Diabetic kidney disease (DKD) is a major microvascular complication of diabetes, associated with high morbidity, mortality, and healthcare costs. Early detection is challenging due to the lack of highly specific diagnostic tools. This study aimed to develop and validate a nomogram for predicting DKD risk in patients with type 2 diabetes mellitus (T2DM) by integrating conventional biochemical indicators with noninvasive lens advanced glycation end product (AGE) measurements. A total of 868 patients with T2DM from Shanghai Fifth People’s Hospital (November 2019 to February 2024) were enrolled. Independent predictors of DKD were identified using logistic regression and incorporated into a predictive nomogram. Model performance was evaluated using receiver operating characteristic curves, calibration plots, and decision curve analysis. The cutoff value for lens AGE fluorescence (0.306) was derived from our previous study using ROC analysis with Youden’s index. Seven variables were independently associated with DKD: systolic blood pressure, glycated hemoglobin, triglycerides, serum cystatin C, 25-hydroxyvitamin D, red blood cell count, and lens AGE values. The nomogram showed good discrimination, with an AUC of 0.809 in the training cohort and 0.806 in the validation cohort. Calibration demonstrated close agreement between predicted and observed risk, and clinical utility was confirmed. This novel nomogram provides a practical and highly specific tool for early DKD screening and individualized risk assessment in T2DM patients.

Background: It remains unclear whether cholesterol-lowering therapy can reduce the incidence of microvascular complications in patients with diabetes. We aim to explore the potential causal relationship between three common types of cholesterol-lowering drugs and diabetic microvascular complications through drug-target Mendelian randomization (MR) study, laying the groundwork for the development of new medications. Methods: In this study, we collected single nucleotide polymorphisms (SNPs) associated with HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) inhibitors, PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors, and NPC1L1 (Niemann-Pick C1-Like 1) inhibitors from published genome-wide association study statistics. Subsequently, drug-target MR analyses were performed to investigate the effects of these inhibitors on low-density lipoprotein cholesterol (LDL-C) level-mediated microvascular complications in diabetes mellitus. Coronary atherosclerosis as a positive control. Primary outcomes included diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy from the FinnGen Consortium. Results: The MR analysis revealed significant associations between HMGCR inhibition and increased risks of diabetic nephropathy (OR [95%confidence interval (CI)] = 1.88 [1.50, 2.36], p = 5.55 × 10-8), retinopathy (OR [95%CI] = 1.86 [1.54, 2.24], p = 6.28 × 10-11), and neuropathy (OR [95%CI] = 2.63 [1.84, 3.75], p = 1.14 × 10-7) using the inverse variance weighted method. PCSK9 inhibitors have been associated with an increased risk of diabetic nephropathy (OR [95%CI] = 1.30 [1.07, 1.58], p = 0.009) and diabetic neuropathy (OR [95%CI] = 1.40 [1.15, 1.72], p = 0.001); NPC1L1 inhibitors significantly reduce the incidence of diabetic retinopathy (OR [95%CI] = 0.48 [0.28, 0.85], p = 0.01). The coronary heart disease as positive control. Conclusions: The findings show that HMGCR inhibitors and PCSK9 inhibitors may significantly increase the risk of diabetic microvascular complications. However, NPC1L1 inhibitors may provide protection against diabetic retinopathy.

While gestational diabetes mellitus (GDM) poses great threat to the health of mothers and children, there is no standard early prediction model for this disease yet. This study developed and evaluated a nomogram for predicting GDM in early pregnancy. Overall, 1824 pregnant women were randomly divided into the training and internal validation sets in the ratio of 7:3, with additional 1604 pregnant women for external validation. Multivariate logistic regression analysis was used to develop a prediction model for GDM, and a nomogram was utilized for model visualization. Risk factors in the prediction model involved age, pre-pregnancy body mass index, reproductive history, family history of diabetes, creatinine level, triglyceride level, low-density lipoprotein level, neutrophil count, and monocyte count. Model performance was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision clinical analysis (DCA). The area under ROC curve (AUC) value of the model was 0.804 for the training set, and similar AUC values were obtained for the internal (0.800) and external (0.829) validation sets, verifying the stability of the model. The calibration curves showed that the probabilities of GDM predicted by the nomogram highly correlated with the observed frequency values. The DCA curves indicated that the prediction model is clinically useful, thus potentially aiding early pregnancy management in women.

