Weijun Gu

Prevalence of microvascular diseases among tertiary care Chinese with early versus late onset of type 2 diabetes

AIMS This study aimed to investigate the impact of early-onset diabetes on the risk of microvascular diseases in Chinese with type 2 diabetes mellitus (T2DM). METHODS A cross sectional survey of 29,442 patients with T2DM in 77 tertiary hospitals in China was conducted in 2011. Early-onset diabetes was defined as diagnosis of diabetes before 40years of age. Microvascular complications and risk factors were documented. Prevalence of microvascular disease was standardized to the Chinese population in 2010. Logistic regression analysis was performed to obtain odds ratios (OR) for early versus late onset of T2DM. RESULTS A total of 1,303 (4.4%) patients had nephropathy, 2,137 (7.3%) had retinopathy and 3,012 (10.2%) had either of them. Early-onset diabetes greatly increased the prevalence of microvascular diseases compared with late-onset diabetes (nephropathy: 5.1% vs. 1.5%; retinopathy: 7.1% vs. 2.7%; either: 9.7% vs. 3.6%), especially among patients from 45 to 59years of age. After adjusting for age and sex, patients with early-onset T2DM were at 1.69-fold (95% CI 1.46-1.95) higher risk of microvascular diseases than those with late-onset T2DM. However, this was not significant after adjusting for traditional risk factors and disease duration (p=0.162). CONCLUSION Chinese patients with early-onset T2DM are at a marked increased risk of microvascular diseases.

Matrix metalloproteinase-9 and -2 and tissue inhibitor of matrix metalloproteinase-2 in invasive pituitary adenomas: A systematic review and meta-analysis of case–control trials

AbstractThe extracellular matrix is important for tumor invasion and metastasis. Normal function of the extracellular matrix depends on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The objective of this meta-analysis was to assess the relationship between expression of MMP-9, MMP-2, and TIMP-2 and invasion of pituitary adenomas.We searched Pubmed, Embase, and the Chinese Biomedical Database up to October 2015. RevMan 5.1 software (Cochrane Collaboration, Copenhagen, Denmark) was used for statistical analysis. We calculated the standardized mean difference (SMD) for data expressed as mean ± standard deviation because of the difference in the detection method.Twenty-four studies (1320 patients) were included. MMP-9 expression was higher in the patients with invasive pituitary adenomas (IPAs) than patients with noninvasive pituitary adenomas (NIPAs) with detection methods of IHC [odds ratio (OR) = 5.48, 95% confidence interval (CI) = 2.61–11.50, P < 0.00001), and reverse transcriptase-polymerase chain reaction (SMD = 2.28, 95% CI = 0.91–3.64, P = 0.001). MMP-2 expression was also increased in patients with IPAs at the protein level (OR = 3.58, 95% CI = 1.63–7.87, P = 0.001), and RNA level (SMD = 3.91, 95% CI = 1.52–6.29, P = 0.001). Meta-analysis showed that there was no difference in TIMP-2 expression between invasive and NIPAs at the protein level (OR = 0.38, 95% CI = 0.06–2.26, P = 0.29). MMP-9 expression in prolactinomas and nonfunctioning pituitary adenomas was also no difference (OR = 1.03, 95% CI = 0.48–2.20, P = 0.95).The results indicated that MMP-9 and -2 may be correlated with invasiveness of pituitary adenomas, although their relationship with functional status of pituitary adenomas is still not clear. TIMP-2 expression in IPAs needs to be investigated further.

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.

