Hsa_circ_0007380 silencing restrains the growth and enhances radiosensitivity in esophagus cancer by miR-644a/Spindlin 1 axis.

Circular RNAs are frequently dysregulated and show important regulatory function of tumorigenesis in cancers. Hsa_circ_0007380 was found to be elevated in human radioresistant esophageal cancer cells. Here, this study aimed to investigate the action and mechanism of hsa_circ_0007380 in esophageal cancer carcinogenesis and radiosensitivity. Quantitative real-time PCR and western blotting were performed to detect levels of genes and proteins. Functional experiments were conducted using MTT assay, EdU assay, clonogenic survival assay, flow cytometry and murine xenograft model assay, respectively. The binding between miR-644a and hsa_circ_0007380 or spindlin1 (SPIN1) was validated using dual-luciferase activity assay. Hsa_circ_0007380 was highly expressed in esophagus cancer tissues and cells, knockdown of hsa_circ_0007380 suppressed esophagus cancer cell proliferation, induced apoptosis and enhanced radiosensitivity in vitro, and the same effects were also confirmed in nude mice. Mechanistically, hsa_circ_0007380 sequestered miR-644a to release SPIN1 expression, implying the hsa_circ_0007380/miR-644a/SPIN1 competing endogenous RNA network esophagus cancer cells. miR-644a was decreased in esophagus cancer, re-expression of miR-644a restrained cell growth and conferred radiosensitivity in esophagus cancer, which were reversed by SPIN1 overexpression. Besides that, inhibition of miR-644a abolished the promoting action of hsa_circ_0007380 knockdown on esophagus cancer apoptosis and radiosensitivity. Hsa_circ_0007380 silencing impedes cell growth and reinforces radiosensitivity in esophagus cancer by miR-644a/SPIN1 axis, suggesting a promising therapeutic target for esophagus cancer combined treatment.

Withdrawn: 'Downregulation of circPPFIA1 elevates radiosensitivity via miR-1299-mediated TXNRD1 inhibition in oesophageal squamous cell carcinoma', Weihui Yu, Ke Ning, Jincheng Xiao, Qiwen Bai and Chenyang Guo. (https://onlinelibrary.wiley.com/doi/10.1111/1440-1681.13751).

The above article, published online on 16 February 2023 in Wiley Online Library (wileyonlinelibrary.com), has been withdrawn by agreement between the journal Editor in Chief, Yang Yang, and John Wiley & Sons Ltd. The withdrawal has been agreed following no response from the authors to requests to sign the journal's publishing license agreement.

Associations of early-life exposure to famine with abdominal fat accumulation are independent of family history of diabetes and physical activity.

The present study aimed to investigate the association of early-life exposure to famine with abdominal fat accumulation and function and further evaluate the influence of first-degree family history of diabetes and physical activity on this association. The present work analysed parts of the REACTION study. A total of 3033 women were enrolled. Central obesity was defined as waist circumferences (W) ≥ 85 cm. Chinese visceral adiposity index (CVAI) was used to evaluate visceral adipose distribution and function. Partial correlation analysis showed BMI, W, glycated Hb and CVAI were associated with early-life exposure to famine (both P < 0·05). Logistic regression showed that the risks of overall overweight/obesity and central obesity in fetal, early-childhood, mid-childhood and late-childhood exposed subgroups were increased significantly (all P < 0·05). Compared with the non-exposed group, the BMI, W and CVAI of fetal, early- to late-childhood exposed subgroups were significantly increased both in those with or without first-degree family history of diabetes and in those classified as physically active or inactive, respectively (all P < 0·05). The associations of BMI, W and CVAI with early-life exposure to famine were independent of their associations with first-degree family history of diabetes (all P < 0·01) or physical activity status (all P < 0·001). Early-life exposure to famine contributed to abdominal fat accumulation and dysfunction, which was independent of the influence of genetic background and exercise habits. Physical activity could serve as a supplementary intervention for women with high risk of central obesity.

