Jingtao Dou

Plasma homocysteine thiolactone associated with risk of macrovasculopathy in Chinese patients with type 2 diabetes mellitus

IntroductionThis study investigated the role of homocysteine thiolactone (HcyT) in the development of macrovascular complications in Chinese patients with type 2 diabetes. HcyT has been proposed as a possible molecular basis for homocysteine (Hcy)-induced vascular damage.MethodsOne hundred and sixty subjects were recruited into this study: 40 healthy controls and 120 patients with type 2 diabetes. Plasma Hcy levels were measured by polarization immunoassay and HcyT concentrations were monitored using high-performance liquid chromatography on a reversephase C18 column with ultraviolet detection. Plasma folic acid and vitamin B12 levels were measured using radioimmunoassay methods.ResultsPlasma Hcy and HcyT concentrations in patients with type 2 diabetes were significantly higher than in healthy controls (Hcy [25th and 75th quartiles]: 9.28 [7.51–11.82] vs. 5.64 [5.17–8.00] μmol/L, P=0.01; HcyT: 3.38 [2.94–4.73] vs. 2.91 [2.77–3.08] nmol/L, P<0.05). Plasma Hcy and HcyT levels in patients with macrovasculopathy (MAVP) were significantly higher compared with patients without MAVP (Hcy: 10.36 [7.67–12.45] vs. 7.85 [6.76–10.52] μmol/L, P<0.05; HcyT: 4.27 [3.02–5.11] vs. 3.12 [2.63–3.77] nmol/L, P<0.05). Plasma HcyT concentrations were positively correlated with urinary excretion of albumin/creatinine (Alb/Cr; r=0.285, P=0.007), duration of diabetes (r=0.249, P=0.019), age (r=0.233, P=0.028), and fibrinogen levels (r=0.289, P=0.034). Plasma HcyT concentrations were negatively correlated with high-density lipoprotein levels (r=−0.223, P=0.037). Binary logistic regression showed that HcyT, Hcy, smoking, serum triglyceride, and urine Alb/Cr were significantly associated with the risk of diabetic MAVP (P<0.05).ConclusionHcy and HcyT levels were associated with the development and progression of diabetic MAVP. HcyT may provide a plausible chemical mechanism for explaining Hcy toxicity in the human vascular endothelium.

Combinational therapy with metformin and sodium-glucose cotransporter inhibitors in management of type 2 diabetes: systematic review and meta-analyses.

AIMS In search of add-on treatments to metformin, sodium-glucose cotransporter-2 (SGLT-2) inhibitors are potential candidates. This meta-analysis examines the potential use of SGLT-2 inhibitors in combination with metformin as a therapeutic option for type 2 diabetes management in patients with inadequate control with metformin. METHODS A literature search was made in several databases for randomized controlled trials (RCTs) utilizing metformin therapy combined with SGLT-2 inhibitors or placebo. Heterogeneity was estimated with I(2) statistics and random effect model was chosen for the meta-analyses of mean differences in changes from baseline in both SGLT-2 inhibitor treated and control groups. RESULTS Seven RCTs were selected for the meta-analysis. In comparison with placebo-MET, the SGLT-2 inhibitor-MET combination therapy resulted in significant HbA1c decline in 12-24 week duration, to less extent after 1 year (-0.37 [-0.77, 0.03]; P=0.07) but not by 2 year (-0.41 [-1.09, 0.28]; P=0.24) duration. SGLT-2 inhibitor-MET significantly lowered FPG and body weight after 24 weeks, 1 year, and 2 years. Systolic and diastolic blood pressure declined only in the short-term (12-24 weeks). After 2 years, neither systolic (-1.80 [-6.18, 2.58]; P=0.42) nor diastolic blood pressure (-0.20 [-2.94, 2.54]; P=0.89) declined significantly more than control. Incidence of suspected genital infections was slightly more in SGLT-2 inhibitor-MET group. CONCLUSION SGLT-2 inhibition in combination with metformin is a potential therapeutic option based on its effects on glycemic control, body weight, and blood pressure, but further trials are required to refine this evidence.

Pituitary stalk interruption syndrome in Chinese people: clinical characteristic analysis of 55 cases.

