Cushing's syndrome (CS) is a clinical syndrome characterized by hypercortisolemia. Cyclic Cushing's syndrome (CCS), which exhibits a periodic or irregular increasing pattern in cortisol, is a rare type of Cushing's syndrome. A 37-yearold man came to our hospital because of repeated dizzy spells, weakness and hypercortisolemia lasting two weeks. Endocrinological examinations indicated CCS with periodic and intermittent increases in cortisol. Enhanced computed tomography (CT) revealed space occupying lesions on the upper lobe of left lung, and biopsy eventually proved that these were pulmonary carcinoid tumors with ectopic ACTH secretion, which was subsequently manifested a Cushing's syndrome. PET-CT, ultrasound and biopsy of the thyroid gland indicated bilateral thyroid papillary carcinoma. CT scan showed bilateral nodular hyperplasia of the adrenal gland. Enhanced magnetic resonance imaging (MRI) confirmed that the high signal disappeared on the posterior lobe of the pituitary gland and that the pituitary stalk shifted left, which was suspected to be nonfunctional pituitary microadenoma. The patient underwent surgery involving resection of the left upper pulmonary lobe and the mediastinal lymph node around the hilus pulmonis, which resulted in complete remission of CCS. The patient then chose elective surgery for the thyroid papillary carcinoma. An analysis of the patient's genomic DNA identified a novel mutation in PDE 11A: c.2032 (exon 12) G > A, which is associated with primary pigmented nodular adrenocortical disease (PPNAD). This is a novel mutation which has been no previous public clinical report on this mutation as it relates to this disease.
Surgical resection is the primary treatment strategy for pheochromocytoma; however, it carries a high risk of morbidity and mortality, especially with respect to cardiovascular complications, which is the most common kinds of morbidity. The risk factors for morbidity remain unclear and require further exploration, moreover no studies focus on risk factors for cardiovascular morbidity. Herein we identified the risk factors for cardiovascular morbidity after pheochromocytoma surgery in Chinese patients. We retrospectively reviewed 262 patients who underwent unilateral surgical resection of pheochromocytoma at our center between 1 January 2007 and 31 December 2016. Patient demographics and extensive perioperative data were recorded and evaluated. Adjusted odds ratios and 95% confidence intervals were determined by multivariate logistic regression. Cut-off values and the area under the curve for continuous risk factors were calculated based on receiver operating characteristic curve analysis. A p-value <0.05 was considered statistically significant. Of the 262 patients, 63 (24.0%) had cardiovascular morbidity. The independent risk factors for cardiovascular morbidity were low body mass index, large radiographic tumor size, coronary heart disease, no preoperative crystal/colloid administration, and intraoperative hemodynamic instability; the corresponding odds ratio were 0.762 (p < 0.001), 1.208 (p = 0.010), 2.378 (p = 0.012), 2.720 (p = 0.011), and 4.764 (p = 0.001), respectively. The optimal cut-off values for body mass index and radiographic tumor size were 24.59 kg/m(2) and 6.05 cm. We found that cardiovascular morbidity is common in patients after pheochromocytoma surgery. We identified five independent risk factors for cardiovascular morbidity. Identification of these risk factors may help to improve treatment strategies.
To explore new methods for intraoperative identification of parathyroid glands, 86 thyroid cancer patients, admitted to Xijing hospital from July 2017 to July 2018, were included. During lymph node dissection, parathyroid glands were firstly judged by clinician eyeballing, based on his clinical experience. Then, cytological detection was used for rapid identification via Diff-quik staining. PM monitoring was performed by PM detection kit. Finally, frozen pathology was examined and regarded as the golden standard. In this study, 172 suspicious parathyroid glands were observed. According to frozen pathology outcome, the accuracy, sensitivity and specificity of clinician eyeballing were calculated as 63.3%, 100%. and 13.9%. Kappa test showed poor consistency (kappa = 0.156), AUC area was 0.569 +/- 0.045, 95%CI = (0.480-0.658), p = 0.123. For cytological and PTH detection, the accuracy, sensitivity and specificity were 91.7% vs. 92.3%, 93.6% vs. 93.8% and 89.0% vs. 90.3%. Kappa value was 0.829 vs. 0.842, indicating good consistency. AUC area was 0.908 +/- 0.027 vs. 0.918 +/- 0.025, 95%CI = (0.856-0.960) vs. (0.869-0.966), p < 0.001, indicating higher diagnositic value. Besides, compared with frozen pathology, cytological detection was easily and rapid. The time-taking between frozen pathology and cytological detection or PTH detection were 39.0 +/- 6.59 min vs. 5.02 +/- 0.78 min and 39.0 +/- 6.59 min vs. 6.1 +/- 1.23 min, p < 0.001. In conclusion, intra-operative cytological detection maybe potential for in-situ preservation of parathyroid glands.