Receptor for advanced glycation end products reveals a mechanism regulating thyroid hormone secretion through the SIRT1/Nrf2 pathway.

Advanced glycation end products (AGEs) play a causative role in the complications involved with diabetes mellitus (DM). Nowadays, DM with hypothyroidism (DM-hypothyroidism) is indicative of an ascended tendency in the combined morbidity. In this study, we examine the role of the receptor (RAGE) played for AGEs in thyroid hormone (TH) secretion via the silent information regulator 1 (SIRT1)/nuclear factor erythroid-derived factor 2-related factor 2 (Nrf2) pathway. Blood samples were collected from patients with type 2 DM (T2DM)-hypothyroidism and from patients with T2DM, followed by detection of serum AGEs level. The underlying regulatory mechanisms of RAGE were analyzed in association with the treatment of high glucose, siRNA against RAGE, AGE, SIRT1, or Nrf2 vector in normal immortalized thyroid Nthy-ori 3-1 cells. Serum of patients with T2DM-hypothyroidism indicated promoted levels of AGEs vs those with just T2DM. Both AGEs and high glucose triggered cellular damage, increased oxidative stress, as well as displayed a decreased survival rate along with TH secretion in the Nthy-ori 3-1 cells. Moreover, AGEs and high glucose also led to RAGE upregulation, both SIRT1 and NRF2 downregulation, and the decreased expression of TH secretion-related proteins in Nthy-ori 3-1 cells. Notably, these alternations induced by the AGEs can be reserved by silencing RAGE or upregulating either SIRT1 or Nrf2, indicating a mechanism of regulating TH secretion through the SIRT1/Nrf2 pathway. Collectively, our data proposed that AGEs and high glucose exerted a potent effect on cellular damage and TH deficiency in Nthy-ori 3-1 cells through the RAGE upregulation as well as SIRT1/Nrf2 pathway inactivation. This mechanism may underlie the occurrence of DM-hypothyroidism.

THE ASSOCIATION BETWEEN FIRST-DEGREE FAMILY HISTORY OF DIABETES AND METABOLIC SYNDROME.

Objective: Because they share genetic and environmental factors with patients with diabetes, the first-degree relatives (FDRs) of patients with diabetes exhibit early signs of metabolic abnormalities. The present study aimed to investigate the correlation between family history of diabetes in FDRs and metabolic syndrome (MS), as well as changes in related risk factors. Methods: The present study population was a part of the baseline survey from the REACTION study. FDRs were defined as individuals having one or more FDRs with diabetes. MS and its components were defined according to the 2007 Joint Committee for Developing Chinese Guidelines. Results: A total of 2,692 individuals with an average age of 57.24 ± 8.35 years were enrolled in the present study. The prevalence of MS in FDRs (36.44%) was significantly higher than that in non-FDRs (25.28%; P<.001). FDRs accounted for 13.37%, 14.32%, 16.67%, 22.47%, 23.53%, and 25.58% of subjects with 0 to 5 MS components, showing an increasing trend (P for trend <.001). After adjusting for gender and age, partial correlation analyses showed significant associations of first-degree family history of diabetes with MS-related indexes (all P<.05). After adjusting for gender, age, lifestyle habits, and total metabolic traits, the first-degree family history of diabetes remained an independent factor that was positively associated with MS (odds ratio, 1.765; P<.001). Conclusion: A first-degree family history of diabetes predisposes individuals to developing MS and stands out as an independent risk factor for MS even without considering the subsequent effects of hyperglycemia. Abbreviations: BMI = body mass index; DBP = diastolic blood pressure; FDR = first-degree relative; FPG = fasting plasma glucose; HbA1c = glycated hemoglobin A1c; HDL-c = high-density-lipoprotein cholesterol; LDL-c = low-density-lipoprotein cholesterol; MAP = mean arterial pressure; MS = metabolic syndrome; OR = odds ratio; SBP = systolic blood pressure; TC = total cholesterol; TG = triglyceride; WC = waist circumference; WHR = waist-to-hip ratio; 2hPG = 2-hour plasma glucose.

