High glucose-induced NCAPD2 upregulation promotes malignant phenotypes and regulates EMT via the Wnt/ß-catenin signaling pathway in HCC.

Diabetes mellitus (DM) is recognized as a risk factor for hepatocellular carcinoma (HCC). High glucose levels have been implicated in inducing epithelial-mesenchymal transition (EMT), contributing to the progression of various cancers. However, the molecular crosstalk remains unclear. This study aimed to elucidate the molecular mechanisms linking DM to HCC. Initially, the expression of NCAPD2 in HCC cells and patients was measured. A series of functional in vitro assays to examine the effects of NCAPD2 on the malignant behaviors and EMT of HCC under high glucose conditions were then conducted. Furthermore, the impacts of NCAPD2 knockdown on HCC proliferation and the ß-catenin pathway were investigated in vivo. In addition, bioinformatics methods were performed to analyze the mechanisms and pathways involving NCAPD2, as well as its association with immune infiltration and drug sensitivity. The findings indicated that NCAPD2 was overexpressed in HCC, particularly in patients with DM, and its aberrant upregulation was linked to poor prognosis. In vitro experiments demonstrated that high glucose upregulated NCAPD2 expression, enhancing proliferation, invasion, and EMT, while knockdown of NCAPD2 reversed these effects. In vivo studies suggested that NCAPD2 knockdown might suppress HCC growth via the ß-catenin pathway. Functional enrichment analysis revealed that NCAPD2 was involved in cell cycle regulation and primarily interacted with NCAPG, SMC4, and NCAPH. Additionally, NCAPD2 was positively correlated with EMT and the Wnt/ß-catenin pathway, whereas knockdown of NCAPD2 inhibited the Wnt/ß-catenin pathway. Moreover, NCAPD2 expression was significantly associated with immune cell infiltration, immune checkpoints, and drugs sensitivity. In conclusion, our study identified NCAPD2 as a novel oncogene in HCC and as a potential therapeutic target for HCC patients with DM.

Association between sleep duration and metabolic syndrome: a population-based study in China.

INTRODUCTION: The relationship between sleep duration and metabolic syndrome (MetS) remains debatable. In the present study, we analysed the link between total sleep duration (including nighttime sleep and nap duration) and MetS as well as its components among the Chinese population. MATERIAL AND METHODS: This was a cross-sectional study from a prospective population cohort including 8616 participants over 40 years in Guangxi, China, evaluated from April 2011 to January 2012. MetS was diagnosed using modified criteria from the National Cholesterol Education Program's Adult Treatment Panel III. Sleep information was obtained through a standard self-report-based questionnaire. The connection between sleep duration and MetS prevalence as well as its components was evaluated using a logistic regression model. RESULTS: After adjusting for potential confoundings, the longer daily sleep duration (≥ 10 hours) group was observed to have the higher odds of having MetS than the reference group with ≥ 7 and < 8 hours of sleep [odds ratio (OR): 1.25, 95% confidence interval (CI): 1.03-1.52, p = 0.023], as well as the highest odds of having elevated triglycerides (OR: 1.25, 95% CI: 1.03-1.52) and fasting blood glucose (OR: 1.21, 95% CI: 1.01-1.45). Further analysis demonstrated that sleeping > 9 hours per night was correlated to MetS in females (OR: 1.27, 95% CI: 1.02-1.58), while napping ≥ 90 minutes was correlated to MetS (OR: 1.44, 95% CI: 1.11-1.87) in males. CONCLUSION: Both longer nighttime sleep duration and longer naps may be associated with the development of MetS.

The Role of Type 2 Diabetes Mellitus-Related Risk Factors and Drugs in Hepatocellular Carcinoma.

With changes in modern lifestyles, type 2 diabetes mellitus (T2DM) has become a global epidemic metabolic disease, and hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. T2DM is a complex metabolic disorder and has been considered an independent risk factor for HCC. Growing evidence supports that T2DM-related risk factors facilitate hepatocarcinogenesis via abundant mechanisms. With the wide implementation of microbiomics, transcriptomics, and immunotherapy, the understanding of the complex mechanisms of intestinal flora and immune cell subsets have advanced tremendously in T2DM-related HCC, uncovering new findings in T2DM-related HCC patients. In addition, reports have indicated the different effects of anti-DM drugs on the progression of HCC. In this review, we summarize the effects of major T2DM-related risk factors (including hyperglycemia, hyperinsulinemia, insulin, chronic inflammation, obesity, nonalcoholic fatty liver disease, gut microbiota and immunomodulation), and anti-DM drugs on the carcinogensis and progression of HCC, as well as their potential molecular mechanisms. In addition, other factors (miRNAs, genes, and lifestyle) related to T2DM-related HCC are discussed. We propose a refined concept by which T2DM-related risk factors and anti-DM drugs contribute to HCC and discuss research directions prompted by such evidence worth pursuing in the coming years. Finally, we put forward novel therapeutic approaches to improve the prognosis of T2DM-related HCC, including exploiting novel diagnostic biomarkers, combination therapy with immunocheckpoint inhibitors, and enhancement of the standardized management of T2DM patients.

