Independent and interactive associations of heart rate and obesity with type 2 diabetes mellites: A population-based study.

BACKGROUND: Although obesity and heart rate (HR) were closely related to the prevalence and development of type 2 diabetes mllitus (T2DM), few studies have shown a co-association effect of them on T2DM. We aimed at assessing the interactive effects of HR and obesity with prevalence of T2DM in Chinese population, providing the exact cutpoint of the risk threshold for blood glucose with high HR. MATERIALS AND METHODS: In the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal study (REACTION) cohorts (N = 8398), the relationship between HR and T2DM was explored by linear regression, logistic regression, and restricted cubic spline, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Interaction terms between HR and body mass index (BMI) and HR and waist circumference (WC) were introduced into the logistic regression model. RESULTS: In those with HR > 88.0 beats/min, fasting plasma glucose and oral glucose tolerance tests were significantly correlated with HR, and the prevalence of T2DM was highly correlated with HR (all p < .05). There were interactive associations of HR and obesity in patients with T2DM with HR < 74 beats/min. CONCLUSION: High HR was in interaction with obesity, associating with prevalence of T2DM. The newly subdivided risk threshold for HR with T2DM might be HR > 88 beats/minute.

Glucose Metabolism Indices and the Development of Chronic Kidney Disease: A Cohort Study of Middle-Aged and Elderly Chinese Persons.

Objective: Chronic kidney disease (CKD) has become a major global health issue, and abnormalities of glucose metabolism are a risk factor responsible for development of CKD. We aimed to investigate associations between glucose metabolism indices and CKD in a Chinese population and determine which index is superior for predicting incident CKD. Methods: We performed a community-based population on 5232 subjects aged ≥40 years without baseline CKD. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g. We examined the associations of glucose metabolism indices, including fasting plasma glucose (FPG), 2-hour (2 h) oral glucose tolerance test (OGTT), hemoglobin A1c (HbA1c), fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA-ß and the development of CKD. Results: With an average follow-up of 3.6 years, 6.4% of the subjects developed CKD. Pearson's correlation analysis revealed that FPG, HbA1c, fasting insulin, and HOMA-IR were all significantly correlated with UACR and eGFR. The association persisted in multivariate linear regression analysis adjusted for age and sex. Compared with other glucose indices, HOMA-IR exhibited the strongest associations with CKD in COX multivariate regression analysis (HR = 1.17, 95% CI: 1.04-1.31). Conclusion: HOMA-IR is superior to other routine indices of glucose metabolism for predicting the development of CKD in middle-aged Chinese persons. Screening with HOMA-IR may help prevent the development of CKD in the general population.

U-shaped association between serum IGF2BP3 and T2DM: A cross-sectional study in Chinese population.

OBJECTIVE: To clarify the expression of N6-methyladenosine (m6 A) modulators involved in the pathogenesis of type 2 diabetes mellitus (T2DM). We further explored the association of serum insulin-like growth factor 2 mRNA-binding proteins 3 (IGF2BP3) levels and odds of T2DM in a high-risk population. METHODS: The gene expression data set GSE25724 was obtained from the Gene Expression Omnibus, and a cluster heatmap was generated by using the R package ComplexHeatmap. Differential expression analysis for 13 m6 A RNA methylation regulators between nondiabetic controls and T2DM subjects was performed using an unpaired t test. A cross-sectional design, including 393 subjects (131 patients with newly diagnosed T2DM, 131 age- and sex-matched subjects with prediabetes, and 131 healthy controls), was carried out. The associations between serum IGF2BP3 concentrations and T2DM were modeled by restricted cubic spline and logistic regression models. RESULTS: Two upregulated (IGF2BP2 and IGF2BP3) and 5 downregulated (methyltransferase-like 3 [METTL3], alkylation repair homolog protein 1 [ALKBH1], YTH domain family 2 [YTHDF2], YTHDF3, and heterogeneous nuclear ribonucleoprotein [HNRNPC]) m6 A-related genes were found in islet samples of T2DM patients. A U-shaped association existed between serum IGF2BP3 levels and odds of T2DM according to cubic natural spline analysis models, after adjustment for body mass index, waist circumference, diastolic blood pressure, total cholesterol, and triglyeride. Multivariate logistic regression showed that progressively higher odds of T2DM were observed when serum IGF2BP3 levels were below 0.62 ng/mL (odds ratio 3.03 [95% confidence interval 1.23-7.47]) in model 4. CONCLUSION: Seven significantly altered m6 A RNA methylation genes were identified in T2DM. There was a U-shaped association between serum IGF2BP3 levels and odds of T2DM in the general Chinese adult population. This study provides important evidence for further examination of the role of m6 A RNA methylation, especially serum IGF2BP3 in T2DM risk assessment.