PREVIOUS DELIVERY OF MACROSOMIA IS ASSOCIATED WITH MATERNAL ADIPOSITY IN LATER LIFE IN CHINESE PAROUS WOMEN WITH NORMAL WEIGHT BEFORE AND/OR AFTER PREGNANCY.

Objective: Obesity has become a major worldwide health challenge. Macrosomic infants are more likely to experience type 2 diabetes mellitus, obesity and hypertension in adulthood. However, whether macrosomia increases the risk of maternal adiposity later in life is still unknown. Methods: One thousand nine hundred eighty-six unrelated parous women of Chinese Han ancestry aged from 40 to 76 years were enrolled. Self-reported information about reproductive status, including age at menarche, number of children, previous delivery of macrosomic infants, and body weight before and after pregnancy were obtained from personal interview by trained interviewers using a standard questionnaire. Macrosomia was defined as birth weight greater than 4,000 g. Adiposity indexes were measured or calculated. Results: Prior delivery of macrosomia was associated with an increased risk of having obesity in parous women with normal weight before pregnancy (odds ratio [OR] = 1.840; 95% confidence interval [CI] 1.028, 3.294; P = .040), as well as a higher risk of overweight/obesity in parous women with normal weight after pregnancy (OR = 1.777; 95% CI 1.131, 2.794; P = .013). In addition, previous delivery of macrosomia was related with 1.919 (95% CI 1.207, 3.050; P = .006) times higher risk of overweight/obesity in parous women with normal weight before and after pregnancy. Conclusion: The present study suggests that prior delivery of macrosomia may be an independent risk factor for adiposity later in life in parous women with normal weight before and/or after pregnancy. Abbreviations: BMI = body mass index; CI = confidence interval; OR = odds ratio; WC = waist circumference; WHR = waist-to-hip ratio; WHtR = waist-to-height ratio.

An anti-inflammatory chalcone derivative prevents heart and kidney from hyperlipidemia-induced injuries by attenuating inflammation.

Obesity is a growing pandemic in both developed and developing countries. Lipid overload in obesity generates a chronic, low-grade inflammation state. Increased inflammation in heart and renal tissues has been shown to promote the progression of heart and renal damage in obesity. Previously, we found that a novel chalcone derivative, L6H21, inhibited lipopolysaccharide-induced inflammatory response. In the present study, we investigated the effects of L6H21 on inflammatory responses in culture and in animal models of lipid overload. We utilized palmitic acid (PA) challenging in mouse peritoneal macrophages and apolipoprotein E knockout (ApoE-/-) mice fed a high fat diet (HFD) to study whether L6H21 mitigates the inflammatory response. Our studies show that L6H21 significantly reduced PA-induced expression of inflammatory cytokines in macrophages by inhibiting mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NFκB) signaling pathways. L6H21 also reduced fibrosis in the kidney and heart tissues, and indices of inflammatory response in the ApoE-/- mice fed a HFD. These effects in vivo were also associated with inhibition of MAPK and NFκB signaling by L6H21. These findings strongly suggest that L6H21 may be a potential agent for high fat diet-induced injuries in heart and kidney.

Association of Pentraxin 3 Gene Polymorphisms with Susceptibility to Diabetic Nephropathy.