Abstract Perinephric adipose tissue (PRAT) is a component of visceral adipose tissue that is considered an important factor in maintaining renal homeostasis. PRAT has a close relationship with the kidney. Under metabolic dysfunction, PRAT inflammation may precede the damage of blood sugar to the kidney. Whether there is a difference between proximal and distal lipids of PRAT and its significance are not clear. For this reason, we used the nontargeted absolute quantitative method for lipid analysis. The nontargeted analysis method can distinguish various types of lipids in a sample. Absolute quantification of lipids against an internal standard can not only determine the difference in lipid levels between groups but also yield the absolute concentration of lipids in each group. Therefore, we compared the amount and lipid level of PRAT between diabetic kidney disease (DKD) mice and nondiabetic mice and the difference in the lipid spectrum between proximal (within 5 mm from the kidney) and distal (outside 5 mm from the kidney) PRAT in DKD mice. The results showed that DKD mice had significantly more PRAT than the control group. Lipid proteomics found that PRAT in the DKD group significantly differed from that in the control group in glycerides, sphingolipids and phospholipids. Glycerides, including TG (41:10e), TG (43:4), TG (45:7e), TG (52:6) and TG (71:5), were significantly upregulated in PRAT of DKD mice, while TG(56:8e) and TG(55:1) were downregulated. The sphingolipids cer(d36:2), cer(d36:1), cer(d34:2), cer(d34:1) and cerP(t39:3) and the phospholipids PC (38:4), PS (36:4), PS(38:4), PI(42:0), CL(85:1) and CL(76:6) were significantly upregulated in the PRAT of the DKD mice, whereas LPE(16:1e) and PG(41:0) were significantly downregulated. TG(38:3), TG(50:5), TG(52:12e) and TG(56:9e) in the proximal end of PRAT in the DKD group were higher than they were in the distal end, especially TG(38:3), but the sphingolipids and phospholipids in the proximal end of PRAT in the DKD group were downregulated. Our results show that the amount and lipid level of PRAT are significantly higher in DKD mice than non-DKD mice, and there are differences between proximal and distal PRAT. Lipid metabolism in the perirenal fat microenvironment may be related to DKD. These new insights into the mechanism of DKD may be helpful for developing therapeutic strategies for this disease.

BACKGROUND:Vitamin D was shown to directly exert a protective effect on diabetic kidney disease (DKD) in our previous study. However, whether it has an effect on perirenal adipose tissue (PRAT) or the intestinal flora and its metabolites (trimethylamine N-oxide, TMAO) is unclear. METHODS:DKD mice were received different concentrations of 1,25-(OH)2D3 for 2 weeks. Serum TNF-α levels and TMAO levels were detected. 16S rRNA sequencing was used to analyze gut microbiota. qPCR was used to detect the expression of TLR4, NF-Κb, PGC1α, and UCP-1 in kidney and adipose tissue. Histological changes in kidney and perirenal adipose tissue were observed using HE, PAS, Masson and oil red staining. Immunofluorescence and immunohistochemistry were used to detect the expression of VDR, PGC1α, podocin, and UCP-1 in kidney and adipose tissue. Electron microscopy was used to observe the pathological changes in the kidney. VDR knockout mice were constructed to observe the changes in the gut and adipose tissue, and immunofluorescence and immunohistochemistry were used to detect the expression of UCP-1 and collagen IV in the kidney. RESULTS:1,25-(OH)2D3 could improve the dysbiosis of the intestinal flora of mice with DKD, increase the abundance of beneficial bacteria, decrease the abundance of harmful bacteria, reduce the pathological changes in the kidney, reduce fat infiltration, and downregulate the expression of TLR4 and NF-κB in kidneys. The serum TMAO concentration in mice with DKD was significantly higher than that of the control group, and was significantly positively correlated with the urine ACR. In addition, vitamin D stimulated the expression of the surface markers PGC1α, UCP-1 and VDR in the PRAT in DKD mice, and TMAO downregulated the expression of PRAT and renal VDR. CONCLUSIONS:The protective effect of 1,25-(OH)2D3 in DKD mice may affect the intestinal flora and its related metabolite TMAO on perirenal fat and kidneys.