Angiopoietin-like protein 8 (ANGPTL8) is a newly discovered adipokine plays an important role in energy homeostasis, obesity and type 2 diabetes (T2D). Although lifestyle modification in obesity and T2D is known to offer metabolic benefits, there is paucity of comprehensive data on change in ANGPTL8. We investigated the effect of lifestyle intervention on ANGPTL8 concentrations. 384 obese/overweight adults with newly diagnosed T2D were randomly assigned (1:1:1) to diet (n=128), diet + activity (n=128) or usual care (control, n=128) groups. All patients received usual care. Besides, the diet group received a calorie-restricted diet aiming for a weight loss of 5-10%. The diet + activity group additionally received a pedometer-based walling program. Primary outcome was change in ANGPTL8 concentration at 6 months. Data were analyzed according to intention-to-treat. From baseline to 6 months, the median ANGPTL8 level changed from 804.38 pg/mL to 792.86 pg/mL, in control group. Compared with control, ANGPTL8 decreased with diet (baseline-adjusted between-group difference was -121.00 pg/mL, 95% CI -177.47 to -64.53; p < 0.0001) and diet + activity (-126.16 pg/mL, -181.21 to -71.11; p < 0.0001). There was no greater effect of diet activity compared with diet (-5.16 pg/mL, -53.63 to 43.31; p= 0.8348). Both effects disappeared after adjusting for change in body fat, but did not differ significantly when adjusting for physical activity. A 6-month intervention inducing weight loss by a calorie-restricted diet or diet + activity, resulted in significant decrease on ANGPTL8 concentration. These effects were established by change in total body fat. and not by change in physical activity.
Premature ovarian insufficiency (POI) is a common endocrine disorder featured by the triad constituting of amenorrhea for at least four months, to date, the molecular pathogenesis of POI is largely undetermined. Despite several investigations have reported an increase in reactive oxygen species (ROS) content in idiopathic POI, the role of mitochondrial DNA (mtDNA) mutations/variants in the progression of POI has not been widely investigated. The current study aimed to explore the association between mt-tRNA mutations/variants and POI; we first used the PCR-Sanger sequencing to detect the mutations/variants in mt-tRNA genes from 50 POI patients and 30 healthy subjects. In addition, we evaluated the mitochondrial functions by using trans-mitochondrial cybrid cells containing these potential pathogenic mt-tRNA mutations. Consequently, five mutations: tRNA(Leu(UUR)) C3303T, tRNA(Met) A4435G, tRNA(Gln) T4363C, tRNA(Cys) G5821A and tRNA(Thr) A15951G were identified. Notably, these mutations occurred at the extremely conserved nucleotides of the corresponding mt-tRNAs and may result the failure in mt-tRNA metabolism and subsequently lead to the impairment in mitochondrial protein synthesis. Furthermore, biochemical and molecular analyses of the cybrid cells containing these mutations showed a significantly lower level of All' production when compared with the controls, whereas the ROS levels were much higher in POI patients carrying these mt-tRNA mutations, strongly indicated that these mt-tRNA mutations may cause the mitochondrial dysfunction, and play active roles in the progression and pathogensis of POI. Together, this study shaded additional light on the molecular mechanism of POI that was manifestated by mt-tRNA mutations.
We conducted a systematic review and meta-analysis to evaluate the effect of Berberine on glucose in patients with type 2 diabetes mellitus and identify potential factors may modifying the hypoglycemic effect. We searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database to identify randomized controlled trials that investigated the effect of Berberine. We calculated weighted mean differences (WMD) and 95% confidence interval (CI) for fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and glycated haemoglobin (HbA1c) levels. Twenty-eight studies were identified for analysis, with a total of 2,313 type 2 diabetes mellitus (T2DM) patients. The pool data showed that Berberine treatment was associated with a better reduction on FPG (WMD = -0.54 mmol/L, 95% CI: -0.77 to -0.30), PPG (WMD = -0.94 mmol/L, 95% CI: -1.27 to -0.61), and HbA1c (WMD = -0.54 mmol/L, 95% CI: -0.93 to -0.15) than control groups. Subgroup-analyses indicated that effects of Berberine on blood glucose became unremarkable as the treatment lasted more than 90 days, the daily dosage more than 2 g/d and patients aged more than 60 years. The efficiency of Berberine combined with hypoglycaemics is better than either Berberine or hypoglycaemic alone. The dosage and treatment duration of Berberine and patients' age may modify the effect.
