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Open access

Xi Zhang, Xiurong Shen, Wan Zhou, Mengyun Xu, Yan Xing, Jianping Weng, Shandong Ye, Suowen Xu, Zhi Zhang, and Wei Wang

A variety of studies have demonstrated the role of lipocalin 2 (LCN2) in both diabetes and neurological disorders. Nevertheless, the relationship between LCN2 and diabetic peripheral neuropathy (DPN) needs to be elucidated in humans. Therefore, this study aimed to investigate the association of LCN2 with DPN in type 2 diabetes (T2D). A total of 207 participants with T2D and 40 participants with normal glucose tolerance (NGT) were included in this study. All participants were classified into DPN group and non-DPN (NDPN) group based on the Toronto Clinical Neuropathy Scoring (TCNS). Demographic and biochemical parameters were measured. Serum LCN2 levels were determined using an ELISA technique. Serum LCN2 levels in NGT group were lower than those in either DPN group (P = 0.000) or NDPN group (P = 0.043), while serum LCN2 levels in DPN group were higher than NDPN group (P = 0.001). Moreover, serum LCN2 levels positively correlated to TCNS scores, which reflects neuropathy severity (r = 0.438, P = 0.000). Multivariate stepwise regression analysis showed that BMI, triglycerides, and diastolic pressure were independently associated with serum LCN2 in DPN. Additionally, logistic regression analysis demonstrated that LCN2 (odds ratio (OR) = 1.009) and diabetes duration (OR = 1.058) were independently associated with the occurrence of DPN in T2D. Our report reveals the association of serum LCN2 with DPN in T2D. LCN2 might be used to evaluate DPN severity and serve a role in the pathogenesis of DPN.

Open access

Rongpeng Gong, Gang Luo, Mingxiang Wang, Lingbo Ma, Shengnan Sun, and Xiaoxing Wei

Background

Clinical data on the relationship between triglycerides (TG)/HDL ratio and insulin resistance (IR) suggest that TG/HDL ratio may be a risk factor for IR. However, there is evidence that different races have different risk of developing IR. The relationship on TG/HDL ratio and IR in various populations needs to be improved. Therefore, we investigated whether TG/HDL ratio was linked to IR in different groups in the United States after controlling for other covariates.

Methods

The current research was conducted in a cross-sectional manner. From 2009 to 2018, the National Health and Nutrition Examination Survey (NHANES) had a total of 49,696 participants, all of whom were Americans. The target-independent variable was TG/HDL ratio measured at baseline, and the dependent variable was IR. Additionally, the BMI, waist circumference, education, race, smoking, alcohol use, alanine transaminase, aspartate transaminase, and other covariates were also included in this analysis.

Results

The average age of the 10,132 participants was 48.6 ± 18.4 years, and approximately 4936 (48.7%) were males. After correcting for confounders, fully adjusted logistic regression revealed that TG/HDL ratio was correlated with IR (odds ratio = 1.51, 95% CI 1.42–1.59). A nonlinear interaction between TG/HDL ratio and IR was discovered, with a point of 1.06. The impact sizes and CIs on the left and right sides of the inflection point were 6.28 (4.66–8.45) and 1.69 (1.45–1.97), respectively. According to subgroup analysis, the correlation was strong in females, alcohol users, and diabetes patients. Meanwhile, the inverse pattern was observed in the aged, obese, high-income, and smoking populations.

Conclusion

In the American population, the TG/HDL ratio is positively associated with IR in a nonlinear interaction pattern.

Open access

Reem Al Argan, Abdulaziz Ramadhan, Ramanakumar V Agnihotram, Jeffrey Chankowsky, and Juan Rivera

