSE), and total sleep time (sTST). Treatment-emergent adverse events (TEAEs) were assessed. Results The diabetic subgroup included 72/949 participants (Period 1: PBO, n=24; LEM5, n=26; LEM10, n=22). The majority of the participants were White (56/72 [77.8%]) and female (51/72 [70.8%]); 8/72 [11.1%] were Asian and 7/72 [9.7%] were Black. Mean age for PBO, LEM5 and LEM10 was 63.8y, 60.2y and 63.5y, respectively. The most common concomitant medication classes taken by participants were alimentary tract and metabolism. Overall, sleep-related outcomes at 6mo in participants with diabetes were consistent with the full study population. sSOL change from baseline (median) at 6mo was -10.77, -20.71, and -30.71 minutes for PBO, LEM5 and LEM10, respectively. Mean (SD) change from baseline at 6mo was for sWASO: PBO, -32.16 [36.93], LEM5, -43.80 [57.27], and LEM10, -57.55 [65.16]; for sSE: PBO, 8.06 [8.41]; LEM5, 13.20 [10.66], and LEM10, 18.08 [15.76]; and for sTST: PBO, 47.36 [59.76]; LEM5, 73.35 [56.0]; and LEM10, 86.32 [76.49]. Most TEAEs were mild or moderate and consistent with the known safety profile of LEM. The most common TEAE was somnolence reported in 4.2, 3.8, 13.6% for PBO, LEM5 and LEM10, respectively. Conclusions Long-term treatment with lemborexant appears effective in improving sleep onset and sleep maintenance variables in diabetic patients with insomnia, consistent with the overall study population. Furthermore, LEM was well-tolerated, and no new safety signals were observed in participants with diabetes, supporting LEM as a potential treatment option. Support: Eisai Inc. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

The relationship between metabolic dysfunction-associated fatty liver disease and low muscle mass in an asymptomatic Korean population.

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) emphasizes the metabolic dysfunction in nonalcoholic fatty liver disease (NAFLD). Although the relationship between low muscle mass and NAFLD has been suggested, the effect of MAFLD on low muscle mass is yet to be investigated. In this study, we examined the relationship between MAFLD and low muscle mass in an asymptomatic Korean population. Examinees who underwent FibroScan® and bioelectrical impedance analyses on the same day during the period of June 2017 to December 2019 were included. Hepatic steatosis was diagnosed using controlled attenuation parameter (CAP) with two cut-off values of 248 and 294dB/m. Low muscle mass was defined based on appendicular skeletal muscle mass/body weight (wt) or body mass index (BMI) ratios of two standard deviations below the sex-specific mean for healthy young adults. Subjects were divided into four subgroups: diabetic MAFLD (presence of diabetes mellitus [DM]), metabolic dysfunction (MD) MAFLD (≥2 metabolic abnormalities without DM), overweight MAFLD (overweight/obese without DM and <2 metabolic abnormalities) and no MAFLD. Among all of the 6414 subjects (mean 53.9years of age; 85.4% male), the prevalence of MAFLD was 49.9% and 22.7% for CAP cut-off values of 248 and 294dB/m, respectively. In the multivariate analysis, MAFLD was associated with an increased risk of both low muscle mass_wt (odds ratio [OR] 1.80, 95% confidence interval [CI] 1.38-2.35, P<0.001) and low muscle mass_BMI (OR 1.31, 95% CI 1.01-1.70, P=0.042). The risk of low muscle mass_wt and low muscle mass_BMI increased the most in the diabetic MAFLD subgroup compared with the no-MAFLD group (OR 2.11, 95% CI 1.51-2.96, P<0.001 and OR 1.51, 95% CI 1.08-2.13, P=0.017). There was an increased risk of low muscle mass_wt in the MD MAFLD subgroup (OR 1.73, 95% CI 1.31-2.28, P<0.001). Comparable results were observed when the CAP cut-off value of 294dB/m was applied. The presence of MAFLD is significantly associated with increased risk of low muscle mass with varying risks according to the MAFLD subgroups. Clinicians should be aware of the differentiated risk of low muscle mass across the subgroups of MAFLD.