Association between uric acid lowering and renal function progression: a longitudinal study.

BACKGROUND: This study aimed to explore the association between uric acid lowering and renal function. MATERIALS AND METHODS: We conducted a population-based cohort study with 1,534 subjects for 4 years from 2012 to 2016. The population was divided into four groups according to the interquartile range of changes in serum uric acid with quartile 1 representing lower quarter. Renal function decline was defined as eGFR decreased more than 10% from baseline in 2016. Renal function improvement was defined as eGFR increased more than 10% from baseline in 2016. Cox regression analysis was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: In the adjusted Cox regression models, compared to quartile 4, quartile 1 (HR = 0.64, 95% CI [0.49-0.85]), quartile 2 (HR = 0.65, 95% CI [0.50-0.84]) and quartile 3 (HR = 0.75, 95% CI [0.58-0.96]) have reduced risk of renal function decline. An increasing hazard ratio of renal function improvement was shown in quartile 1 (HR = 2.27, 95% CI [1.45-3.57]) and quartile 2 (HR = 1.78, 95% CI [1.17-2.69]) compared with quartile 4. CONCLUSIONS: Uric acid lowering is associated with changes in renal function. The management of serum uric acid should receive attention in clinical practice and is supposed to be part of the treatment of chronic kidney disease.

Associations Between Metabolic Profiles and Target-Organ Damage in Chinese Individuals With Primary Aldosteronism.

Purpose: Patients with primary aldosteronism (PA) have an increased risk of target-organ damage (TOD), but whether metabolic syndrome (MetS) is more prevalent and contributes to TOD in PA patients remains unresolved. We aimed to evaluate the associations between MetS profiles and TOD in Chinese PA individuals. Methods: Metabolic parameters and pre-clinical TOD including left ventricular hypertrophy, estimated glomerular filtration, and microalbuminuria; insulin sensitivity or resistance; and islet ß-cell function were assessed by the homeostasis models (HOMA-IR, HOMA-ß) and the other surrogate indexes [composite insulin sensitivity index (ISI), modified ß-cell function index (MBCI)] determined from the oral glucose tolerance test were compared in PA vs. matched essential hypertension (EH) patients. Results: A total of 109 PA patients and 109 essential hypertension (EH) controls individually matched for sex, age, and office systolic blood pressure and duration of hypertension were studied. The prevalence of MetS and its individual components in PA was significantly lower than in EH [MetS: 28 (25.6%) vs. 54 (49.5%), P < 0.001]. PA patients had a higher composite ISI but a lower HOMA-IR, HOMA-ß, and MBCI than EH controls (all P < 0.05). Concerning TOD, PA patients had significantly higher prevalence of microalbuminuria and left ventricular hypertrophy (LVH), and lower levels of estimated glomerular filtration (eGFR) than EH controls (all P < 0.05). On multivariate logistic regression analysis, female gender and elevated plasma aldosterone levels were significantly associated with TOD in PA. However, there were no significant associations between MetS and its individual components and TOD in PA patients. Conclusions: PA patients had a lower MetS prevalence but exhibited more severe TOD than matched EH controls. The study highlights the deleterious effects of aldosterone excess on the development of TOD, whereas MetS or its individual components might be less influential in PA.

Preoperative risk factors for haemodynamic instability during pheochromocytoma surgery in Chinese patients.