Background Advanced glycation end products (AGEs) deposited in the lens are correlated with those in the kidneys, indicating a possible value in evaluating diabetic kidney disease (DKD). This study explored the value of noninvasively measuring lens AGEs to diagnose and evaluate the severity of diabetic nephropathy in patients with type 2 diabetes mellitus (T2DM). Methodology A total of 134 T2DM patients admitted to the Fifth People's Hospital of Shanghai from March 2020 to May 2021 were selected randomly. Patients were divided into low-, medium-and high-risk groups according to the risk assessment criteria for DKD progression and into DKD and non-DKD (non-DKD) groups according to the Guidelines for the Prevention and Treatment of Diabetic Nephropathy in China. The concentrations of noninvasive AGEs in the lens in all the groups were retrospectively analyzed. Results The concentration of noninvasive lens AGEs in the high-risk patients, according to the 2012 guidelines of the Global Organization for Improving the Prognosis of Kidney Diseases, was significantly higher than that in the remaining groups. Regression analysis suggested the value of lens AGEs in diagnosing DKD and evaluating DKD severity. Cox regression analysis indicated that the noninvasive lens AGE concentration was positive correlated with the course of disease. Conclusion The receiver operating characteristic (ROC) curve suggested that using noninvasive lens AGE measurements has clinical value in the diagnosis of DKD (area under the curve 62.4%,95% confidence interval (CI) 52.4%–73.9%, p = 0.014) and in assessing the severity of DKD (area under the curve 83.2%, 95% CI 74.1%–92.3%, P < 0.001). Noninvasive lens AGE testing helps screen T2DM patients for DKD and evaluate the severity of DKD.

Objective:To investigate the effects of persistent isolated hypothyroxinemia in the first and second trimester of pregnancy on complications and adverse outcomes of pregnancy.Methods:A retrospective analysis was conducted in 784 pregnant women including 111 cases of persistent isolated hypothyroxinemia in the first and second trimester of pregnancy and 673 pregnant women with normal thyroid function as control group. All women were registered and delivered in the Department of Obstetrics of our hospital from April 2016 to April 2017. The complications and adverse outcomes of pregnancy in the two groups were analyzed.Results:Age, body weight before pregnancy, body mass index(BMI), 1 h plasma glucose and 2 h plasma glucose during oral glucose tolerance test in persistent isolated hypothyroxinemia group were higher than those in control group( P<0.05), with increased incidence of anemia during pregnancy( P<0.05). However, there were no significant differences in the incidences of gestational diabetes mellitus and gestational hypertension between the two groups( P>0.05). No significant statistical differences were found in macrosomia, stillbirth, neonatal malformation, postpartum hemorrhage, acute delivery, premature delivery, fetal intrauterine development delay, and small full-term infants between the two groups( P>0.05). Logistic regression analysis showed that age( OR=1.1, 95% CI 1.0-1.1, P=0.002) and pre-pregnancy body weight( OR=1.0, 95% CI 1.0-1.1, P=0.046) were risk factors for the occurrence of persistent isolated hypothyroxinemia in the first and second trimesters of pregnancy. Persistent isolated hypothyroxinemia in the first and second trimesters was associated with anemia during pregnancy( OR=1.9, 95% CI 1.1-3.2, P=0.024). Conclusions:Pregnant women who are older and heavier before pregnancy should pay more attention to their thyroid function. Pregnant women with persistent isolated hypothyroxinemia in the first and second trimesters should be concerned for anemia.