BACKGROUND Diabetic nephropathy (DN) is a major microvascular complication of diabetes. Pentraxin 3 (PTX3) is a member of the acute-phase reactants superfamily and altered plasma levels of PTX3 are associated with DN. We performed a case-control study to analyze the relationship between single nucleotide polymorphisms (SNPs) in PTX3 and the risk for DN in patients with type 2 diabetes. MATERIAL AND METHODS The study included 135 DN patients, 155 non-diabetic nephropathy (NDN) patients, and 152 normal controls (NC) (N=442). We genotyped eight PTX3 SNPs (rs2305619, rs2120243, rs1456099, rs7634847, rs1840680, rs2316706, rs2316709, and rs7616177) using the ABI PRISM SNapshot method. RESULTS The genotype frequencies of rs2305619 and rs2120243 differed significantly between the DN and the NDN groups (p=0.017 and p=0.033, respectively). Patients with the GG variant of rs2305619 showed 4.078-fold higher susceptibility to DN than those with the AA variant (OR=4.078, 95% CI=1.370-12.135, p=0.012); patients with the AA variant of rs2120243 had a lower risk of developing DN (OR=0.213, 95% CI=0.055-0.826, p=0.025). Haplotype analysis showed an association between the CAGGG haplotype in block 1 with DN (p=0.0319). CONCLUSIONS Our findings suggested that PTX3 polymorphisms were associated with an increased risk for DN in Chinese patients with type 2 diabetes.

Genome-wide association study identifies three novel loci for type 2 diabetes.

Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component to be clarified. To explore unidentified loci for T2D, we performed a genome-wide association study (GWAS) of 6 209 637 single-nucleotide polymorphisms (SNPs), which were directly genotyped or imputed using East Asian references from the 1000 Genomes Project (June 2011 release) in 5976 Japanese patients with T2D and 20 829 nondiabetic individuals. Nineteen unreported loci were selected and taken forward to follow-up analyses. Combined discovery and follow-up analyses (30 392 cases and 34 814 controls) identified three new loci with genome-wide significance, which were MIR129-LEP [rs791595; risk allele = A; risk allele frequency (RAF) = 0.080; P = 2.55 × 10(-13); odds ratio (OR) = 1.17], GPSM1 [rs11787792; risk allele = A; RAF = 0.874; P = 1.74 × 10(-10); OR = 1.15] and SLC16A13 (rs312457; risk allele = G; RAF = 0.078; P = 7.69 × 10(-13); OR = 1.20). This study demonstrates that GWASs based on the imputation of genotypes using modern reference haplotypes such as that from the 1000 Genomes Project data can assist in identification of new loci for common diseases.

Circ_0001686 knockdown suppresses tumorigenesis and enhances radiosensitivity in esophagus cancer through regulating miR-876-5p/SPIN1 axis.

BACKGROUND: Abnormal expression of circular RNAs (circRNAs) plays an important role in tumorigenesis and radiosensitivity of many cancers. Nevertheless, it is not clear whether circ_0001686 is associated with the development and radiosensitivity of esophagus cancer. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of circ_0001686, microRNA-876-5p (miR-876-5p) and spindlin 1 (SPIN1). Counting Kit-8 (CCK-8) assay, EdU assay, flow cytometry and transwell assay were applied to evaluate cell viability, cell proliferation, cell apoptosis and cell invasion capacities. Radiosensitivity was monitored by colony formation assay. The target relationship between miR-876-5p and circ_0001686 or SPIN1 was identified by dual-luciferase reporter assay. The protein level of SPIN1 was measured by western blot assay. Xenograft tumor models were used to analyze the influence of circ_0001686 on radiosensitivity and tumor growth in vivo. RESULTS: The expression levels of circ_0001686 and SPIN1 were increased, while miR-876-5p was decreased in esophagus cancer tissues and cells. Interference of circ_0001686 constrained cell proliferation and invasion, but promoted cell apoptosis and radiosensitivity. Additionally, miR-876-5p was the target of circ_0001686 and miR-876-5p inhibition effectively ameliorated the impacts of circ_0001686 deficiency on tumorigenesis and radiosensitivity. Moreover, SPIN1 was a direct target of miR-876-5p and SPIN1 overexpression partially overturned the effects of miR-876-5p transfection on tumor progression and radiosensitivity. Importantly, circ_0001686 could sponge miR-876-5p to regulate SPIN1 expression. In addition, circ_0001686 silencing also constrained tumor growth and increased radiosensitivity in vivo. CONCLUSION: Circ_0001686 contributed to the progression and radioresistance of esophagus cancer cells via regulating SPIN1 expression by targeting miR-876-5p, providing a new therapeutic target for improving the prognosis of esophagus cancer patients.