OBJECTIVE: Pheochromocytoma surgery carries a high risk of haemodynamic instability (HI). However, there are few studies investigating the risk factors for HI for pheochromocytoma surgery in a Chinese population. Therefore, our objective was to identify preoperative risk factors for HI during surgery in a Chinese population with pheochromocytoma. PATIENTS AND METHODS: In this retrospective study, 134 patients undergoing surgery for pheochromocytoma at a single university-affiliated hospital between November 2002 and July 2017 were enrolled. Demographics, comorbidities, preoperative medical preparation, operation details and perioperative haemodynamics of these patients were retrospectively collected and analysed. Multivariable logistic regression analysis was performed to identify the preoperative risk factors for intraoperative HI. RESULTS: 32.8% (44/134) patients suffered from intraoperative HI. According to the result of multivariate analysis, tumour diameter >50 mm (odds ratio [OR] 2.526; 95% confidence interval [CI] 1.163-5.485; P = .019), diabetes/prediabetes (OR 2.251; 95% CI 1.039-4.876; P = .040) and preoperative systolic blood pressure fluctuation >50 mm Hg (OR 3.163; 95% CI 1.051-9.522, P = .041) were independent predictors for intraoperative HI. The observed incidence of HI was 8.9%, 42.6%, 47.8% and 60% when zero, one, two or three risk factors were present, respectively. CONCLUSIONS: HI is common among Chinese patients undergoing surgery for pheochromocytoma. Our study identified three predictive factors for intraoperative HI: a large tumour diameter, diabetes/prediabetes and a great preoperative systolic blood pressure fluctuation. Furthermore, patients are more likely to suffer from HI when they have more predictive risk factors. Identification of these risk factors can help to improve perioperative management.

Surgical resection of adrenocortical carcinoma with invasion into the inferior vena cava: a case report and literature review.

Adrenocortical carcinoma (ACC) is a malignant endocrine tumor. Moreover, ACC with invasion into the inferior vena cava is rare. Early diagnosis and treatment are crucial for such cases. Radical surgical resection is the key therapeutic option in ACC.

The intriguing effects of time to glycemic goal in newly diagnosed type 2 diabetes after short-term intensive insulin therapy.

Short-term intensive insulin therapy is effective for type 2 diabetes because it offers the potential to achieve excellent glycemic control and improve ß-cell function. We observed that the time to glycemic goal (TGG) was adjustable. Original data of 138 newly diagnosed type 2 diabetic patients received intensive insulin therapy by continuous subcutaneous insulin infusion for 2-3 weeks were retrospectively collected. Subjects underwent an intravenous glucose tolerance test (IVGTT) and an oral glucose tolerance test (OGTT) pre and post treatment. The glycemic goal was achieved within 6 (4-8) days. Patients were divided into two groups by TGG above (TGG-slow) and below (TGG-fast) the median value. Patients in both groups had significantly better glycemic control. Compared with TGG-fast, TGG-slow required a few more total insulin and performed more improvement of HOMA-ß and IVGTT-AUCIns, but less improvement of HOMA-IR and QUICKI. Multiple linear regression analysis revealed that TGG was always an explanatory variable for the changes (HOMA-ß, IVGTT-AUCIns, HOMA-IR and QUICKI). The hypoglycemia prevalence was lower in TGG-slow (1.48% vs. 3.40%, P<0.01). Multivariate logistic regression analysis indicated that individuals in TGG-slow had a lower risk of hypoglycemia (adjusted OR, 0.700; 95% CI, 0.567-0.864; P<0.05). Multiple linear regression analysis confirmed that the ratio of the incremental insulin to glucose responses over the first 30 min during OGTT (ΔIns30/ΔG30), average insulin dose before achieving targets, initial insulin dose and LDL-c were independent predictors for TGG. It is intriguing to hypothesize that patients with fast time to glycemic goal benefit more in improving insulin sensitivity, but patients with slow time benefit more in improving ß-cell function and reducing the risk of hypoglycemia.

Discordant associations of lipid parameters with albuminuria and chronic kidney disease: a population-based study.