Diabetic kidney disease (DKD) is a complication of diabetes, which is the most common cause of end-stage renal disease (dialysis). DKD has a high mortality rate, and only early detection can nip this disease in the bud. Advanced glycation end products (AGEs)are generally believed to be involved in the occurrence of DKD. Studies have shown that the lens AGEs fluorescence for noninvasive detection has high consistency with the gold standard OGTT, has high sensitivity and specificity, and could be used as a practical tool for the early screening of type 2 diabetes mellitus (T2DM).Therefore, we speculated that the noninvasive lens AGEs fluorescence detection method can be used to predict the occurrence of DKD. This study detected levels of AGEs in multiple cellular and tissues and analyzed the relationships between AGEs and lens, eyeballs, peripheral blood mononuclear cell (PBMC), serum, and kidney. Additionally, we examined the possible role of lens AGEs fluorescence in DKD screening. Our preexperimental study found that lens AGE levels in patients with T2DM were positively correlated with PBM and serum AGE levels. Lens AGE levels in patients with T2DM were negatively correlated with eGFR and positively correlated with urinary ACR. The animal and cell experiments showed that the AGE levels in the eyeballs of DM mice were also positively correlated with those in the serum and kidney. To increase the reliability of the experiment, we increased the sample size. In our results, lens AGEs levels were positively correlated with the occurrence of DKD, and the incidence of DKD in the high lens AGEs group was 2.739 times that in the low lens AGEs group. The receiver operating characteristic (ROC) curves showed that patients with T2DM with a lens AGEs value ≥ 0.306 were likely to have DKD. The area under the ROC curve of the noninvasive technique for identifying DKD was 0.757 (95% Cl: 0.677-0.838, p<0.001), and the sensitivity and specificity were 70.0% and 78.7%, respectively. These results suggest that noninvasive lens AGEs detection technology has certain clinical value in diagnosing whether patients with T2DM have DKD.

Immune dysfunction caused by environmental factors plays an important role in the development of Graves’ disease (GD), and environmental factors are closely related to the intestinal flora. Our previous study showed significant changes in the intestinal flora in GD patients compared with healthy volunteers. This study analyzed the relationships between changes in the intestinal flora, thyroid function and relevant thyroid antibodies in GD patients before and after methimazole treatment. The subjects were divided into the UGD group (18 newly diagnosed GD patients), the TGD group (10 GD patients with normal or approximately normal thyroid function after methimazole treatment) and the NC group (11 healthy volunteers). Their fresh stool samples were sent for 16S rRNA gene amplification and Illumina platform sequencing. The correlations of the relative abundance of Bifidobacterium with the levels of TRAb, TgAb and TPOAb in the NC group and the UGD group were analyzed. A total of 1,562,445 high-quality sequences were obtained. In the UGD group, the abundances of Bifidobacterium and Collinsella were higher than that in the NC group; Bacteroides abundance in the TGD group was higher than that in the NC group, while Prevotella and Dialister abundances were lower than that in the NC group; Prevotella and Collinsella abundances in the UGD group were higher than that in the TGD group. The predominant abundance distribution of Bifidobacteriaceae in the UGD group at the family level was superior to that in the NC group. The abundance of Bifidobacterium was positively correlated with the levels of TRAb, TgAb, and TPOAb. The biological diversity of the intestinal flora was reduced in GD patients. After methimazole treatment, the composition of the intestinal flora was significantly altered. The change in Bifidobacterium abundance was positively correlated with TRAb, TgAb and TPOAb, suggesting that it might be related to the immune mechanism of GD. The results of this study may deepen our understanding of the pathogenesis of GD and provide a new idea for the treatment of GD.

