Serum iron is closely associated with metabolic dysfunction-associated fatty liver disease in type 2 diabetes: A real-world study.

Aims: There is still a debate about the relationship between serum iron and metabolic dysfunction-associated fatty liver disease (MAFLD). Furthermore, few relevant studies were conducted in type 2 diabetes mellitus (T2DM). Therefore, this study aimed to explore the association of serum iron levels with MAFLD in Chinese patients with T2DM. Methods: This cross-sectional, real-world study consisted of 1,467 Chinese T2DM patients. MAFLD was diagnosed by abdominal ultrasonography. Based on serum iron quartiles, the patients were classified into four groups. Clinical characteristics were compared among the four groups, and binary logistic analyses were used to assess the associations of serum iron levels and quartiles with the presence of MAFLD in T2DM. Results: After adjusting for gender, age, and diabetes duration, significantly higher prevalence of MAFLD was found in the second (45.7%), third (45.2%), and fourth (47.0%) serum iron quartiles than in the first quartiles (26.8%), with the highest MAFLD prevalence in the fourth quartile (p < 0.001 for trend). Moreover, increased HOMA2-IR (p = 0.003 for trend) and decreased HOMA2-S (p = 0.003 for trend) were observed across the serum iron quartiles. Fully adjusted binary logistic regression analyses indicated that both increased serum iron levels (OR: 1.725, 95% CI: 1.427 to 2.085, p < 0.001) and quartiles (p < 0.001 for trend) were still closely associated with the presence of MAFLD in T2DM patients even after controlling for multiple confounding factors. Conclusions: There is a positive correlation between the presence of MAFLD and serum iron levels in T2DM patients, which may be attributed to the close association between serum iron and insulin resistance. Serum iron levels may act as one of the indicators for evaluating the risk of MAFLD in T2DM individuals.

Waist-to-height ratio has a stronger association with cardiovascular risks than waist circumference, waist-hip ratio and body mass index in type 2 diabetes.

AIMS: To compare the associations between four anthropometric indices including waist-to-height ratio (WHtR), waist circumference (WC), waist-hip-ratio (WHR) and body mass index (BMI) and cardio-cerebrovascular events (CCBVEs) in Chinese T2DM patients. METHODS: The associations of four anthropometric measures with CCBVEs and metabolic syndrome (MetS) were compared by multiple regression model in 3108 T2DM patients. CCBVEs was defined as a history of myocardial infarction, angina, angioplasty, coronary artery bypass surgery, transient ischemic attack, ischemic or hemorrhagic stroke. RESULTS: After controlling for age, sex and diabetes duration, the prevalence of CCBVEs and MetS significantly increased across the WHtR, WC, WHR and BMI quartiles in T2DM patients, respectively. However, when controlling for these four anthropometric measurements together, although four anthropometric measures were closely associated with MetS prevalence, only WHtR quartile was significantly associated with CCBVEs prevalence (6.5%, 13.8%, 16.9% and 21.3%, p < 0.001 for trend). After adjusting for multiple confounders including four anthropometric parameters, a regression analysis revealed that only WHtR was independently and positively associated with the presence of CCBVEs (p = 0.029). CONCLUSIONS: Compared with WC, WHR and BMI, WHtR have a stronger association with CCBVEs in T2DM subjects. WHtR maybe a better indicator than other anthropometric measurements for evaluating cardiovascular risks in T2DM.

High Glucose Increases the Expression of Inflammatory Cytokine Genes in Macrophages Through H3K9 Methyltransferase Mechanism.

Recent studies suggest that histone modification is one of the mechanisms regulating inflammatory cytokine gene expression in hyperglycemic conditions. However, it remains unknown how histone methylation is initiated and involved in changes of inflammatory cytokine gene expression under high glucose (HG) conditions. Our aim was to investigate whether H3K9 methylation was involved in HG-induced expression of inflammatory cytokines in macrophages. Expression profile of cytokine genes under hyperglycemia in THP-1-derived macrophages was determined by human cytokine antibody array. Based on the results from the human cytokine antibody array analyses, the H3K9me3 levels of 4 inflammatory cytokine genes, including interleukin-6 (IL-6), IL-12p40, macrophage inflammatory protein-1α (MIP-1α), and MIP-1ß under HG were determined by ChIP assays. Furthermore, the expression of these 4 inflammatory cytokine genes under either HG or chaetocin (an inhibitor of SUV39H1 methyltransferase) exposure or overexpression of SUV39H1 (a H3K9me3-specific methyltransferase) was analyzed by quantitative polymerase chain reaction. Macrophages cultured in HG conditions showed increased gene expression and decreased H3K9me3 levels of inflammatory cytokine genes compared with macrophages incubated in normal glucose (NG) culture. Inhibition of SUV39H1 with chaetocin in NG-treated macrophages also increased the expression of IL-6, IL-12p40, MIP-1α, and MIP-1ß. Furthermore, inhibition of SUV39H1 with chaetocin in HG-treated macrophages further increased the expression of these inflammatory cytokines. Contrarily, NG-treated macrophages transfected with SUV39H1 plasmids show decreased expression of inflammatory cytokines. Furthermore, overexpression of SUV39H1 in HG-treated macrophages alleviated the expression of inflammatory cytokines under HG conditions. Finally, HG also increases the expression of inflammation cytokines in mouse bone marrow-derived macrophages. Our data demonstrated that HG increases the expression of inflammatory cytokines in macrophages through decreased H3K9me3 levels, which was partly mediated by SUV39H1. Dysregulation of epigenetic histone modification may be one of the underlying mechanisms for HG-induced inflammatory cytokine expression in macrophages.