Brachial-Ankle Pulse Wave Velocity Mediates the Association between Increased Age and Risk of Sarcopenia among Chinese Patients with Type 2 Diabetes Mellitus.

Background and Aims: Arterial stiffness and sarcopenia are commonly seen in patients with type 2 diabetes mellitus (T2DM), and both are age-related diseases. However, few studies have addressed the causal relationship between age, arterial stiffness, and sarcopenia, especially in patients with T2DM. This study is aimed at investigating the relationship among age, arterial stiffness, and sarcopenia in patients with T2DM. Methods and Results: This cross-sectional study enrolled 557 inpatients with diabetes at the First Affiliated Hospital of Wenzhou Medical University, China, between June 2020 and July 2021. Patients who were diagnosed with T2DM and underwent examination of dual-energy X-ray absorptiometry, handgrip strength, 6-meter walk speed, and brachial-ankle pulse wave velocity (baPWV, a recognized indicator of arterial stiffness) were enrolled. A total of 447 patients were included. A dose-dependent relationship was found between age and sarcopenia. We also found a dose-dependent relationship between age and baPWV. Similarly, significant dose-dependent relationships were found across baPWV tertiles with higher prevalence of sarcopenia. Then, a mediation analysis was performed to explore the mediation effect of arterial stiffness on age-associated sarcopenia. We found that the prevalence of sarcopenia increased by 0.0115 (95% CI, 0.0028-0.0239) per 1 year increase in age by the mediation effect of baPWV and that the direct effect of aging on sarcopenia was 0.0441 (95% CI, 0.0101-0.0909) per 1 year older. baPWV mediated 20.5% of the positive relationship between increased age and the prevalence of sarcopenia. Conclusions: Elevated baPWV partially mediates the association of age and sarcopenia among patients with T2DM.

Genetic variations in APPL2 are associated with overweight and obesity in a Chinese population with normal glucose tolerance.

BACKGROUND: APPL1 and APPL2 are two adaptor proteins, which can mediate adiponectin signaling via binding to N terminus of adiponectin receptors in muscle cells. Genes encoding adiponectin and adiponectin receptors contribute to insulin resistance and the risk of obesity, and genetic variants of APPL1 are associated with body fat distribution. However, the association between genetic variations of APPL2 and metabolic traits remains unknown. In the current study, we aimed to test the impacts of APPL2 genetic variants on obesity in a Chinese population with normal glucose tolerance. METHODS: We genotyped six single nucleotide polymorphisms (SNPs) in APPL2 in 1,808 non-diabetic subjects. Overweight and obesity were defined by body mass index (BMI). Obesity-related anthropometric parameters were measured, including height, weight, waist circumference, hip circumference. BMI and waist-hip ratio (WHR) were calculated. RESULTS: We found significant evidence of association with overweight/obesity for rs2272495 and rs1107756. rs2272495 C allele and rs1107756 T allele both conferred a higher risk of being overweight and obese (OR 1.218, 95% CI 1.047-1.416, p = 0.011 for rs2272495; OR 1.166, 95% CI 1.014-1.341, p = 0.031 for rs1107756). After adjusting multiple comparisons, only the effect of rs2272495 on overweight/obesity remained to be significant (empirical p = 0.043). Moreover, we investigated the effects of these SNPs on obesity-related quantitative traits in all participants. rs2272495 was associated with BMI (p = 0.015), waist circumference (p = 0.006), hip circumference (p = 0.025) as well as WHR (p = 0.047) under a recessive model. Similar associations were found for rs1107756 except for WHR. CONCLUSION: This study suggests that genetic variations in APPL2 are associated with overweight and obesity in Chinese population with normal glucose tolerance.

A common genetic variant of FCN3/CD164L2 is associated with essential hypertension in a Chinese population.