Reducing the 10-year risk of ischemic cardiovascular disease to receive early cardiovascular benefits from bariatric surgery for obesity in China.

BackgroundCardiovascular risk due to obesity can be improved greatly by bariatric surgery. However, there is no research involving appropriate model for evaluating cardiovascular disease risk reduction in bariatric surgery for obesity in China. We selected the ischemic cardiovascular disease (ICVD) risk score that accurately predict cardiovascular risk in Chinese adults to evaluate the 10-year risk of ICVD and estimated early cardiovascular benefits of bariatric surgery in obese Chinese patients through its reduction.MethodsFrom 2017 to 2019 we followed up 107 patients 6 months after surgery and measured the ICVD 10-year risk and other cardiovascular factors before and after surgery.ResultsThere were significant reductions in the ICVD total score (p < 0.001) and ICVD 10-year risk (%) (p < 0.001) 6 months post-operation compared with baseline. Furthermore, we found significant reductions in body mass index (BMI), body adiposity index (BAI), low-density lipoprotein (LDL), small dense-low-density lipoprotein (sd-LDL) and triglycerides (TG) 6 months after surgery compared with pre-operation (all p < 0.05). The decrease in ICVD total score was correlated with excess BMI loss (%EBMIL), reduced BAI, reduced LDL, reduced sd-LDL and reduced TG respectively (all p < 0.05) at 6 months post-operation. Moreover, there were significant reductions in the ICVD total score in the male subgroup [3 (3, 5) vs. 2.5 (2, 4), p < 0.001] and female subgroup [3 (2, 4) vs. 2 (1, 3), p < 0.001] 6 months post-operation compared with baseline. At last there were also significant reductions in the ICVD total score in the diabetic subgroup [5 (4, 6) vs. 4 (3, 5), p < 0.001] and non-diabetic subgroup [2 (2,3) vs. 2 (1, 2), p < 0.001] 6 months post-operation compared with baseline.ConclusionsBariatric surgery could provide early cardiovascular benefits for patients with obesity in China by reducing the 10-year risk of ICVD. Both men and women with obesity achieved cardiovascular benefits according to bariatric surgery, so did diabetic and non-diabetic patients.

The association between long-term statin use and cataract in both primary and secondary prevention of cardiovascular disease – a nationwide, cohort study on 597,605 cataract patients

Abstract Background The purpose of the present study was to determine the association between statin treatment duration and cataract in the entire Danish population. Methods We performed a population-based, nested case-control study with data over 25 years using national registries to identify cataract patients, who were matched with a control by age and gender. For each participant, we computed and categorized the statin treatment duration in never users, 1, 5, and 10 years by summation of all redeemed prescriptions. We performed conditional logistic regression analyses in subgroups of the participants according to history of either ischemic heart disease, diabetes, hypertension, or neither of these conditions. Results A total of 597.605 cataract patients were identified and each matched with a control, making an entire cohort of 1.195.210 participants. We identified 271.838 participants with ischemic heart disease, 79.703 participants had diabetes, 216.442 participants had hypertension, and 627.227 participants had neither of these conditions. The subgroups were each adjusted for co-morbidities, low-density lipoprotein cholesterol serum levels, and concomitant pharmacotherapy. We found no increased hazard of cataract with statin treatment duration at 1, 5, or 10 years compared to never using statins in either of the subgroups with ischemic heart disease, diabetes, or hypertension. There was, however, a statistically significant increased hazard of cataract in the subgroup without any known conditions at 1 year of statin use (1.14, 95%-CI [1.06:1.22]), 5 years (1.06, 95%-CI [1.00:1.12]), and 10 years (1.08, 95%-CI [1.01:1.15]). The median low-density lipoprotein level for the ischemic heart disease subgroup was 2.45 mmol/L, 2.20 mmol/L for the diabetes subgroup, 2.80 mmol/L for the hypertension subgroup, and 3.0 mmol/L for the subgroup without conditions. Conclusions We did not find an association between statin use and cataract in patients with ischemic heart disease, diabetes, or hypertension, however, in patients without any of these conditions we found a moderate association with cataract. Funding Acknowledgement Type of funding sources: None.