BACKGROUND: Although dyslipidemia is related to the pathogenesis of renal insufficiency, which routinely available lipid measure is more applicable in estimation of kidney function is still uncertain. Our objective was to evaluate inconsistent associations of lipid profiles with both albuminuria and chronic kidney disease (CKD). METHODS: We performed a population-based study in 9730 subjects aged 40 years or older. Definitions of abnormalities in albumin excretion were according to the latest guidelines of American Diabetes Association's Standards of Medical Care. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m(2) or the presence of albuminuria. RESULTS: There were 2274 (23.4%) participants categorized as low-grade albuminuria, 639 (6.6%) participants categorized as increased urinary albumin excretion and 689 (7.1%) participants categorized as CKD. Triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), Non HDL-C to HDL-C ratio, TG to HDL-C ratio were significantly correlated with urinary albumin to creatinine ratio (ACR), serum creatinine and eGFR (all P < 0.0001). Compare with other lipid parameters, TG to HDL-C ratio have shown the strongest correlation with increased odds of both increased urinary albumin excretion and CKD. No significant associations between lipid parameters and low-grade albuminuria were observed after adjustments for potential confounding factors. CONCLUSION: Our study lends support to discordant associations of lipid parameters with albuminuria and renal function. TG to HDL-C ratio is a better marker than other routine lipid measures for identifying renal insufficiency and should be given more consideration in the clinical practice.

Association between habitual daytime napping and metabolic syndrome: a population-based study.

OBJECTIVE: Our objective was to evaluate the association between habitual daytime napping and the prevalence of metabolic syndrome. MATERIALS AND METHODS: We conducted a population-based study of 8,547 subjects aged 40 years or older. Metabolic syndrome was defined according to a harmonized definition from a joint statement and the recommended thresholds for the Chinese population. Information about sleep duration was self-reported. RESULTS: The prevalence of metabolic syndrome in the no daytime napping group, the 0 to 1 hour daytime napping group and the more than 1 hour daytime napping group were 35.0%, 36.0% and 44.5% among the females (P<0.0001). Increased daytime napping hours were positively associated with parameters of metabolic syndrome in the female subjects, including waist circumference, systolic blood pressure, triglycerides and fasting plasma glucose (P<0.05 for all). Multivariate adjusted logistic regression analysis revealed that, compared to the no habitual daytime napping females, napping for more than 1 hour was independently associated with an increased prevalence of metabolic syndrome (odds ratio 1.39, 95% confidence interval, 1.13-1.72). Compared to the female subjects in the no daytime napping group, those habitually napped for more than 1 hour exhibited 46% and 26% increases in the prevalence of central obesity and hypertriglyceridemia (all P<0.05). No statistically significant associations were detected between daytime napping hours and metabolic syndrome among the male subjects. CONCLUSION: Daytime napping is associated with an increased prevalence of metabolic syndrome in middle-aged non-obese Chinese women.

AML1-ETO triggers epigenetic activation of early growth response gene l, inducing apoptosis in t(8;21) acute myeloid leukemia.

The t(8;21)(q22;q22) translocation is the most common chromosomal translocation in acute myeloid leukemia (AML), and it gives rise to acute myeloid gene 1 (AML1)-myeloid transforming gene 8 (ETO)-positive AML, which has a relatively favorable prognosis. However, the molecular mechanism related to a favorable prognosis in AML1-ETO-positive AML is still not fully understood. Our results show that the AML1-ETO fusion protein triggered activation of early growth response gene l (EGR1) by binding at AML1-binding sites on the EGR1 promoter and, subsequently, recruiting acetyltransferase P300, which is known to acetylate histones. However, AML1-ETO could not recruit DNA methyltransferases and histone deacetylases; therefore, EGR1 expression was affected by histone acetylation but not by DNA methylation. Both transcription and translation of EGR1 were higher in AML1-ETO-positive AML cell lines than in AML1-ETO-negative AML cell lines, owing to acetylation. Furthermore, when AML1-ETO-positive AML cell lines were treated with C646 (P300 inhibitor) and trichostatin A (histone deacetylase inhibitor), EGR1 expression was significantly decreased and increased, respectively. In addition, treatment with 5-azacytidine (methyltransferase inhibitor) did not cause any significant change in EGR1 expression. Overexpression of EGR1 inhibited cell proliferation and promoted apoptosis, and EGR1 knockout promoted cell proliferation. Thus, EGR1 could be a novel prognostic factor for a favorable outcome in AML1-ETO-positive AML. The results of our study may explain the molecular mechanisms underlying the favorable prognosis in AML1-ETO-positive AML.