Hypopituitarism tends to occur in large pituitary adenomas. However, similar tumors could present with strikingly different hormonal deficiencies. In this study, we looked at MRI characteristics in non-functioning pituitary adenomas (NFPA), which could predict secondary adrenal insufficiency (SAI) and central hypothyroidism (CHT). We reviewed the files of patients with NFPA attending our clinic. Tumor size, invasiveness, MR-signal intensity, and gadolinium enhancement in preoperative MRI were recorded along with documented presurgical hypopituitarism profile. Logistic regression was used to predict SAI, CHT, or both (SAI/CHT) based on MRI and demographic parameters. Receiver operating characteristic curves were used to determine their diagnostic utility. One hundred twenty-one patients were included in the study. Older age (P = 0.021), male sex (P = 0.043), stalk deviation (P < 0.0001), contrast enhancement (P = 0.029), and optic chiasma compression (P = 0.012) were associated with SAI/CHT. Adenoma vertical height, largest diameter, and estimated volume were also strongly associated with SAI/CHT (P < 0.0001). These associations remained significant in a multivariate analysis. No tumor smaller than 12 mm in vertical height, 17 mm in largest diameter, or 0.9 cm3 in volume was associated with SAI/CHT. At cut-off ≥18 mm for vertical height, ≥23 mm for largest diameter, and ≥3.2 cm3 the sensitivity was around 90–92% for detecting SAI/CHT. Only vertical height was significantly associated with any one or more pituitary hormonal deficit (P = 0.001). In conclusion, adenoma size, independent of the measurement used, remains the best predictor of SAI/CHT in NFPA. Dynamic testing to rule out SAI is probably indicated in adenomas larger than 18 mm vertical height, 23 mm largest diameter and 3.2 cm3 adenoma volume.

Open access

Yuan Liu, Siyi Guo, Jinsong Wu, Rongai Wang, Jinbo Liu, Yan Liu, Bin Lv, Nan Liu, Ling Jiang, and Xiaoli Zhang

The clinical presentation of primary hyperparathyroidism (PHPT) differs between patients from developed and developing countries. In China, the clinical pattern has changed over the past few decades. Our aim was to elucidate general changes in the clinical characteristics of PHPT from 2010 to 2021. We enrolled 343 patients with PHPT at the Qilu Hospital of Shandong University, Jinan, China, from January 2010 to May 2021, including both surgical and non-surgical patients. Patients were divided into two subgroups, 2010–2016 (group A, n  = 152) and 2017–2021 (group B, n  = 191), based on the time span. We compared clinical manifestations and laboratory result data between these two groups. The mean patient age was 52.59 ± 13.55 years, and the male-to-female ratio was 1:2.54. Of the 343 patients, 183 (53.35%) had symptomatic PHPT; bone pain, urolithiasis, and fatigue were the most common symptoms. Post-operative pathology showed that 96.20% of the patients had parathyroid adenoma, whereas 2.41% had parathyroid carcinoma. Great changes occurred between 2010 and 2021; the percentage of patients with asymptomatic PHPT (aPHPT) increased from 36.18% in group A to 54.97% in group B. Moreover, patients in group B showed significantly lower serum calcium, alkaline phosphatase, parathyroid hormone, and urinary phosphate levels but higher serum 25-hydroxyvitamin D levels than those in group A. Clinical presentations in group B were also milder. In conclusion, the clinical characteristics of Chinese PHPT patients changed dramatically from 2010 to 2021, with asymptomatic PHPT (aPHPT becoming the predominant type over the last 3 years.

Open access

Yao Su, Li Chen, Dong-Yao Zhang, Xu-Pei Gan, Yan-Nan Cao, De-Cui Cheng, Wen-Yu Liu, Fei-Fei Li, Xian-Ming Xu, and Hong-Kun Wang

Objective

To investigate the characteristics of intestinal flora in overweight pregnant women and the correlation with gestational diabetes mellitus (GDM).

Methods

A total of 122 women were enrolled and divided into four groups according to their pre-pregnancy BMI and the presence of GDM: group 1 (n = 71) with a BMI <24 kg/m2, without GDM; group 2 (n = 27) with a BMI <24 kg/m2, with GDM; group 3 (n = 17) with a BMI ≥24 kg/m2, without GDM; and group 4 (n = 7) with a BMI ≥24 kg/m2 with GDM. Feces were collected on the day that the oral glucose tolerance test was conducted. The V3–V4 variable region of 16S rRNA was sequenced using the Illumina Hiseq 2500 platform, and a bioinformatics analysis was conducted.

Results

There were differences between the four groups in the composition of intestinal flora, and it was significantly different in group 4 than in the other three groups. Firmicutes accounted for 36.4% of the intestinal flora in this group, the lowest among the four groups, while Bacteroidetes accounted for 50.1%, the highest among the four groups, making ratio of these two bacteria approximately 3:5, while in the other three groups, this ratio was reversed. In women with a BMI <24 kg/m2, the insulin resistance index (homeostatic model assessment for insulin resistance (HOMA-IR)) in pregnant women with GDM was higher than in those without (P 3 = 0.026).