Value of estimated glucose disposal rate to detect prevalent left ventricular hypertrophy: implications from a general population

ABSTRACT Background Insulin resistance plays a pivotal role in developing left ventricular hypertrophy (LVH). Researchers have identified the estimated glucose disposal rate (eGDR) as a simple and cost-effective surrogate of insulin resistance. Our work aims to investigate the association between eGDR and the prevalent LVH and explore the incremental value of eGDR to detect prevalent LVH. Methods The present work enrolled 3839 subjects from a cross-sectional survey conducted between October 2019 to April 2020 in the rural areas of southeastern China. eGDR was calculated based on waist-to-hip circumference ratio, hypertension, and glycated hemoglobin. Results The prevalence of LVH was 17.30%. After adjusting demographic, anthropometric, laboratory, and medical history co-variates, each standard deviation increase of eGDR decreased a 29.6% risk of prevalent LVH. When dividing eGDR into quartiles, the top quartile had a 38.4% risk compared to the bottom quartile. Moreover, smooth curve fitting revealed that the association between eGDR and prevalent LVH was linear in the whole range of eGDR. Additionally, subgroup analysis demonstrated that our main finding was robust to age, sex, BMI, hypertension, and diabetes subgroups. Finally, ROC analysis exhibited a significant improvement by adding eGDR into LVH risk factors (0.780 vs. 0.803, P < 0.001), and category-free net reclassification index (0.702, P < 0.001) and integrated discrimination index (0.027, P < 0.001) also confirmed the improvement from eGDR to detect prevalent LVH. Conclusion Our analysis revealed a linear, robust association between eGDR and prevalent LVH and demonstrated the incremental value of eGDR to optimize the detection of prevalent LVH.

Influence of diabetes on sacubitril/valsartan titration and clinical outcomes in patients hospitalized for heart failure.

Diabetes mellitus is associated with worse outcomes and lower attainment of disease-modifying therapies in patients with heart failure with reduced ejection fraction (HFrEF). This post hoc analysis of TRANSITION compared the patterns of tolerability and uptitration of sacubitril/valsartan in patients with HFrEF stabilized after hospital admission due to acute decompensated HF depending on the presence or absence of diabetes as a co-morbidity. TRANSITION, a randomized, open-label study compared sacubitril/valsartan initiation pre-discharge vs. post-discharge (up to14days) in 991 patients hospitalized for acutely decompensated HFrEF. The impact of diabetes status on tolerability and safety was studied at 10-week and 26-week post-randomization. Among the 991 patients analysed at baseline, 460 (46.4%) had diabetes and exhibited a higher risk profile. At 10weeks, sacubitril/valsartan target dose (97/103mg bid) was achieved in a similar proportion of patients in each subgroup, when initiated pre-discharge or post-discharge respectively [diabetes subgroup: 47% (n=105/226) vs. 50% (n=115/228); relative risk ratio (RRR), 0.923; P=0.412; non-diabetes subgroup: 45% (n=119/267) vs. 51% (n=133/261); RRR, 0.878; P=0.155]. The proportions of patients achieving and maintaining either 49/51mg or 97/103mg bid [diabetes subgroup: 61.1% (n=138/226) vs. 67.5% (n=154/228); RRR, 0.909; P=0.175; non-diabetes subgroup: 62.9% [n=168/267] vs 69.3% [n=181/261]; RRR, 0.906; P=0.118] or any dose for ≥2weeks leading to Week 10 [diabetes subgroup: 85% (n=192/226) vs. 88.2% (n=201/228); RRR, 0.966; P=0.356; non-diabetes subgroup: 86.9% (n=232/267) vs. 90.8% (n=237/261); RRR, 0.963; P=0.215] were also similar in each subgroup, when initiated pre-discharge or post-discharge, respectively. At 10weeks, hypotension and renal dysfunction rates were similar, although hyperkalaemia was higher among patients with diabetes (15.9% vs. 9.5%). The rate of permanent discontinuation due to adverse events was similar in the diabetes and non-diabetes subgroups at 10weeks, respectively: pre-discharge (7.5% vs. 7.1%) or post-discharge (5.7% vs. 4.2%). Similar patterns of uptitration and tolerability were observed at 26weeks. Cardiac biomarkers including NT-proBNP (P<0.005) and hs-TnT (P<0.005) reduced significantly from baseline levels in both subgroups at Weeks 4 and 10; however, the response was greater among patients without diabetes. Mortality (diabetes vs. non-diabetes subgroups: 3.3% vs 4.0%; P=0.438) and HF rehospitalization (diabetes vs. non-diabetes subgroups: 36.3% vs. 33.0%; P=0.295) did not differ between the groups at 26weeks. Despite a higher risk profile among patients with diabetes, sacubitril/valsartan initiation either before or shortly after discharge in hospitalized patients with HFrEF resulted in comparable rates of dose up-titration and tolerability as in those without diabetes.