Mutation analyses in pedigrees and sporadic cases of ethnic Han Chinese Kallmann syndrome patients

Kallmann syndrome, a form of idiopathic hypogonadotropic hypogonadism, is characterized by developmental abnormalities of the reproductive system and abnormal olfaction. Despite association of certain genes with idiopathic hypogonadotropic hypogonadism, the genetic inheritance and expression are complex and incompletely known. In the present study, seven Kallmann syndrome pedigrees in an ethnic Han Chinese population were screened for genetic mutations. The exons and intron–exon boundaries of 19 idiopathic hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism)-related genes in seven Chinese Kallmann syndrome pedigrees were sequenced. Detected mutations were also tested in 70 sporadic Kallmann syndrome cases and 200 Chinese healthy controls. In pedigrees 1, 2, and 7, the secondary sex characteristics were poorly developed and the patients’ sense of smell was severely or completely lost. We detected a genetic mutation in five of the seven pedigrees: homozygous KAL1 p.R191ter (pedigree 1); homozygous KAL1 p.C13ter (pedigree 2; a novel mutation); heterozygous FGFR1 p.R250W (pedigree 3); and homozygous PROKR2 p.Y113H (pedigrees 4 and 5). No genetic change of the assayed genes was detected in pedigrees 6 and 7. Among the 70 sporadic cases, we detected one homozygous and one heterozygous PROKR2 p.Y113H mutation. This mutation was also detected heterozygously in 2/200 normal controls and its pathogenicity is likely questionable. The genetics and genotype–phenotype relationships in Kallmann syndrome are complicated. Classical monogenic inheritance does not explain the full range of genetic inheritance of Kallmann syndrome patients. Because of stochastic nature of genetic mutations, exome analyses of Kallmann syndrome patients may provide novel insights.

Non-pharmaceutical factors for poor glycemic control in 13,970 Chinese women with drug-treated type 2 diabetes: a cross-sectional survey in 77 tertiary hospitals in four Chinese cities.

Background Achieving good glycemic control improves clinical outcomes among patients with type 2 diabetes (T2D). This study aimed to explore non-pharmaceutical factors for poor glycemic control in Chinese women with T2D who used antidiabetic drug(s). Methods A cross-sectional survey was conducted in March to June 2011 in 77 top tertiary hospitals in Beijing, Shanghai, Tianjin, and Guangzhou, People’s Republic of China (the coverage rates of the 3A hospitals: 74.4%, 76%, 55%, and 29.3%, respectively). Of 29,502 patients with T2D who used oral antidiabetic drugs (OADs) alone or combined with insulin, 13,970 were women and used in the analysis. Logistic regression analysis was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) of factors for hyperglycemia defined as HbA1c (glycated hemoglobin) ≥77 mmol/mol (7.0%). Results The mean age was 60.3 (standard deviation 11.0) years, with a median of 4 (interquartile range 2–9) years of duration of diabetes, and 65.1% had hyperglycemia. In multivariable analysis, body height of ≥164 cm (OR 1.26, 95% CI 1.15–1.37) and obesity (OR 1.16, 95% CI 1.04–1.31) was associated with increased risk of hyperglycemia, while self-monitoring blood glucose (SMBG) decreased the risk of hyperglycemia (OR 0.78, 95% CI 0.73–0.84). Duration of diabetes ≥3 years (≥3 to <6 years, OR 1.46, 95% CI 1.32–1.62; ≥6 to <10 years, OR 1.65, 95% CI 1.44–1.89), especially ≥10 years (OR 1.95, 95% CI 1.73–2.19), was associated with higher risks of hyperglycemia. Conclusion Body height ≥164 cm, obesity, and duration of diabetes ≥3 years increased while SMBG decreased risk of hyperglycemia in Chinese women with OAD-treated T2D.

Baseline Demographic and Clinical Characteristics of Patients with Adrenal Incidentaloma from a Single Center in China: A Survey