BACKGROUND:Trimethylamine N-oxide (TMAO) serves as a metabolite of intestinal bacteria as well as a urotoxin influencing the prognosis of chronic kidney disease (CKD), which has become a research hotspot in the field of kidney disease. This study preliminarily explored the alternations of the microbial flora and serum TMAO in patients with type 2 diabetes mellitus (T2DM) complicated with diabetic kidney disease (DKD).METHODS:Seventeen T2DM patients at the Affiliated Hospital of Zunyi Medical University between September 2018 and February 2019 were included. Among these patients, 8 patients had T2DM complicated with DKD. Eight healthy volunteers constituted the control group. Fresh stool was collected for Illumina sequencing. Based on the sequencing outcomes, the flora diversity and species differences were analyzed. Serum TMAO, cystatin C, urinary albumin/urine creatinine ratios (ACRs), and routine biochemical outcomes were also compared.RESULTS:The DKD group exhibited a significantly higher TMAO level than the remaining groups. The high-TMAO group had a significantly increased ACR level compared with the low-TMAO group. TMAO positively correlated with the ACR. Compared with the control group, the DKD group exhibited a decreased flora diversity. At the genus level, both the T2DM group and the DKD group showed decreased numbers of Alloprevotella and Megasphaera compared with the control group. The difference in Megasphaera between the DKD group and the control group was significant.CONCLUSIONS:The alternation of the intestinal microbial flora may participate in the development of DKD, and TMAO and chronic inflammation might be important factors for DKD development.

Objective:To investigate the changes of advanced glycosylation end product(AGEs)/sodium-glucose cotransporter-1(SGLT-1) in intestinal and renal tissues and intestinal flora of mice with diabetes kidney disease.Methods:Twenty KKay mice were divided into diabetic group(DM group, n=10) and diabetic kidney disease group(DKD group, n=10). The concentrations of serum AGEs, lipopolysaccharide(LPS), tumor necrosis factor-α(TNF-α), and intereukin-6(IL-6) were measured. Western blot technique was used to detect the protein expression of AGEs and SGLT-1 in kidney and intestinal tissue, and high-throughput sequencing was used to analyze the difference of intestinal flora. Results:The levels of inflammatory markers TNF-α, IL-6, and serum endotoxin in DKD group were significantly higher than those in DM group( P<0.05). The contents of AGEs in serum and intestine and kidney were increased, and the contents of SGLT-1 in intestine and kidney were increased( P<0.05). Metastats test showed that the abundance of Verrucomicrobia decreased and the abundance of Proteobacteria increased in DKD group( P<0.05). G - bacteria such as Aeromonas, Enterobacter, Morgan, Klebsiella, Serratia, and Burkholderia were relatively dominant, and the abundance of Akkermansia was significantly lower than that in DM group( P<0.05). Conclusion:The increase of AGEs in intestinal tract of DKD mice may induce intestinal dysbacteriosis, especially the increase of Proteobacteria, the decrease of Verrucosa and Wilhelm Ackermann, and the leakage of G-bacteria into the blood to produce intestinal endotoxemia and cause inflammatory reaction, this may be an important factor in the development of DKD. SGLT-1 is elevated in intestinal tissue, which may be involved in the development of DKD.

Background: Intestinal flora is associated with Graves’ disease (GD). This study explored the association of serum 25(OH)D with the diversity of the intestinal flora and serum IL-17 in GD patients. Methods: Patients newly diagnosed with GD at 2 centers between 2018 and 2021 were consecutively included. According to their 25(OH)D levels, they were divided into the deficiency group, the insufficiency group, and the sufficiency group. Some patients with vitamin D deficiency or insufficiency were randomly selected and were matched with healthy volunteers (normal control [NC]) in terms of sex, age, and case number. The diversity and differential species of the intestinal flora and serum IL-17 levels were compared. Results: Serum 25(OH)D negatively correlated with serum IL-17, the platelet/lymphocyte ratio, and TSH receptor antibody. The diversity of the intestinal flora decreased in the GD group, with noticeable differences in the composition of the intestinal flora when compared with the NC group. At the phylum level, the GD group exhibited a significantly lower abundance of Firmicutes but a higher abundance of Actinobacteria. At the genus level, the GD group exhibited higher relative abundances of Bifidobacterium, Collinsella, and Pediococcus but lower abundances of Roseburia and Dialister. Conclusions: The changes in the vitamin D level and the composition of the intestinal flora may partially contribute to the development of GD.