Objective Pituitary stalk interruption syndrome (PSIS) is characterized by the absence of pituitary stalk, pituitary hypoplasia, and ectopic posterior pituitary. Due to the rarity of PSIS, clinical data are limited, especially in Chinese people. Herein, we analyzed the clinical characteristics of patients diagnosed with PSIS from our center over 10 years. Patients and Methods We retrospectively analyzed the clinical manifestations and laboratory and MRI findings in 55 patients with PSIS. Results Of the 55 patients with PSIS, 48 (87.3%) were male. The average age was 19.7±6.7 years and there was no familial case. A history of breech delivery was documented in 40 of 45 patients (88.9%) and 19 of 55 patients (34.5%) had a history of dystocia. Short stature was found in 47 of 55 patients (85.5%) and bone age delayed 7.26±5.37 years. Secondary sex characteristics were poor or undeveloped in most patients. The prevalence of deficiencies in growth hormone, gonadotropins, corticotropin, and thyrotropin were 100%, 95.8%, 81.8%, 76.3%, respectively. Hyperprolactinemia was found in 36.4% of patients. Three or more pituitary hormone deficiencies were found in 92.7% of the patients. All patients had normal posterior pituitary function and absent pituitary stalk on imaging. The average height of anterior pituitary was 28 mm, documented anterior pituitary hypoplasia. Midline abnormalities were presented in 9.1% of patients. Conclusions The clinical features of our Chinese PSIS patients seem to be different from other reported patients in regarding to the higher degree of hypopituitarism and lower prevalence of midline defects. In addition, our patients were older at the time of case detection and the bone age was markedly delayed. We also had no cases of familial PSIS.

Whole exome sequencing identifies mutation of EDNRA involved in ACTH-independent macronodular adrenal hyperplasia

ACTH independent macronodular adrenal hyperplasia (AIMAH) is a rare disorder characterized by bilateral macronodular hyperplasia of the adrenal glands and increased cortisol production with subclinical or overt Cushing’s syndrome. Although the family clustering of AIMAH is infrequent, we have tried our best to find such a familial affected pedigree with complete clinical information and successfully collect adrenalectomy tissue samples from two members of this family. Using whole exome sequencing and several variant prioritization strategies based on disease network analysis, we identified Endothelin receptor type A (EDNRA) Ser420Thr mutation as a causative mutation of AIMAH. EDNRA is a member of G protein coupled receptor family and is involved in cardiovascular or polycystic kidney disease. Our findings indicate that the mutation of EDNRA at S420T site should be regard as a potential AIMAH causative variation in familial and sporadic affected patients.

Accurate combined preoperative localization of insulinomas aid the choice for enucleation: a single institution experience over 25 years.

BACKGROUND/AIMS To assess the accuracy of combined preoperative localizations and analyze the change in management strategy of operation of insulinoma. METHODOLOGY One hundred and seventy-two patients with a diagnosis of insulinoma at a tertiary hospital between 1985 and 2010 were reviewed, where accurate combined preoperative localization before surgical exploration was the primary management policy of insulinoma. Operation details for 147 patients were checked. RESULTS An average of 2.89 preoperative localization studies including 1.61 non-invasive studies and 1.28 invasive studies were utilized per patient. Contrast-enhanced ultrasonography (CEUS) was the most sensitive invasive modality (88.1%) whereas magnetic resonance imaging (MRI) was the most sensitive non-invasive modality (64.0%). All 147 patients underwent complete surgical resection which included 126 enucleations and 18 distal pancreatectomies with a cure rate of 95.2% (140/147) at a median follow-up of 45 months (range 1-248). The postoperative morbidity and long-term outcome of enucleation was similar to distal pancreatectomy despite a higher rate of microscopic margin involvement. CONCLUSIONS Accurate combined preoperative localization of insulinomas is useful of the choice of enucleation, eliminates the need for blind distal pancreatectomy and avoids re-operation. Whenever possible, a pancreas-sparing approach such as enucleation should be adopted.

Reassessing the reliability of the salivary cortisol assay for the diagnosis of Cushing syndrome

Objective The cortisol concentration in saliva is 10-fold lower than total serum cortisol and accurately reflects the serum concentration, both levels being lowest around midnight. The salivary cortisol assay measures free cortisol and is unaffected by confounding factors. This study analysed published data on the sensitivity and specificity of salivary cortisol levels in the diagnosis of Cushing syndrome. Methods Data from studies on the use of different salivary cortisol assay techniques in the diagnosis of Cushing syndrome, published between 1998 and 2012 and retrieved using Ovid MEDLINE®, were analysed for variance and correlation. Results For the 11 studies analysed, mean sensitivity and specificity of the salivary cortisol assay were both >90%. Repeated measurements were easily made with this assay, enabling improved diagnostic accuracy in comparison with total serum cortisol measurements. Conclusions This analysis confirms the reliability of the saliva cortisol assay as pragmatic tool for the accurate diagnosis of Cushing syndrome. With many countries reporting a rising prevalence of metabolic syndrome, diabetes and obesity – in which there is often a high circulating cortisol level – salivary cortisol measurement will help distinguish these states from Cushing syndrome.