Aim To investigate the clinical and endocrinological characteristics of patients with adrenal incidentaloma (AI). Materials and Methods This retrospective study enrolled 1941 AI patients hospitalized at the Department of Endocrinology, Chinese PLA General Hospital, Beijing, China, between January 1997 and December 2016. The patient gender, age at visits, imaging features, functional status, and histological results were analyzed. Results Of the 1941 patients, 984 (50.70%) were men. The median age was 52 years (interquartile range: 44–69 years). 140 cases had bilateral AI. Endocrine evaluation showed that 1411 (72.69%) patients had nonfunctional tumor, 152 (7.83%) had subclinical Cushing syndrome (SCS), and 82 (4.33%) had primary hyperaldosteronism. A total of 925 patients underwent operation for removal of 496 cortical adenomas (53.62%), 15 adrenal cortical carcinomas (1.62%), and 172 pheochromocytomas (18.59%). The bilateral group had a higher proportion of SCS (18.57% versus 7.10%, P < 0.001, P = 0.006). A mass size of 46 mm was of great value in distinguishing malignant tumors from the benign tumors, with sensitivity of 88.2% and specificity of 95.5%. Conclusions We reported the baseline demographic and clinical characteristics of patients with AI in a large series from a single center in China.

Non-linear associations of risk factors with mild hypoglycemia among Chinese patients with type 2 diabetes

AIMS The present study aimed to examine the nonlinear associations between risk factors and mild hypoglycemia in Chinese patients with type 2 diabetes mellitus (T2DM). METHODS From May 2013 to August 2013, we conducted a cross sectional survey of 6633 inpatients with T2DM and without severe hypoglycemia, aged 21-77 years, from 81 top tertiary hospitals in China. Mild hypoglycemia was defined as having hypoglycemia with symptoms in one month. Binary logistic regression analysis with restricted cubic splines was used to estimate odds ratio curves of non-linear risk factors for mild hypoglycemia. RESULTS Increasing body mass index was associated with decreasing risk of mild hypoglycemia in a linear manner while age, duration of diabetes, glycated hemoglobin (HbA1c), mean artery pressure and lipids were associated with mild hypoglycemia in non-linear manners. Age ≥40 years, duration ≥2 years, HbA1c ≥7.0-<11.5% (≥53-<102 mmol/mol), triglyceride ≥1.7-<3.6 mmol/L, low-density lipoprotein cholesterol (LDL-C) ≥2.6-<4.8 mmol/L, and high-density lipoprotein cholesterol (HDL-C) ≥1.2-<4.8 mmol/L were associated with increased risks of mild hypoglycemia. CONCLUSIONS Chinese T2DM patients with age≥40 years, duration of diabetes ≥2-<6 years, HbA1c ≥7.0-<11.5% (≥53-<102 mmol/mol), LDL-C ≥2.6-<4.8mmol/L, HDL-C ≥1.2-<4.8 mmol/L or triglyceride ≥1.7-<3.6 mmol/L were at particularly high risk for mild hypoglycemia.

PTH Is a Promising Auxiliary Index for the Clinical Diagnosis of Aldosterone-Producing Adenoma

BACKGROUND Parathyroid hormone (PTH) stimulates aldosterone secretion in human adrenocortex and is regulated by the renin-angiotensin-aldosterone system. We speculated that measurement of PTH may be a valuable aid in the diagnosis of aldosterone-producing adenoma (APA). METHODS To test this hypothesis, we recruited 142 patients with adrenal adenoma, of whom 84 had an APA and 58 had a nonfunctioning adrenal adenoma (NFA). Plasma levels of intact PTH, serum potassium, sodium, calcium, phosphate, 25(OH) vitamin D, plasma aldosterone concentration (PAC), plasma renin activity (PRA), and aldosterone to renin ratio (ARR) were measured in every patient. Computed tomography (CT) scanning of the adrenal gland and adrenal hormone levels was used to evaluate the function of the adrenal adenoma. We also evaluated the impact of renin-angiotensin-aldosterone system (RAAS) components on PTH from the recumbent-upright test in 15 patients with APA and 30 patients with NFA. RESULTS Compared with NFA, PTH levels were significantly increased in patients with APA, and serum calcium and phosphate were significantly decreased. When position was changed from supine to upright, the variation in PTH levels was significantly higher in APA patients compared with NFA patients. Receiver operator characteristic (ROC) curves identified the Youden index, which corresponded to the best tradeoff of combined marker (ARR and PTH) with a sensitivity and specificity of 89.3% and 93.1%, respectively. CONCLUSIONS The baseline and positional variation of serum PTH levels were significant in APA, thus PTH may be a promising auxiliary index for the clinical diagnosis of APA.