Conclusion

The composition of the intestinal flora of pregnant women who were overweight or obese before pregnancy and suffered from GDM was significantly different than women who were not overweight or did not suffer from GDM.

Open access

Xingyan Liu, Mei Xu, Min Qian, and Lindong Yang

The cytochrome P450 family 17 (CYP17) is associated with hyperandrogenism in women and the association between CYP17 gene polymorphism and the risk of polycystic ovary syndrome (PCOS) is not definitive. In order to determine whether the CYP17 T/C (rs74357) gene polymorphism is an exposure risk for PCOS, a comprehensive meta-analysis summarizing 19 studies was performed. The pooled odds ratio (OR) and the corresponding 95 % confidence interval (CI) were measured under 5 genetic models. And the stratified analyses by ethnicity, HWE, testosterone levels and BMI in controls was carried out to identify causes of substantial heterogeneity. The overall results validated that the CYP17 T/C (rs74357) gene polymorphism was significantly associated with PCOS risk in 4 genetic models. Moreover, the outcomes of subgroup analysis by ethnicity were indicated that the frequencies of C allele of the CYP17 T/C polymorphism were markedly higher in women from Asian than Caucasian (T versus C: OR 0.85, 95% CI =0.74–0.99, P < 0.05). Therefore, these findings suggested that the CYP17 T/C (rs74357) gene polymorphism played an indispensable part in increasing the susceptibility of PCOS when carrying the C allele, which proposed that the polymorphism of CYP17 gene may be a predictive factor for the risk of PCOS or an important pathway in PCOS associated metabolic and hormonal dysregulation.

Open access

Mengting Yin, Qianhui Liu, Qingzhong Wang, Yong He, Haolan Song, Xin Nie, and Guixing Li

Background

The diagnosis of primary hyperparathyroidism (PHPT) remains a challenge because of increased asymptomatic PHPT or patients with normocalcaemic PHPT (NPHPT). In addition, some primary hospitals in China have no equipment to measure parathyroid hormone (PTH) levels. Therefore, an additional, simple, and inexpensive laboratory biochemical marker is urgently needed. The calcium/phosphate (Ca/P) ratio and chloride/phosphate (Cl/P) ratio have been proposed as suitable tools to diagnose PHPT in Europe; however, the Ca/P ratio has never been tested in China. We aimed to conduct a confirmatory study to explore the diagnostic performance of the Ca/P ratio for PHPT in China.

Methods

From January 2015 to December 2020, a total of 155 patients who underwent parathyroidectomy (143 PHPT patients and 12 NPHPT patients) and 153 controls were enrolled in this single-center , retrospective study. Serum calcium, phosphate, parathyroid hormone, 25-hydroxyvitamin vitamin D (25(OH) vitamin D), chloride, alanine transaminase (ALT), aspartate aminotransaminase (AST), estimated glomerular filtration rate (eGFR), and creatinine levels were recorded for all the study participants. Pairwise comparisons were made between groups, and the diagnostic performance of the Ca/P ratio was determined using receiver-operating characteristic (ROC) analysis.

Results

Patients with PHPT had a higher Ca/P ratio than controls (P < 0.001). A Ca/P ratio above 2.94 with a sensitivity of 95.5% and specificity of 98.7% can distinguish PHPT patients from healthy individuals. This index was positively correlated with the PTH level (r = 0.875, P < 0.001).

Conclusion

The Ca/P ratio is an ideal and inexpensive indicator for diagnosing PHPT in China when using a cut-off value of 2.94.