Reproductive factors and metabolic syndrome among Chinese women aged 40 years and older.

BACKGROUND: The aim of this study is to explore the relationship between reproductive variables and the prevalence of metabolic syndrome (MetS) and its components among Chinese women aged 40 years and older. METHODS: A cross-sectional study was conducted among 4453 women aged 40 years and older in Guangxi, China. The associations between women's reproductive factors and MetS were analyzed using a logistic regression model. RESULTS: The prevalence of MetS was 23.9% in this population. Women with MetS were mostly older, more likely to be postmenopausal, and had higher parity. Compared to women with one prior live birth, those with three or more live births had the highest odds of having MetS (odds ratio [OR] = 1.56; 95% CI, 1.23-1.99). Similarly, compared to premenopausal women, postmenopausal participants had higher odds of having MetS (OR = 1.86; 95% CI, 1.49-2.31). No associations were observed between MetS and abortion or with age at menarche. CONCLUSIONS: Our study suggests that multiparity and menopausal status may be associated with the development of MetS. The inconsistency seen in epidemiological research to date calls for further investigation.

Whole fresh fruit intake and risk of incident diabetes in different glycemic stages: a nationwide prospective cohort investigation.

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

A rare pituitary tumor associated with hyperthyroidism and acromegaly.

Background: Mixed pituitary TSH/GH adenomas are rare adenomas associated with acromegaly and/or thyrotoxicosis, with or without varying degrees of goiter. In this report, we show a case of pituitary adenoma producing both GH and TSH simultaneously. Case presentation: A 27-year-old man was diagnosed with pituitary adenoma based on various symptoms and clinical findings. For further examination and treatment, he was hospitalized in our institution. It was likely that this subject had pituitary adenoma producing both GH and TSH. In brain magnetic resonance imaging, there was a giant tumor in the sellar region. After the diagnosis of mixed pituitary TSH/GH adenoma, he was treated with octreotide, then underwent tumor resection, and then received hydrocortisone acetate and levothyroxine sodium. After then, GH and IGF-1 levels were suppressed and thyroid function was normalized. Postoperative immunohistochemistry reports showed GH (+) but TSH (-), which may be insensitive to the antibody used to detect TSH or combined with other factors. Conclusions: The diagnosis of mixed pituitary TSH/GH adenoma must be combined with clinical manifestations, immunohistochemical staining and relevant hormone levels, and genetic testing if necessary for comprehensive judgment. For patients with large adenomas, it is recommended to use somatostatin analogs to restore TH levels and control the excessive secretion of GH levels before surgery.

Epidemiological survey of the status of iodine nutrition and thyroid diseases in Guangxi, China.

OBJECTIVE: To survey the status of iodine nutrition and the prevalence of thyroid diseases in Guangxi, China, and to explore the risk factors for positive thyroid antibody. METHODS: We used the multistage stratified cluster random sampling method to select a total of 2488 subjects from an urban and a rural location. All the subjects completed a questionnaire survey, blood and urine samples were also collected, and B-mode thyroid ultrasound was used to determine thyroid function and detect thyroid antibodies. RESULTS: 1) The median level of urinary iodine was 148.53 µg/L in school-age children in Guangxi, China. 2) The prevalence rates for thyroid diseases were as follows: hyperthyroidism, 0.89 %; subclinical hyperthyroidism, 1.05 %; hypothyroidism, 0.69 %; and subclinical hypothyroidism, 8.87 %. The rates of thyroid antibody positivity were as follows: thyroid peroxidase antibody (TPOAb), 13.60 %; thyroglobulin antibody (TGAb), 13.60 %; thyroid antibodies, 18.2 %; and thyroid nodules, 16.94 %. 3) The rate of TPOAb positivity was significantly higher in women aged 18-29, 30-39, 40-49, or 60-69 years than in men in the same age groups (P < 0.05), and the TGAb positivity rate was significantly higher in women than in men of the same age group (P < 0.05). 4) The rate of thyroid antibody positivity was significantly higher in individuals with iodine deficiency than in individuals with adequate iodine (21.6 % vs 18.4 %) or excess iodine (21.6 % vs 15.5 %) (both P < 0.05). 5) The female sex and a family history of thyroid diseases were the major risk factors for thyroid antibody positivity (odds ratio [OR] 3.010, P <0.05; OR 2.486, P <0.05). CONCLUSION: The overall level of iodine is adequate in Guangxi, China; this level should be maintained to prevent the thyroid diseases related with iodine deficiency or excess of iodine. Female sex and a family history of thyroid diseases are independent risk factors for thyroid antibody positivity.