目的 初步探究Graves病(Graves disease,GD)患者肠道菌群的多样性变化.方法 选择遵义医科大学附属医院就诊的初诊Graves病患者(n=18例),同期于体检中心体检的健康人群(n=11例),受试者均排除近1个月内合并感染性疾病、其他自身免疫疾病、应用益生菌及抗生素等.并收集其粪便样本,提取肠道菌群DNA,16S rRNA基因扩增,Illumina平台测序,对测序结果进行物种注释、多样性及物种差异分析.结果 测序共测得1200665条高质量序列,每个样本平均含有(41402±6733)条有效序列.2组间Chao1指数、ACE指数、Shannon指数及Simpson指数没有统计学差异(P>0.05),但GD组均小于NC组,表明Graves病患者肠道菌群多样性降低.2组间肠道菌群组成和结构存在显著差异,门水平上GD组厚壁菌门相对丰度低于NC组,而放线菌门高于NC组(P<0.05).属水平上GD组双歧杆菌属、柯林斯氏菌属、Pediococcus、N09、02d06等相对于NC组优势丰度分布,而罗斯氏菌属、小杆菌属、Thermus、Slackia、[Prevotella]等相对丰度低于NC组(P<0.05).结论 通过对Graves病患者肠道菌群的多样性分析,可得出Graves病患者与正常人肠道菌群确有差异,肠道菌群紊乱导致肠道慢性炎症状态及免疫激活可能是Graves病的发病机制之一.

目的 探讨活性维生素D(VitD)通过维生素D受体(VDR)调控细胞因子信号转导抑制分子(SOCS)、酪氨酸激酶/信号转导和转录激活因子(JAK/STAT)通路在DKD中的作用及可能机制.方法 构建DKD小鼠及沉默VDR基因的DKD小鼠模型,随机分为DKD组、低浓度VitD3干预组(L-VitD3)、高浓度VitD3干预组(H-VitD3)、慢病毒转染沉默VDR基因表达组(Lenti-shVDR)、低浓度VitD3+慢病毒转染组(Lenti-shVDR+L-VitD3)、高浓度VitD3+慢病毒转染组(Lenti-shVDR+H-VitD3).饲养期间每天观察小鼠一般行为学变化,每3～4 d监测BG及体重,第1、4、8周测24小时尿蛋白(24 hUP),HE染色观察肾脏病理改变,Western blot法检测肾脏组织中JAK2、磷酸化JAK2(p-JAK2)、STAT3、p-STAT3、SOCS1和SOCS3蛋白表达水平.结果 与DKD组比较,L-VitD3、H-VitD3组体重、BG和24 hUP降低(P<0.05),H-VitD3组BG和24 hUP低于L-VitD3组(P<0.05),Lenti-shVDR组24 hUP升高(P<0.05).DKD组肾小球增大伴系膜基质增生,L-VitD3、H-VitD3组病变减轻;与DKD组比较,Lenti-shVDR组肾小球病变加重,Lenti-shVDR+L-VitD3、Lenti-shVDR+H-VitD3组病变较Lenti-shVDR组稍减轻.与DKD组比较,L-VitD3、H-VitD3组p-STAT3、SOCS1和SOCS3蛋白表达均降低(P<0.05);JAK2蛋白表达在L-VitD3组降低(P<0.05).与DKD组比较,Lenti-shVDR组JAK2、p-STAT3、SOCS1和SOCS3蛋白表达均增加(均<0.01).与Lenti-shVDR组比较,Lenti-shVDR+H-VitD3组JAK2、p-STAT3、SOCS1和SOCS3蛋白表达降低(P<0.01).结论 VitD可降低DKD小鼠尿蛋白,改善肾脏病理损伤,延缓肾损害.JAK2/STAT3/SOCS途径可能参与DKD进展,沉默VDR基因后可减弱活性VD对JAK/STAT通路激活的影响,提示活性VitD调控SOCS和JAK/STAT通路可能通过特异性受体VDR介导.