Obesity is linked to a low-grade systemic inflammation and lipopolysaccharide (LPS) is a key factor. Sleeve gastrectomy (SO) can significantly cause weight loss, but few reports have looked into the changes of LPS and inflammatory cytokines after surgery. To explore the potential short-term impact of SO on LPS and inflammatory cytokines and their relationship to early metabolic changes in obesity. 30 Chinese adults with obesity (BMI 39.37 +/- 8.22 kg/m(2), 25 female) receiving SG were included in this study. Fasting blood samples were collected at baseline and 30 days after SG. Serum LPS markedly reduced from 336.50 (73.54, 500) pg/mL to 5.00 (5.00, 5.24) pg/mL at 1 month after SO (p < 0.05). There was a significant decrease in plasma IL-6, 1L-8, and serum CRP after SO (all p < 0.05). Insulin resistance improved remarkably after surgery as displayed by reductions in fasting insulin level (FINS, p < 0.001), and HOMA-1R (p < 0.001). In addition, visceral fat area (VFA) decreased from 209.70 +/- 39.96 cm(2) to 193.28 +/- 43.68 cm(2) after SG (p < 0.001). LPS was positively correlated with FINS (r = 0.391, p = 0.033) and HOMA-IR (r = 0.38, p = 0.038) before SO. Meanwhile, VFA was positively associated with CRP (r = 0.388, p = 0.034) before surgery. When assessing 30-days postoperative changes, a positive correlation was found between the variations of LPS, IL-8 and the reduction of WA. After multivariate analyses, only the reduced IL-8 level was independently associated with the reduction of VFA (p = 0.015). In conclusion, SG can significantly relieve the inflammation in obesity in the short term and LPS might be an earlier predictor of inflammatory changes after surgery.
Type 2 diabetic patients are becoming younger and having a tendency to family aggregation, they are easily suspected as maturity-onset diabetes of young (MODY) in the outpatient clinic and send to genetic testing. 9 diabetic families were compared in our outpatient clinic who met the primary diagnosis criteria of MODY. Detailed clinical features and laboratory data including gene sequence were collected and analyzed. The patients met the primary clinical diagnostic criteria of MODY for genetic testing at the first look. However, members of families A1 to A3 had normal Body mass index (BMI) and a lower C-peptide level which indicated impaired pancreatic islet function. In contrast, the members with diabetes of families B1 to B6 had normal or increased C-peptide level which indicated insulin resistance and were overweight with BMI. Genetic testing showed that the mutations in HNFIA, INS, KCNJII and so on in families A were consistent with the diagnosis of MODY. No pathogenic mutation was found in the members of families B which were diagnosed with familial T2D. Before the clinical laboratory testing and the further gene test, BMI and the concentration of C-peptide are important for the promptly differential diagnosis of MODY from familial type 2 diabetes and medication instruction in the outpatient clinic which could help to alleviate the burden of genetic testing for them.
The pathogenesis of type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and beta-cell dysfunction. Earlier studies reported that increased levels of pancreatic fat may lead to the development of (1-cell dysfunction and insulin resistance. The present study aimed to demonstrate the relationship between pancreatic fat content (PFC) and insulin secretion and insulin resistance in Chinese subjects with T2DM. Seventy-eight T2DM subjects and 35 non-diabetic volunteers were recruited in this study. All subjects were subjected to an oral glucose tolerance test (OGTT). We also measured PFC and liver fat content (LFC) by three-point Dixon method (3p-Dixon), and we examined the relations between PFC and (XiTT-derived parameters. T2DM subjects had higher PFC than non-diabetic subjects (p < 0.01). PFC was correlated with body mass index (BMI), liver fat content (LFC) and age in two groups, however, it was only positively associated with insulin secretion, insulin resistance, early- and late-phase insulin secretion in male T2DM subjects, but not in non-diabetic and female T2DM subjects. After adjusting for BMI, LFC and age, the association still existed (all p < 0.05). Furthermore, the relationship was more obvious in male T2DM subjects with a shorter course of disease. PFC was associated with fl-cell dysfunction and insulin resistance in subjects with T2DM and was more obvious in male T2DM subjects with shorter duration of diabetes. Therefore, PFC might represent a potential risk factor for the development of T2DM.