Nonalcoholic fatty liver disease in relation to the remission and progression along the glycemic continuum.

BackgroundThe study aimed to explore the associations of nonalcoholic fatty liver disease (NAFLD) with the remission and progression along the glycemic continuum.MethodsThis prospective cohort study was performed among the general population in 2010–2015. NAFLD was defined as ultrasound‐detected hepatic steatosis with absence of excessive alcohol consumption and other hepatic diseases. Remission of type 2 diabetes referred to glycated hemoglobin <6.5% without hypoglycemic agents for ≥3 months. Prediabetes remission referred to normalization of blood glucose. Multivariable logistic analysis was applied to identify the risk of glycemic metabolic transition.ResultsDuring a median follow‐up of 4.3 years, participants with NAFLD had a significantly higher risk of progressing from normal glucose tolerance to diabetes (3.36 [1.60–7.07]) and lower likelihood of diabetes remission (0.48 [0.30–0.78]). Associations in participants with overweight or obesity and higher probability of hepatic fibrosis remained consistent. Results related to the effect of NAFLD on the specific glucose parameters were generally in line with the changes of glycemic status. NAFLD improvement decreased the risk of prediabetes progressing to diabetes (0.50 [0.32–0.80]) and increased the probability of prediabetes remission (2.67 [1.49–4.79]). NAFLD tended to show the most significant association with glycemic progression and decreased the likelihood in remission of prediabetes and diabetes.ConclusionsPresence of NAFLD increased risk of glycemic progression and decreased likelihood of remission. NAFLD improvement mitigated glycemic deterioration, whereas NAFLD progression impeded the chance of remission. The results emphasized joint management of NAFLD and diabetes and further focused on liver‐specific subgroups of diabetes to tailor early intervention.

A potential link between AQP3 and SLC14A1 gene expression level and clinical parameters of maintenance hemodialysis patients

BackgroundThe transport of water and urea through the erythrocyte membrane is facilitated by aquaporins such as aquaglyceroporin (AQP3), and type B urea transporters (UT-B). As they may play an important role in osmotic balance of maintenance hemodialysis (HD) patients, the aim of the present study was to determine whether any relationship exists between the expression of their genes and the biochemical / clinical parameters in HD patients.MethodsAQP3 and UT-B (SLC14A1) gene expression was evaluated using RT-qPCR analysis in 76 HD patients and 35 participants with no kidney failure.ResultsThe HD group demonstrated significantly higher median expression of AQP3 and UT-B (Z = 2.16; P = 0.03 and Z = 8.82; p < 0.0001, respectively) than controls. AQP3 negatively correlated with pre-dialysis urea serum concentration (R = -0.22; P = 0.049) and sodium gradient (R = -0.31; P = 0.04); however, no significant UT-B correlations were observed. Regarding the cause of end-stage kidney disease, AQP3 expression positively correlated with erythropoietin dosages in the chronic glomerulonephritis (GN) subgroup (R = 0.6; P = 0.003), but negatively in the diabetic nephropathy subgroup (R = -0.59; P = 0.004). UT-B positively correlated with inter-dialytic weight gain% in the GN subgroup (R = 0.47; P = 0.03).ConclusionMaintenance hemodialysis seems significantly modify AQP3 and UT-B expression but their link to clinical and biochemical parameters needs further large-scale evaluation.