BACKGROUND:To identify serum nonylphenol (NP) and glucolipid metabolism-related proteins in Type 2 diabetes (T2D) patients.METHODS:We performed a hospital-based, case-control study in patients admitted to the Department of Endocrinology, Hospital of Zunyi Medical University, Zunyi City, China from Mar to Nov of 2014. The study included 112 T2D cases diagnosed in accordance with the 2013 WHO Expert Committee Diabetes Diagnosing Criteria, and 125 healthy individuals with normal fasting blood glucose (FBG) when receiving physical examination in the same period in the Municipal Physical Examination Center. Blood samples from subjects in the 2 groups underwent detection of biochemical indices, including FBG, blood fat, and NP. Glucolipid metabolism-related proteins, including estrogen receptor (ER), sterol regulatory element-binding protein-1c (SREBP-1c), wingless-type MMTV integration site family member 5a (Wnt5a), and peroxisome proliferator-activated receptor-γ (PPAR-γ). These indices were compared between the 2 groups to analyze the correlation between serum NP levels and glucolipid metabolic proteins.RESULTS:The subjects in the diabetes group had higher triglycerides (TG), total cholesterol (TC), NP, ER, SREBP-1c, Wnt5a, FBG, and TG levels than the healthy group, but lower levels of low-density lipoprotein cholesterol (LDL-C) and PPAR-γ than the healthy group. No significant differences in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were found between the two groups. The serum NP levels were shown to be positively correlated with SREBP-1c but negatively correlated with PPAR-γ.CONCLUSION:The serum NP levels of T2D patients is higher than the levels in healthy controls, and its levels correlate with SREBP-1c and PPAR-γ levels.

The correlation between serum 25-hydroxy vitamin D (25(OH)D) levels and lower extremity atherosclerotic disease and the predictive value of 25(OH)D for early-stage lower extremity atherosclerotic disease in patients with type 2 diabetes mellitus (T2DM) were explored. In total, 620 subjects (590 T2DM patients and 30 healthy subjects) completed a questionnaire. All subjects were divided into four groups according to serum 25(OH)D concentration quartile: Q1 (<12.18 ng/ml), Q2 (12.18~20.65 ng/ml), Q3 (20.65~31.97 ng/ml), and Q4 (>31.97 ng/ml). Participants were also divided into four groups based on the degree of lower extremity arteriostenosis: A1 (T2DM), A2 (T2DM with mild lower extremity vascular lesions (LEVL)), A3 (T2DM with moderate LEVL), and A4 (T2DM with severe LEVL). The incidence of lower extremity artery plaque was significantly higher in groups Q1 and Q2 than in group Q4 (both P < 0.05). The concentration of 25(OH)D was significantly lower in group A4 than in groups A1 and A2. Pearson correlation analysis revealed that the degree of lower extremity vascular stenosis was positively correlated with age, smoking, and HbA1c, CRP, and LDL-C levels and negatively correlated with 25(OH)D concentrations. Logistic regression analysis demonstrated that 25(OH)D concentrations exerted a protective effect against LEVL in T2DM patients. Serum 25(OH)D concentrations may be correlated with the incidence of macrovascular disease in T2DM patients. A low serum 25(OH)D concentration is an independent risk factor for lower extremity vascular pathological changes and acts as a prognostic index for lower extremity atherosclerotic disease.