This study was conducted to assess quality of counseling provided to type 2 diabetic patients. For this cross-sectional study, a simulated patient method was applied in 562 selected community pharmacies of Punjab, Pakistan. A scenario for the metformin oral therapy was developed that illustrates direct counseling for adult diabetic patients. Counseling and communication skills were also assessed. Descriptive statistics and chi-square tests were used for analysis. Only 29.4% of simulated patients received medication counseling directly; 47.6% received it on request. About 32.8% of clients were referred to a physician without counseling. The most frequently provided information was dietary instruction (94.8%) and dose of therapy (84.5%). Only one quarter (25.3%) of simulated patients were asked about disease duration and similar rate (25.0%) was found for discussions of special warnings. The side effects, drug storage, drug-drug interactions and duration of therapy were ignored. Minimal information was provided about other medication during therapy (0.2%) and effect of medicine withdrawal (2.7%). About 59.5% simulated patients were instructed for compliance to medication. Counseling to type 2 diabetic patients in Pakistani community pharmacies is not very satisfactory. Pharmacies' staff have little focus on counseling. Professional training of staff could improve counseling and communication skills.
This article aims to understand the isolated effect of maternal thyroid-stimulating hormone (TSH), free thyroxine (FT4) and antithyroid peroxidase antibodies (TPOAb) in early pregnancy on gestational diabetes mellitus (GDM). Based on a birth cohort, pregnant women presented to maternity hospitals for the first antenatal care from Nov 2008 to Oct 2010 were invited to participate in the study. A self-administered questionnaire was asked to complete to collect data on socio-economic variables, previous adverse pregnancy outcomes, method of conception, previous endocrinic and metabolic diseases, and pregnancy-related anxiety in 1st trimester of the index pregnancy. Pre-pregnancy BMI was measured. Serum samples were collected, and TSH, FT4 and TPOAb were assayed. GDM was confirmed from medical records screened on 24-28 gestational weeks by using oral glucose tolerance test (OGTT). The prevalence of isolated subclinical hypothyroidism, hypothyroidemia and positive TPOAb in early pregnancy was 2.0%, 2.0% and 12.8%. Prevalence of GDM in women with the isolated subclinical hypothyroidism, hypothyroxinemia and positive TPOAb was 2.9%, 2.8% and 3.1%, respectively, which were all higher than that detected in euthyroidism women (1.2%). Women with isolated positive TPOAb had significantly higher TSH and lower FT4 level compared with euthyroidism women. It was found that isolated positive TPOAb in early pregnancy increased the risk of GDM, adjusted RR and 95%CI being 2.541(1.037-6.226). No significant relationships were identified between isolated sub-clinical hypothyroidism or hypothyroxinemia with GDM. In conclusion, isolated thyroid autoimmunity, represented by positive TPOAb, in early pregnancy were associated with GDM independent of TSH and FT4.
The relationship between variations in thyroid function and indices of obesity remains a focus of debate. To explore the associations between thyroid function within the normal range and obesity and to evaluate potential modifying factors, we analyzed a large and well-characterized community cohort in Beijing, China, containing 1,816 men and 1,774 women with serum thyrotropin (TSH) levels within the reference range (0.55-4.78 mu IU/mL). Associations between TSH levels and BMI were identified using correlation analysis, ANOVA and Chi-square tests. Logistic regression analyses were used to estimate the impact of serum TSH on obesity before and after adjustment for possible confounding factors. The mean serum TSH was 2.04 +/- 0.94 mu IU/mL. TSH within the reference range was positively associated with BMI in both genders. Compared with euthyroid adults whose TSH was in the middle quartiles (TSH 1.30-2.60 mu IU/mL) of the reference range, the odds of obesity (BMI >= 28.0 kg/m(2)) and severe obesity (HMI >= 33.0 kg/m(2)) was 38% (OR = 1.38, 95% CI 1.17-1.64) and 58% (OR = 1.58, 95% CI 1.12-1.21) more likely, respectively, among those with TSH in the upper quartile. For women, postmenopausal subjects with lower TSH levels had a lower risk of severe obesity (OR= 0.42, 95% CI 0.20-0.91) than those in the middle TSH quartile. Positive associations were found between serum TSH within the euthyroid range and obesity, and menopause showed a significant influence on the relationship between TSH level and severe obesity.