Ficolin-3, encoded by FCN3, is the predominant recognition molecule of lectin pathway for the activation of complement component 3 (C3), which is an important risk factor for the development of hypertension. In our previous study, we found the complement system including ficolin-3 was overrepresented in the serum of type 2 diabetic patients. Since type 2 diabetes shares some pathogenic components, including excessive serum C3, with hypertension, this study aims to test the hypothesis that common variants at FCN3 might be associated with essential hypertension in our Chinese population. A total of 1797 subjects were recruited. Of them, 573 were with essential hypertension. Based on HapMap data, three tagging single nucleotide polymorphisms (rs2504778, rs10794501, and rs3813800) in FCN3/CD164L2 region were selected for genotyping by using MassARRAY. Logistic regression analysis was performed to evaluate the genetic effects on the prevalence of hypertension after adjusting for covariates. rs2504778, which locates in the upstream of FCN3 and in the intron of CD164L2, was found to be significantly associated with hypertension after adjusting for covariates (OR = 1.28, 95% CI: 1.05, 1.55, P = .015). Correction for multiple testing did not remarkably attenuate the significance (empirical P = .042 with 10 000 permutations). rs2504778 also showed a nominal association with systolic blood pressure (P = .044) in the quantitative trait analysis. No evidence of correlation with hypertension and blood pressure was observed for rs10794501 and rs3813800. We found that a common variant of FCN3/CD164L2 is associated with hypertension in our Chinese population. More studies with larger sample size are needed to confirm this finding.

First-degree family history of diabetes is associated with nonalcoholic fatty liver disease independent of glucose metabolic status.

BACKGROUND: The first-degree relatives of patients with diabetes (FDRs) share a common genetic background with patients with diabetes. Insulin resistance is recognized as a common contributor to diabetes and nonalcoholic fatty liver disease (NAFLD). The present study aimed to investigate the association between a first-degree family history of diabetes (FHD) and NAFLD and the influence of glucose metabolic status. METHODS: The present work analyzed a part of the baseline data of the REACTION study conducted in a community population. A total of 11,162 participants with an average age of 55.57 ± 9.66 years were enrolled, including 9870 non-FDRs and 1292 FDRs. First-degree FHD was defined as at least one patient with diabetes among parents, siblings or children. The fatty liver index (FLI) was calculated to identify NAFLD. RESULTS: The proportions of subjects without NAFLD, with intermediate FLI, and with NAFLD differed significantly between non-FDRs and FDRs (P < 0.001). FLI was one of the metabolic factors independently associated with first-degree FHD (P = 0.006). Multivariate variance analysis revealed positive associations of first-degree FHD and glucose metabolic status (both P < 0.001) with FLI, which were independent of each other (P for interaction = 0.182). Multiple stepwise linear regression analysis identified that first-degree FHD was independently and positively associated with FLI in men, premenopausal women, and postmenopausal women (all P < 0.05). CONCLUSION: A first-degree FHD was an independent risk factor for NAFLD. Regardless of the status of glucose metabolism, FDRs were more susceptible to NAFLD.

Madelung disease: A case report.

BACKGROUND: Madelung disease (MD) is a rare disorder of fat metabolism, resulting in diffuse, symmetrical and painless deposition of adipose tissue in subcutaneous superficial fascial space and/or deep fascia space of the head, neck and shoulders, etc. CASE SUMMARY: We report a case of MD accompanied by type 2 diabetes in a 61-year-old Chinese male. The patient presented with progressive fat deposition over the mandible, neck, abdomen and elbows. He had a history of smoking and alcohol abuse. Excessive fat deposition was seen in the mandible, elbows and the abdominal area of the patient by ultrasonic examination. Computed tomography showed diffuse and marked soft masses (fat density) in the subcutaneous superficial fascia space of the neck. The patient was diagnosed with MD. He was advised to abstain from alcohol and was followed up regularly. CONCLUSION: This report discusses the pathogenesis, diagnosis and treatment of MD, and raises the clinician's awareness of this disease.

A Clinical Epidemiological Analysis of Prognostic Nutritional Index Associated with Diabetic Retinopathy.