748 A Comparison Between Arthroscopic Capsular Release and Hydrodilatation in the Treatment of Frozen Shoulder

Abstract Aim Frozen shoulder (FS) is a common but poorly understood condition with no gold standard identified, two options include arthroscopic capsular release (ACR) and hydrodilatation (HD). Recently, the use of HD has become increasingly popular, and this study aims to compare the outcomes of patients undergoing ACR and HD. Method A retrospective analysis of 171 patients diagnosed with FS and treated with either ACR or HD. Data was collected on demographics, range of motion (pre and post procedure), diabetic or trauma status and outcome. The primary outcome measure was whether the patient required further treatment. The secondary outcome measure was the range of motion. Subgroup analyses were also performed on diabetic and post-traumatic groups with frozen shoulder. Results A total of 71 patients had an ACR and 100 patients had HD, with 73.2% and 70% of patients being discharged respectively. The average age was 54.5 years in the ACR cohort and 54.1 years in the HD cohort. There was a significant improvement in range of motion for both cohorts and no difference in the efficacy of the treatments. The same result was found for diabetic and trauma patient subgroups. However, diabetics were 2.41 times more likely to require further treatment than non-diabetics. Conclusion ACR and HD are effective treatments, however, no significant difference in outcome between the two was found. HD has a lower cost and less risk attached compared to ACR, making it preferable. Where HD isn't successful, ACR provides another reliable option.

Oxidative stress markers as early predictors of diabetes complications in Type 2 diabetic patients

Objectives: Type 2 diabetes mellitus (T2DM) is a complex disease that affects many organs. Oxidative stress plays a key role in the pathogenesis of insulin resistance and β-cell dysfunction. Thus, the present study aimed to use oxidative stress markers as early predictors for the progression of diabetic complications. Materials and Methods: The study sample included 400 individuals (300 T2DM and 100 non-diabetic controls) aged from 35 to 59 years randomly selected from the outpatient clinic of the National Institute for Diabetes and Endocrinology. T2DM patients were divided into subgroups: Subgroup (1) patients without any complications, Subgroup (2) patients with diabetic nephropathy (DN) and Subgroup (3) patients with cardiovascular disorders (CVD). Biochemical markers of fasting blood glucose, glycated haemoglobin (HbA1C), glucose-6-phosphate dehydrogenase (G6PD), lactate, arginase, heme oxygenase-1 (HO-1), haemoglobin (Hb), triglycerides (TG), cholesterol, low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), urea, creatinine, malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT) and nitric oxide (NO) were performed. Results: DM patients showed significant increases in body mass index, systolic blood pressure, diastolic blood pressure, FBS, HbA1C, cholesterol, TG, LDL-C and glomerular filtration rate, while HDL-C decreased. Significant increases were observed in HO-1, MDA and NO, while G6PD/lactate, GSH and CAT decreased in DM patients. The DN and CVD patients exhibited a significant increase in HO-1, MDA and NO; while G6PD/lactate, GSH and CAT decreased compared with DM patients. Receiver operating characteristic analysis showed that the sensitivity and specificity of oxidative stress markers were 66.67–100%. Conclusion: Hexose monophosphate (HMP)/glycolysis pathways are shifted during DM near glycolysis rather than HMP pathway to produce energy where the amount of glucose enters the cells is low, causing oxidative stress. Oxidative stress markers could be used as early predictors of diabetes complications.