MARCH study suggested that acarbose had similar therapeutic effect on glycated hemoglobin reduction compared to metformin in newly diagnosed type 2 diabetes patients as initial therapy in China. We aimed to investigate whether the efficacy of acarbose was still similar to metformin under different beta-cell function status. According to the homeostasis model assessment (HOMA)-beta level, 670 patients were divided into better beta-cell function group, medium beta-cell function group and poor beta-cell function group. Patients received acarbose 300 mg/d or metformin 1,500 mg/d for 48 weeks. We found both acarbose and metformin could decrease glycated hemoglobin to similar levels after 48 weeks treatment in all groups. In medium beta-cell function group, the decrease of fasting blood glucose after metformin treatment was more significant compared to acarbose (p = 0.040); however, the decrease of post-challenge blood glucose after acarbose treatment was more significant compared to metformin (p = 0.020). Moreover, in poor beta-cell function group, the decrease of body weight and body mass index after acarbose treatment were significant compared to metformin (p = 0.004 and p = 0.031, respectively). Therefore, acarbose contributed a similar therapeutic effect to plasma glucose control compared to metformin treatment, even under different beta-cell function status.
Forty-five pregnant women who underwent cesarean section, including 30 cases of gestational diabetes mellitus (GDM) and 15 normal pregnant women, were enrolled in this study to examine the differential expression of circular RNAs (circRNAs) in the placentas of women with GDM by RNA sequencing (RNA-seq) analysis. The differentially expressed circRNAs were analyzed bioinformatically using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and circRNA-microRNA (miRNA) interaction prediction. Quantitative real-time pulymerase chain reaction (qRT-PCR) was used to verify the results. A total of 8,321 circRNAs were identified in the human placenta, among which 46 were differentially expressed (fold change >= 2 and p < 0.05), including three that were upregulated and 43 that were downregulated. According to the GO and KEGG enrichment results, these circRNAs may be associated with vital biological processes, cellular components, molecular functions, and signaling pathways. In particular. KEGG analysis shown they may be involved in advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications, indicating that these circRNAs might participate in the occurrence and pathogenesis of GDM. qRT-PCR verified that the expression of circ_5824, circ_3636, and circ_0395 was consistent with RNA-seq analysis; their expression levels were significantly lower in the GDM group than in the control group. The circRNA-miRNA interaction was analyzed according to the molecular sponge mechanism, and its potential function is discussed. These results shed light on future functional studies of circRNAs related to GDM.
Increasing of arterial stiffness is the pathophysiological characteristic of hypertension. Carotid-femoral pulse wave velocity (CF-PWV) is an index of arterial stiffness. Serum uric acid has been found to be involved the development of hypertension. We investigated the relationship between CF-PWV and serum uric acid in subjects with hypertension and hyperuricemia. 651 subjects (M/F 271/380) were divided into four groups, group 1: subjects without hypertension and hyperuricemia; group 2: hypertension subjects without hyperuricemia; group 3: hyperuricemia subjects without hypertension; group 4: subjects with hypertension and hyperuricemia. CF-PWV was measured by Complior apparatus. Results showed that levels of CF-PWV (10.75 +/- 2.03 vs. 10.06 +/- 1.98 m/s, p < 0.001) and serum uric acid (319.33 +/- 80.12 vs. 298.78 +/- 74.88 umol/L, p = 0.001) were significantly higher in hypertensive (groups 2 + 4) group than in normotensive (groups 1 + 3) group. CF-PWV was significantly higher in group 4 than group 1, group 2 and group 3 (ANOVA analysis: F = 13.348, p < 0.001; 11.78 +/- 2.10 vs. 9.98 +/- 1.98, 10.52 +/- 1.93, 10.56 +/- 1.99 m/s, all p < 0.05, respectively). There was positive correlation between CF-PWV and serum uric acid in entire study group (r = 0.187, p < 0.001), even after adjusting for gender, body mass index, systolic blood pressure (SBP) and diastolic blood pressure (r = 0.100, p = 0.015). Multiple linear regressions showed that SBP, age, benzbromarone, statin and serum uric acid were independent associating factors of CFPWV in all subjects (beta = 0.310, p < 0.001; beta = 0.330, p < 0.001; beta = 0.172, p = 0.002; beta = -0.143, p = 0.006; beta = 0.126, p = 0.027; respectively). In conclusions, CF-PWV was significantly higher in hypertension subjects with hyperuricemia compared to hypertension without hyperuricemia subjects, and serum uric acid was an independent associating factor of CF-PWV.