Open access

Mateo Amaya-Montoya, Daniela Duarte-Montero, Luz D Nieves-Barreto, Angélica Montaño-Rodríguez, Eddy C Betancourt-Villamizar, María P Salazar-Ocampo, and Carlos O Mendivil

Data on dietary calcium and vitamin D intake from Latin America are scarce. We explored the main correlates and dietary sources of calcium and vitamin D in a probabilistic, population-based sample from Colombia. We studied 1554 participants aged 18 to 75 from five different geographical regions. Dietary intake was assessed employing a 157-item semi-quantitative food frequency questionnaire and national and international food composition tables. Daily vitamin D intake decreased with increasing age, from 230 IU/day in the 18-39 age group to 184 IU/day in the 60-75 age group (p-trend<0.001). Vitamin D intake was positively associated with socioeconomic status (SES) (196 IU/d in lowest vs 234 in highest SES, p-trend<0.001), and with educational level (176 IU/d in lowest vs 226 in highest education level, p-trend<0.001). Daily calcium intake also decreased with age, from 1376 mg/day in the 18-39 age group to 1120 mg/day in the 60-75 age group (p-trend<0.001). Calcium intake was lowest among participants with only elementary education, but the absolute difference in calcium intake between extreme education categories was smaller than for vitamin D (1107 versus 1274 mg/d, p-trend 0.023). Daily calcium intake did not correlate with SES (p-trend=0.74) Eggs were the main source of vitamin D overall, albeit their contribution decreased with increasing age. Dairy products contributed at least 48% of dietary calcium in all subgroups, mostly from cheese-containing traditional foods. SES and education were key correlates of vitamin D and calcium intake. These findings may contribute to shape public health interventions in Latin American countries.

Open access

Shatha Alharazy, M Denise Robertson, Susan Lanhman-New, Muhammad Imran Naseer, Adeel G. Chaudhary, and Eman Alissa

Background: Measurement of free 25-hydroyvitamin D (25(OH)D) status has been suggested as a more representative marker of vitamin D status than that of total 25(OH)D. Previously, free 25(OH)D could only be calculated indirectly; however, a newly developed direct assay for the measurement of free 25(OH)D is now available. The aim of this study therefore was to investigate directly measured total and free vitamin D levels association with metabolic health in postmenopausal healthy women living in Saudi Arabia.

Methods: A sample of 302 postmenopausal women aged ≥ 50 years (n=302) living in Saudi Arabia were recruited in a cross-section study design. Blood samples were collected from subjects for measurement of serum levels of total 25(OH)D, directly measured free 25(OH)D, metabolic bone parameters, lipid profile, and other biochemical tests.

Results: A positive correlation was found between directly measured free and total 25(OH)D (r=0.64, P<0.0001). Total, but not free 25(OH)D showed significant association with serum intact parathyroid hormone (P=0.004); whilst free 25(OH)D but not total 25(OH)D showed a significant association with total cholesterol and LDL-C (P=0.032 and P=0.045; respectively).

Conclusions: Free 25(OH)D and total 25 (OH)D were found to be consistently correlated; but with different associations to metabolic health parameters. Further research is needed to determine which marker of vitamin D status would be the most appropriate in population studies.

Open access

Sarah Zaheer, Kayla Meyer, Rebecca Easly, Omar Bayomy, Janet Leung, Andrew W. Koefoed, Mahyar Heydarpour, Roy Freeman, and Gail K. Adler

Glucocorticoid use is the most common cause of secondary osteoporosis. Poor skeletal health related to glucocorticoid use is thought to involve inhibition of the Wnt/β-catenin signaling pathway, a key pathway in osteoblastogenesis. Sclerostin, a peptide produced primarily by osteocytes, is an antagonist of the Wnt/β-catenin signaling pathway, raising the possibility that sclerostin is involved in glucocorticoids’ adverse effects on bone. The aim of this study was to determine whether an acute infusion of cosyntropin (i.e., ACTH [1-24]), which increases endogenous cortisol, increases serum sclerostin levels as compared to a placebo infusion. This study was performed using blood samples obtained from a previously published, double-blind, placebo-controlled, randomized, cross-over study among healthy men and women who received infusions of placebo or cosyntropin after being supine and fasted overnight (ClinicalTrials.gov NCT02339506). A total of seventeen participants were analyzed. There was a strong correlation (R2 = 0.65, p < 0.0001) between the two baseline sclerostin measurements measured at the start of each visit, and men had a significantly higher average baseline sclerostin compared to women. As anticipated, cosyntropin significantly increased serum cortisol levels, whereas cortisol levels fell during placebo infusion, consistent with the diurnal variation in cortisol. There was no significant effect of cosyntropin as compared to placebo infusions on serum sclerostin over 6-24 hours (p = 0.10). In conclusion, this randomized, placebo-controlled study was unable to detect a significant effect of a cosyntropin infusion on serum sclerostin levels in healthy men and women.