Chemerin is an adipocytokine that participates in glycolipid metabolism; however, its association with type 2 diabetes (T2DM) with lower extremity macroangiopathy (T2DM-V) has rarely been reported. This study explored the association of chemerin and inflammatory factors with body fat parameters, glucolipid metabolism, and insulin resistance (IR) in T2DM and T2DM-V. Patients were classified into normal glucose regulation (NGR), T2DM, and T2DM-V groups. Serum chemerin, glucolipid metabolic parameters, transforming growth factor (TGF)-β, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1 and fasting insulin levels were measured along with HOMA-IR, body mass index (BMI), and waist-to-stature ratio (WSR). Serum chemerin, TGF-β, IL-6 and MCP-1 levels were significantly higher in T2DM groups than in NGR group, and BMI, WSR, fasting plasma glucose (FPG), 2hPG, glycated hemoglobin (HbA1c), triglycerides (TG) and HOMA-IR were higher in T2DM-V subgroups with moderate or severe lower extremity macroangiopathy than in NGR group, simple T2DM group, and T2DM-V subgroup with mild macroangiopathy. FPG, 2hPG, HbA1c, TG and HOMA-IR were higher in T2DM-V subgroup with severe macroangiopathy than in T2DM-V with moderate macroangiopathy (p < 0.05). In all groups, serum chemerin levels were positively correlated with BMI, WSR, FPG, 2hPG, HbA1c, fasting insulin, aspartate transaminase, TG, TGF-β, IL-6 and HOMA-IR (p < 0.05) and negatively correlated with high-density lipoprotein cholesterol [HDL-c] (p < 0.05). Multiple stepwise regression analysis showed that 2hPG, HbA1c, and HDL-c were independent predictors of serum chemerin levels (β = -0.768, -0.122, -0.115, and 3.261, respectively; p < 0.01). Collectively, chemerin, factors associated with obesity, pathological and physiological changes in glucolipid metabolism, and inflammatory factors may promote the development of T2DM macroangiopathy.

目的 分析早晚期2型糖尿病肾脏病患者与单纯2型糖尿病、健康人群之间的肠道菌群是否存在差异,探讨2型糖尿病肾脏病的发生发展与肠道菌群改变是否相关.方法 选取性别年龄匹配的单纯2型糖尿病患者、早晚期2型糖尿病肾脏病组及健康志愿者各5例,采集新鲜粪便样本,提取、扩增、检测及分析细菌的16sRNA,比较各组肠道菌群的差异.结果 在门水平,其中厚壁菌门、变形菌门、放线菌门、拟杆菌门共占细菌菌群中绝大部分;与Control组相比,EDN组粪球菌属(Coprococcus)较高;与T2DM组相比,DN.uremia组的Brautia属低于T2DM组.结论早晚期2型糖尿病肾脏病患者与单纯糖尿病、健康人群之间的肠道菌群存在差异.

OBJECTIVES:The pathogenesis of Graves' disease (GD) remains unclear. In terms of environmental factors, GD development may be associated with chronic inflammation caused by alteration of the intestinal flora. This study explored the association of intestinal flora alteration with the development of GD among the Han population in southwest China.DESIGN AND METHODS:Fifteen GD patients at the Affiliated Hospital of Zunyi Medical College between March 2016 and March 2017 were randomly enrolled. Additionally, 15 sex- and age-matched healthy volunteers were selected as the control group during the same period. Fresh stool samples were collected, and bacterial 16S RNA was extracted and amplified for gene sequencing with the Illumina MiSeq platform. The sequencing results were subjected to operational taxonomic unit-based classification, classification verification, alpha diversity analysis, taxonomic composition analysis and partial least squares-discriminant analysis (PLS-DA).RESULTS:The diversity indices for the GD group were lower than those for the control group. The GD group showed significantly higher abundances of Firmicutes, Proteobacteria and Actinobacillus and a higher Firmicutes/Bacteroidetes ratio than the control group. PLS-DA suggested the satisfactory classification of the flora between the GD group and the control group. The abundances of the genera Oribacterium, Mogibacterium, Lactobacillus, Aggregatibacter and Mogibacterium were significantly higher in the GD group than in the control group (P < 0.05).CONCLUSIONS:The intestinal flora of GD patients was significantly different from that of the healthy population. Thus, alteration of intestinal flora may be associated with the development of GD.

肠道菌群组成和结构的变化与自身免疫性甲状腺疾病(AITD)发生发展有关,当肠道菌群失调破坏肠道黏膜屏障功能,耶尔森菌、双歧杆菌、乳杆菌、幽门螺杆菌等菌属某些特定菌株蛋白与TSH-R、TPO、TG等具有相似的氨基酸序列,透过肠道黏膜屏障进入血液,并通过分子模拟等机制打破免疫耐受状态引起针对甲状腺的自身免疫反应,从而诱发AITD;而分节丝状细菌、普雷沃菌、直肠真杆菌等菌属可能通过影响Th17/Treg轴诱导或加重AITD.