Association between HBV Infection and the Prevalence of Coronary Artery Disease in the US Population.

Aims This study aims to investigate the association between HBV infection and coronary artery disease (CAD) prevalence in the US population. A nomogram was proposed to predict CAD based on HBV infection. Methods 25,749 individuals were collected from the 2001-2014 National Health and Nutrition Examination Survey. Participants with hepatitis B core antibody seropositivity were identified with HBV infection, including current and previous HBV infection status. We used adjusted logistic regression and performed sensitivity analysis to investigate the association between HBV infection and the prevalence of CAD. The effect size was evaluated by odds ratio (OR) with a 95% confidence interval (CI). Then, we created a nomogram to predict coronary artery disease. Additionally, we applied the Cox regression model to assess the association between HBV infection and all-cause mortality in those with baseline CAD. Results 1790 (6.95%) individuals were with HBV infection. In the adjusted model, individuals with HBV showed a decreased CAD risk than those without (OR, 0.81; 95% CI, 0.67-0.98). Consistently, reduced risk in self-reported angina (OR, 0.72; 95% CI, 0.52-0.98) and coronary heart disease (OR, 0.76; 95% CI, 0.58-0.98) was observed in the hepatitis B core antibody seropositivity group. The subgroup analysis showed a consistent trend in the subgroups of age (<45 or ≥45), gender (male or female), hypertension (no or yes), and diabetes (no or yes). In the testing set, the proposed predictive model showed good performance with an area under the curve of 0.85 (95% CI, 0.83-0.86). There was no significant association between HBV infection and all-cause mortality in CAD patients (adjusted P = 0.202). Conclusion Our study suggests that HBV infection was associated with lower CAD risk. The proposed nomogram showed good performance in predicting CAD. However, no significant association was observed between HBV and all-cause mortality in CAD patients.

Association of Metabolic Dysfunction-Associated Fatty Liver Disease With Left Ventricular Diastolic Function and Cardiac Morphology

Background and AimNon-alcoholic fatty liver disease (NAFLD) is closely related to cardiovascular diseases (CVD). A newly proposed definition is metabolic dysfunction-associated fatty liver disease (MAFLD), which was changed from NAFLD. The clinical effect of this change on abnormalities of cardiac structure and function is yet unknown. We aimed to examine whether MAFLD is associated with left ventricular (LV) diastolic dysfunction (LVDD) and cardiac remolding and further identify the impact of different subgroups and severity of MAFLD.MethodWe evaluated 228 participants without known CVDs. Participants were categorized by the presence of MAFLD and the normal group. Then, patients with MAFLD were subclassified into three subgroups: MAFLD patients with diabetes (diabetes subgroup), overweight/obesity patients (overweight/obesity subgroup), and lean/normal-weight patients who had two metabolic risk abnormalities (lean metabolic dysfunction subgroup). Furthermore, the severity of hepatic steatosis was assessed by transient elastography (FibroScan®) with a controlled attenuation parameter (CAP), and patients with MAFLD were divided into normal, mild, moderate, and severe hepatic steatosis groups based on CAP value. Cardiac structure and function were examined by echocardiography.ResultsLVDD was significantly more prevalent in the MAFLD group (24.6% vs. 60.8%, p < 0.001) compared to the normal group. The overweight subgroup and diabetes subgroup were significantly associated with signs of cardiac remolding, including interventricular septum thickness, LV posterior wall thickness, left atrial diameter (all p < 0.05), relative wall thickness, and LV mass index (all p < 0.05). Additionally, moderate-to-to severe steatosis patients had higher risks for LVDD and cardiac remolding (all p-values < 0.05).ConclusionMAFLD was associated with LVDD and cardiac remolding, especially in patients with diabetes, overweight patients, and moderate-to-to severe steatosis patients. This study provides theoretical support for the precise prevention of cardiovascular dysfunction in patients with MAFLD.