Regional differences in the prevalence of coronary heart disease and stroke in patients with type 2 diabetes in China.

Background There are large regional variations in the prevalence and mortality of cardiovascular disease in general populations in China. It remains uncertain whether the prevalence in type 2 diabetes mellitus (T2DM) varies by region in China. Methods We analyzed data of 219,522 Chinese patients with T2DM retrieved from the China National HbA1c Surveillance System in 2012. We used the Chinese population distribution in 2010 to standardize prevalence of coronary heart disease (CHD), stroke, and composite of both in 30 provinces and seven geological regions. Multivariable logistic regression was performed to obtain ORs and CIs of provinces/geological regions for CHD, stroke, and composite of both. Results Age and sex standardized prevalence of CHD, stroke, and composite of both was, respectively, 4.59% (95% CI, 4.58 to 4.60), 1.79% (1.79 to 1.80), and 5.85% (5.84 to 5.86), in contrast to 0.60% of CHD, 0.80% of stroke, and 1.37% of composite of both in the general population in China. After adjustment for traditional risk factors, Northeast had the highest risks of CHD, stroke, and composite of both, and North had the second highest risks of CHD, stroke, and composite of both among the seven regions, both being higher than any other regions (all P values < 0.05). The ORs of Northeast vs Southwest were up to 2.60 (2.35 to 2.88) for CHD, 2.49 (2.15 to 2.88) for stroke, and 2.61 (2.38 to 2.86) for composite of both. Conclusions There were large variations in risks of CHD, stroke, and composite of both in T2DM in China with Northeast and North having the highest risks.

Cinacalcet versus Placebo for secondary hyperparathyroidism in chronic kidney disease patients: a meta-analysis of randomized controlled trials and trial sequential analysis

To assess the efficacy and safety of cinacalcet on secondary hyperparathyroidism in patients with chronic kidney disease, Pubmed, Embase, and the Cochrane Central Register of Controlled Trials were searched until March 2016. Trial sequential analysis (TSA) was conducted to control the risks of type I and II errors and calculate required information size (RIS). A total of 25 articles with 8481 participants were included. Compared with controls, cinacalcet administration did not reduce all-cause mortality (RR = 0.97, 95% CI = 0.89–1.05, P = 0.41, TSA-adjusted 95% CI = 0.86–1.08, RIS = 5260, n = 8386) or cardiovascular mortality (RR = 0.95, 95% CI = 0.83–1.07, P = 0.39, TSA-adjusted 95% CI = 0.70–1.26, RIS = 3780 n = 5418), but it reduced the incidence of parathyroidectomy (RR = 0.48, 95% CI = 0.40–0.50, P < 0.001, TSA-adjusted 95% CI = 0.39–0.60, RIS = 5787 n = 5488). Cinacalcet increased the risk of hypocalcemia (RR = 8.48, 95% CI = 6.37–11.29, P < 0.001, TSA-adjusted 95% CI = 5.25–13.70, RIS = 6522, n = 7785), nausea (RR = 2.12, 95% CI = 1.62–2.77, P < 0.001, TSA-adjusted 95% CI = 1.45–3.04, RIS = 4684, n = 7512), vomiting (RR = 2.00, 95% CI = 1.79–2.24, P < 0.001, TSA-adjusted 95% CI = 1.77–2.26, RIS = 1374, n = 7331) and diarrhea (RR = 1.17, 95% CI = 1.05–1.32, P = 0.006, TSA-adjusted 95% CI = 1.02–1.36, RIS = 8388, n = 6116). Cinacalcet did not significantly reduce the incidence of fractures (RR = 0.58, 95% CI = 0.21–1.59, P = 0.29, TSA-adjusted 95% CI = 0.01–35.11, RIS = 76376, n = 4053). Cinacalcet reduced the incidence of parathyroidectomy, however, it did not reduce all-cause and cardiovascular mortality, and increased the risk of adverse events including hypocalcemia and gastrointestinal disorders.