[Biomarkers of endothelial dysfunction and risk of early organ damage: a comparison between patients with primary aldosteronism and essential hypertension].

OBJECTIVE: To compare plasma concentrations of biomarkers of endothelial dysfunction between patients with primary aldosteronism (PA) and essential hypertension (EH), and to determine whether elevated levels of these biomarkers could predict development of early organ damage. METHODS: Thirty-six PA patients and 39 EH patients matched for age, sex, blood pressure and duration of hypertension were included in this study. Plasma levels of biomarkers reflecting endothelial dysfunction (von Willebrand factor, vWF; soluble intercellular adhesion molecule 1, sICAM-1; and oxidized low density lipoprotein, ox-LDL) were detected and compared between PA and EH patients. Left ventricular mass index (LVMI) determined by echocardiography, 24-hour urinary protein quantitative determination and urinary albumin excretion rate (UAER) were analyzed to evaluate early organ damage. Left ventricular hypertrophy was defined as LVMI > 125 g/m(2) in men and > 120 g/m(2) in women, and UAER between 20 µg/min and 200 µg/min was defined as microalbuminuria. RESULTS: vWF [(122.3 ± 53.8)% vs. (113.1 ± 68.3)%], sICAM-1 [(401.0 ± 74.1) µg/L vs. (300.9 ± 87.0) µg/L], ox-LDL [(13.6 ± 10.0) U/L vs. (8.1 ± 5.9) U/L], LVMI [(124.7 ± 33.6) g/m(2) vs. (109.1 ± 25.7) g/m(2)], 24-hour urinary protein quantitation [24 h UPQ, (0.17 ± 0.10) g vs. (0.09 ± 0.04) g] and UAER [(25.9 ± 7.7) µg/min vs. (9.7 ± 5.9) µg/min] were significantly higher in PA group than in EH group (all P < 0.05). Elevated plasma vWF, sICAM-1 levels and plasma aldosterone concentration independently predicted microalbuminuria. Whereas, elevated plasma vWF and ox-LDL levels, plasma aldosterone concentration and systolic blood pressure independently predicted left ventricular hypertrophy. CONCLUSION: Patients with PA have severer endothelial dysfunction reflected by multiple biomarkers and earlier organ damage than patients with EH, and plasma aldosterone concentration and multiple endothelial dysfunction biomarkers could independently predict early organ damage.

[Effect of compound danshen dripping pill on arterial intima-media thickness in patients with newly diagnosed type 2 diabetes mellitus].

OBJECTIVE: To investigate the effect of compound Danshen Dripping Pill (CDDP) on peripheral arterial intima-media thickness (IMT) in patients newly diagnosed as type 2 diabetes mellitus. METHODS: One hundred and eight patients were equally randomized into 3 groups, in addition to the basic hypoglycemic, hypotensive and lipid-regulation treatment, they were administered orally with aspirin (0.1 g, once daily), vitamin E (0.1 g, twice daily) and CDDP (10 pills, thrice daily) for 18 months, respectively. The conventional cardiovascular risk factors, such as hyperglycemia, lipids profile, and homeostasis model assessment of insulin resistance (HOMA-IR) as well as ultrasound measurement of peripheral arterial IMT before and after treatment were compared. RESULTS: In the group treated with CDDP after treatment, the levels of HbA1c, serum total cholesterol and low density lipoprotein cholesterol (LDL-C) were significantly lower (all P<0.01), HOMA-IR was higher than those in the other two groups; while IMTs of carotid, iliac and femoral arteries were insignificantly different among them (P>0.05); however, the increment of carotid IMT in the CDDP treated group was less than that in the aspirin treated group (P<0.05), and that of femoral IMT was less than both the aspirin and vitamin E treated groups (P<0.05). CONCLUSION: For the patients with newly diagnosed type 2 diabetes, additional administration of CDDP to the conventional treatment could exert beneficial effects on blood glucose controling, and lipid profile improvement and delay of arterial intima-media proliferation.