PURPOSE: Prognostic nutritional index (PNI) is an effective tool to evaluate the nutritional conditions and predict prognosis, but clinical data are limited for the use of PNI in diabetic retinopathy (DR). This study aimed to investigate the relationship of PNI with the prevalence and severity of DR in patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: This cross-sectional analysis enrolled 1023 individuals with T2DM hospitalized between 2017-2020. PNI was calculated as 10 × serum albumin (g/l) + 0.005 × total lymphocyte count (cells/mL). DR severity was categorized as no, nonproliferative, and vision-threatened DR (VTDR) according to the modified Airlie House classification. Multivariate-adjusted odds ratio (OR) with 95% confidence interval (CI) for the prevalent DR in the top (Q4) compared with the bottom quartile (Q1) of PNI levels were estimated by using logistic regression analyses. RESULTS: PNI levels were significantly lower in individuals with VTDR than those with no and nonproliferative DR (both P < 0.001), and the proportions of individuals with DR were significantly decreased in the top quartile compared with the bottom quartile of PNI levels (P < 0.001). After adjustments for age, gender, DM duration, obesity-related risk factors and clinical biochemical parameters, the higher levels of PNI were significantly associated with a lower prevalence of DR (Q4 vs Q1: OR = 0.402, 95% CI: 0.250-0.649, P < 0.001), with a 5.9% reduction in the prevalence of DR for a per-unit increment in the levels of PNI (OR = 0.941, 95% CI: 0.911-0.972, P < 0.001). The association of PNI and obesity-related indexes (body mass index and waist circumference) with the severity of DR was independent of each other (P<0.001). CONCLUSION: PNI was inversely and independently associated with the severity and prevalence of DR, which suggested that PNI could likely be used to predict DR prognosis in clinical practice.

A variation in NOS1AP gene is associated with repaglinide efficacy on insulin resistance in type 2 diabetes of Chinese.

AIM: To investigate a potential association between SNP rs10494366 in the neural nitric oxide synthase adaptor protein (NOS1AP) and efficacy of repaglinide (an insulin secretagogue) in newly diagnosed Shanghai Chinese type 2 diabetes patients. METHODS: A total of 104 newly diagnosed type 2 diabetes patients (69 men, 35 women) were recruited and treated with repaglinide for 24 weeks. Anthropometric measurements, clinical laboratory tests were obtained at baseline and after 24-week treatment. Genotyping was performed by sequencing. RESULTS: The baseline value of BMI, HOMA-IR, HOMA-B, and fasting insulin level were significantly different between GG, GT, and TT genotypes (P=0.024, 0.030, 0.005, and 0.007, respectively). Carriers of TT genotype were in significant insulin resistance at baseline. After 24-week repaglinide monotherapy, the Delta value of fasting insulin (P=0.019) and HOMA-IR (P=0.011) were significantly different. TT carriers had the least insulin resistance after treatment. The mixed model analysis showed that the variation had an interaction effect with repaglinide treatment only on HOMA-IR (P=0.013). CONCLUSION: A common variant in rs10494366 is associated with repaglinide monotherapy efficacy on insulin resistance in newly diagnosed Shanghai Chinese type 2 diabetes patients.

Association of Serum Fibroblast Growth Factor 23 Levels with the Presence and Severity of Hepatic Steatosis Is Independent of Sleep Duration in Patients with Diabetes.