Pituitary stalk interruption syndrome in 58 Chinese patients: clinical features and genetic analysis

Pituitary stalk interruption syndrome (PSIS) is rare and its clinical features and pathogenesis are poorly understood. This study characterized the clinical and genetic features of PSIS in Chinese patients.

Impact of night sleep duration on glycemic and triglyceride levels in Chinese with different glycemic status.

The aim of the present study was to assess the relationship between night sleep duration and glycemic and triglyceride (TG) levels among people with different glycemic status.

Characterization of Papillary Thyroid Microcarcinomas Using Sonographic Features in Malignant Papillary Thyroid Cancer: A Retrospective Analysis

AbstractThe diagnosis of malignant thyroid nodules is still a clinical challenge. This study aimed to determine the ultrasonographic characteristics of papillary thyroid carcinoma.The ultrasonographic and pathological data of 2453 thyroid nodules in a cohort of 1895 Chinese patients who underwent thyroidectomy from January 2010 to December 2012 were retrospectively reviewed.Anteroposterior and transversal (AP/TR) diameters ≥1, solid structure, infiltrative margins, hypoechoic appearance, and microcalcifications were more common in malignant nodules than in benign nodules (P < 0.01). These ultrasonographic features were independent risk factors of malignancy (P < 0.01) as determined by logistic regression analysis. Based on multivariate analysis, these characteristics were also present in large nodules (diameter >10 mm). However, in small nodules (diameter ⩽10 mm), only AP/TR ≥1 and infiltrative margins were independent risk factors of malignancy (P < 0.01).Ultrasonography is of high diagnostic value for malignant thyroid nodules and may help to improve the differential diagnosis. Small and large nodules have distinct ultrasonographic features.

Waist-to-hip ratio, dyslipidemia, glycemic levels, blood pressure and depressive symptoms among diabetic and non-diabetic Chinese women: a cross-sectional study.

Objectives To explore the relationship between depressive symptoms and waist-to-hip ratio, dyslipidemia, glycemic levels or blood pressure among diabetic and non-diabetic Chinese women. Methods 11,908 women aged ≥40 years were enrolled in this cross-sectional study, including 2,511 with type 2 diabetes and 9,397 without. Depressive symptoms (defined as having mild-to-severe depressive symptoms) were assessed by the Patient Health Questionnaire-9 (PHQ-9) diagnostic algorithm. The prevalence and the odds ratios (ORs) with 95% confidence intervals (CIs) for having depressive symptoms were estimated using logistic regression analysis. Results The age-adjusted prevalence of depressive symptoms was significantly higher in non-diabetic subjects with waist-to-hip ratio (WHR) ≥0.9 (8.6%, age-adjusted OR 1.51 [95% CI 1.17, 1.95]), total cholesterol (TC)>6.22 mmol/L (8.8%, 1.58 [1.16, 2.15]), and Hemoglobin A1c (HbA1c) ≥6.00 mmol/L (7.7%, 1.69 [1.34, 2.14]), while it was significantly lower in non-diabetic subjects with diastolic blood pressure (DBP) between 80 to 89 mmHg (6.2%, 0.78 [0.64, 0.95]). These relationships remained significant even after controlling for multiple factors (WHR ≥0.9: multivariable-adjusted OR 1.39 [95% CI 1.07, 1.80]; TC>6.22 mmol/L: 1.56 [1.14, 2.12]; HbA1c ≥6.00 mmol/L: 1.64 [1.30, 2.08]; DBP 80-89 mmHg: 0.78 [0.64, 0.95]). However, no significant trend between depressive symptoms and WHC, TC, HbA1c, DBP was observed in diabetic women, and no significant trend relationship between depressive symptoms and BMI, WC, TG, or SBP was observed in both non-diabetic and diabetic women. Moreover, the prevalence of depressive symptoms was significantly higher in previously-diagnosed diabetes, compared with non-diabetic subjects, while no significant differences were observed between newly-diagnosed diabetes and non-diabetic subjects. Conclusion The present study showed a relationship between WHR, TC, HbA1c, DBP and depressive symptoms among non-diabetic women, while no significant relationship between them was observed among diabetic women, even after controlling for multiple confounding factors.