FAM172A protein promotes the proliferation of human papillary thyroid carcinoma cells via the p38 mitogen-activated protein kinase pathway.

Family with sequence similarity 172, member A (FAM172A), was cloned from human aortic tissues and confirmed in our previous study in 2009, however, its functions remain to be fully elucidated. In our previous studies, the protein expression of FAM172A in human aortic smooth muscle cells was found to be upregulated by high glucose in a concentration­ and time­dependent manner. Several reports have shown that insulin resistance is associated with papillary thyroid carcinoma (PTC). Thus, in the present study, the protein expression levels of FAM172A in human papillary thyroid carcinoma were investigated, and the effect of the FAM172A protein on the proliferation of IHH­4 human papillary thyroid carcinoma cells, and its potential molecular underlying mechanisms were examined. Immunohistochemistry and western blotting demonstrated that the protein expression of FAM172A in papillary thyroid carcinoma tissues was not only significantly higher than that in noncancerous tissues adjacent to the carcinoma tissues, but it was also markedly higher than that in normal thyroid and thyroid adenoma tissues. Overexpression of the FAM172A protein activated the p38 MAPK pathway, but not the PI3K and AMPK pathways, in the IHH­4 cells. In addition, overexpression of the FAM172A protein accelerated IHH­4 cell proliferation, compared with the control group, and the pro­proliferative effect of FAM172A protein on IHH4 cells was markedly attenuated by SB202190, an inhibitor of p38 MAPK. Taken together, these results suggest that the FAM172A protein is expressed at high levels in human PTC, which may promote cell proliferation via activation of the p38 MAPK signaling pathway, and be involved in the pathogenesis of PTC.

Decreased urine uric acid excretion is associated with diabetic retinopathy but not with lower limb atherosclerosis in hospitalized patients with type 2 diabetes.

OBJECTIVE: To explore the associations between urine uric acid excretion (UUAE) and diabetic retinopathy (DR)/lower limb atherosclerotic lesions in hospitalized Chinese patients with type 2 diabetes. METHODS: This cross-sectional study was conducted in 2529 hospitalized Chinese patients with type 2 diabetes. UUAE was determined enzymatically using a single 24-h urine collection. The subjects were stratified into quartile based on UUAE levels. DR was determined by digital fundus photography. Lower limb atherosclerotic lesions were assessed by Doppler ultrasound. Both DR and lower limb atherosclerosis were compared among the UUAE quartile groups, respectively. RESULTS: There was a significant decrease in the prevalence of DR in patients across the UUAE quartiles after adjustment for sex, age and diabetic duration (35.0%, 30.7%, 26.1%, and 21.5%, respectively, p = 0.000001 for trend). A fully adjusted multiple logistic regression analyses revealed that UUAE quartiles were markedly inversely associated with the presence of DR (p = 0.030). The prevalence of lower limb plaque (73.9% vs. 62.6%, p = 0.000044) and stenosis (16.3% vs. 9.7%, p = 0.000015) was markedly higher in the diabetics with DR than in those without DR. However, there was no statistical association between the UUAE and lower limb atherosclerotic lesions in type 2 diabetes. CONCLUSIONS: Decreased UUAE was an independent risk factor for DR but not for lower limb atherosclerosis in hospitalized Chinese patients with type 2 diabetes. In selected populations, such as those with type 2 diabetes, the role of uric acid in atherosclerosis may be result from other concomitantly atherosclerotic risk factors, such as DR.

A case with insulinoma localized by combined use of various means.

A patient with insulinoma diagnosed by clinical features and localized preoperatively using a combination of contrast-enhanced ultrasonography (CEUS), dual phase contrast enhanced spiral computed tomography (DPSCT) and arterial stimulation and venous sampling (ASVS) was reported. A 37-year-old man was admitted to our hospital because of hypoglycemic attacks, palpitations, and muscular weakness. Fajans' ratio reported to be an index for insulinoma was positive. Transabdominal computed tomography and ultrasonography failed to detect any abnormalities. CEUS showed a small low echoic lesion in the pancreatic body with blood flow and the early arterial phase of DPSCT revealed a small strengthening focus, which mimicked a pancreatic tumor in the pancreatic body. ASVS showed that the insulin levels in the hepatic vein were extremely increased by calcium injection to the gastroduodenal artery. An open intra-abdominal operation was performed and an insulinoma was confirmed in the pancreatic body. Enucleation of tumor was undertaken and histopathological examination showed an adenoma, insulin expression was positive in immunofluorescence staining. Symptomatic hypoglycemia never happened even without glucose infusion since the operation. His blood glucose level improved to within the normal range.