Case Report: A Novel ABCC8 Variant in a Chinese Pedigree of Maturity-Onset Diabetes of the Young.

Background: We aimed to analyze a novel ABCC8 variant of a Chinese patient with suspected maturity-onset diabetes of the young (MODY) and to provide evidence for precise diagnosis and appropriate treatment. Method: A Chinese family with suspected MODY was recruited in this study, which included a 15-year-old female patient with diabetes. Clinical data and blood samples were collected from the proband and other family members. All of the living relatives were given an oral glucose tolerance test. Next-generation sequencing was performed to identify the mutated genes in the proband. Sanger sequencing was utilized to confirm the location of the pathogenic variant in all subjects. Further treatment was referred to targeted family members according to genetic testing. Results: The proband was found to have a random blood glucose level of 244.8 mg/dl and an HbA1c level of 9.2%. Before this investigation, her grandparents had been diagnosed with diabetes. The second uncle, two aunts, mother, and cousin of the proband were diagnosed with diabetes by abnormal HbA1C (6.5-12.1%) and fasting blood glucose (FBG, 91.4-189.7 mg/dl). The second aunt of the proband had impaired glucose homeostasis (HbA1C = 6.4% and FBG = 88.0 mg/dl). One novel missense variant c.1432G>A (p.A478T) in exon 9 of the ABCC8 gene was detected in the proband with suspected MODY. The variant was also found in six family members with diabetes or impaired glucose homeostasis, including her second uncle, two aunts, mother, and cousin. After the treatment was switched to glimepiride, the fasting blood glucose was adjusted to 99.54 mg/dl, the 2-h postprandial blood glucose was 153.54 mg/dl, serum fructosamine was 259 µmol/l, and HbA1c was 5.8%. The glycemic control remained optimal, and no hypoglycemic episodes were observed in the living relatives. Conclusion: This study revealed one novel missense variant of the ABCC8 gene in Chinese families. The present findings indicated that the members of this family responded to treatment with sulfonylureas as previously seen in ABCC8 MODY.

Use of First-phase Insulin Secretion in Early Diagnosis of Thyroid Diabetes and Type 2 Diabetes Mellitus.

BACKGROUND: A relationship between hyperthyroidism and insulin secretion in type 2 diabetes mellitus (T2DM) has been reported. Therefore, this study explored the use of first-phase insulin secretion in the differential diagnosis of thyroid diabetes (TDM) and T2DM. METHODS: In total, 101 patients with hyperthyroidism were divided into hyperthyroidism with normal glucose tolerance (TNGT), hyperthyroidism with impaired glucose regulation (TIGR), and diabetes (TDM) groups. Furthermore, 96 patients without hyperthyroidism were recruited as control groups (normal glucose tolerance [NGT], impaired glucose regulation [IGR], and T2DM). The following parameters were evaluated: homeostasis model assessment (HOMA)-IR, HOMA-ß, modified ß-cell function index (MBCI), peak insulin/fasting insulin (IP/I0), AUCins-OGTT, and AUCins-OGTT/AUCglu-OGTTfrom the oral glucose tolerance test (OGTT) insulin release test were utilized to assess the second-phase insulin secretion, while the IP/I0, AIR0'~10', and AUCins-IVGTTfrom the intravenous glucose tolerance test (IVGTT) insulin release test were used to assess the first-phase insulin secretion. RESULTS: In the OGTT, the HOMA-ß values of the TNGT and TDM groups were higher than those of the NGT and T2DM groups (all P< 0.05). In the hyperthyroidism groups, the MBCI of the TDM group was lower than that of the TNGT and TIGR groups (all P< 0.05). Among the control groups, the MBCI values of the IGR and T2DM groups were lower than that of the normal glucose tolerance (NGT) group (all P< 0.05). In the IVGTT, insulin secretion peaked for all groups at 2-4 min, except for the T2DM group, which showed a low plateau and no secretion peak. The IP values of the TNGT, TIGR, and TDM groups were higher than those of the NGT, IGR, and T2DM groups (all P< 0.05). The Ip/I0, AIR0'~10', and AUCins-IVGTTvalues of the TDM group were higher than those of the T2DM group but were lower than those of the TNGT, TIGR, NGR, and IGR groups (all P< 0.05). Compared with the other five groups, the Ip/I0, AIR0'~10', and AUCins-IVGTTvalues of the T2DM group were significantly decreased (all P< 0.05). The Ip/I0and AUCins-IVGTTvalues of the TNGT group were higher than those of the NGT group (all P< 0.05). CONCLUSIONS: ß-cell function in TDM patients is superior to that in T2DM patients. First-phase insulin secretion could be used as an early diagnostic marker to differentiate TDM and T2DM.