PURPOSE: Fibroblast growth factor (FGF) 23 is currently recognized to be involved in the occurrence and development of metabolic diseases. The present study aimed to investigate the association between serum FGF23 levels and hepatic steatosis, as well as the influence of sleep duration. PATIENTS AND METHODS: The present study population was selected from patients with diagnosed diabetes hospitalized during February 2018 to April 2019. Serum FGF23 levels were assessed by two-side sandwich enzyme-linked immunosorbent assay. The presence and severity of hepatic steatosis were determined by controlled attenuation parameter (CAP). Hepatic steatosis was determined as CAP≥302 dB/m. RESULTS: Serum FGF23 levels were significantly higher in individuals with hepatic steatosis than in those without hepatic steatosis (P=0.004). The present study population was divided into Q1-Q4 according to serum FGF23 quartiles. The risks of hepatic steatosis were increased more than 3 folds in Q2-Q4 (all P<0.01) compared to Q1. CAP showed an uptrend from Q1 to Q4 (P=0.005), even after adjustment for gender and age (P=0.001). Multivariate variance analyses showed significant differences in CAP among Q1-Q4 (P=0.008) and between individuals with short and long sleep duration (P=0.023), which were independent of each other. Serum FGF23 levels were positively associated with CAP independent of gender, age, total metabolic traits, and sleep duration (P=0.042). CONCLUSION: Serum FGF23 levels were independently and positively associated with the severity of hepatic steatosis. The associations of serum FGF23 levels and sleep duration with hepatic steatosis were independent of each other.

Duration of reproductive years and time since menopause were associated with metabolic syndrome in postmenopausal parous women of Chinese ancestry.

OBJECTIVE: Although duration of reproductive years and time since menopause were previously implicated in the metabolic syndrome, the evidence is more limited. Few of the previous studies were able to take into account related reproductive variables simultaneously. The aim of the present study was to explore the influence of these two reproductive factors on the prevalence of metabolic syndrome in postmenopausal parous women from Southeast China. METHODS: In all, 1,536 postmenopausal parous women were recruited. Self-reported information about reproductive status, including age at menarche, age at menopause, number of children, prepregnancy body weight, and oral contraceptive use, was collected, and duration of reproductive years and time since menopause were calculated. Clinical parameters related with metabolic syndrome were also measured. RESULTS: Longer duration of reproductive years was significantly related with increased presence of the metabolic syndrome (odds ratio [OR] 1.570, 95% confidence interval [CI] 1.091, 2.259 for tertile 2 group; OR 1.850, 95% CI 1.163, 2.944 for tertile 3 group; P for trend = 0.010). Women with more than 20 years since menopause were more likely to experience metabolic syndrome (OR 2.422, 95% CI 1.109, 5.286, P = 0.026) and elevated blood pressure (OR 3.239, 95% CI 1.406, 7.458, P = 0.006) when compared with those with less than 10 years since menopause. CONCLUSIONS: Longer duration of reproductive years and time since menopause were associated with higher prevalence of metabolic syndrome in postmenopausal parous women from Southeast China.

Association of bone mineral density with a first-degree family history of diabetes in normoglycemic postmenopausal women.

OBJECTIVE: A first-degree family history of diabetes (FHD) contributes to increased risks of metabolic and cardiovascular diseases. Bone is an insulin-resistant site and an organ susceptible to microvascular complications. The goal of the present study was to investigate the association of FHD with bone mineral density (BMD) in postmenopausal women. METHODS: In all, 892 normoglycemic postmenopausal women were divided into subgroups of participants with or without a first-degree FHD. BMD was measured using dual-energy x-ray absorptiometry. Fasting plasma insulin and glucose levels were measured, and insulin resistance was evaluated using the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) index. RESULTS: The BMD of the lumbar spine and femoral neck were much higher in the participants with a first-degree FHD than in those without an FHD (all P < 0.05). Lumbar spine BMD and femoral neck BMD were both positively associated with HOMA-IR (P = 0.041 and P = 0.005, respectively). Multiple stepwise regression analysis showed that a first-degree FHD was an independent factor that was positively associated with lumbar spine BMD (standardized ß = 0.111, P = 0.001) and femoral neck BMD (standardized ß = 0.078, P = 0.021). A first-degree FHD was associated with increased BMD, insulin resistance, and hyperinsulinemia. CONCLUSIONS: Our study indicated that normoglycemic postmenopausal women with a first-degree FHD exhibit increased BMD with insulin resistance and hyperinsulinemia. A first-degree FHD was an independent factor associated with elevated BMD in Chinese women after menopause.