[Diagnostic value of parameters of glucose metabolism as screening tests for insulinoma].

OBJECTIVE: To analyze the diagnostic value of employing the parameters of glucose metabolism as screening tests for insulinoma. METHODS: Blood glucose profiles within 72 h were recorded by continuous glucose monitoring system (CGMS). Blood samples were collected to detect the HbA1c and GA levels. All subjects received a delayed 75 g oral glucose tolerance test (OGTT) and a simultaneous insulin and C peptide releasing test. RESULTS: Levels of HbA1c [(4.49 +/- 0.63)% vs (5.60 +/- 0.25)%, (5.28 +/- 0.48)%], fasting blood glucose [(3.44 +/- 0.78) mmol/L vs (4.82 +/- 0.35) mmol/L, (4.70 +/- 0.49) mmol/L] and the lowest blood glucose with CGMS [(2.31 +/- 0.24) mmol/L vs (3.28 +/- 0.45) mmol/L, (3.28 +/- 0.99) mmol/L] in insulinoma group were significantly lower than that in impaired glucose tolerance or diabetic patient group and functional hypoglycemia group (P value < 0.05). On the contrary, the levels of IRI (insulin release index) (0.38 +/- 0.07 vs 0.11 +/- 0.06, 0.16 +/- 0.03), CPI (C-peptide index) (0.03 +/- 0.01 vs 0.02 +/- 0.01, 0.02 +/- 0.01) in insulinoma group were higher than those of two other groups (P value < 0.05). Areas of ROC curve were 0.875, 0.955, 0.974, 0.848, 0.916 respectively as screening tests for insulinoma. CONCLUSION: The measurements of HbA1c, fasting blood glucose, IRI, CPI and the lowest blood glucose with CGMS might be useful screening tools to identify insulinoma.

The protective effect of the RAS inhibitor on diabetic patients with nephropathy in the context of VEGF suppression.

AIM: The aim of the present study was to explore whether renin angiotensin system (RAS) inhibitor can reduce the production of vascular endothelium growth factor (VEGF). Further, we sought to elucidate the correlation between VEGF level and certain clinical parameters, such as albumin excretion rate (AER), before and after treatment with angiotensin type 1 receptor blocker. METHODS: We recruited 166 type 2 diabetic patients at various stages of diabetic nephropathy (DN) and 46 healthy control subjects for a cross-sectional study. We recruited another 42 hypertensive type 2 diabetic patients with microalbuminuria for a longitudinal study involving a 6-month irbesartan treatment protocol. Urinary VEGF (uVEGF) levels were determined using ELISA. RESULTS: In the cross-sectional study, hypertensive type 2 diabetic patients who received RAS inhibitor presented lower uVEGF levels than those who did not receive the RAS inhibitor. Statistical analysis indicated that uVEGF level was independently correlated with the AER. In the longitudinal study involving the 6-month irbesartan treatment, we demonstrated that uVEGF levels decreased significantly in patients who achieved a 50% AER reduction (remission group, n=32). In contrast, uVEGF levels remained unchanged in patients who did not exhibit a 50% AER reduction (nonremission group, n=10). Furthermore, the change in uVEGF was significantly correlated with the change in AER (r=0.65, P<0.01) before and after 6 months of irbesartan treatment. This result held true even after we had adjusted for the decrease in average blood pressure. CONCLUSION: The protective effect of the RAS inhibitor in DN patients is associated with the suppression of VEGF. Accordingly, it may be possible to use uVEGF as a marker of DN progression. We suggest that uVEGF may be an important target for therapeutic intervention in the context of DN.

[Prevalence of peripheral vascular disease in diabetics and impaired glucose regulation subjects: a community-based study].

OBJECTIVE: To investigate the prevalence of peripheral vascular disease (PVD) in patients with diabetes mellitus (DM) and impaired glucose regulation (IGR). METHODS: Follow-up 5 years after the previous epidemiologic study of metabolic syndrome in Chaoyang community, Shanghai, 2000 - 2001 was conducted among 717 patients with DM or IGR. Questionnaire survey about general status and DM-related history and behaviors, including smoking, was carried out. Physical examination was made. Ankle/brachial index (A/BI) was measured. Intermittent claudication was surveyed by Edinburgh claudication questionnaire (ECQ). Blood sugar and blood lipid were detected. 427 patients, 210 males and 217 females, aged 67.3 +/- 14.0 (21 - 104), with intact data were enrolled into the analysis. RESULTS: The overall prevalence of PVD was 12.2% in the hyperglycemic population. The prevalence of PVD in the diabetics was 15.1%, significantly higher than that of the IGP subjects (7.7%, P = 0.022). The rate of intermittent claudication in those with the A/BI